EDGAR 10-K Filing

Company CIK: 1822691
Filing Year: 2023
Filename: 1822691_10-K_2023_0000950170-23-010351.json

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ITEM 1. BUSINESS
Item 1. Business.
Unless the context otherwise requires, for purposes of this section, the terms “we,” “us,” the “Company” or “GreenLight” refer to GreenLight Biosciences Holdings, PBC and its subsidiaries.
Overview
GreenLight has a clear mission: To create products addressing some of humanity’s greatest challenges through the rigorous application of science.
We aim to achieve this goal through our cell-free biomanufacturing platform. This platform enables us to make complex biological molecules-nucleic acids, peptides, carbohydrates, and many others-in a manner that we believe will allow us to manufacture high-quality products at a lower cost than traditional methods using fermentation. We are using this platform to develop and commercialize products that, if they receive appropriate regulatory approvals, address agricultural, human health and animal health issues.
Humanity faces numerous challenges. There are more than eight billion people sharing the diminishing resources of Earth. This growing population needs to produce more food with the same amount of land and, at the same time, honor the global desire-and increasing technical need-to replace chemical pesticides. Not only are these pesticides facing increased consumer opposition and threat of outright bans due to environmental damage, but many are losing their effectiveness.
More than half the world’s population now lives in cities, breathing the same air that carries pathogens and causes infections. Humanity needs to adapt and tackle pandemics both for those who have and for those who do not have access to good health care around the planet.
To address these issues, we need to develop high-quality, cost-effective products that can be deployed widely, including to developing countries. We believe ribonucleic acid, or RNA, can be the critical aspect to these products.
RNA gained broad global prominence in recent years as the COVID-19 pandemic swept through the world’s population, prompting messenger RNA, or mRNA, vaccines to move from a scientific theory to a medical reality. Vaccines made using mRNA proved among the fastest to develop and the easiest to update for newer strains of COVID-19.
While the fast rollout of mRNA vaccines helped change the course of the pandemic, this is just one part of the story. The full potential for RNA in human health has not yet been realized. Beyond human health, RNA-based technology can also be deployed to address other global issues, including agricultural needs for crop protection.
Our technology platform, which was initially developed to produce agricultural crop protection products and is protected by patents and know-how, is capable of synthesizing building blocks (nucleotides), building tools (enzymes), and instructions (DNA templates) to make double-stranded RNA, or dsRNA, within an integrated process. The know-how that we gained from our experience with designing and developing our dsRNA platform process and analytics provided the foundation upon which we designed and developed our mRNA production process and analytics. For more information on our proprietary platform, see “Business-Our Manufacturing Platform and Capabilities.”
We have several dsRNA-based products in our agricultural pipeline that, if commercialized, we believe can change the way in which farmers protect crops, allowing them to better utilize the land dedicated to agriculture and produce foods with less or no pesticide residue. Two of these potential products, CalanthaTM, which is designed to manage Colorado potato beetles, and our varroa mite solution, which is designed to protect bees, have been submitted to the Environmental Protection Agency (EPA) for approval. Our other dsRNA-based agricultural products are in various earlier stages of development, ranging from proof of concept in the lab to proof of technology in the greenhouse and proof of scale in the field. See “Business-Plant Health Product Pipeline” for additional information on the development process. In order to commercialize a product for the U.S. agricultural market, we must complete specified toxicology and environmental studies, submit a registration dossier to the EPA demonstrating that the product does not pose unreasonable risks to human health or the environment, respond adequately to any deficiencies
identified by the EPA through its risk assessment process and obtain the EPA’s approval of our labeling. The EPA must also establish a tolerance level for the product or issue a tolerance exemption. We must separately obtain any applicable state or foreign regulatory approvals where we want to commercialize our products. For more information regarding the regulatory process, see “Business-Government Regulation-Agricultural Products” and “Risk Factors-Risks Related to Our Plant Health Program”.
Our COVID-19 vaccine program and shingles vaccine program are the primary focus areas of our human health pipeline. Other potential product candidates in our human health pipeline are in early stages of pre-clinical research and development. To get to the pre-investigational new drug (“IND”) application phase for our product candidates in our human health pipeline, we must successfully design and test the product candidates in animal models, achieve positive results, select the product candidates to progress to IND-enabling toxicology studies, develop chemistry, manufacturing, and controls (CMC) protocols and create a development plan to discuss with the U.S. Food and Drug Administration (FDA), and other foreign health regulatory authorities, as applicable, as part of pre-consultations, and manufacture, fill and finish the vaccine candidate material. Significant uncertainty exists as to whether any of other potential product candidates will reach the candidate selection phase.
AN INTRODUCTION TO RNA
RNA is present in all known life forms and plays an essential role in numerous biological processes, including the control of gene expression through RNA interference (RNAi) and as a messenger for protein synthesis. Consequently, RNA molecules are being studied for use in potential products in many fields, such as agriculture (e.g., dsRNA-based insecticides or fungicides) and human health (e.g., mRNA-based vaccines and therapies).
RNA can be transformative for human health and plant health:
•Plant health-where dsRNA can be leveraged to regulate the expression of a target protein by interfering with its message. Such RNA-mediated interference can form the basis for highly targeted pesticides or protection against parasites.
•Human health-where mRNA can be used to express specific proteins which form the basis of vaccines as well as other therapies.
RNA in agriculture
New crop-protection strategies are urgently needed as pests become resistant to existing pesticide products. Many existing products are also being limited through primary regulatory action (government regulations) or secondary regulations (food chain regulation) because of concerns about their effects on humans or the environment, with environmental concerns including off-target toxicity and long-term effects on crops, soil, and water. Together, these factors spur the need to develop alternative crop-protection products with new modes of action and improved safety profiles.
Double-stranded RNA products in agriculture exploit a natural biological process called RNA interference (RNAi). This is a biological process found in many eukaryotic organisms, which break down dsRNA that has been taken into a cell into short fragments known as small interfering RNA (siRNA). The presence of these small RNA fragments can lead to the degradation of complementary mRNA, thereby limiting or stopping the synthesis of the protein that is encoded by the mRNA (e.g., a protein that is of vital importance to a harmful pest insect).
RNA-based pesticides may be able to give us more environmentally friendly ways to protect crops and beneficial insects while effectively stopping harmful pests. Much of our ability to design products that are intended to improve the environmental profile associated with crop protection products relies on our ability to design an RNA sequence that is only found in the organism(s) that we desire to manage. In this design process, we will compare the genome of our target species to the genome of other species that may co-exist with it, including humans, with the goal of avoiding off-target effects.
RNA in human health
Messenger RNA’s features make it broadly valuable for potential use in human health, whether as a prophylactic vaccine or a therapy. It is well known that mRNA has been used to make some of the most effective COVID-19 vaccines and that these vaccines have been developed quickly, which is critical for a pandemic response. Far more than a billion doses of mRNA COVID-19 vaccine have already been produced globally. We are developing multiple mRNA vaccine candidates such as shingles vaccine candidates, an improved vaccine designed to be more broadly protective against COVID-19, and personalized oncology vaccines.
DNA encodes the instructions for life to function. DNA is transcribed into mRNA, which is processed and translated by the ribosome as it synthesizes proteins. Instructions to make proteins that perform many critical functions are transcribed from the
DNA to mRNA. mRNA is a polymer generally comprised of four ribonucleotides (adenine, guanine, cytosine, and uracil), the sequence of which determines the composition of the protein that the mRNA encodes. Synthetic mRNA can be produced in manufacturing facilities for delivery into the cellular cytoplasm, enabling the cells to produce proteins as vaccines or for therapy.
mRNA has many useful attributes:
•Wide range of applications: mRNA can encode for any protein (intracellular, membrane-bound, or secreted), giving it many potential uses (e.g., as a component of vaccines or therapies).
•Transient expression: The body has mechanisms to degrade mRNA, allowing for repeat dosing and a dose-response which can be tailored for the needs of the pharmaceutical product.
•Fast development: Relatively simple changes to the mRNA molecule are needed to produce different therapeutic proteins, enabling a fast turnaround from gene selection to product. For instance, if a booster vaccine is needed for a new variant, no changes will need to be made except to the mRNA sequence itself.
•Flexible manufacturing: A single manufacturing facility can produce different vaccines and therapies with appropriate controls in place, as the process of producing the mRNA is essentially the same regardless of the product will little need for major manufacturing changes.
Until recent years, it was very difficult to stabilize mRNA, understand its interaction with the human immune system and avoid innate immune activation, or deliver it into target cells at effective levels. Addressing these challenges has allowed the development of the RNA industry and its rapid deployment as a global healthcare product.
OUR BUSINESS MODEL AND GROWTH STRATEGY
As a company, we aim to make the benefits of RNA, and other biologics, accessible to everyone.
In human health, we are developing vaccines and RNA therapeutics to alleviate or cure critical diseases facing patients worldwide. In agriculture, we are developing products that promote sustainability and supplement or replace traditional pesticides and fungicides with RNA in farmers’ crop-protection and enhancement programs.
Our technology platform provides for integrated discovery, design, and development of RNA-based products and gives rise to three distinct capabilities that underpin a sustainable business model and bring capabilities normally used in advanced pharma discovery to agriculture and human health:
•Identification and design: Machine learning and proprietary algorithms are key tools as we work to identify the best gene target candidates for dsRNA-based products and seek to design safe and effective dsRNA against those targets. For mRNA-based products in human health, we identify the protein that we are seeking to have the patient express (e.g., an antigen for a prophylactic vaccine application) and seek to design safe and effective mRNA according to our design rules. As we accumulate data across our programs throughout their various stages of development, we incorporate learnings for future improvements to our design and discovery processes.
•Develop and optimize: Our ability to produce RNA and formulate it in-house fuels development. Depending on the testing needs of the program and the stage of development, we can produce various RNAs (types, compositions, lengths) at different scales (ranging from micrograms to kilograms) and various levels of purity with fast turnaround. For instance, we might screen dozens to several hundreds of RNAs in early discovery using microgram to milligram quantities that can be produced and analyzed in one week. As lead sequences are identified, we may seek to improve them by further iterating on their designs. In addition, as the leads progress further in development, we will produce them at the milligram to gram scale (e.g., for in vivo animal studies with mRNA in human health or for greenhouse trials with dsRNA in agriculture). We also have kilogram-scale capability for dsRNA (e.g., for supplying global field trials).
•Manufacturing: We have developed two manufacturing processes, one for plant health (dsRNA) and one for human health (mRNA) that both rely on synthesis of RNA from RNA building blocks, enzymes, and DNA templates and require many of the same analytical methods for assessing in-process control and product quality. We can produce dsRNA products through our proprietary cell-free system. Our current production scale is 2,000 liters per batch. Our mRNA process has been used to produce clinical trial material under phase-appropriate current good manufacturing practice (cGMP) regulations for use in human trials. Our mRNA process has been demonstrated at commercial scale (i.e., basis of 50-liter mRNA synthesis reaction) at a contract development and manufacturing organization. See “Business - Our Manufacturing Platform and Capabilities” for additional details.
In the next five years, our pipeline includes seven agricultural products planned for launch and several human health product candidates with clinical milestones, including Phase I clinical trials, in each case, subject to applicable regulatory approvals.
We anticipate this pipeline will demonstrate:
•Fast development of agricultural products. CalanthaTM will, if approved in 2023, have taken five years from first field trials to market compared to a typical 10-year cycle at major agribusinesses.
•Rapid integration of acquisitions. We acquired Bayer’s topical RNA treatment for honeybees that targets the varroa mite in December 2020. By May 2021, we were conducting further field trials. In February 2023, we submitted our dossier for this product to the EPA for review.
•Validation of our mRNA platform. We are working toward clinical proof of concept of our COVID-19 mRNA vaccine candidate. We have updated our clinical strategy to leapfrog monovalent and bivalent vaccines and advance to progressing our pan-sarbecovirus mRNA vaccine candidate.
Our growth strategy in plant health is to pursue significant market opportunities where RNA has the greatest potential to provide growers with improved pest control and the sustainable nature of our products (e.g., benefits to honeybees and low to no residue) delivers the most impact for society and aligns most closely with macro trends from consumers and regulators. When we use the term ‘sustainable,’ we refer to our efforts to align economic development with environmental protection and human well-being as well as our anticipated obligations as a Public Benefit Corporation under § 362(a) of the Delaware General Corporation Law.
For our plant health products, we define total addressable market as the global revenue opportunity available to pesticide solutions controlling a target pest or disease. In most instances, we do this by defining a relevant active ingredient market for the crop or crops where we intend to market our products and then making an assumption as to the percentage of that market that is spent on controlling the target pest or disease. We use data from AgBioinvestor and FAOSTAT (a database run by the Food and Agriculture Organization of the United Nations), and data purchased from third party consultants is used to quantify the market and underpin assumptions. In order to address the total insecticide and fungicide markets we identify pests or diseases in that market, develop targeted dsRNA sequences for them and attempt to develop the best delivery mechanism for that dsRNA. Over time, we intend to expand beyond RNA, building on our capabilities. In human health, we intend to pursue markets where RNA can provide better products (faster, cost effective or more efficacious) to improve standards of care for patients across infectious diseases, oncology/autoimmune products, and in a variety of additional indications through potential third party collaborations.
Planned products and milestones
Agricultural programs we currently have planned for earliest launch opportunity in the next five years include protection against:
Human health programs in our current pipeline include:
See “Plant Health Product Pipeline” and “Human Health Product Pipeline” below for additional information regarding our pipeline programs.
OUR MANUFACTURING PLATFORM AND CAPABILITIES
Our platform, developed through years of research and technology development, is protected by know-how and foundational patents.
Overview of manufacturing process for agriculture
While the potential advantages of dsRNA for use in agriculture have been known for some time, production cost has historically been a barrier. Our proprietary cell-free dsRNA manufacturing process was designed to achieve an economically viable scale (i.e., metric tons per annum) and cost of goods for competing in broadacre agriculture markets (e.g., < $1 per gram of dsRNA technical grade active ingredient). In human health, raw materials from the vaccines industry are not readily available at these scales and at economically viable prices. Cell-based processes (e.g., production of RNA via microbial fermentation) are generally low yielding and of poorer quality, necessitating more expensive larger-scale capital than higher yielding, higher quality cell-free processes.
Our proprietary process begins with cellular RNA obtained from inexpensive, readily available sources (e.g., yeast). This cellular RNA is broken up (depolymerized) into RNA building blocks (nucleoside monophosphates) using a nuclease enzyme. The desired dsRNA is then synthesized from these nucleoside monophosphates using carefully selected enzymes that “energize” the building blocks (into nucleoside triphosphates) and polymerize them into the desired RNA according to a corresponding DNA template. Key to this dsRNA synthesis process and its economic viability is that we employ inorganic polyphosphate as the energy source, which is inexpensive and readily available like the nucleotide source (cellular RNA). We also produce the required enzymes and DNA templates via scalable fermentation-based processes using proprietary microbial strains, all of which were developed at GreenLight with scale and cost in mind. In addition, enzymes that have a high temperature tolerance were selected to facilitate the production of high-energy nucleotides. The utilization of such enzymes allows high temperature to be incorporated in their preparation, providing a way to mitigate undesirable contaminating activities (e.g., RNA-degrading enzymes, DNA-degrading enzymes, nucleotide-degrading/altering enzymes, protein-degrading enzymes) from entering the RNA synthesis portion of the process and affecting quality and yield.
Regarding the scalability of our cell-free manufacturing platform, we have increased our production scale of dsRNA from microliters to our current 2,000-liter capacity with no material impact on quality or process yields. Regarding the flexibility of the platform, we have synthesized numerous dsRNAs of varying lengths and compositions across these scales in order to supply material for testing at all stages of product development from early discovery to greenhouse to field trials. We believe our expertise and proprietary technology will allow us to increase batch sizes to 10,000 liters and beyond, which will allow us to reduce the cost of our dsRNA products.
Our manufacturing for agriculture
Our dsRNA manufacturing facility in Rochester, New York, is designed for process development while generating samples for research and market development with a design basis of 1,000 kg of dsRNA production per year. The facility has a raw material storage and handling area, high bay wet-processing area with floor drains, two 1,200-liter fermenters, two 2,000-liter cell-free reactors, NMP preparation tanks, formulation, packaging, development laboratory, analytical laboratory, loading dock, and cold storage areas. This plant currently has 18 process engineers, technicians, research associates, and quality-control personnel for commercial production of plant health products.
Of our two 2,000-liter reactors, one has been operational since the second quarter of 2021, and we are planning to have the other online by the end of the second quarter of 2023 as part of our plan to increase manufacturing capacity to 1,000 kg of dsRNA per year. If we obtain the appropriate regulatory approvals to commercialize our products as we project in our agricultural product pipeline, we expect that this capacity will enable us to meet our agricultural product needs through mid-2024.
Overview of manufacturing process for human health
Messenger RNA is produced using a state-of-the art process. mRNA is synthesized (via an in vitro transcription reaction) from RNA building blocks (nucleoside triphosphates and a co-transcriptional capping reagent) that are assembled by an enzyme (RNA polymerase) according to a set of molecular instructions (DNA template) that encodes for the desired mRNA. The resulting mRNA is comprised of elements (a 5’-untranslated region, a protein-coding region, a 3’-unstranslated region, and a poly(A) tail) that ultimately enable protein expression (e.g., of an antigen for a prophylactic vaccine application) upon delivery to human cells. The mRNA undergoes several purification steps to reach the highest quality levels for safety. This process scales linearly from milliliter-scale to commercially relevant scale (50 liters), achieving 12 grams of mRNA per liter of reaction.
For our most advanced programs, the purified mRNA is encapsulated in lipid nanoparticles (LNPs) to facilitate delivery to target cells in humans. The LNPs protect the mRNA from degradation and enables its uptake into the cells so that the mRNA can be used to express the protein of interest. The manufacturing process for mRNA-LNP involves two liquid streams colliding at high velocity in a jet-mixing chamber, one of which contains lipids and one of which contains mRNA. After some additional processing, a cryoprotectant is added before the product is sterile-filtered and stored prior to fill-finish.
Our manufacturing for human health
In June 2022, we terminated our lease for cleanrooms in Burlington, Massachusetts. In May 2022, we entered into a lease in Lexington, Massachusetts for office and laboratory space with existing cleanrooms. We are executing on a plan to be able to qualify the cleanrooms for early phase clinical material production (multi-gram scale) by year-end 2023. We will continue to use CMOs to fill/finish and label/pack our clinical material. We plan to use a contract development and manufacturing organization, or CDMO, to produce mRNA in larger quantities. In November 2021, we engaged Samsung Biologics Co., Ltd. (“Samsung”) as a contract development and manufacturing organization (CDMO) for scale up and commercial scale production of our mRNA COVID-19 vaccine candidate pursuant to a Master Services Agreement (the “MSA”) and a Product Specific Agreement (the “PSA”, and together with the MSA, the “Samsung Agreements”). Under the Samsung Agreements, Samsung is performing pharmaceutical development and manufacturing services for us over a period of years at its South Korean facility in exchange for service fees. We agreed that, if we enter into a purchase agreement for commercial quantities of drug product, we will pay Samsung, on a minimum take-or-pay basis for each year under that agreement, for our minimum purchase commitments, as determined pursuant to the terms of the Samsung Agreements. Based on our minimum purchase commitments, we expect to pay Samsung a minimum of approximately $8.8 million in service fees under the Samsung Agreements, excluding the cost of raw materials, which we must supply to Samsung separately. These fees include initial technology and analytical method transfer fees, process development and scale-up fees, process characterization fees, an annual project management fee, and per-batch engineering run fees. Based on our current schedule, we incurred $5.9 million of expense in 2022, with any remaining expense we expect to incur in 2023. If we move to commercial production, the agreement provides for additional process validation, inspection, cleaning, stability testing and commercial production fees, most of which would be incurred on a per-batch basis.
The Samsung Agreements will terminate on December 31, 2026, unless earlier terminated or extended in accordance with their terms. If we terminate the Samsung Agreements, we will generally be responsible for paying the purchase price for our aggregate product commitment for the remainder of the term, less any amounts we have already paid. Samsung agreed that, at or before the end of the term of the Samsung Agreements, it will assist us to transfer the commercial scale manufacturing process to a facility designated by us. The Samsung Agreements impose limits on Samsung’s liability to us for breaches of the agreements.
Supply for research and development
Depending on the testing needs of the program and the stage of development, we can produce various RNAs at various scales and levels of purity with a rapid turnaround.
Our dsRNA high through-put sample production capabilities are based at our Medford, MA site. We are able to produce about 100 products per week at the microgram to milligram scale for use in early discovery efforts to identify lead sequences or later in development to improve on the leads. We can also produce multi-gram scale quantities at a rate of about 10 products per month if required to support studies that necessitate significantly more material (e.g., lab assays on plant material or greenhouse trials). These materials are typically sent to our Durham, North Carolina facility for formulation.
Our mRNA production capabilities are based at our Lexington, MA site. We are able to produce about 100 products per week at the microgram to milligram scale for use in discovery (e.g., antigen screening or antigen selection). We are also able to produce about 15 products per month at the 20 to 250mg scale if required to support translational research studies that necessitate significantly more material (e.g., in vivo studies in animals). For samples that require mRNA encapsulation, we also have this routine capability at our Lexington, MA site.
Supply for clinical trials & toxicology tests
In 2021, we produced clinical material for our COVID-19 vaccine candidate, GLB-COV2-043 under phase-appropriate cGMP regulations for use in human trials. We engaged contract manufacturing organizations (CMOs) to complete the GMP fill/finish and clinical label/pack of these materials. We are in the process of reestablishing our ability to produce GMP clinical trial material in our Lexington facility, which we expect will be completed in the second half of 2023.
We have also produced mRNA and LNP formulations for multiple IND-enabling toxicology studies under Good Laboratory Practice (GLP) procedures in our Lexington facility.
Human Health Product PIPELINE
Overview
The key pillars of our human health strategy are as follows:
•Developing vaccines for infectious diseases, especially those addressing unmet medical needs in lower- and middle- income countries. Consistent with its public benefit corporation status, GreenLight is striving to support global, sustainable vaccine access and pandemic response readiness.
•Developing innovative products to address unmet medical needs in oncology and autoimmune diseases. This work has begun with the collaboration with EpiVax Therapeutics, Inc. to co-develop and commercialize personalized cancer vaccines, with the initial indication for the first potential product candidate targeting bladder cancer.
•Continued advancement of GreenLight’s mRNA technology platform through innovations and to seek potential partnerships with pharmaceutical and biotechnology companies.
Our mRNA platform consists of:
•The manufacturing process used to produce the product (described above)
•The mRNA molecule
•The delivery vehicle it uses to reach the target tissue
All elements of the platform affect product characteristics, such as purity, potency, and immunogenicity, so our teams work on optimizing mRNA molecules and delivery vehicles for a given indication, and the performance and cost of the manufacturing process.
mRNA molecule design
Changes in the mRNA molecule will result in changes in the protein we intend to express, mRNA stability, safety of the product and the immune response to the product.
First, we must choose the right target protein, after which an mRNA has to be designed for it. A well-designed mRNA molecule, with necessary modifications, will carry instructions for the relevant protein to be expressed safely and efficiently and for the desired duration. The mRNA composition can be optimized to avoid undesirable immune responses while increasing protein expression (or potency).
Delivery vehicles
To facilitate the mRNA to reach its destination without degradation, we must formulate it into a delivery vehicle. The delivery system’s design can influence potency, immunogenicity, safety and the product’s shelf life when stored before administration.
One such delivery system consists of encapsulating mRNA in lipid nanoparticles (LNPs). We work with several established companies that have extensive experience in clinical LNPs for our vaccine candidates. We are able to routinely produce our mRNA-containing LNPs to support our research and development efforts. In addition, we work on stabilizing the LNPs to improve the storage conditions and shelf life of our products.
Our human health pipeline
We are currently working on infectious disease and oncology vaccine targets. We are exploring ways to expand our pipeline to include additional therapeutic areas, including gene therapies, in the future.
To get to the candidate selection phase of our product candidates in our human health pipeline, we must design and test the product candidates in vitro and in animal models, select the top product candidate to progress to IND-enabling toxicology studies, develop chemistry, manufacturing, and controls protocols and processes, create a clinical development plan to discuss with national health regulatory authorities as part of pre-consultation meetings, and manufacture, fill and finish the vaccine candidate material.
In order to begin Phase I clinical trials for any type of vaccine candidate in the United States, we must first successfully complete the required pre-clinical pharmacology and toxicology study for demonstrating reasonable safety of the product candidate, submit an IND application to the FDA, which will include the scope of our proposed Phase I clinical trial, and satisfy all requirements required by the FDA for approval of the IND. We can offer no assurance that any clinical trial applications we
may file will be approved by regulatory authorities. Additionally, in order to begin Phase I clinical trials, we must first produce the Phase I IND candidates in compliance with applicable cGMP regulations and conformity to our chemistry, manufacturing and controls protocols. See “Risk Factors-Risks Relating to Our Manufacturing Platform.”
Prophylactic vaccines for infectious diseases
The objective of a prophylactic vaccine is to expose the body to a protein (called the antigen) that is present in the disease-causing virus or bacterium so that it can generate a protective immune response in the absence of the pathogen and be prepared to fight the actual infection, should it occur in the future. mRNA could be used to encode the antigen as a way to expose the body to a component of the pathogen, avoiding the use of whole infectious agents.
Vaccines that use mRNAs present significant advantages compared to non-mRNA vaccines, including:
•The antigen expressed is a true match to the protein present in the pathogen, thus increasing the potential for an effective immune response as compared to vaccines produced through other methods in which manufacturing processes may result in changes to the antigen.
•The short development time from antigen selection to clinical trials and rapid manufacturing makes mRNA ideal for emerging epidemics or pandemic response. This is why the two mRNA COVID-19vaccines were among the fastest to be authorized.
•The same manufacturing plant can be used to produce mRNA vaccines against multiple potential indications.
Opportunity
Immunization with prophylactic vaccines has become one of the most successful of all healthcare interventions. It is estimated that vaccines prevent 6 million deaths every year.
Our COVID-19 vaccine candidate
Unmet need
Although a large portion of the population in high-income countries has been vaccinated against COVID-19, widespread vaccination in mid- and low-income countries (“LMICs”) has lagged behind the developed world. As we enter the fourth year of the COVID-19 pandemic, continuous and substantial viral evolution create challenges to the ongoing public health response, including timely decisions on modifications to COVID-19 vaccine antigen composition to provide protection. The rapid evolution of the virus and subsequent emergence of new variants which have exhibited a degree of immune escape from vaccination or prior infection has meant that there is a need for boosters which will be more broadly protective. There is also a need to improve the durability of the immune response for longer protection and intervals between boosters. The trajectory and timeline of further virus evolution are uncertain and delays between recommendations to update vaccine antigen composition and roll-out of updated vaccines significantly and disproportionately impact LMICs.
Product concept
Our initial COVID-19 vaccine candidate, GLB-COV2-043, used mRNA to encode the full-length spike protein of the Wuhan strain, formulated in LNPs. Concurrent with the development of GLB-COV-2-043, a monovalent booster candidate, we have been developing a pan-sarbecovirus vaccine candidate, which we are currently evaluating various potential candidates in preclinical studies for their ability to provide protection against a broad panel of sarbecoviruses, including SARS-CoV-2. As previously announced, we are updating our clinical strategy to accelerate the development of this pan-sarbecovirus vaccine candidate instead of advancing the GLB-COV2-043 (monovalent) vaccine candidate as originally planned.
Achievements to date and future milestones
As part of the toxicology and pre-clinical testing, for our initial COVID-19 vaccine candidate, hamsters (16/group) were immunized at day 0 and 21 at three dose levels of 5 µg, 30 µg, and 100 µg of vaccine or controls of saline or LNP. At day 40 of the study, the animals were intra-nasally challenged with live SARS-CoV-2 virus (isolate USA-WA1/2020). Animals were followed for 14 days, and their weights taken daily. This hamster challenge study revealed that all doses of GLB-COV2-043 provided protection from SARS-CoV-2 challenge using percent body weight (% BW) change as a criterion. We observed a statistically significant (p < 0.0001) reduction in weight loss, compared to controls on Day 6, the peak of disease, and Day 14, the end of the challenge study.
Body weight changes of vaccinated hamsters after SARS-CoV-2 viral challenge
Hamsters (8/group) were immunized at day 0 and 21 at three dose levels of 5 µg, 30 µg, and 100 µg of vaccine or controls of saline or LNP (GLuc). Blood draws at day 21 (pre-boost: before injection of the second vaccine dose), and day 39 (post-boost: that is, 18 days after the second dose) were tested for neutralizing antibody titers against live SARS-CoV-2 virus (isolate USA-WA1/2020).
All vaccine doses tested induced significantly higher levels of SARS-CoV-2 neutralization titer compared to controls, both Pre- and Post-Boost. The 100 µg and 30 µg doses of GLB-COV2-043 induced significantly or trending towards significantly higher titers of neutralizing antibodies compared to control immunized animals. The GLB-COV2-043 vaccine candidate displayed a clear dose response after boost, demonstrating that is induces high titers of functional anti-SARS-CoV-2 capable of neutralizing virus entry into cells.
SARS-Cov-2 Serum neutralizing antibody titers for hamsters vaccinated with GLB-Cov-2-043. Day 21: 3 weeks after 1st vaccination dose. Day 39: 18 days after 2nd vaccination dose (*:p<0.05, ***: p<0.001: ns: p=0.0523)
After we completed pre-clinical testing, we were able to produce, fill, and finish the drug product using our own GMP facilities.
As previously announced, GreenLight received approval from the Rwanda Food and Drugs Authority (Rwanda FDA) to initiate a Phase I/II study of its GLB-CoV2-043 (monovalent) vaccine booster candidate. However, given the global shift in the standard of care for COVID-19 vaccination to the Wuhan/Omicron bivalent vaccine and new availability of the bivalent vaccine in Rwanda, GreenLight is updating its clinical strategy to leapfrog monovalent and bivalent vaccines by accelerating development of its pan-sarbecovirus vaccine candidate instead of advancing the GLB-COV2-043 (monovalent) vaccine candidate as originally planned. We are aiming to produce a potential vaccine that will be effective against current and future COVID variants, including preparing for future potential pandemics.
Our Shingles Vaccine Candidate
In March 2022 we granted Serum Institute of India Private Limited (SIIPL), an exclusive license to use our proprietary technology platform to develop, manufacture and commercialize an mRNA shingles (herpes zoster) product and up to two other mRNA products in all territories other than the United States, the 27 member states of the European Union, the United Kingdom, Australia, Japan, New Zealand, Canada, South Korea, China, Hong Kong, Macau, and Taiwan. Pursuant to our arrangement with SIIPL, we have engaged in designing and performing preclinical research to develop a shingles vaccine candidate.
Unmet need
Ninety-five percent of people older than 50 years of age have had chicken-pox. The varicella zoster virus causing this disease remains dormant in the body and reactivates periodically, which may result in herpes zoster or shingles. The lifetime risk of herpes zoster exceeds 30%, with global incidence rates estimated at 3 to 5 per 1,000 person-years overall, 5-11 per 1,000 person-years among adults ≥ 50 years of age and increasing age-specific incidence rates over the last 60 years. Increasing age is also associated with an increasing risk of debilitating complications with a significant impact on quality of life, functional status and productivity, and healthcare costs. The availability and cost of the vaccine currently available for herpes zoster prevention is prohibitively high for many in low- and middle-income countries where the associated impaired quality of life, morbidity, healthcare costs and lost productivity of herpes zoster and its complications have a disproportionate impact.
Our product concept
Our mRNA-based formulations are targeting key viral antigens known to play a critical role in the viral entry and life-cycle. We believe correctly selected antigens and formulations will produce a vaccine candidate with a competitive product profile.
Achievements to date and future milestones
Since March 2022, our Shingles vaccine program has progressed from the stage of concept evaluation to the stage of antigen design and pre-clinical evaluation in small animals. As part of our pre-clinical evaluation of our Shingles vaccines antigen in mice, we evaluated three antigens: VZV antigen#1, VZV antigen#2 and VZV antigen#3. We formulated these three mRNA vaccine antigens in three different lipid nano-particle (LNP) formulations: LNP#1, LNP#2 and LNP#3. Mice were primed with Varivax (attenuated VZV) and thereafter immunized intramuscularly with each of the mRNA-LNP candidates twice, at 0 and 8 weeks. Two doses were evaluated. We observed that all vaccine candidates were immunogenic and elicited high-levels of antigen-specific antibodies (IgG) after the first and second administration (panel A and B, below), comparable to the active control vaccine. These antigen-specific antibody levels were maintained up to 3 months (24 weeks) after the last administration (panel C, below), demonstrating the durability of the humoral immune response.
In addition, the mRNA vaccine candidates formulated with LNP#1 (and LNP#3) were more potent in eliciting strong cellular immune response, when compared to the active control vaccine.
Finally, when we evaluated the memory response, we observed that at 24 weeks, the mRNA vaccine candidates formulated with LNP#1 maintained memory T cells (panel A, below) and memory B cells (panel B, below) responses at levels similar to comparator vaccine (active control), demonstrating ‘durability’ of the immune response.
Based on the pre-clinical studies and evaluation of the three potential candidates highlighted above, GreenLight has selected a lead candidate to progress towards clinical development. We are in active discussions with SIIPL regarding potential plans forward for this vaccine candidate.
Oncology Vaccine Program
On January 8, 2023, we entered into an exclusive collaboration agreement with EpiVax Therapeutics, Inc. (“EVT”), pursuant to which GreenLight and EVT agreed to exclusively collaborate with each other to develop, manufacture and commercialize mRNA-based oncology vaccines using GreenLight proprietary technology and EVT proprietary technology.
Unmet need
mRNA vaccines represent a therapeutic option with potentially improved product profiles and faster development pathways than current oncology therapeutics. We believe that an mRNA-based vaccine could solve some of the biggest unmet needs in oncology.
Under our collaboration with EVT, the first indication we plan to target is bladder cancer, an area with significant unmet needs. Bladder cancer is the fourth most common cancer in men globally but inadequately addressed by existing therapies. Surgery (cystectomy) yields only a 50-60% 5-year survival rate, and radical cystectomy is debilitating even with reconstructive surgery. Cisplatin (chemotherapy) is another option, but 50% of the patient population is ineligible. Lastly, less than 30% of patients respond to checkpoint inhibitors, and those that do typically experience severe side effects.
Our potential product concepts
We are currently in the early stages of our collaboration and work with EVT. Under the collaboration, we envision using EVT’s high-speed, automated, secure, cloud-based commercial platform, Ancer, to process cancer protein sets and identify patient-specific neoantigens and their neoepitopes.
GreenLight plans to take the personalized, multi-antigenic, mutanome-directed therapeutic peptide (comprised of, e.g., 20-40 neoepitopes) identified and created by EVT’s proprietary platform and append/apply our mRNA and DNA design rules, experience, and know-how to create a personalized mRNA that encodes for the peptide such that the peptide is expressed by target cells in the cancer patient. Rapid turnaround (e.g., estimated at 4-8 weeks) from patient tumor biopsy/sequencing to a personalized drug product that is ready for administration is important. Our research-scale mRNA-LNP production capabilities routinely support fast turnaround of material for pre-clinical studies (in vitro, in vivo) and GLP toxicology testing that is of the same scale that we anticipate will be required for an mRNA-based personalized cancer vaccine. We plan to combine our small-scale fast turnaround process with our experience with cGMP regulations and available cleanroom space at our Lexington, MA site to create a capability that can generate phase-appropriate material for early-stage clinical trials.
Global RNA Manufacturing Network
Our vision is to enable Africa, Asia, and Latin America and other potential LMICs to meet local demand through production outside the United States and Europe, from drug substance to product to fill and finish of mRNA vaccines and therapies, ideally in the country where the vaccine will be sold. If our vaccines and therapies are approved in these jurisdictions, we intend to contract with local manufacturers to produce our products, which we believe will enable the accessibility and cost competitiveness of our products.
If we obtain applicable regulatory approvals, we intend to create an interoperable network with local production facilities deploying our manufacturing process using modular design concepts that can be constructed off-site and set up more quickly than traditional construction models, so each facility will rely less on international supply chains to create vaccines and therapies for local needs.
Strategic Collaborations
Collaborators are part of our core strategy as we seek to accelerate our development of RNA therapies. We have relationships with research hospitals, universities, foundations, biotechnology companies, pharmaceutical companies, and nongovernmental organizations with expertise in our pipeline programs. During research and development stages, we seek collaborators to complement our preclinical studies and manufacturing capabilities. At the clinical development stage, we will seek established collaborators to codevelop or commercialize our product candidates. For vaccines, we are seeking companies with commercial capabilities that will receive rights to develop and commercialize our vaccine candidate(s). In this way, we can share the risk and reward of our portfolio while acquiring the capabilities required to launch commercial products. We seek partners aligned with our mission of making RNA accessible to the world.
Our decision to partner will be determined by the partner’s geographic scope and the complementary capabilities that partner can bring to support the commercialization of products. For example, our partnership with SIIPL is focused on unmet medical needs in infectious diseases for LMICs and our collaboration with EVT focuses on personalized cancer vaccines globally. We continue to evaluate and consider when potential partnerships can bring strategic advantages to the company and when we may choose to commercialize some early-stage programs without partners, as large-scale commercial capabilities may not be required for programs with a small patient population.
PLANT HEALTH PRODUCT PIPELINE
Overview
We plan to design, build, and sell a complete portfolio of products that growers can use throughout the food chain, from field to fork, to enhance, protect, and preserve produce and animals.
Our product pipeline is based on double-stranded RNA, or dsRNA, which works by regulating the expression of a carefully selected protein in the target organism, be it in plants, fungi, or animals (primarily insects or arachnids). This method can, with careful selection of the appropriate target, potentially be used to control a wide range of unwanted pests and problems.
The success of our plant health product pipeline will depend on us inventing and bringing to market new uses of RNA in agriculture. Since our product candidates are first of a kind, we typically do not project the timing of a product candidate coming to market until later stages of our development process when we draft a Federal Insecticide, Fungicide, and Rodenticide Act ("FIFRA") dossier for internal review. While we believe our projected timelines are reasonable, given that we are introducing new modes of action for pest control, it is difficult to predict when we will be able to obtain the regulatory approvals required for commercial sales and our expected timelines may be subject to change. Our initial experience with bringing RNA-based agricultural products to market were based on the conception, development and testing of CalanthaTM and we continue to grow our development and regulatory experience as we develop RNA solutions to manage a range of target pests.
GreenLight intends to use, and has taken steps to use, its platform to expand its market access by progressing its product development from generation 1, high-value crops (e.g. single target solutions designed to demonstrate proof-of-concept for dsRNA-based agricultural solutions intended to be primarily registered and commercialized by GreenLight), to generation 2, multitarget products (e.g.solutions designed to address multiple targets, anticipated to be developed in collaboration with partners that possess significant distribution capabilities for large markets and retained in house for high value), to generation 3, systemic delivery capabilities (e.g. solutions delivered to the plant to target weeds, nematodes or improve nutrition; intended primarily to be developed in partnership with crop fertility and other potential partners).
An introduction to dsRNA and agriculture
As a tool for crop protection, dsRNA has several advantages. It is designed to impact the target pest and limit harm to any non-targeted organisms. Unlike many other pesticides, dsRNA degrades quickly in the environment, so it is typically undetectable after a few days, meaning in typical use, treated produce would contain low to no pesticide residue. Finally, in the event any residue remains, there is an established history of safe consumption of RNA molecules in human and animal food. According to a September 2020 report published by the Environmental Directorate of the Organization for Economic Cooperation and Development (“OECD”) entitled Considerations for the Environmental Risk Assessment of the Application of Sprayed or Externally Applied ds-RNA-Based Pesticides, there is a long-established view that dietary intake of nucleic acids, including dsRNAs from plant viruses, does not present a health risk to humans and other vertebrates, and, as a result, the adoption of RNAi technology in agriculture is likely to present a lower human health risk than the use of conventional pesticides.
Process for developing new products
GreenLight uses an internally-developed five-phase product development process for plant and animal health products, which sets forth key activities and requirements to achieve for each potential product from proof of concept through commercial launch (Phase 1a: discovery/lab studies and greenhouse trials; Phase 1b: confirmatory trials; Phase 2: proof of concept field trials; Phase 3 and 4: regulatory submission). In general, in order for a product to move to a particular stage, it must successfully have met the requirements of the preceding stages. This process enables us to have a disciplined product development path with defined inflection points that we believe will increase our likelihood of success in bringing a product to market.
Market opportunity
Given the versatility of RNA-based solutions, we believe that the markets for our products are large. In the near term, we intend to pursue addressable target markets for plant health, with the commercial launch of our first product anticipated by the end of 2023 assuming regulatory approval earlier in the year.
We intend to develop products for our own distribution as well as for commercial partners. In doing so, we will focus our attention on the fresh fruits, vegetables, and nuts markets, which urgently need residue-free crop-protection products or have a strong association with the need to conserve honeybees. We will seek to serve the broadacre markets and international markets through partnerships with established multinational crop-protection companies and distributors. We intend to develop products that farmers trust and incorporate as a regular part of their annual crop-protection program.
Each of the initial products we are developing is intended to be specific to one target pest based on grower needs. We have also begun research and development of potential products that target multiple pests or that can be systemically delivered to plants. We believe that we can continue to leverage on our expertise in RNA as well as use our manufacturing platform and experience to make novel products at a cost that works for farmers.
What specific problems are we trying to solve?
Our plant health team is working to provide growers with highly effective tools to use within their normal cultural practices that avoid disrupting non-target organisms while leaving low to no residue in the foodstuffs. Today there are very few commercially available products that successfully combine these characteristics that growers, regulators, and consumers desire. Our primary focus for this mission is the successful deployment of carefully designed dsRNA. In order for our products to function successfully, the pest that needs to be managed must possess the appropriate cellular apparatus to process exogenous dsRNA to regulate protein biosynthesis. For these organisms, we intend to develop a portfolio of insecticides, acaricides, fungicides, and products that impact crop physiology and health, such as bio stimulants, improved stress tolerance and herbicides.
Insecticides and acaricides
Our insecticides and acaricides program is currently working on six major pest complexes. These projects are distributed across various phases ranging from the most advanced, which is in the pre-commercial phase awaiting regulatory approval, to nascent candidates. We calculate addressable markets for our projects using market data from AgbioInvestor and FAOSTAT and
information purchased from third-party consultants. We use this data as well as our industry knowledge to inform assumptions around expenditures to control the target pest or disease to arrive at the addressable market.
Colorado potato beetle
CalanthaTM, our product candidate for the Colorado potato beetle (Leptinotarsa decemlineata), which decimates plants in the nightshade family and accounts for more than $500 million in crop loss annually, has gone from discovery to Environmental Protection Agency (EPA) submission in four years. The formulated product is mixed with water and sprayed using standard agricultural practice over crops at a rate of 9.9 grams per hectare-less than one-tenth the rate at which many conventional industrial chemicals are normally used on fields. Consumption of the dsRNA, which itself degrades within days, causes the Colorado potato beetle to stop eating and expire from its own toxins while beneficial insects are unaffected. In the United States, we have tested this product over the last four annual growing seasons in Oregon, Washington, Wisconsin, New York, Maine and Idaho. We have also conducted field tests of the product in Spain, Germany and France.
Based on the results of our toxicity testing, GreenLight requested a tolerance exemption from the EPA for the active ingredient contained in CalanthaTM. If granted, such an exemption would be consistent with a category IV toxicity level, the EPA’s lowest level of pesticide toxicity under the Federal Insecticide, Fungicide and Rodenticide Act (“FIFRA”).
We believe the addressable market for protecting crops from the Colorado potato beetle is approximately $350 million. Assuming EPA approval in 2023, we anticipate to commercially launch by the end of 2023.
Widely recognized for its ability to develop resistance to pesticides, the Colorado potato beetle was first described as a pest in the United States in 1859.
We expect the price and performance of CalanthaTM, the first-ever foliar RNA product to be competitive with other products currently available to farmers. We have conducted more than 200 field trials over five years to develop a product that has shown to be effective at just 9.9 g/hectare, an extremely low active ingredient use rate, equivalent to a spoonful of sugar spread on a football field.
Our testing has shown that CalanthaTM is safe for honeybees, butterflies, and several other non-target insects and mammals at use rates 100 times higher than our recommended rate. It degrades in water and soil within three days to benign, natural nucleotides. The product works well with standard growers’ programs to control first-or second-generation Colorado potato beetles. It effectively controls all stages of the life of this beetle but is most effective on young larvae up to one-quarter inch in length.
In addition to being water soluble, this product contains additional inert ingredients to allow it to be mixed with other agricultural products and applied by farmers in a single spraying using common methods, including low-water volume (aerial or ground) or chemigation. Although conventional pesticides can require special protective equipment for farmers, we anticipate just basic work gloves will be required for this product.
Varroa mites
Having acquired the rights to portions of Bayer’s topical RNA intellectual property portfolio, which include bee-health assets, we are developing an RNA-based syrup that targets reproductive mites, is easy to use, and will add another tool in the limited Varroa-control market.
We have been field testing our RNA-based product candidate for the Varroa destructor mite, which many beekeepers consider to be the top threat to honeybees and which has been detected in up to 90% of US hives, since March 2021 with the assistance of commercial beekeepers in Georgia, California, Florida, Louisiana, North Carolina and Maine. To date, these tests demonstrate a measurable improvement in mite control and hive health.
Mite control is measured in number of mites per 100 bees. Trials conducted in 2022 showed lower mite levels using GreenLight’s 4 g/L solution when compared to a chemical control or an untreated control over the course of 18 weeks after first treatment. We also evaluated hive survival rates and found that the GreenLight 4 g/L solution statistically outperformed the untreated control, the chemical control, and the GreenLight 2 g/L solution over the course of 30 weeks after first treatment.
About 3 million commercial honeybee colonies in the United States are used to pollinate more than 100 crops annually that are worth an estimated $18 billion in 2022, according to the U.S. Department of Agriculture. The parasitic Varroa mite reproduces in hives, feeds on honeybees, and spreads disease, destroying colonies across the globe. Our product candidate targets the Varroa mite to protect bees, beekeepers, and pollination-dependent crops.
When we acquired rights from Bayer relating to its bee-health assets, Bayer disclosed to us that in laboratory tests its original Varroa mite product had been observed to have adverse effects on ladybugs. We are developing our own version of this product using our proprietary manufacturing process, and our product has a different composition than the Bayer product. We have observed adverse effects on ladybugs in laboratory tests of products made with our dsRNA manufacturing process but only at 10x higher use rates than Bayer observed. We do not believe that such data will negatively impact our ability to secure a registration from the EPA or impact the attractiveness of our product to potential customers for two reasons. First, during the normal course of use, our product would be delivered in a sealed package directly to beehives, and it is atypical for ladybugs to enter a treated beehive during the proposed treating season. Accordingly, it is unlikely that the organisms that may be negatively affected would be exposed to the product during the normal course of use. Second, we believe that customers would conclude that the benefits of controlling Varroa mites outweigh the potential risks to ladybugs. See “Risk Factors-Risks Related to our Animal Health Program” for a discussion of several risks factors relating to our Varroa mite product.
As part of our preparation for seeking EPA approval of our Varroa mite product, we conducted laboratory and field tests, including a required high-dose test to assess risks associated with potential overexposure to the product. When we tested our Varroa mite product in the laboratory at the required level of ten times the field use rate, the higher concentration of the product caused the treated bee food to become highly viscous, which limited consumption and resulted in bee starvation. We did not observe these adverse effects either when our product was administered at the field use rate or when our product was administered at the high-dose rate in the field. Because our product is delivered in a ready-to-use formulation through a pre-measured pouch delivery system, rather than through conventional spraying, we do not believe that our product presents a material risk that bees will be exposed to concentrations greater than the field use rate. For more information regarding potential adverse effects on regulatory approval of our Varroa mite product, see “Risk Factors-Risks Related to our Animal Health Program-The EPA will evaluate our Varroa mite product without a precedent product, which may result in the need to conduct additional field trials and lengthen the regulatory review period. If we cannot demonstrate bee safety, the EPA may not approve our product or may impose labeling requirements that materially limit the commercial attractiveness of the product.”
In preparation for submission to the EPA, we completed additional studies, including additional bee studies. We have also continued to conduct additional non-target organism studies for dossier inclusion and submission. Additionally, the viscosity of our formulation makes it difficult for us to rely solely on a Tier 1 toxicity study under the EPA guidance, and we have therefore recently conducted and completed Tier 2 toxicity studies. For the United States registration of our Varroa mite product, we submitted a registration dossier to the EPA in February 2023. In certain foreign jurisdictions, including the European Union, we expect that we will be required to apply for authorization of our Varroa mite product as an animal health product under applicable veterinary medicine regulations.
Vegetable Caterpillar Complex
The Diamond Back Moth (Plutella xylostella) is sometimes called the cabbage moth because of its voracious appetite for consuming brassicas plants, which include cabbage, Brussels sprouts, and cauliflower, among others. It represents a global challenge to farmers and growers because its short life cycle allows it to rapidly develop resistance to existing crop protection products.
By testing Diamond Back Moth larvae in greenhouse assays (where they are fed foliage treated with their specific RNA sequence combined with the different delivery technologies we have developed), we believe that the Diamond Back Moth can be controlled with a dsRNA-based pesticide. We are now testing delivery methods by which the product would be delivered to the field. Small scale field tests in the US and Spain have demonstrated activity of formulated dsRNA against Diamond back moth. We anticipate expanding the spectrum of our product my carefully modifying trigger design to include other moth species of importance in vegetable crops before moving into our pre-development phase in 2023 and the development phase in 2024, with the goal of a launch after 2026, subject to receipt of regulatory approval.
Spider Mite Complex
Two spotted spider mites (Tetranychus urticae) (TSSM) are not insects but arachnids that feed on plants. All life cycle stages of the mite will cause damage to the plants upon which they feed. TSSM use their mouthparts to pierce cells on the surface of the leaf to suck out the contents, rendering the cell useless. TSSM will feed on a wide range of crops from Glasshouse ornamentals to tree nuts and fruits to corn and soybeans and can be found almost anywhere crops are grown. This project is currently in the discovery phase where we are seeing from our early research results, good control from our on-plant assays without any need for specific delivery technology. We plan to expand the spectrum of our product by carefully modifying trigger design to include other plant feeding mite species of importance before progression into pre-development in 2024 and move rapidly on to development in 2025 by having an initial focus on controlled environment crops.
Fungicides
Our fungicides program currently has six major targets in the pipeline. This includes botrytis, fusarium, powdery mildew, downy mildew, Asian soybean rust, and rice blast. We calculate addressable markets for our projects using market data from AgbioInvestor and FAOSTAT and information purchased from third-party consultants. We use this data as well as our industry knowledge to inform assumptions around expenditures to control the target pest or disease to arrive at addressable market.
Gray Mold +
Botrytis cinerea, which causes gray mold and bunch rot, is an ever-present global threat for fresh fruit and vegetables that affects 80% of crops grown and can result in up to 30% yield loss. Even greater losses can occur when botrytis develops en route to the consumer. Given how frequently crops such as grapes, berries, and onions need to be sprayed, resistance to existing chemical fungicides can build quickly and produce can carry residues of multiple products. Botrytis has long been a target for new biological fungicides, but excessive rain or humidity means that very few of these products can be relied on to work consistently.
We began testing our Botrytis product in California, New York and Italy in 2021 and are currently working to add additional spectrum to our final end use product prior to commencing the studies for our regulatory dossier in 2023. California, a major market for this product, could lag EPA approval by up to a year or more. Because this product demonstrated disease control in the field on both of the crops that we tested (strawberries and grapes), we progressed into the pre-development phase at our portfolio review in December 2021. We are currently working on proof-of-concept development field trials and expanding the spectrum of our product by carefully modifying trigger design to include other fungal species of importance in vegetable and fruits and berry crops before continuing to advance the development of this program. At this stage of development, we believe we can bring this potential product, subject to receipt of regulatory approval, into the market after 2027.
Powdery mildew complex
Powdery mildew, caused by Erysiphe necator, is the most common and destructive disease affecting grapes. Mostly observed on the upper surface of leaves as a dusty gray or white coating, the disease also strikes the lower surface, young stems, buds, flowers, canes, and fruit. Severely infected leaves may exhibit mottling or deformity, including leaf curling and withering. Infected fruit turn grayish-white first, then exhibit a brown, rusted appearance and may crack, shrivel, or drop from clusters.
We conducted our first season of field trials in 2021 in New York and California, and we were able to demonstrate disease control comparable to current leading chemical-control products. We anticipate one more year of field trials with the goal of regulatory submission in 2024. Assuming the EPA approves the product in 2026, we would expect to begin commercialization that year. California, a major market for this product, could lag EPA approval by up to a year or more, and non-US grape growing
regions such as France could also take one or more additional years to obtain approval. Because this product demonstrated disease control in the field on both of the crops that we tested (strawberries and grapes), we progressed the project into the pre-development phase at our portfolio review in December 2021. We are currently working on expanding the spectrum of our product by carefully modifying trigger design to include other powdery mildew species of importance in a range of crops before conducting development trials and advancing towards formulation development and believe we can bring this potential product, subject to receipt of regulatory approval, into the market by 2026.
Mycotoxin control
Fusarium Head Blight is a disease of cereal crops most typically caused in the United States and Europe by Fusarium graminearum, though some other Fusarium species are implicated. Fusarium species have a wide host range and can cause many different types of damage to crops depending upon the type of crop plant and its growth stage at the time of infection. In the form of the disease which infects the flowering ear of the cereal crop, Fusarium does not necessarily rob the farmer of yield but instead frequently produces mycotoxins as part of its metabolic process. These mycotoxins can cause serious illness and even death when consumed in small quantities (the primary mycotoxin is deoxynivalenol, or DON, known colloquially as vomitoxin), so there is a detection limit in process food stuffs of 11 ppm. dsRNA can be designed to inhibit the metabolic pathway that produces the mycotoxins. We believe the ability to do this is a key differentiator for GreenLight. The current fungicides available to the grower may control the pathogen but do not provide reliable suppression of the mycotoxins. This product is currently in greenhouse trials, with GreenLight having demonstrated under controlled conditions that it can stop mycotoxin production on growing wheat. Aflatoxins cause food spoilage and are thought to be a primary cause of liver cancer in Africa. Their control is currently an unmet need that organizations, such as the Partnership for the Control of Aflatoxins in Africa, are trying to solve. We believe we can modify our DON control sequences to suppress aflatoxin production. Once designed, we expect that we will need to complete two seasons of field testing given the importance of mycotoxin control for public health. Based on our product development to date, we believe we can move this project into later stages of our development process in late 2024, which we believe would allow us to move through the remaining development phases and into the market, subject to prior regulatory approval, by 2026 at the earliest.
Crop physiology
Our activities in crop physiology, crop stress tolerance, and herbicides have taught us how to deliver dsRNA into many different types of cells, so we are expanding our research to give us further opportunities in the stress tolerance and crop-protection market. GreenLight believes there is promise in emergent technologies that can deliver dsRNA into the plant by spray, seed treatment or root uptake. If we can advance these technologies sufficiently, we will begin to select new projects to develop products that can exploit the markets requiring such properties.
Limitations we are working to overcome
The use of dsRNA as a crop-protection technology has been proposed since the discovery of the mechanisms of RNAi in the 1990s. A key barrier to the development of dsRNA was the cost of manufacturing RNA itself.
Our proprietary cell-free technology aims to solve this problem. Other technical, commercial, and social challenges remain, with delivery as the next challenge. Not all organisms will readily uptake dsRNA in the way that the Colorado potato beetle and Varroa mite do, and we need to deploy strategies that overcome barriers for lepidoptera (the rate of breakdown in the gut) or plants (passage across membranes). Much of our mid and long-term pipeline target work relates to addressing the challenge of extending environmental stability both within the gut of target insects and on the leaves of sprayed plants.
Another perceived limitation of dsRNA is associated with its highly specific nature. While we believe that this specificity is a benefit because it can make the technology safer for beneficial insects and humans, we realize most products on the market are broad-spectrum, which is appealing to farmers because they enable farmers to control multiple pests or diseases at once. Understanding this need, we are also now working to develop and include in our pipeline, multi-target products as described above.
Finally, delivering dsRNA to the insects targeted for control is one of the most significant challenges in using dsRNA as a pesticide since each insect and insect habitat represent unique challenges. Delivery methods can include spray (which we use with CalanthaTM), injection, seed treatment or root uptake. We continue to explore alternative means of delivery.
Biotechnology and agriculture have a complicated history. We know that building trust with stakeholders is critical to ensuring smooth adoption. We seek to educate about dsRNA and the benefits of what it can do. By increasing awareness of the benefits of RNA biopesticides, we hope to form strong relationships with other sustainability-oriented initiatives and industry stakeholders who can help tell our story.
HUMAN CAPITAL RESOURCES
Our people and culture
At GreenLight, we celebrate the power of working together to address humanity’s challenges, meet the needs of underserved populations, and push the boundaries of scientific discovery. Our culture represents a team united by a common purpose of creating a more sustainable future by bringing food security, medicine, and healthcare to everyone. From the very beginning, our founders believed that our way forward would be based on equality, diversity, and inclusion (ED&I). These founding principles guide us every day as we seek to identify, attract, retain, incentivize, and develop a highly talented workforce.
Qualified team
Building a platform through RNA manufacturing to address food and agriculture markets and human health markets in vaccines and therapies requires deep technical and scientific expertise. We make every effort to recruit and retain the most qualified and mission-oriented team members. As of March 15, 2023, we have 262 full-time employees. Within our workforce, the substantial majority of our employees are engaged in research and development, supply chain and manufacturing operations and the remainder are engaged in the shared business-enabling functions. About 54% of our team members who are focused on research and development have masters degrees or higher, a majority of whom have PhDs. Our employees are not represented by any labor union nor any collective-bargaining arrangement with respect to their employment with us.
In addition to our regular workforce, we are grateful for the collaboration, contributions, and support of a network of industry advisors, consultants, contractors, and temporary staff who make up the overall GreenLight team.
In October 2022, we announced a corporate realignment to focus on key anticipated near-term value drivers and extend the Company's cash runway. With the realignment, the Company is seeking to improve its organizational structure through certain team integrations that are expected to allow the Company to more efficiently support its research, development and commercialization goals.
With ED&I principles as the foundation, we are focused on cultivating a team with diverse backgrounds and perspectives. We consider how we can better serve our colleagues of different genders, ethnicities, generations, educational achievements, sexual orientations, workstyles, and more. Our current senior management team is diverse: 60% of our executive management team members are female as of March 2023. Our management team is committed to continuing to build a diverse team and a culture of inclusion to ensure that diverse perspectives thrive.
Numbers alone cannot capture the rich diversity of our company. However, we collect and report these numbers for transparency and as a marker of our continued efforts. As of March 15, 2023, 47% of our full-time employees self-identify as female and 45% of full-time employees self-identify as a non-Caucasian racial or ethnic group (Black or African American, Hispanic or Latino, American Indian or Alaska Native, Asian or Native Hawaiian, other Pacific Islander, or two or more races). While we acknowledge that there is still work to be done, we are committed to doing our part to make real changes to address systemic bias and inequities.
Environmental, Social, and Governance (ESG) Strategy
Environmental and social impact is inherent to our purpose and the underlying reason our company was launched. We were founded to develop sustainable products for some of the biggest issues facing humanity and the planet. GreenLight scientists are developing new products for public health challenges and sustainable food production to feed a growing population. We believe our ESG strategy is fundamental to achieving our mission and underscores everything we do at GreenLight.
We are striving to optimize the environmental impact of our facilities and operations, but we recognize the greatest potential for impact is through our product development process and in our goal to design and manufacture RNA-based products to support human, animal and plant health more naturally and safely. Furthermore, we believe that our technology platform could be used to enable low- and middle-income countries and underserved populations to have access to potential human health and plant health solutions that are currently difficult to obtain.
Environmental
There is a need to take immediate action to address the environmental crisis that is forcing the reconsideration of how products are made, from our homes to our food, to our clothing. Many modern approaches to produce food and drugs to keep the growing population healthy have had a negative effect on the health of the planet. Clear cutting forests for crops, chemical residues on food, in the water and in the soil, nitrogen blooms in rivers, declining soil productivity, the loss of bees and other beneficial insects-these are all clear signs that the current system is not sustainable.
For years, farmers have used effective petroleum-based chemical pesticides in the form of neonicotinoids, pyrethroids, carbamates, and organophosphates. Over time, these non-targeted products can have unintended negative consequences, including damage to beneficial insects and plants, and they can linger in the environment for years, eroding soil quality and polluting water resources.
Using RNA, we can create targeted biocontrols for agriculture. Biology also offers a fundamental shift in how things are made and disposed of in a world where things grow and decay, creating circular, regenerative processes. Our goal is to have products that can help the environment, not harm it. GreenLight’s RNA is produced from materials using an enzymatic process and after application our RNA product candidates disappear in a few days. We believe that, because the active RNA ingredients in our product candidates quickly degrade in the environment, our product candidates will have the potential to be more sustainable, or greener, than traditional petroleum-based chemical pesticides.
We aim to provide farmers with safe-to-use, cost-effective, targeted biocontrols that stop pests while protecting crops, honeybees, and land before and after harvest. If we help farmers create greener, cleaner crops, they can provide consumers with the greener, cleaner foods they demand. Additionally, we also intend to provide farmers with safer products to handle, while helping farming families promote more sustainable land for future generations.
When we refer to a product or process as ‘green’ in the context of potential agricultural products, we are referring to the fact that dsRNA-based pesticides have the potential to leave little to no residue behind after use, resulting in a significant potential reduction in the toxins or other foreign matter released into local waterways, aquifers, or the food chain. Additionally, when we use the term ‘sustainable,’ we refer to our efforts to align economic development with environmental protection and human well-being as well as our obligations as a Public Benefit Corporation under § 362(a) of the Delaware General Corporation Law.
Social
Values and biases can be embedded in the technologies that are made, in the applications that are considered, and in the ways problems are addressed. Inclusion of those who have historically been left out of the development of new technologies is essential to building equitable and positive outcomes. GreenLight was born from a passion to make our world more sustainable and more equitable. Our vision is to enable Africa, Asia, Latin America, and other LMICs to meet local demand of RNA based products through local production.
An ecosystem thrives with more diversity, and the inclusion of many different voices is essential to growing our company. Team members are empowered to bring their best ideas forward, and leaders are always open to listen and act. We challenge one another to discover breakthroughs that advance our science to deliver on a common cause: sustaining the planet, protecting our food, saving lives. With equity, diversity, and inclusion principles as the foundation, we are relentlessly focused on cultivating a team with diverse backgrounds and perspectives. We are always thinking about how we can better serve our colleagues of different genders, ethnicities, generations, educational achievement, sexual orientation, and workstyles. These values and initiatives are not just a top-down corporate statement; they are an intrinsic part of our culture.
Governance
At GreenLight, we celebrate the power of working together to address humanity’s challenges, meet the needs of underserved populations, and push the boundaries of scientific discovery. Our culture represents a team united by a common purpose of creating a more sustainable future by bringing food security, medicine, and healthcare to everyone. From the very beginning, our founders believed that our way forward would be based on equality, diversity, and inclusion (ED&I). These founding principles guide us every day as we identify, attract, retain, incentivize, and develop a highly talented workforce.
The following values are deeply coded within our business, mission, and culture:
•Care for everyone
•Courage to achieve the impossible
•Collaboration to propel our success
•Commitment to science and doing the right thing, always
Our culture is built on care, transparency, diversity, employee ownership and engagement, and a deep, humble respect for science. Transparency is essential to how we operate, to enable sharing of the insights and tools that enable our platform to grow, as well as to build trust and accountability with all our stakeholders.
We have selected independent directors and scientific advisory board members with decades of experience. Our board of directors and management team will leverage that experience and consider the interests of stockholders, customers, employees, suppliers, academic researchers, governments, communities, and other stakeholders to pursue long-term value for our company and drive the sustained health of our global community.
Competition
We are aware of only one large company, Bayer AG, that has human health and agricultural capabilities similar to our company. Other competitors split into either human health or agricultural market categories.
Human health
Our competitors are biotechnology companies working on indications similar to our pipeline, mRNA companies, large pharmaceutical companies, and academia.
We are aware of several large pharmaceutical and biotechnology companies, as well as smaller, early-stage companies, pursuing the development of products and disease indications we are targeting. These include major vaccine and therapeutics companies such as Roche Holding AG, AbbVie, GlaxoSmithKline (GSK), Merck & Co Inc, Sanofi, Pfizer, AstraZeneca, Johnson & Johnson, and Novavax.
Among RNA specialist companies, BioNTech and Moderna already have COVID-19 vaccines on the market, while CureVac N.V., Arcturus Therapeutics Inc., Daiichi Sankyo, Elixirgen Therapeutics, and Providence Therapeutics have clinical trials underway. Specialized therapeutics companies such as Alnylam Pharmaceuticals, Editas Medicine, and Dicerna Pharmaceuticals also compete against GreenLight. In the personalized cancer vaccine space, a number of companies have clinical stage candidates, such as Moderna, BioNTech, Gritstone, Evaxion, Nykode, StemiRNA, Nouscom and Geneos.
Agriculture
We believe that our technology platform coupled with our research and development expertise and commercial strategy set us apart from others in the food and agricultural market. Because crop protection is a mature industry, there are several companies targeting similar insects and fungi and investing in effective products. These include larger companies such as Syngenta and Bayer, as well as smaller companies such as Provivi, Vestaron, and Biotalys. Creating the sustainable food system we know is possible will require the expertise and dedication of many people bringing many new products to market. We look forward to collaborating with many companies, even those we have called out as competitors, to achieve that future.
Platform
Our platform, and our ability to manufacture biological molecules, is a key competitive advantage and driver of future growth. Ginkgo Bioworks, and Codexis, among others, have sophisticated know-how and may emerge as competitors.
Facilities
Our principal facilities are located in the metropolitan area of Boston, Massachusetts, Rochester, New York, and Durham, North Carolina. We lease all our facilities.
Our corporate headquarters is located in Lexington, Massachusetts, where we lease approximately 59,000 square feet of office and laboratory space. Our lease for this facility expires in June 2032.
We believe our facilities are adequate and suitable for our current needs. To support future organic growth or merger-and-acquisition activity, we may enter into new leases, assume lease obligations, or acquire property both domestically and internationally. We believe that suitable or alternative space will be available if and when needed.
Agricultural Manufacturing Facilities
Our manufacturing facilities for our dsRNA agricultural products are located in Rochester, New York. Our lease for this facility commenced in January 2020 and expires in March 2026. Our existing manufacturing operations occupy approximately 24,000 square feet and include two 2,000-liter bioreactors, one of which has been operational since second quarter of 2021 and the other of which has been installed and we expect to be operational in the second quarter of 2023. Activation of the second bioreactor and additional associated packaging equipment requires an estimated investment of approximately $1.4 million, of which $0.3 million had been committed as of December 31, 2022. As of December 31, 2022, we leased approximately 5,000 square feet of additional space in the Rochester facility for storage.
Agricultural Laboratory and Greenhouse
We currently lease approximately 63,000 square feet of laboratory, office and greenhouse space for our agricultural operations at our facility in Durham, North Carolina. Our lease for this facility commenced in January 2022 and expires in December 2033.
In March 2022, the Company entered into a lease for land in Spain to enable agricultural research and development activities. The lease term expires in March 2042.
In December 2022, the Company entered into a lease for land in Colusa County, California to enable it to conduct certain agricultural research and development activities. The lease term expires in December 2032.
Human Health Facilities
In March 2022, we leased approximately 59,000 square feet in Lexington, Massachusetts for research and development activities, including clean rooms for early-phase clinical material manufacturing for our human health program. Our lease for this facility commenced in May 2022 and expires in 2032. We plan to establish our ability to produce GMP clinical trial material in Lexington in the second half of 2023.
We currently have approximately 69,000 square feet of office and lab space in Medford, Massachusetts and Woburn, Massachusetts. Approximately 52,000 square feet of office and lab space has a lease expiry of February 2024. The remaining 17,000 square feet of office and lab space in Medford has a lease expiry of February 2025. GreenLight is actively marketing to sublease approximately 55,000 of the lab and office space between these two locations.
Intellectual property
We strive to protect and enhance proprietary technology, inventions, and improvements that are commercially important to the development of our business, including seeking, maintaining, and defending patent rights, whether developed internally or licensed from third parties. We also rely on trade secrets to develop, strengthen, and maintain proprietary positions that may be important for the development of our business. We additionally may rely on regulatory protection afforded through data exclusivity, market exclusivity, and patent-term extensions, where available.
Our commercial success may depend in part on our ability to: obtain and maintain patent and other proprietary protection for commercially important technology, inventions and know-how related to our business; defend and enforce our patents and patent applications; preserve the confidentiality of our trade secrets; maintain and defend our trademark registrations and applications; and operate without infringing the valid, enforceable patents and other intellectual property and proprietary rights of third parties. Our ability to limit third parties from making, using, selling, offering to sell, or importing our products or using our proprietary methods may depend on the extent to which we have rights under valid and enforceable licenses, patents, trademarks or trade secrets that cover these activities. We cannot be sure that patents will be granted with respect to any of our pending patent applications or with respect to any patent applications filed by us in the future, nor can we be sure that any of our existing patents or any patents that may be granted to us in the future will be commercially useful in protecting our commercial products or methods of manufacturing and using the same or that they will prevent others from commercializing competing products or technology.
Patents
As of March 10, 2023, we had approximately 40 patent families (the term “patent family” is used here to denote patents and applications claiming priority to a common patent application) in various fields of our business. Of those patent families, approximately six families relate to RNA production; approximately seven families relate to other human health-related technologies; approximately 18 families relate to crop protection and bee health; approximately three families relate to production of sugars; and approximately six families relate to process control and compound production. The number of families may change if we file additional applications or obtain additional issued patents or if we abandon any of our pending or issued patents. We continue to evaluate the costs and potential benefits of patent protection in various jurisdictions. In connection with such evaluations, we may abandon pending applications or issued patents.
Individual patent terms extend for varying periods of time, depending on the date of filing of the patent application, the date of patent issuance, and the legal term of patents in the countries in which they are obtained. In most countries in which patent applications are filed, including the United States, the patent term is 20 years from the date of filing of the first non-provisional application to which priority is claimed. Under certain circumstances, a patent term can be extended. For example, in the United States, a patent’s term may be lengthened by patent term-adjustment, which compensates a patentee for administrative delays by the U.S. Patent and Trademark Office in reviewing and granting a patent; by patent-term extension for certain patents covering products requiring regulatory approval prior to being sold or methods of using or making such products; or may be shortened if a patent is terminally disclaimed over an earlier-filed patent. However, the actual protection afforded by a patent varies on a product-by-product basis, from country to country, and depends on many factors, including the type of patent, the scope of its coverage, the availability of legal remedies in a particular country, and the validity and enforceability of the patent.
Our six RNA production patent families include four families directed to RNA production platforms. All four families, including all of the issued patents in such families, contain claims directed to methods of manufacture of RNA and/or related processes. One platform family includes U.S. Patent No. 10,858,385, the issued claims of which protect certain aspects of our process for production of dsRNA. This family also includes issued patents in Australia and Israel, a pending U.S. continuation and a number of foreign applications pending in Argentina, Australia, Brazil, Canada, Chile, China, Costa Rica, the European Patent Office, Japan, Hong Kong, India, Indonesia, Malaysia, Mexico, New Zealand, Russia, Singapore, South Africa, South Korea, Thailand, and Ukraine. The projected expiration for U.S. Patent No. 10,858,385 is in 2037, not including any term adjustments or extensions if applicable.
Another RNA production platform family also contains claims that protects certain aspects of our processes for production of dsRNA. This family contains U.S. Patent No. 10,954,541 along with a pending U.S. continuation, issued patents in Australia, India, Indonesia, and Japan and a number of foreign applications pending in jurisdictions including Australia, Brazil, Canada, Chile, China, Costa Rica, the European Patent Office, Hong Kong, Israel, Japan, Malaysia, Mexico, New Zealand, South Korea, Singapore, Thailand, and Ukraine. The projected expiration for U.S. Patent No. 10,954,541 is in 2037, not including any term adjustments or extensions if applicable.
The third RNA production platform family contains U.S. Patent No. 11,274,284, along with a pending U.S. continuation, issued patents in China, Indonesia, Israel, Japan and Singapore, and additional foreign applications pending in jurisdictions including the European Patent Office, India and South Korea. The projected expiration date for U.S. Patent No. 11,274,284 is in 2036, not including any term adjustments or extensions if applicable.
The fourth RNA production platform family relates to methods for production of mRNA that may have applicability to our next generation approach for such production. This family contains a United States application along with pending applications in a number of foreign jurisdictions, including, Australia, Canada, China, the European Patent Office, India, Israel, Japan, Korea, Malaysia, Singapore, and South Africa. All applications in this family are national or regional stage applications from International Application No. PCT/US2020/025824. If the U.S. patent application in this family were allowed, the projected expiration of the resultant patent would be in 2040, not including any term adjustments or extensions if applicable.
The RNA production families also contain patent applications directed to various improved compositions and processes. These include two families related to plasmid templates for production of RNA products, proteins and enzymes of interest. One family consists of national and regional stage applications stemming from international application No. PCT/US2021/047111 and the other consists of national and regional stage applications stemming from international application No. PCT/US2020/063490. Both families contain applications pending in the U.S. as well as a number for foreign jurisdictions. If we were to obtain U.S. patents in either family, they would have projected expiration dates in 2040 and 2041, not including any term adjustments or extensions if applicable.
Other Human Health Patent Families
We currently have seven additional human health specific patent families. One family includes a U.S. patent application directed to compositions and methods of treatment related to our ongoing research in the field of gene therapy. This family also includes a number of national and regional stage applications that claim priority to the related International Application No. PCT/US2021/042015, including applications filed with ARIPO and EPO, as well as in Australia, Brazil, Canada, China, India, Israel, Japan, Singapore, and South Korea. If the U.S. patent application were to be allowed, the projected expiration of the resultant patent would be in 2041, not including any term adjustments or extensions if applicable. Another family contains a pending United States provisional patent application related to the same research. Another of the families contains a U.S. application and an international application directed to mRNA compositions, including certain mRNA vaccine designs. One family contains a recently-filed PCT application directed to improved formulations for mRNA vaccines and therapeutics. Another family contains a pending provisional application related to improved formulations for mRNA vaccines and therapeutics. One family contains a pending provisional application related to improved mRNA constructs for vaccines and therapeutics. And the seventh family contains a pending provisional application directed to pan-sarbecovirus mRNA vaccine designs.
Bee Health and Crop Protection Families
Our 16 bee health and crop protection patent families include seven bee health patent families and nine crop protection patent families.
Bee Health Patent Families
Four of our Bee Health patent families contain claims directed to or related to our proposed varroa mite product and/or its use. The first such family is co-owned with Yissum Research and Development Company of the Hebrew University of Jerusalem LTD ("Yissum") and subject to an exclusive license to us of Yissum’s ownership interest in commercial rights to this patent family. For more information on this license, see “-Intellectual Property Agreements-Bayer Acquisition Agreement.” This family consists of U.S. Patent Nos. 8,962,584, 9,662,348, and 10,801,028, which contain composition and method of treatment claims expected to expire in 2030, not including any term adjustments or extensions if applicable. This family further includes issued patents in China, France, Germany, Israel, Italy, Mexico, New Zealand, Russia, South Africa, Turkey, the United Kingdom, and Ukraine and pending patent applications in Canada, Chile, China, and Mexico.
Another such Bee Health patent family is co-owned with the United States Department of Agriculture. This family consist of U.S. Patents Nos. 10,100,306, 10,927,374, and 9,540,642 with composition and method of treatment claims expected to expire in 2034, not including any term adjustments or extensions if applicable. The family further includes a pending U.S. continuation; issued patents in Australia, Israel, India, Russia, Ukraine, and South Africa; and pending applications in Australia, Argentina, Canada, Chile, China, European Patent Office, Mexico, New Zealand, and Uruguay.
The third such Bee Health patent family includes U.S. Patent No. 10,907,152, which has composition and method of treatment claims and is expected to expire in 2036, not including any term adjustments or extensions if applicable. This family further comprises a pending U.S. continuation; foreign patents in China, Israel, and South Africa; and 12 pending foreign applications in jurisdictions including Argentina, Australia, Brazil, Canada, Chile, European Patent Office, India, Mexico, New Zealand, Russia, Ukraine and Uruguay.
The fourth such Bee Health patent family contains a pending U.S. application, Serial No. 17/013,330 along with pending applications in Australia and New Zealand. If claims of the U.S. application were to be allowed, the resultant patent would have a projected expiration in 2040, not including any term adjustments or extensions if applicable.
Crop Protection Patent Families
We have eleven Crop Protection patent families. Three such families relate to nucleic acid compositions for control of Colorado potato beetle. One of those three families includes U.S. Patent No. 11,142,768 (expected to expire in 2039, not including any term adjustments or extensions if applicable) with composition claims directed to CalanthaTM, our proposed Colorado potato beetle product, along with two pending related U.S. applications, and pending foreign patent applications in Australia, Brazil, Canada, China, European Patent Office, India, Japan, New Zealand, Russia, and Ukraine. Another of those three Colorado potato beetle patent families contains U.S. Patent No. 11,185,079, which has composition claims and an expected expiration in 2039 (not including any term adjustments or extensions if applicable), and additional pending United States and European Patent Office applications.. The third such family has one pending U.S. patent application.
Our eight additional Crop Protection patent families include: one family containing pending applications in the United States, China, and Japan, directed to compositions for controlling lepidopteran pests; two families, each of which has a pending U.S. patent application and an international patent application directed to compositions for control of fungi; a U.S. application and an international application directed to compositions for improved dsRNA stability; three provisional applications directed to compositions for controlling fungi; and an application, co-owned with the University of Massachusetts, directed to compositions and methods of controlling insect pests using biocapsules
.
Sugar Platform Patent Families
We have three patent families related to enzymatic production of sugars. One family consists of issued U.S. Patent Nos. 10,316,342, 10,577,635, and 10,704,067, all of which contain method of production claims and are expected to expire in 2038, not including any term adjustments or extensions if applicable. That family also consists of a pending U.S. continuation and foreign applications in Australia, Brazil, Canada, China, Colombia, European Patent Office, Hong Kong, India, Indonesia, Japan, Mexico, Russia, South Korea, and Thailand.
A second sugar platform family comprises United States and pending foreign applications in a number of jurisdictions filed as national and regional stage entries of International Application No. PCT/US2019/067113. If the U.S. patent application in this family were to be allowed, the resultant patent claims would have a projected expiration in 2039, not including any patent term adjustments or extensions if applicable.
Our third family consists of a pending international patent application directed to improved compositions useful for production of sugars.
Trade secrets
GreenLight’s technology-related intellectual property that are not patent-protected are maintained as confidential information and trade secrets. We employ a variety of safeguards to protect our confidential information and trade secrets, including contractual arrangements that impose obligations of confidentiality and security, digital security measures, and physical security precautions.
With respect to contractual arrangements, we protect our confidential and proprietary information by requiring our employees to execute nondisclosure and assignment of invention agreements upon commencement of their employment. Agreements with our employees also bar them from using the proprietary rights of third parties in the course of their employment or disclosing to us any confidential information of third parties.
We require confidentiality and material transfer agreements from third parties that receive our confidential data or materials, and we also incorporate confidentiality and material transfer precautions into our research and collaboration agreements.
We also seek to preserve the integrity and confidentiality of our data and trade secrets by maintaining physical security of our premises and physical and electronic security of our information technology systems
Trademark and domain names
GreenLight owns four U.S. trademark applications relating to the GreenLight name and logo and the CalanthaTM brand in the United States and other jurisdictions around the world. We are still evaluating whether we want to release some or all of our products under the GreenLight brand, or whether we want to develop new brands applicable to specific product pipelines. We also have a registered domain name for our website found at www.greenlightbiosciences.com.
Intellectual Property Agreements
Bayer Acquisition Agreement
We entered into an Assignment and License Agreement with Bayer CropScience LLP (“Bayer”) dated December 10, 2020 (the “Bayer Acquisition Agreement”), pursuant to which we acquired from Bayer certain intellectual property rights related to (i) RNA technology used to control Varroa mites, Nosema, and bee viruses, which includes assignments of patents and a license to research, develop and sell methods and products in such field with the use of Bayer “know-how” with respect to such technology, and the assignment of Bayer’s rights under a license agreement with Yissum Research and Development Company of the Hebrew University of Jerusalem LTD (the “Yissum License”), and (ii) technology used to control the Colorado potato beetle and canola flea beetle, including a license to research, develop and sell methods and products in such field with the use of Bayer patents and “know-how” with respect to such technology. Under the Bayer Acquisition Agreement, we were obligated to make a closing payment to Bayer equal to $2,000,000 as well as certain milestone payments equal to up to $2,000,000 in the aggregate, in the event that certain regulatory approvals are achieved with respect to the aforementioned technologies.
We also agreed to indemnify Bayer against losses arising out of GreenLight’s recklessness, willful misconduct, violation of law or breaches of representations or warranties under the Bayer Acquisition Agreement or activities related to the use of intellectual property assigned to GreenLight thereunder. The Bayer Acquisition Agreement shall survive for so long as the assigned patents remain in effect; provided, that the parties do not terminate the Bayer Acquisition Agreement earlier in accordance with its terms.
Under the Bayer Acquisition Agreement, GreenLight was assigned Bayer’s rights and obligations under the Yissum License. Pursuant to the Yissum License, we were granted an exclusive, worldwide license to make use of the relevant technology to develop, manufacture, market, distribute, or sell covered products, including an exclusive, worldwide license under Yissum’s interest in any bee health patents jointly owned with GreenLight. Notwithstanding the exclusive license, Yissum retains the right to practice the jointly-owned patents in ways that will not result in competition with GreenLight, including the right of the Hebrew University of Israel (the “University”) to practice the inventions for the University’s own internal research and educational purposes, and to license other academic and not-for-profit research organizations to do the same, provided that no such license directly or indirectly harms our commercial interest in the relevant patents and products.
We also have the right, but not the obligation, to prosecute in our own name and at our own expense any infringement of patents jointly owned with Yissum, but in making our decision whether to assert infringement, we must give consideration to the views of Yissum. In order to settle any such infringement suit, we must obtain the consent of Yissum.
Pursuant to the Yissum License, we agreed to pay Yissum a running royalty percentage in the low single digits on net sales of the licensed products. The License ends on a country-by-country basis upon the later of the date of expiration of the last valid licensed patent, the end of regulatory exclusivity for a product, or 20 years from the date of first sale.
Pursuant to the Yissum License, we are liable for any loss, injury or damage whatsoever caused to our employees or to any person acting on our behalf or to the employees of Yissum or to any person acting on our behalf or to any third party, by reason of GreenLight’s acts or omissions pursuant to the Yissum License or by reason of any use made by GreenLight of the licensed technology and products. Moreover, we will compensate, indemnify, defend, and hold harmless Yissum or any person acting on its behalf or any of its employees or the University or representatives of the University against any liability imposed upon them by GreenLight’s acts or omissions or which derive from GreenLight’s use, development, manufacture, marketing, sale or sublicensing of any product or licensed technology unless it has been determined by an adjudicator of last resort that that the particular damage, loss or expense was caused by a particular indemnitee’s gross negligence or willful misconduct.
Either party may terminate the Yissum License upon written notice in the event of a bankruptcy or similar proceeding of the other party. Yissum may terminate the license agreement if we do not commercialize products within a reasonable timeframe, with certain exceptions, if it provides written notice and we do not cure such failure within a certain timeframe; or if we have an uncured lapse in necessary insurance coverage; or if we unreasonably fail to respond to third-party claims against the patents or technology licensed under the Yissum License.
Patent expiration is a legal determination under the laws of each relevant jurisdiction worldwide. Third parties may review public patent filings and make their own determination as to patent expiration based on the available documents. The last to expire U.S. Patent under the Yissum License is expected to expire in 2031.
Bill & Melinda Gates Foundation
We entered into a Grant Agreement with the Bill and Melinda Gates Foundation (the “Gates Foundation”) dated July 20, 2020, as amended by that certain Amendment 1 to Grant Agreement dated May 25, 2021 (as amended, the “Gates Grant”) pursuant to which we were awarded a grant in the amount of approximately $3.3 million, payable in milestone tranches, for research regarding treatment and curative therapies for sickle cell disease and/or durable suppression of HIV in developing countries. We utilize the Gates Grant funds to explore new, low cost capabilities for the in vivo functional cure of sickle cell disease as well as the durable suppression of HIV. In the event that GreenLight has materially breached the Grant Agreement, the Foundation may demand repayment of the Gates Grant funds. As previously announced, we paused work on our gene therapy program for sickle cell disease, and as a result, we ceased any ongoing research work under the Gates Grant and are in the process of closing out all related activities. We are in the process of delivering the final report to the Gates Foundation and returning any remaining unused funds to the Gates Foundation.
Acuitas Therapeutics
Development & Option Agreement
In August 2020, we and Acuitas entered into a development and option agreement, or the Acuitas Option Agreement. Under the Acuitas Option Agreement, the parties agreed to jointly develop certain products combining our RNA constructs with Acuitas’s LNPs. Each party granted the other party a worldwide, non-exclusive, royalty-free license under its proprietary technology to conduct the joint research. We pay Acuitas’s personnel costs and external expenses incurred in performing research in accordance with a work plan under the Acuitas Option Agreement. Under the Acuitas Option Agreement, Acuitas granted us options to obtain non-exclusive, worldwide, sublicensable licenses under Acuitas’s patent rights and know-how related to LNP technology, or Acuitas LNP Technology, with respect to three specified targets, or Reserved Targets, to develop and commercialize one or more therapeutic products incorporating Acuitas LNP Technology and our RNA constructs. We paid Acuitas a technology access fee of $750,000 at the outset of the Option Agreement. Thereafter, we are obligated to pay an annual technology maintenance fee of $250,000 for each option that has not been exercised and target reservation and maintenance fees of $100,000 per Reserved Target until such Reserved Target is removed from the Reserved Target list or until we exercise an option with respect to such Reserved Target.
On exercise of the first option, we were required to pay a $1.5 million option exercise fee after execution of the first non-exclusive license. On exercise of the second and third options, we are required to pay a $1.75 million and $2.75 million option exercise fee after execution of the second and third non-exclusive licenses, respectively.
Unless earlier terminated, the Acuitas Option Agreement will remain in effect until the first to occur of (1) all options are exercised, and (2) three years from the effective date, except that we can choose to extend the three-year term for an additional two years. Either party may terminate the Acuitas Option Agreement for an uncured material breach of the other party or upon the other party’s bankruptcy or a similar event. We may terminate the Acuitas Option Agreement at our convenience following written notice to Acuitas. To GreenLight’s knowledge, the last to expire U.S. patent under the Acuitas Option Agreement will expire in 2041 if the last filed relevant U.S. patent application currently identified by Acuitas is allowed. However, additional intellectual property, including patents, may still be added to the Acuitas Option Agreement or may not be known to us. Therefore the last to expire patent under that Option Agreement may change. Moreover, patent expiration is a legal determination under the laws of each relevant jurisdiction worldwide. Third parties may review public patent filings and make their own determination as to patent expiration based on the available documents.
Any jointly developed intellectual property under the Acuitas Option Agreement is jointly owned by the parties in an undivided one-half interest to such joint intellectual property.
Non-Exclusive License Agreement
In January 2021, we exercised the first option under the Acuitas Option Agreement and entered into a non-exclusive license agreement with Acuitas, or the Acuitas License Agreement. Acuitas granted us a non-exclusive, worldwide, sublicensable license under the Acuitas LNP Technology to research, develop, manufacture, and commercially exploit a vaccine product consisting of our RNA constructs and Acuitas’s LNPs. We paid Acuitas an option exercise fee of $1.5 million. Under the Acuitas License Agreement, we are required to pay Acuitas an annual license maintenance fee of $1 million until we achieve a particular development milestone. Acuitas is entitled to receive potential clinical, regulatory, and commercial milestone payments of up to $17.25 million in the aggregate. With respect to the sale of each licensed product by us, our affiliates or our sublicensees, Acuitas is entitled to receive low single digit percentage royalties on net sales of the licensed product in a given country until the last to occur, in such country, of (i) the expiration of all licensed patent rights covering the licensed product, (ii) expiration of any regulatory exclusivity for the licensed product, or (iii) ten years from the first commercial sale of the licensed product, or Royalty Terms. We are entitled to certain royalty reductions and offsets with respect to each licensed product in a given country if no licensed patents cover the licensed product or if we are required to obtain rights to third party patents that relate to LNP technology. Unless earlier terminated, the Acuitas License Agreement will remain in effect until the expiration of the last-to-expire Royalty Term. Either party may terminate the Acuitas License Agreement for an uncured material breach of the other party or upon the other party’s bankruptcy or a similar event. We may terminate the Acuitas License Agreement at our convenience following written notice to Acuitas.
Additional intellectual property, including patents, may still be added to the Acuitas License Agreement or may not be known to us. Therefore the last to expire patent under that License Agreement may change. Moreover, patent expiration is a legal determination under the laws of each relevant jurisdiction worldwide. Third parties may review public patent filings and make their own determination as to patent expiration based on the available documents. To GreenLight’s knowledge the last to expire U.S. patent under the Acuitas License Agreement will expire in 2041 if the last filed relevant U.S. patent application currently identified by Acuitas is allowed.
Serum Institute License Agreement
GreenLight entered into a License Agreement dated as of March 10, 2022 with Serum Institute of India Private Limited (“SIIPL”), pursuant to which GreenLight granted SIIPL an exclusive, sub-licensable, royalty-bearing license to use GreenLight’s proprietary technology platform to develop, manufacture and commercialize up to three mRNA products in all territories other than the United States, the 27 member states of the European Union, the United Kingdom, Australia, Japan, New Zealand, Canada, South Korea, China, Hong Kong, Macau, and Taiwan (the “SIIPL Territory”). The first licensed product target will be a shingles product, and SIIPL has an option to add up to two additional product targets through the end of 2024.
Pursuant to the SIIPL License Agreement, SIIPL agreed to pay GreenLight an upfront license fee of $5.0 million, as well as payments upon target selection and reservation of exclusivity. In addition, GreenLight may receive up to a total of an additional $17.0 million in milestone payments across all three product targets, as well as manufacturing technology transfer payments up to $10.0 million. SIIPL agreed to make royalty payments on the sale of products resulting from the licensed technology for the term of the SIIPL License Agreement. The SIIPL License Agreement shall terminate on a product-by-product and country-by-country
basis on the later of the expiration of the patent rights owned by GreenLight or the tenth anniversary of the first commercial sale of the applicable product(s) in the applicable country.
SIIPL is responsible for the development, formulation, filling and finishing, registration and commercialization of the products in the SIIPL Territory, subject to oversight from a joint steering committee composed of representatives of GreenLight and SIIPL. SIIPL agreed to use commercially reasonable efforts to develop and obtain regulatory approval for the products in the countries in the SIIPL Territory. The SIIPL License Agreement includes terms customary in the industry for provisions related to sublicensing, intellectual property, and termination, and customary representations and warranties of GreenLight and SIIPL, along with certain customary covenants, including confidentiality, limitation of liability and indemnity provisions.
EpiVax Therapeutics Collaboration Agreement
On January 8, 2023, GreenLight entered into a Collaboration and License Agreement with EpiVax Therapeutics, Inc. (“EVT”), pursuant to which GreenLight granted EVT an exclusive, royalty-free sublicensable license to use GreenLight’s proprietary technology platform and EVT granted GreenLight an exclusive, royalty-free sublicensable license to use EVT’s proprietary immunoinformatics tools, in each case, to develop, manufacture and commercialize mRNA-based oncological vaccines (whether therapeutic, prophylactic or otherwise) in all territories worldwide. Furthermore, GreenLight and EVT each agreed to exclusively develop, manufacture, commercialize and collaborate with each other on mRNA-based pharmaceutical preparation, substance, formulation or dosage (whether singly or in combination with any other product, materials, or technology) that uses the GreenLight technology and the EVT technology for the treatment of diseases through mRNA-based oncological vaccines. The initial indication for the first potential product candidate will target bladder cancer. GreenLight, at its option, will be the sole manufacturer for such jointly developed products under the Collaboration Agreement.
Pursuant to the Collaboration Agreement, GreenLight and EVT will initially bear their own costs of development until achievement of certain agreed upon events, and thereafter, each of GreenLight and EVT will bear fifty percent (50%) of all development costs. Furthermore, beginning on the first commercial sale of a product, the parties will share in the pre-tax profit (loss) from commercialization of products under the Collaboration Agreement with each of GreenLight and EVT bearing (and entitled to) fifty percent (50%) of the pre-tax profit (loss) for such products.
After one-hundred eighty (180) days from the effective date of the Collaboration Agreement, either party may terminate the Collaboration Agreement with fifteen (15) days’ prior notice. The Collaboration Agreement includes terms customary in the industry for provisions related to sublicensing, intellectual property, and termination, and customary representations and warranties of GreenLight and EVT, along with certain customary covenants, including confidentiality, limitation of liability and indemnity provisions.
Government regulation
We are using our RNA manufacturing platform to develop products for human health and agriculture, and we are subject to laws and regulations for those markets. These regulations currently apply to development and testing of our products and in the future will apply to manufacturing, import, export, marketing, and sale of products.
Human health products
We are developing human health products that include vaccines for COVID-19, shingles and oncology. In the United States, the FDA regulates drugs under the Federal Food, Drug, and Cosmetic Act (“FDCA”) and biologics under the Public Health Service Act (“PHSA”). Both drugs and biologics also are subject to other federal, state, and local statutes and regulations. The FDA and other regulatory authorities at federal, state, and local levels, as well as in foreign countries, extensively regulate, among other things, the research, development, testing, manufacture, quality control, import, export, safety, effectiveness, labeling, packaging, storage, distribution, record keeping, approval, advertising, promotion, marketing, post-approval monitoring, and post-approval reporting of drugs and biologics. We, along with third-party contractors, will be required to navigate the various preclinical, clinical and commercial approval requirements of the governing regulatory agencies of the countries in which we wish to conduct studies or seek approval or licensure of our product candidates. The process of obtaining regulatory approvals and the subsequent compliance with applicable federal, state, local and foreign statutes and regulations require the expenditure of substantial time and financial resources.
U.S. biologics regulation
In the United States, biological products such as gene therapies and vaccines are subject to regulation under the Federal FDCA, the PHSA, and other federal, state, local and foreign statutes and regulations. The process required by the FDA before biologics may be marketed in the United States generally involves the following:
•completion of preclinical laboratory tests and animal studies performed in accordance with the FDA’s Good Laboratory Practice requirements (“GLPs”);
•submission to the FDA of an investigational new drug application (“IND”), which must become effective before clinical trials may begin;
•approval by an institutional review board (“IRB”) or ethics committee at each clinical site before the trial is commenced;
•performance of adequate and well-controlled human clinical trials to establish the safety, purity and potency of the proposed biologic product candidate for its intended purpose;
•preparation of and submission to the FDA of a biologics license application (“BLA”), after completion of all pivotal clinical trials;
•satisfactory completion of an FDA Advisory Committee review, if applicable;
•a determination by the FDA within 60 days of its receipt of a BLA to file the application for review;
•satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities at which the proposed product is produced to assess compliance with cGMP, and to assure that the facilities, methods and controls are adequate to preserve the biological product’s continued safety, purity and potency, and of selected clinical investigation sites to assess compliance with Good Clinical Practices (“GCPs”); and
•FDA review and approval of the BLA to permit commercial marketing of the product for particular indications for use in the United States.
Prior to beginning the first clinical trial with a product candidate in the United States, we must submit an IND to the FDA. An IND is a request for authorization from the FDA to administer an investigational new drug to humans. The central focus of an IND submission is on the general investigational plan and the protocol(s) for clinical studies. The IND also includes results of animal and in vitro studies assessing the toxicology, pharmacokinetics, pharmacology, and pharmacodynamic characteristics of the product; chemistry, manufacturing, and controls information; and any available human data or literature to support the use of the investigational product. An IND must become effective before human clinical trials may begin. The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day time period, raises safety concerns or questions about the proposed clinical trial. In such a case, the IND may be placed on clinical hold and the IND sponsor and the FDA must resolve any outstanding concerns or questions before the clinical trial can begin. Submission of an IND therefore may or may not result in FDA authorization to begin a clinical trial.
Clinical trials involve the administration of the investigational product to human subjects under the supervision of qualified investigators in accordance with GCPs, which include the requirement that all research subjects provide their informed consent for their participation in any clinical study. Clinical trials are conducted under protocols detailing, among other things, the objectives of the study, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated. A separate submission to the existing IND must be made for each successive clinical trial conducted during product development and for any subsequent protocol amendments. Furthermore, an independent IRB for each site proposing to conduct the clinical trial must typically review and approve the plan for any clinical trial and its informed consent form before the clinical trial begins at that site, and must monitor the study until completed. Regulatory authorities, the IRB or the sponsor may suspend a clinical trial at any time on various grounds, including a finding that the subjects are being exposed to an unacceptable health risk or that the trial is unlikely to meet its stated objectives. Some studies also include oversight by an independent group of qualified experts organized by the clinical study sponsor, known as a data safety monitoring board, which provides authorization for whether or not a study may move forward at designated check points based on access to certain data from the study and may halt the clinical trial if it determines that there is an unacceptable safety risk for subjects or other grounds, such as no demonstration of efficacy. There are also requirements governing the reporting of ongoing clinical studies and clinical study results to public registries.
For purposes of BLA approval, human clinical trials are typically conducted in three sequential phases that may overlap or be combined:
•Phase 1-The investigational product is initially introduced into healthy human subjects or patients with the target disease or condition. These studies are designed to test the safety, dosage tolerance, absorption, metabolism and
distribution of the investigational product in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on effectiveness.
•Phase 2-The investigational product is administered to a limited patient population with a specified disease or condition to evaluate the preliminary efficacy, optimal dosages and dosing schedule and to identify possible adverse side effects and safety risks. Multiple Phase 2 clinical trials may be conducted to obtain information prior to beginning larger and more expensive Phase 3 clinical trials.
•Phase 3-The investigational product is administered to an expanded patient population to further evaluate dosage, to provide statistically significant evidence of clinical efficacy and to further test for safety, generally at multiple geographically dispersed clinical trial sites. These clinical trials are intended to establish the overall risk/benefit ratio of the investigational product and to provide an adequate basis for product approval.
In some cases, the FDA may require, or companies may voluntarily pursue, additional clinical trials after a product is approved to gain more information about the product. These so-called Phase 4 studies may also be made a condition to approval of the BLA. Concurrent with clinical trials, companies may complete additional animal studies and develop additional information about the biological characteristics of the product candidate, and must finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements. The manufacturing process must be capable of consistently producing quality batches of the product candidate and, among other things, must develop methods for testing the identity, strength, quality and purity of the final product. Additionally, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.
BLA submission and review by the FDA
Assuming successful completion of all required testing in accordance with all applicable regulatory requirements, the results of product development, nonclinical studies and clinical trials are submitted to the FDA as part of a BLA requesting approval to market the product for one or more indications. The BLA must include all relevant data available from preclinical and clinical studies, including negative or ambiguous results as well as positive findings, together with detailed information relating to the product’s chemistry, manufacturing, controls, and proposed labeling, among other things. Data can come from company-sponsored clinical studies intended to test the safety and effectiveness of a use of the product, or from a number of alternative sources, including studies initiated by independent investigators. The submission of a BLA requires payment of a substantial application user fee to the FDA, unless a waiver or exemption applies.
Within 60 days following submission of the application, the FDA reviews a BLA submitted to determine if it is substantially complete before the FDA accepts it for filing. The FDA may refuse to file any BLA that it deems incomplete or not properly reviewable at the time of submission and may request additional information. In this event, the BLA must be resubmitted with the additional information. Once a BLA has been accepted for filing, the FDA’s goal is to review standard applications within ten months after the filing date, or, if the application qualifies for priority review, six months after the FDA accepts the application for filing. In both standard and priority reviews, the review process may also be extended by FDA requests for additional information or clarification. The FDA reviews a BLA to determine, among other things, whether a product is safe, pure and potent and the facility in which it is manufactured, processed, packed or held meets standards designed to assure the product’s continued safety, purity and potency. The FDA may also convene an advisory committee to provide clinical insight on application review questions. The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.
Before approving a BLA, the FDA will typically inspect the facility or facilities where the product is manufactured. The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP and are adequate to assure consistent production of the product within required specifications. Additionally, before approving a BLA, the FDA will typically inspect one or more clinical sites to assure compliance with GCP. If the FDA determines that the application, manufacturing process or manufacturing facilities are not acceptable, it will outline the deficiencies in the submission and often will request additional testing or information. Notwithstanding the submission of any requested additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval.
After the FDA evaluates a BLA and conducts inspections of manufacturing facilities where the investigational product and/or its drug substance will be produced, the FDA may issue an approval letter or a Complete Response Letter (CRL). An approval letter authorizes commercial marketing of the product with specific prescribing information for specific indications. A CRL will describe all of the deficiencies that the FDA has identified in the BLA, except that where the FDA determines that the data supporting the application are inadequate to support approval, the FDA may issue the CRL without first conducting required
inspections, testing submitted product lots, and/or reviewing proposed labeling. In issuing the CRL, the FDA may recommend actions that the applicant might take to place the BLA in condition for approval, including requests for additional information or clarification. The FDA may delay or refuse approval of a BLA if applicable regulatory criteria are not satisfied, require additional testing or information and/or require post-marketing testing and surveillance to monitor safety or efficacy of a product.
If regulatory approval of a product is granted, such approval will be granted for particular indications and may entail limitations on the indicated uses for which such product may be marketed. For example, the FDA may approve the BLA with a Risk Evaluation and Mitigation Strategy (REMS) to ensure the benefits of the product outweigh its risks. A REMS is a safety strategy implemented to manage a known or potential serious risk associated with a product and to enable patients to have continued access to such medicines by managing their safe use, and could include medication guides, physician communication plans, or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools. The FDA also may condition approval on, among other things, changes to proposed labeling or the development of adequate controls and specifications. Once approved, the FDA may withdraw the product approval if compliance with pre- and post-marketing requirements is not maintained or if problems occur after the product reaches the marketplace. The FDA may require one or more Phase 4 post-market studies and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization, and may limit further marketing of the product based on the results of these post-marketing studies.
Expedited development and review programs
The FDA offers a number of expedited development and review programs for qualifying product candidates. For example, the fast track program is intended to expedite or facilitate the process for reviewing product candidates that are intended to treat a serious or life-threatening disease or condition and demonstrate the potential to address unmet medical needs for the disease or condition. Fast track designation applies to the combination of the product candidate and the specific indication for which it is being studied. The sponsor of a fast track product candidate has opportunities for more frequent interactions with the applicable FDA review team during product development and, once a BLA is submitted, the product candidate may be eligible for priority review. A fast track product candidate may also be eligible for rolling review, where the FDA may consider for review sections of the BLA on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission of the sections of the BLA, the FDA agrees to accept sections of the BLA and determines that the schedule is acceptable, and the sponsor pays any required user fees upon submission of the first section of the BLA.
A product candidate intended to treat a serious or life-threatening disease or condition may also be eligible for breakthrough therapy designation to expedite its development and review. A product candidate can receive breakthrough therapy designation if preliminary clinical evidence indicates that the product candidate, alone or in combination with one or more other drugs or biologics, may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. The designation includes all of the fast track program features, as well as more intensive FDA interaction and guidance beginning as early as Phase 1 and an organizational commitment to expedite the development and review of the product candidate, including involvement of senior managers.
Any marketing application for a drug or biologic submitted to the FDA for approval, including a product candidate with a fast track designation and/or breakthrough therapy designation, may be eligible for other types of FDA programs intended to expedite the FDA review and approval process, such as priority review and accelerated approval. A BLA is eligible for priority review if the product candidate is designed to treat a serious or life-threatening disease or condition, and if approved, would provide a significant improvement in safety or effectiveness compared to available alternatives for such disease or condition. For original BLAs, priority review designation means the FDA’s goal is to take action on the marketing application within six months of the 60-day filing date (as compared to ten months under standard review).
Additionally, product candidates studied for their safety and effectiveness in treating serious or life-threatening diseases or conditions may receive accelerated approval upon a determination that the product candidate has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments. As a condition of accelerated approval, the FDA will generally require the sponsor to perform adequate and well-controlled post-marketing clinical studies to verify and describe the anticipated effect on irreversible morbidity or mortality or other clinical benefit. Products receiving accelerated approval may be subject to expedited withdrawal procedures if the sponsor fails to conduct the required post-marketing studies or if such studies fail to verify the predicted clinical benefit. In addition, the FDA currently requires as a condition for accelerated approval pre-approval of promotional materials, which could adversely impact the timing of the commercial launch of the product.
Fast track designation, breakthrough therapy designation, priority review, and accelerated approval do not change the standards for approval but may expedite the development or approval process. Even if a product candidate qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification or decide that the time-period for FDA review or approval will not be shortened.
Post-approval requirements
Biologics are subject to pervasive and continuing regulation by the FDA, including, among other things, requirements relating to record-keeping, reporting of adverse experiences, periodic reporting, product sampling and distribution, and advertising and promotion of the product. After approval, most changes to the approved product, such as adding new indications or other labeling claims, are subject to prior FDA review and approval. There also are continuing, annual program fees for any marketed products. Biologic manufacturers and their subcontractors are required to register their establishments with the FDA and certain state agencies, and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with cGMP, which impose certain procedural and documentation requirements. Changes to the manufacturing process are strictly regulated, and, depending on the significance of the change, may require prior FDA approval before being implemented. FDA regulations also require investigation and correction of any deviations from cGMP and impose reporting requirements. Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain compliance with cGMP and other aspects of regulatory compliance.
The FDA may withdraw approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market. Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information; imposition of post-market studies or clinical studies to assess new safety risks; or imposition of distribution restrictions or other restrictions under a REMS program. Other potential consequences include, among other things:
•restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls;
•fines, warning letters, or untitled letters;
•clinical holds on clinical studies;
•refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of product license approvals;
•product seizure or detention, or refusal to permit the import or export of products;
•consent decrees, corporate integrity agreements, debarment or exclusion from federal healthcare programs;
•mandated modification of promotional materials and labeling and the issuance of corrective information;
•the issuance of safety alerts, Dear Healthcare Provider letters, press releases and other communications containing warnings or other safety information about the product; or
•injunctions or the imposition of civil or criminal penalties.
The FDA closely regulates the marketing, labeling, advertising and promotion of biologics. A company can make only those claims relating to safety and efficacy, purity and potency that are approved by the FDA and in accordance with the provisions of the approved label. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses. Failure to comply with these requirements can result in, among other things, adverse publicity, warning letters, corrective advertising and potential civil and criminal penalties. Physicians may prescribe legally available products for uses that are not described in the product’s labeling and that differ from those tested and approved by the FDA. Such off-label uses are common across medical specialties. Physicians may believe that such off-label uses are the best treatment for many patients in varied circumstances. The FDA does not regulate the behavior of physicians in their choice of treatments. The FDA does, however, restrict manufacturer’s communications on the subject of off-label use of their products.
Biosimilars and reference product exclusivity
The Affordable Care Act, signed into law in 2010, includes a subtitle called the Biologics Price Competition and Innovation Act, or BPCIA, which created an abbreviated approval pathway for biological products that are biosimilar to or interchangeable with an FDA-licensed reference biological product. The FDA has issued several guidance documents outlining an approach to review and approval of biosimilars.
Biosimilarity, which requires that there be no clinically meaningful differences between the biological product and the reference product in terms of safety, purity, and potency, can be shown through analytical studies, animal studies, and a clinical study or studies. Interchangeability requires that a product is biosimilar to the reference product and the product must demonstrate that it can be expected to produce the same clinical results as the reference product in any given patient and, for products that are administered multiple times to an individual, the biologic and the reference biologic may be alternated or switched after one has been previously administered without increasing safety risks or risks of diminished efficacy relative to exclusive use of the reference biologic. However, complexities associated with the larger, and often more complex, structures of biological products, as well as the processes by which such products are manufactured, pose significant hurdles to implementation of the abbreviated approval pathway that are still being worked out by the FDA.
Under the BPCIA, an application for a biosimilar product may not be submitted to the FDA until four years following the date that the reference product was first licensed by the FDA. In addition, the approval of a biosimilar product may not be made effective by the FDA until 12 years from the date on which the reference product was first licensed. During this 12-year period of exclusivity, another company may still market a competing version of the reference product if the FDA approves a full BLA for the competing product containing that applicant’s own preclinical data and data from adequate and well-controlled clinical trials to demonstrate the safety, purity and potency of its product. The BPCIA also created certain exclusivity periods for biosimilars approved as interchangeable products. At this juncture, it is unclear whether products deemed “interchangeable” by the FDA will, in fact, be readily substituted by pharmacies, which are governed by state pharmacy law.
A biological product can also obtain pediatric market exclusivity in the United States. Pediatric exclusivity, if granted, adds six months to existing exclusivity periods and patent terms. This six-month exclusivity, which runs from the end of other exclusivity protection or patent term, may be granted based on the voluntary completion of a pediatric study in accordance with an FDA-issued “Written Request” for such a study.
Laboratory licensing and certification requirements
We are planning to partner with contract laboratories who are subject to the Clinical Laboratory Improvement Amendments of 1988 (“CLIA”), which requires all clinical laboratories to meet certain quality-assurance, quality-control, and personnel standards.
Agricultural products
We are developing insecticides and fungicides to protect crops and acaricides to protect honeybees that are beneficial to crops. In the United States, the development, testing, and commercialization of these products are regulated by the EPA through the Federal Food, Drug, and Cosmetic Act (“FFDCA”), the Food Quality Protection Act (“FQPA”) and the Federal Insecticide, Fungicide and Rodenticide Act (“FIFRA”).
In general, FIFRA prohibits the sale or distribution of any pesticide, a product category that includes the insecticides, fungicides, and acaricides we are developing, unless that pesticide is registered with the EPA. To register a pesticide with the EPA, the applicant must demonstrate that the product will not cause unreasonable adverse effects on human health or the environment. These adverse effects include any unreasonable risk to man or the environment, taking into account the economic, social, and environmental costs and benefits of the use of the pesticide, as well as any human dietary risk from residues that result from use of the pesticide in or on any food consistent with the FFDCA. In the course of its evaluation of a pesticide, EPA assesses the impact that a pesticide may have on endangered species and non-target organisms.
Because our products contain novel RNA-based active ingredients, there will generally be no previously registered pesticide product containing that active ingredient and, as a result, the use of each of our products will require a new registration under FIFRA and the establishment of a tolerance under Section 408 of the FFDCA or the issuance of a tolerance exemption.
In order for the EPA to register a pesticide:
•the applicant must first conduct specified studies to evaluate mammalian toxicology, toxicological effects to non-target organisms in the environment (ecotoxicological exposures), and the product’s physical and chemical properties;
•the applicant must then submit to the EPA a registration dossier that includes data demonstrating that the product does not pose unreasonable risks;
•the EPA will conduct both scientific and administrative reviews of the dossier, including a thorough evaluation of submitted safety data and completion of risk assessments for human dietary and ecotoxicological exposures;
•if the EPA identifies any risks that appear to exceed regulatory standards or any other deficiencies in the dossier, it will ordinarily issue a letter identifying the deficiencies;
•the applicant will have one or more opportunities to address any deficiencies, including the submission of factors that mitigate any risks identified in the EPA’s risk assessments; this process may involve ongoing submissions and coordination with the EPA to address any unresolved concerns; and
•the EPA will undertake various stages of internal review prior to making a final decision on the application.
The Pesticide Registration Improvement Act, enacted in 1996 and subsequently renewed, can serve to reduce the data requirements and timeline related to regulatory approvals for biopesticides when compared to other pesticides, with EPA approvals typically received within 16 to 24 months, compared with 36 months or longer for conventional chemical pesticides.
As part of the pesticide registration process, the EPA under its FFDCA authority establishes tolerances for pesticide chemicals, which consist of limits on pesticide residues that may remain on feed or feed commodities. In some cases, the EPA may issue a tolerance exemption when the chemical will have no impact on human health.
Even if a FIFRA registration is granted, the EPA has the authority to revoke the registration or impose limitations on the use of any of our pest management products if we do not comply with the regulatory requirements, if unexpected problems occur with a product, or if the EPA receives other newly discovered adverse information.
In addition to the approval by the EPA, we are required to obtain regulatory approval from the appropriate regulatory authorities in individual states and foreign jurisdictions before we can market or sell any pest management product in those jurisdictions. In most U.S. states, local authorizations typically take one to three months after EPA approval. In other states, such as California, Arizona and New York, regulatory authorities require additional data specific to their respective jurisdictions, and the process for having a product approved or denied can last an additional two to three months, or longer, for these states.
Outside the United States, the registration process varies by jurisdiction and can take between 24 and 84 months to complete. In most instances, initial submissions to foreign regulatory authorities will not occur until after a U.S. registration has been secured. Moreover, foreign governments typically require up to two seasons of locally generated field efficacy data on crop/pest combinations before a product dossier can be submitted for review. For example, in the EU, we would need to obtain authorization under Regulation (EC) No 1107/2009, which sets forth rules for the authorization, sale, use, and control of plant protection products, in order to market our products, and regulators may seek to require our products to comply with maximum residue levels under Regulation (EC) NO 396/2005.
In some instances, California and Canada will conduct joint reviews with the EPA, which allows some pesticides to receive concurrent approvals in California, Canada and the United States. California and foreign jurisdictions also require us to submit product efficacy data. Historically, the EPA has not required the submission of product efficacy data, but may request it.
The microbial strains used in our agricultural manufacturing process are also regulated by the EPA under the Toxic Substances Control Act (“TSCA”). In some circumstances, TSCA requires entities to provide notice to the EPA prior to the manufacture or importation of new microorganisms, called a Microbial Commercial Activity Notice (“MCAN”). Persons intending to manufacture or import these microorganisms for commercial purposes in the United States must submit an MCAN to the EPA at least 90 days before such manufacture or importation. The EPA has 90 days to review the submission in order to determine whether the microorganism may present an unreasonable risk to human health or the environment. If the EPA makes that determination, the EPA may impose appropriate regulatory restrictions on the microorganism.
Finally, a number of our products may require registration or approval under various state regulatory programs, including those relating to fertilizers, auxiliary plant substances, soil amendments, beneficial substances and/or biostimulants.
Corporate Information
We were incorporated as Environmental Impact Acquisition Corp. (Nasdaq: ENVI) on July 2, 2020. On February 2, 2022, we consummated the business combination, or the Business Combination, contemplated by the Business Combination Agreement (the “Business Combination Agreement”), dated August 9, 2021, by and among our company (formerly known as Environmental Impact Acquisition Corp. (“ENVI”)), GreenLight Biosciences, Inc. (“GreenLight”) and Honey Bee Merger Sub, Inc., pursuant to which Honey Bee Merger Sub, Inc. was merged with and into GreenLight, with GreenLight surviving the merger (the “Merger”). As a result of the Merger, and upon consummation of the Merger and the other transactions contemplated by the Business Combination Agreement, GreenLight became a wholly owned subsidiary of ENVI. Upon the closing of the Business
Combination, we changed our name to GreenLight Biosciences Holdings, PBC (“New GreenLight”), with stockholders of GreenLight becoming stockholders of New GreenLight.
Available Information
Our principal place of business is located at 29 Hartwell Avenue, Lexington, Massachusetts 02421, and our telephone number is (617) 616-8188. Our website is located at www.greenlightbiosciences.com. Our website and the information contained on, or that can be accessed through, the website is not deemed to be incorporated by reference in, and is not considered part of, this Annual Report. Access to our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, and our Proxy Statements, and any amendments to these reports, is available via a link through the investors tab, free of charge, after we file or furnish them with the SEC and they are available on the SEC's website.

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ITEM 1A. RISK FACTORS
Item 1A. Risk Factors.
In evaluating our Company and our business, you should carefully consider the risks and uncertainties described below, together with the other information in this Annual Report on Form 10-K, including our consolidated financial statements and the related notes and the section titled "Management's Discussion and Analysis of Financial Condition and Results of Operations". We believe the risks described below are the risks that are material as of the date of this Annual Report on Form 10-K. If any of the following risks actually occur, our business, results of operations and financial condition would likely be materially and adversely affected. In these circumstances, the market price of the Company's Common Stock could decline, and you may lose part or all of your investment. Unless otherwise indicated, reference in this section and elsewhere in this Annual Report on Form 10-K to our business being adversely affected, negatively impacted or harmed will include an adverse effect on, or a negative impact or harm to, our business, reputation, financial condition, results of operations, revenue or our future prospects. The material and other risks and uncertainties summarized above in this Annual Report on Form 10-K and described below are not intended to be exhaustive and are not the only ones we face. Additional risks and uncertainties not presently known to us or that we currently deem immaterial may also impair our business. This Annual Report on Form 10-K also contains forward-looking statements that involve risks and uncertainties. See the section titled “Cautionary Note Regarding Forward-Looking Statements.” Our actual results could differ materially and adversely from those anticipated in these forward-looking statements as a result of certain factors, including, but not limited to, those set forth below.
Risks Related to Our Financial Position and Capital Needs
We have not generated any product revenues to date and expect to incur losses and negative cash flow for the foreseeable future.
We have generated substantial accumulated losses since inception. Our net losses were $167.1 million, $112.3 million and $53.3 million for the years ended December 31, 2022, 2021, and 2020, respectively. As of December 31, 2022, we had an accumulated deficit of $420.6 million. We will need to generate significant revenues to achieve profitability, and we may not be able to achieve and maintain profitability in the near future. We have derived substantially all of our revenues through license and collaboration agreements as well as grants and research partnerships with third parties and we are unable to accurately predict whether these sources of revenue will be available to us in the future. Our future success will depend on our ability to bring products to market for the first time and grow consistent revenue associated with those products. The research, testing and regulatory pathways for each of the products in our product pipeline are complex and we can offer no assurance that we will bring the products in our pipeline to market, that any of those products will be profitable or that we will generate overall profit or positive cash flow in the future. The net losses we incur may fluctuate significantly from year-to-year and quarter-to-quarter, such that a period-to-period comparison of our results of operations may not be a good indication of our future performance. These fluctuations may cause our stock to be volatile compared to other stocks in the market.
Our recurring losses from operations raise substantial doubt regarding our ability to continue as a going concern.
We have incurred significant losses since our inception and have never generated revenue or profit, and it is possible we will never generate revenue or profit. As of December 31, 2022, we held approximately $68.1 million in cash and cash equivalents and an accumulated deficit of $420.6 million. Based on our current operating plan and assumptions, we believe that our existing cash and cash equivalents will be sufficient to enable us to fund our operating expenses and capital expenditure requirements into the second quarter of 2023, but will not be sufficient to fund our operations for twelve months from the date of the filing of this Annual Report on Form 10-K. These factors raise substantial doubt about our ability to continue as a going concern. We will need to raise additional capital to fund our future operations and remain as a going concern. There can be no assurance that we will be able to obtain additional funding on acceptable terms, if at all. To the extent that we raise additional capital through future equity offerings, the ownership interest of common stockholders will be diluted, which dilution may be significant. However, we cannot guarantee that we will be able to obtain any or sufficient additional funding or that such funding, if available, will be obtainable on terms satisfactory to us. In the event that we are unable to obtain any or sufficient additional funding, there can be no assurance that we will be able to continue as a going concern, and we will be forced to delay, reduce or discontinue our product development programs or commercialization efforts.
Substantial doubt about our ability to continue as a going concern may materially and adversely affect the price per share of our common stock, and it may be more difficult for us to obtain financing. If potential collaborators decline to do business with us or potential investors decline to participate in any future financings due to such concerns, our ability to increase our cash position may be limited. The perception that we may not be able to continue as a going concern may cause others to choose not to deal with us due to concerns about our ability to meet our contractual obligations.
We have prepared our consolidated financial statements on a going concern basis, which contemplates the realization of assets and the satisfaction of liabilities and commitments in the normal course of business. Our consolidated financial statements
included in this Annual Report on Form 10-K do not include any adjustments to reflect the possible inability to continue as a going concern within one year after the date of the filing of this Annual Report on Form 10-K. If we are unable to continue as a going concern, you could lose all or part of your investment.
We will require substantial additional funds to complete our research and development activities, and, if additional funds are not available, we may need to significantly scale back or cease our business.
From inception in 2008 through December 31, 2022, we raised net proceeds of $436.2 million from the sale of capital stock, and from January 1, 2020 to December 31, 2022, we raised $67.0 million from the issuance of debt and convertible notes (including approximately $13.5 million of the PIPE Prepayment) which we have dedicated to the development of our RNA platform, human health product pipelines and plant health product pipelines. As of December 31, 2022, we held approximately $68.1 million in cash and cash equivalents. On February 2, 2022, we consummated the Business Combination and raised aggregate gross proceeds of approximately $136.4 million, which included funds held in ENVI’s trust account (after giving effect to redemptions of $194.9 million) and proceeds from the February 2022 PIPE Financing of $124.3 million (inclusive of the PIPE Prepayment), before deducting transaction expenses of $26.7 million. On August 11, 2022, we entered into the August 2022 PIPE Subscription Agreements with the August 2022 PIPE Investors, pursuant to which we sold 27,640,301 shares of common stock at a purchase price of $3.92 per share in a private placement, resulting in aggregate gross proceeds of approximately $108.3 million. We have invested and will continue to invest in property and equipment, and human capital and will require substantial funds to bring the current products in our product pipeline to market and to grow our business by researching, developing, and protecting products not currently in our product pipeline.
Based on our history of losses, we do not expect that we will be able to fund our longer-term capital and liquidity needs through our current cash balances and operating cash flow alone. To fund our longer-term capital and liquidity needs, we will need to secure additional capital. The amount of capital we will need will be subject to change depending on, among other things, the success of our efforts to grow revenue and our efforts to continue to effectively manage expenses.
When we raise additional funds through future issuances of equity or convertible debt securities, our existing stockholders could suffer significant dilution, and any new equity securities we issue could have rights, preferences and privileges superior to those of holders of our common stock. Any debt financing that we may secure in the future could involve restrictive covenants relating to our capital raising activities and other financial and operational matters, which may make it more difficult for us to obtain additional capital and to pursue business opportunities, including potential acquisitions. We may not be able to obtain additional financing on terms favorable to us, if at all. If we are unable to obtain adequate financing or financing on terms satisfactory to us when we require it, our ability to continue to support our business growth and to respond to business challenges and opportunities could be significantly impaired, and our business may be adversely affected.
Our financing needs may also increase substantially depending on the results of our research, trials and development for products and costs arising from additional regulatory approvals. We may not succeed in raising additional funds in a timely manner. The timing of our need for additional funds will depend on a number of factors, which are difficult to predict or may be outside of our control, including:
•the resources, time and costs required to initiate and complete our research and development and to initiate and complete studies and trials and to obtain regulatory approvals for additions to our product pipeline;
•progress in our research and development programs;
•the timing and amount of milestone, royalty and other payments; and
•costs necessary to protect any intellectual property rights.
If our estimates and predictions relating to any of these factors are incorrect, we may need to modify our business plans.
Our ability to raise funds will depend upon many factors, including conditions in the debt and equity capital markets, as well as investor perception of our creditworthiness and prospects. If we are unable to raise funds on acceptable terms, we may not be able to execute our business plan, take advantage of future opportunities, or respond to competitive pressures or unanticipated requirements. This may seriously harm our business, financial condition and results of operations. If we are not able to continue operations, investors may suffer a complete loss of their investments in our securities.
Failure to timely access the Company’s cash on deposit with Silicon Valley Bank (“SVB”) and ability to access its cash equivalents and marketable securities may result in a material adverse effect on the Company, its business operations, financial condition and results of operations.
On March 10, 2023, the Company became aware that SVB was closed by the California Department of Financial Protection and Innovation (the “CDFPI”), which appointed the Federal Deposit Insurance Corporation (the “FDIC”) as receiver and SVB was subsequently transferred into a new entity, Silicon Valley Bridge Bank, N.A (“SVB Bridge Bank”). All of the Company’s cash was held in accounts with SVB and is now held in accounts with SVB Bridge Bank, almost all of which is in money market funds purchased pursuant to sweep account agreements with SVB, as agent. Based on a joint statement issued by the Department of Treasury, Federal Reserve Board and FDIC on March 12, 2023, all such accounts at SVB will be fully insured. While the Company has been able to access its cash on deposit with SVB Bridge Bank, there remains some uncertainty as to if we will be able to continue accessing such cash and the stability of SVB Bridge Bank under receivership. If the Company is unable to access its capital in the short term, there will be material adverse impacts on its business operations, financial condition and results of operations, as the Company will be unable to fund working capital, its payment obligations or other cash requirements. In this event, if the Company is unable to quickly access additional capital, the Company may be required to scale back its business operations to manage its cash flow needs. Such delays could expose the Company to late fees, interest, penalties, fines, defaults, liabilities, or termination rights to its partners, suppliers, regulators and employees. As a result of the uncertainty and stability that remains related to the closure of SVB and the timing and ability of the Company’s continued access to its cash deposits, the Company’s business operations, financial conditions and results of operations may be materially affected.
Adverse developments affecting the financial services industry, such as actual events or concerns involving liquidity, defaults, or non-performance by financial institutions or transactional counterparties, could adversely affect the Company’s current and projected business operations and its financial condition and results of operations.
Actual events involving limited liquidity, defaults, non-performance or other adverse developments that affect financial institutions, transactional counterparties or other companies in the financial services industry or the financial services industry generally, or concerns or rumors about any events of these kinds or other similar risks, have in the past and may in the future lead to market-wide liquidity problems. For example, and as noted above, on March 10, 2023, SVB was closed by CDFPI, which appointed the FDIC as receiver. Similarly, on March 12, 2023, Signature Bank and Silvergate Capital Corp. were each swept into receivership. Although a statement by the Department of the Treasury, the Federal Reserve and the FDIC indicated that all depositors of SVB would have access to all of their money, including funds held in uninsured deposit accounts, borrowers under credit agreements, letters of credit and certain other financial instruments with SVB, Signature Bank or any other financial institution that is placed into receivership by the FDIC may be unable to access undrawn amounts thereunder. If any of our lenders or counterparties to any such instruments were to be placed into receivership, we may be unable to access such funds. In addition, if any of our customers, suppliers or other parties with whom we conduct business are unable to access funds pursuant to such instruments or lending arrangements with such a financial institution, such parties’ ability to pay their obligations to us or to enter into new commercial arrangements requiring additional payments to us could be adversely affected. In this regard, counterparties to SVB credit agreements and arrangements, and third parties such as beneficiaries of letters of credit (among others), may experience direct impacts from the closure of SVB and uncertainty remains over liquidity concerns in the broader financial services industry. Similar impacts have occurred in the past, such as during the 2008-2010 financial crisis. The loan and security agreement with SVB contains customary affirmative and negative covenants (including an obligation to maintain cash in accounts at SVB in an amount equal to 110% of the outstanding loan obligations thereunder) and customary events of default. We granted a first-priority, perfected security interest in substantially all of our present and future personal property and assets, excluding intellectual property, to secure our obligations to SVB. For more information on our term loan with SVB, see “Management's Discussion and Analysis of Financial Condition and Results of Operations-Liquidity and Capital Resources-Silicon Valley Bank Loan Agreement.”
Inflation and rapid increases in interest rates have led to a decline in the trading value of previously issued government securities with interest rates below current market interest rates. Although the U.S. Department of Treasury, FDIC and Federal Reserve Board have announced a program to provide up to $25 billion of loans to financial institutions secured by certain of such government securities held by financial institutions to mitigate the risk of potential losses on the sale of such instruments, widespread demands for customer withdrawals or other liquidity needs of financial institutions for immediately liquidity may exceed the capacity of such program. Additionally, there is no guarantee that the U.S. Department of Treasury, FDIC and Federal Reserve Board will provide access to uninsured funds in the future in the event of the closure of other banks or financial institutions, or that they would do so in a timely fashion.
Although we assess our banking and customer relationships as we believe necessary or appropriate, our access to funding sources and other credit arrangements in amounts adequate to finance or capitalize our current and projected future business operations could be significantly impaired by factors that affect the Company, the financial institutions with which the Company
has loan agreements or other arrangement with directly, or the financial services industry or economy in general. These factors could include, among others, events such as liquidity constraints or failures, the ability to perform obligations under various types of financial, credit or liquidity agreements or arrangements, disruptions or instability in the financial services industry or financial markets, or concerns or negative expectations about the prospects for companies in the financial services industry. These factors could involve financial institutions or financial services industry companies with which the Company has financial or business relationships, but could also include factors involving financial markets or the financial services industry generally.
The results of events or concerns that involve one or more of these factors could include a variety of material and adverse impacts on our current and projected business operations and our financial condition and results of operations. These could include, but may not be limited to, the following:
•Delayed access to deposits or other financial assets or the uninsured loss of deposits or other financial assets;
•Delayed or lost access to, or reductions in borrowings available under revolving existing credit facilities or other working capital sources and/or delays, inability or reductions in the company’s ability to refund, roll over or extend the maturity of, or enter into new credit facilities or other working capital resources;
•Potential or actual breach of contractual obligations that require the Company to maintain letters of credit or other credit support arrangements;
•Potential or actual breach of financial covenants in our credit arrangements;
•Potential or actual cross-defaults in other credit agreements, credit arrangements or operating or financing agreements; or
•Termination of cash management arrangements and/or delays in accessing or actual loss of funds subject to cash management arrangements.
In addition, investor concerns regarding the U.S. or international financial systems could result in less favorable commercial financing terms, including higher interest rates or costs and tighter financial and operating covenants, or systemic limitations on access to credit and liquidity sources, thereby making it more difficult for us to acquire financing on acceptable terms or at all. Any decline in available funding or access to our cash and liquidity resources could, among other risks, adversely impact our ability to meet our operating expenses, financial obligations or fulfill our other obligations, result in breaches of our financial and/or contractual obligations or result in violations of federal or state wage and hour laws. Any of these impacts, or any other impacts resulting from the factors described above or other related or similar factors not described above, could have material adverse impacts on our liquidity and our current and/or projected business operations and financial condition and results of operations.
In addition, any further deterioration in the macroeconomic economy or financial services industry could lead to losses or defaults by our customers or suppliers, which in turn, could have a material adverse effect on our current and/or projected business operations and results of operations and financial condition. For example, a customer may fail to make payments when due, default under their agreements with us, become insolvent or declare bankruptcy, or a supplier may determine that it will no longer deal with us as a customer. In addition, a customer or supplier could be adversely affected by any of the liquidity or other risks that are described above as factors that could result in material adverse impacts on the Company, including but not limited to delayed access or loss of access to uninsured deposits or loss of the ability to draw on existing credit facilities involving a troubled or failed financial institution. Any customer or supplier bankruptcy or insolvency, or the failure of any customer to make payments when due, or any breach or default by a customer or supplier, or the loss of any significant supplier relationships, could result in material losses to the Company and may have a material adverse impact on our business.
Risks Relating to Our Business and Industry
We are an early-stage biotechnology company without any products or services currently available for sale and we may not be able to successfully develop or bring products or services to market.
In our human health program, we have several pre-IND product candidates, while in our plant health program, we have seven product candidates we hope to bring to market by 2027; however, there is no assurance that we will succeed in bringing any of our product candidates to market or that such product candidates, if approved, or any of our other operations will generate any revenue. If we cannot develop a marketable product or generate sufficient revenues, we may be required to suspend or cease operations.
Our strategy assumes that we will collaborate with larger companies to develop and commercialize the products in our pipeline and if those collaborations are not successful or available to us at all, we may not be able to successfully commercialize our products.
We are seeking and will continue to seek collaboration arrangements with third parties for the development or commercialization of our products. These arrangements are complex and time-consuming to negotiate, document, implement and maintain and, as a small company, we may not have the same bargaining power as the larger companies we seek to collaborate with and the terms of any collaborations or other arrangements that we may establish may not be favorable to us.
Due to our limited resources and access to capital, we must make decisions on the allocation of resources to certain programs and product candidates; these decisions may prove to be wrong and may adversely affect our business.
We have limited financial and human resources and intend to initially focus on research programs and product candidates for a limited set of indications and limited set of target pests. As a result, we may forgo, delay, or abandon pursuit of opportunities with other product candidates or for other indications that later prove to have greater commercial potential or a greater likelihood of success. For example, we recently paused work on our early-stage research programs, including our gene therapy program for sickle cell disease and our programs for antibody therapy and supra-seasonal flu. To the extent we have received grants to support some of the work we have paused, we may need to return unused grant money to the applicable sponsors, such as the Bill and Melinda Gates Foundation.
It is difficult to predict the time and cost of development of our pipeline products, which are produced by or based on a relatively novel and complex technology and are subject to many risks, any of which could prevent or delay revenue growth and adversely impact our market acceptance, business and results of operations. We may also determine not to pursue, or change the timing or order of, our product candidates.
We have a limited operating history and funding, which may make it difficult to evaluate our product development, product prospects and overall likelihood of success.
We commenced operations in 2008. We have a limited operating history as a company, which makes it difficult to predict future operations. The product candidates and the markets we hope to serve have shifted since we commenced operations and as such, our operational experience with our current product pipeline and target markets is shorter than the full period of our operations. We have been operating our plant health product pipelines since 2016 and our human health product pipelines since 2019. Our approach to the discovery and development of product candidates had not been validated by the commercial introduction of products and we cannot guarantee that the products currently in our product pipeline, or any other products or services, will have future commercial value. Our programs will require substantial additional development and research, both in time and resources, before we are in a position to receive regulatory approvals and begin generating revenue in connection with the sale of product candidates. We have not yet demonstrated the ability to complete a large-scale, pivotal clinical trial, obtain regulatory approval for any product in human health or plant health, manufacture a product at commercial scale, or arrange for a third party to do so on our behalf, or conduct sales and marketing activities necessary for successful product commercialization. Consequently, predictions about our future success or viability may not be as accurate as they could be if we had a longer operating history or a history of successfully developing and commercializing products.
All of our products require rigorous, time-consuming and expensive regulatory examination and approval before they can be commercialized and some or all of our products may not receive this approval.
Any products that we are currently developing or may develop in the future will be subject to extensive governmental regulations relating to development, trials, manufacturing and commercialization. Rigorous studies, clinical trials and extensive regulatory licensure and approval processes are required to be successfully completed in the United States and in many foreign jurisdictions, such as Africa, the European Union and Japan, before a new product may be offered and sold in any of these countries or regions. Satisfaction of these and other regulatory requirements is costly, time-consuming, uncertain and subject to unanticipated delays. We have experienced and may continue to experience additional unanticipated delays in our efforts to satisfy regulatory requirements relating to our product candidates. For example, in April 2022, we applied for a Clinical Trials Application, or CTA, with the South African Health Products Regulatory Authority, or SAHPRA, for a phase I/II single-vaccination booster study. That application was rejected on the basis that the application failed to identify specific benefits our testing efforts and a resulting vaccine would bring to South Africa considering the ready availability of other COVID-19 vaccines in that country. We can offer no assurance that any clinical trial applications we may file will be accepted by regulatory authorities.
Studies and trials for regulatory licensure and approval are expensive and difficult to design and implement, in part because they are subject to rigorous regulatory requirements. Because many products that we develop in the future will be based on new technologies, we expect that they will require extensive research and development and necessitate substantial manufacturing and processing costs. In addition, costs to treat potential side effects that may result from a product we develop may be significant.
Furthermore, with respect to our plant health product pipeline, because our products contain novel RNA-based active ingredients, there will generally be no previously registered pesticide product containing that active ingredient and, as a result, the use of each of our products in the United States will require a new registration under FIFRA and the establishment of a tolerance under Section 408 of the FFDCA or the issuance of a tolerance exemption. We will also need regulatory approval from other jurisdictions if we want to commercialize our products globally where we will face similar challenges in obtaining approval. We have experienced and may continue to experience additional unanticipated delays. We can offer no assurance on timing of regulatory review and approval or that any of our applications filed will be accepted by the applicable regulatory authorities. Without the required regulatory approval, we will be unable to commercialize any of our products.
Please refer to risk factor sections on our human health, plant health and animal health products for more regulatory risk information.
Our company has product candidates with very complex and different sales marketing and distribution channels, which we have yet to establish, and if we are unable to establish these capabilities, we may not be successful in commercializing our product candidates if they are approved.
We will have very different sales and marketing channels if the products in our pipeline are to reach customers in their respective markets, requiring us to develop distinct sales, marketing, and distribution methods. In particular, the human, agricultural and plant health markets have different customers and distribution channels. We have not yet established a sales, marketing or product distribution infrastructure for our product candidates, which are still in various stages of development. To achieve commercial success for any product for which we obtain marketing approval, we will need to establish a sales and marketing organization within the United States and develop a strategy for sales outside of the United States. Building, managing and maintaining such a sales and marketing infrastructure will require us to hire experts in the field, implement complex systems, establish collaborations with third parties effectively across various geographies and understand disparate regulatory regimes. In addition, as we begin to commercialize our products, we will need to hire, develop, train personnel with expertise in marketing and selling products in each of those markets. Our ability to effectively engage in these steps is untested, making it impossible for us to accurately predict the level of success we will achieve.
Our growth strategy requires us to introduce new products, in addition to those in our current pipeline, that achieve market acceptance.
In order to reach our growth objectives, we must introduce new products in addition to our current pipeline of product candidates, and future new products. Research, development and regulatory approval for our products involve risks of failure inherent in the development of novel and complex products. These risks include the possibility that:
•our products may not perform as expected;
•we may be unable to capitalize on successful innovation because we may choose not to incur the expense of patenting our discoveries in all jurisdictions or may be unable to obtain patents in the jurisdictions in which we wish to obtain patents;
•any strategy of discovering additional vertical markets beyond plant, animal and human health for the use of RNA may be infeasible, limiting our growth;
•our products may not receive necessary regulatory permits and governmental clearances in the markets in which we intend to sell them;
•our competitors may develop new products or improve existing products that may make our products uncompetitive;
•we may create production capacity that we are unable to use either because we do not bring related products to market or because the timing to bring those products to market is delayed;
•the lower cost of RNA produced by us may not translate equally or at all into lower prices for the products that use it;
•our products may be difficult to produce on a large scale;
•intellectual property and other proprietary rights of third parties may prevent us or our collaborators from making, marketing or selling our products;
•we or our collaborators may be unable to fully develop or commercialize products in a timely manner or at all; and
•third parties may develop superior or equivalent products.
Accordingly, if we experience any significant delays in the development or introduction of new products or if our new products do not achieve market acceptance, our business, operating results and financial condition would be adversely affected.
Our corporate restructuring and the associated headcount reduction may not result in anticipated savings, could result in total costs and expenses that are greater than expected and could disrupt our business.
In October 2022, we undertook an organizational restructuring that reduced our workforce by approximately 25%. We may not realize, in full or in part, the anticipated benefits, savings, and improvements in our cost structure from our restructuring efforts due to unforeseen difficulties, delays or unexpected costs. If we are unable to realize the expected operational efficiencies and cost savings from the restructuring, our operating results and financial condition would be adversely affected. Furthermore, our restructuring plan may be disruptive to our operations. For example, our headcount reductions could yield unanticipated consequences, such as increased difficulties in implementing our business strategy, including retention of our remaining employees. Employee litigation related to the headcount reduction could be costly and prevent management from fully concentrating on the business.
We will need to modify the size of our organization from time to time, and we may experience difficulties in managing these changes, which could disrupt operations.
We will continue to slow our hiring in the near future as we assess capacity, capital needs and the scope of our operations. The skills we seek are typically in high demand and we may have difficulty identifying, hiring, integrating, motivating and retaining additional employees, consultants, and contract personnel, particularly in light of our recent workforce reduction. Also, our management may need to divert a disproportionate amount of their attention away from our day-to-day activities and devote a substantial amount of time to simultaneously manage rightsizing and growth activities. We may not be able to effectively manage changes in the size of our operations, which may result in weaknesses in our infrastructure, give rise to operational mistakes, loss of business opportunities, loss of employees and reduced productivity among remaining employees. Any future growth could require significant capital expenditures and may divert financial resources from other projects, such as the development of product candidates. If our management is unable to effectively manage our rightsizing efforts while scaling the Company, our expenses may increase more than expected, our ability to generate and/or grow revenues could be reduced, and we may not be able to implement our business strategy. Our future financial performance and our ability to commercialize our product candidates and compete effectively will depend, in part, on our ability to effectively manage the size of our organization.
Many of the companies that we compete against for qualified personnel and consultants have greater financial and other resources, different risk profiles, more established brands and a longer history in the industry than we do. If we are unable to continue to attract, motivate, and retain high-quality personnel and consultants, the rate and success at which we can discover and develop product candidates and operate our business will be limited.
We use RNA-based molecular biology triggers for many of the products in our product pipeline and the successful commercialization of these products will depend on public perceptions of RNA-based products.
The successful commercialization of our product candidates depends, in part, on public acceptance of modern biotechnology techniques and the use of RNA to regulate the expression of genes and production of proteins in human health and agricultural products. Negative public perceptions about RNA and molecular regulation of gene expression can also affect the regulatory environment in the jurisdictions in which we are targeting the sale of our products and the commercialization of our product candidates. Any increase in such negative perceptions or any restrictive government regulations in response to RNA-based products could have a negative effect on our business and may delay or impair the sale of our products or the development or commercialization of our product candidates. Public pressure may lead to increased regulation and legislation for products produced using biotechnology and this could adversely affect our ability to sell our product or commercialize our product candidates.
Our accounting predecessor, GreenLight, has identified material weaknesses in its internal controls of financial reporting. If we are unable to remediate the material weaknesses, or if we identify additional material weaknesses or otherwise fail to maintain effective internal control over financial reporting, this may result in material misstatements or restatements of our consolidated financial statements or cause us to fail to meet our periodic reporting obligations.
As a public company, the Company is required to maintain internal control over financial reporting. Management may be unable to effectively and timely implement controls and procedures that adequately respond to the increased regulatory compliance and reporting requirements of a public company. If we are unable to comply with the requirement to maintain internal control over financial reporting, we may be unable to maintain compliance with securities law requirements regarding timely filing of periodic reports or applicable stock exchange listing requirements, investors may lose confidence in our financial reporting, and our stock price may decline as a result.
Two material weaknesses have been identified in our internal control over financial reporting as of December 31, 2022. A material weakness is a deficiency, or a combination of deficiencies, in internal control over financial reporting such that there is a reasonable possibility that a material misstatement of our annual or interim financial statements will not be prevented or detected on a timely basis. The two material weaknesses identified in our internal controls result from:
•The failure to maintain a sufficient complement of personnel in our accounting and reporting department to ensure adequate segregation of duties such that appropriate review and monitoring of our financial records are executed.
•The failure to design and implement adequate information systems controls, including access and change management controls.
Two material weaknesses were identified in connection with the preparation and audit of GreenLight’s financial statements as of December 31, 2020 (which audit was completed in September 2021), and had not been remediated as of December 31, 2022.
We have begun implementation of a plan to remediate these material weaknesses. These remediation measures are ongoing and include performing routine testing over financial reporting including general IT controls and performing a comprehensive risk assessment. These remediation measures may be time-consuming and costly, and there is no assurance that they will ultimately have the intended effects. If we identify any new material weaknesses or significant deficiencies in the future, any such newly identified material weakness or significant deficiency could limit our ability to prevent or detect a material misstatement of our annual or interim financial statements.
Moreover, our independent registered public accounting firm is not required to attest to the effectiveness of our internal control over financial reporting until after we are no longer an “emerging growth company” as defined in the JOBS Act. At that time, our independent registered public accounting firm may issue an adverse report if it is not satisfied with the level at which our internal control over financial reporting is documented, designed, or operating.
Under applicable employment laws, we may not be able to enforce covenants not to compete.
Our employment agreements generally include covenants not to compete. These agreements prohibit our employees, if they cease working for us, from competing directly with us or working for our competitors for a limited period. We may be unable to enforce these agreements under the laws of the jurisdictions in which our employees work.
Our business may be affected by litigation and government investigations.
We may from time to time receive inquiries and subpoenas and other types of information requests from government authorities and others and we may become subject to claims and other actions related to our business activities. While the ultimate outcome of investigations, inquiries, information requests and legal proceedings is difficult to predict, defense of litigation claims can be expensive, time-consuming and distracting, and adverse resolutions or settlements of those matters may result in, among other things, modification of our business practices, costs and significant payments, any of which could have a material adverse effect on our business, financial condition, results of operations and prospects.
We may be subject to claims that our employees have wrongfully used or disclosed alleged trade secrets of their former employers.
Many of our employees, including our senior management, were previously employed at other biotechnology or pharmaceutical companies, including our potential competitors. Some of these employees may have executed proprietary rights, non-disclosure and non-competition agreements in connection with such previous employment. Although we try to ensure that
our employees do not use the proprietary information or know-how of others in their work for us, we may be subject to claims that we or these employees have used or disclosed intellectual property, including trade secrets or other proprietary information, of any such employee’s former employer. We are not aware of any threatened or pending claims related to these matters or concerning the agreements with our senior management, but future litigation may be necessary to defend against such claims. If we fail in defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel. Even if we are successful in defending against such claims, litigation could result in substantial costs and be a distraction to management.
We are exposed to a risk of substantial loss due to claims that may be filed against us in the future because our insurance policies may not fully cover the risk of loss associated with our operations.
We are exposed to the risk of having claims seeking monetary damages being filed against us for loss or harm suffered by participants of our preclinical and clinical studies or for loss or harm suffered by users of any products that may receive approval for commercialization in the future, or in connection with loss or harm from any other product, for example, agricultural products, that may be tested or receive approval for commercialization in the future. In either event, the FDA, EPA or the regulatory authorities of other countries or regions may commence investigations of the safety and effectiveness of any such trial or commercialized product, the manufacturing processes and facilities or marketing programs utilized in respect of any such trial or products, which may result in mandatory or voluntary recalls of any commercialized product or other significant enforcement action such as limiting the indications for which any such product may be used, or suspension or withdrawal of approval for any such product. Similar risks exist in connection with the testing, use, or sale of any product we may develop or commercialize. If our products are used for an application they are not intended for, become adulterated or mislabeled we may need to recall such products. A widespread product recall could result in significant losses due to the costs of a recall, the destruction of product inventory, and lost sales due to the unavailability of product for a period of time. We could also suffer losses from a significant product liability judgment against us. A significant product recall or product liability case could also result in adverse publicity, damage to our reputation, and a loss of confidence in our products, which could have an adverse effect on our business,
Significant disruptions of information technology systems or security breaches could adversely affect our operations.
We are increasingly dependent upon information technology systems, infrastructure and data to operate our business ourselves and on vendors who operate aspects of our technology infrastructure for us. In the ordinary course of business, we collect, store and transmit large amounts of confidential information (including, among other things, trade secrets or other intellectual property, proprietary business information and personal information). It is critical that we do so in a secure manner to maintain the confidentiality and integrity of such confidential information.
Attacks on information technology systems are increasing in their frequency, levels of persistence, sophistication and intensity, and they are being conducted by increasingly sophisticated and organized groups that include state actors, criminal organizations and individuals who can bring significant resources and expertise to bear. Public reports indicate that state actors have specifically targeted companies developing COVID-19 vaccines with the intent of stealing trade secrets or disabling information technology systems associated with vaccine development and we may be unable to defend against these state actors who have significantly more resources at their disposal than we do.
Our information technology systems, and those of third-party vendors with whom we contract are also vulnerable to service interruptions, security breaches from inadvertent or intentional actions by our employees, third-party vendors, and/or business partners, or from cyber-attacks by malicious third parties. Cyber-attacks could include the deployment of harmful malware, ransomware, denial-of-service attacks, social engineering and other means to affect service reliability, and could threaten the confidentiality, integrity, and availability of information. For example, we have previously experienced a ransomware attack that briefly interrupted access to two of our servers. Although in this instance we were able to rely on our backup systems to restore access promptly, without making a ransom payment and without loss of data, our defenses against future cyber-attacks may not be successful.
Significant disruptions of our information technology systems, or those of our third-party vendors, or security breaches could adversely affect our business operations and/or result in the loss, adulteration, misappropriation and/or unauthorized access, use or disclosure of, or the prevention of access to, confidential information, including, among other things, trade secrets or other intellectual property, proprietary business information and personal information, and could result in financial, legal, business, and reputational harm to us.
Any failure or perceived failure by us or any third-party collaborators, service providers, contractors or consultants to comply with our privacy, confidentiality, data security or similar obligations to third parties, or any data security incidents or other security breaches that result in the unauthorized access, release or transfer of sensitive information, including personally
identifiable information, may result in governmental investigations, enforcement actions, regulatory fines, litigation or public statements against us, could cause third parties to lose trust in us or could result in claims by third parties asserting that we have breached our privacy, confidentiality, data security, or similar obligations, any of which could have a material adverse effect on our reputation, business, financial condition, or results of operations. Moreover, data security incidents and other security breaches can be difficult to detect, and any delay in identifying them may lead to increased harm. While we have implemented data security measures intended to protect our information technology systems and infrastructure, there can be no assurance that such measures will successfully prevent service interruptions or data security incidents.
We are subject to anti-corruption, anti-bribery and anti-money laundering laws and regulations in various jurisdictions around the world which are subject to rigorous enforcement, and we can face serious consequences for violations.
We expect our non-U.S. activities to increase over time and to include countries that have more prevalent corruption than found in the U.S., increasing our exposure to anti-corruption, anti-bribery and anti-money laundering laws and regulations. These include the U.S. Foreign Corrupt Practices Act of 1977, and as amended, the U.S. domestic bribery statute contained in 18 U.S.C. § 201, the U.S. Travel Act, the U.K. Bribery Act and other anti-corruption, anti-bribery and anti-money laundering laws and regulations in the jurisdictions in which we do business, both domestic and abroad. The FCPA and other anti-corruption laws generally prohibit companies, their employees, agents, representatives, business partners and third-party intermediaries from corruptly promising, authorizing, offering, or providing, directly or indirectly, anything of value to government officials, political parties, or candidates for public office for the purpose of obtaining or retaining business or securing an improper business advantage. The UK Bribery Act and other anti-corruption laws also prohibit commercial bribery not involving government officials, and requesting or accepting bribes; and anti-money laundering laws prohibit engaging in certain transactions involving criminally-derived property or the proceeds of criminal activity.
We and third parties we do business with, as well as our representatives and agents, will have direct or indirect interactions with officials and employees of government agencies or state-owned or affiliated universities or other entities (for example, to obtain necessary permits, licenses, patent registrations and other regulatory approvals), which increases our risks under the FCPA and other anti-corruption laws. We also engage contractors, consultants and other third parties from time to time to conduct business development activities abroad. We may be held liable for the corrupt or other illegal activities of our employees or third parties even if we do not explicitly authorize such activities.
The FCPA also requires that we keep accurate books and records and maintain a system of adequate internal controls. We have recognized several material weaknesses in our internal control over financial reporting, which may compromise our ability to detect inappropriate payments (see the risk factor associated with “material weaknesses in our internal control over financial reporting”). Furthermore, we cannot assure you that our employees, agents, representatives, business partners or third-party intermediaries will always comply with our policies and applicable law, for which we may be ultimately held responsible.
Any allegations or violation of the FCPA or other applicable anti-bribery, anti-corruption laws and anti-money laundering laws may result in whistleblower complaints, sanctions, settlements, investigations, prosecution, enforcement actions, substantial criminal fines and civil penalties, disgorgement of profits, imprisonment, debarment, tax reassessments, breach of contract and fraud litigation, loss of export privileges, suspension or debarment from U.S. government contracts, adverse media coverage, reputational harm and other consequences, all of which may have an adverse effect on our reputation, business, financial condition, results of operations and prospects. Responding to an investigation or action can also result in a materially significant diversion of management’s attention and resources and significant defense costs and other professional fees.
Our future depends on the continued contributions of our senior management team and our ability to attract and retain other highly qualified personnel; in particular, Andrey Zarur, our President and Chief Executive Officer, is critical to our future vision and strategic direction.
Our success depends in large part on our ability to attract and retain high-quality management in sales, market access, product development, software engineering, marketing, operations, finance and support functions, especially in the Boston and Rochester areas. We compete for qualified technical personnel with other life sciences and biotechnology companies. Competition for qualified employees is intense in these industries, and the loss of even a few qualified employees, or an inability to attract, train, retain and motivate additional highly skilled employees required for the planned expansion of our business could harm our operating results and impair our ability to grow. The loss of one or more of our key employees, and any failure to have in place and execute an effective succession plan for key executives, could seriously harm our business.
As we continue to grow, we may be unable to continue to attract or retain the personnel needed to maintain our competitive position. To attract, train and retain key personnel, we use various measures, including competitive compensation and benefit
packages (including an equity incentive program), which may require significant investment. These measures may not be enough to attract and retain the personnel required to operate our business effectively and efficiently.
Moreover, if the perceived value of our equity awards declines, it may materially and adversely affect our ability to attract and retain key employees. If we do not maintain the necessary personnel to accomplish our business objectives, we may experience staffing constraints that materially and adversely affect our ability to support programs and operations.
Many of our employees may receive proceeds from sales of our equity in the public markets, which may reduce their motivation to continue to work for us.
In addition, our future also depends on the continued contributions of our senior management team and other key personnel, each of whom would be difficult to replace. In particular, Dr. Andrey Zarur, our President and Chief Executive Officer, is critical to our future vision and strategic direction. We rely on our executive team in the areas of operations, research and development, commercial, and general and administrative functions. We also do not maintain key person life insurance for our key employees.
From time to time, there may be changes in our senior management team that may be disruptive to our business. If our senior management team, including any new hires that we may make, fails to work together effectively and to execute our plans and strategies on a timely basis, our business, results of operations and financial condition could be harmed.
Risks Related to Our Manufacturing Platform
We are designing an mRNA commercial manufacturing process in parallel with our product and process development. We currently intend to use CDMOs, such as Samsung Biologics Co., Ltd., to produce material for our COVID-19 product candidate for late-stage clinical trials and commercial launch. There is risk that the final manufacturing process and facility could be incompatible with the CDMO facility, requiring modification and resulting in delays and inefficient deployment of capital.
In an effort to bring our mRNA-related product candidates, particularly our pre-clinical COVID-19 vaccine candidate, to market more quickly, we are designing some aspects of our manufacturing process in parallel with selecting the exact manufacturing equipment and CDMO for that process. Steps to build the infrastructure include design, engineering, site selection and equipment procurement.
As we seek to increase the manufacturing output for commercial production and particular programs from the smaller quantities needed for IND-enabling studies to the larger quantities needed for commercial production, we intend to seek to continuously improve the manufacturability of our product candidates. Accordingly, we may change our manufacturing processes for a particular program during the course of development. However, any change in the manufacturing process may require resupplying clinical material to trial sites, which could increase our expenses, delay completion of clinical trials or otherwise adversely affect commercialization of the product.
We plan to acquire additional laboratory, manufacturing and other space to accommodate our expected growth. If we are not able to access appropriate or sufficient space at reasonable cost, our business and results of operations could be adversely affected.
Our business and results of operations are dependent on locating and successfully negotiating leases for adequate access to laboratory and office space and suitable physical infrastructure, including electrical, plumbing, HVAC and network infrastructure, to conduct our operations and accommodate our growth. These resources are constrained and expensive in the areas in which we operate. If we are unable to access enough space or experience failures of our physical infrastructure, our business and results of operations could be adversely affected.
In order to properly conduct our business, we need access to sufficient laboratory space and equipment to perform the activities necessary to advance and complete our programs. Additionally, we need to ensure that our laboratories and corporate offices remain operational at all times, which includes maintaining suitable physical infrastructure, including electrical, plumbing and HVAC, logistics and transportation systems and network infrastructure. We lease our laboratories and office spaces, and we rely on the landlords for basic maintenance of our leased laboratories and office buildings. If one of our landlords has not maintained a leased property sufficiently, we may be forced into an early exit from the facility, which could be disruptive to our business.
Our dsRNA and mRNA product candidates are based on innovative technologies and any product candidates we develop may be more complex and more difficult to manufacture than initially anticipated. We may encounter difficulties with manufacturing processes, manufacturing at higher volumes, product releases, product shelf life and storage, supply chain management, or shipping for any of our medicines, for both our agricultural or human health product candidates, including our COVID-19 vaccine. If we or any of our third-party vendors encounter such difficulties, our ability to supply commercial product or material for clinical trials could be delayed or stopped.
The manufacturing processes for our product candidates using our dsRNA and mRNA platforms are innovative and complex. There are no mRNA medicines currently manufactured at commercial scale utilizing our manufacturing process. Due to the nature of this technology and our limited experience at commercial scale production, we could encounter difficulties with manufacturing processes, manufacturing at higher volumes, product releases, product shelf life and storage, supply chain management, or shipping.
These difficulties could be due to any number of reasons including, but not limited to, complexities of producing batches at any volume, equipment failure, choice and quality of raw materials and excipients, analytical testing technology, and product instability. In an effort to optimize product features, we may make changes to a product candidate in our manufacturing and stability formulation and conditions, which may result in our having to resupply batches for pre-clinical or clinical activities when there is insufficient product stability during storage and insufficient supply. Insufficient stability or shelf life of our product candidates could materially delay our or our strategic collaborators’ ability to continue the clinical trial for that product candidate or require us to begin a new clinical trial with a newly formulated drug product, due to the need to manufacture additional pre-clinical or clinical supply.
Due to the nature of our products and manufacturing platform, there may also be a high degree of technological change that can negatively impact product comparability during and after clinical development. Furthermore, technology changes may drive the need for changes in, modification to, or the sourcing of new manufacturing infrastructure or may adversely affect third-party relationships.
The process to generate dsRNA or mRNA product candidates encapsulated in LNPs is complex and, if not developed and manufactured under well-controlled conditions, can adversely impact pharmacological activity and may result in one or more of our product candidates’ failure.
We have limited experience in manufacturing or commercializing proposed product candidates and may encounter difficulties, delays or other unanticipated hurdles before we are able to begin manufacturing our product candidates in the quantities needed to achieve our business plans.
We have limited experience in manufacturing or commercializing our proposed product candidates. As we increase manufacturing volume, we may encounter unexpected difficulties and delays that require adjustments or changes to our manufacturing process. Changes in our manufacturing processes may lead to failure of batches, which could lead to a substantial delay in pre-clinical studies and clinical trials or the delivery of commercial product. Any such changes could adversely affect clinical or commercial supply of our products. Such changes might also cause delays in or increase the cost of commissioning our facility and adversely affect our commercialization plans.
We have increased the batch size for our mRNA production to accommodate the supply requirements of some of our current and anticipated pre-clinical and clinical programs. However, in some cases, we may have to utilize multiple batches of substance and product to meet the clinical supply requirement of a single clinical trial. If we or our contract manufacturers fail to successfully and consistently produce mRNA at larger batch sizes, it could lead to a substantial delay in our clinical trials or in the commercialization of any products that may receive regulatory approval.
If our cell-free manufacturing platform does not perform as expected, or if our competitors develop and market technologies or products more rapidly than we do or that are more effective, outperform, safer or less expensive than our manufacturing platform technology, our commercial opportunities will be negatively impacted.
It is anticipated that we will face increased competition in the future as new companies enter the markets and as scientific developments progress. If we are unable to compete effectively, our opportunity to discover new products or generate revenue from the sale of such new products or our existing product candidates could be adversely affected.
We have established laboratory, clean room, and manufacturing facilities in Massachusetts, North Carolina and New York to support our activities, which is resulting in the incurrence of significant investment with no assurance that such investment will be recouped.
In order to support our future growth and our agriculture and human health product pipeline, we have invested in facilities to develop products or produce materials. This investment has significantly increased our capital and operating expenses. Moreover, based on our current business plan, we anticipate that in the future we will need to expand our facilities for research and development and production capacity, which we currently expect to accomplish by expanding the capacity of existing facilities. We may need to, or decide to, build additional commercial mRNA manufacturing facilities using our platform technology in the U.S. and in countries outside of the U.S. There can be no assurance that any additional manufacturing capacity that we may acquire will be necessary or that this investment will be recouped.
If we are unable to adequately and timely manufacture and supply our products and product candidates or if we do not fully utilize our manufacturing facilities, our business may be adversely affected. Charges resulting from excess capacity would have a negative effect on our financial condition and results of operations.
We will depend on relationships with third parties for revenues, and for the development, regulatory approval, commercialization and marketing of certain of our products and product candidates, which are outside of our full control.
We rely on a number of third-party relationships for our leases, construction of our facilities, and the development, regulatory approval and commercialization of certain of our product candidates. Certain aspects of our regulatory affairs and clinical development relating to our products and product candidates are also outsourced to third parties. Reliance on third parties subjects us to a number of risks, including:
•the inability to control the resources such third parties devote to our programs, products or product candidates;
•disputes may arise under an agreement and the underlying agreement may fail to provide us with significant protection or may fail to be effectively enforced if such third parties fail to perform;
•failure or perceived failure by us to comply with our obligations under an agreement with a third party could cause the third party to make public statements against us or could result in litigation asserting that we have breached our obligations, any of which could have a material adverse effect on our reputation, business, financial condition, or results of operations;
•the interests of such third parties may not always be aligned with our interests, and such parties may not pursue regulatory approvals or market a product in the same manner or to the same extent that we would, which could adversely affect revenues, or may adopt tax strategies that could have an adverse effect on our business, results of operations or financial condition;
•third-party relationships require the parties to cooperate, and failure to do so effectively could adversely affect product development or the clinical development or regulatory approvals of product candidates under collaborative control, could result in termination of the research, development or commercialization of product candidates or could result in litigation or arbitration;
•any failure on the part of such third parties to comply with applicable laws, including tax laws, regulatory requirements and/or applicable contractual obligations or to fulfill any responsibilities they may have to protect and enforce any intellectual property rights underlying product candidates could have an adverse effect on revenues as well as give rise to possible legal proceedings;
•any failure on the part of such third parties to meet their contractual obligations to us because of supply chain related failures, including supply chain failures resulting from the ongoing global COVID-19 pandemic, wars such as the war in Ukraine, political and tariff disputes, macroeconomic conditions, or other causes, any one of which could give that third party the ability to not perform its obligations to us under a claim of force majeure; and
•any improper conduct or actions on the part of such third parties could subject us to civil or criminal investigations and monetary and injunctive penalties, impact the accuracy and timing of financial reporting and/or adversely impact our ability to conduct business, operating results and reputation.
Given these risks, there is considerable uncertainty regarding the success of current and future collaborative efforts. If these efforts fail, our product development or commercialization of product candidates could be delayed, revenues from products could decline and/or the anticipated benefits of these arrangements may not be realized.
Manufacturing issues could substantially increase costs, limit supply of products and/or reduce revenues.
The process of manufacturing our products is complex, highly regulated and subject to numerous risks, including:
•Risks of Reliance on Third Parties and Single Source Providers. We rely on third-party suppliers and manufacturers for many aspects of our manufacturing process for products and product candidates. In some cases, due to the unique manner in which our products and product candidates are manufactured, we rely on single source providers of raw materials and manufacturing supplies. For example, the dsRNA processes use specific yeast microbial RNA, the most effective forms of which are sourced from suppliers in China. These third parties, as well as our other suppliers, are independent entities subject to their own operational, geopolitical and financial risks that are outside of our control, including the impact of the COVID-19 pandemic and intellectual property protection. These third parties may not perform their obligations in a timely and cost-effective manner or in compliance with applicable laws and regulations, and they may be unable or unwilling to increase production capacity commensurate with demand for existing or future products. Finding alternative providers could take a significant amount of time and involve significant expense due to the specialized nature of the services and the need to obtain regulatory approval of any significant changes to suppliers or manufacturing methods. We cannot be certain that we could reach an agreement with alternative providers or that the FDA or other regulatory authorities would approve the use of such alternatives.
•Risks Relating to Compliance with cGMP. We and our third-party providers are generally required to maintain compliance with cGMP and other stringent requirements and are subject to inspections by the FDA and other regulatory authorities to confirm compliance. Any delay, interruption or other issues that arise in the manufacture, fill-finish, packaging or storage of products or product candidates as a result of a failure of our facility or operations or those of third parties to pass any regulatory agency inspection could significantly impair our ability to develop and commercialize our products and product candidates. Significant noncompliance could also result in the imposition of monetary penalties or other civil or criminal sanctions and damage our reputation.
•Global Supply Risks. We rely on our laboratories and manufacturing facilities for the production of drug substance for our product candidates. The supply of these products and product candidates depends on the uninterrupted and efficient operation of our facility and laboratory, which could be adversely affected by equipment failures, labor shortages, public health epidemics, natural disasters, power failures, cyber-attacks and many other factors. Additionally, there can be no assurance that we will be able to meet expected timelines or that there will not be any direct or indirect delays resulting from the COVID-19 pandemic, macroeconomic conditions, wars or supply chain disruptions. We have had delays, and might experience additional delays, in bringing our current and planned facilities online and we may not have sufficient manufacturing capacity to meet our long-term manufacturing requirements.
•Risk of Product Loss. The manufacturing process for our products is susceptible to product loss due to contamination, equipment failure or improper installation or operation of equipment or vendor or operator error. Even minor deviations from planned manufacturing processes could result in reduced production yields, product defects and other supply disruptions. If microbial, viral or other contaminations are discovered in our products and product candidates, laboratory or manufacturing facility, we may need to close our laboratory or manufacturing facility for an extended period of time to investigate and remediate the contaminant.
Any adverse developments affecting manufacturing operations or the operations of third-party suppliers and manufacturers may result in shipment delays, inventory shortages, lot failures, product withdrawals or recalls or other interruptions and/or delays in the clinical development or commercial supply of our products. Additionally, we may also have to take inventory write-offs and incur other charges and expenses for products that fail to meet specifications, undertake costly remediation efforts or seek more costly manufacturing alternatives. Such developments could increase manufacturing costs, cause revenue loss or loss of market share as patients and physicians turn to competing therapeutics, diminish profitability or damage our reputation.
In addition, although we have business continuity plans to reduce the potential for manufacturing disruptions or delays and reduce the severity of a disruptive event, there is no guarantee that these plans will be adequate, which could adversely affect our business and operations.
Risks Related to the Production of dsRNA and mRNA
Our proposed products are temperature sensitive and may have other attributes that lead to limited shelf life. These attributes may pose risks to supply, inventory, availability, product relevance and waste management and increased cost of goods.
Our mRNA and dsRNA product candidates may prove to have a stability profile that leads to a lower than desired shelf life of the final approved mRNA medicine. This poses risk in supply requirements, product obsolescence, clinical trial delays, wasted stock, and higher cost of goods.
Our products and product candidates are temperature sensitive, and we may learn that any or all of our product candidates are less stable than desired. It is also possible that we may find that transportation conditions negatively impact product quality. This may require changes to the formulation or manufacturing process for one or more of our product candidates and result in delays or interruptions to clinical or commercial supply. In addition, the cost associated with such transportation services and the limited pool of vendors may also add additional risks of supply disruptions.
We have established a number of analytical assays, and may have to establish several more, to assess the quality of our dsRNA and mRNA product candidates. We may identify gaps in our analytical testing strategy that might prevent release of product or could require product withdrawal or recall. For example, new impurities that have an impact on product safety, efficacy, or stability may be discovered. This may lead to an inability to release mRNA product candidates until the manufacturing or testing process is rectified.
Risks Related to Raw Materials and Reliance on Third Parties
The materials used in the processes by which we manufacture RNA and our derivative products, such as dsRNA or mRNA, may become difficult to obtain in the quality or quantity required for our business plans or at the prices that are currently projected.
Many of our processes and products rely on materials purchased from third parties and should these materials increase in prices, have supply constraints, or become unavailable, it could impact our ability to develop products or bring them to market either on time, at competitive prices or at all. For example, our dsRNA processes use specific yeast microbial RNA, the most effective forms of which are sourced from suppliers in China. Should that particular yeast become unavailable, it could impair the effectiveness, yield or availability of the dsRNA produced for the agricultural markets.
Moreover, some enzymes that are used in our RNA platform and our down-stream products are specific in nature and sourced from third parties, some of whom have proprietary processes which give them an advantage in cost or effectiveness that they pass on to us. Some materials come from single sources, such as LNPs, which are licensed from a third party and which are used to produce mRNA. We may need to license other materials from third parties, and if we are unable to do so on reasonable terms, or at all, it could have a material adverse effect on our business.
Some of the raw materials are being employed in an innovative manner and may not be scaled to a level to support commercial supply and we could experience unexpected manufacturing or testing failures, or supply shortages. Such issues with raw materials and excipients could cause delays or interruptions to clinical and commercial supply of products or product candidates.
Single or limited sources for some materials may impact our ability to secure supply.
Our dependence on single-source, limited-source or preferred suppliers exposes us to certain risks, such as:
•a disruption to suppliers’ operations which could leave us with no other means of continuing the research, development, or manufacturing operations for which the supplier provides inputs;
•the inability to locate a suitable replacement on acceptable terms or on a timely basis, if at all;
•existing suppliers may cease or reduce production or deliveries, raise prices, or renegotiate terms;
•delays caused by supply issues may harm our reputation, frustrate customers, and cause them to turn to our competitors; and
•Our ability to progress the development of existing programs and the expansion of capacity to begin future programs could be materially and adversely impacted if the single-source, limited-source or preferred suppliers upon which we rely were to experience a significant business challenge, disruption, or failure due to issues such as
financial difficulties or bankruptcy, issues relating to other customers such as regulatory or quality compliance issues, or other financial, legal, regulatory, or reputational issues.
Should any of the above risks, or should any consequences of unpredictable risks, come to fruition, such events could have a material adverse effect on operations.
We rely on highly specialized equipment and consumables for the production of RNA and our derivative products, dsRNA and mRNA, and any disruption to the supply chain or any malfunction of that equipment may adversely impact our operations.
The equipment and consumables used to produce RNA and our derivative products, dsRNA and mRNA, continue to be supply constrained across all suppliers, which may cause delays in development, testing or marketing of our human health products and may require us to ultimately increase prices should our products become available to consumers.
Additionally, we will be dependent on a number of equipment providers and CMOs who are also implementing innovative technology. If such equipment malfunctions or if we encounter unexpected performance issues, we could encounter delays or interruptions to clinical and commercial supply. Due to the number of different programs, we may have cross contamination of product candidates inside of our factories, CROs, suppliers, or in the clinic that affect the integrity of our product candidates.
Delay or unavailability of products, services, or equipment provided by suppliers could require us to change the design of our research, development, and manufacturing processes based on the functions, limitations, features, and specifications of the replacement items or seek out a new supplier to provide these items. Additionally, as we grow, our existing suppliers may not be able to meet our increasing demand, and additional suppliers may need to be found. We may not be able to secure suppliers who provide lab supplies at, or equipment and services to, the specification, quantity, and quality levels that we demand (or at all) or be able to negotiate acceptable fees and terms of services with such suppliers.
Risks Related to Market Acceptance
Even if any of the product candidates we develop receives regulatory approval, we may nonetheless fail to achieve the degree of market acceptance by physicians, patients, healthcare payors, and others in the medical community on the human health side and by growers, farmers, and others in the agricultural community on the plant and animal health side, in each case, necessary for commercial success.
The commercial success of any of our product candidates will depend upon its degree of market acceptance by physicians, patients, third party payors, and others in the medical community with respect to human health products and by growers, farmers, and others in the agricultural community with respect to plant and animal health products. Even if any product candidates we develop receive regulatory approval, they may nonetheless fail to gain sufficient market acceptance by physicians, patients, healthcare payors, and others in the medical community. The degree of market acceptance of any product candidates we may develop, if approved for commercial sale, will depend on a number of factors, including:
With respect to human health products:
•the wider acceptance by patients of products derived from RNA manufacturing processes;
•the efficacy and safety of such product candidates as demonstrated in pivotal clinical trials published in peer-reviewed journals;
•the potential and perceived advantages compared to alternative treatments;
•the ability to offer our products for sale at competitive prices;
•the ability to offer appropriate patient access programs, such as co-pay assistance;
•the extent to which physicians recommend our products to their patients;
•convenience and ease of dosing and administration compared to alternative treatments;
•the clinical indications for which the product candidate is approved by the FDA, EMA or other comparable foreign regulatory agencies;
•product labeling or product insert requirements of the FDA, EMA or other comparable foreign regulatory authorities, including any limitations, contraindications or warnings contained in a product’s approved labeling;
•restrictions on how the product is distributed;
•the timing of market introduction of competitive products;
•publicity concerning our products or competing products and treatments;
•the effectiveness of marketing and distribution efforts by us and other licensees and distributors;
•sufficient governmental third party coverage or reimbursement; and
•the prevalence and severity of any side effects.
With respect to plant and animal health products:
•the wider acceptance by growers, farmers, and others in the agricultural community to adopt a dsRNA-based product;
•the efficacy of such dsRNA-based products;
•the compatibility of such dsRNA-based products to be used with other products;
•the potential and perceived advantages compared to alternative solutions;
•the ability to offer our products for sale at competitive prices;
•convenience and ease of using such dsRNA-based products;
•the timing of market introduction of competitive products;
•publicity concerning our products or competing products and solutions;
•the effectiveness of marketing and distribution efforts by us and other distributors; and
•potential off-target effects.
If any product candidates developed by us does not achieve an adequate level of acceptance by physicians, healthcare payors, patients and the medical community with respect to human health products and by growers, farmers, and the agricultural community with respect to plant and animal health products, we will not be able to generate significant revenue, and may not become or remain profitable. The failure of any product candidates to find market acceptance could harm our business prospects.
Legal requirements as well as ethical and social concerns about synthetic biology and genetic engineering could limit or prevent the use of our technologies and limit revenues.
Our platform technology, including how dsRNA and mRNA is extracted, includes the use of synthetic biology and genetic engineering. In some countries, drugs made using genetically modified organisms may be subject to a more stringent legal regime, which could prove to be complex and very challenging. For example, in the European Union, the rules on genetically modified organisms could apply in addition to the general rules on medicinal products or cosmetic products. The rules on advanced therapy medicinal products may also apply.
Additionally, public perception about the safety and environmental hazards of, and ethical concerns over, synthetic biology and genetic engineering could influence public acceptance of our technologies, product candidates and processes, particularly in the case of human medicines such as our COVID-19 vaccine product candidate. If we, our collaborators or other third parties are not able to overcome the legal challenges as well as the social concerns relating to synthetic biology and genetic engineering, our technologies, product candidates and processes may not be accepted. These challenges and concerns could result in increased expenses, regulatory scrutiny and increased regulation, trade restrictions on imports of our product candidates, delays or other impediments to our programs or the public acceptance and commercialization of our products.
While we aim to produce agricultural products that leave low to no residue in foodstuffs, there may be instances of residue when our products are used on certain materials with high preservatives.
While GreenLight designs its products to be low-residue, there may be instances of use case or formulations where some residue may exist for longer periods because of environmental factors or the product being used with other materials. While we do not believe that residues present a health risk to humans, the existence, duration or amount of residues could limit adoption of products containing those residues.
While we carefully design our dsRNA products to be specific and with the goal of avoiding off-target effects, we cannot guarantee that such products will have zero off-target effects.
Our dsRNA products are designed to be specific for targeted invasive pests and with the goal of having no off-target effects on non-target organisms. In designing our products, we compare the genome of our target species to the genome of other species that may co-exist with it to enable us to avoid off-target effects; however, it is not feasible or practicable to test our dsRNA products against every organism and there may be off-target effects on organisms that we are not aware of or that could cause effects that would limit the regulatory approval or commercial adoption of our products.
Our product candidates could have unintended consequences, which could have a material adverse effect on our business, financial condition, or results of operations, and may expose us to liability for any resulting harm.
We design and produce product candidates with characteristics comparable or superior to those found in naturally occurring organisms or enzymes in a controlled laboratory; however, the release of such organisms into uncontrolled environments could have unintended consequences. Any adverse effect resulting from such a release could have a material adverse effect on our business, financial condition or results of operations, and may expose us to liability for any resulting harm.
Risks Related to Global Expansion
Our planned manufacturing, sales and operations are subject to the risks of doing business internationally.
In the future, we intend to expand the reach of our platform technology into international markets, including certain countries in Africa, Asia and Latin America where the need for locally produced vaccines and achieving food security is high, subjecting us to many risks that could adversely affect our business and revenues. There is no guarantee that our efforts and strategies to expand manufacturing and sales in international markets will succeed. Emerging market countries may be especially vulnerable to periods of global and local political, legal, regulatory and financial instability and may have a higher incidence of corruption and fraudulent business practices. Certain countries may require local clinical trial data as part of the drug registration process in addition to global clinical trials, which can add to overall drug development and registration timelines. We may also be required to increase our reliance on third-party agents and unfamiliar operations and arrangements previously utilized by companies we collaborate with or acquire in emerging markets.
Our manufacturing, sales and operations are subject to the risks of doing business internationally, including:
•difficulties and challenges relating to the building, commissioning and complying with regulatory requirements related to manufacturing facilities in foreign countries;
•the inability to obtain necessary foreign regulatory or pricing approvals of products in a timely manner;
•limitations and additional pressures on our ability to obtain and maintain product pricing or receive price increases, including those resulting from governmental or regulatory requirements;
•the inability to successfully complete preclinical studies or subsequent or confirmatory clinical trials in countries where our experience is limited;
•the willingness of regulatory agencies to accept data from preclinical studies or clinical trials conducted in other jurisdictions;
•the willingness of and time required for regulatory bodies and agencies to review and approve new dsRNA-based agricultural products;
•longer payment and reimbursement cycles and uncertainties regarding the collectability of accounts receivable;
•fluctuations in foreign currency exchange rates that may adversely impact our revenues, net income and value of certain of our investments;
•the imposition of governmental controls;
•diverse data privacy and protection requirements;
•increasingly complex standards for complying with foreign laws and regulations that may differ substantially from country to country and may conflict with corresponding U.S. laws and regulations;
•the far-reaching anti-bribery and anti-corruption legislation in the U.K., including the Bribery Act, and elsewhere and escalation of investigations and prosecutions pursuant to such laws;
•compliance with complex import and export control laws;
•changes in tax laws;
•the imposition of tariffs or embargoes and other trade restrictions;
•the impact of public health epidemics, such as the COVID-19 pandemic, on the global economy and the delivery of healthcare treatments;
•less favorable intellectual property or other applicable laws; and
•known and unknown risks related to local and geopolitical unrest;
In addition, our future potential international operations are subject to regulation under U.S. law, and non-compliance with those laws may subject us to severe criminal and civil penalties. For example, the FCPA prohibits U.S. companies and their representatives from paying, offering to pay, promising to pay or authorizing the payment of anything of value to any foreign government official, government staff member, political party or political candidate for the purpose of obtaining or retaining business or to otherwise obtain favorable treatment or influence a person working in an official capacity. In many countries, the health care professionals with whom we may regularly interact may meet the FCPA’s definition of a foreign government official. Failure to comply with domestic or foreign laws could result in various adverse consequences, including possible delay in approval or refusal to approve a product, recalls, seizures or withdrawal of an approved product from the market, disruption in the supply or availability of our products or suspension of export or import privileges, the imposition of civil or criminal sanctions, the prosecution of executives overseeing our international operations and damage to our reputation. Any significant impairment of our ability to sell products outside of the U.S. could adversely impact our business and financial results.
Our goal of expanding outside the U.S. will depend on our ability to successfully manage the complexity of multiple global supply chains in countries with poor infrastructure, in which we have limited experience.
Logistics, regulatory environments, business customs, local and geopolitical concerns and end user markets differ country by country. As we expand globally to enable the production of our dsRNA and mRNA products in countries outside the U.S., we will face material risks that could cause us to expend significant resources. There can be no guarantee when such efforts will be successful, if at all. As we expand our platform globally, we will have to familiarize ourselves with the regulatory environment in that country, which could significantly diverge from the regulatory regimes in the U.S. and which may not necessarily approve our product candidates, even if such product candidates achieve regulatory approval in the U.S.
In each country in which we intend to utilize our manufacturing platform, it may also be necessary to create partnerships with local enterprises, which come with inherent risks, including corruption, violation of U.S. laws and regulations relating to anti-corruption laws, intellectual property theft, divergence from our quality and health standards and a number of unknown risks that could delay or cause our international expansion to fail entirely.
We will have to become familiar with these and other factors in order to be effective; however, our ability to do so is untested as is our ability to obtain and retain experts in these areas to implement an international supply chain serving any facility other than those in the United States. Moreover, any of our suppliers could go out of business, lose operating licenses or be subject to regulatory actions and be unable to supply us, which could result in production delays or stoppages.
Risks Related to Competition
We face significant competition, and if our competitors develop and market technologies or products more rapidly than we do or that are more effective, safer or less expensive than the product candidates we develop, our commercial opportunities will be negatively impacted.
We believe one of our key competitive advantages is the cost and quality at which we can make RNA and recover dsRNA from it for use in agricultural products or mRNA for use in human health products. Should other processes match or beat that cost or quality, we could lose a key competitive advantage as an RNA producer which could in turn have negative effects on the products in our pipeline which depend on the quality and cost of the RNA produced by us to be competitive. Fermentation is currently the most popular method competing with our process for the production of RNA. While we believe fermentation is currently more expensive and tends to produce more down-stream impurities than our proprietary process, innovation or scale in the fermentation process could cause these drawbacks to be overcome to produce a product that is cost competitive with ours. Conventional cell-free processes, such as in-vitro transcription are cost prohibitive for agricultural applications and require special inputs. New innovations in cell-free processes could outperform our cell-free processes and make our technology obsolete.
Rapidly changing technology and emerging competition in the biotechnology industry could make the platform, programs, and products we are developing obsolete or non-competitive unless development of our platform and pursuit of new market opportunities continues.
The biotechnology industry is still emerging and is characterized by rapid and significant technological changes, frequent new product introductions and enhancements, and evolving industry demands and standards. Our future success will depend on our ability to develop, manufacture and commercialize our product candidates on a timely and cost-effective basis.
Our competitors, either alone or together with collaborators, may have significantly greater financial, manufacturing, marketing, drug development, technical and human resources and commercial expertise than we do. Our competitors may also have more experience:
•developing drug candidates;
•conducting preclinical and clinical trials;
•obtaining regulatory approvals; and
•commercializing product candidates.
Risks Related to our Human Health Program
Even if we successfully design and complete our preclinical studies, our preclinical human health product candidates, and similar products in the future, must still go through clinical studies, which may reveal significant adverse events, including negative immune system responses, and may result in a safety profile that could prevent or delay regulatory approval or licensure or market acceptance of candidate products.
There is typically an extremely high rate of attrition for product candidates across categories of medicines proceeding through clinical trials. These product candidates may fail to show the desired safety and efficacy profile in later stages of clinical trials despite having progressed through nonclinical studies and initial clinical trials. A number of companies in the biopharmaceutical industry have suffered significant setbacks in later stage clinical trials due to lack of efficacy or unacceptable safety profiles, notwithstanding promising results in earlier trials. Most investigational medicines that commence clinical trials are never approved as products and there can be no assurance that any of our current or future clinical trials will ultimately be successful or support further clinical development of any of our investigational medicines. Certain aspects of our investigational medicines may induce immune reactions from either the mRNA or the lipid as well as adverse reactions within liver pathways or degradation of the mRNA or the lipid nanoparticle (LNP), any of which could lead to significant adverse events in one or more of our clinical trials. Many of these types of side effects have been seen for previously developed LNPs. There may be resulting uncertainty as to the underlying cause of any such adverse event, which would make it difficult to accurately predict side effects in future clinical trials and would result in significant delays in our programs.
If unacceptable side effects, including materialized risks of immunogenicity, arise in the development of our product candidates, the FDA, a comparable foreign regulatory authority or the Institutional Review Boards (IRBs) at the institutions in which its studies are conducted, or the Data Safety Monitoring Board, if constituted for its clinical studies could recommend a suspension or termination of our clinical studies, or the FDA or comparable foreign regulatory authorities could order us to cease further development of or deny licensure or approval of a product candidate. In addition, side effects could affect patient
recruitment or the ability of enrolled patients to complete a trial or result in potential product liability claims. In addition, these side effects may not be appropriately recognized or managed by the treating medical staff. We expect to have to train medical personnel using our product candidates to understand the side effect profiles for our clinical studies and upon any commercialization of any of our product candidates. Inadequate training in recognizing or managing the potential side effects of our product candidates could result in patient injury or death.
Even if such side effects do not preclude the drug from obtaining or maintaining marketing approval, any such approval may be for a more narrow indication than we seek or an unfavorable benefit risk ratio may inhibit market acceptance of the approved product due to its tolerability versus other therapies. In addition, regulatory authorities may not approve the labeling claims that are necessary or desirable for the successful commercialization of any product candidates we develop. Consequently, the commercial prospects of such product candidates may be harmed, and our ability to generate product revenues from any of these product candidates may be delayed or eliminated. Any of these occurrences may harm our business, financial condition and prospects significantly.
Additionally, if one or more of our product candidates receives marketing licensure and/or approval, and we or others later identify undesirable side effects caused by such products, a number of potentially significant negative consequences could result, including:
•regulatory authorities may withdraw licensures and/or approvals of such product;
•regulatory authorities may require additional warnings on the label, such as a “black box” warning or contraindication;
•additional restrictions may be imposed on the marketing of the particular product or the manufacturing processes for the product or any product component;
•we may be required to restrict the conductions under which the product may be distributed, including through implementation of a Risk Evaluation and Mitigation Strategy, or REMS;
•we may be required to change the way a product candidate is administered or conduct additional clinical trials;
•we could be sued and held liable for harm caused to patients;
•the product may become less competitive; and
•our reputation may suffer.
Any of these events could prevent us from achieving or maintaining market acceptance of a product candidate, if approved, and could significantly harm our business, results of operations and prospects.
Our human health markets are highly competitive. If we are unable to compete effectively with existing products, new treatment methods, new technologies or supply chain efficiencies, we may be unable to commercialize any products that we may develop in the future.
The biotechnology market is highly competitive, is subject to rapid technological change and is significantly affected by existing rival products and medical procedures, new product introductions and the market activities of other participants. Pharmaceutical and biotechnology companies, academic institutions, governmental agencies and other public and private research organizations may pursue the research and development of technologies, products or other therapeutic products for the treatment of some or all of the diseases that we target. We also may face competition from products that have already been approved or licensed and accepted by the medical community for the treatment of these same indications. Our competitors may develop products more rapidly or more effectively than us. Many of our competitors have:
•much greater experience, financial, technical and human resources than we have at every stage of the discovery, development, manufacture and commercialization process;
•more extensive experience in preclinical studies, conducting clinical trials, obtaining and maintaining regulatory approvals or licensures and manufacturing and marketing products;
•products that have been approved or licensed or are in late stages of development;
•established distribution networks that can include preferential pricing, delivery or other terms with other participants in their supply chains;
•collaborative arrangements with leading companies and research institutions; and
•entrenched and established relationships with healthcare providers and payors.
In addition, many of these companies, in contrast to us, are well-capitalized. As a result of any of the foregoing factors, our competitors may develop or commercialize products with significant advantages over any product that we may develop in the future. If our competitors are more successful in commercializing their products than us, their success could adversely affect our competitive position and harm our business prospects.
If we encounter difficulties enrolling patients in our clinical studies, including due to global health matters such as COVID-19, our clinical development activities could be delayed or otherwise adversely affected.
We may experience difficulties in patient enrollment in our clinical studies for a variety of reasons. The timely completion of clinical studies in accordance with their protocols depends, among other things, on our ability to enroll a sufficient number of patients who remain in the trial until its conclusion. The enrollment of patients depends on many factors, including:
•the patient eligibility and exclusion criteria defined in the protocol;
•the severity of the disease under investigation;
•the size of the patient population required for analysis of the trial’s primary endpoints and the process for identifying patients;
•the proximity of patients to trial sites;
•the design of the trial;
•our ability to recruit clinical study investigators with the appropriate competencies and experience;
•clinicians’ and patients’ perceptions as to the potential advantages and risks of the product candidate being studied with respect to other available therapies, including any new products that may be approved for the indications we are investigating;
•the availability of competing commercially available therapies and other competing product candidates’ clinical studies;
•the ability to monitor patients adequately during and after treatment;
•efforts to facilitate timely enrollment in clinical trials;
•our ability to obtain and maintain patient informed consents; and
•the risk that patients enrolled in clinical studies will drop out of the trials before completion.
Further, timely enrollment in clinical studies is reliant on clinical study sites, which may experience delays or otherwise be adversely affected by disruptions due to global health matters, including COVID-19 and other pandemics.
If successfully released for sale, our COVID-19 vaccine candidate may fail to gain market acceptance.
Even if our mRNA vaccine for COVID-19 successfully completes clinical trials and is approved for commercial marketing, it may fail to meet the same high level of efficacy demonstrated by competitors and our ability to obtain revenues from the vaccine may be diminished or eliminated altogether. Moreover, the addressable market for our COVID-19 candidate may be limited if competing products have saturated some or all markets, particularly the most profitable markets. Further, any delays in commercialization may result in any approved COVID-19 vaccine becoming obsolete as the COVID-19 virus continues to mutate, which in turn may require us to obtain the production resources for replacement material, redevelop the material and restart the regulatory approval process or cancel the development of that product candidate.
We may incur additional costs or experience delays in completing the development and commercialization of our product candidates.
Clinical testing is expensive, difficult to design and implement, can take many years to complete and is uncertain as to timing and outcome. A failure of one or more clinical studies can occur at any stage in the process. We may experience delays in initiating or completing clinical studies. We may also experience numerous unforeseen events during, or as a result of, any future
clinical studies that could delay or prevent our ability to receive marketing licensure and approval to commercialize our product candidates, including:
•Regulators, or IRBs, Data Safety Monitoring Boards, or ethics committees may not authorize us or our investigators to commence a clinical study or conduct a clinical study at a prospective trial site or may impose burdensome restrictions on or cause delays of the clinical study at a prospective trial site;
•the FDA or other comparable regulatory authorities may disagree with our clinical study design, including with respect to dosing levels administered in our planned clinical studies, which may delay or prevent us from initiating our clinical studies with our originally intended trial design;
•the FDA or other comparable regulatory authorities may not accept the results of any of our clinical studies conducted in other geographic locations or outside their country’s jurisdiction;
•we may experience delays in reaching, or fail to reach, agreement on acceptable terms with prospective trial sites and prospective Contract Research Organizations (CROs), which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites;
•the number of subjects required for clinical studies of any product candidates may be larger than we anticipate or subjects may drop out of these clinical studies or fail to return for post-treatment follow-up at a higher rate than we anticipate;
•our third-party contractors may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all, or may deviate from the clinical study protocol or drop out of the trial, which may require that we add new clinical study sites or investigators;
•we may experience delays and interruptions to clinical studies, we may experience delays or interruptions to our manufacturing supply chain, or we could suffer delays in reaching, or we may fail to reach, agreement on acceptable terms with third-party service providers on whom we rely;
•additional delays and interruptions to our clinical studies could extend the duration of the trials and increase the overall costs to finish the trials as its fixed costs are not substantially reduced during delays;
•we may elect to, or regulators, IRBs, Data Safety Monitoring Boards or ethics committees may require, that we or our investigators, suspend or terminate clinical research or trials for various reasons, including noncompliance with regulatory requirements or a finding that the participants are being exposed to unacceptable health risks;
•we may need to amend or submit new clinical protocols because of changes in regulatory requirements and guidance;
•we may not have the financial resources available to begin and complete the planned trials, or the cost of clinical studies of any product candidates may be greater than we anticipate; and
•the supply or quality of our product candidates or other materials necessary to conduct clinical studies of our product candidates may be insufficient or inadequate to initiate or complete a given clinical study.
Our product development costs will increase if we experience additional delays in clinical testing or in obtaining marketing approvals or licensure. We do not know whether any of our clinical studies will begin as planned, will need to be restructured or will be completed on schedule, or at all. If we do not achieve our product development goals in the time-frames we announce and expect, the approval, licensure, and commercialization of our product candidates may be delayed or prevented entirely. Significant clinical study delays also could shorten any periods during which we may have the exclusive right to commercialize our product candidates and may allow our competitors to bring products to market before we do, potentially impairing our ability to successfully commercialize our product candidates and harming our business and results of operations. Any delays in our clinical development programs may harm our business, financial condition and results of operations significantly.
The time and expense required to obtain regulatory approvals for our preclinical and clinical trials could be significantly greater than for more conventional therapeutic technologies or products. If clinical trials of any product candidates fail to demonstrate safety and efficacy to the satisfaction of regulatory authorities, do not otherwise produce positive results or are for other reasons not satisfactory to those authorities, we may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of such product candidates.
In the United States, the products that we intend to develop and market are regulated by the FDA under its drug and biologic development and review processes. Before such products can be marketed, we must obtain multiple authorizations and licensures from the FDA, first through submission and authorization of an investigational new drug application, or IND, then
through successful completion of human testing under three phases of clinical trials and finally through submission of a biologics license application, or BLA. Even after successful completion of clinical testing, there is a risk that the FDA may refuse to file our BLA submissions, request further information from us, disagree with our findings, undertake a lengthy review of our BLA submissions or deny our application.
The time required to obtain approval or licensure by the FDA and other comparable regulatory authorities is unpredictable but typically takes many years following the commencement of clinical trials, if at all, and depends upon numerous factors, including the substantial discretion of the regulatory authorities. In addition, approval and licensure policies, regulations or the type and amount of clinical data necessary to gain approval or licensure may change during the course of a product candidate’s clinical development and may vary among jurisdictions. We have not obtained marketing approval or licensure for any product candidate, and it is possible that none of our existing product candidates, or any product candidates we may seek to develop in the future, will ever obtain approval for clinical trials, marketing approval or licensure.
Our product candidates could fail to receive regulatory approval for clinical trials, marketing or licensure in the United States or other countries for many reasons, including the following:
•the regulatory authority may disagree with the design, implementation or location of our clinical trials;
•we may be unable to demonstrate to the satisfaction of the regulatory authority that a product candidate is safe, pure, potent or sufficiently distinguishable from existing therapies already in the market;
•results of clinical trials may not meet the level of statistical significance required for licensure;
•unanticipated delays in starting clinical trials could result in test material becoming obsolete when compared to other therapies or going past its useful life which in turn would require us to obtain the production resources for replacement material, redevelop the material or cancel the development of that product candidate;
•we may be unable to demonstrate that a product candidate’s clinical and other benefits outweigh its safety risks;
•regulators may disagree with our interpretation of data from preclinical studies or clinical trials;
•data collected from clinical trials of our product candidates may not be sufficient to support the submission of a BLA to the FDA or other submission or to obtain marketing licensure in the United States;
•the FDA may find deficiencies with or fail to approve the manufacturing processes or facilities of third-party manufacturers with which we contract for clinical and commercial supplies; and
•the licensure policies or regulations of the FDA may significantly change in a manner rendering our clinical data insufficient for licensure.
This lengthy licensure process as well as the unpredictability of future clinical trial regulatory approvals and results may result in our failing to obtain licensure to market any of our product candidates, which would significantly harm our business, results of operations, financial condition and prospects. The FDA and its counterparts in other countries have substantial discretion in approving clinical trials, granting licenses and determining when or whether regulatory licensure will be obtained for any of our product candidates. Even if we believe the data collected from clinical trials of our product candidates are promising, such data may not be sufficient to support licensure.
In addition, even if we were to obtain licensure, regulatory authorities may approve any of our product candidates for fewer or more limited indications than we request, may not approve the price we intend to charge for our products, may grant a license contingent on the performance of costly post marketing clinical trials, or may approve or license a product candidate with a label that does not include the labeling claims necessary or desirable for the successful commercialization of that product candidate. Any of the foregoing scenarios could materially harm the commercial prospects for our product candidates.
If we decide to market any product that we develop in jurisdictions in addition to the United States, we may incur the same costs or more in satisfying foreign regulatory requirements governing the conduct of preclinical and clinical trials, manufacturing and marketing and commercialization of any product that we develop in the future. Approval or licensure by the FDA by itself does not assure approval by regulatory authorities outside the United States. Each of these foreign regulatory approval processes includes all of the risks associated with the FDA approval or licensing process, as well as risks attributable to having to satisfy local regulations within each of these foreign jurisdictions and the possibility that our management team will be unfamiliar with that country’s regulatory regime. Our inability to obtain regulatory approval outside the United States may also adversely compromise our business prospects.
We may have difficulties convincing the medical community and third-party payors to accept and use any product that we are able to develop in the future even following our receipt of regulatory approval or licensure for commercialization. Key participants in pharmaceutical marketplaces, such as distributors, physicians, third-party payors and consumers, may not accept a product that we develop and we may be unable to compete with multiple-product or portfolio discounts larger competitors may offer. Even if such a product is accepted by these participants, the medical community may not consider effectiveness and safety alone as a sufficient basis for prescribing such as product in lieu of other alternative treatment methods and medications that are available.
We may not be successful in our efforts to identify, develop, or commercialize potential product candidates.
The success of our business depends primarily upon our ability to identify, develop, and commercialize products based on our mRNA platform. Research programs to identify new product candidates require substantial technical, financial, and human resources. We may focus our efforts and resources on potential programs or product candidates that ultimately prove to be unsuccessful. As our development candidates and investigational medicines progress, we or others may determine that: certain of our risk allocation decisions were incorrect or insufficient; we made platform level technology mistakes; individual programs or our mRNA science in general have technology or biology risks that were unknown or under-appreciated; our choices on how to develop our infrastructure to support our needs would likely result in an inability to manufacture our investigational medicines for clinical trials or would otherwise impair our manufacturing; or we have allocated resources in such a way that large investments would not be recovered and capital allocation would not be subject to rapid re-direction. All of these risks may relate to our current and future programs sharing similar science (including mRNA science) and infrastructure, and in the event material decisions in any of these areas turn out to have been incorrect or under-optimized, we may experience a material adverse impact on our business and ability to fund our operations and we may never realize what we believe is the potential of mRNA. If any of these events occur, we may be forced to abandon our development efforts for one or more programs, which would have a material adverse effect on our business, financial condition, results of operations, and prospects.
The successful commercialization of our human health product candidates will depend in part on the extent to which third-party insurers and payors establish adequate coverage, reimbursement levels and pricing policies. Failure to obtain or maintain coverage and adequate reimbursement for our product candidates, if approved, could limit our ability to market those products and decrease our ability to generate revenue.
The availability and extent of coverage and adequate reimbursement by third-party payors, including government health administration authorities, private health coverage insurers, managed care organizations and other third-party payors is essential for most patients to be able to afford expensive treatments. Sales of any of our product candidates that receive marketing approval will depend substantially, both in the United States and internationally, on the extent to which the costs of such product candidates will be covered and reimbursed by third-party payors. If reimbursement is not available, or is available only to limited levels, we may not be able to successfully commercialize our product candidates. Even if coverage is provided, the approved reimbursement amount may not be high enough to allow us to establish or maintain pricing sufficient to realize an adequate return on our investment. Coverage and reimbursement may impact the demand for, or the price of, any product candidate for which we obtain marketing approval. If coverage and reimbursement are not available or reimbursement is available only to limited levels, we may not successfully commercialize any product candidate for which we obtain marketing approval.
There is significant uncertainty related to third-party payor coverage and reimbursement of newly approved products. In the United States, for example, principal decisions about reimbursement for new products are typically made by the Centers for Medicare & Medicaid Services, or CMS, an agency within the U.S. Department of Health and Human Services. CMS decides whether and to what extent a new product will be covered and reimbursed under Medicare, and private third-party payors often follow CMS’s decisions regarding coverage and reimbursement to a substantial degree. However, one third-party payor’s determination to provide coverage for a product candidate does not assure that other payors will also provide coverage for the product candidate. Further, no uniform policy for coverage and reimbursement exists in the United States, and coverage and reimbursement can differ significantly from payor to payor. As a result, the coverage determination process is often time-consuming and costly. This process will require us to provide scientific and clinical support for the use of our products to each third-party payor separately, with no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance.
We cannot predict the likelihood, nature, or extent of health reform initiatives that may arise from future legislation or administrative action.
Changes in healthcare policy could increase our costs, decrease our revenue and impact sales of and reimbursement for our future products, if approved. We expect to experience pricing pressures in connection with the sale of our product candidates due to the trend toward managed health care, the increasing influence of health maintenance organizations and additional legislative
changes. The United States, through the Inflation Reduction Act of 2022, and some foreign jurisdictions are considering or have enacted a number of legislative and regulatory proposals to change the healthcare system in ways that could affect our ability to sell our products profitably once approved. Among policy makers and payors in the United States and elsewhere, there is significant interest in promoting changes in healthcare systems with the stated goals of containing healthcare costs, improving quality or expanding access. Current and future legislative proposals to further reform healthcare or reduce healthcare costs may limit coverage of or lower reimbursement for the procedures associated with the use of our product candidates once approved and, as a result, they may not cover or provide adequate payment for our product candidates. The downward pressure on healthcare costs in general, particularly prescription drugs and biologics and surgical procedures and other treatments, has become intense. As a result, increasingly high barriers are being erected to the entry of new products. The cost containment measures that payors and providers are instituting and the effect of any healthcare reform initiative implemented in the future could impact our revenue from the sale of our products once approved.
We believe that there will continue to be proposals by legislators at both the federal and state levels, regulators and third-party payors to reduce costs and potentially affect individual healthcare benefits. Certain of these changes could impose additional limitations on the rates we will be able to charge for any future products or the amounts of reimbursement available for any future products from governmental agencies or third-party payors.
We are and will continue to be dependent on third parties for strategically important tasks, and our ability to develop our products, obtain regulatory approval or bring products to market may fail if these third parties do not perform as we expect.
We are subject to risks related to our reliance on third parties in that we will:
•seek to enter into collaboration arrangements to fund development and commercialization of our products;
•rely on CROs to conduct key elements of research by which our products are developed;
•rely on Contract Development Organizations (“CDOs”) to develop key components of our products;
•retain individual contractors or contracting organizations to perform critical functions in our company, including functions associated with senior management positions; and
•seek to enter into joint development agreements for the manufacture of both our RNA materials and human health products with partners outside the U.S.
The activities performed by these third parties may be delayed or suspended in light of the ongoing COVID-19 pandemic, which may impact our ability to successfully develop and test our product candidates and research programs in a timely manner.
Our reliance on these third parties for research and development activities will reduce our control over these activities but will not relieve us of our responsibilities. For example, we will remain responsible for ensuring that each of our clinical trials is conducted in accordance with the general investigational plan and protocols for the trial. Moreover, the FDA requires us to comply with standards, commonly referred to as Good Clinical Practices, or GCPs, for conducting, recording, and reporting the results of clinical trials to assure that data and reported results are credible and accurate and that the rights, integrity, and confidentiality of trial participants are protected. We also are required to register ongoing clinical trials and post the results of completed clinical trials on a government-sponsored database, ClinicalTrials.gov, within certain timeframes. Failure to comply with these responsibilities can result in fines, adverse publicity, and civil and criminal sanctions.
The FDA enforces GCP regulations through periodic inspections of clinical trial sponsors, principal investigators, and trial sites. If we or our CROs fail to comply with applicable GCPs, the clinical data generated in our clinical trials may be deemed unreliable and the FDA or comparable foreign regulatory authorities may require us to perform additional clinical trials before approving our marketing applications. We cannot assure you that, upon inspection, the FDA will determine that any of our future clinical trials will comply with GCPs. In addition, our clinical trials must be conducted with investigational medicines produced in accordance with the requirements in cGMP regulations. Our failure or the failure of our CROs to comply with these regulations may require us to repeat clinical trials, which would delay the regulatory approval process and could also subject us to enforcement action.
Communicating with outside parties can also potentially lead to mistakes as well as difficulties in coordinating activities. Furthermore, these third parties may also have relationships with other entities, some of which may be our competitors.
If any of these third parties, or others we have business relationships with, fail to meet their obligations to us it will increase our expenses, damage our reputation and could result in the delay or shutdown of the projects they support and result in our inability to bring some or all of our products to market.
Our collaboration arrangements may restrict or prevent our future business activity in certain markets or industries, which could harm our ability to grow our business.
We will seek to enter into collaborations by which, in exchange for funding of infrastructure, development or marketing of our products, we will grant to other parties exclusive rights to the development, production, marketing or distribution of selected products in specific geographies. For example, in March 2022, we granted Serum Institute of India Private Limited (“SIIPL”) an exclusive, sub-licensable, royalty-bearing license to use our proprietary technology platform to develop, manufacture and commercialize an mRNA shingles product and up to two other mRNA products in all territories other than the United States, the 27 member states of the European Union, the United Kingdom, Australia, Japan, New Zealand, Canada, South Korea, China, Hong Kong, Macau, and Taiwan. These rights may keep us from entering into alternative collaborations which may keep us from using capital effectively and limit our ability to grow our business. Any failure on the part of our collaboration partners to comply with applicable laws, regulatory requirements and/or applicable contractual obligations or to fulfill any responsibilities they may have to protect and enforce any intellectual property rights underlying product candidates could harm our reputation, including with regulatory authorities, have an adverse effect on revenues, as well as give rise to possible legal proceedings. Moreover, the failure or perceived failure by us to comply with our obligations under a collaboration agreement with any of our collaboration partners could cause the partner to make public statements against us or could result in litigation asserting that we have breached our obligations, any of which could have a material adverse effect on our reputation, business, financial condition, or results of operations.
If we bring our human health products to market as planned, our relationships with customers and third-party payors will be subject to applicable anti-kickback, fraud and abuse and other healthcare laws and regulations, which could expose us to criminal sanctions, civil penalties, program exclusion, contractual damages, reputational harm and diminished profits and future earnings.
Healthcare providers, physicians and third-party payors play a primary role in the recommendation of any product for which we obtain marketing licensure or approval. Our future arrangements with third-party payors and customers may expose us to broadly applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we market, sell and distribute products for which we obtain marketing approval. Efforts to ensure that our business arrangements with third parties comply with applicable healthcare laws and regulations will involve substantial costs. It is possible that governmental authorities will conclude that our business practices may not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations. If our operations are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, damages, fines and exclusion from government funded healthcare programs, such as Medicare and Medicaid, and the curtailment or restructuring of our operations. If any of the physicians or other providers or entities with whom we expect to do business are found not to be in compliance with applicable laws, they may be subject to criminal, civil or administrative sanctions, including exclusions from government-funded healthcare programs.
We are subject to significant regulation with respect to manufacturing our products. The manufacturing facilities on which we will rely may not continue to meet regulatory requirements and have limited capacity.
All entities involved in the preparation of vaccines and products for clinical studies or commercial sale, including other contract manufacturers we have used or may use, are subject to extensive regulation. Components of a finished therapeutic product approved or licensed for commercial sale or used in late-stage clinical studies must be manufactured in accordance with applicable good manufacturing practice requirements, or GMP. These regulations govern manufacturing processes and procedures (including record keeping) and the implementation and operation of quality systems to control and assure the quality of investigational products and products approved or licensed for sale. Poor control of production processes can lead to the introduction of adventitious agents or other contaminants, or to inadvertent changes in the properties or stability of our product candidates that may not be detectable in final product testing. We or our contract manufacturers must supply all necessary documentation in support of a BLA on a timely basis and must adhere to the FDA’s good laboratory practices, or GLP, and GMP regulations enforced by the FDA through its facilities inspection program. Our facilities and quality systems and the facilities and quality systems of some or all our third-party contractors must pass a pre-approval inspection for compliance with the applicable regulations as a condition of regulatory licensure and approval of our product candidates. In addition, the regulatory authorities may, at any time, audit or inspect a manufacturing facility involved with the preparation of our product candidates or the associated quality systems for compliance with GMP and other regulations applicable to the activities being conducted. If these facilities do not pass a pre-approval plant inspection or do not have a GMP compliance status acceptable for the FDA, FDA approval or licensure of the products will not be granted.
As product candidates proceed through preclinical studies to late-stage clinical trials towards potential approval and commercialization, various aspects of the development program, such as manufacturing methods and formulation, are commonly altered along the way in an effort to optimize processes and results. Such changes carry the risk that they will not achieve these intended objectives. Any of these changes could cause our product candidates to perform differently and affect the results of planned clinical trials or other future clinical trials conducted with the materials manufactured using altered processes. Such changes may also require additional testing, FDA notification or FDA approval. This could delay or prevent completion of clinical trials, require conducting bridging clinical trials or the repetition of one or more clinical trials, increase clinical trial costs, delay or prevent approval of our product candidates and jeopardize our ability to commence sales and generate revenue.
The regulatory authorities also may, at any time following licensure or approval of a product for sale, audit our manufacturing facilities or those of our third-party contractors. If any such inspection or audit identifies a failure to comply with applicable regulations or if a violation of our product specifications or applicable regulations occurs independent of such an inspection or audit, we or the relevant regulatory authority may require remedial measures that may be costly and/or time-consuming for us or a third-party to implement and that may include the temporary or permanent suspension of a clinical study or commercial sales or the temporary or permanent closure of a facility. Any such remedial measures imposed upon us or third parties with whom we contract could materially harm our business.
If we or any of our third-party manufacturers fail to maintain regulatory compliance with applicable GMP requirements, the FDA can impose regulatory sanctions including, among other things, refusal to approve a pending application for a new product or biologic product, or revocation of a pre-existing approval. As a result, our business, financial condition and results of operations may be materially harmed.
Additionally, if supply from one approved manufacturer is interrupted, there could be a significant disruption in commercial supply. An alternative manufacturer would need to be qualified through a BLA supplement which could result in further delay. The regulatory agencies may also require additional studies if a new manufacturer is relied upon for commercial production. Switching manufacturers may involve substantial costs and is likely to result in a delay in our desired clinical and commercial timelines.
These factors could cause the delay of clinical studies, regulatory submissions, required approvals or commercialization of our product candidates, cause us to incur higher costs and prevent us from commercializing our products successfully. Furthermore, if our suppliers fail to meet contractual requirements, and we are unable to secure one or more replacement suppliers capable of production at a substantially equivalent cost, our clinical studies may be delayed, or we could lose potential revenue.
If we, or if our service providers or any third-party manufacturers, fail to comply with regulatory requirements, we or they could be subject to enforcement actions, which could adversely affect our ability to market and sell a product we develop in the future.
We have a limited ability to manufacture materials for our research programs and preclinical studies and we do not operate any significant manufacturing facilities. We primarily rely on third-party contract manufacturing organizations (“CMOs”) for the manufacture of our materials for preclinical and clinical studies and expect to continue to do so and for commercial supply of any product candidates that we develop and for which we or our collaborators obtain marketing approval. Additionally, the activities performed by our CMOs may be delayed or suspended in light of the ongoing COVID-19 pandemic, which may impact our ability to successfully develop and test our product candidates, including in clinical trials, and research programs in a timely manner.
Reliance on third-party manufacturers entails additional risks, including: the possible breach of the manufacturing agreement by the third party; the possible termination or nonrenewal of the agreement by the third party at a time that is costly or inconvenient for us; and reliance on the third party for regulatory compliance, quality assurance, safety, and pharmacovigilance and related reporting. Third-party manufacturers may not be able to comply with cGMP regulations or similar regulatory requirements outside the United States.
If we, or if our service providers or any third-party manufacturers, fail to comply with applicable federal, state or foreign laws or regulations, we could be subject to enforcement actions, which could adversely affect our ability to successfully develop, market and sell a product we develop in the future and could harm our reputation. These enforcement actions may include:
•restrictions on, or prohibitions against, marketing;
•restrictions on importation;
•suspension of review or refusal to approve new or pending applications;
•suspension or withdrawal of product approvals;
•product seizures or recalls;
•operating restrictions;
•injunctions; and
•civil and criminal penalties and fines.
Risks related to creating a new class of mRNA products
We have not yet succeeded and may not succeed in demonstrating the efficacy and safety of any of our product candidates in clinical trials or in obtaining marketing approval thereafter. We have not yet completed a clinical trial of any product candidate and we have not yet assessed safety of any product candidate in humans. As such, there may be adverse effects from treatment with any of our current or future product candidates that we cannot predict at this time.
Other than the approvals of the Pfizer-BioNTech COVID-19 Vaccine and the Moderna Spikevax COVID-19 Vaccine, and the previous Emergency Use Authorizations for these COVID-19 vaccines, no mRNA medicines have been granted EUA or have been granted full approval or licensure to date by the FDA or other regulatory agencies. Moreover, it is possible that FDA and other regulators will decline to accept new EUA submissions for COVID-19 vaccine candidates if it is determined that the underlying health emergency no longer exists or warrants such authorization. Successful discovery and development of other mRNA medicines by us or our strategic collaborators is highly uncertain and depends on numerous factors, many of which are beyond our or their control. We have made and will continue to make a series of business decisions and take calculated risks to advance our development efforts and pipeline, including those related to mRNA technology, delivery technology, and manufacturing processes, which may be shown to be incorrect based on further work by us, our strategic collaborators, or others. Our products that appear promising in the early phases of development may fail to advance, experience delays in the clinic, experience clinical holds, or fail to reach the market for many reasons, including:
•discovery efforts at identifying potential mRNA medicines may not be successful;
•nonclinical or preclinical study results may show potential mRNA medicines to be less effective than desired or to have harmful or problematic side effects;
•clinical trial results may show potential mRNA medicines to be less effective than expected (e.g., a clinical trial could fail to meet one or more endpoint(s)) or to have unacceptable side effects or toxicities;
•adverse effects in any one of our clinical programs or adverse effects relating to our mRNA, or our lipid nanoparticles (“LNPs”), may lead to delays in or termination of one or more of our programs;
•the insufficient ability of translational models to reduce risk or predict outcomes in humans, particularly given that each component of investigational medicines and development candidates may have a dependent or independent effect on safety, tolerability, and efficacy, which may, among other things, be species-dependent;
•manufacturing failures or insufficient supply of cGMP materials for clinical trials, or higher than expected cost could delay or set back clinical trials, or make mRNA-based medicines commercially unattractive;
•our improvements in the manufacturing processes for this new class of medicines and potential medicines may not be sufficient to satisfy the clinical or commercial demand of our investigational medicines or regulatory requirements for clinical trials;
•changes that we make to optimize our manufacturing, testing or formulating of cGMP (cGMP regulations as enforced by the FDA) materials could impact the safety, tolerability, and efficacy of our investigational medicines and development candidates;
•pricing or reimbursement issues or other factors may delay clinical trials or make any mRNA medicine uneconomical or noncompetitive with other therapies;
•failure to timely advance our programs or receive the necessary regulatory approvals or a delay in receiving such approvals, due to, among other reasons, slow or failure to complete enrollment in clinical trials, withdrawal by trial participants from trials, failure to achieve trial endpoints, additional time requirements for data analysis, data integrity issues, preparation of a BLA, or the equivalent application, discussions with the FDA or EMA, a
regulatory request for additional nonclinical or clinical data, or safety formulation or manufacturing issues may lead to our inability to obtain sufficient funding; and
•the proprietary rights of others and their competing products and technologies that may prevent our mRNA medicines from being commercialized.
Currently, mRNA is considered a gene therapy product by the FDA. Unlike certain gene therapies that irreversibly alter cell DNA and could act as a source of side effects, mRNA-based medicines are designed to not irreversibly change cell DNA; however, side effects observed in gene therapy could negatively impact the perception of mRNA medicines despite the differences in mechanism. In addition, because no product in which mRNA is the primary active ingredient has been approved without first being authorized for emergency use, the regulatory pathway for approval is uncertain. The number and design of the clinical trials and preclinical studies required for the approval of these types of medicines have not been established, may be different from those required for gene therapy products, or may require safety testing like gene therapy products. Moreover, the length of time necessary to complete clinical trials and to submit an application for marketing approval for a final decision by a regulatory authority varies significantly from one pharmaceutical product to the next, and may be difficult to predict.
Adverse events in clinical trials of our investigational medicines or in clinical trials of others developing similar products and the resulting publicity, as well as any other adverse events in the field of mRNA medicine, or other products that are perceived to be similar to mRNA medicines, such as those related to gene therapy or gene editing, could result in a decrease in the perceived benefit of one or more of our programs, increased regulatory scrutiny, decreased confidence by patients and clinical trial collaborators in our investigational medicines, and less demand for any product that we may develop. In addition, responses by U.S., state, or foreign governments to negative public perception may result in new legislation or regulations that could limit our ability to develop any investigational medicines or commercialize any approved products, obtain or maintain regulatory approval, or otherwise achieve profitability. More restrictive statutory regimes, government regulations, or negative public opinion would have an adverse effect on our business, financial condition, results of operations, and prospects and may delay or impair the development of our investigational medicines and commercialization of any approved products or demand for any products we may develop.
Risks Related to Our Plant Health Program
Our inability to obtain regulatory approvals, or to comply with ongoing and changing regulatory requirements, could delay or prevent sales of the products we are developing and commercializing.
The field testing, manufacture, sale and use of crop protection, plant health and plant nutrition products are extensively regulated by the EPA and other state, local and foreign governmental authorities. These regulations substantially increase the time and cost associated with bringing our products to market. If we do not receive the necessary governmental approvals to test, manufacture and market our products, or if regulatory authorities revoke our approvals, do not grant approvals in a timely manner or grant approvals subject to restrictions on their use, we may be unable to sell our products in the United States or other jurisdictions, which could result in a reduction in our future revenues.
As we introduce new formulations of and applications for our products, we may need to seek EPA approval prior to commercial sale. For any such approval, the EPA may require us to fulfill certain conditions within a specified period of time following initial approval. We will also be required to obtain regulatory approval from other state and foreign regulatory authorities before we market our products in their jurisdictions, some of which have taken, and may take, longer than anticipated.
Some of these states and foreign countries may apply different criteria than the EPA in their approval processes. Although federal pesticide law preempts separate state and local pesticide registration requirements to some extent, state and local governments retain authority to control pesticide use within their borders.
There can be no assurance that we will be able to obtain regulatory approval for marketing any of our products or new product formulations and applications we are developing. Although the EPA has in place a registration procedure for biopesticides there can be no assurance that all of our products or product extensions will be eligible for this streamlined procedure or that additional requirements will not be mandated by the EPA that could make the procedure more time consuming and costly for our future products.
Additionally, for certain state registration and registration in jurisdictions outside of the United States, all products need to be proven efficacious for each proposed crop-pest combination, which can require costly field trial testing, and a favorable result is not assured. Because many of the products that may be sold by us must be registered with one or more government agencies, the registration process can be time consuming and expensive, and there is no guarantee that the product will obtain all required registrations. We may seek registration in some jurisdictions and not in others. California is one of the largest and most important
producers of agricultural products in the world. As such, we view California as one of the most natural and attractive markets for our products, but it is also very stringent in its regulations, generally requiring more time and effort, and lacking legally mandated deadlines for its reviews of reduced-risk biopesticides. Therefore, gaining concurrent approvals with the EPA, other states and other countries may not always be achievable. Even if we obtain all necessary regulatory approvals to market and sell our products, they will be subject to continuing review and extensive regulatory requirements, including periodic re-registrations. The EPA, as well as state and foreign regulatory authorities, could withdraw a previously approved product from the market upon receipt of newly discovered information, including an inability to comply with their regulatory requirements or the occurrence of unanticipated problems with our products, or for other reasons.
If our field trials are unsuccessful, we may be unable to obtain regulatory approval of, or commercialize, our products on a timely basis.
The successful completion of multiple field trials in various climates around the world and on various crops is critical to the success of our product development and marketing efforts. If our ongoing or future field trials are unsuccessful or produce inconsistent results or unanticipated adverse side effects on crops or on non-target organisms, or if we are unable to collect reliable data, regulatory approval of our products could be delayed, or we may be unable to commercialize our products. In addition, more than one growing or treatment season may be required to collect sufficient data and we may need to collect data from different geographies to prove performance for customer adoption. Although we have conducted many successful field trials we cannot be certain that additional field trials conducted on a greater number of acres, or on crops for which we have not yet conducted field trials, will be successful. Moreover, the results of our ongoing and future field trials are subject to a number of conditions beyond our control, including weather-related events such as drought or floods, severe heat or frost, hail, tornadoes and hurricanes, or low or no natural occurrence of the pests intended for testing. Generally, we pay third parties, such as growers, consultants and universities to conduct field tests on our behalf. Incompatible crop treatment practices or misapplication of our products by these third parties or lack of sufficient occurrence of the identified pests in nature for a particular trial could impair the success of our field trials.
Crop protection products must be extensively tested for safety, efficacy and environmental impact before they can be registered for production, use, sale or commercialization in a given market.
The regulatory approvals process is lengthy, costly, complex and in some markets unpredictable, with requirements that can vary by product, technology, industry and country. The regulatory approvals process for products that incorporate novel modes of action or new technologies can be particularly unpredictable and uncertain due to the then-current state of regulatory guidelines and objectives, as well as governmental policy considerations and non-governmental organization and other stakeholder considerations. In certain jurisdictions, we will need to periodically renew any regulatory approvals which may require us to demonstrate compliance with shifting or more stringent requirements as time passes.
The markets for biological agricultural products are intensely competitive, rapidly changing and undergoing consolidation. We may be unable to compete successfully against our current and future competitors, which may result in price reductions, reduced margins and the inability to achieve market acceptance for our products.
Many entities with significantly greater resources than us are engaged in developing biological agricultural products, including BASF SE, Valent BioSciences Corporation, Corteva Agriscience, UPL Limited, and FMC Corporation. Each of these competitors is a major multinational agrichemical company with longer operating histories, significantly greater resources, greater brand recognition, established global sales channels and a larger base of customers than we have. As a result, they may be able to devote greater resources to the manufacture, promotion or sale of their products, receive greater resources and support from independent distributors, initiate or withstand substantial price competition, offer full-line discounts we cannot match, or more readily take advantage of acquisition or other opportunities. Further, many of the large agrichemical companies have a more diversified product offering, which may give these companies an advantage in meeting customers’ needs by enabling them to offer a broader range of crop protection, plant nutrition and plant health products. In addition, we could face competition in the future from new, well-financed start-up companies.
Customers in the agricultural sector tend to be loyal to major brands and distributors and are generally cautious in adopting new products and technologies, making the barriers to entry high in this market. If new products or technologies fail to achieve immediate results, they may never achieve significant customer adoption and, even if immediate and positive results are achieved, adoption may take several growing seasons as multi-year purchasing agreements expire and product-specific equipment is replaced.
Products incorporating biotechnology-derived traits and crop protection products must be extensively tested for safety, efficacy and environmental impact before they can be registered for production, use, sale or commercialization in a given market.
In certain jurisdictions, we must periodically renew our approvals for both biotechnology and crop protection products, which typically require us to demonstrate compliance with then-current standards which generally are more stringent since the prior registration. The regulatory approvals process is lengthy, costly, complex and in some markets unpredictable, with requirements that can vary by product, technology, industry and country. The regulatory approvals process for products that incorporate novel modes of action or new technologies can be particularly unpredictable and uncertain due to the then-current state of regulatory guidelines and objectives, as well as governmental policy considerations and non-governmental organization and other stakeholder considerations.
Changes in the regulatory environment could adversely impact our ability to produce and/or sell certain products in domestic and foreign markets or could increase the cost of doing so.
Changes in the regulatory environment, particularly in the U.S., Brazil, China, India, Argentina and the European Union, could adversely impact our ability to produce and/or sell certain products in domestic and foreign markets or could increase the cost of doing so. Additionally, changes to the regulatory environment may be influenced by non-government public pressure as a result of negative perception regarding the use of our crop protection products. We are sensitive to this regulatory risk given the need to obtain and maintain pesticide registrations in every country in which we sell our products. Many countries require re-registration of pesticides to meet new and more challenging requirements; while we defend our products vigorously, these re-registration processes may result in significant additional data costs, reduced number of permitted product uses, or potential product cancellation. Compliance with changing laws and regulations may involve significant costs or capital expenditures or require changes in business practice that could result in reduced profitability. In the European Union, the regulatory risk specifically includes the chemicals regulation known as REACH (Registration, Evaluation, and Authorization of Chemicals), which requires manufacturers to verify through a special registration system that their chemicals can be marketed safely, as well as Regulation (EC) No 1107/2009, governing plant protection products, which sets forth rules for the authorization, sale, use, and control of plant protection products.
Customers have historically perceived biological agricultural products as more expensive and less effective than conventional products. To succeed, we will need to continue to change that perception. To the extent that the market for biological agricultural products does not further develop or customers elect to continue to purchase and rely on conventional chemical products, our market opportunity will be limited.
Any decline in U.S. agricultural production could have a material adverse effect on the market for biopesticides and on our results of operations and financial position.
Conditions in the U.S. agricultural industry will significantly impact demand for our products. The U.S. agricultural industry has contracted in recent periods, and can be affected by a number of factors, including weather patterns and field conditions, current and projected grain inventories and prices, domestic and international demand for U.S. agricultural products and U.S. and foreign policies regarding trade in agricultural products. State and federal governmental policies, including farm subsidies and commodity support programs, as well as the prices of fertilizer products and the prices at which produce may be sold, may also directly or indirectly influence the number of acres planted, the mix of crops planted and the use of pesticides for particular agricultural applications.
Sales of our plant health products will depend upon weather conditions, seasonal variation and other factors.
We expect to commercially launch CalanthaTM, our RNAi Colorado potato beetle product in 2023, assuming we are able to obtain EPA and state approvals according to our current plans, which assumes EPA approval by or before the first half of 2023. If and when we do begin selling our product to farmers, our sales will be subject to weather conditions and other factors beyond our control, which may cause our operating results to fluctuate significantly quarterly and annually.
Weather conditions, natural disasters and other factors affect planting and growing seasons and incidence of pests and plant disease, and accordingly affect decisions by our distributors, direct customers and end users about the types and amounts of pest management and plant health products to purchase and the timing of use of such products. In addition, disruptions that cause delays by growers in harvesting or planting can result in the movement of orders to a future quarter, which would negatively affect the quarter and cause fluctuations in our operating results. Customers also may purchase large quantities of our products in a particular quarter to store and use over long periods of time or time their purchases to manage their inventories, which may cause significant fluctuations in our operating results for a particular quarter or year.
Our activities are subject to extensive federal, state, local and foreign governmental regulations. These regulations may prevent us or our collaborators from developing or commercializing products in a timely manner or under technically or commercially feasible conditions and may impose expenses, delays and other impediments to our product development and registration efforts.
In the United States, the EPA regulates our bio-based pest management products under the Federal Food, Drug and Cosmetics Act (“FFDCA”), the Food Quality Protection Act (“FQPA”) and the Federal Insecticide, Fungicide and Rodenticide Act (“FIFRA”). In addition, some of our plant health products are regulated as fertilizers, auxiliary plant substances, soil amendments, beneficial substances and/or biostimulants in each of the fifty states.
In general, FIFRA prohibits the sale or distribution of any pesticide, a product category that includes the insecticides, fungicides, and acaricides we are developing, unless that pesticide is registered with the EPA. To register a pesticide with the EPA, the applicant must demonstrate that the product will not cause unreasonable adverse effects on human health or the environment. These adverse effects include any unreasonable risk to man or the environment, taking into account the economic, social, and environmental costs and benefits of the use of the pesticide, as well as any human dietary risk from residues that result from use of the pesticide in or on any food consistent with the FFDCA. In the course of its evaluation of a pesticide, EPA assesses the impact that a pesticide may have on endangered species and non-target organisms.
In order to commercialize a product for the U.S. agricultural market, we must complete specified toxicology studies, submit a registration dossier to the EPA demonstrating that the product does not pose unreasonable risks to human health or the environment, respond adequately to any deficiencies identified by the EPA through its risk assessment process and obtain the EPA’s approval of our labeling. The EPA must also establish a tolerance level for the product or issue a tolerance exemption. We must separately obtain any applicable state or foreign regulatory approvals. Moreover, because our products contain novel RNA-based active ingredients, there will generally be no previously registered pesticide product containing that active ingredient and, as a result, the use of each of our products will require a new registration under FIFRA and the establishment of a tolerance under Section 408 of the FFDCA or the issuance of a tolerance exemption.
We have not previously obtained any EPA approvals for our biopesticides, and it is uncertain whether the EPA will approve any of our products or whether it will place conditions of approval that adversely impact our ability to sell them. Although the EPA has evaluated and approved other companies’ RNA products before, our products may differ materially from the products that have previously received approval, and the lack of precedent makes it more difficult to predict whether or when the EPA will grant approval or the conditions that it might impose on approval.
Even if our biopesticide product candidates are approved by the EPA, as with any pesticide, they would continue to be subject to review by the EPA and state regulatory agencies. The EPA has the authority to revoke the registration or impose limitations on the use of any of our pest management products if we do not comply with the regulatory requirements, if unexpected problems occur with a product or if the EPA receives other newly discovered adverse information. Our inability to obtain regulatory approvals, or to comply with ongoing and changing regulatory requirements, could delay or prevent sales of the products we are developing and commercializing.
Inadequate funding, staffing or shutdowns of the government agencies that regulate us could prevent new products and services from being developed or commercialized in a timely manner or otherwise prevent those agencies from performing normal business functions on which the operation of our business may rely, which could negatively impact our business.
Our research and development activities are also subject to federal, state and local worker safety, air pollution, water pollution and solid and hazardous waste regulatory programs, ongoing compliance requirements, permitting requirements, and periodic inspection. Any significant noncompliance could impact our ability to operate. In addition, any future expansion of our manufacturing capabilities may require additional or expanded permitting, and such permitting requirements may impede or prevent our ability to operate.
Our agricultural products may fail to meet the criteria for desirable certifications such as “non-GMO” or “organic” and may cause the plants or products to which they are applied also to lose these certifications, reducing the addressable market for and value of our products.
The use of products created through synthetic biology processes is generally prohibited in organic food supply chains and the U.S. Department of Agriculture and similar regulators outside the U.S. will not permit an “organic” certification unless the supply chain from field to table is free of such products. We do not currently expect any of our agricultural products to qualify for “organic” certifications, which will keep us from selling into a market with potentially higher returns and which will limit the size of the addressable market for which our products can be used. In addition, the standards associated with certifications such as
“non-GMO” and “organic” can differ significantly between countries and jurisdictions within countries (such as states and cities) and, even when these standards are clearly established, the application of the standards for certification may differ depending on the third-party organizations conducting verification.
Genetically modified products are currently subject to public debate and heightened regulatory scrutiny, either of which could prevent or delay the adoption of our products. Claims that genetically modified products are unsafe or pose a danger to the environment may influence public attitudes and lead to our product not gaining public acceptance. The subject of genetically modified organisms has received negative publicity in the United States and particularly in Europe, and such publicity has aroused public debate. The adverse publicity in Europe could lead to greater regulation and trade restrictions.
We may have product liability claims if our agricultural products damage individuals or property and may need to recall items which do or could cause such damage.
Our agricultural products are intended to be used to improve yield in the human food supply chain. If our products are used for an application they are not intended for, become adulterated or mislabeled we may need to recall such products. A widespread product recall could result in significant losses due to the costs of a recall, the destruction of product inventory, and lost sales due to the unavailability of product for a period of time. We could also suffer losses from a significant product liability judgment against us. A significant product recall or product liability case could also result in adverse publicity, damage to our reputation, and a loss of confidence in our products, which could have an adverse effect on our business, results of operations and financial condition and the value of our brands.
Risks Related to our Animal Health Program
We currently have one animal health product which is intended to control the Varroa destructor mite, a honeybee parasite; however, the honeybee ecosystem is complex and it difficult to measure the overall efficacy of this product since there are multiple factors other than Varroa mites contributing to the decline in honeybee populations.
The one animal health product in our product pipeline, which we call GS15, is intended to support the health of honeybees by using dsRNA to discourage the spread of the Varroa destructor mite, a honeybee parasite. A multitude of stressors can contribute to declines in honeybee health, making it difficult to determine whether or the degree to which GS15 benefits honeybees and, by implication, beekeepers. Other factors that impact honeybee health include pesticides, environmental stressors, inadequate nutrition, parasites, pathogens, and poor management practices. No one factor has been identified as the primary cause of honeybee health decline or “bee colony collapse,” including the Varroa destructor mite parasite which GS15 is designed to control. Determining dominating stressors to honeybee health is challenging to characterize and pinpoint. To complicate matters, many of the factors contributing to honeybee health decline interact, making it difficult in some circumstances to identify dominant factors. Unless we are able to develop clear correlations between GS15 use and specific successful outcomes in beehives, GS15 (assuming it obtains regularly approval) may not have strong or any commercial prospects.
Delivering the active ingredient in our bee health product effectively to Varroa mites is challenging.
Until we complete our field trials, it is unclear whether we will be able to deliver our product first to bees and, through bees, to Varroa mites, in a manner that will effectively impede mite function. Challenges in active ingredient delivery may interfere with the effectiveness of our product.
When testing our Varroa mite product under the high-dose conditions commonly required by the EPA for pesticide approval, we have observed a dose response in bees and an increase in bee mortality.
Although our product is intended to impact Varroa mites and not bees, it may have unanticipated impacts on bee health. The EPA typically seeks a 10x dose safety factor in order to approve a product for commercial use. We tested our product at this concentration and observed significant bee mortality. At the concentrations we would expect under normal conditions, however, our recent field trials demonstrated no negative effects. Our most recent data indicates that bee mortality at the 10x dose safety factor likely results from the extremely high viscosity of RNA when administered at that concentration, which prevents bees from feeding. If there is a significant relationship between our product and bee mortality, that relationship may undercut our product’s intended function of protecting bees and may impair our ability to obtain regulatory approval of our product.
The EPA will evaluate our Varroa mite product without a precedent product, which may result in the need to conduct additional field trials and lengthen the regulatory review period. If we cannot reduce bee mortality experienced in high-dose safety factor testing, the EPA may not approve our product or may impose labeling requirements that materially limit the commercial attractiveness of the product.
Our Varroa mite product is subject to EPA approval under FIFRA. Although the EPA has evaluated and approved RNA products before, our product may differ materially from previously approved products. After we perform our planned field trials and studies, the EPA may request further studies and data to effectively evaluate and approve our product. We anticipate that this process will require additional time to complete and may delay regulatory approval and commercialization. Moreover, other markets, such as those in the European Union, may require additional data or information prior to granting approval, and they may impose more stringent conditions on any approval.
One challenge we face in securing EPA approval for our Varroa mite product is that EPA typically seeks to ensure that a product does not cause adverse effects even when administered at a dose equal to ten times the dose that bees and other organisms would likely receive in typical use. Ordinarily, pesticides are applied at high doses in the field to account for anticipated losses to the environment resulting from degradation, runoff and other factors, and these losses are anticipated to reach as high as 95%. As a result, in a conventional field application scenario, organisms are generally expected to receive the actual field use rate, even when the product is applied at ten times that rate. When we tested our Varroa mite product in the laboratory at the required level of ten times the field use rate, the higher concentration of the product caused the treated bee food to become highly viscous, which limited consumption and resulted in bee starvation. We did not observe these adverse effects either when our product was administered at the field use rate or when our product was administered at the high-dose rate in the field. Because our product is delivered in a ready-to-use formulation through a pre-measured pouch delivery system, rather than through conventional spraying, we do not believe that our product presents a material risk that bees will be exposed to concentrations greater than the field use rate. We are negotiating with the EPA to modify its customary 10x safety factor protocol for both bees and non-target organisms to account for differences between the delivery system for our product and traditional field application methods. We may not be successful in these negotiations, and extended negotiations, even if ultimately successful, could delay regulatory approval and commercial introduction of the product. If the EPA does not modify its safety factor protocol for our Varroa mite product, we may be unable to obtain regulatory approval to commercialize the product in the United States, which would limit our growth opportunities. Even if the product receives EPA approval, it may receive labeling with warnings of potentially harmful effects on bees or other organisms, which would materially limit the commercial attractiveness of the product to potential customers.
We purchased some of the intellectual property related to our RNA honeybee product from Bayer Crop Science, a subsidiary of Bayer, which now owns Monsanto. It is well known that Monsanto has had significant pushback from environmental groups regarding its technology and practices, and our product may be hard to market since it was purchased from Bayer.
Despite rigorous testing during the pre-commercialization phase, if GS15 comes to market, there may be opponents of our RNA technology or synthetic biology generally who raise concerns about the potential for adverse effects of our products on human or animal health, plants and the environment. Because GS15 in part originated with Monsanto, the many negative public perceptions associated with Monsanto could impair our ability to bring GS15 to market and can affect the timing of, and whether we are able to obtain, government approvals for our products.
Even after approvals are granted for GS15, public concern may lead to increased regulation or legislation or litigation against government regulators concerning prior regulatory approvals, which could affect our sales and results of operations, and which may adversely affect sales of GS15 to beekeepers, including due to their concerns about available markets for the sale of crops or other products including those derived from biotechnology. Genetically modified products are currently subject to public debate and heightened regulatory scrutiny, either of which could prevent or delay the adoption of GS15. Claims that genetically modified products are unsafe or pose a danger to the environment may influence public attitudes and lead to our product not gaining public acceptance. The subject of genetically modified organisms has received negative publicity in the United States and particularly in Europe, and such publicity has aroused public debate. The adverse publicity in Europe could lead to greater regulation and trade restrictions.
In addition, opponents of agricultural synthetic biology have attacked facilities used by agricultural biotechnology companies, and may launch future attacks against beekeepers’ hives and our field testing sites and research, production, or other facilities, which could affect our sales and our costs.
The research and development process for GS15 is expensive with little immediate return, and the field trials associated with honeybees in general are susceptible to circumstances outside of our control.
Although our field trial operators are under agreement not to extract honey from their hives during field trials, there is the risk that honey could be extracted impermissibly and find their way into the commercial market thereby impairing our ability to meet regulatory requirements or obtain regulatory approval.
Furthermore, beekeepers tend to be migratory as they serve the needs of seasonal crops and the environments in which the hives are placed can vary. These variables introduce the risk that hives could be damaged or otherwise compromised so as to require their removal from the field trials or field trial results which make it difficult for us to accurately measure the effects of GS15.
Beekeeping practices and results also vary and are subject to factors outside of our control. For example, the overall health and productivity of a beehive is dependent on the queen, how she is mated, how well the nurse bees are taking care of her and larvae, and how well forager bees are able to bring back food to the hive. One hive may have bees that go north and a hive right next to it may have bees that go south to look for food, which causes variability in food sources and potentially in test results. This variability in testing can make it difficult or impossible for us to accurately isolate the effects of GS15 which may in turn increase the cost of field testing, the length and likelihood of regulatory approval and the commercial viability of the GS15 product.
Our GS15 product is intended to be used in commercial beehives and used in a fashion which will expose the product only to bees and the Varroa destructor mite. If GS15 is used inappropriately and is consumed by invertebrates other than the Varroa destructor mite, it could be harmful to those invertebrates.
According to a September 2020 report published by the Environmental Directorate of the Organization for Economic Cooperation and Development (“OECD”) entitled Considerations for the Environmental Risk Assessment of the Application of Sprayed or Externally Applied ds-RNA-Based Pesticides, there is a long-established view that dietary intake of nucleic acids, including dsRNAs from plant viruses, does not present a health risk to humans and other vertebrates, and, as a result, the adoption of RNAi technology in agriculture is likely to present a lower human health risk than the use of conventional pesticides. Notwithstanding this history of safe consumption in vertebrates like humans, our GS15 product negatively impacts ladybugs and could also negatively impact other invertebrates if our use instructions are ignored and the invertebrates gain access to and consume the GS15 product. Moreover the honey from hives using GS15 may have trace elements of GS15 which could have the potential to be harmful to invertebrates consuming that honey in extreme circumstances.
It may be difficult to convince beekeepers to adopt our product, and to use it in the way prescribed for maximum effect.
Although we foresee that our product will be effective in controlling mites that impact bees, beekeepers may ultimately perceive shortcomings in treatment efficacy. This may result in reduced demand for our product or the selection of other treatment options.
Additionally, we will not be able to control how beekeepers will ultimately use our product, and misuse may result in reduced product efficacy, and thus reduced demand. For example, if beekeepers were to dilute our product formulation before application, the diluted product might leave hives subject to microbial contamination and allow microbes to consume our product, impeding its ability to affect mite function.
GS15 is susceptible to purity risks associated with scaling up manufacturing and we are also developing our own process for manufacturing our product at scale.
Commercial production of our product candidates will involve quantities several orders of magnitude higher than our current level of production. We may face challenges producing a product that meets applicable purity specifications at that scale, and may encounter other issues related to scaled up manufacturing.
While Bayer Crop Science (from which we obtained some intellectual property for the product) had its own proprietary methods for manufacturing, we did not license these methods, and we are developing our own methods of manufacturing GS15. We are currently developing a way to make this product with our cell-free platform so that it is economical to produce. Uncertainties related to this platform may ultimately limit our ability to produce the product.
Our product may require approval from other federal and state regulatory bodies.
As discussed above, state regulatory approvals may also be required for our product, which may delay commercialization. In addition, the EPA may not be the only federal agency with jurisdiction over products designed to eliminate honeybee pests. In 2017, the FDA, EPA, and USDA released a document entitled “Modernizing the Regulatory System for Biotechnology Products: Final Version of the 2017 Update to the Coordinated Framework for the Regulation of Biotechnology.” That document outlines the role that the three agencies have in biotechnology approvals. While it is clear that EPA has jurisdiction over pesticide and insecticide products pursuant to FIFRA, USDA also asserts jurisdiction over honeybees in some circumstances. As a result, we may need USDA evaluation and approval of our product, in addition to other unanticipated regulatory approvals. These additional approvals may delay commercialization.
Risks Related to Intellectual Property
If we are unable to obtain and maintain sufficient intellectual property protection for our products, platform, methods, and technology, or if the scope of the intellectual property protection obtained is not sufficiently broad, competitors could develop and commercialize products similar or identical to ours, and our ability to successfully commercialize our products may be impaired.
Our commercial success depends in part on our ability to protect our intellectual property and proprietary technologies. We rely on a combination of patent, trade secret and trademark laws, and nondisclosure, confidentiality and other contractual restrictions to protect our intellectual property and proprietary technology. However, these legal means afford only limited protection and may not adequately protect our rights or permit us to gain or keep any competitive advantage. If we fail to obtain, maintain and protect our intellectual property, third parties may be able to compete more effectively against us and our competitive position could be adversely affected, as could our business, financial condition, results of operations and prospects. In addition, we may incur substantial costs related to litigation or other patent proceedings in our attempts to recover or restrict use of our intellectual property.
To the extent that our intellectual property offers inadequate protection, or is found to be invalid or unenforceable, we would be exposed to a greater risk of direct competition. If our intellectual property does not provide adequate coverage of our competitors’ products and methods, our competitive position could be adversely affected, as could our business, financial condition, results of operations and prospects. Both the patent application process and the process of managing patent and other intellectual property disputes are generally unpredictable, time-consuming and expensive.
Our success depends in large part on our own and any future licensor’s ability to obtain and maintain protection of the intellectual property we may own or license, whether solely or jointly, particularly patents, in the United States and other countries with respect to our products, platform, methods, and technologies. We apply for patents to protect our products, platform, methods, technologies and commercial activities, as we deem appropriate. However, obtaining and enforcing patents is costly, time-consuming and complex, and we may fail to apply for patents on important products, methods, and technologies in a timely fashion or at all, or we may fail to apply for patents in potentially relevant jurisdictions. Moreover, we may fail to obtain issuance of any of the patent applications that we do file. Publications of discoveries in scientific literature often lag behind the actual discoveries, and patent applications in the United States and other jurisdictions are typically not published until 18 months after filing, or in some cases not at all. Therefore, we cannot know with certainty whether we were the first to make the inventions claimed in our patents or pending patent applications, or whether we were the first to file for patent protection of such inventions.
We may not be able to file and prosecute all necessary or desirable patent applications, or maintain, enforce and license any patents that may issue from such patent applications, at a reasonable cost or in a timely manner or in all jurisdictions. It is also possible that we will fail to identify patentable aspects of our research and development output before it is too late to obtain patent protection. Moreover, we may not develop additional proprietary products, methods and technologies that are patentable. Even if we believe an innovation to be patentable and file patent applications, the United States Patent Office (“USPTO”) and other patent offices may not find our innovations to be patentable and may refuse to grant patent rights. We may not have the right to control the preparation, filing and prosecution of patent applications, or to maintain the rights to patents which may be licensed from or to third parties or held jointly with third parties. In connection with any future licensing arrangements with third parties, these patents and applications may not be prosecuted and enforced by such third parties in a manner consistent with the best interests of our business. We currently own and may in the future own patents, patent applications, and other intellectual property jointly with third parties. In certain jurisdictions, including in the United States, joint owners of a patent are free to license rights under the patent to third parties without any compensation to or permission from co-owners. If we are unable to negotiate licenses on commercially reasonable terms with co-owners of patents, in order to exclusively control commercial licensing or commercial use of our co-owned patents or if agreements allowing us such control are found unenforceable, then co-owners may be able to license to our competitors and other third parties without our permission and without compensation to us. Failure to control
exclusive rights under intellectual property as discussed above may have an adverse effect on our competitive position, business, financial condition, and results of operations.
We may become involved in lawsuits to enforce our intellectual property or defend against third-party claims of infringement, misappropriation, or other violations of intellectual property which could be expensive, time consuming, and unsuccessful and may prevent or delay development and commercialization efforts, and could harm our competitive position and business prospects.
Litigation may be necessary for us to enforce our patent and proprietary rights, defend against intellectual property claims brought by third parties and/or determine the scope, coverage and validity of third parties’ intellectual property rights. Litigation on these matters has been prevalent in our industries and we expect that this will continue. To determine the priority of inventions, we may have to initiate and participate in interference proceedings declared by the U.S. Patent and Trademark Office that could result in substantial legal fees and could substantially affect the scope of our patent protection. Also, our intellectual property may be subject to significant litigation and administrative proceedings such as invalidity, unenforceability, IPR, re-examination, opposition, or other post-grant proceedings against our patents. The outcome of any litigation or other proceeding is inherently uncertain and might not be favorable to us and we might not be able to obtain licenses to technology that we require or a competitor may have already obtained an exclusive license to such technology in the relevant fields. Even if such licenses are obtainable, they may not be available at a reasonable cost. We could therefore incur substantial costs related to royalty payments for licenses obtained from third parties, which could negatively affect our competitive position, business, financial condition, or results of operations and/or make it unfeasible to commercialize a given product. In some cases, the outcome of litigation may be to enjoin us from commercializing or using a technology protected by third-party intellectual property. We could encounter delays in product introductions, or interruptions in product sales, as we develop alternative methods or products or we may need to cease sales of a product altogether if we are unable to develop alternatives that avoid the relevant third-party intellectual property.
If we resort to legal proceedings to enforce our intellectual property rights or to determine the validity, scope and coverage of the intellectual property or other proprietary rights of others, the proceedings could be burdensome, time-consuming, and expensive, even if we were to prevail. Moreover, it may not be possible for us to enforce jointly owned patents in the U.S. or other jurisdictions without the cooperation of other owners.
Our commercial success may depend in part on our non-infringement of the patents or proprietary rights of third parties and/or the invalidity or unenforceability of such patent or proprietary rights of others. Numerous significant intellectual property issues have been litigated, and will likely continue to be litigated, between or among existing and new participants in our relevant markets and competitors may assert that our products or methods infringe their intellectual property rights as part of a business strategy to impede the successful entry into or continued presence in those markets. Third parties may assert that we are employing their proprietary technology without authorization. For example, numerous third-party patents exist in fields relevant to the Company’s business and planned products, such as biologics, mRNA vaccines and therapies, and RNA interference (“RNAi”) for crop protection. Our competitors and others have patents and may in the future obtain patents and may claim that use, manufacture, sale, or importation of our products infringe these patents. Moreover, as we move into new markets and applications for our technologies, incumbent participants in such markets may assert their patents and other proprietary rights against us as a means of slowing or preventing our entry into such markets, or as a means to extract substantial license and royalty payments from us.
We have received notice in the past that our proposed products or methods may require an intellectual property license from others in order to be developed, produced, used, or sold. In each instance, we have reviewed the underlying intellectual property and either negotiated for a license or determined that no license was necessary. For future notices, if we are unable to successfully negotiate licenses or determine that no license is necessary, we may be unable to bring impacted products to market. Moreover, allegations that we violate third-party intellectual property could lead to disputes, including litigation.
The outcome of litigation is uncertain and even if we believe that we do not violate asserted third-party intellectual property or that such intellectual property is invalid or unenforceable or otherwise not legally protectable, our defense may be unsuccessful. If a court were to find that we have violated the intellectual property rights of a third party, an injunction and/or an award of damages may have an adverse effect on our business, financial condition, and results of operations. Remedies for intellectual property infringement or misappropriation may include an injunction against future sales of products or use of methods, statutory damages, enhanced damages, punitive damages, attorney’s fees, an award of lost profits and/or a reasonable royalty and prejudgment interest. Damages may in some cases exceed our own profits on sales found to be infringing. Even if we are successful in defending claims, defending intellectual property litigation, particularly patent or trade secret litigation, can be prohibitively burdensome and expensive.
We may be required in the future to license patent rights from third-party owners in order to develop or continue to sell or use a product or method. If we cannot obtain such licenses, or if such owners do not properly maintain or enforce the patents underlying such licenses, our competitive position and business prospects will be harmed.
We develop products, platform, and methods in technological areas and industries that are critical to public health and agriculture-areas in which there is considerable competition. A third-party may hold intellectual property rights, including patent rights and trade secrets that are important or necessary to the development, manufacture, or commercialization of our current or future product candidates. It may be necessary for us to use the patented or proprietary technology of one or more third parties to manufacture or commercialize our product candidates, in which case we would be required to obtain a license from these third parties on commercially reasonable terms, or our business could be harmed. If any such patents were to be asserted against us, there is no assurance that a court would find in our favor or that, if we choose to or are required to seek a license, that a license to any of these patents would be available to us on acceptable terms or at all.
To the extent that we enter into any patent licenses with third parties, if such third parties fail to properly maintain the licensed patents or if those patents are found to be invalid or unenforceable, then we could be subject to additional competition due to the loss of exclusive or non-exclusive rights.
Defending and protecting intellectual property rights in foreign jurisdictions is costly and sometimes prohibitively expensive.
Obtaining patent protection in every country is prohibitively expensive and, as we attempt to choose jurisdictions for intellectual property protection, we may fail to protect our intellectual property in relevant jurisdictions where we do business, and thereby cause a loss of revenue and profits or other impacts on our ability to manufacture and export our products.
Competitors may use our proprietary technologies in jurisdictions where we have not obtained patent protection to manufacture or develop their own products. Such competitors may export otherwise infringing products, or products made through otherwise infringing methods, to territories where we may have or obtain patent protection, but where patent enforcement is not as strong as in the United States or where no protection is available for products made abroad through methods that infringe a local patent. These products may also compete with our products in jurisdictions where we do not have any issued or licensed patents and any future patent claims or other intellectual property rights may not be effective or sufficient to prevent them from so competing.
Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions. The legal systems of some countries do not favor the enforcement of patents and other intellectual property protection, which could make it difficult for us to stop the infringement of our patents or trademarks or the misappropriation of our trade secrets generally. Proceedings to enforce our intellectual property rights in foreign jurisdictions could result in substantial costs and divert our efforts and attention from other aspects of our business, could put our patents at risk of being invalidated or interpreted narrowly and our patent applications at risk of not issuing and could provoke third parties to assert claims against us. We may not prevail in any lawsuits that we initiate, and the damages or other remedies awarded, if any, may not be commercially meaningful.
Many countries, including India, Japan, China, and some European nations have compulsory licensing laws under which a patent owner may be compelled under specified circumstances (including a matter of public policy) to grant licenses to third parties. In those countries, we may have limited remedies if patents are infringed or if we are compelled to grant a license to a third-party, which could diminish the value of those patents. This could limit our potential revenue opportunities. Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license.
The United States has the absolute right to manufacture and use patented inventions and to allow others to manufacture and use patent inventions for the United States, for reasonable compensation.
Pursuant to 28 U.S.C. § 1498, the United States government has the absolute right to use or manufacture any patented inventions for reasonable compensation. No injunction of patent infringement is available against the United States and damages are limited to reasonable compensation only. Moreover, a patent owner may not obtain damages or an injunction against a private entity for its infringing use or manufacture for the United States. Such suits may only be brought against the United States and only for reasonable compensation. In the past the United States has relied on such rights to use or manufacture inventions from third parties other than the patentee. In the future, the United States may rely on its rights to infringe our current and future patents or to allow others to make or use our inventions on behalf of the United States. If the United States were to use, or allow others to use for the United States, our patented technology, platform, methods, or products, then we would only be entitled to reasonable compensation and would not be entitled to an injunction to prevent infringement. As with all intellectual property
litigation, proceedings against the United States for patent infringement could be burdensome, time-consuming, and expensive. Even if we were to prevail on a patent infringement action against the United States, any remedy would not likely compensate us for the full extent of the financial harm from such infringement due to the limited remedies available against the United States under the law. Such infringement could adversely affect our competitive position, business, financial condition, results of operations, and prospects.
When inventions are developed with government funding, the United States retains a paid-up license to such inventions and may compel us to grant licenses to third parties for little or no compensation.
Under 35 U.S.C. § 200 et seq., when inventions arise, even in part, through use of public funds, the United States may retain an irrevocable, paid-up license to practice or have practiced on its behalf, such inventions, whether protected by patent or trade secret. That is, the United States has the absolute right to use, and allow others to use on its behalf, such intellectual property without any compensation to the holder of the intellectual property. We have acquired and developed and may in the future acquire or develop trade secrets or obtain patents on inventions developed, in full or in part, with funding from the United States government. A court could also find that one or more of our current patents or applications are covered by 35 U.S.C. § 200 et seq. In such cases, the United States would have the right to use, or allow others to use on its behalf, our inventions, whether protected by patent or trade secret, without any compensation to us.
For inventions subject to 35 U.S.C. § 200 et seq., the United States also retains march-in rights. These march-in rights apply in certain situations, including, for example, when action is necessary to alleviate public health or safety needs or when an inventor is not taking reasonable steps to make its technology useful to the public. In such situations, the United States has the right to compel the innovator to grant licenses to third parties. If such a finding were made with respect to our current or future patents or trade secrets, then we may not be able to prevent competitors from practicing our patented inventions and/or may be compelled to license our competitors to practice our inventions for little or no monetary compensation. Any of the foregoing events could have an adverse effect on our business, financial condition and results of operations.
Confidentiality agreements with employees and others may not adequately prevent disclosure of trade secrets and other proprietary information.
We currently rely, and intend to rely in the future, on trade secrets, know-how and technology that are not protected by patents to maintain our competitive position. In order to protect our proprietary technology and processes, we also rely in part on confidentiality agreements with our collaborators, employees, consultants, and sponsored researchers and other advisors. These agreements may not effectively prevent disclosure of confidential information and may not provide an adequate remedy in the event of unauthorized disclosure of confidential information. These agreements may be found by a court to be unenforceable or invalid. We may fail to enforce our agreements in Court if we are compelled to present them as evidence but are unable to locate and provide copies. Moreover, when employees with knowledge of our trade secrets and confidential information leave us and join new employers, it may be difficult or impossible for us to detect or prove misappropriation of our confidential information and trade secrets by the former employee and/or the former employee’s new employer. In addition, others may independently discover trade secrets and proprietary information, and in such cases, we could not assert any trade secret rights against such party. Costly and time-consuming litigation could be necessary to enforce and determine the scope of our proprietary rights, and failure to obtain or maintain trade secret protection could adversely affect our competitive position, business, financial condition and results of operations.
Changes in patent laws or patent jurisprudence could diminish the value of patents in general, thereby impairing our ability to protect our products and platforms.
The patent position of biotechnology, life sciences, and pharmaceutical companies generally is highly uncertain, involves complex legal and factual questions and has in recent years been the subject of much litigation. In addition, the laws of foreign countries may not protect our rights to the same extent as the laws of the United States. For example, European patent law restricts the patentability of methods of treatment of the human body more than United States law does. In another example, some jurisdictions prevent the patenting of certain biotechnology inventions outside of narrow coverage for exact nucleotide sequences.
As a result, the issuance, scope, validity, enforceability and commercial value of our patent rights are highly uncertain. Our pending and future patent applications may not result in patents being issued which protect our technology, platform, methods, or products, in whole or in part, or which effectively prevent others from commercializing competitive products. Our issued patents may be found to be invalid or unenforceable in a post grant proceeding before patent offices or in patent litigation before courts in the United States or other countries. Changes in either the patent laws or interpretation of the patent laws in the United States and other countries may diminish the value of our patents, narrow the scope of our patent protection, or result in the invalidity or unenforceability of our patents.
Various courts, including the U.S. Supreme Court, have recently rendered decisions that impact the scope of patentability of certain inventions or discoveries relating to our technology and commercial goals. Specifically, these decisions have substantially increased the probability that patent claims will be ruled patent ineligible for reciting a natural phenomenon, law of nature or abstract idea. Furthermore, in view of these decisions, the USPTO has published and continues to publish revised guidelines for patent examiners to apply when examining claims for patent eligibility. Patent claims relating to software algorithms, biologically-derived compositions, methods for analyzing biological systems and other subject matters that underlie our technology and commercial goals are impacted by these changes.
On September 16, 2011, the Leahy-Smith America Invents Act (the “Leahy-Smith Act”) was signed into law. The Leahy-Smith Act made a number of significant changes to United States patent laws. These include provisions that affect the way patent applications are prosecuted and challenged at the USPTO and may also affect patent litigation. The USPTO has developed and continues to develop regulations and procedures to govern administration of the Leahy-Smith Act, and many of the substantive changes to patent law associated with the Leahy-Smith Act, and in particular, the first to file provisions, became effective on March 16, 2013. Accordingly, it is not clear what, if any, impact the Leahy-Smith Act, subsequent rulemaking, and judicial interpretation of the Leahy-Smith Act and regulations will have on the operation of our business in the future. The Leahy-Smith Act and its continued implementation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement and/or defense of our issued patents, all of which could have an adverse effect on our business and financial condition.
Actions taken by the U.S. Congress, federal courts and USPTO have from time to time narrowed the scope of patent protection available in certain circumstances and weakened the rights of patent owners in certain situations. Similar changes have been made by authorities in other jurisdictions. In addition to increasing uncertainty with regard to the ability to obtain patents in the future, such changes create uncertainty with respect to the value of patents, once obtained. Depending on decisions by authorities in various jurisdictions, the laws and regulations governing patents could change in unpredictable ways that may have an adverse effect on our ability to obtain new patents and to defend and enforce our existing patents and patents that we might obtain in the future, harming our business, competitive position, financial condition, results of operations, and prospects.
Patent reform legislation could increase uncertainties and costs surrounding the prosecution of our patent applications and the enforcement, validity, or defense of our issued patents. There has been recent public discussion around loosening of patent protection for inventions important to addressing the SARS-CoV-2 pandemic. Such reforms or similar changes in connection with future pandemics or other public health emergencies, could have an adverse effect on any patent protection on our products and methods.
We cannot assure you that our patent portfolio will not be negatively impacted by the current uncertain state of the law, new court rulings or changes in guidance or procedures issued by governments or patent offices around the world. From time to time, the U.S. Supreme Court, other federal courts, the U.S. Congress or the USPTO may change the standards of patentability, scope and validity of patents within the biotechnology, life sciences, and other relevant technologies and any such changes, or any similar adverse changes in the patent laws of other jurisdictions, could have a negative impact on the our business, financial condition, prospects and results of operations.
Moreover, we may be subject to a third-party pre-issuance submission of prior art to the USPTO, or become involved in opposition, derivation, reexamination, inter parties review, post-grant review or interference proceedings challenging our patent rights or the patent rights of others. An adverse determination in any such submission, proceeding or litigation could reduce the scope of, or invalidate, our patent rights, allow third parties to commercialize our technology or products or use our proprietary methods and compete directly with us, without payment to us, or result in our inability to manufacture or commercialize products without infringing third-party patent rights.
Our current or future issued patents could be found invalid or unenforceable if challenged or could be construed narrowly such that they do not cover our products or methods or those used by our competitors.
It is possible that none of our current or future pending patent applications will result in issued patents in a timely fashion or at all. Even if our patent applications issue as patents, they may not issue in a form that will provide us with any meaningful protection, prevent competitors from competing with us or otherwise provide us with any competitive advantage. Moreover, we cannot predict the breadth of claims that may be allowed or enforced in our patents. Our issued patents may not be construed to cover our own or our competitors’ products or methods. Our competitors may be able to circumvent or design around our patents by developing similar or alternative technologies or products in a non-infringing manner. In addition, if the breadth or strength of protection provided by our patents and patent applications is threatened, it could dissuade companies from collaborating with us to license, develop or commercialize current or future product candidates.
The issuance of a patent is not conclusive as to its inventorship, scope, validity or enforceability, and our patents may be challenged in the courts or patent offices in the United States and abroad. Such challenges may result in loss of exclusivity, in patent claims being narrowed or invalidated, or in patents being held unenforceable which could limit our ability to stop others from using or commercializing similar or identical technology, methods, and products, or limit the duration of the patent protection of our technology, methods, and products.
The inventorship and/or ownership rights for our patents and patent applications may be challenged by third parties. Such challenges could result in invalidation of such patents, the loss of ownership of such patents, or loss of exclusive rights to such patents, which could result in increased competition and could limit or eliminate our ability to stop others from using or commercializing similar or identical technology, methods, and products or require us to obtain a license from third parties on commercially reasonable terms to secure exclusive rights, or our business could be harmed. If any such challenges to inventorship and/or ownership were asserted, there is no assurance that a court would find in our favor or that, if we choose to seek a license, such license would be available to us on acceptable terms or at all.
Patent terms may be inadequate to protect our competitive position for an adequate amount of time.
Patents have a limited lifespan. In the United States, the natural expiration of a patent is generally 20 years after the first non-provisional filing date. In the United States, a patent’s term may, in certain cases, be lengthened by patent term adjustment, which compensates a patentee for administrative delays by the USPTO in examining and granting a patent, or in certain cases, by patent term extension for patents covering certain pharmaceutical products requiring regulatory approval. In the United States a patent’s term also may be shortened if a patent is terminally disclaimed over a commonly owned patent or a patent naming a common inventor and having an earlier expiration date. The life of a patent, and the protection it affords, is limited. Therefore, even if patents covering our products and methods are obtained, once the patent life has expired, for our current or future platform, products, methods or technologies, we may be open to competition, including, for example, from biosimilar or generic versions of our products. Given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized. As a result, our owned and licensed patent portfolio may not provide us with sufficient rights to exclude others from commercializing products similar or identical to ours.
Obtaining and maintaining patent protection depends on compliance with various procedural, document submission, fee payment and other requirements imposed by governmental patent agencies, and our patent protection could be reduced or eliminated for non-compliance with these requirements.
The USPTO and European and other patent agencies require compliance with a number of procedural, documentary, fee payment and other similar provisions during the patent application process. In addition, periodic maintenance, renewal and annuity fees on any issued patent are due to be paid to the USPTO and European and other patent agencies over the lifetime of a patent. While an inadvertent failure to make payment of such fees or to comply with such provisions can in many cases be cured by additional payment of a late fee or by other means in accordance with the applicable rules, there are situations in which such noncompliance will result in the abandonment or lapse of the patent or patent application, and the partial or complete loss of patent rights in the relevant jurisdiction. Non-compliance events that could result in abandonment or lapse of a patent or patent application include failure to respond to official actions within prescribed time limits, non-payment of fees and failure to properly legalize and submit formal documents within prescribed time limits. If we or our licensors fail to maintain the patents and patent applications covering our platform, technology, methods, or products or if we or our licensors otherwise allow patents or patent applications to be abandoned or lapse, our competitors might be able to enter the market, which would hurt our competitive position and could impair our ability to successfully commercialize our product candidates, which could have an adverse effect on our business and financial condition.
We may become subject to claims for ownership of intellectual property, payment, or royalties for assigned invention rights by our employees, contractors, and collaborators, which could result in litigation and adversely affect our business.
We may be subject to claims that former employees, collaborators or other third parties have an interest in, or right to compensation, with respect to our current patent and patent applications, future patents and patent applications, or other intellectual property as an inventor or co-inventor. For example, we may have inventorship or ownership disputes from consultants, former employees, or others who are involved in developing a product for us. Litigation may be necessary to defend against these and other claims challenging inventorship or ownership or claiming the right to compensation. If we fail in defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights, such as ownership of, exclusive ownership of, or the right to use and/or exclude others from using, valuable intellectual property. Such an outcome could have an adverse effect on our business, financial condition, results of operations, and prospects. Even if we are
successful in defending against such claims, litigation could result in substantial costs and be a distraction to management and other employees.
We generally enter into assignment-of-invention agreements with our employees pursuant to which such individuals assign to us all rights to any inventions created in the scope of their employment or engagement with us. If compelled to provide copies of relevant agreements as evidence of such arrangements, we may not be able to locate and provide copies of such agreements and may therefore be unable to assert such agreements. Moreover, such agreements could be found to be invalid or unenforceable. Although our employees have agreed to assign to us invention rights and have specifically waived their right to receive any special remuneration for such assignment beyond their regular salary and benefits, we may face claims demanding ownership of inventions or remuneration in consideration for assigned inventions.
We may not be able to protect and enforce our trademarks and trade names, or build name recognition in our markets of interest or may be subject to claims of trademark infringement thereby harming our competitive position.
We have filed, and may continue in the future to file trademark applications to protect certain of our intellectual property; however, we cannot guarantee that we will be successful in registering our trademarks. Our registered or unregistered trademarks or trade names may be challenged, infringed, circumvented, declared generic, lapsed or determined to be infringing on or dilutive of other marks. We may not be able to protect our rights in these trademarks and trade names, which we need in order to build name recognition. In addition, third parties have filed, and may in the future file, for registration of trademarks that may impede our ability to build brand identity and possibly leading to market confusion. Third parties have identified potential conflicts between their marks and our marks that may arise in the future. In addition, there could be potential trade name or trademark infringement claims brought by owners of trademarks or trademarks that incorporate variations of our trademarks or trade names. Such claims may require us to cease use of our trademarks or change our company or product names. Further, we may in the future enter into agreements with owners of such third-party trade names or trademarks to avoid potential trademark litigation which may limit our ability to use our trade names or trademarks in certain fields or territories. Over the long term, if we are unable to establish name recognition based on our trademarks and trade names, then we may not be able to compete effectively, and our business, financial condition, results of operations and prospects may be adversely affected. Our efforts to enforce or protect our proprietary rights related to trademarks, domain names, or other intellectual property may be ineffective and could result in substantial costs and diversion of resources. Any of the foregoing events could have an adverse effect on our business, financial condition and results of operations.
Intellectual property rights do not necessarily address all potential threats to our competitive advantage.
The degree of future protection afforded by our intellectual property rights is uncertain because intellectual property rights have limitations, and may not adequately protect our business, or permit us to maintain our competitive advantage. The following examples are illustrative:
•Others may be able to develop or make products, platform, methods or technology that are similar to products, platform, methods or technology we have developed or will develop, but that are not covered by the claims of the patents that we own or have licensed and are not protectable through trade secret law.
•We or our licensors or strategic partners might not have been the first to make the inventions covered by the issued patent or pending patent application that we own or have exclusively licensed, and therefore our patents may be found to be invalid or our patent applications may be rejected.
•We or our licensors or strategic partners might not have been the first to file patent applications covering certain of our inventions, and therefore our patents may be found to be invalid or our patent applications may be rejected.
•Others may independently develop or make similar or alternative products, platform, methods or technology or duplicate any of our products, platform, methods or technology without infringing our intellectual property rights. For example, independent development of such products, platform, methods or technology would make it impossible for us to assert trade secret rights against such third parties. If such third parties publish the details of such independently developed products, platform, methods or technology, then we could lose any trade secret protection even as against others.
•It is possible that our pending patent applications will not lead to issued patents.
•Issued patents that we own or have exclusively licensed may not provide us with any competitive advantages, or may be held invalid or unenforceable, as a result of legal challenges by our competitors.
•Our competitors might conduct research and development activities in countries where we do not have patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets.
•Our competitors may use our manufacturing methods to produce products in jurisdictions in which we do not have patent protection on our manufacturing methods and may export such products for sale in other jurisdictions, including our major commercial markets for us. Patents on such methods in our major commercial markets may not protect against such product sales.
•We may not develop additional proprietary technologies that are patentable or protectable through other intellectual property rights.
•The intellectual property rights of others may have an adverse effect on our business.
Should any of these events occur, they could significantly harm our business, competitive position, financial condition, results of operations and prospects.
Risks Related to Ownership of Our Common Stock
An active trading market for our Common Stock may never develop or be sustained.
We cannot assure you that an active trading market for the Common Stock will develop on the Nasdaq or elsewhere. If an active trading market does not develop, or develops but is not maintained, you may have difficulty selling any shares of our Common Stock due to the limited public float. Accordingly, we cannot assure you of your ability to sell your shares of our Common Stock when desired or the prices that you may obtain for your shares.
The market price of our Common Stock may be volatile, which could result in substantial losses for investors.
The market price of our Common Stock may fluctuate due to a variety of factors, including:
•the need to obtain regulatory approval for our product candidates;
•the risk that clinical trials will not demonstrate that our therapeutic product candidates are safe and effective;
•the risk that our product candidates will have adverse side effects or other unintended consequences, which could impair their marketability;
•the risk that our product candidates do not satisfy other legal and regulatory requirements for marketability in one or more jurisdictions;
•the risks of enhanced regulatory scrutiny of RNA-based products, including mRNA and dsRNA;
•the potential inability to achieve our goals regarding scalability, affordability and speed of commercialization of our product candidates;
•the anticipated need for additional capital to achieve our business goals;
•changes in the industries in which we operate; changes in laws and regulations affecting our business,
•the potential inability to implement or achieve business plans, forecasts, and other expectations after the completion of the proposed transaction;
•actual or anticipated fluctuations in our operating results, including fluctuations in our quarterly and annual results;
•operating expenses being more than anticipated;
•the failure or discontinuation of any of our product development and research programs;
•the success of existing or new competitive businesses or technologies;
•announcements about new research programs or products of our competitors;
•developments or disputes concerning patent applications, issued patents or other proprietary rights;
•the recruitment or departure of key personnel;
•litigation and governmental investigations involving us, our industry or both;
•investor perceptions of us or our industry;
•negative perceptions of publicly traded companies that have gone public through business combinations with publicly traded special purpose acquisition companies;
•sales of our Common Stock by us or by our insiders or other stockholders;
•the expiration of market standoff or lock-up agreements;
•general economic, industry and market conditions; and
•the COVID-19 pandemic, natural disasters or major catastrophic events.
Recently, stock markets in general, and the market for life sciences technology companies in particular, have experienced significant price and volume fluctuations that have often been unrelated or disproportionate to changes in the operating performance of the companies whose stock is experiencing those price and volume fluctuations, particularly in light of the ongoing COVID-19 pandemic and current macroeconomic conditions. Broad market and industry factors may seriously affect the market price of our Common Stock, regardless of our actual operating performance. These fluctuations may be even more pronounced in the trading market for our Common Stock. Following periods of such volatility in the market price of a company’s securities, securities class action litigation has often been brought against that company. Because of the potential volatility of the price of our Common Stock, we may become the target of securities litigation in the future. Securities litigation could result in substantial costs and divert management’s attention and resources from our business.
If we fail to regain compliance with the continued listing requirements of Nasdaq, our Common Stock may be delisted and the price of our Common Stock and our ability to access the capital markets could be negatively impacted.
From February 8, 2023 through March 22, 2023, the bid price of our Common Stock has closed below the $1.00 per share minimum bid price requirement for continued inclusion on Nasdaq. On March 23, 2023, we received a deficiency letter from the Listing Qualifications Department of the Nasdaq Stock Market, or Nasdaq, notifying us that, for the last 30 consecutive business days, the bid price for our Common Stock had closed below the minimum $1.00 per share requirement for continued inclusion on the Nasdaq Global Market, referred to as the minimum bid price rule. In accordance with Nasdaq Listing Rules, we have an initial period of 180 calendar days, or until September 19, 2023, to regain compliance with the minimum bid price rule. To date, we have not regained compliance with the minimum bid price rule. If at any time before September 19, 2023, the bid price for our Common Stock closes at $1.00 or more per share for a minimum of 10 consecutive business days, the Nasdaq Listing Qualifications Department staff will provide written notification to us that we are in compliance with the minimum bid price rule, unless the staff exercises its discretion to extend this 10-day period pursuant to the Nasdaq Listing Rules. If we do not regain compliance with the minimum bid price rule by the required date and we are not eligible for any additional compliance period at that time, the Nasdaq Listing Qualifications Department staff will provide us written notification that our Common Stock may be delisted. At that time, we may appeal the staff’s delisting determination to a Nasdaq Listing Qualifications Panel. We expect that our Common Stock would remain listed pending the panel’s decision. However, there can be no assurance that, even if we appeal the staff’s delisting determination to the Nasdaq Listing Qualifications Panel, such appeal would be successful. We intend to monitor the closing bid price of our Common Stock and may, if appropriate, consider available options to regain compliance with the minimum bid price rule, which could include seeking to effect a reverse stock split. However, there can be no assurance that we will be able to regain compliance with the minimum bid price rule. There are many factors that may adversely affect our minimum bid price, including those described throughout this section titled “Risk Factors.” Many of these factors are outside of our control. As a result, we may not be able to sustain compliance with the minimum bid price rule in the long term. Any potential delisting of our Common Stock from the Nasdaq Global Market would likely result in decreased liquidity and increased volatility for our Common Stock and would adversely affect our ability to raise additional capital or to enter into strategic transactions. Any potential delisting of our Common Stock from the Nasdaq Global Market would also make it more difficult for our stockholders to sell our Common Stock in the public market.
Pre-revenue biotechnology companies like GreenLight require continuing capital infusion to survive. The capital markets are generally constrained at this point and this is particularly true for biotechnology companies. As a result, we may be unable to obtain continued financing or the financing we do obtain could significantly dilute current shareholders. We believe our stock is significantly undervalued and we therefore represent an attractive acquisition target. If our Board does decide to make some or all of the Company available for sale, it is obligated to take the interests of multiple stakeholders into account and, if faced with competing offers, may not take the offer that maximizes shareholder return.
The exercise of registration rights may adversely affect the market price of the our Common Stock.
Certain of our stockholders have registration rights for certain securities. Pursuant to the Subscription Agreements for the PIPE Financings and the Investor Rights Agreement, we have registered a substantial number of shares of our Common Stock for resale and for issuance upon exercise of the Public Warrants. We are obligated to file one or more resale “shelf” registration statements to register such securities, use commercially reasonable efforts to cause such registration statements to be declared effective by the SEC within specified periods, and keep such registration statements effective for up to three years thereafter. We are also obligated to file other registration statements, including for underwritten offerings of our Common Stock, in specified circumstances. Sales of a substantial number of shares of our Common Stock pursuant to these registration statements in the public market could occur at any time. These sales, or the perception in the market that the holders of a large number of shares intend to sell shares, could reduce the market price of our Common Stock.
If securities or industry analysts do not publish or cease publishing research or reports about GreenLight, our business, or our market, or if they change their recommendations regarding our securities adversely, the price and trading volume of our securities could decline.
The trading market for our securities will be influenced by the research and reports that industry or securities analysts may publish about us, our business, markets or competitors. Securities and industry analysts do not currently, and may never, publish research on GreenLight. If no securities or industry analysts commence coverage of us, our share price and trading volume would likely be negatively impacted.
Reports published by analysts, including projections in those reports that differ from our actual results, could adversely affect the price and trading volume of our Common Stock.
Securities research analysts may establish and publish their own periodic projections for GreenLight. These projections may vary widely and may not accurately predict the results we actually achieve. The share price of our Common Stock may decline if our actual results do not match the projections of these securities research analysts. If any of the analysts who may cover GreenLight issue an adverse or misleading opinion regarding GreenLight, our business model, our intellectual property or our stock performance, change their recommendation regarding shares of our Common Stock adversely, provide relatively more favorable recommendations about our competitors or if the clinical trials and operating results fail to meet the expectations of analysts, the price of shares of our Common Stock would likely decline. If one or more of these analysts ceases coverage of GreenLight or fails to publish reports on GreenLight regularly, the share price or trading volume of our Common Stock could decline. If no analysts commence coverage of GreenLight, the market price and volume for our Common Stock could be adversely affected.
We have broad discretion in the use of the net proceeds from the exercise of outstanding public and private warrants, if any, and may not use them effectively.
As of December 31, 2022, we had outstanding Public Warrants to purchase 10,244,880 shares of Common Stock and private placement warrants to purchase 2,062,500 shares of Common Stock, in each case for an exercise price of $11.50 per share. The warrants may never be exercised for cash, in which case we will not receive any proceeds from such exercise. Because of this uncertainty, we have no specific plans for the proceeds that we may receive from warrant exercises, if any, and we intend to use any such proceeds for general corporate purposes and working capital, including the funding of our clinical programs. Our management will have broad discretion in the application of the net proceeds. Our management may spend a portion or all of the net proceeds in ways that our stockholders may not desire or that may not yield a favorable return. The failure by our management to apply these funds effectively could harm our business, financial condition, results of operations and prospects. Pending their use, we may invest the net proceeds from the exercise of such warrants, if any, in a manner that does not produce income or that loses value.
We do not expect to pay any dividends for the foreseeable future. Investors may never obtain a return on their investment.
You should not rely on an investment in our Common Stock to provide dividend income. We do not anticipate that we will pay any dividends to holders of our Common Stock in the foreseeable future. Instead, we plan to retain any earnings to maintain and expand our existing operations, fund our research and development programs and continue to invest in our commercial infrastructure. In addition, any future credit facility or financing we obtain may contain terms prohibiting or limiting the amount of dividends that may be declared or paid on our Common Stock. Accordingly, investors must rely on sales of their shares after price appreciation, which may never occur, as the only way to realize any return on their investment. As a result, investors seeking cash dividends should not purchase our Common Stock.
The Charter designates the Delaware Court of Chancery as the exclusive forum for specified disputes between New GreenLight and our stockholders and also provides that the federal district courts are the exclusive forum for resolving any complaint asserting a cause of action arising under the Securities Act, each of which could limit the ability of our stockholders to choose the judicial forum for disputes with GreenLight or our directors, officers or employees.
Our Charter provides that, unless we consent in writing to the selection of an alternative forum (an “Alternative Forum Consent”), to the fullest extent permitted by the applicable law, the Court of Chancery of the State of Delaware will be the sole and exclusive forum for any stockholder (including a beneficial owner) to bring (i) any derivative action or proceeding brought on behalf of GreenLight, (ii) any action asserting a claim of breach of a fiduciary duty owed by any director, officer or other employee of GreenLight to us or our stockholders, (iii) any action asserting a claim against GreenLight, our directors, officers or employees arising pursuant to any provision of the DGCL, the Charter or the Bylaws, or (iv) any action asserting a claim against GreenLight, our directors, officers or employees governed by the internal affairs doctrine, subject to specified exceptions. This provision will not apply to suits brought to enforce a duty or liability created by the Securities Exchange Act of 1934, as amended, for which claims may be brought in any U.S. federal court, or any other claim for which the federal courts have exclusive jurisdiction.
To prevent having to litigate claims in multiple jurisdictions and the threat of inconsistent or contrary rulings by different courts, among other considerations, the Charter also provides that, unless we give an Alternative Forum Consent, the federal district courts of the United States will, to the fullest extent permitted by law, be the exclusive forum for the resolution of any complaint asserting a cause of action arising under the Securities Act or the rules and regulations promulgated thereunder. However, Section 22 of the Securities Act creates concurrent jurisdiction for federal and state courts over all such actions. Accordingly, both state and federal courts have jurisdiction to entertain such claims, and there is uncertainty whether a court would enforce the Charter’s choice of forum provision applicable to Securities Act claims.
Any person or entity purchasing or otherwise acquiring any interest in any of our securities shall be deemed to have notice of and consented to the foregoing charter provisions. Although we believe these exclusive forum provisions benefit us by providing increased consistency in the application of Delaware law and federal securities laws in the types of lawsuits to which each applies, the exclusive forum provisions may limit a stockholder’s ability to bring a claim in a judicial forum of its choosing for disputes with GreenLight or any of our directors, officers, or other employees, which may discourage lawsuits with respect to such claims against GreenLight and our current and former directors, officers, or other employees. In addition, a stockholder that is unable to bring a claim in the judicial forum of its choosing may be required to incur additional costs in the pursuit of actions which are subject to the exclusive forum provisions described above. Our stockholders will not be deemed to have waived our compliance with the federal securities laws and the rules and regulations thereunder as a result of our exclusive forum provisions. Further, in the event a court finds either exclusive forum provision contained in the Charter to be unenforceable or inapplicable in an action, we may incur additional costs associated with resolving such action in other jurisdictions, which could harm our results of operations.
Delaware law and provisions in our Charter and Bylaws might discourage, delay or prevent a change in control of our company or changes in our management and, therefore, depress the trading price of our Common Stock.
Our status as a Delaware corporation and the anti-takeover provisions of the Delaware General Corporation Law may discourage, delay or prevent a change in control by prohibiting us from engaging in a business combination with an interested stockholder for a period of three years after the person becomes an interested stockholder without the approval of holders of 662/3% of the voting power of our stockholders other than the interested stockholder, even if a change of control would be beneficial to our existing stockholders. In addition, our Charter and Bylaws contain provisions that may make the acquisition of our company more difficult, including the following:
•Our board of directors is classified into three classes of directors with staggered three-year terms, and directors can only be removed from office for cause by the affirmative vote of holders of a majority of the voting power of our then-outstanding capital stock;
•certain amendments to our Charter will require the approval of stockholders holding three-fourths of the voting power of our then-outstanding capital stock;
•any stockholder-proposed amendment to the Bylaws that is not recommended by the Board will require the approval of stockholders holding three-fourths of the voting power of our then-outstanding capital stock;
•our stockholders are only able to take action at a meeting of stockholders and cannot take action by written consent for any matter;
•vacancies on our board of directors can be filled only by our board of directors and not by stockholders;
•only the Board of Directors of the Company (the "Board"), pursuant to a written resolution adopted by a majority of the Board, is authorized to call a special meeting of stockholders;
•certain litigation against GreenLight can only be brought in Delaware;
•the Charter authorizes undesignated preferred stock, the terms of which may be established by the Board, which shares may be issued without the approval of the holders of our capital stock; and
•advance notice procedures apply for stockholders to nominate candidates for election as directors or to bring matters before an annual meeting of stockholders.
These anti-takeover defenses could discourage, delay, or prevent a transaction involving a change in control of GreenLight. These provisions could also discourage proxy contests and make it more difficult for stockholders to elect directors of their choosing or to cause us to take other corporate actions they desire, any of which, under certain circumstances, could limit the opportunity for our stockholders to receive a premium for their shares of our capital stock.
The ability to use our net operating losses to offset future taxable income may be subject to numerous limitations.
As of December 31, 2022, GreenLight had U.S. federal and state net operating loss carryforwards, or NOLs, of $276.2 million and $237.8 million, respectively. If not utilized, the federal NOLs generated before 2018 of approximately $27.1 million will expire at various dates through 2037 and the state NOLs will expire at various dates through 2040. The federal NOLs generated after 2017 of approximately $249.1 million have an indefinite carryforward period. GreenLight may potentially use these U.S. federal and state NOLs to offset against taxable income for U.S. federal and state income tax purposes. However, the use of these NOLs may be subject to numerous limitations under the U.S. Internal Revenue Code of 1986, as amended, or the Code, and under state tax laws. Among such limitations, Section 382 of the Code may limit the use of these NOLs in any year for U.S. federal income tax purposes in the event of certain past or future changes in ownership of GreenLight. An ownership change under Section 382 of the Code, referred to in this discussion as an ownership change, generally occurs if one or more stockholders or groups of stockholders who own at least 5% of a company’s stock increase their ownership by more than 50 percentage points over their lowest ownership percentage within a rolling three-year period. An ownership change in respect of GreenLight also could be deemed to be an ownership change in respect of GreenLight. We have not conducted a Section 382 study to determine whether the use of our NOLs is impaired under Section 382 of the Code as a result of any prior ownership change. GreenLight may have previously undergone one or more ownership changes. In addition, the Business Combination and the PIPE Financings, or future issuances or sales of our stock, including certain transactions involving our stock that are outside of our control, could result in future ownership changes. Ownership changes that have occurred in the past or that may occur in the future, including in connection with the Business Combination and the PIPE Financings, could result in the imposition of an annual limit under Section 382 of the Code on the amount of pre-ownership change NOLs and other tax attributes that GreenLight can use to reduce its taxable income, potentially increasing or accelerating its liability for income taxes, and also potentially causing those tax attributes to expire unused. States may impose similar limitations on the use of applicable NOLs. Any limitation on using NOLs, whether under Section 382 of the Code or otherwise under U.S. federal or state tax laws, could, depending on the extent of such limitation and the NOLs previously used, result in GreenLight retaining less cash after payment of U.S. federal and state income taxes in respect of any year in which GreenLight has taxable income, rather than losses, than GreenLight would be entitled to retain if such NOLs were available as an offset against such income for U.S. federal and state income tax reporting purposes, which could adversely impact GreenLight’s operating results.
GreenLight is an “emerging growth company” and a “smaller reporting company”, and the reduced disclosure requirements applicable to emerging growth companies and smaller reporting companies may make our Common Stock less attractive to investors.
We are an “emerging growth company,” as defined in the JOBS Act. For so long as we remain an emerging growth company, we are permitted by SEC rules to, and plan to, rely on exemptions from certain disclosure requirements that are applicable to other SEC registered public companies that are not emerging growth companies. These exemptions include not being required to comply with the auditor attestation requirements of Section 404 of the Sarbanes Oxley Act, not being required to comply with any requirement that may be adopted by the Public Company Accounting Oversight Board regarding mandatory audit firm rotation or a supplement to the auditor’s report providing additional information about the audit and the financial statements, reduced disclosure obligations regarding executive compensation and exemptions from the requirements of holding a nonbinding advisory vote on executive compensation and any golden parachute payments not previously approved. As a result, the information we provide to stockholders will be different than the information that is available with respect to other public companies that are not emerging growth companies. In this Annual Report on Form 10-K, not all of the executive compensation-related information that would be required if we were not an emerging growth company has been included. If we were to continue to qualify as a “smaller reporting company,” as such term is defined in Rule 12b-2 under the Securities Exchange Act of 1934,
after we cease to qualify as an emerging growth company, we would continue to be permitted to make certain reduced disclosures in our periodic reports and other documents that we file with the SEC. We expect to cease to qualify as a smaller reporting company before we cease to qualify as an emerging growth company. We cannot predict whether investors will find our Common Stock less attractive if we rely on these exemptions. If some investors find our Common Stock less attractive as a result, there may be a less active trading market for our Common Stock and our stock price may be more volatile.
In addition, the JOBS Act provides that an emerging growth company can take advantage of an extended transition period for complying with new or revised accounting standards. This allows an emerging growth company to delay the adoption of certain accounting standards until those standards would otherwise apply to private companies. We have elected to avail ourselves of this exemption from new or revised accounting standards and, therefore, we will not be subject to the same new or revised accounting standards as other public companies that have not made or cannot make a similar election. As a result, our consolidated financial statements may not be comparable to companies that comply with new or revised accounting pronouncements as of public company effective dates.
We will incur significant increased costs and management resources as a result of operating as a public company.
As a public company, we have incurred and will continue to incur significant legal, accounting, compliance and other expenses that GreenLight did not incur as a private company and that do not appear in our historical consolidated financial statements. These expenses may increase even more after we are no longer an “emerging growth company.” Our management and other personnel will need to devote a substantial amount of time and incur significant expense in connection with compliance initiatives. For example, we will need to implement additional internal controls, both generally and to address the material weaknesses discussed in “Risks Relating to Our Business and Industry”, and disclosure controls and procedures. As a public company, we will bear all of the internal and external costs of preparing and distributing periodic public reports in compliance with our obligations under the securities laws.
In addition, regulations and standards relating to corporate governance and public disclosure, including the Sarbanes-Oxley Act, and the related rules and regulations implemented by the SEC and Nasdaq, have increased legal and financial compliance costs and will make some compliance activities more time-consuming. For example, Nasdaq imposes requirements to obtain stockholder approval for the issuance of equity securities in a variety of circumstances, and this requirement can limit the financing alternatives available to us and thereby increase the cost of capital, which could reduce shareholder returns. We intend to invest resources to comply with evolving laws, regulations and standards, and this investment will result in increased general and administrative expenses and may divert management’s time and attention from our other business activities. If our efforts to comply with new laws, regulations and standards differ from the activities intended by regulatory or governing bodies due to ambiguities related to practice, regulatory authorities may initiate legal proceedings against us, and our business may be harmed. In the future, it may be more expensive or more difficult for us to obtain director and officer liability insurance, and we may be required to accept reduced coverage or incur substantially higher costs to obtain coverage. These factors could also make it more difficult for us to attract and retain qualified members of our board of directors, particularly to serve on our audit committee and compensation committee, and qualified executive officers.
Risks Related to Being a Public Benefit Corporation
Although we are a public benefit corporation, we cannot provide any assurance that we will achieve our PBC Purpose.
In connection with the Business Combination, we became a public benefit corporation under Delaware law, and our public benefit purpose is set forth in the Charter. Our public benefit purpose is to improve the public health and wellbeing of people and the environment by engineering, developing and commercializing biological products that can reduce chemicals in our environment and promote health through delivery of high quality, affordable products that improve outcomes for people and the planet. As a public benefit corporation, we are required to operate in a responsible and sustainable manner, balancing our stockholders’ pecuniary interests, the best interests of those materially affected by our conduct and our public benefit purpose. When we use the term ‘sustainable,’ we refer to our efforts to align economic development with environmental protection and human well-being as well as our obligations as a public benefit corporation under § 362(a) of the Delaware General Corporation Law. There is no assurance that we will be able to achieve our public benefit purpose or that the expected positive impact from being a public benefit corporation will be realized, which could have a material adverse effect on our reputation, which in turn may have a material adverse effect on our business, results of operations and financial condition.
As a public benefit corporation, our focus on a specific public benefit purpose and producing a positive effect for society may negatively impact our financial performance.
Unlike traditional corporations, whose directors have a fiduciary duty to focus exclusively on maximizing stockholder value, our directors have a fiduciary duty to balance (i) the pecuniary interests of our stockholders, (ii) the best interests of those materially affected by our conduct and (iii) our public benefit purpose, as set forth in the Charter. Therefore, we may take actions that we believe will be in the best interests of those stakeholders materially affected by our public benefit purpose even if those actions do not maximize our financial results. While we intend for this public benefit designation and obligation to provide an overall net benefit to us and our stakeholders, it could instead cause us to make decisions and take actions without seeking to maximize the income generated from our business, and hence available for distribution to our stockholders. Our pursuit of longer-term or non-pecuniary benefits may not materialize within the timeframe we expect or at all, yet may have an immediate negative effect on any amounts available for distribution to our stockholders. Accordingly, being a public benefit corporation could have a material adverse effect on our business, results of operations and financial condition, which in turn could cause our stock price to decline.
Also, as a public benefit corporation, because the Board is required by the DGCL to manage or direct our business and affairs in a manner that balances the pecuniary interests of our stockholders, the best interests of those materially affected by our conduct, and our public benefit purpose, we believe that our public benefit corporation status could make it more difficult for another party to obtain control of us without maintaining our public benefit corporation status and purpose. While Delaware common law, as stated in Revlon, Inc. v. MacAndrews & Forbes Holdings, Inc., 506 A.2d 173 (Del. 1986), and related cases, may impose upon directors of a traditional corporation a duty to maximize short-term stockholder value in certain ‘sale of the company’ transactions, a public benefit corporation board’s decision-making would not be subject to those same constraints. Any of the foregoing provisions could limit the price that investors might be willing to pay in the future for shares of our capital stock, and they could deter potential acquirers of our company, thereby reducing the likelihood that you would receive a premium for your shares of our Common Stock in an acquisition.
Further, public benefit corporations may not be attractive targets for activists or hedge fund investors because new directors would still have to consider and give appropriate weight to the public benefit along with shareholder value, and shareholders committed to the public benefit can enforce this through derivative suits. By requiring that boards of directors of public benefit corporations consider constituencies in addition to shareholder value, Delaware public benefit corporation law could potentially make it easier for a board to reject a hostile bid, even where the takeover would provide the greatest short-term financial yield to investors.
Our directors have a fiduciary duty to consider not only our stockholders’ interests, but also our specific public benefit and the interests of other stakeholders affected by our actions. If a conflict between such interests arises, there is no guarantee such a conflict would be resolved in favor of our stockholders.
While directors of traditional corporations are required to make decisions they believe to be in the best interests of their stockholders, directors of a public benefit corporation have a fiduciary duty to consider not only the stockholders’ interests, but also the company’s specific public benefit and the interests of other stakeholders affected by the company’s actions. Under Delaware law, directors are shielded from liability for breach of these obligations if they make informed and disinterested decisions that serve a rational purpose. Thus, unlike traditional corporations whose directors must focus exclusively on stockholder value, our directors are not merely permitted, but obligated, to consider our specific public benefit and the interests of other stakeholders. In the event of a conflict between the interests of our stockholders and the interests of our specific public benefit or our other stakeholders, our directors must only make informed and disinterested decisions that serve a rational purpose; thus, there is no guarantee such a conflict would be resolved in favor of our stockholders, which could have a material adverse effect on our business, results of operations and financial condition, which in turn could cause our stock price to decline.
As a public benefit corporation, we are required to comply with various new reporting requirements, which, even if complied with, could result in harm to our reputation.
As a public benefit corporation, we are required to publicly disclose a report at least biennially on our overall public benefit performance and on our assessment of our success in achieving our specific public benefit purpose. If we are not timely or are unable to provide this report, or if the report is not viewed favorably by parties doing business with us or regulators or others reviewing our credentials, our reputation and status as a public benefit corporation may be harmed and the value of our stock could decrease as a result.
While not required by Delaware law or the terms of the Charter, we may elect to have our environmental, social and governance (“ESG”) performance assessed against ESG standards, including proprietary criteria established by independent
non-profit organizations. For example, we may seek a Certified B Corporation certification. The requirements for these certifications may change over time. These standards may not be appropriately tailored to the legal requirements of publicly traded companies or to the operational requirements of larger companies. Additionally, our management team might have to spend significant time considering and meeting such certifications or such standards (including preparation of relevant applications and reports) and therefore will be spending less time on operating our business. Further, our reputation could be harmed if we obtain and then lose ESG certifications, whether by our choice or by our failure to meet certification requirements, or if that change in status were to create a perception that we are more focused on financial performance and are no longer as committed to the values shared by certifying organizations. Likewise, our reputation could be harmed if scores given to us by certifying organizations decline, since this might create a perception that we have slipped in our satisfaction of such standards. Similarly, our reputation could be harmed if we take actions that are perceived to be misaligned with our values.
As a public benefit corporation, we may be subject to increased derivative litigation concerning our duty to balance stockholder and public benefit interests, the occurrence of which may have an adverse impact on our financial condition and results of operations.
Stockholders of a Delaware public benefit corporation (if they, individually or collectively, own at least 2% of its outstanding capital stock or at least $2.0 million in market value) are entitled to file a derivative lawsuit claiming that its directors failed to balance stockholder and public benefit interests. This potential liability does not exist for traditional corporations. Therefore, we may be subject to the possibility of increased derivative litigation, which would require the attention of management and, as a result, may adversely impact management’s ability to effectively execute our strategy. Any such derivative litigation may be costly and have an adverse impact on our financial condition and results of operations.
Our status as a public benefit corporation could make an acquisition of our company, which may be beneficial to our stockholders, more difficult.
While Delaware common law, as stated in Revlon, Inc. v. MacAndrews & Forbes Holdings, Inc., and related cases, may impose upon directors of a traditional corporation a duty to maximize short-term stockholder value in certain ‘sale of the company’ transactions, a public benefit corporation board’s decision-making would not be subject to those same constraints. Our Board could reject a bid to acquire GreenLight in favor of pursuing other stakeholder interests or the specified public benefit, to the detriment of stockholders. Consideration of these competing interests would not preclude our Board from accepting a bid that maximizes short-term stockholder value. Rather, our Board could weigh the merits of accepting the short-term value offered by a bid against other options that may generate greater long-term value or have other meaningful effects on those materially affected by our conduct or public benefit purpose and, if appropriate, could accept a bid that does not maximize short-term value.

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ITEM 1B. UNRESOLVED STAFF COMMENTS
Item 1B. Unresolved Staff Comments.
None

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ITEM 2. PROPERTIES
Item 2. Properties.
Our principal facilities are located in the metropolitan area of Boston, Massachusetts, Rochester, New York, Durham, North Carolina and Spain. We lease all our facilities.
Our corporate headquarters is located in Lexington, Massachusetts, where we lease approximately 59,000 square feet of office and laboratory space. Our leases for this facility expires in June 2032.
Agricultural Manufacturing Facilities
Our manufacturing facilities for our dsRNA agricultural products are located in Rochester, New York. Our lease for this facility commenced in January 2020 and expires in March 2026. Our existing manufacturing operations occupy approximately 24,000 square feet and include two 2,000-liter bioreactors, one of which is operational with the second bioreactor expected to be brought online in the second quarter of 2023.
We estimate that we can currently produce 500 kg of dsRNA per year and that, when the second bioreactor is brought online, we could produce up to 1,000 kg of dsRNA per year. Packaging equipment would also be required. We estimate that the activation of the second bioreactor and packaging equipment would require an additional investment of approximately $1.4 million, of which $0.3 million had been incurred as of December 31, 2022. We are currently designing an expansion of our Rochester facility to increase our manufacturing capacity for agricultural use.
Agricultural Laboratory and Greenhouse
We currently lease approximately 63,000 square feet of laboratory, office and greenhouse space for our agricultural operations at our facility in Durham, North Carolina. Our lease for this facility commenced in December 2022 and expires in December 2033. We estimate that the total cost to build out the new facility will be approximately $13.0 million, pending final adjustments and has been incurred as of December 31, 2022. Approximately $7.6 million has been funded through a tenant incentive allowance provided to us by the Landlord.
In March 2022, the Company entered into a lease for land in Spain to enable agricultural research and development activities. The lease term expires in March 2042.
In December 2022, the Company entered into a lease for land in Colusa Country, California to enable it to conduct certain agricultural research and development activities. The lease term expires in December 2032.
Human Health Facilities
In March 2022, we leased approximately 59,000 square feet in Lexington, Massachusetts for research and development activities, including clean rooms for early-phase clinical material manufacturing for our human health program. Our lease for this facility commenced in May 2022 and expires in June 2032. We expect that the total cost to build out this facility, excluding GMP readiness, will be approximately $3.6 million, pending final adjustments and has been incurred as of December 31, 2022. We anticipate reestablishing our ability to produce GMP clinical trial material in Lexington in the second half of 2023.
We currently have approximately 69,000 square feet of office and lab space in Medford, Massachusetts and Woburn, Massachusetts. Approximately 52,000 square feet of office and lab space has a lease expiry of February 2024. The remaining 17,000 square feet of office and lab space in Medford has a lease expiry of February 2025. GreenLight is actively marketing for sublease approximately 55,000 of the lab and office space between these two locations.
We believe our facilities are adequate and suitable for our current needs. To support future organic growth or merger-and-acquisition activity, we may enter into new leases, assume lease obligations, or acquire property both domestically and internationally. We believe that suitable or alternative space will be available if and when needed.

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ITEM 3. LEGAL PROCEEDINGS
Item 3. Legal Proceedings.
We currently are not a party to any material litigation or other material legal proceedings. From time to time, we may be subject to legal proceedings and claims in the ordinary course of business.

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ITEM 4. MINE SAFETY DISCLOSURE
Item 4. Mine Safety Disclosures.
Not applicable.
PART II

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ITEM 5. MARKET FOR REGISTRANT'S COMMON EQUITY
Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities.
Market Information
The Common Stock and the Public Warrants are listed on Nasdaq under the symbols “GRNA” and “GRNAW,” respectively. Prior to the consummation of the Business Combination, the ENVI Class A Common Stock, ENVI Units and ENVI Public Warrants were traded on Nasdaq under the symbols “ENVI,” “ENVIU” and “ENVIW,” respectively.
Holders
As of March 15, 2023, there were 131 holders of record of our Common Stock. The number of holders of record does not include “street name” holders or beneficial holders whose shares of Common Stock are held of record by banks, brokers and other financial institutions.
Dividend Policy
We have not paid any cash dividends to date. We currently intend to retain all available funds and future earnings, if any, for the operation and expansion of our business and do not anticipate declaring or paying any dividends in the foreseeable future. The payment of cash dividends in the future will depend on our revenues and earnings, if any, capital requirements and general financial condition. The payment of any cash dividends will be within the discretion of our Board at such time. The terms of our existing loan agreements generally preclude us from paying cash dividends without consent. Our ability to declare dividends may also be limited by restrictive covenants under any future debt financing agreements.
Use of Proceeds from the IPO
ENVI’s registration statement on Form S-1 (SEC File No. 333-251593) for its IPO was declared effective on January 13, 2021. Of total proceeds of $207.0 million, $250,000 was used to pay underwriting fees and expenses, and the remaining net proceeds of $206,750,000 were placed in the trust account (the “IPO Net Proceeds”). The underwriting fees and expenses were paid to ENVI’s qualified independent underwriter, selling group members and other third-party service providers unaffiliated with ENVI. For more information regarding the IPO and the trust account, see the Explanatory Note at the beginning of this Annual Report.
In connection with the closing of the Business Combination, 19,489,626 shares of ENVI Class A Common Stock were redeemed for an aggregate payment of approximately $194.9 million. The redemption price was paid from the IPO Net Proceeds held in the trust account. The remaining IPO Net Proceeds of approximately $12.1 million were disbursed to New GreenLight, which used those funds to pay a portion of the expenses incurred in connection with the Business Combination.
The expenses of the Business Combination included payments of approximately $5.8 million to Canaccord Genuity LLC for services rendered in connection with the Business Combination pursuant to the terms of the Business Combination Marketing Agreement. Canaccord is an affiliate of the Sponsor and the employer of Daniel Coyne, ENVI’s President and Chief Executive Officer and a director of ENVI until the Closing Date, Marc Marano, ENVI’s Chief Financial Officer and Treasurer until the Closing Date, and Jennifer E. Pardi, a director of ENVI and a current director of New GreenLight. The balance of the IPO Net Proceeds was used to pay a portion of the fees and expenses of SVB Leerink LLC and Credit Suisse Securities (USA) LLC for their services as placement agents for the PIPE Financing.

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ITEM 6. SELECTED FINANCIAL DATA
Item 6. [Reserved]

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ITEM 7. MANAGEMENT'S DISCUSSION AND ANALYSIS
Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations.
The following discussion and analysis of the financial condition and results of operations of GreenLight Biosciences Holdings PBC and its consolidated subsidiaries should be read together with the Company’s audited consolidated financial statements, together with the related notes thereto, included elsewhere in this Annual Report on Form 10-K (this “Report”). This discussion contains forward-looking statements that involve numerous risks and uncertainties, including, but not limited to, those described under the heading “Risk Factors” in Item 1A of Part I of this Report. See “Cautionary Note Regarding Forward-Looking Statements” at the beginning of this Report. All references to years, unless otherwise noted, refer to the Company’s fiscal years, which end on December 31. For purposes of this section, all references to “we,” “us,” “our,” “New GreenLight” or the “Company” refer to GreenLight Biosciences Holdings PBC and its consolidated subsidiaries.
Overview
GreenLight Biosciences Holdings, PBC is a pre-commercial stage biotechnology company with a proprietary cell-free ribonucleic acid (RNA) production platform for the discovery, development, and commercialization of high-performing products to promote healthier plants, foods, and people. Our vision is to pave the way for a sustainable planet through widely available and affordable RNA products. We are developing RNA products for plant and life science applications to advance crop management, plant protection, animal health, vaccine development and pandemic preparation. We have a pipeline of product candidates across various stages of development.
Since our inception in 2008, we have devoted substantially all of our efforts and financial resources to conducting research and development activities for our programs, acquiring, in-licensing, and discovering product candidates, securing related intellectual property rights, raising capital, and organizing and staffing our company. We do not have any products approved for sale and have not generated any revenue from product sales. From our founding through December 31, 2022, we have funded our operations primarily through proceeds from the sale of our capital stock, the Business Combination (including the related PIPE financing), the Private Placement in August 2022, debt financings, the issuance of convertible notes and collaboration agreements.
We have incurred significant operating losses since inception. Our ability to generate product revenue sufficient to achieve profitability will depend heavily on the successful development and eventual commercialization of one or more of our current or future product candidates. Our net losses were $167.1 million and $112.3 million for the years ended December 31, 2022 and 2021, respectively. As of December 31, 2022 and 2021, we had an accumulated deficit of $420.6 million and $253.6 million, respectively. Notwithstanding our corporate restructuring and realignment in October 2022, we expect to continue to incur significant expenses and operating losses as we pursue our remaining programs, particularly if and as we:
•conduct field and clinical trials for our product candidates;
•continue to develop additional product candidates;
•maintain, expand, and protect our intellectual property portfolio;
•hire additional and/or replacement clinical, scientific manufacturing and commercial personnel;
•expand external and/or establish internal commercial manufacturing sources and secure supply chain capacity sufficient to provide commercial quantities of any product candidates for which we may obtain regulatory approval;
•acquire or in-license other product candidates and technologies;
•seek regulatory approvals for any product candidates that successfully complete field trials or clinical trials;
•establish a sales, marketing, and distribution infrastructure to commercialize any products for which we may obtain regulatory approval; and
•add operational, financial and management information systems and personnel to support our product development, clinical execution and planned future commercialization efforts, as well as to support our operations as a public company.
As a result, we will need substantial additional funding to support our continuing operations and pursue our growth strategy. We expect to finance our operations through the sale of equity securities, debt financings or other capital sources, which may continue to include collaborations with other companies or other strategic transactions. The fundraising environment for early-stage biotechnology companies like ours continues to be extremely challenging, and we may be unable to raise additional funds or enter into such other agreements or arrangements when needed on favorable terms, or at all. If we fail to raise sufficient capital or enter into such agreements or arrangements as and when needed, we may have to significantly delay, scale back, or
discontinue the development and commercialization of one or more of our product candidates and delay or discontinue the pursuit of potential in-license or acquisition opportunities.
Because of the numerous risks and uncertainties associated with product development, we are unable to predict the timing or amount of increased expenses or when or if we will be able to achieve or maintain profitability. Even if we are able to generate product sales, we may not become profitable. If we fail to become profitable or are unable to sustain profitability on a continuing basis, then we may be unable to continue our operations at planned levels and be forced to further reduce or terminate our operations. The Company expects that its existing cash and cash equivalents of $68.1 million as of December 31, 2022 will last through the second quarter of 2023 but will not be sufficient to fund its operations for twelve months from the date these financial statements are issued. We are continuing to evaluate a range of additional opportunities to extend cash runway, including management of program spending, platform licensing collaborations and potential financing activities.
Macroeconomic Conditions
We are currently operating in a period of economic uncertainty and capital markets disruption, which has been significantly impacted by geopolitical instability, including in Europe, and record inflation. GreenLight’s business, financial condition and results of operations could be materially and adversely affected by any negative impact on the global economy and capital markets resulting from these global economic conditions, particularly if such conditions are prolonged or worsen.
Economic uncertainty in various global markets, including the U.S. and Europe, caused by political instability and conflict and economic challenges caused by the ongoing COVID-19 pandemic, have led to market disruptions, including significant volatility in commodity prices, credit and capital market instability and supply chain interruptions, which have caused record inflation globally. While we recognize that the United States public health emergency for Covid is planned to end in May 2023, the full impact of the ongoing COVID-19 pandemic to date and current macroeconomic conditions, including changes in inflation, interest rates and overall economic conditions and uncertainties on our business, operations and product development timelines and plans remains uncertain, and will depend on certain developments, including its impact on our field trial completion, clinical trial initiation and enrollment, trial sites, contract research organizations (“CROs”), contract manufacturing organizations (“CMOs”), and other third parties with whom we do business, as well as its impact on regulatory authorities and our key scientific and management personnel.
While we are experiencing limited financial and operational impacts at this time, given the global economic slowdown, the overall disruption of global healthcare systems and the other risks and uncertainties associated with these macroeconomic conditions, including potential uncertainty with the stability of banks and other financial institutes in light of the Silicon Valley Bank closure in March 2023, it is impossible to predict the extent to which GreenLight’s operations will be impacted in the short and long term, or the ways in which such instability could impact our business and results of operations. The extent and duration of these market disruptions, whether as a result of the military conflict between Russia and Ukraine, geopolitical tensions, record inflation or otherwise, are impossible to predict, but could be substantial. Furthermore, the impacts from the COVID-19 pandemic have resulted and will likely continue to result in significant disruptions to the global economy and capital markets around the world. GreenLight cannot predict the future progression or full impact of the outbreak and its effects on GreenLight’s business and operations. We continue to closely monitor the global economic and geopolitical conditions as we evolve our business continuity plans, clinical development plans and response strategy.
Recent Developments
Human Health Programs
COVID-19 Vaccine Program
As previously announced, GreenLight received approval from the Rwanda Food and Drugs Authority (Rwanda FDA) to initiate a Phase I/II study of its GLB-CoV2-043 (monovalent) vaccine booster candidate in February 2023. However, given the global shift in the standard of care for COVID-19 vaccination to the Wuhan/Omicron bivalent vaccine and new availability of the bivalent vaccine in Rwanda, GreenLight has decided to update its clinical strategy to proceed with its pan-sarbecovirus vaccine candidate instead of the GLB-COV2-043 (monovalent) vaccine candidate as originally planned. GreenLight is accelerating the development of its pan-sarbecovirus vaccine candidate, which is designed to provide broader coverage against current circulating and future emerging variants of SARS-CoV-2 and support future pandemic preparedness and is planning a follow-up filing on this candidate
to the Rwanda FDA and the Rwanda National Ethics Committee (RNEC). GreenLight will be working expeditiously and closely with its Rwandan partners to advance these efforts over the coming months and is also starting conversations with potential partners in other countries that have expressed interest in supporting the clinical development of a broader pan-sarbecovirus vaccine. GreenLight Biosciences has completed the design and in vitro selection of the pan-sarbecovirus vaccine candidates and is currently evaluating them in animal studies for subsequent progression to clinical development subject to those study results.
Shingles Vaccine Program
GreenLight has selected a lead candidate to progress towards clinical development after evaluation of multiple antigen designs and formulations in animal studies. Based on immunological response evaluations in pre-clinical studies of three potential candidates, the pre-clinical data from these studies showed that the lead vaccine candidate: (a) induced antibody levels similar to comparator vaccine (current standard of care), (b) was more potent than comparator vaccine at inducing strong cellular immune response, and (c) maintained memory B and T cells responses at levels similar to comparator vaccine, 3 months after vaccine candidate administration, demonstrating durability of the immune response. The Serum Institute of India Private Limited (SIIPL) will be responsible for the clinical development, manufacturing, and commercialization of the vaccine candidate in lower- and middle- income countries under its license agreement with GreenLight while GreenLight retains the clinical development, manufacturing, and commercial rights in the developed world. We are in active discussions with SIIPL regarding potential plans forward for this vaccine candidate.
Plant Health Programs
Colorado Potato Beetle Program - CalanthaTM
Subject to receiving regulatory approval and applicable state registrations in the US, we anticipate and are in active preparations for commercial launch prior to the end of 2023. As part of this effort, we are in active discussions with territory-relevant distributors across the US as potential partners to support our planned commercial launch. Furthermore, we are planning to submit CalanthaTM for regulatory approval in the EU, UK, Mexico, Canada and Ukraine.
Varroa Mite Program
In February 2023, GreenLight submitted a registration dossier to the EPA for our RNA solution that targets the varroa destructor mite, which threatens the role of honeybees in pollinating more than 100 crops annually. We are also planning to submit this solution for regulatory approval in Canada, New Zealand, the EU, and UK, with other potential territories under consideration. As previously described, our field trial data has shown that there are >40% fewer Varroa destructor mites at 12 and 18 weeks in hives compared with a leading chemical control product and with higher hive survival rates compared to the chemical control. Through our ongoing mode of action studies with Victoria University of Wellington (NZ), data shows that the average number of mite offspring decreased approximately 95% compared to control with no detectable negative impact on the growth and development of juvenile bees. Furthermore, our 2022 trials showed that our varroa mite solution used in spring and fall will more than double the rate of hive survival compared to not treating for varroa mite.
Multitarget Solutions
GreenLight is expanding certain dsRNA-based fungal, insecticide, and acaricide programs into solutions that are designed to address multiple targets.
Powdery Mildew Complex
A complex of diseases that impacts a wide range of crops and plants consisting of multiple species that are slightly genetically diverse. GreenLight has further developed its powdery mildew solution by modifying our lead sequence to enable potential control of multiple targets (i.e. cucurbits PM, cereal PM, and ornamentals PM in addition to original target of vine PM). Our field trials have demonstrated that sprayed unformulated (naked) dsRNA decreases disease severity in grapes and performed similarly to the biological standard in field trials. In a similar field trial on zucchini, data showed that our naked dsRNA sequences performed well but inferior to field trial standards. However, when formulated with adjuvants, our trial results showed that our formulated dsRNA provided a larger reduction in disease severity compared to the industry standard. We are targeting the first regulatory submission of our powdery mildew program in 2024 in the US.
Gray Mold +
Gray mold is a disease that impacts a wide range of crops and plants. GreenLight has modified its lead sequences to add additional target species (i.e. sclerotinia sclerotiorum in addition to original target of botrytis cinerea as described above). Data from recent field trials show that dsRNA can provide multi-species control with commercially relevant spray intervals and naked dsRNA applied on snap beans performed similar to the chemical standard. We are targeting our first regulatory submission of our gray mold program for 2025.
Systemic Delivery
We are in the very early stages of development of potential systemic delivery solutions. Through data from early experiments and subsequent field trial studies conducted last year, GreenLight has demonstrated stability of RNA through a standard seed treatment process and dsRNA delivery into plants, showing decreased fusarium disease severity in lettuce seed treatment field trials across two locations and three lettuce varieties and very preliminary indications of herbicidal activity.
Business Combination and Public Company Costs
On August 9, 2021, the Company and Merger Sub entered into the Business Combination Agreement with GreenLight Biosciences, Inc. (the "Business Combination Agreement" and the transactions contemplated by the Business Combination Agreement, the "Business Combination"). On February 2, 2022, the Business Combination was consummated, pursuant to which Merger Sub merged with and into GreenLight Biosciences, Inc., with GreenLight Biosciences, Inc. surviving the Merger as a wholly owned subsidiary of the Company. On February 2, 2022, in connection with the consummation of the Merger, the Company changed its name to GreenLight Biosciences Holdings, PBC and became a public benefit corporation.
Immediately before the closing of the Business Combination, the Company held approximately $207 million in a trust account for its public stockholders. In connection with the Business Combination, the Company's public stockholders redeemed shares of public common stock for $194.9 million, and the funds remaining after such redemptions became available to finance transaction expenses and the future operations of the Company. In connection with the Business Combination, the Company entered into agreements with new investors and existing investors in GreenLight Biosciences, Inc. to subscribe for and purchase an aggregate of approximately 12.4 million shares of the Company's Class A Common Stock (the “February 2022 PIPE Financing”). The February 2022 PIPE Financing was consummated on February 2, 2022 and resulted in gross proceeds of approximately $136.4 million (of which $35.3 million had been advanced to GreenLight Biosciences, Inc. by the Prepaying PIPE Investors).
The Merger was accounted for as a reverse recapitalization, whereby for accounting and financial reporting purposes, GreenLight Biosciences, Inc. was the acquirer. A reverse recapitalization does not result in a new basis of accounting, and the financial statements of the Company represent the continuation of the consolidated financial statements of GreenLight Biosciences, Inc. in many respects. The shares of the Company remaining after redemptions of shares of the Company's public common stock and the unrestricted net cash and cash equivalents on the date the Business Combination was consummated were accounted for as a capital infusion to GreenLight Biosciences, Inc.
The most significant change in the Company's financial position and results of operations resulting from the consummation of the Business Combination (including the February 2022 PIPE Financing) was an estimated cash inflow (as compared to GreenLight Biosciences, Inc. balance sheet at December 31, 2021) of approximately $136.4 million, prior to payment of the transaction costs. Total direct and incremental transaction costs of $26.7 million were treated as a reduction of the cash proceeds with capital raising costs being deducted from GreenLight Biosciences, Inc.'s additional paid-in capital.
As a consequence of the Business Combination, GreenLight Biosciences, Inc. effectively became the successor to a publicly traded and Nasdaq-listed company, which required it to hire additional personnel and is requiring it to implement procedures and processes to address public company regulatory requirements and customary practices. The Company expects to incur additional annual expenses as a public company for, among other things, directors’ and officers’ liability insurance, director fees and additional internal and external accounting, legal and administrative resources, including increased audit and legal fees.
Financial Overview
Components of Our Results of Operations
Revenue
For the year ended December 31, 2022, we have not recognized any revenue from product sales. If our development efforts for our product candidates are successful and result in regulatory approval, or license agreements with third parties, we may
generate revenue in the future from product sales or license agreements. However, there can be no assurance as to when we will generate such revenue, if at all.
License and Collaboration Revenue
License revenue is related to our license agreement with Serum Institute of India Private Limited (“SIIPL”) which was entered into in March 2022, pursuant to which the Company granted SIIPL an exclusive, sub-licensable, royalty-bearing license to use the Company’s proprietary technology platform to develop, manufacture and commercialize up to three mRNA products. The first licensed product target will be a shingles product target, and SIIPL has an option to select the additional two licensed product targets through the end of 2024. Under the terms of the Agreement with SIIPL, the Company will provide research services related to the shingles product target to develop a “proof of concept” and will provide manufacturing technology transfer services. In addition, GreenLight retains the option to purchase research and clinical trial data, developed by SIIPL, for 50% of the cost of the research studies and clinical trials for use in the Company’s own development.
Pursuant to the License Agreement, SIIPL will pay the Company an upfront license fee of $5.0 million, as well as payments upon additional target selection and reservation of exclusivity. The Company may receive up to a total of an additional $17.0 million in development, regulatory and commercial (net sales) based milestone payments across all three product targets, as well as manufacturing technology transfer payments up to $10.0 million. SIIPL shall pay royalty payments in the mid-double digits, based on the net sales of products resulting from the licensed technology for the term of the License Agreement. The License Agreement shall terminate on a product-by-product and country-by-country basis on the later of the expiration of the patent rights owned by the Company or the tenth anniversary of the first commercial sale of the applicable product(s) in the applicable country. For the year ended December 31, 2022, we recognized $6.4 million of revenue primarily related to the delivery of IP and research services, which includes manufacturing technology transfer services.
Grant Revenue
In July 2020, we entered into a grant agreement with the Bill & Melinda Gates Foundation to advance research in in vivo gene therapy for sickle cell disease and to explore new, low-cost capabilities for the in vivo functional cure of sickle cell and/or durable suppression of HIV in developing countries. We were approved to receive a grant of $3.3 million in the aggregate. As of December 31, 2022, we had received the entire grant amount. The grant agreement provides for payments to reimburse qualifying costs, including general and administrative costs, incurred to perform our obligations under the agreement. Revenue from this grant agreement is recognized as the qualifying costs related to the grant are incurred, and any amounts received in excess of revenue recognized are initially recorded as deferred revenue on our consolidated balance sheets and later recognized as revenue when qualified costs are incurred. The revenue recognized through December 31, 2022 under the grant was related to qualifying research and development expenditures that we incurred. As previously announced, we paused work on our gene therapy program for sickle cell disease, and as a result, we ceased any ongoing research work under the Gates Grant and are in the process of closing out all related activities. We are in the process of delivering the final report to the Gates Foundation and returning any remaining unused funds to the Gates Foundation.
Operating Expenses
Research and Development Expenses
Research and development expenses consist primarily of costs incurred for our research activities, including our discovery efforts and the development of our product candidates. We expense research and development costs as incurred. These expenses include:
Program expenses:
•external research and development expenses incurred under agreements with CMOs, CROs, universities and research laboratories that conduct our field trials, preclinical studies and development services;
•costs related to manufacturing material for our field trials and preclinical studies;
•laboratory supplies and research materials;
•payments made in cash or equity securities under third-party licensing agreements and acquisition agreements;
•costs to fulfill our obligations under the grant agreement with the Bill & Melinda Gates Foundation; and
•costs related to compliance with regulatory requirements;
Personnel expenses:
•employee-related expenses, including salaries, bonuses, benefits, stock-based compensation, and other related costs for employees involved in research and development efforts;
Facilities and other expenses:
•costs of outside consultants engaged in research and development functions, including their fees and travel expenses; and
•facilities, depreciation, and other allocated expenses, which include direct and allocated expenses for rent, utilities, and insurance.
Costs for certain activities are recognized based on an evaluation of the progress to completion of specific tasks using data such as information provided to us by our vendors and analyzing the progress of our field trials and preclinical studies or other services performed.
This process involves reviewing open contracts and purchase orders, communicating with our personnel to identify services that have been performed on our behalf and estimating the level of service performed and the associated cost incurred for the service when we have not yet been invoiced or otherwise notified of actual costs. Nonrefundable advance payments for goods or services to be received in the future for use in research and development activities are recorded as prepaid expenses. Such amounts are recognized as an expense as the goods are delivered or the related services are performed, or until it is no longer expected that the goods will be delivered, or the services rendered.
Our direct research and development expenses are tracked on a program-by-program basis for our product candidates and consist primarily of external costs, such as fees paid to outside consultants, CROs, CMOs and research laboratories in connection with our pre-clinical development, field trials, process development, manufacturing, and clinical development activities. Our direct research and development expenses by program also include fees incurred under license, acquisition, and option agreements. We do not allocate costs associated with our discovery efforts, laboratory supplies, employee costs or facility expenses, including depreciation or other indirect costs, to specific programs because these costs are deployed across multiple programs and, as such, are not separately classified. We use internal resources primarily to conduct our research and discovery as well as for managing our pre-clinical development, field trials, process development, manufacturing, and clinical development activities.
General and Administrative Expenses
General and administrative expense consists primarily of employee-related costs, including salaries, bonuses, benefits, stock-based compensation, and other related costs. General and administrative expense also includes professional services, including legal, accounting and audit services, consulting fees and facility costs not otherwise included in research and development expenses, insurance, and other general administrative expenses.
We anticipate that our general and administrative expenses will increase commensurate with future commercialization of our products and expansion of research collaboration work. We also have incurred significantly increased accounting, audit, legal, regulatory, compliance and director and officer insurance costs as well as investor and public relations expenses associated with operating as a public company.
Other (Expense) Income, Net
Other (expense) income, net consists of interest income, interest expense and any change in the fair value of our warrant liabilities.
Other Income, net
Other income, net primarily consists of income earned in connection with our investments in money market funds.
Interest Expense
Interest expense consists of interest on outstanding borrowings under our loan agreements with Trinity Capital, Silicon Valley Bank and Horizon Technology Finance, our convertible debt and tenant improvement loans payable with our lessors. Interest expense also includes amortization of debt discount and debt issuance costs.
Fair Value of Warrant Liabilities
Change in fair value of warrant liabilities consists of the remeasurement gains or losses associated with changes in the fair value of the warrant liabilities. Until settlement, fluctuations in the fair value of our warrant liabilities are based on the remeasurement at each reporting period.
Provision for Income Taxes
Our income tax provision consists of an estimate for U.S. federal, state and foreign income taxes based on enacted rates, as adjusted for allowable credits, deductions, uncertain tax positions, changes in deferred tax assets and liabilities and changes in tax law. The Company has a provision for income taxes for the year ended December 31, 2022, related to the foreign withholding taxes on payments made by SIIPL, pursuant to the research and collaboration agreement. There is no provision for U.S. federal and state income taxes for the year ended December 31, 2021, as we have historically incurred net operating losses, and expect to continue to generate net operating losses. Based on this history of net operating losses, we also maintain a full valuation allowance against our U.S. federal and state deferred tax assets.
Results of Operations
Comparison of the Years Ended December 31, 2022 and 2021
The following table summarizes our results of operations for the years ended December 31, 2022 and 2021:
YEARS ENDED
DECEMBER 31,
INCREASE /
(DECREASE)
($ in thousands)
License and collaboration revenue
$
6,384
$
-
$
6,384
Grant revenue
1,595
(1,199
)
Total revenue
6,780
1,595
5,185
Operating expenses:
Research and development
133,810
89,832
43,978
General and administrative
35,930
20,321
15,609
Restructuring expenses
-
Total operating expenses
170,699
110,153
60,546
Loss from operations
(163,919
)
(108,558
)
(55,361
)
Other income (expenses):
Other income, net
Interest expense
(4,123
)
(2,419
)
(1,704
)
Change in fair value of warrant liability
1,184
(1,370
)
2,554
Total other expense, net
(2,044
)
(3,752
)
1,708
Net loss before income tax
(165,963
)
(112,310
)
(53,653
)
Income tax expense
1,092
-
1,092
Net loss
$
(167,055
)
$
(112,310
)
$
(54,745
)
License and Collaboration Revenue
For the year ended December 31, 2022, we recognized $6.4 million of revenue from our license agreement with SIIPL primarily related to the delivery of IP and research services, which includes manufacturing technology transfer services. As the license and collaboration agreement was executed in March 2022, we did not recognize any revenue under this agreement for the year ended December 31, 2021.
Grant Revenue
Grant revenue was $0.4 million for the year ended December 31, 2022, compared to grant revenue of $1.6 million for the year ended December 31, 2021. All of our grant revenue is derived from a grant made by the Bill & Melinda Gates Foundation in July 2020. The decrease in grant revenue is due to a decrease of costs incurred under this grant.
Research and Development Expenses
YEARS ENDED
DECEMBER 31,
INCREASE /
(DECREASE)
($ in thousands)
Program expense
$
57,143
$
36,323
$
20,820
Personnel costs
48,875
35,844
13,031
Other
27,792
17,665
10,127
Total research and development expenses
$
133,810
$
89,832
$
43,978
Research and development expense was $133.8 million for the year ended December 31, 2022, compared to $89.8 million for the year ended December 31, 2021. The increase of $44.0 million resulted primarily from increased program costs related to commercial-scale engineering run, specifically costs of approximately $17.7 million related to research and development materials, manufacturing and service fees supporting the commercial-scale engineering run, pre-clinical trial activities and personnel expenses, as well as facilities costs such as rent and depreciation expenses.
Our headcount supporting research and development activities increased, which generated additional personnel-related costs of $13.0 million. Other research and development costs increased by approximately $10.1 million, primarily related to a $7.6 million increase in rental expense as we expanded our footprints and entered into multiple leases during 2022 and 2021, and an increase of $2.4 million in depreciation expense due to an increase in capitalized expenditures for lab equipment and lab space leasehold improvements.
General and Administrative Expenses
General and administrative expense was $35.9 million for the year ended December 31, 2022, compared to $20.3 million for the year ended December 31, 2021. The increase of $15.6 million was primarily due to an increase of $5.8 million in personnel-related costs in general and administrative functions, which resulted from increased headcount supporting general and administrative activities; a $4.6 million increase in professional services fees to support the Business Combination Agreement and costs associated with being a publicly traded company; a $3.2 million increase in insurance for directors and officers coverage; and an increase of $0.9 million related to facilities as we expanded our footprints and entered into multiple leases during 2022 and 2021.
Restructuring Expenses
Restructuring expense was $1.0 million for the year ended December 31, 2022, primarily related to severance benefits. This was a result of a restructuring plan to realign operating costs to better focus on near-term value drivers announced in October 2022.
Other Income, net
For the year ended December 31, 2022, other income was $0.9 million for the year ended December 31, 2022 compared to $37 thousand for the year ended December 31, 2021. This increase was driven by an increase in our cash and cash equivalents due to capital raises in 2022 and an increase in the interest rate yield on our cash and cash equivalents.
Interest Expense
Interest expense was $4.1 million for the year ended December 31, 2022, compared to $2.4 million for the year ended December 31, 2021. The increase of $1.7 million is primarily related to interest accrued on the various loan agreements we entered into during the second half of 2021 as well as increases in interest rates on our variable rate debt throughout 2022.
Change in Fair Value of Warrant Liabilities
Other income attributable to the change in fair value of warrant liabilities was $1.2 million for the year ended December 31, 2022, compared to an expense of $1.4 million for the year ended December 31, 2021. The entire decrease of $2.6 million in the fair value of our warrant liabilities was due to the decrease in the fair value of the private placement warrants driven by a decrease in our stock price during 2022.
Income Tax Expense
For the year ended December 31, 2022, income tax expense was $1.1 million for the year ended December 31, 2022 related to foreign withholding tax from the Agreement with SIIPL. There was no income tax expense recorded for the year ended December 31, 2021.
Liquidity and Capital Resources
Sources of Liquidity
Since our inception, we have generated recurring net losses. We do not have any products approved for sale and have not yet commercialized any product. Since our inception, we have funded our operations primarily through proceeds from the issuance of capital stock and to a lesser extent through debt financings, the issuance of convertible notes, and collaboration agreements. From our founding through December 31, 2022, we have raised proceeds from the sale of our capital stock, the Business Combination (including the related PIPE financing), the August 2022 PIPE Financing, and from the issuance of debt and convertible notes. As of December 31, 2022, we had cash and cash equivalents of $68.1 million.
Private Placement and Securities Subscription Agreement
On August 11, 2022, we entered into Securities Subscription Agreements (the “August 2022 PIPE Subscription Agreements”) with certain institutional accredited investors (collectively, the “August 2022 PIPE Investors”), providing for the sale by us of 27,640,301 shares (the “August 2022 PIPE Shares”) of our Common Stock at a purchase price of $3.92 per share, in a private placement (the “August 2022 PIPE Financing” and together with the February 2022 PIPE Financing, the "PIPE Financings"). The August 2022 PIPE Shares were issued (the “Closing”) simultaneously with the execution and delivery of the August 2022 PIPE Subscription Agreements. The aggregate gross proceeds for the Private Placement were approximately $108.3 million. The gross proceeds do not reflect transaction costs of $2.3 million. We intend to use the net proceeds from the August 2022 PIPE Financing to fund ongoing clinical development and commercialization of our existing product pipeline.
Business Combination and PIPE Financing
In February 2022, we consummated the Business Combination with ENVI, which generated gross proceeds to New GreenLight of approximately $136.4 million, including $124.3 million from the PIPE Financing and $12.1 million from the trust account (after redemptions). The gross proceeds do not reflect transaction costs of $26.7 million. For more information, see “-Recent Developments-Business Combination and Public Company Costs” above.
Horizon Loan Agreement
In December 2021, we entered into a loan and security agreement with Horizon Technology Finance Corporation and Powerscourt Investments XXV, LP (together, “Horizon”), which provided for a term loan facility in an aggregate principal amount of up to $25.0 million, $15.0 million of which was borrowed at the closing and the remainder of which may be borrowed following the achievement of certain milestones, but not after June 30, 2022. As of June 30, 2022, we had not borrowed, and could no longer borrow the remainder of the term loan. Under the agreement, in January 2022 the lenders were granted 10-year warrants to purchase shares of common stock of GreenLight. The warrants are exercisable in the aggregate for a number of shares equal to 3% of the total term loan facility (assuming we borrow the full facility amount of $25.0 million) divided by the exercise price of the warrants. Upon the closing of the Business Combination, the warrants became warrants to purchase shares of New GreenLight Common Stock based on the exchange ratio under the Business Combination Agreement.
Accrued interest is payable monthly. Under the terms of our agreement, this loan accrues interest at a floating rate per annum equal to the one-month prime rate as reported in the Wall Street Journal on a date that is 5 business days prior to the funding date of the Loan plus 5.75%. The principal of each term loan must be repaid in equal monthly installments beginning February 1, 2023, with a scheduled final maturity date of July 1, 2025. We may prepay the term loans in full, but not in part, without premium or penalty, other than a premium equal to (i) 3% of the principal amount of any prepayment made within 12 months after the applicable funding date, (ii) 2% of the principal amount of any prepayment made between 12 and 24 months after the applicable funding date and (iii) 1% of the principal amount of any prepayment made more than 24 months after the applicable funding date. On the earlier of the scheduled final maturity date and the prepayment in full of the term loans, we must pay a final payment fee equal to 3.0% of the original principal amount of the funded term loans.
The agreement contains customary affirmative and negative covenants (including an obligation to maintain certain amounts of cash in accounts subject to springing control in favor of the lenders) and customary events of default; it does not contain a financial covenant. We granted a second-priority, perfected security interest in substantially all of our present and future personal
property and assets, excluding intellectual property, to secure our obligations to the lenders, which security interest is subordinated to the security interest granted to Silicon Valley Bank.
In April 2021, we entered into a joinder agreement with Horizon pursuant to which the Company became a party to the Horizon loan agreements as a co-borrower. Under the joinder agreement, the Company also granted Horizon a continuing security interest in its existing and after-acquired personal property and assets, excluding intellectual property.
Silicon Valley Bank Loan Agreement
In September 2021, we entered into a loan and security agreement with Silicon Valley Bank, or SVB, providing for a term loan facility in an aggregate principal amount of up to $15.0 million, $10.0 million of which we borrowed at the closing and the remainder of which we may borrow following the achievement of certain milestones, but not after March 31, 2022. We did not borrow any additional amounts from SVB before March 31, 2022. At the closing, we granted SVB a 10-year warrant to purchase up to 34,427 shares of GreenLight Common Stock (assuming we borrow the entire $15.0 million from SVB and giving effect to the reverse recapitalization). Upon the closing of the Business Combination, the warrants became warrants to purchase shares of New GreenLight Common Stock based on the exchange ratio under the Business Combination Agreement.
Accrued interest is payable monthly. Under the terms of our agreement, this loan accrues interest at a floating rate per annum equal to the greater of (i) three and one half of one percent (3.50%) and (ii) the prime rate (as stated in the Wall Street Journal) plus the prime rate margin of one quarter of one percent (0.25%). The principal of each term loan must be repaid in equal monthly installments beginning April 1, 2022 (or October 1, 2022, if the Company borrows any of the remaining $5.0 million), with a scheduled final maturity date of September 1, 2024. On the earlier of the scheduled final maturity date and the prepayment in full of the term loans, the Company must pay a final payment fee equal to 4.0% of the original principal amount of the term loans. The Company may prepay the term loans in increments of $5.0 million and without premium or penalty, other than a premium equal to (i) with respect to any prepayment made on or before September 22, 2022, 3% of the principal so prepaid, (ii) with respect to any prepayment made after September 22, 2022 and on or before September 22, 2023, 2% of the principal so prepaid and (iii) with respect to any prepayment made after September 22, 2023 and on or before September 1, 2024, 1% of the principal so prepaid.
The loan and security agreement with SVB contains customary affirmative and negative covenants (including the obligation to maintain all of its cash in accounts at SVB, including at all times amounts sufficient to repay all loan obligations, which if not met constitute an event of default under the agreement) and customary events of default; it does not contain a financial covenant. We granted a first-priority, perfected security interest in substantially all of our present and future personal property and assets, excluding intellectual property, to secure our obligations to SVB.
In April 2021, we entered into a joinder agreement and first amendment to loan and security agreement with SVB pursuant to which the Company became a party to the SVB loan agreements as a borrower. Under these agreements, the Company also granted SVB a continuing security interest in its existing and after-acquired personal property and assets, excluding intellectual property. These agreements also amended certain terms of the original SVB loan agreement to, among other things, add representations, affirmative and negative covenants, and events of default regarding the Company’s obligations as a public benefit corporation. Under the amended terms, it is an event of default for there to be any pending or threatened litigation by a shareholder alleging that we or our directors failed to satisfy any obligations under Delaware law regarding our status as a public benefit corporation, if the litigation is likely to result in a final monetary judgment against us in excess of $250,000. In addition, if any action, investigation, or proceeding is pending or known to be threatened in writing against us with respect to such a claim, the bank may not need to make further loans to us.
On March 10, 2023, SVB was closed by the California Department of Financial Protection and Innovation, and the Federal Deposit Insurance Corporation (“FDIC”) was appointed as receiver and SVB was subsequently transferred into a new entity, Silicon Valley Bridge Bank, N.A (“SVB Bridge Bank”).
Trinity Capital Equipment Financing Agreement
In March 2021, we entered into a master equipment financing agreement with Trinity Capital (Trinity) authorizing equipment financing with an aggregate borrowing capacity of $11.3 million, with up to $5.0 million available immediately and the remaining principal balance available to be drawn before September 2021. We entered into this loan to finance our capital purchases associated primarily with our research and manufacturing programs. The monthly payment factors for each draw are determined by Trinity based on the Prime Rate reported in the Wall Street Journal on the first day of the month in which an equipment financing schedule for such draw is executed. As of December 31, 2021, the Company had drawn the entire $11.3 million, which is repayable in monthly installments starting April 2021.
Funding Future Operations; Going Concern
The Company estimates that its existing cash and cash equivalents of $68.1 million as of December 31, 2022 will last through the second quarter of 2023 but will not be sufficient to fund its operations for twelve months from the date these financial statements are issued. As a result, there is substantial doubt about our ability to continue as a going concern for at least one year from the date of issuance of these financial statements, as discussed in Note 1 - Nature of Business and Basis of Presentation of the notes to our consolidated financial statements as of December 31, 2022 and for the year ended December 31, 2022, included elsewhere herein.
Based on our existing cash and cash equivalents, we are evaluating a range of opportunities to extend cash runway, including management of program spending, platform licensing collaborations and potential financing activities.
We expect to incur significant expenses and operating losses for the foreseeable future as we advance our product candidates through preclinical and clinical development and field trials, seek regulatory approval, and pursue commercialization of any approved product candidates. We anticipate that our general and administrative expenses will increase commensurate with future commercialization of our products and expansion of research collaboration work. In addition, in light of the completion of the Business Combination, we have incurred and expect to incur continuing costs associated with operating as a public company. Because of the numerous risks and uncertainties associated with research, development, and commercialization of our product candidates, we are unable to estimate the exact amount of our working capital requirements. Our future capital requirements will depend on many factors, including:
•the design, initiation, timing, costs, progress, and results of our planned clinical trials and field trials;
•the progress of preclinical development and possible clinical trials of our current and future earlier- stage programs;
•the scope, progress, results and costs of our research programs and preclinical development of any additional product candidates that we may pursue;
•the development requirements of other product candidates that we may pursue;
•our headcount and associated costs and establish a commercial infrastructure;
•the timing and amount of milestone and royalty payments that we are required to make or eligible to receive under our current or future collaboration and license agreements;
•the outcome, timing and cost of meeting regulatory requirements established by the FDA, EPA and other regulatory authorities;
•the costs and timing of future commercialization activities, including product manufacturing, marketing, sales and distribution, for any of our product candidates for which we receive marketing approval;
•the cost of expanding, maintaining, and enforcing our intellectual property portfolio, including filing, prosecuting, defending, and enforcing our patent claims and other intellectual property rights;
•the cost of defending potential intellectual property disputes, including patent infringement actions brought by third parties against us or any of our product candidates;
•the effect of competing technological and market developments;
•the cost and timing of completion of commercial-scale manufacturing activities;
•the extent to which we partner our programs, acquire or in-license other product candidates and technologies or enter into additional collaborations;
•the revenue, if any, received from commercial sales of any future product candidates for which we receive marketing approval; and
•the costs of operating as a public company.
Until we can generate product revenues to support our cost structure, if any, we expect to finance our cash needs through a combination of equity offerings, debt financings, collaborations, and other similar arrangements. To the extent that we raise additional capital through the sale of equity or convertible securities, the ownership interest of our stockholders will be or could be diluted, and the terms of these securities may include liquidation, dividend, redemption, and other preferences that adversely affect the rights of our common stockholders. Debt financing and equity financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures, or declaring dividends. If we raise funds through collaborations, or other similar arrangements with third parties, we
may have to relinquish valuable rights to our technologies, future revenue streams, research programs or product candidates or grant licenses on terms that may not be favorable to us and/or may reduce the value of our Common Stock. If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market our product candidates even if we would otherwise prefer to develop and market such product candidates ourselves.
Cash Flows
The following table summarizes our cash flows for each of the periods presented:
YEARS ENDED
DECEMBER 31,
INCREASE /
(DECREASE)
($ in thousands)
Net cash (used in) operating activities
$
(136,731
)
$
(91,832
)
$
(44,899
)
Net cash (used in) investing activities
(26,510
)
(15,039
)
(11,471
)
Net cash provided by financing activities
200,851
43,531
157,320
Net increase (decrease) in cash, cash equivalents
and restricted cash
$
37,610
$
(63,340
)
$
100,950
Operating Activities
Cash flows from operating activities represent the cash receipts and disbursements related to all our activities other than investing and financing activities. Operating cash flow is derived by adjusting our net loss for non-cash operating items such as depreciation, amortization, and stock-based compensation as well as changes in operating assets and liabilities, which reflect timing differences between the receipt and payment of cash associated with transactions and when they are recognized in our results of operations.
During 2022, net cash used in operating activities was $136.7 million of cash, primarily resulting from our net loss of $167.1 million, adjusted for non-cash items and the effect of changes in operating assets and liabilities. Non-cash adjustments primarily include stock-based compensation expense of $8.8 million, depreciation and amortization expense of $8.1 million, and non-cash lease expense of $5.6 million; offset by a change in the fair value of our warrant liabilities of $1.2 million. Net cash used by changes in our operating assets and liabilities consisted primarily of a $6.6 million decrease in accounts payable, an increase of $12.9 million in accrued expenses, lease liabilities and other liabilities, a $1.5 million increase in prepaid expenses, other current assets and other non-current assets, partially offset by an increase in deferred revenue of $3.6 million. The decrease in accounts payable is related to timing of vendor invoicing and payments. The increase in accrued expenses, lease liabilities and other liabilities and prepaid expenses and other assets was due to our increased level of research collaborations and manufacturing development activities related to our product candidates. The increase in deferred revenue was due to our license agreement we entered into with SIIPL in 2022.
During 2021, net cash used in operating activities was $91.8 million. Net cash used in operating activities consists of net loss of $112.3 million, adjusted for non-cash items and the effect of changes in operating assets and liabilities. Non-cash adjustments primarily include depreciation and amortization expense of $5.8 million, stock-based compensation of $2.0 million, change in fair value of warrant liabilities of $1.4 million, and non-cash interest expense of $0.8 million. Net cash provided by changes in our operating assets and liabilities for the year ended December 31, 2021, consisted of a $11.9 million increase in accounts payable and other current liabilities, partially offset by a $0.9 million increase in prepaid expenses, other current assets and other non-current assets. The increase in accounts payable and other liabilities related to the timing of vendor invoicing and payments. The increase in prepaid expenses, other current assets and other non-current assets was primarily due to our increased level of research collaborations and manufacturing development activities related to our product candidates.
Investing Activities
During 2022, investing activities used $26.5 million of cash, consisting primarily of purchases of property and equipment, of which a substantial majority related to laboratory and facilities improvements in Durham, North Carolina and Lexington, Massachusetts as well as purchases of laboratory equipment and facilities improvements for our manufacturing facility in Rochester, New York.
During 2021, investing activities used $15.0 million of cash consisting of purchases of property and equipment, of which a substantial majority related to purchases of laboratory equipment and facilities improvements for our manufacturing plant in
Rochester, New York, construction of cleanrooms and preclinical manufacturing capacity in our facility in Burlington, Massachusetts, and laboratory construction in our facility in Woburn, Massachusetts.
Financing Activities
During 2022, financing activities provided $200.9 million of cash, consisting primarily of $106.0 million of net proceeds raised in the August 2022 PIPE financing, $78.5 million of net proceeds from the Business Combination, net of transaction costs, $21.8 million in proceeds from issuance of convertible debt from PIPE Investors, and $1.2 million of proceeds from the exercise of public warrants, which were partially offset by $7.2 million of repayments on our debt and finance lease obligations.
During 2021, financing activities provided $43.5 million of cash, consisting primarily of $24.9 million of net proceeds from secured term loans, $13.5 million of net proceeds from convertible debt issuances, and net proceeds of $10.4 million from a new secured debt agreement, partially offset by $2.9 million of deferred offering costs, $1.8 million of repayments on our secured debt, and $0.6 million of payments related to our capital lease obligations.
Contractual Obligations and Commitments
Operating Lease Obligations
We have non-cancelable operating lease obligations, consisting primarily of lease payment obligations for our facilities, including our headquarters in Lexington, Massachusetts, comprised of office and laboratory space; office, laboratory and greenhouse space in Durham, North Carolina; laboratory and office space in Medford and Woburn, Massachusetts; our manufacturing facilities in Rochester, New York; and farm land located in Spain. The leases for these facilities expire on various dates through 2042, unless extended.
In March 2022, the Company entered into a lease for new office, laboratory and clean room space in Lexington, Massachusetts, which commenced in May 2022. The lease term expires in July 2033. The base rent for this lease is approximately $3.9 million per year, subject to a 3% increase each year.
In March 2022, the Company entered into a lease for land in Spain. The lease term expires in March 2042. The base rent for this lease is approximately $0.1 million per year.
In June 2022, we terminated our lease for manufacturing clean rooms in Burlington, Massachusetts.
In December 2022, the Company entered into a lease for farm land located in Colusa County, California, which commences in January 2023. The lease term expires in December 2032. The base rent for this lease is approximately $0.1 million per year, subject to annual increases based on the consumer price index beginning on January 1, 2024.
See Note 16, Leases, of the notes to our consolidated financial statements for the years ended December 31, 2022 and 2021, for further information on our operating lease obligations.
Purchase Obligations
In the normal course of business, we enter into contracts with third parties for field trials, preclinical studies and research and development supplies. These contracts generally do not contain minimum purchase commitments and provide for termination on notice, and therefore are cancellable contracts.
License Agreement Obligations
In December 2020, we entered into an assignment and license agreement with Bayer CropScience LLP (“Bayer”) under which we may be obligated to make milestone and royalty payments. These payment obligations are contingent upon future events, such as achieving certain development, regulatory, and commercial milestones or generating product sales. The timing of these events is uncertain; accordingly, we cannot predict the period during which these payments may become due. We have agreed to pay up to $2.0 million in milestone payments under this assignment and license agreement when certain development milestones are met. The Company assessed the milestones for the year ended December 31, 2022 and concluded no such milestone payments were deemed probable nor due.
In August 2020, we entered into a license agreement with Acuitas Therapeutics, Inc. (“Acuitas”) under which we are obligated to make potential milestone payments, royalty payments, or both. These payment obligations are contingent upon future
events, such as achieving certain clinical and regulatory milestones and generating product sales. Such payments are dependent upon the development of products using the intellectual property licensed under the agreements and are contingent upon the occurrence of future events. The potential clinical and regulatory milestone payments that Acuitas is entitled to receive is in the low double-digit millions for the first option exercised. With respect to the sale of each licensed products, the Company is also obligated to pay Acuitas royalties in the low single digit percentages on net sales of the licensed products by the Company and its affiliates and sublicensees in a given country until the last to occur, in such country, of (i) the expiration or abandonment of all licensed patent rights covering the licensed product, (ii) expiration of any regulatory exclusivity for the licensed product, or (iii) ten years from the first commercial sale of the licensed product. For the year ended December 31, 2022, none of these events were deemed probable and hence no expenses were recorded.
Debt Obligations
See Note 10, Debt, of the notes to our consolidated financial statements included elsewhere in this filing for further information on our future debt repayment obligations.
Manufacturing Commitments and Obligations
In November 2021, we engaged Samsung Biologics Co., Ltd. (“Samsung”) as a contract development and manufacturing organization for scale up and commercial scale production of our mRNA COVID-19 vaccine pursuant to a Master Services Agreement and a Product Specific Agreement with Samsung (collectively, the “Samsung Agreements”). Pursuant to the Samsung Agreements, we must, among other things, (a) pay Samsung service fees for its pharmaceutical development and manufacturing services, (b) purchase certain minimum quantities of drug products, and (c) pay Samsung, on a minimum take-or-pay basis for each year under the agreement, for our minimum purchase commitments, as determined under the terms of the Samsung Agreements. Based on our minimum purchase commitments, we expect to pay Samsung a minimum of approximately $8.8 million in service fees under the Samsung Agreements, excluding the cost of raw materials. For the year ended December 31, 2022, the Company has incurred approximately $5.9 million in costs under this service agreement. Based on our current schedule, we expect to incur the remainder of the costs throughout 2023.
Critical Accounting Policies and Significant Judgments and Estimates
Our consolidated financial statements have been prepared in accordance with generally accepted accounting principles in the United States. The preparation of these consolidated financial statements requires us to make judgments and estimates that affect the reported amounts of assets, liabilities, revenues and expenses, and the disclosure of contingent assets and liabilities in our financial statements. We base our estimates on historical experience, known trends and events and various other factors that we believe are reasonable under the circumstances, the results of which form the basis for making judgments about the carrying values of assets and liabilities that are not readily apparent from other sources. Our actual results may differ from these estimates under different assumptions or conditions. On a recurring basis, we evaluate our judgments and estimates in light of changes in circumstances, facts, and experience. The effects of material revisions in an estimate, if any, will be reflected in the consolidated financial statements prospectively from the date of the change in the estimate.
We believe that the following accounting policies are those most critical to the judgments and estimates used in the preparation of our financial statements.
Revenue Recognition
License and Collaboration Revenue
In March 2022, we entered into a License Agreement (the “Agreement”) with Serum Institute of India Private Limited (“SIIPL”), pursuant to which we granted SIIPL an exclusive, sub-licensable, royalty-bearing license to use our proprietary technology platform to develop, manufacture and commercialize up to three mRNA products in all territories other than the United States, the 27 member states of the European Union, the United Kingdom, Australia, Japan, New Zealand, Canada, South Korea, China, Hong Kong, Macau, and Taiwan (the “SIIPL Territory”). The first licensed product target will be a shingles product target, and SIIPL has an option to select the additional two licensed product targets through the end of 2024. Under the terms of the Agreement with SIIPL, we will provide research services related to the shingles product target to develop a “proof of concept” and will provide manufacturing technology transfer services. In addition, we retain the option to purchase research and clinical trial data, developed by SIIPL, for 50% of the cost of the research studies and clinical trials for use in our own development.
SIIPL is responsible for the development, formulation, filling and finishing, registration and commercialization of the products in the SIIPL Territory, subject to oversight from a joint steering committee composed of representatives of us and SIIPL. SIIPL will use commercially reasonable efforts to develop and obtain regulatory approval for the products in the countries in the SIIPL Territory. The License Agreement includes terms customary in the industry for provisions related to sublicensing, intellectual property, and termination, and customary representations and warranties of GreenLight and SIIPL, along with certain customary covenants, including confidentiality, limitation of liability and indemnity provisions.
Pursuant to the License Agreement, SIIPL will pay us an upfront license fee of $5.0 million, as well as payments upon additional target selection and reservation of exclusivity. We may receive up to a total of an additional $17.0 million in development, regulatory and commercial (net sales) based milestone payments across all three product targets, as well as manufacturing technology transfer payments up to $10.0 million. SIIPL shall pay royalty payments in the mid-double digits, based on the net sales of products resulting from the licensed technology for the term of the License Agreement. The License Agreement shall terminate on a product-by-product and country-by-country basis on the later of the expiration of the patent rights owned by us or the tenth anniversary of the first commercial sale of the applicable product(s) in the applicable country.
We have determined that the Agreement falls within the scope of ASC 606, Revenue Recognition, ("ASC 606") as it includes a customer-vendor relationship as defined by ASC 606 and thus represents a contract with a customer. We have determined that the license of IP granted is not distinct from the research services, which includes manufacturing technology transfer services, and thus should be combined. The Agreement contains a single performance obligation for the combined License of IP and research services. Revenue from the contract will be recognized over time, using an input-method based on labor costs as a percentage of total expected labor costs. We use key assumptions in recognizing revenue, which include estimated development timelines, actual internal and external costs incurred, estimated costs to be incurred, and probabilities of technical success.
Research and Development Expense
We have committed significant resources into the research and development of our product candidates and intend to continue to do so for the foreseeable future. Research and development expenses are generally expensed as incurred.
Research and development expenses are comprised of costs incurred in performing research and development activities, including salary, benefits, share-based compensation, and other employee-related expenses; laboratory supplies and other direct expenses; facilities expenses; third-party contractual costs relating to nonclinical studies and clinical trial activities and related contract manufacturing expenses, development of manufacturing processes and other outside expenses.
Clinical trial expenses include expenses associated with contract research organizations, or CROs. The invoicing from CROs for services rendered can lag several months. We accrue the cost of services rendered in connection with CRO activities based on our estimate of site management, monitoring costs, project management costs, and investigator fees. We maintain regular communication with our CRO vendors to gauge the reasonableness of our estimates. We make estimates of our clinical trial accrued expenses as of each balance sheet date in our financial statements based on facts and circumstances known to us. If timelines or contracts are modified based upon changes in the clinical trial protocol or scope of work to be performed, we assess our estimates of accrued expenses accordingly. Differences between actual clinical trial expenses and estimated clinical trial expenses recorded have not been material and are adjusted for in the period in which they become known. However, if we incorrectly estimate activity levels associated with the CRO services at a given point in time, we could be required to record material adjustments in future periods.
Stock-Based Compensation
We measure stock-based awards granted to employees, non-employees and directors based on their fair value on the date of the grant using the Black-Scholes option-pricing model for options and the fair value of our Common Stock for restricted common stock awards. Compensation expense for those awards is recognized over the requisite service period, which is generally the vesting period of the respective award for employees and directors and the period during which services are performed for non-employees. We use the straight-line method to record the expense of awards with service-based vesting conditions. We recognize stock-based compensation for performance awards based on grant date fair value over the service period to the extent achievement of the performance condition is probable.
The fair value of our stock option awards is estimated using a Black-Scholes option-pricing model that uses the following inputs: (1) fair value of our Common Stock, (2) assumptions we make for the expected volatility of our common stock, (3) the expected term of our stock option awards, (4) the risk-free interest rate for a period that approximates the expected term of our stock option awards, and (5) our expected dividend yield, if any. The computation of expected volatility is based on an average historical share price volatility based on an analysis of reported data for a peer group of comparable publicly traded companies,
which were selected based upon industry similarities. However, these estimates are neither predictive nor indicative of the future performance of the our stock. Due to our limited operating history and a lack of company specific historical and implied volatility data, we have based our estimate of expected volatility on the historical volatility of stock of companies within our defined peer group. The interest rate for periods within the expected term of the award is based on the U.S. Treasury risk-free interest rate in effect at the time of grant.
Off-Balance Sheet Arrangements
We did not have during the periods presented, and we do not currently have any off-balance sheet arrangements, as defined in the rules and regulations of the SEC.
Recently Adopted Accounting Pronouncements
A description of recently issued accounting pronouncements that may potentially impact our financial position, results of operations or cash flows is provided in Note 2 - Summary of Significant Accounting Policies to our consolidated financial statements appearing elsewhere herein.
We adopted ASC 842 during the quarter ended December 31, 2022, with an effective date of January 1, 2022, using the modified retrospective approach and utilizing the effective date as its date of initial application. As a result, prior period financial statements continue to be presented in accordance with ASC 840. The Company used the optional transition method to the modified retrospective approach in which Topic 842 will not be applied to comparative periods presented and incremental disclosures are not required for periods before the Company’s adoption of Topic 842. As a result of implementing this guidance, the Company recorded a right-of-use asset of $15.2 million and an operating lease liability of $15.9 million, respectively, as of January 1, 2022 and also derecognized total deferred rent liabilities and unamortized lease incentives of $0.7 million that existed as of December 31, 2021 on the Company's Balance Sheets.
Emerging Growth Company and Smaller Reporting Company Status
The Company is an “emerging growth company,” as defined in Section 2(a) of the Securities Act, as modified by the Jumpstart Our Business Startups Act of 2012 (the “JOBS Act”), and it may take advantage of certain exemptions from various reporting requirements that are applicable to other public companies that are not emerging growth companies, including, but not limited to, not being required to comply with the auditor attestation requirements of Section 404 of the Sarbanes Oxley Act, reduced disclosure obligations regarding executive compensation in its periodic reports and proxy statements, and exemptions from the requirements of holding nonbinding stockholder advisory votes on executive compensation and any golden parachute payments not previously approved.
Further, Section 102(b)(1) of the JOBS Act exempts emerging growth companies from being required to comply with new or revised financial accounting standards until private companies (that is, those that have not had a Securities Act registration statement declared effective, have not filed and not withdrawn a Securities Act registration statement that has not become effective or do not have a class of securities registered under the Exchange Act) are required to comply with the new or revised financial accounting standards. The JOBS Act provides that a company can elect to opt out of the extended transition period and comply with the requirements that apply to non-emerging growth companies but any such election to opt out is irrevocable. The Company has elected not to opt out of such extended transition period, which means that when a standard is issued or revised and it has different application dates for public or private companies, The Company, as an emerging growth company, can adopt the new or revised standard at the time private companies adopt the new or revised standard. This may make comparison of the Company's financial statements with certain other public companies difficult or impossible because of the potential differences in accounting standards used.
The Company will remain an emerging growth company until the earlier of: (i) the last day of the fiscal year (a) following the fifth anniversary of the closing of ENVI’s initial public offering, (b) in which the Company has total annual gross revenue of at least $1.235 billion, or (c) in which the Company is deemed to be a large accelerated filer, which means the market value of its common equity that is held by non-affiliates exceeds $700 million as of the last business day of its most recently completed second fiscal quarter; and (ii) the date on which the Company has issued more than $1.0 billion in non-convertible debt securities during the prior three-year period. References herein to “emerging growth company” have the meaning associated with it in the JOBS Act.
We are also a “smaller reporting company” as defined in the Exchange Act. We may continue to be a smaller reporting company even after we are no longer an emerging growth company. We may take advantage of certain of the scaled disclosures available to smaller reporting companies and will be able to take advantage of these scaled disclosures for so long as the market
value of our voting and non-voting Common Stock held by non-affiliates is less than $250.0 million measured on the last business day of our second fiscal quarter, or our annual revenue is less than $100.0 million during the most recently completed fiscal year and the market value of our voting and non-voting Common Stock held by non-affiliates is less than $700.0 million measured on the last business day of our second fiscal quarter.

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ITEM 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK
Item 7A. Quantitative and Qualitative Disclosures About Market Risk.
We are exposed to certain market risks in the ordinary course of our business. Market risk represents the risk of loss that may impact our financial position due to adverse changes in financial market prices and rates.
Interest Rate Risk
As of December 31, 2022 and 2021, we had cash and cash equivalents which consisted of cash and money market funds. Interest income is sensitive to changes in the general level of interest rates; however, due to the nature of these investments, an immediate 10% change in interest rates would not have a material effect on the fair market value of our investment portfolio.
We have exposure to interest rate risk from our variable rate debt. We do not hedge our exposure to changes in interest rates. As of December 31, 2022, we had $22.0 million in variable rate debt outstanding. A 10% change in interest rates would have an immaterial impact on annualized interest expense.
Foreign Currency Exchange Risk
Our reporting and functional currency is the U.S. dollar. We currently do not have significant exposure to foreign currencies as we hold no foreign exchange contracts, option contracts, or other foreign hedging arrangements. Our operations may be subject to fluctuations in foreign currency exchange rates in the future.
Effects of Inflation
Inflation generally affects us by increasing our cost of labor and research and development contract costs. We do not believe that inflation currently has had a material effect on our business, financial condition or results of operations. Our operations may be affected by inflation in the future.

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ITEM 8. FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA
Item 8. Financial Statements and Supplementary Data.
Our consolidated financial statements, together with the independent registered public accounting firm report thereon, appear beginning on page of this Annual Report on Form 10-K.

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ITEM 9. CHANGES IN AND DISAGREEMENTS WITH ACCOUNTANTS
Item 9. Changes in and Disagreements With Accountants on Accounting and Financial Disclosure.
Not Applicable.

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ITEM 9A. CONTROLS AND PROCEDURES
Item 9A. Controls and Procedures.
Evaluation of Disclosure Controls and Procedures
Our management, with the participation of the Chief Executive Officer ("CEO") and Chief Financial Officer ("CFO"), evaluated the effectiveness of our disclosure controls and procedures as of December 31, 2022. We maintain disclosure controls and procedures, as defined in Rules 13a-15(e) and 15d-15(e) under the Securities Exchange Act of 1934, as amended, or the Exchange Act, which are designed to ensure that information required to be disclosed in the reports that we file or submit under the Exchange Act is recorded, processed, summarized and reported within the time periods specified in the Securities and Exchange Commission’s rules and forms and that such information is accumulated and communicated to our management, including our CEO and CFO, as appropriate to allow timely decisions regarding required disclosure.
Due to the material weaknesses identified as of December 31, 2021, two of which remain unremediated as of December 31, 2022, which are disclosed in Management's Annual Report on Internal Control Over Financial Reporting, the CEO and the CFO concluded that the disclosure controls were not effective, to provide reasonable assurance that information required to be disclosed by the Company in the reports that it files or submits under the Exchange Act is accumulated and communicated to management, including the CEO and CFO, as appropriate, to allow timely decisions regarding required disclosure and were not effective to provide reasonable assurance that such information is recorded, processed, summarized and reported within the time periods specified by the SEC’s rules and forms.
Management’s Annual Report on Internal Control Over Financial Reporting
Management of the Company is responsible for establishing and maintaining adequate internal control over financial reporting. Internal control over financial reporting as defined in Rules 13a-15(e) and 15d-15(e) of the Exchange Act as a process
designed by, or under the supervision of, the Company's Chief Executive Officer and Chief Financial Officer and effected by the Company's Board of Directors, management and other personnel to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles, and includes those policies and procedures that:
•pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect the transactions and dispositions of the assets of the Company;
•provide reasonable assurance that transactions are recorded as necessary to permit preparation of financial statements in accordance with GAAP, and that receipts and expenditures of the Company are being made only in accordance with authorizations of management and directors of the Company; and
•provide reasonable assurance regarding prevention or timely detection of unauthorized acquisition, use or disposition of the Company's assets that could have a material effect on the financial statements.
Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Also, projections of any evaluation of effectiveness to future periods are subject to the risks that controls may become inadequate because of changes in conditions or that the degree of compliance with the policies or procedures may deteriorate.
Management of the Company has assessed the effectiveness of the Company's internal control over financial reporting as of December 31, 2022. In making its assessment of internal control over financial reporting, management used the criteria described in Internal Control-Integrated Framework (2013 framework) issued by the Committee of Sponsoring Organizations of the Treadway Commission, (“COSO”). Based on our assessments and those criteria, management determined that we did not maintain effective internal control over financial reporting as of December 31, 2022, due to unremediated material weakness in our internal control over financial reporting which are as follows:
•The failure to maintain a sufficient complement of personnel in its accounting and reporting department to ensure adequate segregation of duties such that appropriate review and monitoring of its financial records are executed.
•The failure to design and implement adequate information systems controls including access and change management controls.
This Annual Report on Form 10-K does not include an attestation report of our independent registered public accounting firm due to our status as an emerging growth company under the JOBS Act.
Changes in Internal Control over Financial Reporting
Other than the remediated material weakness related to the failure of the Company to maintain a sufficient complement of accounting and financial reporting resources commensurate with the Company’s financial reporting requirements, there was no change in our internal controls over financial reporting during the quarter ended December 31, 2022, identified in connection with the evaluation required by Rules 13a-15(d) and 15d-15(d) of the Exchange Act that has materially affected, or is reasonably likely to materially affect, our internal control over financial reporting.
Remediation Plan
We are committed and are taking steps necessary to remediate the control deficiencies that constituted the above material weaknesses by implementing changes to our internal control over financial reporting. During the year ended December 31, 2022, we made the following enhancements to our control environment including the following:
•We implemented a new ERP system with defined user roles to ensure proper segregation of duties within our accounting systems which will provide a stronger internal control infrastructure for financial reporting and for our internal control procedures;
•We engaged internal control consultants to assist us in performing a financial reporting risk assessment as well as identifying and designing our system of internal controls necessary to mitigate the risks identified;
Our remediation activities are continuing in 2023. In addition to the above activities, we expect to engage in additional activities including:
•Identify and document the remaining controls needed to mitigate the risks identified in our comprehensive risk assessment of our financial reporting processes; and
•Perform routine testing of the operating effectiveness of the identified controls over financial reporting including general IT controls.
Limitations on Effectiveness of Controls and Procedures
In designing and evaluating our disclosure controls and procedures, management recognizes that any controls and procedures, no matter how well designed and operated, can provide only reasonable assurance of achieving the desired control objectives. In addition, the design of disclosure controls and procedures must reflect the fact that there are resource constraints and that management is required to apply judgment in evaluating the benefits of possible controls and procedures relative to their costs.

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ITEM 9B. OTHER INFORMATION
Item 9B. Other Information.
On March 23, 2023, the Company received a deficiency letter from the Listing Qualifications Department (the “Staff”) of the Nasdaq Stock Market (“Nasdaq”) notifying the Company that, for the last 30 consecutive business days, the bid price for the Company’s Common Stock had closed below the $1.00 per share minimum bid price requirement for continued inclusion on the Nasdaq Global Market pursuant to Nasdaq Listing Rule 5450(a)(1) (the “Bid Price Requirement”).
In accordance with Nasdaq Listing Rule 5810(c)(3)(A) (the “Compliance Period Rule”), the Company has been provided a period of 180 calendar days, or until September 18, 2023 (the “Compliance Date”), to regain compliance with the Bid Price Requirement. If, at any time before the Compliance Date, the bid price for the Common Stock closes at $1.00 or more for a minimum of 10 consecutive business days as required under the Compliance Period Rule (unless the Staff exercises its discretion to extend this ten-day period pursuant to Nasdaq Listing Rule 5810(c)(3)(H)), the Staff will provide written notification to the Company that it has regained compliance with the Bid Price Requirement.
If the Company does not regain compliance with the Bid Price Requirement by the Compliance Date, the Company may be eligible for an additional 180 calendar day compliance period. To qualify, the Company would need to transfer the listing of the Common Stock to the Nasdaq Capital Market, provided that it meets the continued listing requirement for the market value of publicly held shares and all other initial listing standards, with the exception of the Bid Price Requirement. To effect such a transfer, the Company would also need to pay an application fee to Nasdaq and will need to provide written notice to the Staff of its intention to cure the deficiency during the additional compliance period by effecting a reverse stock split, if necessary. As part of its review process, the Staff will make a determination of whether it believes the Company will be able to cure this deficiency.
Should the Staff conclude that the Company will not be able to cure the deficiency, or should the Company determine not to submit an application for transfer to the Nasdaq Capital Market or notify the Staff of its intention to cure the deficiency, the Staff will provide written notification to the Company that the Common Stock will be subject to delisting. At that time, the Company may appeal the Staff’s delisting determination to a Nasdaq Listing Qualifications Panel (the “Panel”). However, there can be no assurance that, if the Company receives a delisting notice and appeals the delisting determination by the Staff to the Panel, such appeal would be successful.
The Company intends to monitor the closing bid price of the Common Stock and may, if appropriate, consider available options to regain compliance with the Bid Price Requirement, which could include seeking to effect a reverse stock split. However, there can be no assurance that the Company will be able to regain compliance with the Bid Price Requirement.

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ITEM 10. DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE
Item 10. Directors, Executive Officers and Corporate Governance.
The following sets forth certain information, as of the date of this report, concerning the directors and officers.
Name
Age
Position
Executive Officers
Andrey J. Zarur, Ph.D.
Chief Executive Officer, President and Class III Director
Carole Cobb, M.B.A.
Chief Operating Officer
Susan Keefe, M.B.A.
Chief Financial Officer
Nina Thayer *
General Counsel
Non-Employee Directors
Charles Cooney, Ph.D.
Class III Director
Ganesh Kishore, Ph.D.
Class III Director
Eric O'Brien
Class I Director
Jennifer E. Pardi
Class I Director
Martha Schlicher, Ph.D.
Class II Director
Matthew Walker
Class II Director
* David Kennedy, former General Counsel, retired from the Company as of March 2023. Mr. Kennedy will continued to be engaged by the Company as an advisor.
Executive Officers
Andrey Zarur, Ph.D. Dr. Zarur, a co-founder of GreenLight, has served as the Chief Executive Officer and President and as a member of the Board of each of New GreenLight and GreenLight since February 2022 and August 2008, respectively. Dr. Zarur is also the co-founder of Lumicell Inc., an oncology company delivering advanced imaging solutions for cancer surgery, and has served as its Chairman of the Board since January 2010. Dr. Zarur co-founded and served as the Chairman of the Board of Solid Biosciences, Inc. (NASDAQ: SLDB), a gene therapy company targeting Duchenne muscular dystrophy, from February 2014 to June 2020, and served as the Managing General Partner of Kodiak Venture Partners, a venture capital firm that is a major shareholder of GreenLight, from February 2006 to February 2014. Dr. Zarur previously served as a senior executive in various companies in the healthcare and clean energy sectors, including as Chief Executive Officer of BioProcessors Corporation, a microscale bioreactor platform developer, from January 2002 to December 2006 and Chief Operating Officer of Starlab NV/SA, a research incubator, from January 1999 to January 2002. Dr. Zarur earned his Doctor of Philosophy degree from the Chemical Engineering Department at the Massachusetts of Technology and a post-graduate certificate in Immunology from Harvard Medical School. Dr. Zarur also holds a Master’s of Science in Engineering Practice from the Chemical Engineering Department at the Massachusetts Institute of Technology and an undergraduate degree from the Universidad Nacional Autónoma de México. We believe Dr. Zarur’s background and track record of leading biopharmaceutical businesses across the discovery, preclinical, and clinical development, commercialization and product life-cycle management states makes him well qualified to serve on the Board.
Carole Cobb, M.B.A. Ms. Cobb has served as the Chief Operating Officer of New GreenLight since February 2022 and as GreenLight's Chief Operating Officer since 2016. In that role, Ms. Cobb is responsible for process development and manufacturing for products developed through GreenLight’s science and innovation. Ms. Cobb’s career has ranged from development and research engineering to managing global manufacturing operations and she was the first female manufacturing Plant Manager at Genencor International, Inc., a research and development company. She was promoted to Vice President of Worldwide Manufacturing in 1997 and from 1999 to 2008, Ms. Cobb was a Senior Vice President of Global Supply at Genencor and continued in that position following its acquisition by Danisco A/S in 2005. In this role, she was responsible for driving strategy, tactics and implementation for Genencor’s global supply chain. Ms. Cobb earned her Master’s in Business Administration from the Finance Department at the University of Rochester and earned two undergraduate degrees, one from the Department of Chemical Engineering and the other from the Department of Biochemistry, and Cell and Molecular Biology both at the State University of New York at Buffalo.
Susan Keefe, M.B.A. Ms. Keefe has served as the Chief Financial Officer and interim Chief Accounting Officer of New GreenLight since February 2022 and as GreenLight’s Chief Financial Officer since May 2019. In these roles, Ms. Keefe has been responsible for overseeing all aspects of our finance and accounting operations. She brings 25 years of experience in financial positions across the biotech, consumer packaged goods, and consulting industries. Most recently, Ms. Keefe served as a financial consultant to a range of life science companies with Danforth Advisors, a financial services consulting company focused on life
sciences, from October 2018 to May 2019. From July 2013 to April 2018, Ms. Keefe served as Vice President of Finance and Corporate Treasurer at Aushon Biosystems Inc., a developer of microarray technologies for life science companies, where she was responsible for finance, accounting and human resources. She has also served in various roles at SeraCare Life Sciences Inc., most recently as the Director, Corporate Development and Business Analytics (2007 to 2013), The Procter & Gamble Company, most recently as Finance Manager (2003 to 2007), as Finance Manager at Lante Corporation (2000 to 2001) and PricewaterhouseCoopers LLP, most recently as Manager, Transaction Services (1996 to 2000). Ms. Keefe earned her B.A. in Business Administration from the University of Iowa and an M.B.A. from the University of Chicago, Booth Graduate School of Business.
Nina Thayer. Nina Thayer has served as General Counsel, Chief Compliance Officer and Corporate Secretary to New GreenLight since March 2023. She also served as Deputy General Counsel to New GreenLight from January 2023 to March 2023. In these roles, Ms. Thayer is responsible for the Company's legal and compliance functions. Prior to joining New GreenLight, Ms. Thayer served as Vice President, Legal Affairs at Gemini Therapeutics, Inc. (formerly NASDAQ: GMTX), a biotechnology company, from May 2021 through December 2022, and in various roles, most recently of which as Vice President and General Counsel, at Allied Minds plc (LSE: ALM), a publicly traded venture firm focused on early stage company investment and development within the technology and life science sectors, from September 2015 to May 2021. At Gemini Therapeutics and Allied Minds, Nina advised on corporate and securities laws matters, governance, and financing, commercial, and licensing transactions. Prior to Allied Minds, Nina was a corporate associate with Goodwin Procter LLP where she represented private equity and venture capital firms as well as a wide range of public and private companies. Ms. Thayer earned her B.S. in Business Administration from Boston University and her J.D. from Boston University School of Law.
David Kennedy. David Kennedy has served as the General Counsel and Corporate Secretary to each of New GreenLight and GreenLight since February 2022 and June 2020, respectively, until March 2023. He has also served as Principal of Kennedy, LLP, a law firm, since January 2017. Mr. Kennedy has served in various leading roles at public and private companies, including as General Counsel and Corporate Secretary in Residence at Criteo S.A. (NASDAQ: CRTO), a commerce marketing technology company, from February 2018 to September 2018, Executive Vice President, General Counsel and Chief Compliance Officer for Infosys Limited (NYSE: INFY), an information technology company, from October 2014 to January 2017, Chief Legal Officer for JDA Software, Inc. (now Blue Yonder Group, Inc.), a digital fulfillment platform company, from April 2012 to January 2014, General Counsel and Corporate Secretary for Better Place, an electric battery company, from April 2009 to October 2011, General Counsel and Corporate Secretary for SAP Business Objects, an enterprise software company, from April 2007 to April 2009 and Associate General Counsel for International Business Machines Corporation (NYSE: IBM) from 1989 to 2007. Mr. Kennedy earned his J.D. with honors from the University of Connecticut School of Law and his B.S. from the University of Connecticut in Business Administration, where he graduated Magna Cum Laude.
Non-Employee Directors
Charles L. Cooney, Ph.D. Dr. Cooney has served as a member and chairperson of the Board and as a member of its audit committee since February 2022. Dr. Cooney served as a member of the GreenLight Board from December 2010 until the closing of the Business Combination in February 2022, including as its chairperson after February 2018. Dr. Cooney joined the MIT faculty in 1970 and has been the Robert T. Haslam Professor of Chemical and Biochemical Engineering in the Department of Chemical Engineering at MIT since 2007. In 2015 he became Professor, Emeritus. Dr. Cooney was the founding Faculty Director of the Deshpande Center for Technological Innovation at MIT, from 2002 to 2014. Dr. Cooney also serves as a member of the board of directors of various public and private biotechnology companies, including Elektrofi, a biotechnology company focused on the delivery of biologics to treat diseases, since March 2018; Codiak Biosciences, Inc. (NASDAQ: CDAK), a biotechnology company focused on the development of exosome-based therapeutics, since July 2017, where he also serves as a member of the audit committee and environmental, social, governance and impact committee; LayerBio, Inc., a biotechnology company focused on sustained-release technology for use with intraocular lenses, since November 2016; Levitronix LLC, a developer of magnetically levitated bearing less motor technology, since January 2016; Innovent Biologics, Inc. (OTCMKTS: IVBXF), a developer of monoclonal antibody drug candidates, since December 2015; and Boyd Technologies, Inc., a developer of membrane products since September 2013. Previously, Dr. Cooney served as a board member at Axcella Health,Inc. (formerly Pronutria Biosciences, Inc.) (NASDAQ: AXLA), a biopharmaceutical company focused on treating diseases and supporting health using endogenous metabolic modulators, from February 2011 to June 2018. Dr. Cooney earned a B.S. in Chemical Engineering from the University of Pennsylvania and an M.S. and Ph.D. in Biochemical Engineering from MIT. We believe that Dr. Cooney’s extensive experience as a researcher and an educator in the biotechnology field and his experience as a director of both public and private biotechnology companies qualify him to serve as a member of the Board.
Ganesh Kishore, Ph.D. Dr. Kishore has served as a member of the Board and as the chairperson of its compensation committee and a member of its environmental, social, governance and impact committee since February 2022. Dr. Kishore,
served on the GreenLight Board from 2015 until the closing of the Business Combination in February 2022. Dr. Kishore has also served as a Managing Partner at Spruce Capital Partners LLC, a venture capital management firm, since February 2013 and as a Co-Manager of MLSCF II (GP) (Labuan), LLP, the General Partner of MLS Capital Fund II. Previously he served as the Chief Executive Officer of Malaysian Life Sciences Capital Fund Ltd., a life sciences venture fund, between April 2007 and June 2015. Additionally, from April 2007 to December 2008, Dr. Kishore served as the Managing Director of Burrill & Company, a life sciences private equity and venture capital firm, in its Venture Group and from 1980 to 2000, Dr. Kishore served as President, Nutrition & Consumer Division, Distinguished Science Fellow and Chief Biotechnologist of Monsanto Company. Dr. Kishore also served as the Chief Technology Officer for Agriculture & Nutrition Platform and Chief Biotechnology Officer of DuPont between 2002 and 2007. Dr. Kishore earned his Ph.D. in Biochemistry from the Indian Institute of Science and received postdoctoral training and was a Robert A. Welch Fellow in Microbiology and Chemistry at the University of Texas at Austin. We believe that Dr. Kishore’s knowledge of the biotechnology sector and his finance experience make him well suited to serve on the Board.
Eric O’Brien, M.B.A. Mr. O’Brien has served as a member of the Board and as a member of its compensation committee since February 2022. Mr. O’Brien served as a member of the GreenLight Board from June 2019 until the closing of the Business Combination in February 2022. Mr. O’Brien is also a co-founder and has served as Managing Director of Fall Line Capital, a private equity firm focused on investments in farmland and agricultural technologies, since June 2011. Mr. O’Brien has served on the boards of directors of many public and private companies, including PCH International Company, a custom design manufacturing company, from September 2008 to December 2016; Aquantia Corporation, a manufacturer of high-speed transceivers, from December 2005 to April 2015; Evolv, Inc. (now Cornestone OnDemand), a workforce performance solution analytics company, from January 2008 to November 2014; Partners in School Innovation, a non-profit service organization, from June 2002 to June 2014; and Lemon, Inc., a mobile wallet developer, from September 2008 to December 2013. Prior to his role at Fall Line Capital, Mr. O’Brien was the Managing Director of Lightspeed Venture Partners, a venture capital firm, from February 2000 to December 2011. Mr. O’Brien earned his M.B.A. from the Stanford University Graduate School of Business and an A.B. in Economics from Harvard College. We believe that Mr. O’Brien is qualified to serve on the Board due to his experience and knowledge of GreenLight’s business and his experience in venture capital and finance.
Jennifer E. Pardi. Ms. Pardi has served as a member of the Board since inception and has served as a member of its audit committee and environmental, social, governance, and impact committee since February 2022. Ms. Pardi has over 17 years of experience in corporate finance, equity and debt capital markets and has completed transactions in diverse industries and with complex structures. She currently serves as Global Head of Equity Capital Markets of Canaccord, where she has been since September 2003 and has extensive US and cross-border experience having been involved in the completion of over 1,000 transactions with an aggregate value of over $150 billion. Ms. Pardi holds a B.A. in Economics from the University of Connecticut and an M.B.A. (with distinction) from Suffolk University. We believe that she is well qualified to serve on the Board due to her extensive experience in corporate finance and capital markets.
Martha Schlicher, Ph.D. Dr. Schlicher has served as a member of the Board and as chairperson of its audit committee and as a member of its compensation committee since February 2022. Dr. Schlicher, served as a member of the GreenLight Board since February 2018 and as the chair of GreenLight’s audit committee since October 2020. Since February 2020, Dr. Schlicher has been the Executive in Residence of BioGenerator, the investment arm of BioSTL and an evergreen investor that creates, grows and funds life-science companies and entrepreneurs in the St. Louis region. Since April 2020, Dr. Schlicher has also served as the Chief Executive Officer of Impetus Agriculture Inc., a company developing biological methods for insect control, and since July 2020, she has served as the Chief Executive Officer of Plastomics Inc., a start-up plant biotechnology company. From February 2016 to December 2019, Dr. Schlicher served as the Vice President of Research and Development of Mallinckrodt Pharmaceutical Company (OTCMKTS: MNKKQ), a manufacturer of specialty pharmaceuticals. Prior to that Dr. Schlicher served in many technical, regulatory, strategy and commercial executive leadership roles at Monsanto, last being as the Vice-President of Sustainability. We believe that Dr. Schlicher’s experience on the GreenLight Board, as well as her experiences running biotechnology companies, make her well qualified to serve on the Board.
Matthew Walker, Esq., M.B.A. Mr. Walker has served as a member of the Board and chairperson of its environmental, social, governance, and impact committee and a member of its compensation committee since February 2022. Mr. Walker served as a member of the GreenLight Board from December 2018 until the closing of the Business Combination in February 2022. Mr. Walker has also served as Managing Director at Builders Vision, LLC, an impact platform that includes S2G Ventures, and a major shareholder of GreenLight, since October 2014. Mr. Walker has served as a member of the board of Solarea Bio, Inc., a biotechnology company focused on solutions for health disorders, since September 2020; a member of the board of directors of Future Meat Technologies, a biotechnology company focused on global meat production, since April 2018; as Chairman of the Board of Directors of Hazel Technologies, Inc., a company developing biotechnology for reducing waste in the agricultural supply chain, since February 2018; a board member of Mercaris, a data service company and online trading platform focused on the organic and non-GMO commodities market place, since May 2017; and a board member of Farmer Focus-Shenandoah Valley
Organic, an organic meat brand, since December 2016. Previously, from August 2011 to February 2014. Mr. Walker was an investment banking associate at Perella Weinberg Partners, a financial services firm, where he focused on merger and acquisitions and restructuring transactions across a range of industries. Prior to that role, from July 2007 to July 2009, Mr. Walker was a securities attorney in the Funds, Regulation, and Equity Derivatives practice at Cadwalader, Wickersham & Taft, LLP, a law firm. Mr. Walker earned his M.B.A. from The University of Chicago Booth School of Business, a J.D. from New York University School of Law, and a B.S. in Mechanical Engineering from the University of Michigan. Mr. Walker is also a member of the Illinois Board of Trustees of The Nature Conservancy. We believe that Mr. Walker’s experience in finance and biotechnology companies, as well as his experience as a member of the GreenLight Board, makes him qualified to serve on the Board.
Number and Terms of Officers and Directors
Our Board consists of seven members. In accordance with our Second Amended and Restated Certificate of Incorporation (the "Charter"), the Board is divided into three classes. At each annual general meeting of stockholders, the successors to directors whose terms then expire will be elected to serve from the time of election and qualification until the third annual meeting following the election. The directors are divided among the three classes as follows:
•the Class I directors are Eric O’Brien and Jennifer Pardi, and their terms will expire at the annual meeting of stockholders to be held in 2023.
•the Class II directors are Martha Schlicher and Matthew Walker, and their terms will expire at the annual meeting of stockholders to be held in 2024.
•the Class III directors are Andrey Zarur, Charles Cooney, and Ganesh Kishore, and their terms will expire at the annual meeting of stockholders to be held in 2025.
We expect that any additional directorships resulting from an increase in the number of directors will be distributed among the three classes so that, as nearly as possible, each class will consist of one-third of the directors. The division of the board of directors into three classes with staggered three-year terms may delay or prevent a change of our management or a change in control.
Committees of the Board of Directors
The Board has three standing committees: an audit committee, a compensation committee, and an environmental, social, governance, and impact committee.
Audit Committee
Martha Schlicher, Charles Cooney and Jennifer Pardi serve on our Audit Committee, which is chaired by Dr. Schlicher. Under the Nasdaq listing rules (the "Listing Standards") and applicable SEC rules, we are required to have at least three members of the audit committee. The rules of the Nasdaq and Rule 10A-3 of the Exchange Act require that the audit committee of a listed company be composed solely of directors who satisfy the heightened independence requirements for audit committee purposes. The Board has determined that each member of the Audit Committee qualifies as an independent director for audit committee purposes under applicable rules. Furthermore, the Board has determined that each of Charles Cooney, Jennifer Pardi and Martha Schlicher is financially literate with the requisite financial expertise required under the applicable requirements of the Nasdaq Stock Market and that Martha Schlicher qualifies as an “audit committee financial expert” as defined in applicable SEC rules. In arriving at this determination, the Board has examined each Audit Committee member's scope of experience and nature of their background in the corporate finance sector.
The primary purpose of the Audit Committee is to discharge the responsibilities of the Board with respect to our accounting, financial, and other reporting and internal control practices and to oversee our independent registered public accounting firm. Specifically, the Audit Committee has the responsibility to, among other things:
•select, retain, compensate, evaluate, oversee and, where appropriate, terminate GreenLight’s independent registered public accounting firm;
•review and approve the scope and plans for the audits and the audit fees and approve all non-audit and tax services to be performed by the independent registered public accounting firm;
•evaluate the independence and qualifications of GreenLight’s independent registered public accounting firm;
•review GreenLight’s financial statements, and discuss with management and New GreenLight’s independent registered public accounting firm the results of the annual audit and the quarterly reviews;
•review and discuss with management and GreenLight’s independent registered public accounting firm the quality and adequacy of GreenLight’s internal controls and GreenLight’s disclosure controls and procedures;
•discuss with management GreenLight’s procedures regarding the presentation of GreenLight’s financial information, and review earnings press releases and guidance;
•oversee the design, implementation and performance of GreenLight’s internal audit function, if any;
•set hiring policies with regard to the hiring of employees and former employees of GreenLight’s independent registered public accounting firm and oversee compliance with such policies;
•review, approve and monitor related party transactions;
•review and monitor compliance with GreenLight’s Code of Business Conduct and Ethics and consider questions of actual or possible conflicts of interest of GreenLight’s directors and officers;
•adopt and oversee procedures to address complaints regarding accounting, internal accounting controls and auditing matters, including confidential, anonymous submissions by GreenLight’s employees of concerns regarding questionable accounting or auditing matters;
•review and discuss with management and GreenLight’s independent registered public accounting firm the adequacy and effectiveness of GreenLight’s legal, regulatory and ethical compliance programs; and
•review the Company's compliance with applicable laws and regulations and review and oversee the Company's policies, procedures and programs designed to promote and monitor legal, ethical and regulatory compliance; and
•review and discuss with management and GreenLight's independent registered public accounting firm GreenLight's guidelines and policies to identify, monitor and address enterprise risks.
GreenLight’s Audit Committee operates under a written charter that satisfies the applicable rules and regulations of the SEC and the listing standards of Nasdaq.
Compensation Committee
Ganesh Kishore, Eric O’Brien, Martha Schlicher and Matthew Walker serve on our Compensation Committee, which is chaired by Dr. Kishore. The Board has determined each member is a “non-employee director” as defined in Rule 16b-3 promulgated under the Exchange Act. The Board has determined that each member of the Compensation Committee is independent under the Listing Standards. The primary purpose of the Compensation Committee is to discharge the responsibilities of the Board to oversee its compensation policies, plans and programs and to review and determine the compensation to be paid to its executive officers, directors and other senior management, as appropriate. Specifically, the Compensation Committee has the responsibility to, among other things:
•review and approve or recommend to the Board for approval the compensation for GreenLight’s executive officers, including GreenLight’s chief executive officer;
•review, approve and administer GreenLight’s employee benefit and equity incentive plans;
•advise the Board on stockholder proposals related to executive compensation matters;
•establish and review the compensation plans and programs of GreenLight’s employees, and ensure that they are consistent with GreenLight’s general compensation strategy;
•oversee the management of risks relating to executive compensation plans and arrangements;
•monitor compliance with any stock ownership guidelines, as applicable;
•approve the creation or revision of any clawback policy as applicable;
•select independent compensation consultants and assess whether there are any conflicts of interest with any of the committee’s compensation advisors;
•review and approve, or recommend that our Board approve, incentive compensation and equity plans, severance agreements, change-of-control protections and any other compensatory arrangements for our executive officers and other senior management, as appropriate;
•review and approve or recommend to the Board for approval non-employee director compensation; and
•review executive compensation disclosure in GreenLight’s SEC filings and prepare the compensation committee report required to be included in GreenLight’s annual proxy statement.
GreenLight’s compensation committee operates under a written charter, that satisfies the applicable rules and regulations of the SEC and the listing standards of Nasdaq.
Compensation Committee Interlocks and Insider Participation
No member of the compensation committee was at any time during 2022, or at any other time, one of our officers or employees. None of our executive officers has served as a director or member of a compensation committee (or other committee serving an equivalent function) of any entity, one of whose executive officers served as a member of our board of directors or member of our compensation committee.
Environmental, Social, Governance and Impact Committee
Matthew Walker, Ganesh Kishore, and Jennifer Pardi serve on our Environmental, Social, Governance and Impact Committee, which is chaired by Mr. Walker. The Board has determined each member of the Environmental, Social, Governance and Impact Committee is independent under the Listing Standards.
GreenLight’s Environmental, Social, Governance and Impact Committee has the responsibility to, among other things:
•review, assess and make recommendations to the Board regarding desired qualifications, expertise and characteristics sought of board members;
•identify, evaluate, select or make recommendations to the Board regarding nominees for election to the Board;
•develop policies and procedures for considering stockholder nominees for election to the Board;
•review GreenLight’s succession planning process for GreenLight’s chief executive officer and any other members of GreenLight’s executive management team;
•review and make recommendations to the Board regarding the composition, organization and governance of the Board and its committees;
•review and make recommendations to the Board regarding GreenLight’s corporate governance guidelines and corporate governance framework;
•oversee director orientation for new directors and continuing education for New GreenLight’s directors;
•oversee GreenLight’s ESG and sustainability programs and related disclosures and communications;
•oversee the evaluation of the performance of the Board and its committees;
•administer policies and procedures for communications with the non-management members of the Board;
•oversee GreenLight's goals to positively effect society as a public benefit corporation, establish public benefit metrics, and review public benefit metrics and achievement; and
•oversee sustainability, environmental impact and social responsibility policies and practices.
GreenLight’s environmental, social, governance, and impact committee operates under a written charter that satisfies the applicable rules and regulations of the SEC and the listing standards of Nasdaq.
Delinquent Section 16(a) Reports
Section 16(a) of the Securities Exchange Act of 1934, as amended, requires our officers, directors and persons who beneficially own more than ten percent of our ordinary shares to file reports of ownership and changes in ownership with the SEC. These reporting persons are also required to furnish us with copies of all Section 16(a) forms they file. Based solely on a review of the copies of the forms received by it during the fiscal year ended December 31, 2022 and written representations that no other reports were required, we believe that each person who, at any time during such fiscal year, was a director, officer or beneficial owner of more than ten percent of the Company’s Common Stock complied with all Section 16(a) filing requirements
during such fiscal year, except for (1) a non-timely Form 4 reporting a single transaction for each of Carole B. Cobb, Charles L. Cooney, Susan Keefe, David Kennedy, Amin Khan, Ganesh Kishore, Charu Manocha, Eric O’Brien, Marta Ortega-Valle, Jennifer E. Pardi, Martha Schlicher, Mark Singleton and Matthew Alan Walker, (2) a non-timely Form 4 reporting a transaction for the acquisition of Company Options for Marta Ortega-Valle, and (3) a non-timely Form 3 reporting holdings for Matthew Walker, Eric O'Brien, Ganesh Kishore, PhD., Dr. Andrey Zarur, Carole Cobb, Susan E. Keefe, Marta Ortega-Valle, David Kennedy, Charles Cooney, PhD., Amin Khan, Martha Schlicher, PhD. and Jennifer Pardi.
Code of Business Conduct and Ethics and Committee Charters
We have adopted a Code of Business Conduct and Ethics (“Code of Ethics”) that applies to all of our directors, officers and employees that complies with the rules and regulations of the Nasdaq. Copies of our code of ethics and our Board committee charters are available on our website (https://www.greenlightbiosciences.com). You may review these documents by accessing our public filings at the SEC’s web site at www.sec.gov. In addition, a copy of the Code of Ethics will be provided without charge upon request to us in writing at 29 Hartwell Avenue, Lexington, MA 02421. If we make any amendments to our Code of Ethics other than technical, administrative or other non-substantive amendments, or grant any waiver, including any implicit waiver, from a provision of the Code of Ethics applicable to our principal executive officer, principal financial officer, principal accounting officer or controller or persons performing similar functions requiring disclosure under applicable SEC or Nasdaq rules, we will disclose the nature of such amendment or waiver on our website. The information included on our website, or any of the websites of entities that we are affiliated with, is not incorporated by reference into this Annual Report on Form 10-K or in any other report or document we file with the SEC, and any references to our website are intended to be inactive textual references only.
Liability and Indemnification of Officers and Directors
The Charter limits the liability of our directors to the fullest extent permitted by the Delaware General Corporation Law (“DGCL”), and the Bylaws provide that we will indemnify them to the fullest extent permitted by such law. We have entered and expect to continue to enter into agreements to indemnify our directors, executive officers and other employees as determined by our Board. Under the terms of such indemnification agreements, we are required to indemnify each of our directors and officers, to the fullest extent permitted by the laws of the state of Delaware, if the basis of the indemnitee’s involvement was by reason of the fact that the indemnitee is or was a director or officer of the Company or any of its subsidiaries or was serving at our request in an official capacity for another entity. We must indemnify our officers and directors against all reasonable fees, expenses, charges and other costs of any type or nature whatsoever, including any and all expenses and obligations paid or incurred in connection with investigating, defending, being a witness in, participating in (including on appeal), or preparing to defend, be a witness or participate in any completed, actual, pending or threatened action, suit, claim or proceeding, whether civil, criminal, administrative or investigative, or establishing or enforcing a right to indemnification under the indemnification agreement. The indemnification agreements also require us, if so requested, to advance within 30 days of such request all reasonable fees, expenses, charges and other costs that such director or officer incurred, provided that such person will return any such advance if it is ultimately determined that such person is not entitled to indemnification by us. Any claims for indemnification by our directors and officers may reduce our available funds to satisfy successful third-party claims against us and may reduce the amount of money available to us.

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ITEM 11. EXECUTIVE COMPENSATION
Item 11. Executive Compensation.
GreenLight aims to pay competitively to attract, develop and retain highly talented employees. We provide rewards for high performance and critical skills and design compensation programs and structures to provide transparency around what is expected, encourage and reward delivery of annual objectives that are aligned with our stockholders’ long-term interests, and ultimately, support the achievement of GreenLight’s business strategy. GreenLight’s executive compensation program consists primarily of base salaries, an annual performance-based bonus program, and our equity-based incentive compensation program under the GreenLight 2022 Equity and Incentive Plan (the “GreenLight Equity Plan”) and the GreenLight 2022 Employee Stock Purchase Plan, which are described in more detail below.
This section provides an overview of GreenLight’s executive compensation programs, including a narrative description of the material factors necessary to understand the information disclosed in the summary compensation table below.
At December 31, 2022, GreenLight's named executive officers are:
•Andrey Zarur, President and Chief Executive Officer
•Carole B. Cobb, Chief Operating Officer
•Susan E. Keefe, Chief Financial Officer
•Amin Khan, Ph.D., Former Chief Scientific Officer
The following table presents information regarding the total compensation awarded to, earned by, and paid to our named executive officers for services rendered to us in all capacities for 2022.
Name and Principal Position
Year
Salary ($)
Bonus ($) (1)
Option awards ($)(2)
Non-equity incentive plan compensation ($)(3)
All other compensation ($)(4)
Total ($)
Dr. Andrey Zarur
575,000
-
-
-
1,552
576,552
President and Chief Executive Officer
500,000
-
-
227,500
727,779
Amin Khan, Ph.D.
440,000
75,000
1,524,034
-
18,292
2,057,326
Former Chief Scientific Officer (5)
Carole B. Cobb
440,000
-
860,523
-
2,362
1,302,885
Chief Operating Officer
425,000
-
-
154,700
579,979
Susan E. Keefe
415,000
-
860,523
-
1,424
1,276,947
Chief Financial Officer
380,000
-
-
172,900
553,179
(1)
The amount reported for Dr. Khan represents a second tranche to a signing bonus paid to him pursuant to the terms of the employment agreement between the Company and him.
(2)
In accordance with SEC rules, this column reflects the aggregate grant date fair value of the stock option awards granted during the year ended December 31, 2022, computed in accordance with FASB ASC 718. These amounts do not reflect the actual economic value that will be realized by the named executive officer upon the vesting of the stock options, the exercise of the stock options, or the sale of the shares underlying such stock options. There were no stock options granted in the year ended December 31, 2021. For a description of the determination of the fair value of the stock option awards, see “Management’s Discussion and Analysis of Financial Condition and Results of Operations of GreenLight-Critical Accounting Policies and Significant Judgments and Estimates-Determination of the Fair Value of Common Stock”. For additional information regarding the stock option awards, see “-Outstanding Equity Awards at December 31, 2022,” “-Employment Arrangements with Officers” and “-GreenLight 2022 Equity and Incentive Plan.”
(3)
The amounts reported represent performance-based cash bonuses based upon the achievement of goals for 2021. Performance-based goals for 2021 were earned in 2021 and paid in 2022. The performance-based goals for 2022 were earned in 2022 and paid in 2023. GreenLight’s bonus program is more fully described below under the section titled “GreenLight Executive Compensation-Non-Equity Incentive Plan Compensation.”
(4)
These amounts represent life insurance premiums paid by GreenLight for the benefit of the named executive officers. The amount reported for Dr. Khan includes payment of accrued vacation.
(5)
Dr. Khan was not a named executive officer during 2021. He was appointed Chief Scientific Officer of the Company in April 2021. Dr. Khan ceased to be an employee as of December 2, 2022.
Base Salaries
Base salary is a fixed element within a total compensation package intended to attract and retain the talent necessary to successfully manage GreenLight’s business and execute its business strategies. Base salaries for GreenLight’s named executive officers are established based on the scope of their responsibilities, taking into account relevant experience, internal pay equity, tenure, GreenLight’s ability to replace the individual, and other factors deemed relevant.
Base salaries for the named executive officers as of January 1, 2023 and 2022 were increased as follows:
Name and Principal Position
2023 Base Salary
2022 Base Salary
Increase (Decrease) ($)
Andrey J. Zarur, Ph.D., Chief Executive Officer and President
$
575,000
$
575,000
$
-
Carole Cobb, M.B.A., Chief Operating Officer
$
220,000
$
440,000
$
(220,000
)
Susan Keefe, M.B.A., Chief Financial Officer
$
415,000
$
415,000
$
-
Amin Khan, Ph.D., Former Chief Scientific Officer
-
$
440,000
-
Effective as of March 23, 2023, Ms. Cobb will be employed by the Company on a part-time basis and her base salary for 2023 was reduced accordingly to $220,000.
Ms. Keefe's 2023 base salary shall increase to $435,000 upon achievement of certain milestones by the Company.
Non-Equity Incentive Plan Compensation
At the beginning of 2022 and 2021, the GreenLight Board set the company goals for 2022 and 2021 with the objective of paying cash bonuses in 2023 and 2022 based on achievement of the 2022 and 2021 goals, respectively. Company goals consisted of both corporate development and product development goals to be measured and granted at the sole discretion of the GreenLight Board in 2023 and 2022.
Based on GreenLight's performance against the company goals for 2022 and in light of GreenLight's current cash position, the GreenLight Board determined to award each of the named executive officers 0%. Based on GreenLight’s performance against the company goals for 2021, the GreenLight Board determined to award each of Dr. Zarur and Ms. Cobb 91% of his or her target bonus amount for that year and to award Ms. Keefe approximately 114% of her target bonus amount for that year.
The amounts in the Summary Compensation Table under the column “Non-equity incentive plan compensation” are based on each named executive officer’s individual target bonus amount multiplied by the achievement percentage set by the GreenLight Board.
The target bonus amounts for the named executive officers under the employee bonus program, as a percentage of base salary, were increased as follows as of January 1, 2023 and 2022:
Name and Principal Position
2023 Target Bonus Amount
2022 Target Bonus Amount
Increase (%)
Andrey J. Zarur, Ph.D., Chief Executive Officer and President
%
%
%
Carole Cobb, M.B.A., Chief Operating Officer
%
%
%
Susan Keefe, M.B.A., Chief Financial Officer
%
%
%
Amin Khan, Ph.D., Former Chief Scientific Officer
-
%
-
Equity Based Incentive Awards
GreenLight’s equity-based incentive awards are designed to more closely align GreenLight’s interests and those of GreenLight’s stockholders with those of GreenLight’s employees and consultants, including GreenLight’s named executive officers. The GreenLight Board is responsible for approving equity grants to GreenLight’s employees and consultants, including GreenLight’s named executive officers.
All options are granted with an exercise price per share that is no less than the fair market value of a share of GreenLight Common Stock on the date of grant of such award. GreenLight’s stock option awards generally vest over a four-year period and may be subject to acceleration of vesting and exercisability under certain termination and change in control events. See “-Outstanding Equity Awards at December 31, 2022.”
Outstanding Equity Awards at December 31, 2022
The following table provides information with respect to equity awards granted to GreenLight’s named executive officers that remain outstanding as of December 31, 2022. The number of securities underlying unexercised options as of December 31, 2022 represent shares of our Common Stock, and such numbers and the associated exercise prices give effect to the conversion of such options upon the consummation of the Business Combination on February 2, 2022 into options to acquire shares of our Common Stock at an exchange ratio of 0.6656 (the “Exchange Ratio”) shares of our Common Stock for each share of pre-Business Combination GreenLight Common Stock.
Option awards (1)
Name
Grant Date
Number of securities underlying unexercised options (#) exercisable
Number of securities underlying unexercised options (#) unexercisable
Equity incentive plan awards: Number of underlying unexercised unearned options (#)
Option exercise price ($) (2)
Option expiration date
Dr. Andrey Zarur
10/16/2015
70,319
-
-
$
0.35
7/22/2025
9/13/2018 (3)
926,330
-
-
$
0.34
9/13/2028
12/29/2019 (3)
1,590,867
1,060,571
-
$
0.50
12/29/2029
12/1/2020 (4)
152,422
-
140,228
$
0.98
12/1/2030
12/1/2020 (5)
953,472
953,471
-
$
0.98
12/1/2030
Amin Khan
3/25/2021 (5)
232,959
299,520
-
$
1.24
5/16/2023
5/10/2022 (5)
-
318,751
-
$
7.96
5/10/2023
Carole B. Cobb
7/22/2015 (5)
427,752
-
-
$
0.35
7/22/2025
10/21/2016 (3)
43,863
-
-
$
0.35
10/21/2026
2/14/2018 (3)
459,264
-
-
$
0.34
2/14/2028
9/13/2018 (3)
172,179
15,652
-
$
0.34
9/13/2028
12/29/2019 (3)
304,529
203,018
-
$
0.50
12/29/2029
12/1/2020 (5)
163,075
163,068
-
$
0.98
12/1/2030
5/10/2022 (5)
-
180,000
-
$
7.96
5/10/2032
Susan E. Keefe
5/10/2019 (3)
341,928
146,538
-
$
0.50
5/10/2029
12/1/2020 (5)
282,883
282,876
-
$
0.98
12/1/2030
5/10/2022 (5)
-
180,000
-
$
7.96
5/10/2032
(1)
All of the outstanding stock option awards were granted and subject to the terms of the GreenLight 2022 Equity and Incentive Plan, described below under "- GreenLight 2022 Equity and Incentive Plan."
(2)
The stock option awards were granted with a per share exercise price equal to the fair market value of one share of our Common Stock on the date of grant, as determined in good faith by the GreenLight Board.
(3)
The stock option award vests as to 20% of the total number of shares subject to the award on the first anniversary of the vesting start date (which in some cases precedes the date of grant), and the remainder vests in 48 equal monthly installments thereafter.
(4)
The stock option award is subject to performance-based vesting conditions. The award will vest as described in footnote (5) below, provided that GreenLight consummates a specified new investment (which for this purpose includes the Business Combination) by March 31, 2022.
(5)
The stock option award vests as to 25% of the total number of shares subject to the award on the first anniversary of the vesting start date (which in some cases precedes the date of grant), and the remainder vests in 36 equal monthly installments thereafter.
Employment Arrangements with Officers
Andrey Zarur, Ph.D.
GreenLight entered into an Amended and Restated Employment Agreement with Dr. Andrey Zarur, dated May 25, 2015 (the “Zarur Agreement”) which governs Dr. Zarur’s role as President and Chief Executive Officer of GreenLight. Dr. Zarur’s employment under the Zarur Agreement is at-will and will continue until terminated at any time by either party. Pursuant to the Zarur Agreement, Dr. Zarur was initially entitled to receive a specified annual base salary for 2015. Dr. Zarur’s salary was most recently increased to $575,000 effective as of January 1, 2022. Dr. Zarur was also initially eligible to receive a discretionary annual bonus equal to up to 40% of his base salary (which was increased to 55% effective as of January 1, 2022) and options to purchase shares of our Common Stock (as detailed in the Zarur Agreement), subject to vesting over five years. The Zarur Agreement provides for acceleration of vesting of any unvested options upon termination without Cause or for Good Reason (each, as defined in the Zarur Agreement) in connection with a Change of Control Event (as defined in the Zarur Agreement). Additional information regarding Dr. Zarur’s outstanding option awards can be found under the section titled “Outstanding Equity Awards at December 31, 2022.” Dr. Zarur is also entitled to participate in GreenLight’s employee benefit plans and paid time-off policies.
If Dr. Zarur’s employment is terminated by GreenLight without Cause (as defined in the Zarur Agreement) or due to illness, accident or disability prohibiting him from performing his duties for three months in a 12-month period, or by Dr. Zarur for Good Reason (as defined in the Zarur Agreement), then Dr. Zarur will be entitled to severance equal to one year’s salary
payable over the succeeding 12-month period. If payments owed to Dr. Zarur at the time of termination would trigger the acceleration or increase of tax payable under Section 409A of the Code, GreenLight agreed to defer the commencement of such payments until the date that is at least six months following such termination, at which time GreenLight will pay Dr. Zarur a lump-sum payment equal to the cumulative amounts that would have otherwise been previously paid to Dr. Zarur during such period of deferral. Dr. Zarur’s right to severance is contingent upon his execution of a general release of claims in favor of GreenLight and his continued compliance with his non-competition and confidentiality agreement with GreenLight.
Carole B. Cobb
GreenLight entered into an offer letter with Carole B. Cobb, dated July 21, 2015, that provides for her at-will employment as GreenLight’s Senior Vice President of Operations. Ms. Cobb was subsequently named our Chief Operations Officer. The offer letter initially provided for Ms. Cobb to receive a specified annual base salary for 2015. Ms. Cobb’s salary was most recently increased to $440,000 effective as of January 1, 2022. Ms. Cobb was also initially eligible to receive a discretionary annual bonus equal to up to 30% of her annual base salary (which was increased to 45% effective as of January 1, 2022) and an option to purchase shares of our Common Stock, subject to vesting over five years. The offer letter provides for acceleration of vesting of any unvested options in the event of termination without Cause or by Ms. Cobb for Good Reason (each, as defined in the offer letter) in connection with a Change of Control Event (as defined in the offer letter).
If Ms. Cobb’s employment is terminated by GreenLight without Cause (as defined in the offer letter) or by Ms. Cobb for Good Reason (as defined in the offer letter), she will be entitled to severance equal to three months’ salary, payable in a lump sum within seven days of her termination of employment. Ms. Cobb’s right to severance is contingent upon her execution of a general release of claims in favor of GreenLight. Ms. Cobb is also entitled to participate in GreenLight’s employee benefit plans and paid-time off policies.
Susan E. Keefe
GreenLight entered into an offer letter with Susan E. Keefe, dated May 1, 2019, that provides for her at-will employment as GreenLight’s Chief Financial Officer. The offer letter provided for Ms. Keefe to receive a specified annual base salary for 2019. Ms. Keefe’s salary was most recently increased to $415,000 effective as of January 1, 2022. Ms. Keefe was also initially eligible to receive a discretionary annual bonus equal to up to 30% of her annual base salary (which was increased to 45% effective as of January 1, 2022), and an option to purchase shares of our Common Stock subject to vesting over five years. The offer letter provides for acceleration of vesting of any unvested options upon termination without Cause (as defined in the offer letter) in connection with a Change in Control Transaction (as defined in the offer letter). Pursuant to the offer letter, Ms. Keefe was also eligible to receive (and did receive) an additional option grant subject to performance milestones. If Ms. Keefe’s employment is terminated by GreenLight without Cause (as defined in the offer letter) or by Ms. Keefe for good reason (as defined in the offer letter), she will be entitled to severance equal to six months’ salary payable over the six months following such termination. Ms. Keefe is also entitled to participate in GreenLight’s employee benefit plans and paid time-off policies.
Amin Khan, Ph.D.
GreenLight entered into an offer letter with Mohammed Amin Khan (Amin) dated February 7, 2021, that provides for his at-will employment as GreenLight’s Chief Scientific Officer. The offer letter provided for Dr. Khan to receive a specified annual base salary for 2021. Dr. Khan’s salary was most recently increased to $413,000 effective as of January 1, 2022. Dr. Khan was also initially eligible to receive a discretionary annual bonus equal to up to 40% of his annual base salary (which was increased to 45% effective as of January 1, 2022), and an option to purchase shares of our Common Stock subject to vesting over four years. Dr. Khan was also entitled to participate in GreenLight’s employee benefit plans and paid time-off policies. Dr. Khan ceased to be an employee of GreenLight as of December 2022 but continues to be engaged by GreenLight as an advisor.
Potential Payments Upon Termination or Change of Control
Regardless of the manner in which a named executive officer’s service terminates, that named executive officer is entitled to receive amounts earned during his or her term of service, including unpaid salary and unused vacation, as applicable.
Each named executive officer holds stock options granted subject to the general terms of the GreenLight 2022 Equity and Incentive Plan. Pursuant to the Business Combination Agreement, upon the consummation of the Business Combination, all stock options outstanding under the GreenLight 2012 Equity Plan were converted into stock options under the GreenLight Equity Plan. A description of the termination and change-in-control provisions in the GreenLight Equity Plan and applicable to the stock options granted to GreenLight’s named executive officers is provided below under “- GreenLight 2022 Equity and Incentive Plan.”
For additional information regarding potential payments and acceleration of stock options upon termination or change of control, see “- Employment Arrangements with Officers” above.
Benefits and Perquisites
GreenLight provides benefits to its named executive officers on the same basis as provided to all of its employees, including health, dental and vision insurance; life insurance; accidental death and dismemberment insurance; short-and long-term disability insurance; and a tax-qualified Section 401(k) plan for which no match is provided by GreenLight.
Retirement Benefits
GreenLight maintains a 401(k) retirement savings plan, for the benefit of employees, including its named executive officers, who satisfy certain eligibility requirements. The 401(k) plan provides eligible employees with an opportunity to save for retirement on a tax-advantaged basis. Under the 401(k) plan, eligible employees may elect to defer a portion of their compensation, within the limits prescribed by the Code and the applicable limits under the 401(k) plan, on a pre-tax or after-tax (Roth) basis, through contributions to the 401(k) plan. All of a participant’s contributions into the 401(k) plan are 100% vested when contributed. The 401(k) plan is intended to qualify under Sections 401(a) and 501(a) of the Code. As a tax-qualified retirement plan, pre-tax contributions to the 401(k) plan and earnings on those pre-tax contributions are not taxable to the employees until distributed from the 401(k) plan, and earnings on Roth contributions are not taxable when distributed from the 401(k) plan. GreenLight does not provide a match for participants’ elective contributions to the 401(k) plan, nor does GreenLight provide to employees, including its named executive officers, any other retirement benefits, including without limitation any tax-qualified defined benefit plans, supplemental executive retirement plans and nonqualified defined contribution plans.
New GreenLight 2022 Equity and Incentive Plan
The following is a summary of the material features of the New GreenLight Equity Plan (the “Equity Plan”). This summary is qualified in its entirety by the full text of the Equity Plan, a copy of which is filed as an exhibit to this annual report. The Equity Plan has been adopted by the Board and approved by our stockholders. The Equity Plan became effective immediately prior to the consummation of the Business Combination (the “Equity Plan Effective Date”). The Equity Plan allows us to make equity and equity-based incentive awards, as well as cash awards, to employees, directors and consultants. The Board anticipates that providing such persons with a direct stake in the Company will assure a closer alignment of the interests of such individuals with those of the Company and its stockholders, thereby stimulating their efforts on the Company’s behalf and strengthening their desire to remain with the Company.
Purposes of the Equity Plan
The purposes of the our Equity Plan are to attract and retain personnel for positions with us or any of our subsidiaries; to provide additional incentive to employees, directors, and consultants; and to promote the success of our business. These incentives will be provided through the grant of stock options, stock appreciation rights, restricted stock unrestricted stock, restricted stock units, dividend equivalent rights, and cash awards as the administrator of the Equity Plan may determine.
Eligibility
As of December 31, 2022 approximately 272 individuals are eligible to participate in the Equity Plan, which includes approximately 6 non-employee directors, 4 officers and 262 employees who are not officers. In addition, our consultants are also generally eligible to participate in the Equity Plan.
The awards that are to be granted to any participant or group of participants are indeterminable at the date of this annual report because participation and the types of awards that may be granted under the Equity Plan are subject to the discretion of the plan administrator. Consequently, no new plan benefits table is included in this annual report.
No awards may be granted under the Equity Plan after the date that is ten years from the Equity Plan Effective Date, and awards of incentive stock options may not be granted after the date that is ten years from the date the Equity Plan was approved by the Board.
Authorized Shares
We had initially reserved 31,750,000 shares of our Common Stock for issuance under the Equity Plan (the “Initial Limit”), and shares subject to the Rollover Options count against this limit. The Equity Plan provides that the number of shares of our Common Stock reserved and available for issuance under the Equity Plan will automatically increase each January 1, beginning on January 1, 2023 and on each January 1 thereafter, by 4% of the outstanding number of shares of our Common Stock on the immediately preceding December 31, or such lesser amount as determined by the plan administrator (the “Annual Increase”). As of the date of this report, the total shares of Common Stock available under the Equity Plan was increased by 6,063,487 shares of Common Stock as a result of the Annual Increase on January 1, 2023. This limit is subject to adjustment in the event of a reorganization, recapitalization, reclassification, stock split, stock dividend, reverse stock split or other similar change in our
capitalization. The maximum aggregate number of shares of our Common Stock that may be issued upon exercise of incentive stock options under the Equity Plan may not exceed the Initial Limit cumulatively increased on January 1, 2023 and on each January 1 thereafter by the lesser of the Annual Increase or a number of shares of our Common Stock equal to twice the Initial Limit. Shares underlying any awards under the Equity Plan that are forfeited, cancelled, held back upon exercise of an option or settlement of an award to cover the exercise price or tax withholding, reacquired by us prior to vesting, satisfied without the issuance of stock or otherwise terminated (other than by exercise) will be added back to the shares available for issuance under the Equity Plan and, to the extent permitted under Section 422 of the Code and the regulations promulgated thereunder, the shares may be issued as incentive stock options. In addition, to the extent consistent with the requirements of Section 422 of the Code, awards granted or stock issued upon assumption of, or in substitution or exchange for, awards previously granted by an entity that we acquire or merge with or into, shall not reduce the shares available for issuance under the Equity Plan, nor will the shares underlying such awards be added back to the shares available for issuance under the Equity Plan in the event of any forfeiture, cancelation, reacquisition, expiration, termination, cash settlement or non-issuance of such shares.
The Equity Plan contains a limitation whereby the value of all awards under the Equity Plan and all other cash compensation paid by the Company to any non-employee director may not exceed $375,000 in any calendar year, except that the limit will be $500,000 for the first calendar year a non-employee director is initially appointed to the Board. The foregoing limitation will be calculated without regard to amounts paid to any non-employee director (including retirement benefits and severance payments) in respect of any services provided in any capacity (including employee or consultant) other than as a non-employee director. The Board may make exceptions to this limit for a non-executive chair of the Board with the approval of a majority of the disinterested directors.
Plan Administration
The Equity Plan will be administered by the compensation committee of the Board, the Board or another board committee pursuant to the terms of the Equity Plan. The plan administrator, which initially is the compensation committee of the Board, will have full power to select, from among the individuals eligible for awards, the individuals to whom awards will be granted, to make awards to participants, and to determine the specific terms and conditions of each award, subject to the provisions of the Equity Plan. The plan administrator may, without the approval of our stockholders, reduce the exercise price of any outstanding stock option or stock appreciation right, effect the repricing of such awards through cancellation and re-grants, or cancel such awards in exchange for cash or other awards. The plan administrator’s determinations under the Equity Plan need not be uniform. The plan administrator may delegate to one or more officers the authority to grant stock options and other awards to employees who are not subject to the reporting and other provisions of Section 16 of the Exchange Act, subject to certain limitations and guidelines. Persons eligible to participate in the Equity Plan are the directors, officers, employees and consultants of the Company and its affiliates as selected from time to time by the plan administrator in its discretion.
The Equity Plan requires the plan administrator to make appropriate adjustments to the number of shares of our Common Stock that are subject to the Equity Plan, to certain limits in the Equity Plan, and to any outstanding awards to reflect stock dividends, stock splits, extraordinary cash dividends and similar events.
Stock Options
The Equity Plan permits the granting of both options to purchase shares of our Common Stock intended to qualify as incentive stock options under Section 422 of the Code and options that do not so qualify. Options granted under the Equity Plan will be non-qualified options if they fail to qualify as incentive stock options or exceed the annual limit on incentive stock options. Incentive stock options may only be granted to employees of the Company and its subsidiaries.
Non-qualified options may be granted to any persons eligible to receive awards under the Equity Plan. The option exercise price of each option will be determined by the plan administrator but generally may not be less than 100% of the fair market value of our Common Stock on the date of grant or, in the case of an incentive stock option granted to a ten percent stockholder, 110% of such share’s fair market value on the date of grant. The term of each option will be fixed by the plan administrator and may not exceed ten years from the date of grant, subject to limited exceptions as described in the Equity Plan. The plan administrator will determine at what time or times each option may be exercised, including the ability to accelerate the vesting of such options.
Upon exercise of an option, the option exercise price must be paid in full either in cash, by certified or bank check or other instrument acceptable to the plan administrator or by delivery (or attestation to the ownership) of shares of our Common Stock that are beneficially owned by the optionee free of restrictions or were purchased in the open market. The exercise price may also be delivered by a broker pursuant to irrevocable instructions to the broker from the optionee. In addition, the plan administrator may permit options to be exercised using a “net exercise” arrangement that reduces the number of shares issued to the optionee by the largest whole number of shares with a fair market value that does not exceed the aggregate exercise price.
Stock Appreciation Rights
The plan administrator may award stock appreciation rights subject to such conditions and restrictions as it may determine. Stock appreciation rights entitle the recipient to receive shares of our Common Stock, or cash to the extent provided for in an award agreement, equal to the value of the appreciation in our Common Stock price over the exercise price. The exercise price generally may not be less than 100% of the fair market value of our Common Stock on the date of grant. The term of each stock appreciation right will be fixed by the plan administrator and may not exceed ten years from the date of grant, subject to limited exceptions as described in the Equity Plan. The plan administrator will determine at what time or times each stock appreciation right may be exercised.
Restricted Stock, Restricted Stock Units, Unrestricted Stock, Dividend Equivalent Rights
The plan administrator may award restricted shares of our Common Stock and restricted stock units subject to such conditions and restrictions as it may determine. These conditions and restrictions may include the achievement of certain performance goals and/or continued employment through a specified vesting period. The plan administrator may also grant shares of our Common Stock that are free from any restrictions under the Equity Plan. Unrestricted stock may be granted or sold to participants in recognition of past services or for other valid consideration and may be issued in lieu of cash compensation due to such participant. The plan administrator may grant dividend equivalent rights to participants that entitle the recipient to receive credits for dividends that would have been paid if the recipient had held a specified number of shares of our Common Stock.
Cash Awards
The plan administrator may grant cash-based awards under the Equity Plan to participants, subject to such vesting and other terms and conditions as the plan administrator may determine.
Payments by Participants
Participants in the Equity Plan are responsible for the payment of any federal, state, local or foreign taxes that the Company or its subsidiaries are required by law to withhold upon the exercise of options or stock appreciation rights or vesting of other awards. The plan administrator may cause any tax withholding obligation of the Company or its subsidiaries to be satisfied, in whole or in part, by the applicable entity withholding from shares of our Common Stock to be issued pursuant to an award a number of shares with an aggregate fair market value that would satisfy the withholding amount due. The plan administrator may also require any tax withholding obligation of the Company or its subsidiaries to be satisfied, in whole or in part, by an arrangement whereby a certain number of shares issued pursuant to any award are immediately sold and proceeds from such sale are remitted to the Company or its subsidiaries in an amount that would satisfy the withholding amount due.
Non-Transferability of Awards
The Equity Plan generally does not allow for the transfer or assignment of awards, other than by will or by the laws of descent and distribution or pursuant to a domestic relations order; however, the plan administrator may permit the transfer of nonstatutory stock options by option holders by gift to an immediate family member, to trusts for the benefit of family members, or to partnerships in which such family members are the only partners.
Merger or Change in Control
The Equity Plan provides that upon the effectiveness of a “change in control transaction,” as defined in the Equity Plan, an acquirer or successor entity may assume, continue or substitute for the outstanding awards under the Equity Plan. To the extent that awards granted under the Equity Plan are not assumed, continued or substituted by the successor entity, all awards granted under the Equity Plan shall terminate and, in such case (except as may be otherwise provided in the relevant award agreement), all stock options and stock appreciation rights with time-based vesting conditions or restrictions that are not vested and/or exercisable immediately prior to the effective time of the change in control transaction shall become fully vested and exercisable as of immediately prior to the effective time of the transaction, all other awards with time-based vesting conditions or restrictions shall become fully vested and nonforfeitable as of immediately prior to the effective time of the transaction, and all awards with conditions and restrictions relating to the attainment of performance goals may become vested and nonforfeitable in connection with the change in control transaction in the plan administrator’s discretion or to the extent specified in the relevant award agreement. In the event of such termination, individuals holding options and stock appreciation rights will, for each such award, either (a) receive a payment in cash or in kind for each share subject to such award that is exercisable in an amount equal to the per share value of the consideration payable to stockholders in the change in control transaction less the applicable per share exercise price (provided that, in the case of an option or stock appreciation right with an exercise price equal to or greater than the per share cash consideration payable to stockholders in the transaction, such option or stock appreciation right shall be cancelled for no consideration) or (b) be permitted to exercise such options and stock appreciation rights (to the extent exercisable) within a period of time prior to the transaction as specified by the plan administrator. The plan administrator shall also have the option (in its sole discretion) to make or provide for a payment, in cash or in kind, to participants holding other awards in an amount equal
to the per share value of the consideration payable to stockholders in the change in control transaction multiplied by the number of vested shares under such awards.
Amendment or Termination
The plan administrator may establish subplans and modify exercise procedures and other terms and procedures in order to facilitate grants of awards subject to the laws and/or stock exchange rules of countries outside of the United States.
All awards will be subject to any GreenLight clawback policy as set forth in such clawback policy or the applicable award agreement.
The Board may amend or discontinue the Equity Plan and the plan administrator may amend or cancel outstanding awards for purposes of satisfying changes in law or any other lawful purpose, but no such action may materially and adversely affect rights under an award without the holder’s consent. Certain amendments to the Equity Plan will require the approval of our stockholders.
GreenLight 2022 Employee Stock Purchase Plan
The following is a summary of the principal features of the GreenLight 2022 Employee Stock Purchase Plan ("GreenLight ESPP") and its operation. This summary does not contain all of the terms and conditions of the GreenLight ESPP and is qualified in its entirety by reference to the GreenLight ESPP, which is filed as an exhibit to this annual report.
The GreenLight ESPP has been adopted by the Board and approved by our stockholders. It is the intention of the Board that the GreenLight ESPP qualify as an “employee stock purchase plan” under Section 423 of the Code. The Board believes that the adoption of the GreenLight ESPP will benefit us by providing employees with an opportunity to acquire shares of our Common Stock and will help us to attract, retain and motivate valued employees.
Purpose
The purpose of the GreenLight ESPP is to provide eligible employees with an opportunity to purchase shares of our Common Stock through accumulated contributions, which generally will be made through payroll deductions. The GreenLight ESPP permits the administrator of the GreenLight ESPP to grant purchase rights that qualify for preferential tax treatment under Section 423 of the Code. In addition, the GreenLight ESPP authorizes the grant of purchase rights that do not qualify under Code Section 423 pursuant to rules, procedures or sub-plans adopted by the administrator that are designed to achieve desired tax or other objectives.
Shares Available for Issuance
We have initially reserved 2,000,000 shares of our Common Stock for issuance under the GreenLight ESPP. The GreenLight ESPP provides that the number of shares of our Common Stock reserved and available for issuance under such plan will automatically increase each January 1, beginning on January 1, 2023 and on each January 1 thereafter, by the least of 4,000,000 shares of our Common Stock, 4% of the outstanding number of shares of our Common Stock on the immediately preceding December 31, or such lesser amount as determined by the plan administrator. This limit is subject to adjustment in the event of a reorganization, recapitalization, reclassification, stock split, stock dividend, reverse stock split or other similar change in our capitalization.
Administration
The GreenLight ESPP will be administered by the compensation committee of the Board, the Board or another board committee pursuant to the terms of the GreenLight ESPP. The plan administrator, which initially is the compensation committee of the Board, has full authority to make, administer and interpret such rules and regulations regarding the GreenLight ESPP as it deems advisable.
Eligibility
Any employee of New GreenLight or one of its affiliates or subsidiaries that has been designated to participate in the GreenLight ESPP is eligible to participate in the GreenLight ESPP so long as the employee is customarily employed for at least 20 hours a week and more than five months in a calendar year. No person who owns or holds, or as a result of participation in the GreenLight ESPP would own or hold, our Common Stock or options to purchase our Common Stock that together equal 5% or more of the total combined voting power or value of all classes of capital stock of New GreenLight or any parent or subsidiary thereof is entitled to participate in the GreenLight ESPP. No employee may be granted an option under the GreenLight ESPP that permits the employee’s rights to purchase our Common Stock to accrue at a rate of more than $25,000 (determined using the fair market value of the stock at the time such option is granted) in any calendar year.
Participation in the GreenLight ESPP is limited to eligible employees who authorize payroll deductions equal to a whole percentage of base pay for allocation to the GreenLight ESPP. Employees may authorize payroll deductions with a minimum of 1% of base pay and a maximum of 15% of base pay. As of December 31, 2021, approximately 281 employees would be eligible to participate in the GreenLight ESPP. Once an employee becomes a participant in the GreenLight ESPP, that employee will automatically participate in successive offering periods, as described below, until such time as that employee withdraws from the GreenLight ESPP, becomes ineligible to participate in the GreenLight ESPP, or his, her or their employment ceases.
Offering Periods and Purchase Periods
Unless otherwise determined by the plan administrator, each offering of our Common Stock under the GreenLight ESPP will be for a period of six months, which is referred to as an “offering period.” The first offering period under the GreenLight ESPP will begin and end on such date or dates as determined by the plan administrator. Subsequent offerings under the GreenLight ESPP will generally begin on the first business day occurring on or after each January 1 and July 1 and will end on the last business day occurring before the following July 1 and January 1, respectively. Shares are purchased on the last business day of each offering period, with that day being referred to as an “exercise date.” The plan administrator may establish different offering periods or exercise dates under the GreenLight ESPP. The GreenLight ESPP will include a component, or the “423 Component,” that is intended to qualify as an “employee stock purchase plan” under Code Section 423, and a component that does not comply with Code Section 423, or the “Non-423 Component.” For purposes of this summary, a reference to the GreenLight ESPP generally will mean the terms and operations of the 423 Component.
Except as may be permitted by the plan administrator in advance of an offering, a participant may not increase or decrease the amount of his, her or their payroll deductions during any offering period but may increase or decrease his, her or their payroll deduction with respect to the next offering period by filing a new enrollment form within the period beginning 15 business days before the first day of such offering period and ending on the day prior to the first day of such offering period. A participant may withdraw from an offering period at any time without affecting his, her or their eligibility to participate in future offering periods. If a participant withdraws from an offering period, that participant may not again participate in the same offering period, but may enroll in subsequent offering periods. An employee’s withdrawal will be effective as of the next business day following the date that the plan administrator receives the employee’s written notice of withdrawal under the GreenLight ESPP.
Exercise of Purchase Right
On the exercise date of each offering period, the employee is deemed to have exercised the option, at the exercise price, for the lowest of (i) a number of shares of our Common Stock determined by dividing such employee’s accumulated payroll deductions or contributions on such exercise date by the exercise price; (ii) the number of shares of our Common Stock determined by dividing $25,000 by the fair market value of our Common Stock on the first day of such offering period; or (iii) such lesser number as established by the plan administrator in advance of the offering. The exercise price is equal to the lesser of (i) 85% the fair market value per share of our Common Stock on the first day of the offering period or (ii) 85% of the fair market value per share of our Common Stock on the exercise date. The maximum number of shares of our Common Stock that may be issued to any employee under the GreenLight ESPP in a calendar year is a number of shares of our Common Stock determined by dividing $25,000 by the fair market value of our Common Stock, valued at the start of the offering period, or such other lesser number of shares as determined by the plan administrator from time to time.
Termination of Participation
In general, if an employee is no longer a participant on an exercise date, the employee’s option will be automatically terminated, and the amount of the employee’s accumulated payroll deductions will be refunded.
Non-Transferability
A participant will not be permitted to transfer rights granted under the GreenLight ESPP other than by will or the laws of descent and distribution, and such rights are generally exercisable during the lifetime of the participant only by the participant.
Merger or Change in Control
In the case of and subject to the consummation of a “change in control,” the plan administrator, in its discretion, and on such terms and conditions as it deems appropriate, may take any one or more of the following actions under the GreenLight ESPP or with respect to any right under the GreenLight ESPP or to facilitate such transactions or events: (a) provide for either (i) termination of any outstanding option in exchange for an amount of cash, if any, equal to the amount that would have been obtained upon the exercise of such option had such option been currently exercisable or (ii) the replacement of such outstanding option with other options or property selected by the plan administrator in its sole discretion; (b) provide that the outstanding options under the GreenLight ESPP shall be assumed by the successor or survivor corporation, or a parent or subsidiary thereof,
or shall be substituted for similar options covering the stock of the successor or survivor corporation, or a parent or subsidiary thereof, with appropriate adjustments as to the number and kind of securities and prices; (c) make adjustments in the number and type of shares of our Common Stock (or other securities or property) subject to outstanding options under the GreenLight ESPP and/or in the terms and conditions of outstanding options and options that may be granted in the future; (d) provide that the offering with respect to which an option relates will be shortened by setting a new exercise date on which such offering will end; and (e) provide that all outstanding options shall terminate without being exercised and all amounts in the accounts of participants shall be promptly refunded.
Amendment; Termination
The GreenLight ESPP will automatically terminate on the tenth anniversary of the effective date of the GreenLight ESPP. The New GreenLight Board may, in its discretion, at any time, terminate or amend the GreenLight ESPP. However, without the approval within 12 months of such New GreenLight Board action by the stockholders, no amendment shall be made to the GreenLight ESPP increasing the number of shares specifically approved to comply with the requirements of Section 423(b) of the Code or any other changes to the components of the GreenLight ESPP intended to comply with the requirements of Section 423(b) of the Code that would require stockholder approval in order for the GreenLight ESPP, as amended, to qualify as an “employee stock purchase plan” under Section 423(b) of the Code.
GreenLight Director Compensation
Unless the context otherwise requires, any reference in this section of this Annual Report to “GreenLight,” “we,” “us” or “our” refer to GreenLight and its consolidated subsidiaries prior to the consummation of the Business Combination and to New GreenLight and its consolidated subsidiaries following the Business Combination.
GreenLight currently has no formal policy under which non-employee directors receive compensation for their service on the GreenLight Board or its committees. Certain non-employee directors receive cash fees for their service as a director of GreenLight. GreenLight’s policy is to reimburse non-employee directors for reasonable and necessary out-of-pocket expenses incurred in connection with attending board and committee meetings or performing other services in their capacities as non-employee directors, and GreenLight occasionally grants stock options to non-employee directors.
Director Compensation
The following table provides information regarding the compensation of each person serving as a director of GreenLight for 2022, other than Dr. Zarur, our President and Chief Executive Officer. Dr. Zarur does not receive any compensation for service in his capacity as a director. His compensation as a named executive officer is set forth above in “- Executive Compensation.”
2022 Director Compensation Table
Name
Fees Earned or Paid in Cash ($)
Option Award ($) (1)
All Other Compensation ($)
Total ($)
Dr. Charles Cooney
-
429,528
-
429,528
Dr. Ganesh Kishore
-
293,234
-
293,234
Eric O'Brien
-
293,234
-
293,234
Dr. Martha Schlicher
-
293,234
-
293,234
Jennifer E. Pardi
-
293,234
-
293,234
Matthew Walker
-
293,234
-
293,234
(1)
In accordance with SEC rules, this column reflects the aggregate grant date fair value of the stock option awards granted during the year ended December 31, 2022, computed in accordance with FASB ASC 718. These amounts do not reflect the actual economic value that will be realized by the named executive officer upon the vesting of the stock options, the exercise of the stock options, or the sale of the shares underlying such stock options.
Non-Employee Director Compensation
The Board expects to review director compensation periodically to ensure that director compensation remains competitive so that GreenLight will be able to recruit and retain qualified directors. In 2022, no cash compensation was paid to any director. Each non-employee director of the Company was granted a stock option award to purchase a number of shares of Common Stock equal to 65,000 stock options and 95,000 stock options in the case of the chairman, which awards vests in (i), vests in 12 equal quarterly installments and (ii) vests in 4 equal quarterly installments, subject to continued service through such vesting dates.
Compensation Risk Assessment
We believe that although a portion of the compensation provided to our executive officers is performance-based, our executive compensation program does not encourage excessive or unnecessary risk taking. This is primarily because its compensation programs are designed to create a greater focus on long-term value creation while balancing the need to meet shorter-term goals. The framework and goals of our annual performance-based incentive plan are consistent for all employees. Further all compensation decisions for our officers are approved by the Compensation Committee, while the Chief Executive Officer’s compensation requires further approval by the Board.
In addition, the Compensation Committee is responsible for reviewing and approving the design, goals and payouts under our annual bonus plan and equity incentive program for our named executive officers. The Compensation Committee directly engages an independent compensation consultant who advises on market competitive and best practices, as well as any potential risks related to its compensation programs. This includes pay mix, compensation vehicles, pay for performance alignment, performance measures and goals, payout maximums, vesting periods and Compensation Committee oversight and independence. Based on all the factors mentioned, we believe our compensation policies, programs and practices do not create risks that are reasonably likely to have a material adverse effect on us.

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ITEM 12. SECURITY OWNERSHIP OF CERTAIN BENEFICIAL OWNERS
Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters.
Principal Stockholders
Equity Compensation Plan Information
The following table summarizes our equity compensation plan information as of December 31, 2022:
Plan Category
Number of shares to be issued upon exercise of outstanding options, warrants and rights
Weighted-average exercise price of outstanding options, warrants and rights
Number of securities remaining available for future issuance under equity compensation plans (excluding securities reflected in column a)
Equity compensation plans approved by security holders:
2022 Equity and incentive plan
23,051,188
$
2.35
7,905,273
2022 Employee stock purchase plan
-
-
-
Equity compensation plans not approved by security holders
-
-
-
Total
23,051,188
$
2.35
7,905,273
The following table provides information regarding the beneficial ownership of our Common Stock as of March 15, 2023 by:
•each person known by GreenLight to be the beneficial owner of more than 5% of GreenLight Common Stock;
•named executive officers of GreenLight
•each director of GreenLight;
•all directors and executive officers of GreenLight as a group.
Beneficial ownership is determined according to the rules of the SEC, which generally provide that a person has beneficial ownership of a security if the person possesses sole or shared voting or investment power over that security, including options and warrants that are currently exercisable or that will become exercisable within 60 days after March 15, 2023. Unless otherwise indicated, GreenLight believes that all persons named in the table below have sole voting and investment power with respect to the voting securities beneficially owned by them. Unless otherwise indicated, the address of each beneficial owner listed in the table is Company's address set forth on the first page of this Annual Report on Form 10-K.
The beneficial ownership of GreenLight Common Stock is based on 151,681,314 shares of GreenLight Common Stock issued and outstanding as of March 15, 2023:
Name of Beneficial Owner
Number
Percentage
Five Percent or Greater Holders
Builders Vision, LLC (1)
22,348,123
14.7
%
Morningside Venture Partners (2)
16,919,153
11.2
%
Fall Line Endurance Fund, LP (3)
11,452,834
7.6
%
Kodiak Venture Partners (4)
9,809,898
6.5
%
Cormorant Asset Management, LP (5)
9,188,659
6.1
%
Directors and Named Executive Officers
Matthew Walker (1)(6)
22,453,565
14.8
%
Eric O'Brien (3)(7)
11,494,501
7.6
%
Ganesh Kishore (8)(7)
5,860,242
3.9
%
Dr. Andrey Zarur (9)
5,147,591
3.4
%
Carole Cobb (10)
1,704,450
1.1
%
Susan E. Keefe (10)
769,449
*
Charles Cooney (11)
365,514
*
Amin Khan (10)
255,146
*
Martha Schlicher (7)
41,667
*
Jennifer Pardi (7)
41,667
*
All directors and executive officers as a group
48,517,942
31.7
%
*
Indicates beneficial ownership of less than 1%.
(1)
The amount shown and the following information are derived from the Schedule 13 G/A filed on February 14, 2023 by Builders Vision, LLC, reporting beneficial ownership as of December 31, 2022. Includes (a) 11,551,245 shares held by S2G Builders Food & Agriculture Fund III, LP (“Fund III”); (b) 2,087,043 shares held by S2G Ventures Fund I, L.P. (“Fund I”); (c) 8,582,284 shares held by S2G Ventures Fund II, L.P (“Fund II”); and (d) 127,551 shares held by Builders GRNA Holdings, LLC. (“SPV” and, together with Fund I, Fund II and Fund III, the “S2G Funds”). Builders Vision, LLC is the Manager of Funds I, II and SPV, and the General Partner of Fund III, and has power to vote or direct the voting of shares held by the S2G Funds. The General Partners of Fund I and Fund II are S2G Ventures, LLC and S2G Ventures II, LLC, respectively (collectively, "S2G Ventures"). Mr. Walker, a director of GreenLight, is a Managing Director of Builders Vision, LLC, the impact platform founded by Lukas T. Walton, which includes S2G Ventures. By virtue of the foregoing, S2G Ventures, LLC, S2G Ventures II, LLC, Mr. Walker and Mr. Walton may be deemed to indirectly beneficially own (as defined in Rule 13d-3 of the Exchange Act) the shares of GreenLight Common Stock held by the S2G Funds and SPV. Mr. Walker and Mr. Walton each disclaims beneficial ownership of these shares of GreenLight Common Stock except to the extent of any pecuniary interest therein. The business address for Builders Visions, LLC is 110 N.W. 2nd Street, Suite 300, Bentonville, Arkansas 72712.
(2)
The amount shown and the following information are derived from Form 4 filed on August 15, 2022 by Morningside Venture Investments LTD. Includes (a) 15,919,155 shares held by Morningside Venture Investments Limited, and (b) 1,000,000 shares held by MVIL, LLC (together with Morningside Venture Investments Limited, “Morningside”). Frances Anne Elizabeth Richard, Jill Marie Franklin, Peter Stuart Allenby Edwards and Cheung Ka Ho are the directors of Morningside and have shared voting power over the securities held by Morningside. Each of these individuals disclaims beneficial ownership of the shares owned by Morningside. The address of Morningside is c/o THC Management Services S.A.M., 2nd Floor, Le Prince de Galles, 3-5 Avenue des Citronniers, MC 98000, Monaco.
(3)
Represents shares held by Fall Line Endurance Fund, LP (“Fall Line”). Mr. Eric O’Brien, a director of GreenLight, is the co-founder and Managing Director of Fall Line and has the power to vote, or to direct the voting of, the shares of GreenLight Common Stock held by Fall Line. By virtue of the foregoing, Mr. O’Brien may be deemed to indirectly beneficially own (as that term is defined in Rule 13d-3 of the Exchange Act) the shares of GreenLight Common Stock held by Fall Line. Mr. O’Brien disclaims beneficial ownership of these shares of GreenLight Common Stock except to the extent of any pecuniary interest therein. The business address of Fall Line and Mr. O’Brien is 119 South B Street, Suite B, San Mateo, CA 94401.
(4)
Includes (a) 9,573,157 shares held by Kodiak Venture Partners III, L.P., and (b) 236,741 shares held by Kodiak III Entrepreneurs Fund, L.P. (together with Kodiak Venture Partners III, L.P. “Kodiak”). Kodiak Ventures Management III, L.P. (“Kodiak Ventures”) is the General Partner for Kodiak, Kodiak Venture Management (GP), LLC is the General Partner for Kodiak Ventures and Kodiak Ventures Management Company, Inc. is the Member of Kodiak Ventures Management (GP), LLC (“Kodiak Ventures Management”). Mr. David Furneaux is the Chief Executive Officer of Kodiak Ventures Management Company, Inc. Each therefore has the power to vote, or direct the voting of, the shares of our Common Stock held by Kodiak. By virtue of the foregoing, each of Kodiak Ventures Management and Mr. Furneaux may be deemed to indirectly beneficially own (as that term is defined in Rule 13d-3 of the Exchange Act) our Common Stock held by Kodiak.
Mr. Furneaux disclaims beneficial ownership of these shares of our Common Stock except to the extent of any pecuniary interest therein. The business address for Kodiak, Kodiak Ventures Management and Mr. Furneaux is 11 Peter Grover Road, Bethel, Maine 04217.
(5)
The amount shown and the following information are derived from the Schedule 13 G/A filed on February 14, 2023 by Cormorant Asset Management, LP, reporting beneficial ownership as of December 31, 2022. Includes (a) 4,751,020 shares of GreenLight Common Stock held by Cormorant Global Healthcare Master Fund, LP (“Master Fund”), and (b) 4,437,639 shares of GreenLight Common Stock held by Cormorant Private Healthcare Fund II, LP (“Fund II”). Cormorant Global Healthcare GP, LLC and Cormorant Private Healthcare GP II, LLC serve as the general partners of the Master Fund and Fund II, respectively. Cormorant Asset Management, LP serves as the investment manager to Master Fund and Fund II. Bihua Chen serves as the Managing Member of Cormorant Global Healthcare GP, LLC, Cormorant Private Healthcare GP II, LLC and the general partner of Cormorant Asset Management, LP (together with Master Fund and Fund II, the “Cormorant Entities”). By virtue of the foregoing, each of Bihua Chen and the Cormorant Entities may be deemed to indirectly beneficially own (as that term is defined in Rule 13d-3 of the Exchange Act) the shares held by each of the relevant Cormorant Entities. Each of Bihua Chen and the Cormorant Entities disclaims beneficial ownership of such shares except to the extent of her or its pecuniary interest therein. The business address of each of Bihua Chen and the Cormorant Entities is 200 Clarendon St., 52nd Floor, Boston, Massachusetts
(6)
Includes (a) 63,775 shares of GreenLight Common Stock held by Mr. Walker and (b) 41,667 shares subject to options exercisable within 60 days of March 15, 2023.
(7)
Includes 41,667 shares subject to options exercisable within 60 days of March 15, 2023.
(8)
Represents shares held by MLS Capital Fund II, L.P. (“MLS”). Mr. Kishore, a director of GreenLight, is a Co-Manager of MLSCF II (GP) (Labuan), LLP, the General Partner of MLS, and has the power to vote, or to direct the voting of, the shares held by MLS. By virtue of the foregoing, Mr. Kishore may be deemed to indirectly beneficially own (as that term is defined in Rule 13d-3 of the Exchange Act) the shares held by MLS. Mr. Kishore disclaims beneficial ownership of these shares except to the extent of any pecuniary interest therein. The business address of MLS and Mr. Kishore is c/o Spruce Capital Partners LLC, 660 4th Street, #295, San Francisco, California 94107.
(9)
Includes (a) 896,058 shares of GreenLight Common Stock held by Dr. Zarur and (b) 4,251,533 shares subject to options exercisable within 60 days of March 15, 2023.
(10)
Represents shares subject to options exercisable within 60 days of March 15, 2023.
(11)
Includes (a) 305,514 shares of GreenLight Common Stock held by Dr. Cooney and (b) 60,000 shares subject to options exercisable within 60 days of March 15, 2023.

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ITEM 13. CERTAIN RELATIONSHIPS AND RELATED TRANSACTIONS
Item 13. Certain Relationships and Related Transactions, and Director Independence.
Policies and Procedures Regarding Related Transactions
We have a written related party transaction policy that sets forth the following policies and procedures for the review and approval or ratification of related party transactions. Our policy requires us to avoid, wherever possible, Related Party Transactions (as defined below) that could result in actual or potential conflicts of interests, except under guidelines approved by the Board or the Audit Committee of the Board.
A “Related Party Transaction” is any transaction, arrangement, or relationship, or any series of similar transactions, arrangements, or relationships, in which (a) the Company (or any of its wholly-owned subsidiaries) is or will be a participant, (b) the aggregate amount involved will or may be expected to exceed $120,000 in any fiscal year, and (c) any Related Party has or will have a direct or indirect material interest. A “Related Party” means (i) any current or former (since the beginning of the last fiscal year for which the Company has filed an Annual Report on Form 10-K) director or executive officer of the Company, (ii) any director nominee, (iii) security holders known to the Company to beneficially own more than 5% of any class of the Company’s voting securities, (iv) the immediate family members (as defined below) of any of the persons listed in items (i) - (iii), or other persons identified from time to time under Item 404 of Regulation S-K. A Related Party’s “immediate family members” includes any child, stepchild, parent, stepparent, spouse, sibling, mother-in-law, father-in-law, son-in-law, daughter- in-law, brother-in-law, sister-in-law or any other person (other than a tenant or employee) sharing the household of such Related Party.
The Audit Committee of the Board has the responsibility for administering such policy and reviewing and approving any Related Party Transactions. In reviewing any Related Party Transaction, the Audit Committee will take into account, among other factors that it deems appropriate, whether the Related Party Transaction is being undertaken in the ordinary course of business, whether transaction is on terms no less favorable to us than terms generally available in a transaction with an unaffiliated third-party under the same or similar circumstances, the purpose of and potential benefits to the Company of the Related Party Transaction, and the extent of the Related Party’s interest in the Related Party Transaction. We will not enter into any such transaction unless the Audit Committee and a majority of our disinterested “ independent” directors determine that the terms of
such transaction are no less favorable to us than those that would be available to us with respect to such a transaction from unaffiliated third parties. Additionally, we require each of our directors and officers to complete a directors’ and officers’ questionnaire that elicits information about related transaction.
These procedures are intended to determine whether any such related transaction impairs the independence of a director or presents a conflict of interest on the part of a director, employee or officer.
Certain Related Transactions
Below are our Related Party Transactions since January 1, 2022, to which we have been a party, other than compensation, termination, change in control and other arrangements which are described in the section titled “Executive Compensation”.
Business Combination Marketing Agreement
On January 13, 2021 ENVI entered into the Business Combination Marketing Agreement with Canaccord, an affiliate of CG Investments Inc. VI, a Canadian corporation (“Sponsor”), pursuant to which ENVI engaged Canaccord as an advisor in connection with a business combination, to assist ENVI in arranging meetings with its stockholders to discuss the potential business combination and the target business’ attributes, introduce ENVI to potential investors that may be interested in purchasing ENVI securities, assist in obtaining stockholder approval for the business combination and assist with the preparation of ENVI press releases and public filings in connection with the business combination. For such services, ENVI agreed to will pay Canaccord upon the consummation of a business combination, including the Business Combination, a cash fee in an amount equal to 3.76% of the gross proceeds of the initial public offering (or $7,783,200) (exclusive of any applicable finders’ fees which might become payable). Pursuant to the terms of the Business Combination Marketing Agreement, no fee would have been paid if ENVI did not complete a business combination. At the closing of the Business Combination, the parties agreed to reduce the cash fee to $5.8 million, and such amount was paid.
Investor Rights Agreement
Concurrently with the execution of the Business Combination Agreement, ENVI, the initial stockholders and certain stockholders of GreenLight, entered into the Investor Rights Agreement pursuant to which, among other things, the initial stockholders and such stockholders of GreenLight were granted certain registration rights, in each case subject to, and conditioned upon and effective as of, the effective time of the Merger.
Pursuant to the terms of the Investor Rights Agreement, GreenLight was obligated to file a registration statement to register the resale of certain shares of GreenLight Common Stock within 45 days after the closing of the Business Combination and to maintain the effectiveness of such registration statement for a period of up to three years from its date of effectiveness. In addition, pursuant to the terms of the Investor Rights Agreement and subject to certain requirements and conditions, including with regard to the number of demand rights that may be exercised, the February 2022 PIPE Investors who are parties to the Investor Rights Agreement may demand at any time or from time to time that GreenLight file a registration statement on Form S-3 (or on Form S-1 if Form S-3 is not available) to register the resale of the securities of GreenLight held by such holders, including certain rights to conduct underwritten offerings and registered block trades. The Investor Rights Agreement also provides such holders with certain “piggy-back” registration rights, subject to certain requirements and customary conditions.
The Investor Rights Agreement will terminate on the earliest of (i) the fifth anniversary of the Effective Time, (ii) the date on which neither the stockholders party thereto nor any of their permitted assignees holds any securities registrable thereunder, (iii) certain acquisitions of New GreenLight or substantially all of its assets and (iv) its liquidation, dissolution or winding up.
The Investor Rights Agreement amended and restated the previous registration rights agreement by and among the Company and certain of the initial stockholders in connection with the Company’s initial public offering.
Business Combination Arrangements
Certain of GreenLight’s stockholders, directors and executive officers entered into agreements with ENVI in connection with Business Combination. The agreements described in this section, or forms of such agreements, are filed as exhibits to this Annual Report on Form 10-K and forms a part, and the following descriptions are qualified by reference thereto. These agreements include:
•the February 2022 PIPE Subscription Agreements, which were executed and delivered by the following holders of more than 5% of GreenLight’s outstanding capital stock or an affiliate thereof: S2G Builders Food & Agriculture Fund III, LP (an affiliate of Builders Vision, LLC), Morningside, Fall Line, and MLS Capital Fund II, L.P. (“MLS”);
Subscription Agreements for the February 2022 PIPE Financing
Concurrently with the execution of the Business Combination Agreement and in November 2021, ENVI entered into the Subscription Agreements (the “February 2022 PIPE Subscription Agreements”) with each of the investors named therein (the “February 2022 PIPE Investors”), pursuant to which the February 2022 PIPE Investors subscribed for and purchased, and the Company issued and sold to the February 2022 PIPE Investors an aggregate of 12,425,000 shares of ENVI Class A Common Stock at a price of $10.00 per share, for aggregate gross proceeds of $124,525,000. The shares of ENVI Class A Common Stock issued pursuant to the February 2022 PIPE Subscription Agreements were not registered under the Securities Act and were issued in reliance upon the exemption provided in Section 4(a)(2) of the Securities Act. The February 2022 PIPE Financing was contingent upon, among other things, the substantially concurrent closing of the Business Combination. In connection with the Business Combination, all of the issued and outstanding shares of ENVI Class A Common Stock, including the shares of ENVI Class A Common Stock issued in the February 2022 PIPE Financing, and all of the issued and outstanding ENVI Class B Common Stock became shares of GreenLight Common Stock.
February 2022 PIPE Subscription Agreements were executed by the following holders of GreenLight’s outstanding capital stock or an affiliate thereof, as follows:
Name
Number of Shares
Subscription Amount
S2G Builders Food & Agriculture Fund III, LP (1)
1,500,000
$
15,000,000
Morningside Venture Investments Limited
1,000,000
$
10,000,000
Fall Line Endurance Fund, LP
700,000
$
7,000,000
MLS Capital Fund II, LP
75,000
$
750,000
(1)
S2G Builders Food & Agriculture Fund III, LP is an affiliate of Builders Vision, LLC.
The February 2022 PIPE Subscription Agreements granted the February 2022 PIPE Investors certain resale registration rights in connection with the February 2022 PIPE Financing. The Company agreed to file a registration statement with the SEC within 30 days after the February 2022 PIPE Closing to register the resale of the shares acquired in the February 2022 PIPE Financing. The Company agreed to use its commercially reasonable efforts to have the registration statement declared effective as soon as practicable after filing but no later than the earlier of (i) the 60th day (or 90th day if the SEC notifies the Company that it will “review” the registration statement) following the February 2022 PIPE Closing and (ii) the 10th business day after the date the Company is notified by the SEC that the registration statement will not be “reviewed” or will not be subject to further review.
Subscription Agreements for the August 2022 PIPE Financing
Concurrently with the execution of the subscription agreements, dated August 11, 2022 (the “August 2022 PIPE Subscription Agreements”), entered into with certain investors named therein (the “August 2022 PIPE Investors"), pursuant to which the August 2022 PIPE Investors subscribed for and purchased, and the Company issued and sold to the August 2022 PIPE Investors, an aggregate of 27,640,301 shares of the Company’s Common Stock at a price per share of $3.92 per share, for aggregate gross proceeds of approximately $108.3 million.
The shares of our Common Stock issued pursuant to the August 2022 PIPE Subscription Agreements were not registered under the Securities Act and were issued in reliance upon the exemption provided in Section 4(a)(2) of the Securities Act.
The August 2022 PIPE Subscription Agreements were executed by the following affiliated stockholders, or stockholders holding more than 5% of the Company’s outstanding capital stock as of August 11, 2022:
Name
Number of Shares
Subscription Amount
Builders Vision, LLC (1)
6,505,102
$
25,500,000
Morningside Venture Partners
3,061,224
$
12,000,000
Fall Line Endurance Fund, LP
2,551,020
$
10,800,000
Cormorant Asset Management, LP
2,551,020
$
10,000,000
Matthew A. Walker
63,775
$
249,998
(1)
S2G Builders Food & Agriculture Fund III, LP and Builders GRNA Holdings, LLC are each affiliates of Builders Vision, LLC.
The August 2022 PIPE Subscription Agreements grant the August 2022 PIPE Investors certain resale registration rights in connection with the August 2022 PIPE Financing. The Company agreed to file a registration statement with the SEC within 45 days after the August 2022 PIPE Closing to register the resale of the shares acquired in the August 2022 PIPE Financing. The Company agreed to use its commercially reasonable efforts to have the registration statement declared effective as soon as practicable after filing but no later than the earlier of (i) the 90th calendar day (or 120th calendar day if the SEC notifies the
Company that it will “review” the Registration Statement) or (ii) the 10th business day after the date the Company is notified by the SEC that the Registration Statement will not be “reviewed” or will not be subject to further review. The shares issued under the August 2022 PIPE Subscription Agreements are registered under Registration No. 333-267619.
Fall Line Lease Agreement
The Company is party to a Lease Agreement (the “Farmland Lease”) with Mendocino View Farm, LLC, which is a wholly-owned subsidiary of Fall Line Endurance Fund, LP (“Fall Line”). Fall Line is a greater than 5% shareholder of the Company and Eric O’Brien, a director on the Company’s Board of Directors, is the co-founder and Managing Director of Fall Line. Pursuant to the terms of the Farmland Lease, the Company is leasing approximately 81.25 acres of farmland for research and development purposes at an annual rental rate of $90,000 plus operating expenses (NNN lease). The initial term of the Farmland Lease is ten years commencing on January 1, 2023, subject to an option to extend for an additional ten years. Under the Farmland Lease, the Company agreed to pay $350,000 as additional rent, payable in two installments of $175,000 on each of January 1, 2023 and January 1, 2024. Fall Line provided the Company an allowance of $70,000 towards tenant improvements. Either party under the Farmland Lease may terminate the Farmland Lease subject to a termination fee of $200,000. Finally, the Company has a right of first offer to purchase the leased farmland in the event Fall Line intends to sell all or any portion of the leased farmland.
Corporate Governance
Indemnification under our Charter and Bylaws; Indemnification Agreements
The Company’s Second Amended and Restated Certificate of Incorporation (the “Charter”) and the Company’s Amended and Restated Bylaws provide that GreenLight will indemnify its directors and officers to the maximum extent permitted by the Delaware General Corporation Law (“DGCL”), subject to certain exceptions. In addition, the Charter provides that our directors will not be liable for monetary damages for breach of fiduciary duty to the maximum extent permitted by the DGCL.
GreenLight entered into indemnification agreements with each of its directors. The indemnification agreements provide the indemnitees with contractual rights to indemnification, and expense advancement and reimbursement, to the maximum extent permitted under the DGCL, subject to certain exceptions contained in those agreements.
Director Independence
Current Nasdaq listing guidelines require that a majority of our Board be independent. An “independent director” is defined generally as a person other than an executive officer or employee of the Company or any other individual having a relationship which, in the opinion of our Board, would interfere with the exercise of independent judgement in carrying out the responsibilities of a director. The Board has determined that each individual who serves on the Board, other than Dr. Zarur, qualifies as an independent director under the Listing Standards. In making such independence determination, our Board considered the relationships that each non-employee director has with us and all other facts and circumstances that our Board deemed relevant in determining their independence.

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ITEM 14. PRINCIPAL ACCOUNTING FEES AND SERVICES
Item 14. Principal Accounting Fees and Services.
Principal Accountant Fees and Services
We regularly review the services and fees of Deloitte & Touche LLP, our independent registered public accounting firm. These services and fees are also reviewed by the Audit Committee on an annual basis. The aggregate fees billed for the fiscal years ended December 31, 2022 and 2021 for each of the following categories of services are as follows:
Fees
Audit Fees (1)
$
1,475,536
$
2,074,967
Audit Related Fees (2)
-
-
Tax Fees (3)
-
-
All Other Fees (4)
1,895
1,895
Total Fees
$
1,477,431
$
2,076,862
(1)
Audit fees consist of fees billed for professional services rendered for the audit of year-end consolidated financial statements, reviews of quarterly interim financial statements and services that are normally provided by the independent registered public accounting firm in connection with statutory and regulatory filings, as well as fees incurred in connection with the preparation and filing of registration statements with the SEC. The above amounts include interim procedures and audit fees, as well as attendance at audit committee meetings.
(2)
Audit related fees consist of fees billed for assurance and related services that are reasonably related to performance of the audit or review of year-end consolidated financial statements and are not reported under “Audit Fees.” These services include attest services that are not required by statute or regulation and consultation concerning financial accounting and reporting standards.
(3)
Tax fees consist of fees billed for professional services relating to tax compliance, tax planning and tax advice.
(4)
All other fees consist of an annual license fee for the use of accounting research software.
PART IV

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ITEM 15. EXHIBITS, FINANCIAL STATEMENT SCHEDULES
Item 15. Exhibits and Financial Statement Schedules.
(1)For a list of the financial statements included herein, see Index to the Consolidated Financial Statements on page of this Annual Report on Form 10-K, incorporated into this Item by reference.
(2)Financial statement schedules have been omitted because they are either not required or not applicable or the information is included in the consolidated financial statements or the notes thereto.
(3)Exhibits:
Exhibit
Number
Description
2.1
Business Combination Agreement, dated as of August 9, 2021, by and among Environmental Impact Acquisition Corp., Honey Bee Merger Sub, Inc., and GreenLight Biosciences, Inc. (incorporated by reference to Annex A to the Proxy Statement/Prospectus included in the Registration Statement on Form S-4 filed with the Securities and Exchange Commission on January 13, 2022).
3.1
Certificate of Incorporation of GreenLight Biosciences Holdings, PBC (incorporated by reference to Exhibit 3.1 to the Registration Statement on Form S-1 filed with the Securities and Exchange Commission on February 7, 2022).
3.2
Amended and Restated Bylaws of GreenLight Biosciences Holdings, PBC (incorporated by reference to Exhibit 3.2 to the Registration Statement on Form S-1 filed with the Securities and Exchange Commission on February 7, 2022).
4.1
Specimen Warrant Certificate (incorporated by reference to Exhibit 4.3 the Registration Statement on Form S-1 filed with the Securities and Exchange Commission on December 21, 2020).
4.2
Warrant Agreement, dated January 13, 2021, between Environmental Impact Acquisition Corp. and Continental Stock Transfer & Trust Company (incorporated by reference to Exhibit 4.1 to the Current Report on Form 8-K filed with the Securities and Exchange Commission on January 20, 2021).
4.3
Description of the Company’s Securities Registered Pursuant to Section 12 of the Securities Exchange Act of 1934 (incorporated by reference to Exhibit 4.3 to the Registration Statement on Form 10-K filed with the Securities and Exchange Commission on March 31, 2022).
10.1
Commercial Lease, dated April 27, 2009, by and between Cummings Properties, LLC and GreenLight Biosciences Inc., as amended (incorporated by reference to Exhibit 10.18 to the Registration Statement on Form S-4 filed with the Securities and Exchange Commission on September 7, 2021, as amended).
10.2
License and Sponsored Research Agreement, dated April 2010, between Yissum Research Development Company of the Hebrew University of Jerusalem LTD and Beeologics, Inc. (incorporated by reference to Exhibit 10.30 to the Registration Statement on Form S-4 filed with the Securities and Exchange Commission on December 6, 2021).
10.3
Assignment Agreement, dated December 10, 2020, by and between Beeologics, Inc. and GreenLight Biosciences, Inc. (incorporated by reference to Exhibit 10.31 to the Registration Statement on Form S-4 filed with the Securities and Exchange Commission on December 6, 2021).
10.4+
Amended and Restated Employment Agreement dated May 25, 2015, between GreenLight Biosciences, Inc. and Andrey Zarur (incorporated by reference to Exhibit 10.12 to the Registration Statement on Form S-4 filed with the Securities and Exchange Commission on October 19, 2021).
10.5+
Employment Offer Letter, dated July 21, 2015, between GreenLight Biosciences, Inc. and Carole Cobb (incorporated by reference to Exhibit 10.13 to the Registration Statement on Form S-4 filed with the Securities and Exchange Commission on October 19, 2021).
10.6+
Employment Offer Letter, dated April 29, 2019, between GreenLight Biosciences, Inc. and Susan Keefe (incorporated by reference to Exhibit 10.14 to the Registration Statement on Form S-4 filed with the Securities and Exchange Commission on October 19, 2021).
10.7+*
Employment Offer Letter, dated February 7, 2021, between GreenLight Biosciences, Inc. and Amin Khan.
10.8
Grant Agreement, dated July 20, 2020, by and between the Bill & Melinda Gates Foundation and GreenLight Biosciences, Inc. (incorporated by reference to Exhibit 10.21(a) to the Registration Statement on Form S-4 filed with the Securities and Exchange Commission on October 19, 2021).
10.9
Amendment to Grant Agreement, dated July 20, 2020, by and between the Bill & Melinda Gates Foundation and GreenLight Biosciences, Inc. (incorporated by reference to Exhibit 10.21(b) to the Registration Statement on Form S-4 filed with the Securities and Exchange Commission on October 19, 2021).
10.10
Development and Option Agreement, dated August 24, 2020, by and between Acuitas Therapeutics, Inc. and GreenLight Biosciences, Inc. (incorporated by reference to Exhibit 10.22 to the Registration Statement on Form S-4 filed with the Securities and Exchange Commission on October 19, 2021).
10.11
Non-Exclusive License Agreement, dated September 1, 2020, by and between Acuitas Therapeutics, Inc. and GreenLight Biosciences, Inc. (incorporated by reference to Exhibit 10.23 to the Registration Statement on Form S-4 filed with the Securities and Exchange Commission on October 19, 2021).
10.12
Assignment and License Agreement dated December 10, 2020 by and between Bayer CropScience LLP and GreenLight Biosciences, Inc. (incorporated by reference to Exhibit 10.24 to the Registration Statement on Form S-4 filed with the Securities and Exchange Commission on October 19, 2021).
10.13
Master Equipment Financing Agreement, dated March 29, 2021, by and between Trinity Capital Inc. and GreenLight Biosciences, Inc. (incorporated by reference to Exhibit 10.25 to the Registration Statement on Form S-4 filed with the Securities and Exchange Commission on September 7, 2021, as amended).
10.14
Investor Rights Agreement, dated August 9, 2021, by and Among Environmental Impact Acquisition Corp., and the signatories identified on Schedule A attached thereto (incorporated by reference to Annex F to the Proxy Statement/Prospectus included in the Registration Statement on Form S-4 filed with the Securities and Exchange Commission on January 13, 2022).
10.15
Loan and Security Agreement, dated September 22, 2021, by and between Silicon Valley Bank and GreenLight Biosciences, Inc. (incorporated by reference to Exhibit 10.19 to the Registration Statement on Form S-4 filed with the Securities and Exchange Commission on October 19, 2021).
10.16
Warrant to Purchase Shares of Common Stock, dated September 22, 2021, by and between Silicon Valley Bank and GreenLight Biosciences, Inc. (incorporated by reference to Exhibit 10.20 to the Registration Statement on Form S-4 filed with the Securities and Exchange Commission on October 19, 2021).
10.17
Lease Agreement, dated September 30, 2021, by and between ARE-NC Region No. 17 LLC and GreenLight Biosciences, Inc. (incorporated by reference to Exhibit 10.16 to the Registration Statement on Form S-4 filed with the Securities and Exchange Commission on October 19, 2021).
10.18
Master Services Agreement, dated November 24, 2021, between Samsung Biologics Co., LTD. and GreenLight Biosciences, Inc, as amended (incorporated by reference to Exhibit 10.33 to the Registration Statement on Form S-4 filed with the Securities and Exchange Commission on December 6, 2021).
10.19
Product Specific Agreement, dated November 24, 2021, between Samsung Biologics Co., LTD. and GreenLight Biosciences, Inc. (incorporated by reference to Exhibit 10.34 to the Registration Statement on Form S-4 filed with the Securities and Exchange Commission on December 23, 2021).
10.20
Venture Loan and Security Agreement, dated December 10, 2021, between Horizon Technology Finance Corporation, Powerscourt Investments XXV, LP, and GreenLight Biosciences, Inc. (incorporated by reference to Exhibit 10.35 to the Registration Statement on Form S-4 filed with the Securities and Exchange Commission on December 23, 2021).
10.21
Form of 2021 Indemnity Agreement (incorporated by reference to Exhibit 10.6 to the Registration Statement on Form S-1 filed with the Securities and Exchange Commission on December 21, 2020).
10.22
Form of 2022 Indemnification Agreement (incorporated by reference to Exhibit 10.17 to the Registration Statement on Form S-4 filed with the Securities and Exchange Commission on January 10, 2022).
10.23+
GreenLight Biosciences Holdings, PBC 2022 Equity and Incentive Plan (incorporated by reference to Exhibit 99.1 to the Registration Statement on Form S-8 filed with the Securities and Exchange Commission on April 12, 2022).
10.24+
GreenLight Biosciences Holdings, PBC 2022 Employee Stock Purchase Plan (incorporated by reference to Exhibit 99.2 to the Registration Statement on Form S-8 filed with the Securities and Exchange Commission on April 12, 2022).
10.25+
Form of Nonstatutory Stock Option Agreement under the GreenLight Biosciences Holdings, PBC 2022 Equity and Incentive Plan (incorporated by reference to Exhibit 10.7 to the Registration Statement on Form S-4 filed with the Securities and Exchange Commission on December 23, 2021).
10.26+
Form of Incentive Stock Option Agreement under the GreenLight Biosciences Holdings, PBC 2022 Equity and Incentive Plan (incorporated by reference to Exhibit 10.8 to the Registration Statement on Form S-4 filed with the Securities and Exchange Commission on December 23, 2021).
10.27+
Form of Restricted Stock Unit Agreement under the GreenLight Biosciences Holdings, PBC 2022 Equity Incentive Plan (incorporated by reference to Exhibit 10.9 to the Registration Statement on Form S-4 filed with the Securities and Exchange Commission on December 23, 2021).
10.28+
Form of Restricted Stock Award Agreement under the GreenLight Biosciences Holdings, PBC 2022 Equity Incentive Plan (incorporated by reference to Exhibit 10.10 to the Registration Statement on Form S-4 filed with the Securities and Exchange Commission on December 23, 2021).
10.29
License Agreement, dated March 10, 2022, between GreenLight Biosciences, Inc. and Serum Institute of India Private Limited (incorporated by reference to Exhibit 10.32 to Post-Effective Amendment No. 1 to Form S-1 Registration Statement filed with the Securities and Exchange Commission on April 5, 2022).
10.30*
Lease Agreement, dated March 9, 2022 between ARE-MA Region No.8, LLC GreenLight Biosciences, Inc.
10.31*
Collaboration and License Agreement, by and between the Company and EpiVax Therapeutics, Inc., dated January 8, 2023
21.1*
List of Subsidiaries
23.1
Consent of Deloitte & Touche LLP
24.1
Power of Attorney (included on the signature page to the Annual Report)
31.1*
Certification of Principal Executive Officer Pursuant to Rules 13a-14(a) and 15d-14(a) under the Securities Exchange Act of 1934, as Adopted Pursuant to Section 302 of the Sarbanes-Oxley Act of 2002.
31.2*
Certification of Principal Financial Officer Pursuant to Rules 13a-14(a) and 15d-14(a) under the Securities Exchange Act of 1934, as Adopted Pursuant to Section 302 of the Sarbanes-Oxley Act of 2002.
32.1*
Certification of Principal Executive Officer and Principal Financial Officer Pursuant to 18 U.S.C. Section 1350, as Adopted Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002.
101.INS
Inline XBRL Instance Document - the instance document does not appear in the Interactive Data File because XBRL tags are embedded within the Inline XBRL document.
101.SCH
Inline XBRL Taxonomy Extension Schema Document
101.CAL
Inline XBRL Taxonomy Extension Calculation Linkbase Document
101.DEF
Inline XBRL Taxonomy Extension Definition Linkbase Document
101.LAB
Inline XBRL Taxonomy Extension Label Linkbase Document
101.PRE
Inline XBRL Taxonomy Extension Presentation Linkbase Document
Cover Page Interactive Data File (embedded within the Inline XBRL document)
* Filed herewith.
+ Indicates management contract or compensatory plan.
 Certain identified information has been excluded from this exhibit because either (a) the information is both not material and the type of information that the Registrant treats as private or confidential or (b) disclosure of such information would constitute a clearly unwarranted invasion of personal privacy.