Report on Debiopharm Group
About the Company• https://www.debiopharm.com• A Swiss-headquartered global biopharmaceutical group which includes 5 companies thatare active in the life science areas of drug development, GMP manufacturing ofproprietary drugs, diagnostic tools and investment management• Family-owned business• Sole Proprietorship• Besides drug development, Debiopharm has recently developed in-house skills in theield of companion diagnostics• Debiopharm Group independently funds the worldwide development of all of its products
while providing expertise in all areas• The company was founded in 1979 by Dr Rolland-Yves Mauvernay• Total revenue: about $25 billion USD• Subsidiaries:• Debiopharm International SA - searches, evaluates and in-licenses candidates ortechnologies, develops them, and then licenses them to 3rd parties for for worldwide marketing and sales• Debiopharm Research and Manufacturing SA - pharmaceutical research,development and production facility, inspected and registered with the main
regulatory authorities.
• Provides contract manufacturing and contract research services to
Debiopharm• Debiopharm Investment SA - manages group’s money and invests in real estateand in other companies• Their main objectives is the preservation of capital of Debiopharm Group, andthe generation of regular inancial incomes for Debiopharm Group's
companies• Debiopharm Innovation Fund SA (formerly knowns as Debiopharm Diagnostics the strategic investment fund of the Debiopharm Group• Company size: About 400 employees• They have 2 completed the development and licensed out 2 compounds:
1. Oxalipatin - for the treatment of cancer
2. Depot formulations of triptorelin - a gonadotropin-releasing hormone agonist
that is approved to treat advanced prostate cancer• In 2017, Debiopharm acquired a phase 2 drug candidate from ImmunoGen that intends totarget Non-Hodgkin lymphomaffEugene Consulting Inc.
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Eugene Consulting Inc.
1602- 111 St. Clair Ave W
Toronto, ON
M4V 1N5Awards and Grants

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• The JCA-Mauvernay Award• Launched in 2005, the Japanese Cancer Association (JCA) and Debiopharm Group
have co-organized the JCA-Mauvernay Award• The award has a total value of CHF 25000 and it aims at recognizing outstandingachievements in the ield of oncology amongst Japanese researchers, in both thefundamental and clinical aspects• The Debiopharm-Inartis Challenge• Co-created by the Inartis Foundation and Debiopharm Group• This aims to encourage innovation in the health sector by rewarding projects
intended to improve patient comfort and quality of life
• Goal = speed up the implementation and/or commercialization of successful entries• The Challenge has a total lvalue of CHF75,000, of which 25,000 will go to the chosen
project• Innovation Debiopharm Academica Leman (IDEAL)• Partnering with lemanic institutions• The Lemanic region has a rich ecosystem of scienti ic, academic andpharmaceutical organizations that focus on new breakthrough therapies forcancer patients• Through IDEAL, Debiopharm is aiming to accelerate the translation of scienti ic
discoveries of the Lemanic region into new anti-cancer and anti-infective
treatments with global reach• The initiative allows Debiopharm to establish pre-agreed collaborations withacademic and medical institutions to enable researchers to mature and tailor earlystage innovations in the ield of oncology and antibiotics, with the inancial supportof Debiopharm, up to a stage where promising programs could be in-licensed forfurther development• Those who have an early-stage oncology of anti-infective compound can send
their project proposals for reviews by their Steering Committee• If the project is selected for IDEAL funding, a research and development planis de ined
• At the end of the project, partners are asked to send a inal report of theirresearch and results for evaluation and if they are to advance to become a
Debiopaharm development program, they enter into negotiation for apartnership through license or research collaboration• Current partners:• Universit de Gen ve - involved in most cutting-edge sectors and active ininterdisciplinary research• Institut des Sciences pharmaceutiques de Suisse occidentale - conducts
research to discover new therapeutic agents and develop novel formulationand delivery strategies

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The Company’s Social Responsibilities• Dialogue G n rations - an association created by Debiopharm to foster knowledge andnew ideas• They are supporters of L pac’s project of ‘Novel Atlas des Future du Monde 2038’ - ananalysis of humanity’s future societies, lifestyles, needs and aspirations
Philanthropic project
1. Foundation T l thon Action Suisse - Debiopharm has been a supported since 2014
• https://telethon.ch/
2. Kantuta Association - Debiopharm has been involved with the Kantuta Association whichis active with street children in Bolivia since its creation in 200• http://www.association-kantuta.org/?ln=en
3. Les Pinceaus Magiques - Debiopharm supports an organization which gives hope tohospitalized children• https://www.pinceauxmagiques.ch/
4. Prix George Math - They are supported of the Prix George Math , which promotes
therapeutic advances and translational research in medical oncology and immunotherapy• This prize was established in 2010 and in organized each year by the Institut duCancer et d’Immunog n tique (ICIG)
Chair• Debiopharm supports the creation of the ‘Debiopharm Chair for Family Philanthropy’ at
IMD business school in Lausanne with a donation of several million Swiss francs over the
next 15 years

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Entrepreneurship• Debiopharm has a stake in Polutech Ventures - a seed fund that offers early stage
investment to technology companies in Western Switzerland• https://polytechventures.ch/• Debiopharm support the National Pre-Seed Fund venture kick, which contributes to thedevelopment of high potential business ideas at Switzerland’s institutes of higher
learning and universities• https://www.venturekick.ch/index.cfm?
page=119286&c id=189324746&cftoken=13287858• Debiopharm supports FIT (Foundation pour l’Innovation Technologique), which assists
innovative technological projects in link with one of the universities of the French
speaking part of Switzerland• https://fondation- it.ch/Eugene Consulting Inc.
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Clinical trials• When screening, extensive medical examinations are conducted to con irm whether
someone can participate in the clinical trial• Participants are continuously monitored during and after the trail to measureeffectiveness and ensure there are no long-term side-effects

Drug Development• Debiopharm identi ies high potential compounds for inlicensing• They look for promising oncology and antibacterial
compounds to transform them into valuable treatments• They also conduct clinical development and select large
pharmaceutical commercialization partners to maximize
patient access across the globe• Debiopharm partners with universities, biotech, and big
Pharma• Their main areas are in oncology and bacterial infections

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Commercialized Products
1) Oxaliplatin - a diaminocyclohexane (DACH) platin• The active substance of the branded Eloxatin®/Elplat®/Dacotin®/Dacplat• Oxaliplatin is a worldwide standard treatment in metastatic and adjuvant colorectal
cancer as well as metastatic and adjuvant pancreatic cancer• It is also used to treat liver cancer in China• Product Characteristics• 3 dosages: 50 mg - 100mg - 200mg• IV infusion• Freeze-dried and solution formulations• Commercial partners:• Sano i, Yakult, Dr. Reddy’s Laboratories, P izer
• In March 2015, Yakult Honsha announced the approval of Elplat® (oxaliplatin) for
patients with unresectable advanced or recurrent gastric cancer• In March 2017, Debiopharm International appealed to the Supreme Court of Japanagainst the decision from the Grand Panel of the IP High Court, according to which thegeneric product of Elplat® commercialized by Towa Pharmaceuticals Co. Ltd have notinfringed the Japanese patent JP 3547755, which is owned by Debiopharm andexclusively licensed to Yakult Honsha Co. Ltd in Japan• A similar appeal was iled before the Supreme Court of Japan against the decision form
the IP High Court, according to which the generic product of Elplat® commercialized by
Nippon Kayaku Co., Ltf. have not infringed the Japanese patent JP 4430229, which isowned by Debiopharm and exclusively licensed to Yakult Honsha Co. Ltd in JapanEugene Consulting Inc.
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M4V 1N5• Debiopharm stated that they will continue to take legal actions against any activity
that infringes the intellectual property rights owned by Debiopharm and exclusively
licensed to Yakult• In August of 2018. Prof Thierry Control, medical oncologist and Director of the Institut deCancerologie de Lorraine presented at ASCO 2018 the results of phase II study tocompare adjuvant chemotherapy with gemcitabine versus mFol irinox in patients withresected pancreatic adenocarcinomas• mFol irinox is a modi ied regimen containing Debiopharm’s Oxaliplatin, combinedwith irinotecan, luorouracil and leucovorin• Results showed a signi icant improvement of the OS and disease-free survival

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2) Triptorelin - a gonadotropin releasing hormone (GnRH) agonist• The active substance of Decapeptyl®/Trelstar®/
Triptodur®1, 3 and 6-month formulation and Moapar®/Salcacyl®
• Triptorelin decreases the serum testosterone to castratelevels (estradiol in females)• Andorgen deprivation stops the growth of the androgen
dependent prostate cancer, alleviating pain and improving
the quality of life of patients• GnRH agonist treatment achieves similar overall survival
rates in advanced prostate cancer as surgical castration• Indications:Eugene Consulting Inc.
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M4V 1N5• Advanced prostate cancer• Endometriosis• In-vitro fertilization programs• Uterine ibroids• Precocious puberty• Product characteristics:• 3 dosages, 1 month (3.75mg), 3 month (11.2 mg), and 6 months (22.5mg)• Commercialization partners:• Ach Laborat rios Farmac uticos SA• Verity Pharmaceuticals Inc.
• Arbor Pharmaceuticals• Dr. Reddy’s Laboratories• Ferring International Center• Ipsen Pharma• Orient Europharma• Tecnofarma International• Unilab• Debiopharm• Knight Therapeutics Inc.

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• In May 2015, it was presented at PAS 2015 San Diego that Triptorelin 6-monthformulations show good ef icacy and safety in patients with central precocious puberty• https://www.debiopharm.com/wp-content/uploads/2018/08/2015-CPP.pdf

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f• Following this, in January 2016, Debiopharm International SA and Arbor
Pharmaceuticals, LLC announced their US commercialization partnership for Triptorelinin Central Precocious Puberty• This gave Arbor exclusive commercial rights for triptorelin 22.5mg in the U.S for the
CPP indicator• The product will be exported from Debiopharm Research and Manufacturing SA to
Arbor• In January 2017, Debiopharm Group’s Triptorelin 6-month formulation received approval
for the treatment of central precocious puberty in 22 European countries• The 6 month formulation was already registered for the treatment of prostatecancer• Developed by Debiopharm, the product is manufactured in Switzerland by
Debiopharm Research & Manufacturing SA and licensed for distribution under
exclusive rights to Ipsen for Europe and other parts of the world.
• In June 2017, the FDA approved Triptodur for the treatment of paediatric patients 2 years
and older with CPP• Triptodur™, a gonadotropin-releasing hormone (GnRH) agonist administeredthrough intramuscular injection (IM), is the irst GnRH agonist to offer once-every
six-month dosing approved for the treatment of CPP in the U.S.
• In a phase III clinical trial, Triptodur™ demonstrated a return to pre-pubertal
luteinizing hormone (LH) levels in 93 percent of patients, with pre-pubertal LH
suppression maintained at 12 months by 98 percent of patients• The most common adverse reactions in clinical studies were injection site reactions,
menstrual (vaginal) bleeding, hot lush, headache, cough, and infections (bronchitis,
gastroenteritis, in luenza, nasopharyngitis, otitis externa, pharyngitis, sinusitis, andupper respiratory tract infection• In October 2019, Triptodur became commercially available in the U.S for the treatment of
paediatric patients 2 years and older diagnosed with CPP• In June 2019, Debiopharm and Ipsen Extended their strategic Decapeptyl® (Triptorelin)partnership for another 15 years through 2034
• This extends and strengthens their strategic partnership for the development,
manufacturing and distribution of Decapeptyl® across Europe and certain Asianand African markets• Their collaboration was established in the 1980s• Under the renewed agreement, both parties will co-develop novel formulations andexplore additional indications for other patient populations with high unmet needs• In January 2020, Debiopharm and Knight Therapeutics enter into an exclusive agreementthat grants Knight the right to commercialize Trelstar® (Triptorelin) in Canda• Knight took over commercial activities from Allergan• In June 2020, Debiopharm and Verity Pharmaceuticals enter into an exclusive agreementthat grants Verity Pharmaceuticals the right to commercialize Trelstar® (Triptorelin) forthe palliative treatment of prostate cancer in the U.S

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Xevinapan• A potent, orally available, inhibitor of IAPs (Inhibitor of Apoptosis Proteins)• This class of products is particularly suited to be combined with widely used but often
sub-optimal chemo- and radiotherapy (CRT)• Xevinapant established proof of ef icacy in high-risk locally advanced squamous cell
carcinoma of the head and neck (LASCCHN) patients for which the combination provided
highly signi icant and sustainable clinical bene it as compared to CRT alone• Xevinapant is currently being investigated in the pivotal Phase III TrilynX study forpreviously untreated high-risk locally advanced squamous cell carcinoma of the head andneck (LA SCCHN), in combination with platinum-based chemotherapy and standard
fractionation intensity-modulated radiotherapy• 3-year follow-up results from the Phase II trial in high-risk LA-SCCHN patients revealed
signi icant improvement in overall survival, progression free survival and duration of
response with Debio 1143 in combination with CRT vs. CRT alone• In February 2020, the FDA granted Breakthrough Therapy Designation to xevinapant for
front-line treatment of Head & Neck Cancer• Xevinapant (Debio 1143) is being investigated in a phase I in combination withavelumab*, a human anti-PD-L1 IgG1 monoclonal antibody, in patients with advanced
solid tumors including non-small cell lung cancer (NSCLC)• The trial is being conducted under a clinical collaboration agreement between
Debiopharm International SA and the Merck-P izer Alliance• SMARTPLUS-106 is an exploratory study investigating the safety and ef icacy of
xevinapant (Debio 1143) in combination with the Immune Checkpoint Inhibitor (ICI),
nivolumab, in patients with advanced solid tumors, such as small cell lung cancer (SCLC)
or squamous cell carcinoma of the head & neck (SCCHN), who have progressed during or
immediately after anti-PD-1/PD-L1 treatment• CATRIPCA is a Phase I study initiated by Dr. Phillippe Cassier, combining xevinapant(Debio 1143) with Merck Sharpe & Dohme’s (MSD) anti-PD1 Keytruda®
(pembrolizumab).
• The study focuses on two cancer patient populations with conditions that are
intrinsically resistant to Immune Checkpoint Inhibitors (ICI)• The trial will recruit patients without other available therapeutic options in Nonmicrosatellite instability (non-MSI)-high colorectal cancer (CRC) and pancreatic
ductal adenocarcinoma cancer (PDAC)• The safety and preliminary ef icacy of the combination will be assessed with theprimary endpoint of the study extension being the Objective Response rate
• On March 21, 2021 Debiopharm announced an exclusive license agreement with Merck,
for the development and commercialization of xevinapant (Debio1143) worldwide

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Naratuximab emtansine (Debio 1562)• An antibody-drug conjugate targeting CD37

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M4V 1N5• The naratuximab emtansine ADC binds with high af inity and speci icity to CD37,
obstructing cell proliferation pathways while allowing internalization, processing,and intracellular release of the DM1 payload• As a result of its ability to disrupt microtubule assembly, DM1 subsequently
induces cell cycle arrest and apoptosis.
• A potential new treatment for patients with B-cell malignancies, such as non-Hodgkin’s
lymphomas (NHL)• Demonstrated evidence of anti-cancer activity in NHL in a Phase 1 monotherapy
trial and successfully completed a safety lead-in study in combination withrituximab• Phase II data has shown promise for the treatment of non-Hodgkin’s lymphoma• The response rate was 31.6% in all patients with diffuse large B cell
lymphoma and 32% in patients with more than 2 prior therapies• 8% of patients stopped treatment due to side effects• The product is currently in phase IIb in relapsed/refractory diffuse large-cell B-cell
lymphoma (R/R DLBCL) for which it bene its from Orphan Drug status• Debiopharm is currently investigating naratuximab emtansine in a phase II, open-label
study to establish the safety and ef icacy pro ile of this CD37 ADC in combination with
CD20 targeting rituximab in patients with R/R DLBCL and other forms of NHL• Naratuximab emtansine targets the CD37 antigen to release a toxic DM1 payload• On June 14, 2021, the company announced that naratuximab emtansine coadministered with rituximab revealed meaningful ef icacy and high complete
response rates (CRR), especially in heavily pre-treated patients with ≥2 prior linesof treatment• The safety pro ile was predictable and manageable, with a low rate of treatment
discontinuation due to adverse events (8%) and low incidence of serious febrileneutropenia (4%).
• Results were particularly impressive for heavily pre-treated DLBCL patients forwhom options are remain limited• The high response rates and durability combined with the manageable safety
pro ile offer a strong rationale for further research of naratuximab emtansine in Bcell malignancies.
• It has also shown promising signs of ef icacy in Marginal Zone Lymphoma and Follicular
Lymphoma and has potential in Acute Myeloid Leukemia.

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Debio 1124 - Clinical stage Radio-conjugate• Debio 1124 is a radioconjugated minigastrin analogue designed to target theCholeCystoKinin 2 Receptor (CCK2R) expressed in certain tumors• Debio 1124 belongs to the emerging class of Peptide Receptor Radionuclide Therapies(PRRT) which selectively delivers radiotherapy to cells expressing CCK2R• With Debio 1124, the speci ic receptor-binding property of gastrin peptides is
exploited by using them as carriers to guide the radioactivity to the tumors that
express their speci ic receptors

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M4V 1N5• Debio 1124 has been formulated to transport radiotherapy speci ically to cells
harbouring CCK2R receptors, in order to reduce the toxicity burden observed withsystemic radiation• When the compound binds to tumor cell surfaces expressing CCK2R, theradionuclide is released to destroy the cells’ DNA and thereby inducing cell death.
• The product is being developed in Medullary Thyroid Cancer (MTC) and is also being
studied in Small Cell Lung Cancer (SCLC)• The compound can also be used as a sensitive diagnostic tool, therefore, an initial imaging
step allows the selection of patients whose tumor expresses the target receptor and soare expected to bene it from this innovative treatment• In August 2020, a multicenter, single-arm, open-label Phase 1 study was initiated toassess the safety, distribution, and dosing of Debio 1124 in patients with advanced,
unresectable pulmonary and extrapulmonary small cell carcinoma.
Debio 0123
• Debio 0123 is a Wee1 kinase inhibitor currently in phase I research in refractory solid
tumors• Inhibition of WEE1 prevents cells to arrest to repair DNA damages and force thento prematurely continue through the cell cycle, therefore accumulating unrepaired
DNA damages ultimately leading to cell death• Asc• Pre-clinical models have shown anti-tumor activity both as a single agent and incombination with carboplatin• The primary objective of the Phase 1, irst-in-human, study (NCT03968653) is todetermine the recommended phase 2 dose of Debio 0123 in combination withcarboplatin in participants with advanced solid tumors that have recurred or progressedfollowing prior platinum based therapy
Debio 0228 - Currently in Lead Optimization stage• The Debio 0228 program is set to identify a Development Candidate with best-in-classpotential, designed to selectively destroy tumor cells that express the CAIX target• The selected compound will be developed using a theranostic approach, a combination ofdiagnostic and therapeutic features with the same compound, allowing the preidenti ication of patients who have the receptors necessary to respond to the targetedradiotherapy

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Debio 4028
• This program leverages the immunomodulatory, pro-apoptotic of a new generation ofpotent, Inhibitor of Apoptosis Proteins (IAP) antagonists to treat various types of cancer.

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Afabicin (Debio1450• A fabiotics, that inhibits fatty acid synthesis in staphylococci by targeting the Fabl enzyme• The FabI enzyme is essential for bacterial growth and survival and it is highly
conserved across all staphylococcal species

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M4V 1N5• By inhibiting FabI, Fabiotics represent a novel antibacterial class that has thepotential to address challenges of bacterial resistance• Afabicin speci ically targets staphylococci while preserving intestinal microbiota• A phase II study was conducted in patients with staphylococcal Acute Bacterial Skin andSkin Structure Infections (ABSSSI) demonstrating the ef icacy and safety with the twodoses tested vs. active comparator vancomycin / oral linezolid• Treatment with Debio 1450 at both doses was safe and well tolerated.
• The compound in both oral and intravenous formulations currently is in phase II research
for the treatment of Bone and Joint infections (BJI) due to staphylococci• It is also being researched in staphylococcal acute bacterial skin and skin structure
infections (ABSSSI)
Debio 1561
• Debio 1561 FibroTrap is a unique sample preparation technology for the concentration ofbacteria and other microorganisms in blood samples of patients with bloodstream
infections• The technology will enable faster identi ication and diagnosis of pathogens directly frompatient samples and will promote an accelerated selection of more appropriate
antibiotics to improve treatment outcomes
Alisporivir - Debio 025• A class of drugs called cyclophilin inhibitors• Alisporivir was irst thoroughly investigated for its antiviral properties in hepatitis C andHIV patients• Pre-clinical in vitro research from the Mondor Institute of Biomedical Research (INSERM
U955) has shown evidence for the effectiveness of alisporivir against the replication of
SARS-COV-2 (COVID-19)• Alisporivir is currently tested in a phase II study conducted in France by the AP-HP(Greater Paris University Hospitals) to assess the ef icacy and safety of the compound
Debio 1453
• A FabI inhibitor speci ically targeting N. gonorrhoeae developed in collaboration with
Nobelex• Belongs to a family of narrow-spectrum antiobiotics that combines a very potent activity
on pathogens of interest while reducing the selective pressure on other bacterial strains
and sparing the microbiome

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Debio 1454/S• A FabI inhibitor targeting a combination of enteric bacteria species - A. baumannii,
Enterobacter Spp., Klebsiella pneumoniae and E.coli.
• Belongs to a family of narrow-spectrum antiobiotics that combines a very potent activity
on pathogens of interest while reducing the selective pressure on other bacterial strains
and sparing the microbiome

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Debio 1454M - Currently in drug candidate identi ication stage• The Debio 1454M program includes novel microbiome therapeutics for the treatment ofgastrointestinal (GI) disorders.
• The program aims to identify effective treatment against in lammatory bowel
disease (IBD) and other GI disorders• In June 2020, Debiopharm announced an exclusive license agreement and researchcollaboration with Takeda Pharmaceutical Company Limited (Takeda) to develop novel
microbiome therapeutics for the treatment of gastrointestinal disorders• Under the agreement, Takeda will screen and optimize compounds derived from
Debiopharm’s discovery Debio 145M program to identify candidates for further
development for the treatment of in lammatory bowel disease (IBD) and other GI
disordersRecent Scienti ic Publications

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• June 12, 2021 - A phase 2 study on the safety and ef icacy of CD37- Targeting
Naratuximab Emtansine plus Rituximab in diffuse large B-cell lymphoma and other nonhadgkin’s B-cell lymphomas was presented at EHA 2021
• https://www.debiopharm.com/wp-content/uploads/2021/06/2021-Debiopharmnaratuximab-emtansine-PhaseII-EHA-compresse.pdf• In March of 2021, Debiopharm published ani interview with 2 key opinion leadersregarding CD37-trageted therapy as a viable alternative in the treatment of diffuseb-cell lymphoma• Key points from the interview are as follows:• CD37 (tetraspanin TSPAN26) is a B-cell surface antigen widely expressed on
mature B cells. CD37 is involved in immune regulation and tumour
suppression.
• CD37 forms complexes with other tetraspanins and major histocompatibility
complex (MHC) Class II antigens on B cells.
• CD37 is also important for T-cell–B-cell interaction, IgG/IgA production, and abalance between immune responses and tolerance.
• The loss of CD37 results in increased IL-6 signalling and STAT3 activation,
which are both known to be involved in the pathogenesis of haematologicalmalignancies.
• A study by Oostindie et al. demonstrated that the combinations ofhexamerisation-enhanced CD20 and CD37 antibodies co-operated in C1q
binding and induced superior and synergistic complement-dependent
cytotoxicity in patient-derived cancer cells, compared with the single agents.
Consistent with these data, a strategy of dual-ligand immunoliposomes ofanti-CD20 combined with anti-CD37 demonstrated highly speci ic targeting toboth leukaemia cell lines and B-cell chronic lymphocytic leukaemia patient
cells.

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M4V 1N5• Compared with the single-antibody immunoliposomes, the combination
demonstrated superior delivery ef iciency and apoptosis induction to B-cellchronic lymphocytic leukaemia patient cells.
• These indings provide novel insights into the mechanisms of synergy inantibody-mediated, complement-dependent cytotoxicity, provide a rationale
to enhance the co-operativity and therapeutic ef icacy of antibody
combinations, and provide a preferred strategy of personalised nanomedicine
for the treatment of B-cell malignancies• Naratuximab emtansine (IMGN529 or Debio 1562 [Debiopharm, Lausanne,
Switzerland]) is an investigational ADC comprising a CD37-targeting antibody
conjugated to the maitansine-derived microtubule disruptor DM1 via a
succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC)
linker, forming a nonreducible thioether bond• Naratuximab emtansine binds with high af inity and speci icity to CD37,
obstructing cell proliferation pathways while allowing internalisation,
processing, and intracellular release of the DM1 payload. As a result of its
ability to disrupt microtubule assembly, DM1 subsequently induces cell cycle
arrest and apoptosis• Naratuximab emtansine binds with high af inity and speci icity to CD37,
obstructing cell proliferation pathways while allowing internalisation,
processing, and intracellular release of the DM1 payload. As a result of its
ability to disrupt microtubule assembly, DM1 subsequently induces cell cycle
arrest and apoptosis

Manufacturing, Research & Development• Debiopharm International SA focuses on the development of prescription drugs thattarget unmet medical needs• The company in-licenses and develops promising drug candidates• The Company is a world leader in polylactic-co-glycolic acid (PLGA)-based
injectable, sustained-release technology.
• The products are commercialized by pharmaceutical out-licensing partners to give accessto the largest number of patients worldwide

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Multilink• Multilink is a new cleavable linker platform suited for
multi drug attachment and compatible with any
conjugation technology to produce ADCs with highDAR (drug-to-antibody ratio)• Multilink™ is a unique and innovative technology inthat it allows the loading of multiple payloads on an
antibody• Goal = To allow any biotech or pharma company withan antibody to generate a proprietary clinical-stage

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M4V 1N5ADC (using our Linker Multilink™) that is signi icantly
more effective and better tolerated• They claim to be able to generate nonclinical proof-ofconcept (POC) material in just a few weeks• On June 16 2021, Debiopharm and a South Koreabased biotech company, UBIX Therapeutics announced
their co-research agreement combining 2 novel
proprietary technologies to speci ically target cancer
cells (https://www.pharmaceutical-technology.com/
features/debiopharm-ubix-anti-cancer-modality/)• The two companies are aiming to develop a new drug modality known as Antibody
Degraducer® Conjugates (ADC), by combining one of Ubix’s Degraducer®
molecule, with Debiopharm’s antibody drug conjugate linker Multilink™
• Degraducer® is a powerful, bifunctional, inhibitor technology that enables selective
protein degradation and prolonged therapeutic effects.
• ADCs combine monoclonal antibodies with the cancer-killing drugs, designed
to attack cancer cells while avoiding healthy cells• Degraducer® linked to therapeutic antibodies via MultilinkTM will improve drug
targeting and could have a synergistic effect on tumor cells, thereby resulting in
improved ef icacy and safety of cancer therapies• Linkers are crucial to the function of ADCs, helping to attach the cytotoxic
payload to the antibody, stabilise the molecule during circulation and release
the toxic payload speci ically into the target tissue.
• In February 2021, Debiopharm and Genome & Company entered a research collaboration
for the discovery of innovative cancer therapies in the expanding antibody-drug
conjugates (ADC) class• The collaboration between the two companies is built on the rapidly expanding Genome& Company’s novel target-based oncology drug pipeline and Debiopharm’s proven trackrecord in oncology• Genome & Company, having generated several antibodies against novel oncology targets
discovered based on its own drug development platform , GNOCLE , which will now bearmed with Debiopharm’s Multilink technology to deliver cytotoxic payloads to tumor
cells

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Abylink• AbYlink™ is an antibody conjugation technology ideally suited for therapeutic anddiagnostic applications• Thanks to AbYlink™, cytotoxic or imaging cargos can be selectively attached to the
Fc portion of any IgG without prior modi ication of the antibody• This technology preserves the original af inity of the antibody to its target• Aby link is compatible with any human IgG as well as with bispecifc antibodies andprotein-Fc fusions

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M4V 1N5• Their Goal = to provide a solution to biotech or pharma partners to generate rapidly aproprietary antibody drug conjugates or imaging antibody.
• Key features:• De ined, reproducible and invariable conjugation with no impact on antigenbinding regions• Homogenous antibody conjugation• Conjugation process completed in less than 1 hour
• Non enzymatic conjugation process• No prior antibody puri ication or modi ication necessary• Compatible with most linker technologies for Antibody Drug conjugations• Compatible with most imaging agents for use as PET, SPECT and luorescent tracers• Compatible with all IgG formats• GMP-compatible technology

Digital Health Investments - Debiopharm Innovation Fund

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• Founded in 2008
• CEO: Tanja Dowe
• President: Thierry Mauvernay• Director: Dr Tom Gibbs• Debiopharm Innovation Fund twitter: https://twitter.com/debiopharmfund?lang=en• Debiopharm Innovation Fund SA invests in Digital Health, Smart Data & innovative techstart-ups with a focus on oncology and infectious disease applications• Smart Data - companies that leverage medical data and AI to have an impact oneither the patient journey or the development of pharmaceutical products• Digital Health - tools and technologies that add medical value to patient care
• Their mission is to support start ups that aim to improve the cancer patient journey andreimagine how clinical trials are conducted, as well as digital health companies that focus
on bacterial infections by providing expertise in drug development, regulatory processes,
reimbursement and market access, as well as management of health-tech companies• They aim to increase the pace of these companies scale-up process, provide long-term
funding, work alongside these companies’ teams to achieve a positive return on

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investment for all stakeholders, and to drive their portfolio investments towards
successful exits• Typically the fund invests in therapeutic startups at the preclinical stage, in diagnostics atthe development stage, and in smart data at the early commercialization stage.
• Debiopharm has invested 120 million USD since 2008 and led 19 out of 25 lastinvestment rounds• Their portfolio companies have achieved 10 FDS clearance, 13 CE marks, 2 IPOS, and 4
trade exits• Cumulative equity raised across companied amounts to over 500 million USD• Criteria they look for in a company:• Investment round: A or B
• Debiopharm Innovation Fund prefers to fund companies during the Series A
and B inancing round• Initial investment can be in the range of $3M – 5M
• Pre-commercial to commercial stage• Large pilots and early clients to validate commercial interest• Strong management• Management team with entrepreneurial and industry experience• Innovative technology• Product answering a need with a clear USP• Market with tangible entry barriers.
• Execution plan
• Well de ined operational plan and commercial strategy with a realistic budget• What Debiopharm offer as investors:• Active participation in the board of directors• Pharma & healthcare development, regulatory and market expertise• Experience in growing small companies• Focus on long term value creation• Past Investments:• Kaiku health - A digital health start-up that provides a personalized digital healthintervention for every cancer patient• Treatment modality speci ic algorithms screen symptoms, alert care team andprovide personalized support for patients in order to optimize the personalcare journeys.
• https://kaikuhealth.com/• Acquired by Elekta in May 2020
• Biocartis - an innovative molecular diagnostics company committed to
revolutionize molecular testing with its unique proprietary IdyllaTM platform• Biocartis’ proprietary molecular diagnostics (MDx) IdyllaTM platform is a fully
automated sample-to-result, real-time PCR system that offers accurate, highly
reliable molecular information from virtually any biological sample, invirtually any setting, allowing fast and effective treatment selection andtreatment progress monitoringEugene Consulting Inc.
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• They offer tests supporting melanoma, colorectal and lung cancer, as well as
tests for SARS-CoV-2 and sepsis.
• IPO in April 2015
• https://www.biocartis.com/en• OSE Immune Therapeutics - An integrated biotechnology company focused on
developing and partnering therapies to control the immune system for immuneoncology and autoimmune diseases• They immunology research and development platform focuses on 3 areas: Tcell based vaccination, Immune-oncology, auto-immunity and in lammation• They utilize several scienti ic and technological approaches including
neoepitopes and agonist/antagonist monoclonal antibodies, all ideally
positioned to ight cancer and autoimmune diseases• https://ose-immuno.com/en/about/• ABAC Therapeutics - committed to inding therapeutic solutions for patients thatare infected with highly antibiotic-resistant bacterial pathogens and that leave
affected patients with few (or no) treatment options• Their goal is to create precision treatments of serious bacterial infections
with pathogen-speci ic, novel-mechanism antibacterials that selectively
eliminate the targeted pathogen while sparing the normal lora andminimizing the selective pressure on non-targeted strain• http://www.abactherapeutics.com/• Spinmix - A Swiss technology platform company providing innovative sample
processing solutions to the life sciences sector• In 2015, Debiopharm Group acquired Spinomix’ FibroTrap sample processing
technology• FibroTrap is a ibrinogen-based technology allowing the highly speci ic
separation and ef icient concentration of target molecules from liquidsamples within a simple, routine sample-collection tube
• This technology greatly simpli ies the sample processing work low,
improves sensitivity and signi icantly shortens the time taken fromsample collection to delivery of results• FibroTrap is applicable to a wide variety of matrices (blood, urine,swabs, food, etc.) to isolate a large spectrum of targets (bacteria,
viruses, tumor cells, etc.) and hence could provide a breakthrough insample processing applied to clinical diagnostics and the food industry• Diagnoplex - A molecular diagnostic company that developed COLOX, a noninvasive peripheral blood-based test for the early detection of Colorectal Cancer• The company has performed a 140 patient prospective pilot study
demonstrating technical and clinical feasibility of its colorectal cancer
screening test COLOX as wellas its high sensitivity and speci icity• They entered the Switzerland market in collaboration with Novigenix in 2014
• Neovacs - A French Biotechnology company that develops products and invests ininnovative companies

Eugene Consulting Inc.
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M4V 1N5• 2 main activities: R&D and Investment• At research and development, their activities revolve aroundthe Kinoid technological platform in two main therapeutic indications, lupus
disease and allergies• They also invest in promising projects, both in the development of drugcandidates and medical devices• Current vaccine development efforts are in Crohn’s disease, rheumatoid
arthritis and lupus - Phase IIb/II• https://www.neovacs.com/fr/
Companies they are currently invested inf• Voluntis is a leader in the ield of digital therapeutics• https://www.voluntis.com/• They create digital therapeutics that empower cancer patients and people with chronic
conditions to self-manage their treatment• Their solutions combines mobile and web apps, use clinical algorithms to deliver
personalized recommendations to patients and their care teams• On their Theraxium technology platform, they operate multiple digital therapeutics,
especially in oncology and diabetes• Reason for investing in Voluntis:• Belief that all oncology drugs will have a digital companion in the future• Due to side effects, it will be important for cancer patients to be empowered to
manage their treatment, receive personalized support and guidance through digital
therapeutic apps
• On June 7 2021, Voluntis received the FDA 510(k) clearance for a new version of Insulia
supporting an additional basal insulin product, expanding the scope of insulins coveredby the solution• Voluntis has integrated this new product version within the scope of its CE mark for
Insulia• This enables the use of this solution in countries of the EU and European Free Trade
Association• This is Voluntis’ 14th regulatory clearance for a digital therapeutic• On May 12 2021, Voluntis received the CE mark for a new version of Oleena (digital
therapeutic for people with cancer) featuring expanded clinical intelligence• The new version of Oleena embeds new clinical algorithms that provide decision
support recommendations to patients• It is designed to facilitate self-management of an increased number of symptoms
that people with cancer may experience along their treatment journeyEugene Consulting Inc.
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M4V 1N5• This new CE-marked version of Oleena, a Class IIa medical device in Europe, is also
authorized for marketing in the United States• On April 27 2021, Voluntis announced a collaboration agreement with Eisai (headquarter:
Tokyo) to design and develop innovative digital therapeutics (DTx) to support patientstreated for cancer as well as a strategic investment from Eisai in Voluntis• By leveraging Voluntis’ Theraxium technology platform, the two companies will
collaborate on novel DTx speci ically designed for patients and healthcare
professionals to support cancer treatment• Ultimately, the companies would collaborate on the commercialization of theDTx, once authorized for marketing by regulatory authorities• The new assets will be designed with the intent to be commercialized in the
US, Japan and European markets.
• In addition to their partnership in oncology, the partners will explore otheropportunities of collaboration to develop, evaluate and commercialize digital
therapeutics based on the Theraxium platform in the ield of neurology, anotherarea of strategic focus for Eisai notably for Alzheimer’s disease and dementia• On February 15, 2021 Voluntis announced the issuance of a new patent by the European
Patent Of ice for intelligent patient support in drug dosing applied in the ield of diabetes
for insulin titration support• This new patent covers the management of the sensitivity of the titration
algorithms to changes in the patient's blood glucose levels to optimize theachievement and maintenance of the dose enabling glycemic control.

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• Oncomfort is a start-up in digital therapy for pain and anxiety
management• They are the inventor and leader in Digital Sedation - a completely
new method for relieving patients’ pain and anxiety before, during
and after medical intervention• They combine clinical hypnosis and evidence-based integrative therapy techniquesthrough virtual reality• Headquarter: Brussels, Belgium• https://www.oncomfort.com/en• Reason for investing in Oncomfort:• Clinical methods for diagnosing and treating cancer cause pain and anxiety to thepatients and while Debiopharm develops drugs for cancer, they also want to seethat patients are treated on a holistic level

Eugene Consulting Inc.
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M4V 1N5• They are con ident of the power of Digital Sedation with the strong clinical data
supporting Oncomfort’s approach• The management team at Debiopharm tested the Sedakit(TM) and believe that
Oncomfort can actually help patients control pain and anxiety without medication• On September 9 2020, Debiopharm co-lead a 10 million euro Series A funding round in
Oncomfort to scale up its Virtual Reality Digital Solution with Credit Mutuel Innovation• Debiopharm will join Oncomfort’s board of directorff• NucleAI is a leading provider of AI-powered precision oncology technology• They use AI to develop precision oncology biomarkers to drive research and treatment
decisions• NucleAI’s core technology analyzes large and unique datasets of tissue images using
computer vision and machine learning methods to model the spatial characteristicsof tissues, such as both the tumor and the patient’s immune system cells, creating
unique signatures that are predictive of patients response• These biomarkers allow further strati ication of responder/non-responder patient
populations, improve the success rate of clinical trials, and shorten time-to-market
for pharmaceutical treatments• The company is at the early commercial stage• Headquarter: Tel Aviv, Israel• https://www.nucleaimd.com/• Reason for investing in nucleAI:• Pathology slides, and paticularly tumor biopsies, contain a wealth of pertinent
information that may be captured/measured easily with image analysis to generate
new biomarkers• They believe NucleAI has the ultimate technical skills and will be a strong force indeveloping treatments that work better• On March 16 2021, NucleAI entered a strategic data partnership with ARC Innovation
Center at Sheba Medical Center to accelerate the use of AI pathology in drug development
and clinical testing• This new partnership will sallow NucleAI to gain access to millions of patient
records at Israel's largest hospital, which will include pathology images, clinicaldata, genomics and radiomics, along with other data modalities• The two have an existing collaboration to work on identifying the histologicalbiomarkers that can predict the body's response to immunotherapy for non-smallcell lung cancer patients

Eugene Consulting Inc.
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Toronto, ON
M4V 1N5• One success to come out of this partnership was a successful study that
demonstrated the prediction ef iciency of tumor microenvironment AI-based
analysis for breast cancer• On January 14 2021, NucleAI and Debiopharm entered into a long-term collaboration toleverage NucleAI’s AI-powered biomarker research and discovery platform for one of
Debiopharm’s clinical stage oncology assets• Debiopharm has multiple therapeutic development programs in oncology that they
believe may bene it from this digital pathology biomarker and imaging platform,
enabling better patient selection and improved clinical performance• The agreement includes an initial installment to Nucleai followed by success-based
milestone payments should Debiopharm integrate Nucleai’s biomarkers in its
clinical studies and further develop them as companion diagnostics• In July 2002, Debiopharm led a $6.5 million series-A investment in Nucleai

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• Carevive Systems is an oncology-focused health technology company dedicated tounderstanding and improving the cancer patient experience• Founded in 2013
• Their platform enables providers to deliver better quality cancer care, and patients to be
more engaged in their treatment, which will improve survival outcomes• Use of Carevive unlocks critical data on the real-world cancer patient experience tocontinuously improve patient care
• https://www.carevive.com/• Reason for investing in Carevive:• Based on belief that bringing the patient experience into the clinical pathway is
critical for patient-centric medicine• The data collected using Carevive’s system forms registries of real world evidence,that could be used to improve drug development and Debiopharm wants to be in
the forefront of this• On February 19, 2021, Carevive announced that it has completed its Series C fund-raising
led by Philips Health Technology Ventures with Qure Ventures, Debiopharm Innovation
Fund, OurCrowd’s digital health fund, HLM Venture Partners, LRVHealth, Cerner, andfounder Madelyn Trupkin Herzfeld• In November 2020, Carevive won the irst P izer Patient Reported Outcomes Challenge designed to identify innovative PRO-based platforms and technologies that can provide
novel patient-centric support & insight mechanisms for cancer patients• The award was presented Carevive based on demonstrated experience with
oncology PROs, proven partnership capabilities, and success in supporting valuebased contracting models

• Initially, the collaboration with P izer will focus on developing PRO-based
longitudinal datasets to uncover insights along the cancer patient journey tosupport value-based agreements• To generate these data and insights, Carevive will work within its growing networkof 26 health system customers, including sites that are participating in the Carevive
Oncology Pragmatic Trial Investigator Network (Carevive OPT-IN®)f

f• Nova Discovery is a pioneer in silicon medicine• They simulate clinical trails with virtual patients to de-risk research programs andoptimize clinical development• Jink is Nova’s in silico clinical trials platform that uses AI and virtual populations at theheart of it• Nova builds mathematical models of disease and treatment to optimise trial design,
to capture best responders, and to demonstrate value to payers• Headquarter: Lyon, France• https://www.novadiscovery.com/• Reason for investing in Nova Discovery:• Nova introduces a new category, in silico clinical trials, that reduces the need fortrial and error, helping pharma to focus on those treatments that more likely workfor given patient groups• This can help to reduce research & development (R&D) costs and time-tomarket of novel drugs• As model informed drug development has become a strategic priority also forreglators worldwide, Debiopharm wanted to partner with the best and build thefuture together• On March 26 2021, NOA announced that they have entered into a new collaboration with
Takeda Pharmaceutical Company Limited aimed at incorporating clinical simulation
technology on virtual patients into Takeda France’s access strategy• This agreement builds on an existing relationship they began in 2017
• Takeda, through its association with NOVA, is leading the way in incorporating
disease modelling and trial simulation in virtual populations in its pipeline
development programs.
• On February 16 2021, NOVA announced they raised 2.5 million euros in a Series A2
inancing round from Sano iōfEugene Consulting Inc.
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Eugene Consulting Inc.
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M4V 1N5• On January 19 2021, Nova was awarded 2.4 million euros to leverage Jinko to conduct insilicon studies for graft0vs-host disease• The results will be used to support future regulatory approval applications by
ElsaLys for inolimomab in Europe• In January 2020, Debiopharm led a 5 million euro Series A round

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• BC platforms is a world leader in genomic data management solutions• They provide a powerful genomic and clinical data management and analysis platform forpersonalized medicine, accelerating the translation of insights into clinical practice• Their genomic data discovery platform enables lexible data integration, secure
analysis and interpretation of molecular and clinical information• BC Platforms aims to build the world’s leading analytics platform for healthcare andindustry and to revolutionize decision making in drug development bringing clinicalbene its to patients• Headquarter: Zurich, Switzerland• https://www.bcplatforms.com/• Reason for investing in BC Platforms:• BC Platforms has the technology and the means to federate clinical and genomic
data• With BC Platforms, precision medicine becomes a reality for healthcare providers,and big data enabled drug development becomes a real tool for pharma industry• Both bene it Debiopharm’s ultimate goal: better care for patients• On February 23 2021, BC Platforms and Genomenon announced that they will partner tobring together Genomenon’s Mastermind tools and BC Platforms’ clinical genomics
pipeline and research platform• With the vision to advance clinical genomics, Genomenon’s Mastermind Genomic
Search Engine will be integrated into BC Platforms’ genomic analysis andinterpretation platform BC|GENOME• On the research side, Mastermind will also be integrated into BC Platforms’
research platform BC|INSIGHT to facilitate complex genomic research bysimplifying genomic data annotations and thus enabling AI/ML applications• On January 26 2021, the Finnish Institute for Health and Welfare (THL) and RIKEM joined
forces in an international research effort to support development of a precisionprediction model to identify those most at risk from COVID-19.
• BC Platforms is providing its BC|INSIGHT platform to enable the curation,
integration and analysis of THL’s clinical data of 300 to 1,000 Finnish COVIDprog
research subjects using RIKEN’s algorithms

Eugene Consulting Inc.
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M4V 1N5• This is to identify a ‘COVID-19 prediction procedure’ that can estimate symptoms
and outcomes of COVID-19 based on health records of infected patients obtained
before SARS-CoV-2 infection.
• In May 2017, BC platforms closed a USD$ 10 million series B inancing round led by
Debiopharm Innovation Fund

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• Immunexpress is a molecular diagnostic company committed to improving outcomes for
suspected sepsis patients and healthcare providers• They are a pioneer in the analysis of the immune system to rapidly detect sepsis• Their technology uses a gene expression in the blood with a speci ic algorithm to detect apatient’s immune response to a pathogen, rather than the traditional approach of trying
to identify a causative pathogen• Their mission is to develop diagnostic technologies to help clinicians and patients to ight
this life-threatening disease• Headquarter: Seattle, Washington• https://immunexpress.com/• Reason for investing in Immunexpress:• Debiopharm recognizes that sepsis is one of the biggest killers globally and therapid diagnosis in sepsis is key to effective management of patients• They recognize the power in Imunexpress’ approach of measuring the hostresponse on a quick sample-to-result platform• In October 2020, Immunexpress’ rapid test for sepsis, SeptiCyte® RAPID, launched inEurope on Biocartis’ Idylla platform• This is a 1 hour molecular diagnostic test that runs on the Biocartis Idylla platformthat can swiftly differentiate infection positive (sepsis) from infection negative
systemic in lammation in patients• This is the irst rapid, fully-integrated, immune response-based test to aid clinicianswith sepsis diagnosis• This launch follows the CE marking announced in March 2020
• The immediate EU commercialization in partnership with Biocartis NV wasintended to support the use of the technology to improve the ef iciency with
COVID-19 patient triage

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M4V 1N5• The test can be used to quickly identify patients with worsening prognoses
and ensuring rapid initiation of sepsis management protocols that canincrease the potential to save lives• Agendia is the only molecular diagnostics company focused solely on breast cancer• They believe in the power of genomic testing to better inform the patient journey as it
sheds light on complex treatment decisions, leading to the most relevant and targeted
approach for each individual patient• They create genomic testing that provides patients with actionable insights throughout
their breast cancer journey• They have been on the market since 2004 in Europe and 2008 in the U.S.
• https://agendia.com/• Agendia MammaPrint - a test that shows the likelihood of a patient’s breast cancer
recurring• The MammaPrint® test analyzes the 70 most important genes associated withbreast cancer recurrence• Results are typically available in 6 days or less
• MammaPrint enables quicker, more informed decisions on pre- and post-operative
treatment and can easily be integrated into diagnostic workups• Agendia BluePrint - a test that determines the underlying genomics driving the growthof a tumour• The test looks at 80 genes and the tumour is accurately classi ied as one of threesubtypes, which reveal valuable information about its behavior, long-term
prognosis and response to systemic therapy• Results are typically available in <6 daysf

• Eclosion Ventures manages the Exclusion life science investment fund, that helps
translate breakthrough science into drugs by providing an incubator and resources foryoung biotechs

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f• They support portfolio companies from seed to capital stage up to clinical proof ofconcept• They focus on highly innovative science and early stage companies developing new
approaches to address high unmet medical needs• Their portfolio companies have developed irst-in-class drugs with high potential value inpatients in ields such as multiple sclerosis, ibrosis and oncology• They have 4 portfolio companies, 3 in clinical stage, 1 IPO and 1 merger wit ha publiccompany• Debiopharm supports programs that support entrepreneurship such as Exclusion