ERYTECH Corporate Presentation Jefferies 2015 Healthcare Conference New York, June 4, Gil Beyen, Chairman & CEO

Transcription

1 ERYTECH Corporate Presentation Jefferies 2015 Healthcare Conference New York, June 4, 2015 Gil Beyen, Chairman & CEO

2 Forward Looking Statements This document does not constitute or form part of any offer or invitation to sell or issue, or any solicitation of any offer to purchase or subscribe for, any shares in the Company, nor shall any part of it nor the fact of its distribution form part of or be relied on in connection with any contract or investment decision relating thereto, nor does it constitute a recommendation regarding the securities of the Company. This document may contain forward-looking statements and estimates made by the Company, including with respect to the anticipated future performance of ERYTECH and the market in which it operates. They include all matters that are not historical facts. Such statements, forecasts and estimates are based on various assumptions and assessments of known and unknown risks, uncertainties and other factors, which were deemed reasonable when made but may or may not prove to be correct. Actual events are difficult to predict and may depend upon factors that are beyond the Company's control. Therefore, actual results, the financial condition, performance or achievements of ERYTECH, or industry results, may turn out to be materially different from any future results, performance or achievements expressed or implied by such statements, forecasts and estimates. Forward-looking statements, forecasts and estimates only speak as of the date of this document and no representations are made as to the accuracy or fairness of such forwardlooking statements, forecasts and estimates. ERYTECH disclaims any obligation to update any such forwardlooking statement, forecast or estimates to reflect any change in the Company s expectations with regard thereto, or any change in events, conditions or circumstances on which any such statement, forecast or estimate is based. 2

3 A late-stage orphan oncology company Targeting markets with high unmet medical needs Acute leukemia Selected solid tumors Seven orphan drug designations Highly innovative and industrialized technology Encapsulation of therapeutic compounds in red blood cells Broad application potential Strong IP protection Late stage clinical pipeline Positive Phase III results ALL Expanded Access Program in ALL Phase IIb in AML >70% accrued Phase II in pancreas cancer Phase I/II in ALL in US Solid corporate basis Listed on Euronext (ERYP.PA) and OTC US ADR1 (EYRYY) EUR 34 million cash (31/03/15) Partnerships with Recordati in Europe and TEVA in Israel in AL ALL: Acute Lymphoblastic Leukemia; AML: Acute Myeloid Leukemia; AL: Acute Leukemia 3

4 Innovative and versatile technology platform Entrapment of drug substance inside red blood cells (RBC) using hypotonic/hypertonic stress Proprietary osmotic fragility process ensures quantifiable amounts of drug are captured in each RBC batch Controlled lysis (hypotonic stress) Protected by 13 patent families Resealing (hypertonic stress) Industrialized in commercial scale GMP manufacturing facility 4

5 Industrialized solution ready for the commercial phase Photo salle de contrôle 1 Sourcing 2 Preparation 3 4 Encapsulation Batch release Prescription Purchase of pack of compatible RBCs and API Identification of the key parameters* Automated process Ca 3 hours Quality control Release by QP Patient Min ca 6 hours Robust & reproducible: >500 batches administered with 100% delivery Centralized EU GMP production facility in Lyon, France, for clinical and commercial production. Sized for the first two years of marketing. GMP & ISO certified US production facility in Philadelphia, at the premises of the American Red Cross, validated for clinical trial production * Measurement of osmotic fragility, verification of blood typing, expiry date, volume, hematological parameters. 5

6 Asparaginase: an essential weapon against acute leukemia, but toxic The principle Tumor starvation The key nutrient: Asparagine Starving cancer cells by affecting their supply of essential nutrients Asparagine, essential nutrient for most tumor cells, but not for normal cells The weapon: Asparaginase The issues: Toxicity and short half-life Asparaginase, degrades asparagine and deprives tumor cells of key nutrient Proven efficacy in ALL; cornerstone in all pediatric ALL treatment protocols Asparaginase can cause severe side effects (allergies, coagulation disorders and pancreas/liver problems) especially in fragile patients Asparaginase has a short half-life (<1 day; high dose and frequent administrations need) 6

7 Encapsulation of asparaginase: ERY-ASP/GRASPA, a novel bioreactor The asparaginase is definitively encapsulated in the red blood cell The circulating asparagine is actively pumped into the red blood cell Asparagine Y The RBC membrane prevents interactions between the asparaginase and the antibodies Longer half-life Less toxicity Asparaginase Y Antibodies where the encapsulated asparaginase destroys it 7

8 Targeting the unmet need of fragile acute leukemia patients Children Adults Seniors AML 34,000 new cases per year Unmet need: >$ 1 billion 82% of patients ALL 16,000 new cases 18% of patients Addressed needs: $ 300 m per year Native asparaginase ($ 15 m) PEG-asparaginase - Oncaspar ($ 95 m) Erwinase ($ 200 m) Children Adults Seniors 82% of patients with acute leukemia receive little or no treatment with existing asparaginases Source: Erytech; Jazz Pharmaceutical/ European and US data 8

9 Late stage clinical development: 6 trials in acute leukemia GRASPA ALL - Europe Adults & children in relapse Phase I/II Phase II/III Marketing authorization ALL - France Adults >55 yrs first line ALL - France Children & adults at risk ALL US Adults > 40 yrs in first line AML Europe Seniors > 65 years in first line Phase II Filing EAP Phase I/II Phase IIb Completed Ongoing In Acute Lymphoblastic Leukemia (ALL) European pivotal Phase II/III trial completed with positive results (N = 80) Expanded Access Program (EAP) for patients intolerant to current asparaginases Phase I/II ongoing in US; 3 centers enrolling (N = 12 to 18) In Acute Myeloid Leukemia (AML) More than two thirds of patients recruited in Phase IIb trial (N = 123) Positive DSMB safety reviews on first 30 and 60 patients 9 9 9

10 ALL Pivotal trial: study design A multicentre, randomized, Phase II/III study, evaluating efficacy and safety of erythrocytes encapsulating L-asparaginase (ERY001-GRASPA ) versus reference L- asparaginase treatment in combination with standard chemotherapy in patients with first recurrence of Philadelphia negative Acute Lymphoblastic Leukemia N = 80 (1-55 years). Ph-negative ALL First ALL relapse PS score 2. No allergy RANDOMIZE 1:1 Known allergy to L-ASP GRASPA - ERY001 + Chemotherapy L-ASP + Chemotherapy GRASPA - ERY001 + Chemotherapy 10

11 ALL - Pivotal trial: both primary endpoints met with high significance Endpoint Non-allergic patients GRASPA N=26 Ref L-aspa N=28 Allergic pts GRASPA N=26 Number (%) of patients who experienced 1 hypersensitivity reaction during induction** Number (%) with severe hypersensitivities (Grade 3) Mean duration of asparaginase activity above 100 IU/L during induction treatment** 0 (0%) 13 (46%) 3 (12%) 0 (0%) 7 (25%) 0 (0%) 20.5 days 9.4 days 18.6 days ** statistically significant (p<0.001) 11

12 ALL - Pivotal trial: favorable overall safety profile Summary of adverse events (AE) reported during indiction Non-allergic patients GRASPA N=26 Ref L-aspa N=28 Allergic pts GRASPA N=26 Patients with at least 1 AE 25 (96) 28 (100) 26 (100) Patients with at least 1 drug-related AE 18 (69) 28 (100) 16 (62) Patients with drug-related Grade 3 AE 13 (50) 25 (89) 11 (42) Patients with SAE 11 (42) 15 (54) 8 (31) Patients with at least 1 drug-related SAE 1 (4) 7 (25) 2 (8) Patients with AE leading to discontinuation 0 12 (43) 0 Patients with AE outcome of death 0 4 (14) 1 (4) 12

13 ALL - Pivotal trial: favorable overall safety profile Non-allergic patients Allergic pts Key AEs of interest in >10 % GRASPA Ref L-aspa GRASPA of patients during induction N=26 N=28 N=26 Impaired coagulation parameters 9 (35%) 24 (86%) 15 (58%) Hypofibrinogenemia 7 (27%) 19 (68%) 9 (35%) Anti-thrombin III decreased 2 (8%) 20 (71%) 6 (23%) Activated PT time prolonged 1 (4%) 3 (11%) 3 (11%) Prothrombin level decreased 0 (0%) 3 (11%) 0 (0%) Study drug-related coagulation events 9 (35%) 23 (82%) 9 (35%) Pancreatic events 8 (31%) 14 (50%) 8 (31%) Biochemical pancreatitis 8 (31%) 14 (50%) 8 (31%) Clinical pancreatitis 2 (8%) 2 (7%) 0 (0%) Study drug-related pancreatic events 7 (27%) 14 (50%) 7 (27%) Hepatic event 12 (46%) 14 (50%) 14 (54%) Transaminase increased 9 (35%) 9 (32%) 8 (31%) GGT increased 4 (15%) 3 (11%) 6 (23%) Bilirubin increased 2 (8%) 6 (21%) 2 (8%) Hepatotoxicity 2 (8%) 6 (21%) 6 (23%) Study drug-related hepatic events 5 (19%) 12 (43%) 7 (27%) 13

14 ALL Pivotal trial: improved clinical benefit Endpoint Non-allergic patients ERY001 N=26 Ref L-aspa N=28 Allergic patients ERY001 N=26 Complete Remission rate (CR)* 17 (65%) 11 (39%) 14 (54%) Minimum Residual Disease < (35%) 7 (25%) 7 (27%) 12 month Overall Survival (OS) 76.9% 67.9% 50.0% 12 month Event Free Survival (EFS) 64.9% 48.6% 50.3% * statistically significant (p < 0.05) 14

15 ALL - Positive Phase III results: conclusions and next steps Key conclusions: GRASPA is a safe and efficacious asparaginase for the treatment of patients with relapsed ALL Reduced risk of allergic reactions Longer asparaginase activity Favorable overall safety profile Improved clinical benefit Favorable result in patients with prior hypersensitivity reactions Submission for EU Marketing Authorization Application ongoing Important validation of ERYTECH s encapsulation technology and basis for broadening the indication and further leveraging the product and platform in other oncology indications 15

16 ALL - Expanded Access Program: treating double allergic patients The expanded access program (#NCT ) was set up to provide access to GRASPA to ALL patients, in first line or relapse, who are at risk of hypersensitivity reactions due to previous allergies to both the E. Coli and Erwinia derived asparaginases. Initial results presented at ASH Positive DSMB on first 7 patients treated double allergic patients (prior allergies to E.Coli and Erwinia derived asparaginases) Children and adults First line and relapse 12 patients enrolled to date. Program will be open until Marketing Authorization 16

17 ALL - Phase I/II study ongoing in the US Open label dose escalation study with ERY-ASP in 12 to 18 adult ALL patients over 40 years of age in frontline therapy Participating centers University of Chicago Richard Larson (Principal Investigator) Duke Medical Center University of Ohio Medical Center Other sites being opened Discussion with FDA being prepared to accelerate study and discuss overall development plan 17

18 Additional indication for GRASPA, AML in Phase IIb AML, a logical extension of indication Large unmet medical need: est new patients per year (US & EU) Predominantly senior patients (median age: 67 years), where the favorable safety profile of GRASPA may be a particular advantage Most AML blasts are deficient in ASNS activity and have shown to be sensitive to asparaginase Increased CR rates observed with asparaginase in AML (Cappizi ea, 1988) Phase IIb study ongoing in AML patients over 65 years of age in Europe Multinational, randomized Phase IIb study (N=123), comparison of GRASPA plus low dose cytarabine versus low dose cytarabine alone More than two-thirds of patients recruited Positive safety evaluations by DSMB on 30 and 60 patients 18

19 Partnerships established for commercialization in acute leukemia Licensing deal with Recordati Orphan Europe for Europe Commercialisation of GRASPA in ALL and AML in Europe Up to ca. 50 million in payments (upfront, development funding and milestones) 5 million equity participation in the IPO Up to 45% of net sales retained by ERYTECH (transfer price + royalties) Licensing deal with TEVA for Israel Commercialisation of GRASPA in ALL in Israel 50:50 revenue sharing agreement 19

20 Mode of action confirmed in other oncology indications Asparagine synthetase (ASNS) expression of tumors Tumors sensitive to asparagine depletion Source: Dufour e.a., Pancreas 2012 (in collaboration with MD Anderson Cancer Center Houston) 20

21 Pancreas cancer: Phase II trial ongoing One of most agressive cancers. Ca new patients per year in Europe and the USA; 5 year overall survival <10% Phase I study performed in 12 patients Monotherapy in dose escalation; single injection No dose limiting toxicities Conclusion: ERY-ASP given in last line therapy is well tolerated even at the highest dose (150 IU/kg) 72% of >600 biopsies analyzed have no or low expression of ASNS Phase II study launched to evaluate efficacy in association with current chemotherapy and with a stratification of patients based on expression of ASNS Ca 90 patients in second line treatment 2-to-1 randomization to standard chemotherapy alone DSMB on first 24 patients expected mid 15 21

22 NH Lymphomas: preparing Phase II study in DLBCL NH Lymphomas represent a large unmet medical need: ca new cases per year in Europe and the US combined L-asparaginase is well known to physicians treating lymphomas. Particular need and rationale in Diffuse Large B-Cell Lymphoma (DLBCL) representing 30-40% of all Non- Hodgkin Lymphomas More than 85% of DLBCL biopsies analyzed have been shown to be ASNS deficient (sensitive to asparaginase) 100% Based on the available data in acute leukemia, ERYTECH is preparing a Phase II study in DLBCL for launch in 2015 in Europe 75% 50% 25% 0% DLBCL (n=110) Tumors sensitive to asparagine depletion (no/low ASNS) 22

23 Other enzymes to strengthen the personalized medicine approach At least two other amino acids and their respective enzymes have been identified as relevant for tumor starvation treatments Enzymes Indications Asparaginase Leukemia Lymphoma Myeloma Pancreas Liver Bladder Ovary Lung Colorectal CNS & Brain Leukemia Lung Pancreas Colorectal Melanoma Gastric Prostate Methionine-γliase Argininedeaminase Liver Melanoma Leukemia Sarcoma Pancreas Lymphoma ERYTECH is the lead partner in a syndicate R&D program and benefits from 7M government funding over 7 years to develop additional encapsulated enzyme products with their companion tests and bring them to the clinic ERY-MET, methioninase in RBCs, identified as promising new product candidate. Start of Phase I clinical trial aimed in 1H 2016

24 Solid cash balance and shareholder base 30 M raised in private placement end October % from specialized US investors Cash balance 31/12/2014: 37 M 31/03/2015: 34 M Net cash consumption (in operating and investing activities) 2014: 7.6 M 1Q15: 3.0 M Capital structure (fully diluted): Shares outstanding: 6,882,761 Stock options: 557,180 Free float 57% Management 8% Recordati 6% Auriga Venture 16% Idinvest 5 % Baker Bros 9% 24

25 Dense news flow and significant value inflection points ahead Launch Phase II solid tumor study: pancreas First patient US ALL study 2 nd DSMB Phase IIb AML study Results Phase III ALL study 30 M capital increase ADR level 1 listing DSMB Pancreas cancer Phase II study DSMB AML Phase II study EU MAA submission ALL Updates on US Phase I/II ALL study and development plan Launch Phase II in NH Lymphoma Launch ERY-MET Phase I trial EU marketing authorization ALL Results Phase II pancreas cancer Results US Phase I/II ALL study Results Phase IIb AML study 25

26 Thank you ERYTECH Pharma SA 60 Avenue Rockefeller Lyon France