Eugene Consulting Inc.
408-25 Montgomery Ave
Toronto, ONM4R 0A1

August/September 2021 Reportfffffff- Erasca Inc. is a clinical-stage precision oncology company that focuses on discovering,developing, and commercializing therapies for patients with RAS/MAPK pathway-driven
cancers- They have now been named one of the industry’s most promising biotechnology
companies- In September, Erasca announced a clinical trial collaboration and supply agreement with
P izer Inc. for the BRAF inhibitor encorafenib (BRAFTOVI®)- This agreement will support a clinical proof-of-concept study evaluating ERAS-007,and oral ERK1/2 inhibitor, in combination with encorafenib and the EGFR inhibitor
cetuximab for the treatment of patients with BRAF V600E-mutant mCRC
- This combination of encorafenib and cetuximab was approved in April 2020
for previously treated patients with BRAF V600E-mutant mCRC
- The combination demonstrated improved overall survival compared to thechemotherapy control arm- This combination will be investigated as part of the Phase 1b/2 HERKULES-3 trial
expected to initiate in the second half of 2021
- Erasca will sponsor the study and P izer will supply encorafenib- The two companies will then form a Joint Development Committee to review theclinical trial results- Later in the month, the company announced dosing of the irst patient in theHERKULES-2 Phase 1b/2 trial evaluating ERAS-007 in combination with various agents inpatients with advanced non-small cell lung cancer- HERKULES-2 is a master protocol designed to inhibit multiple oncogenic drivers ofthe RAS/MAPK pathway to address high unmet needs in lung cancer- The focus will irst be on patients with mutant EGFR or KRAS NSCLC- HERKULES-2 will initially examine the safety, tolerability, and preliminary ef icacyof ERAS-007 in combination with osimertinib (TAGRISSO®) in patients withadvanced NSCLC harboring an epidermal growth factor receptor mutation (EGFRm)- At the end of the month they announced dosing of the irst patient in HERKULES-3, aPhase 1b/2 master protocol clinical trial evaluating ERAS-007 in combination withvarious agents in patients with gastrointestinal cancer, with initial focus on patients withadvanced colorectal cancer- The initial focus is on CRC subtypes with BRAF V600E, KRAS, or NRAS mutations- HERKULES-3 will examine the safety, tolerability, and preliminary ef icacy ofERAS-007 in combination with other cancer therapies in study participants with GImalignancies

Eugene Consulting Inc.
408-25 Montgomery Ave
Toronto, ON
M4R 0A1- The dose escalation portions of the irst two sub-studies will assess ERAS-007 incombination with the current standard of care, encorafenib (Braftovi®) andcetuximab (Erbitux®), in patients with BRAF V600E-mutant mCRC, and ERAS-007
in combination with the CDK4/6 inhibitor palbociclib (Ibrance®) in patients withKRAS- or NRAS-mutant mCRC
- The Phase 2 dose expansion portion will further evaluate the safety and ef icacy ofeach combination at the recommended dose identi ied in patients with previously
treated mCRC
- Future sub-studies of HERKULES-3 will explore ERAS-007 in combination withother agents in patients with different mutational subtypes of GI cancers.
Amazon and Healthcare- In July 2021, Amazon launched Dx, a service that offers at-home testing for COVID-19- Consumers order a kit off amazon.com and send it back for testing and results
within 24 hours- Amazon is looking to expand its medical diagnostics operations on a global scale- The company’s aspirations are evident in their recent job postings - ex. A position
for a medical regulatory of icer to be based in Seattle where the headquarters arebased- The medical regulatory of icer would work with developers of new diagnostic
tests or processes and serve as the sole contact with key regulators, building
relationships with agencies- They would also build a team to monitor changes in local, state, and federal/national regulations, and manage the team to drive revised or new processchanges to maintain regulatory complianceffffffAmazon Care
https://amazon.care- Amazon stated that they have attracted multiple companies that are interested in using
its telehealth service, Amazon Care
- One of which is Precor - a Washington-based itness equipment company that wasacquired by Peloton- The service started as a pilot program for employees in and around the Seattle area andprovides virtual urgent care list and free telehealth consults and in-home visits frommedical professionals- Other services Amazon Care offers:- In-app text chat with clinicians- Prescription delivery from a care courier- In March, the company announced that it would expand the virtual care part of theprogram nationally for its employees and other companies starting this summer- Their plan is to expand its services to more than 20 major U.S. cities this year and in2022

Eugene Consulting Inc.
408-25 Montgomery AveToronto, ON
M4R 0A1- To start, the added in-person services will only be offered in Washington state and metro
areas including Baltimore and Washington, D.C.
- The company’s vision is to make the full Amazon Care service abatable to other parts ofthe country, including rural areas- Thousands of employees will need to be hired to reach this scale
Amazon invests millions in a pre-revenue company with a system for measuring
human proteins - Aug. 5, 2021
https://www.cnbc.com/2021/08/05/amazon-invested-millions-in-nautilusbiotechnology.html- Amazon has invested millions in a pre-revenue biotechnology company, Nautilus
Biotechnology, that went public after merging wit ha special-purpose acquisition
company in early June
- This move its Amazon’s efforts to build a presence in health care:- They now operate an online pharmacy called Amazon Pharmacy, following the $753
million acquisition of start-up PillPack in 2018
- Last year, they partnered with employee health provider Crossover Health to launchneighbourhood health clinics for warehouse workers and their families in a handfulof cities a- They have a telehealth service called Amazon Care which was launched in 2019 as apilot program for employees- Nautilus has built a prototype for a device that can measure the human proteome, whichis constantly changing based on food consumption and other factors- Organizations could use Nautilus’ system for drug discovery, as well as clinical diagnostics
and precision medicine- Studying the proteome could also help researchers ind treatments for people whoend up with severe lung damage after contracting COVID-19- In 2020, Genetech agreed to use Nautilus’ system- Jeff Bezos’ venture-capital irm, Bezos Expeditions, also invested in Nautilus as wellfffNautilus
https://www.nautilus.bio- Nautilus’ vision is to bring to market a complete, end-to-end, massive-scale protein
analysis platform- Their hope is that in the same way that democratizing access to the genome was acatalyst for the development of a broad and vibrant genomes ecosystem, theNautilus’ proteomics innovation will unlock high-value applications in precisionand personalized medicine, drug discovery, and diagnostics- The Nautilus Proteomic Analysis Platform leverages a nano fabricated, large-scale, singlemolecule protein array, multi-cycle imaging, and machine learning analysis to potentially
identify and quantity the proteome with extreme sensitivity and scaleEugene Consulting Inc.
408-25 Montgomery Ave
Toronto, ONM4R 0A1- First, individual, intact protein molecules are immobilized via conjugation toproprietary scaffolds for deposition onto an array with billions of landing pads
- Next, multi-cycle imaging allows repetitive, non-destructive probing of individual
proteins with unique binding reagents- The results are digitized and analyzed to decode the proteome, potentially enabling
quantitative analysis at unprecedented scale over an exceptionally large dynamic
range- Isolated protein from blood, tissue, or cells is bound to a proprietary scaffold for singlemolecule, single-protein deposition onto one of the 10 billion landing pads found on theNautilus array- The array’s hyper-dense surface is designed with the goal of allowing identi icationand quanti ication of millions of individual protein molecules simultaneously

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- The protein array is loaded onto the platform where luorescent af inity-probes low over
the array to bind short, de ined protein motifs and binding events are measured

Eugene Consulting Inc.
408-25 Montgomery Ave
Toronto, ONM4R 0A1- Since samples are not degraded, they can be washed and probed repeatedly with a varietyof unique af inity-probes, each designed to target speci ic motifs on multiple proteins- Every new cycle provides unique information and increases the resolution of individual
protein identity- Using this approach, the platform aims to sensitively measure tens of billions of molecules
across hundreds of cycles in a day- Their machine-learning analysis software is designed with the goal of converting binding
information to protein identi ies and quantities- The binding results from each cycle are digitized and the Nautilus software is used todecode the binding sequence into broad-scale proteomics information- As the database grows, the systems’ ability to decode the proteome will continually
improvefff- Second Quarter 2021 Financial Results- Operating expenses were $10.7 million- 215% increased from $3.4 million in June 2020 - increase in operating
expenses mainly due to increase in headcount to support ongoingdevelopment of products and for costs associated with being a publiccompany- Net loss was %10.7 million- Compared to a net loss of $3.4 million for the corresponding prior year period- Cash, cash equivalents and investments: $338.4 million as of June 30, 2021
- In June, Nautilus completed a business combination transaction with ARYA Sciences
Acquisition Corp III and became a publicly traded company- Gross proceeds from this transaction totalled approximately $345.5 million

Eugene Consulting Inc.
408-25 Montgomery Ave
Toronto, ONM4R 0A1

Pandemic driving capital into the biotechnology sector- Increased interest in the novel technology during the pandemic has driven a lot of capital
into the biotechnology sector- This has fuelled record inancings and IPOs
- The iShares Biotechnology ETF, which tracks the biotech industry’s biggest players
has surged roughly 62% over the last 2 years- This beat the performance of the S&P 500, which has jumped by about 47% overthe same time period
BBV154 by Bharat Biotech
https://www.bharatbiotech.com/intranasal-vaccine.html- Indian vaccine maker Bharat Biotech’s nasal COVID-10 vaccine candidate, BBV154, hasreceived regulatory approval to conduct a Phase II clinical trial- BBV154 is a novel adenovirus vectored, intranasal vaccine for COVID-19

f- The intranasal vaccine stimulates a broad immune response - neutralizing IgG,
mucosal IgA, and T cell responses- The idea is that the nasal route has excellent potential for vaccination due to theorganized immune systems of the nasal mucosa and immune responses in the nasal
mucosa is essential for blocking both infection and transmission of COVID-19- The vaccine increases the ease of administration as it does not require trained
health care workers- They also believe they are able to meet global demands with scalable
manufacturingEugene Consulting Inc.
408-25 Montgomery Ave
Toronto, ON
M4R 0A1

f-The
vaccine candidate has been completed in subjects aged 18 to 60 years and the doses were
found to be well tolerated- Mice, hamsters, and macaques that were immunized with a single dose of thevaccine candidate demonstrated superior protection against SARS-CoV-2 challenge
and post challenge, viral clearance was observed in both lower and upper airways
in all animal models- The company also has COVAXIN, an injectable COVID-19 vaccine that has already been
approved for emergency use approval in India- The vaccine was developed in collaboration with the Indian Council of Medical
Research (ICMR) - National Institute of Virology (NIV)- The vaccine is developed using Whole-Vision Inactivated Vero Cell derived platform
technology- Inactivated vaccines do not replicate and are therefore unlikely to revert andcause pathological effects- They contain dead virus, incapable of infecting people but still able to instruct
the immune system to mount a defensive reaction against an infection- Conventionally, inactivated vaccines have been around for decades andnumerous vaccines for diseases such as Seasonal In luenza- COVAXIN® is included along with immune-potentiators, also knows as vaccine
adjuvants, which are added to the vaccine to increase and boost its immunogenicity- It is a 2-dose vaccination regime given 28 days apart- No sub-zero storage is required - it is stable at 2-8˚C

Eugene Consulting Inc.
408-25 Montgomery AveToronto, ONM4R 0A1fffff- Pre-clinical studies demonstrated strong immunogenicity and protective ef icacy inanimal challenge studies conducted in hamsters and non-human primates- The vaccine received DCGI approval for Phase I and II Human Clinical Trials in July
2020
- COVAXIN® demonstrated 77.8% vaccine ef icacy against symptomatic COVID-19
disease, through evaluation of 130 con irmed cases, with 24 observed in the vaccine
group vs. 106 in the placebo group- The ef icacy against severe symptomatic COVID-19 disease is shown to be 93.4%- The ef icacy data demonstrates 63.6% protection against asymptomatic COVID-19- Safety analysis demonstrates adverse events reported were similar to placebo, with
12% of subjects experiencing commonly known side effects and less than 0.5% ofsubjects feeling serious adverse events.