CORPORATE PRESENTATION - FEBRUARY 2020 - Erytech
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Forward Looking Statements The statements made in this presentation may include forward-looking statements regarding the future operations of ERYTECH Pharma S.A., including estimates of target market opportunity, timing of planned clinical trials and results from those trials, regulatory strategy and timing of planned regulatory submissions, manufacturing capabilities and strategy for expansion of the ERYCAPS platform. Although we believe that the expectations contained in this presentation are reasonable, these forward-looking statements are only estimates based upon the information available to ERYTECH Pharma S.A. as of the date of this presentation. Except as required by law, we expressly disclaim any responsibility to publicly update or revise our forward-looking statements, whether as a result of new information, future events or otherwise. Thus, the forward- looking statements herein involve known and unknown risks and uncertainties and other important factors such that actual future operations, opportunities or financial performance may differ materially from these forward-looking statements. Undue reliance should not be placed on forward- looking statements, which speak only as of the date hereof. All forward-looking statements contained herein are qualified in their entirety by the foregoing cautionary statement.
Leader in Red Blood Cell-based Cancer Therapeutics Reproducible encapsulation of therapeutic compounds in red blood cells Phase 2b in 2L Pancreatic Cancer OVERALL SURVIVAL (ITT) Focus on oncology, targeting cancer cells’ altered amino acid metabolism through encapsulated asparaginase Lead product candidate eryaspase, first asparaginase to show 40% efficacy in solid tumors; strongest survival benefit observed in any reduction in 2L pancreatic cancer study to date risk of death (HR, 0.60; Phase 3 trial in 2L pancreatic cancer ongoing in EU and US; on P=0.008) track for readout 1H21; interim (for superiority) expected 3Q20; Phase 2 in 1L TNBC and Phase 2 IST in 2L ALL ongoing Industrialized production: own cGMP production facilities in the United States and Europe Months Listed on Nasdaq and Euronext; cash runway into 2021; key Hammel et al., European Journal of Cancer, 2019 shareholders including BVF and RA Capital ALL: Acute Lymphoblastic Leukemia; TNBC: Triple-Negative Breast Cancer 3
Late Stage Clinical Pipeline and Preclinical Programs Product Candidate Phase 3/ Next Anticipated Mode of action Indication Discovery Pre-clinical Phase 1 Phase 2 or Program Pivotal Milestone Pancreatic Cancer Interim: Q320 TRYbeCA-1 2L Final: 1H21 Triple Negative TRYbeCA-2 Final: 2021 ® Breast Cancer 1L eryaspase/GRASPA Cancer metabolism (asparaginase) Acute Lymphoblastic Interim: 1H20 NOPHO IST Tumor starvation Leukemia 2L Final: 2H20 Pancreatic cancer IST Launch: 2H20 1L erymethionase Solid tumors (methionine-γ-lyase) Immune Immune-oncology TBD* modulation Tolerance induction Enzyme Therapeutic Metabolic diseases replacement enzymes 1L First Line; 2L Second Line; IST Investigator Sponsored Trial; NOPHO : Nordic Organization of Pediatric Hematology and Oncology * To be determined by SQZ Biotech 4
Red Blood Cells, Ideal Carriers for Amino Acid Lowering Agents Readily available at blood Permeable membrane banks Potential to load with drugs Established sourcing Plasma metabolites can pass Well known Protective membrane biocompatibility Reduced toxicity Routine allogeneic use Prolonged activity Most abundant cell in Long circulating life human body Prolonged activity Extensive biodistribution 5
ERYCAPS, an Innovative Technology Platform Reproducibly encapsulating drug substances inside allogeneic red blood cells using proprietary hypotonic loading technology Drug substance Reproducible proprietary ‘osmotic fragility’ process enables reproducible loading Pores Fast industrialized process can deliver tailored therapy within 24 hours Controlled Hypotonic Loading Broad range peptides, RNA, proteins, antibodies, … Hypertonic Strong IP Resealing 265 granted patents in 15 patent families 6
Industrialized and Scalable Process 1 2 3 4 5 1 Sourcing 2 Preparation 3 Encapsulation Batch4release Shipping 5 PRESCRIPTION SOURCING PREPARATION ENCAPSULATION BATCH RELEASE SHIPPING Sourcing of Identification of key ERYCAPS automated QC Control Patient Manufacturing Shipping compatible RBC parameters (3-5 hours) Release by QP Possible in 24h Validated supply & Fully-owned GMP Established partnerships More than a decade manufacturing model – 2000+ production capacity in EU with blood banks in EU and experience in manufacturing batches, 460+ patients treated, and the US the US and supply chain management 9 countries 7
Targeting Cancer Cells Amino Acid Metabolism, an Emerging Field Many cancers exhibit increased demand Amino acids for specific amino acids, becoming dependent on exogenous supply or de Depleting select amino novo synthesis of these amino acids1-3 acids in blood (e.g. asparaginase) Blocking uptake by blocking transporters (e.g., LAT 1-4) Inhibiting biosynthetic or catabolic enzymes (e.g. arginase inhibitor) 1. Lukey et al., Drug Discovery Today, 2017 2. Pavlova & Thompson, Cell Metabolism, 2016 3. Luengo et al., Cell Chemical Biology, 2017 8
Asparaginase, First Amino Acid Targeting Anticancer Drug1 Mode of action MODE OF Asparaginase breaks down circulating asparagine (and glutamine), and deprives ACTION tumor cells of amino acids essential for their growth Current use • Cornerstone treatment in Phi-neg pediatric acute lymphoblastic leukemia (ALL) • Four forms of L-asparaginase products currently marketed in ALL; worldwide sales est. $400M in 2018 CURRENT USE • E-coli derived: Native asparaginase: e.g., Kidrolase (Kyowa Hakko) Recombinant asparaginase: Spectrila (medac) Pegylated asparaginase: Oncaspar (Servier) • Erwinia derived: Erwinaze (Jazz Pharmaceuticals) Limitations • Important side effects (e.g., allergies, coagulation disorders, pancreatic and hepatic toxicities) limit therapeutic window to essentially pediatric ALL • Beyond ALL, some use in AML and lymphoma; no known use in solid tumors 1. Lukey et al., Drug Discovery Today, 2017 9
Eryaspase (GRASPA®), Enabling Broader Use of Asparaginase A novel circulating ‘bioreactor’ to degrade asparagine (and glutamine) Y Y Active transporters in membrane of red cell pump circulating Y Prolonged activity Y asparagine and glutamine into Y the red cell… Y Reduced toxicity Y Asparaginase Y Potential to provide Asparagine and glutamine asparaginase to patients …where the encapsulated that are unable to Degradation products L-asparaginase hydrolyzes the tolerate non- Antibody asparagine and glutamine encapsulated products Y 10
Positive Results in ALL Confirmed Proof of Concept • ERYTECH started development in fragile ALL patients, confirming the concept of prolonged activity and reduced toxicity in different clinical trials, including a Phase 2/3 trial in Relapsed/Refractory ALL: Key results of Phase 2/3 trial in R/R ALL Eryaspase (N=26) L-ASP (N=28) % of patients with ≥ 1 hypersensitivity reaction during induction** 0% 46% Mean duration of asparaginase activity above 100 U/L during induction (days)** 18.9 8.5 Complete Remission rate (CR)* 65% 36% • Overall Survival (OS) HR = 0.72 ** Statistically significant (p
Pancreatic Cancer, Large Unmet Medical Need • Pancreatic cancer is one of the leading causes of cancer death in the world, with an Lung and bronchus 160 increasing incidence1,2 Projected cancer deaths in the US (1000’s) • In 2018, approximately 185,000 people were 140 newly diagnosed with pancreatic cancer in 80 Europe and the United States1 Pancreas 60 Colon and rectum • Overall prognosis for pancreatic cancer is Liver poor, with a 5-year survival rate of
Altered Metabolic Pathways in PAC, a Role for Asparaginase? • Pancreatic cancer (PAC) is characterized by extensive reprogramming of cellular metabolism leading to increased asparagine and glutamine requirements. Deprivation of glutamine and asparagine results in loss of cancer cell viability1 • In vitro studies demonstrated promising anti-cancer effects for asparaginase against human pancreatic tumor cell lines2-3 • Attempts at evaluating asparaginase in solid tumor indications in the clinic have been unsuccessful due to toxicity4-7 • In a Phase 1 trial in metastatic pancreatic cancer, eryaspase demonstrated an acceptable safety profile8-9 • The tolerability of eryaspase and the potential role of metabolic dysregulation in this disease provided rationale for further clinical evaluation 1. Kawanda Int J Clin Oncol 2017; 2. Cui, Cancer Res 2007; 3. Dufour, Pancreas 2012; 4. Lessner Cancer Treat Rep 1980; 5. Hays Molec Clin Oncol 2013; 6. Agrawal Cancer 2003; 7. Borad Cancer Investigation 2015; 8. Bachet Pancreas 2015; 9. ClinicalTrials.gov: NCT01523808 13
Phase 2b Trial in 2L Pancreatic Cancer Launched in 2014 Patients (N=141) Co-primary endpoints Eryaspase + 03 Randomize 2 to 1 • ≥18 years chemotherapy PFS and OS in ASNS 0/1 • Stage III or IV (gemcitabine or subpopulation • One prior systemic mFOLFOX) option Key secondary endpoints chemotherapy in advanced setting • PFS and OS (all comers) Chemotherapy alone • Objective response rate • Measurable disease (gemcitabine or • Disease control rate • ECOG PS 0 or 1 mFOLFOX) • Safety and tolerability Stratified by chemotherapy • Quality of life Trial in collaboration with the GERCOR in 16 clinical sites in France Reference: ClinicalTrials.gov: NCT02195180 ECOG: Eastern Cooperative Oncology Group, PS: performance status, FOLFOX: 5FU, leucovorin and oxaliplatin; GERCOR: Multidisciplinary Group in Oncology ASNS 0/1 subpopulation: patients with no/low asparagine synthetase expressing tumors 14
Clear Overall Survival (OS) Benefit1 Eryaspase Phase 2b Trial 40% I T T P O P U L AT I O N reduction in risk of 100 Eryaspase + death 90 chemotherapy Chemotherapy 80 (n=95) (n=46) (HR 0.60; P=0.008) Survival probability (%) 70 Events, Events nn(%) (%) 82 (86.3) 79 (83%) 42 (91.3) 40 (87%) 60 Median OS, CI) OS HR (95% 0.60 (0.40, 0.88) P-value months 6.0 0.008 4.4 For reference: Onyvide Phase 3: HR 0.67 50 (95% CI) (4.8–6.6) (3.0–5.0) 40 Median OS (mo) 6.0 4.4 P OSvalue rate at 1yr 15.8% 0.008 6.5% 30 OS rate at 18m 8.4% 0% 20 10 0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 No. at risk Months E +CT 95 83 67 45 29 24 15 11 8 8 4 4 4 1 1 1 1 0 CT 46 35 22 15 8 6 3 0 I T T P O P U L AT I O N HR, Hazard Ratio; OS, Overall Survival 1. Hammel et al., European Journal of Cancer, 2019; 15
Overall Survival Benefit Consistent Across Subgroups1 Eryaspase Phase 2b Trial All patients (E+CT n=95, CT n=46) 0.60 (0.40, 0.87) ITT POPULATION ASNS category ASNS 0/1+ (E+CT n=66, CT n=32) 0.63 (0.39, 1.01) ASNS 2+/3+ (E+CT n=29, CT n=14) 0.52 (0.26, 1.03) Gender Male (E+CT n=53, CT n=30) 0.47 (0.29, 0.77) Female (E+CT n=42, CT n=16) 0.95 (0.51, 1.79) Time from randomization
Similar Progression-Free Survival Benefit1 44% Eryaspase Phase 2b Trial ITT POPULATION reduction in the Progression-free survival probability (%) 100 I T +T P O P U L A T I O N Eryaspase risk of chemotherapy Chemotherapy 90 progression (n=95) (n=46) 80 (HR, 0.56; P=0.005) Events n (%) Events, n 70 70(74%) 36 (78%) 36 70 (%)HR (95% CI) (73.7)0.56 (0.37, 0.84) (78.3) OS 60 P-value Median PFS, 0.005 50 monthsPFS Median 2.08.6 1.6 6.9 40 (95% CI) (weeks) (1.8–3.4) (1.4–1.8) 30 P value 0.006 20 10 0 0 2 4 6 8 10 12 14 16 Months No. at risk E +CT 95 36 18 12 6 4 3 0 CT 46 9 6 1 1 1 0 1. Hammel et al., European Journal of Cancer, 2019; 17 17 17
Improved Response Rates and Fewer New Lesions1 new lesions Eryaspase Phase 2b Trial ITT POPULATION PD 50 45 47,4 Eryaspase + chemotherapy 40 Chemotherapy SD 35 30 Patients, % ** ** CR OR 25 23,9 20 SD new lesions 15 PD SD 10 11,6 5 OR 6,5 OR 0 SD Disease control rate Overall response rate PD = Progressive disease OR SD = Stable disease PR = Partial response CR= Complete response OR = Overall response (PR +CR) 1. Hammel et al., European Journal of Cancer, 2019; 18 DCR = Disease control rate (OR+SD) 18
No Additional Toxicity Over Chemotherapy Alone All grade adverse events (%) 0 10 20 30 40 50 60 70 Eryaspase 80 Phase 2b Trial ITT POPULATION Asthenia Nausea Anemia Vomiting Thrombocytopenia Abdominal pain Diarrhea Decreased appetite Pyrexia Constipation Neutropenia TREATMENT EMERGENT EVENTS GGT increased REGARDLESS OF RELATIONSHIP TO Physical health deterioration STUDY DRUG Antibody test positive 86% Weight decreased Peripheral edema 77% Upper abdominal pain Stomatitis ALT increased Hypokalemia Neuropathy peripheral 50% Fatigue 45% Back pain Cough Mucosal inflammation Alopecia Hyperthermia Lymphopenia Chemotherapy Hyperglycemia AST increase Anxiety Eryaspase + Hypoalbuminemia Patients > Gradewith 3/4 ≥1 Patients >=1 SAEwith chemotherapy Insomnia Grade 3 or 4 AE ≥1 SAE 19
Trybeca-1, Phase 3 trial in 2L Pancreatic Cancer Launched in 2018 Pascal Hammel Manuel Hidalgo Co-PI, Hôpital Beaujon, Paris, France Co-PI, Weil Cornell Medicine, New York, U.S. Patients (N ≈ 500) Chemotherapy Primary endpoint (gemcitabine+nabpaclitaxel 03 Randomize 1:1 • ≥18 years • Overall Survival or FOLFIRI) • Stage III or IV PAC plus eryaspase Key secondary endpoints • One prior systemic option chemotherapy in Chemotherapy alone • Progression-free survival advanced setting (gemcitabine+nabpaclitaxel • Objective response rate • Measurable disease or FOLFIRI) • Disease control rate • ECOG PS 0 or 1 • Safety and tolerability Stratification by ECOG PS, chemotherapy regimen • Quality of life and time since diagnosis of advanced disease Trial expected to run in approximately 100 clinical sites in 11 European countries and the U.S. Reference: ClinicalTrials.gov: NCT03665441 ECOG, Eastern Cooperative Oncology Group; PS, performance status FOLFIRI, 5FU/leucovorin/irinotecan; the irinotecan can be Onivyde (nanoliposomal irinotecan or NALIRI) 20
Trybeca-1 on Track for Complete Enrollment in 3Q20 • More than 50% of projected patients enrolled (since Dec 2019) • Trial enrolling patients since September 2018 in Europe • Clinical trial authorizations in 11 European countries • 50+ clinical sites activated • Trial opened for enrollment in the United States in October 2019 • First sites activated; approximately 20 U.S. sites targeted • Safety data of first 150 patients reviewed by independent data monitoring committee in October 2019: • No safety issues identified • Recommendation to continue trial as planned • Trial on track for full enrollment in Q3 2020 • Interim analysis (for superiority) expected in Q3 2020 • Based on comparison of OS when 2/3 of events will have occurred • Two outcomes possible: continue as planned or stop for superiority (no futility analysis planned) 21
Broadening Scope to Other Solid Tumor Indications Phase 2 proof of concept trial ongoing in Triple-Negative Breast Cancer (TNBC) • Randomized Phase 2 proof-of-concept trial in Europe • Approximately 64 patients with newly diagnosed metastatic disease • Chemotherapy (gemcitabine/carboplatin) +/- eryaspase • Primary endpoint: objective response rate • Clinical trial authorizations obtained in all four participating countries PI: Ahmed Awada Head of the Medical Oncology • Close to 20 sites activated; patient enrollment ongoing Clinic at Jules Bordet Cancer Institute Brussels, Belgium • Results expected in 2021 Broadening of indication scope to first line (1L) pancreatic cancer in preparation • Investigator sponsored Phase 1 trial (IST) of eryaspase in combination with FOLFIRINOX in the United States 22
Industrialized and Scalable Manufacturing Own cGMP production in Europe and US, scaled for clinical and early-commercial manufacturing • Europe: Lyon (France) • 12 cleanrooms • Producing GMP batches for clinical trials • United States: Princeton, NJ • 16 cleanrooms, 4 equipped • Ready to manufacture cGMP batches for clinical trials 23
Preclinical Programs Gastric adenocarcinoma Tumor regression in gastric cancer model Erymethionase, methionine-gamma-lyase encapsulated in RBC 1800 **** Mean tumor volume (mm 3 + SEM) 1600 Erymethionase + PN • Promising preclinical data in gastric cancer and glioblastoma 1400 1200 suggest potential as a new treatment approach against cancers 1000 800 ** *** that rely on methionine metabolism 600 400 • Further preclinical data show potential synergistic effect of 200 0 methionine restriction with immune checkpoint inhibitors and 0 10 20 30 40 50 60 70 80 Days post-tum or im plantation asparaginase Vehicle Erymethionase 80 U/kg ERYZYME, encapsulating enzymes used in certain enzyme therapies to treat rare metabolic diseases • E.g. Arginase-1-deficiency: preclinical data showing sustained lowering of arginine levels with arginine deiminase encapsulated in RBC in arginase deficient mice 24
Strategic Collaboration with SQZ Biotechnologies • ERYTECH granted SQZ Biotechnologies, a Cambridge (MA) based cell therapy company, an exclusive worldwide license to develop antigen-specific immune modulating therapies employing red blood cell-based technology. • SQZ to develop RBC-derived therapeutics to induce antigen-specific immune modulation by combining SQZ’s Cell Squeeze® cell engineering platform with ERYTECH’s IP and knowhow related to RBC-based therapeutics • ERYTECH is eligible to receive: • Upfront and potential milestone payments up to $57 million for the first product successfully developed by SQZ under agreement • Royalties on sales, and potential commercial milestone payments up to $50 million for each additional approved product or approved indication 25
Q3 2019 Financial Results • Net loss of €43.3 million at 09-2019 09-2018 (Cumulative figures in '000€) Var° in K€ Var° in % end of Q3 2019 (9 months), (9 months) (9 months) up €13.6 million yoy Revenues Other income 3 881 2 666 1 216 46% Total operating income 3 881 2 666 1 216 46% Total Research and development (36 977) (25 726) (11 251) 44% • Cash position of €81.9 General and administrative (13 743) (10 566) (3 177) 30% Total operating expenses (50 720) (36 292) (14 427) 40% ($89.2) million as of Total operating loss (46 839) (33 627) (13 212) 39% September 30, 2019 Financial income 3 975 3 994 (19) Financial expenses (392) (15) (377) Financial income (loss) 3 582 3 979 (396) -10% Income tax 1 (1) 2 -150% Net loss (43 256) (29 649) (13 606) 46% • Cash variation of €52.4 million in the first nine months of 2019 • Cash runway confirmed into 2021 26
Key Milestones Anticipated over Next 12 Months ü Start of GMP production at Princeton facility ü Safety review by IDMC of first 150 patients in TRYbeCA-1 q Interim results of Phase 2 IST in 2L acute lymphoblastic leukemia (ALL) q Interim (superiority) analysis in TRYbeCA-1 q Initiation of Phase 1 IST with eryaspase in 1L pancreatic cancer 27
Shareholder Base Retail 20-25% Institutional EU/RoW 30-35% Institutional US 40-45% Source: Euroclear Identifiable Bearer Securities (‘TPI’), June 28, 2019 28
Leadership Team Jérôme Bailly Gil Beyen Jean-Sébastien (JS) Cleiftie VP Pharmaceuticals Operations & Qualified Person Chief Executive Officer Chief Business Officer
Board of Directors Jean-Paul Kress Sven Andréasson Philippe Archinard Gil Beyen Chairman Independent Director Independent Director Chief Executive Officer & Director Luc Dochez Martine George Hilde Windels Independent Director Independent Director Independent Director 30
ERYTECH Pharma SA ERYTECH Pharma Inc 60 Avenue Rockefeller 1 Main Street 69008 Lyon Cambridge, MA 02142 France USA www.erytech.com
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