EFTA01113739.pdf

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K 4 13. n R / / G OSE Pharmar12)' Dominique Costantini, M.D CEO Severe Orphan Emile Loria, M.D. Lung Diseases Chairman Corporate Presentation February 2013 EFTA01113739  OSE Pharma Investment Thesis Substantial late stage clinical assets: Phase 3 study for advanced lung cancer (NSCLC): targeted cancer immune therapy 100M$ Epimmune investment from R&D to the completed Phase Ilb Phase 2 study for Cystic Fibrosis: re-profiling existing drug with safety package Experienced team with solid track records Emile Loria, M.D., Former Epimmune Pres & CEO Dominique Costantini, M.D., Former BioAlliance founder & CEO More than 100M€ raised publicly with approved EU/US products OSE Pba-Th 2 EFTA01113740  OSE Pharma Investment Thesis 1st round to be raised: 5M€ plus commitment to 10% IPO GMP Material for phase 3 FDA /EMA Protocols acceptance Orphan designations IPO preparation in 12-18 Months 2nd round to be raised: 20M€ through public market Clinical Phase 3 execution for Lung cancer (vsac. Non Small Cell Lung Cancer) Clinical Phase 2 execution for Cystic Fibrosis (amucoviscidose» a genetic disorder) OSE Pba 3 EFTA01113741  OSE Pharma Market opportunity : €1.4B OSE 2101 targeted cancer immune therapy: EUROPE HLA A2 positive NSCLC: 123 000 Pts Peak Market share 15% : 18 450 Pts (cost 45 K€ to 50K€) OSE 2101 Market Estimate €16 0SE1101: molecule for Cystic Fibrosis EU & US Cystic Fibrosis Pts: 65 000 Pts Peak Market share 15%: 9770 Pts (cost 35K€ to 50K€) OSE1101 Market Estimate: 400M€ OSE Pba EFTA01113742 OSE Pharma assets in late stage products OSE 2101 Targeted immunotherapy assets:(10 years investments / $100M) 1. R&D Epitopes algorithms definition and selection 2. Original combination of epitopes and analogs (granted PI) 3. Solid Know-how (former Epimmune team: bio batches & GMP site) 4. Up to Phase Ilb positive results under US IND 5. Phase II status in colon cancer OSE1101 reprofiling a molecule previously marketed 1. safety package 2. H4R agonist patent in the US 3. Cystic Fibrosis Patent filed in 2012 OSE EFTA01113743  OSE Pharma advanced pipeline Drug Mkt Pre clinical Phase I Phase II Phase III discovery application OSE2101: targeted Cancer Immune Therapy A2+ Lung cancer Phase III status A2+ Colon cancer Phase II status A2+ Breast cancer A2+ Ovarian cancer OSE1101: H aganftst Cystic Fibrosis Phase II status OSE Pr's —3 6 EFTA01113744 OSE Pharma OSE 2101 PHASE 3-.) OPPORTUNITY in advanced NSCLC EFTA01113745 NSCLC: New therapies critically needed NSCLC treatments insufficiently effective: 5-year survival at 4% for patients with distant disease (Horner et al. 2009) Active cancer Immunotherapy today: promising new treatments in Phase III Cancer vaccines targeting only one Tumoral antigen : i.e. MAGE or MUC in clinical development in first line (or maintenance) treatment in advanced NSCLC Ipilimumab Yervoy ® acting on CTLA4 checkpoint ( increasing T cell responses) and registered in melanoma / New anti PD1 acting on PD1 checkpoint. OSE Pha EFTA01113746 NSCLC: New therapies critically needed NSCLC treatments insufficiently effective: 5-year survival at 4% for patients with distant disease (Horner et al. 2009) Current therapies registered for advanced NSCLC stages: Stable disease after 1st line chemotherapy + platinum: survival —12 months; 1 year survival at 50% (i.e. erlotinib, permetrexed, gemcitabine, docetaxel..) Aggressive disease after first line failure: survival —8 months; 1 year survival at 33% (2nd or 3rd line) TKI or chemotherapy (i.e erlotinib, docetaxel, permetrexed..) ALK Inhibitors Crizotinib Xalkory® registered in ALK+ NSCLC pts (3-5% NSCLC pts) OSE EFTA01113747 OSE 2101:Phase Ill Protocol & Objectives HLA A2 NSCLC population, open, randomized, multi-center comparative study: 500pts ■ Versus reference drug (Treatment of Physician's Choice) after at least failure of first line chemotherapy in locally advanced Illb or metastatic IV NSCLC patients ■ Exclusion criteria: specific mutations EGFR — ALK ■ Primary Endpoint: Overall Survival (OS) One year survival rate ■ Secondary Endpoints: Safety, PFS, QOL OSE Pb 10 EFTA01113748  OSE 2101:Principal Investigators ■ John Nemunaitis, M.D. Oncology Mary Crowley center, Dallas o Principal investigator for Phase II; expertise in numerous cancer vaccine trials ■ Benjamin Besse , M.D, Oncology Gustave Roussy center, Paris o Cancer expertise in numerous cancer vaccine trials; Expert in Lung cancers (ESMO) OSE P-a 11 EFTA01113749  OSE2101 Product Manufacturing Epitopes Antigens 10 H LA A2 multi-epitopes targeting 5 usEwpippv CEA.24V9 Tumors Antigens expressed in NSCLC YLSG*DLNL CEA.605D6 IMIGHLVGV CEA.691H5 Mineral oil adjuvant (Montanide' ISA 51) EP2101 JKVFG.SLAFV HER2.369V2V9 RLLQETELV HER2.689 1. SINGLE VIAL (5MG/ML) , LulLvi"GIEV MAGE2.157 2. 3 year stability of peptide emulsion KVAEIVHFL. MAGE3.11215 3. Manufacturing: Althea, San Diego Kuipvcumv p53.139L2B3 4. Subcutaneous Injection SMPPPGTRV p53.149M2 aKXVAAWTLKAAa Thelper PADRE OSE P. harrnaq4 12 EFTA01113750  OSE 2101 Phase II positive results Stage III-II and IV NSCLC Patients Design: Open multicenter study : 135 patients ■ 64 HLA A2 positive patients received OSE2101(stage Illb :21; Stage IV: 43) ■ 71 HLA A2 negative concurrent control patients (one year survival follow up) ■ Inclusion criteria - Stage III-I3 and IV NSCLC Patients o ECOG status of ≤ 1; At least 4 weeks from last chemotherapeutic regimen o no limit in previous lines treatment (36% received more than 3 previous lines) o 6 subcutaneous doses at 3 week intervals, maintenance doses at 3 month intervals ■ Immune monitoring (made for 5 of the 10 epitopes) ■ At baseline, week 9, weeks 18, 22, 30, and months 9 and 12 ■ Primary Endpoints: Safety and overall survival ■ Secondary Endpoints: Progression-free survival, immunogenicity OSE 13 EFTA01113751  Phase 11 Immune Responses and Survival • 91% (30/33) monitored for CTL showed CEA24 (n= 33) Axed- positive responses to 1 or more, 64% to at Anchor HER2.369 In= 33) Analogs p53-149 least 3 epitopes In =11) p53.139 (n=11) • Significant relationship of epitope response AIM In = 33) level to survival of treated patients ( Janus Heteroclitc CEA64:6 Analogs CEA691 n=11) review 2012) MAGE3.112 In = 33) Low: 0-1-epitopes: 406 ± 58 days of survival (n-5, 95% CI for mean 292 -520)* Wild-Type MAGE2.157 (n = 33) Epitopes HER2.689 In= 11) Medium: 2 to 3-epitopes : 778 ± 72 days of survival (n-15, 95% CI for mean 637 -919) 0 10 20 30 40 50 60 70 80 90 100 II Analog peptide High: 4 to 5-epitopes: 875 ± 67 days of survival Wild-type peptide Patients with Response (%) (n=13; 95%Cl for mean 743- 1007) Barve et al JCO 2008 and J. Clin Oncol 26: 2008 (May 20 suppl; abst 8057) In all categories stated above: p < .001 OSE Pharma9L1', 14 EFTA01113752  Phase II Overall Survival at 1 Year Survival Functions Received OSE2101 10 :7 No Yes 08- No-censored • Yes-censored 1--tell01144rtni474, 135 patients 7 V) I Green = OSE2101 Treated =64 (29 deaths) 04 - It Blue = Control =71 (42 deaths) t.) A2 negative parallel selection 0 2 -• One-year survival: p=0.063 Control A2 negative patients= 49% 0 0- better prognosis established- Nagata 2009 ; 30 0 200 400 600 DaysSurvived Treated A2 positive patients= 59% *M Barve et al; l Clin Oncol 26: 2008 (May 20 suppl; abstr 8057); l Neimunatis et al; International Society for Biological therapy of cancer 2007 Abs :phase II trial of Median survival (days):p 0.086 a 10- epitope CTL vaccine in metastatic NSCLC Control patients= 361 ± 59 Treated patients= 583 ± 138 7.5 months of difference OSE Pharma1; ', 15 EFTA01113753  Phase II Overall Survival at 4 Years One Year Survival Two Year Survival Three Year Survival Paient Estimate Estimate Estimate Group N (95% CI) (95% CI) (95% CI) All 64 56% (44-68) 39% (26-51) 27% (15-39) Stage IV age IIlb 21 74% (54-94) 48% (25-70) 24% (2-46) Stage IV 43 48% (33-63) 35% (20-50) 28% (14-43) 67% OSE Pharmafi))1, 16 EFTA01113754  OSE 2101 Positive Phase II Conclusions • Strong clinical efficacy signal observed in locally advanced or metastatic NSCLC patients: median survival better than 17 months • 89% of patients demonstrated stable disease • 25% overall long term survival rate at 4 years • 85% of patients tested presented an immune response A minimum of 2 epitopes; n=33 for the 5 epitopes tested • Longer survival shown in patients achieving response to 2 or more epitopes o P < .001, n=33 for 5 epitopes tested • Primary adverse effect: injection site reaction OSE Pka s 17 EFTA01113755  OSE 2101 Milestones & Use of Proceeds OSE 2101 targeted cancer immune therapy with positive phase II: Phase III in advanced HLA A2+ NSCLC pts: global costs: €23M (including team and G&A) 12/18 months Milestones: Total 4M€ • Orphan status • FDA/ EMA Phase III Agencies green lights • Scale up / GMP Biobatches OSE Pharmaq;' 18 EFTA01113756  OSE 2101 Timelines & Costs Subject Date €19.3M ■ Orphan status for NSCLC A2 population : Q1 2013 ■ GMP Matterial Phase 3 FDA/EMA acceptance : 2013 €4M ■ Pivotal clinical program : 2014-2016 €15.3M ■ Phase 3 results (one year OS rates) 2016 -2017 OSE Pba 19 EFTA01113757  OSE 2101 Intellectual property OSE 2101 key patent: EP2101 ten epitopes describing HLA A2 Epitopes and or analogs combinations from different Tumor Associated Antigens (HER2/neu, CEA, MAGE2; MAGE3; p 53) plus synergy obtained by the original combination : Granted in Europe (PCT application WO2004094454) filed in April 2004 - protection until 2024 Other multi-epitopes patents are using modified epitopes: epitopes identification, selection and modification based on immunogenicity results and HLA binding for immune therapy and constitute a barrier to entry New patents in the course of development Know-how: manufacturing of a multi-epitopes composition; process and methods of preparation of 10 peptides combination OSE P-a 20 EFTA01113758  OSE 2101 Business Strategy Partnering opportunities in non core territories Major Pharma deal or sale of assets post phase 3 Market Opportunity: €1B . • OSE Pharma0', 21 EFTA01113759 OSE PharmaW, r OSE 1101 PHASE 211 OPPORTUNITY in Cystic Fibrosis - CF EFTA01113760 OSE 1101 CF Phase II independent product OSE1101 (tritoqualine) was selected • As indicated in severe lung disease: Cystic Fibrosis • Cystic Fibrosis qualified for Orphan designation • independent development risk • Same regulatory and development team as EP2101 • Molecule with a proven safety profile previously marketed in Europe • Original new anti -inflammatory properties for a CF application OSE P- EFTA01113761 CF: New therapies critically needed With current treatment strategies, 80% of patients should reach adulthood, Cystic Fibrosis remains a life-limiting disease (median survival : 36.9 years) OSE1101 is a new anti-inflammatory molecule (H4R agonist/IL8 decrease) Maintaining lung function Mucolytic agents (i.e. dornase alfa ,Pulmozyme®) Nebulized, inhaled, oral, or intravenous antibiotics Bronchodilators Anti-inflammatory agents Current new therapies registered for CF Agents acting to reverse chloride transport abnormalities ( Kalydeco , ivacaftor ) on specific mutation (4% of CF /annual cost 294 000$) hydrating the airway surface : Inhalated mannitol Bronchitol® (EU Australia) OSE Pba—is EFTA01113762  OSE 1101 in Cystic Fibrosis ■ OSE1101 as a new H4R agonist & histamine modulator ■ Role on histamine level and interleukin release as IL8 ■ IL8 is a potent chemo-attractant playing a key pro-inflammatory role in stimulating conditions (bacterial and viral infections) or in chronic conditions related to CFTR gene in CF patients ■ OSE1101 is an innovative potent anti-Inflammatory compound targeting H4R expressed in CF and decreasing IL8 release ■ OSE1101 protects mice against bronchospasm induced by two types of provocation tests ( in vivo Ovabulmine/TLR 7). ■ OSE1191 induced rise in breath-flow in human intra nasal provocation tests (n = 49-600mg/d - 5 days - Gastpar, H. and Sauer, P.H.) OSE P-a 25 EFTA01113763  OSE 1101 proven safety Profile ■ OSE1101 previously marketed for allergic disorders as a histidine decarboxylase inhibitor: histamine modulator o Decreases the tissue formation of endogen histamine from histidine ■ Marketed internationally since 1960 (Chiesi — Novartis consumer health) for the treatment of various allergic conditions o 300 to 900mg/d with no obvious side effects o Clinical dossier based on extensive prior human use and clinical efficacy on nasal or allergic symptomatology OSE P-3 26 EFTA01113764 OSE 1101 Milestones & Use of Proceeds OSE1101 H4R agonist for CF Patients reprofiled molecule Phase II in CF pts: total €3.8M ($5M) PK/PD/dose efficacy and safety in young CF patients (age >10) endpoint : FEV1 improvement vs placebo (follow up 24 / 48 weeks 12/18 months Milestones: Total 1M€ ■ CF in vivo results : P Barbry, IPMC Director (Sophia Antipolis) ■ Orphan status ■ FDA/ EMA Phase II Agencies green lights ■ GMP Biobatches OSE EFTA01113765  OSE 1101 Timelines & Costs Date Capital €3.8M ■ Orphan status for CF population : Q1 2013 ■ Scale up and bio batches stability : 2013 €0.8M ■ Phase II clinical program : 2013-2015 €3M ■ Phase 2 results: 2015 OSE P 28 EFTA01113766  OSE 1101 Intellectual Property ■ H4 Receptor agonist, US Patent # 8,207,188 - E Loria, M Nicolaou.. Granted in the US until 2029 ■ Cystic Fibrosis application: April 2012, OSE Pharma EP 12305487.6 opening International protection until 2032 ■ New patent in the course of development ■ EU US Orphan status protection to be filed in 2013 OSE 29 EFTA01113767  OSE1101 Business Strategy Partnering opportunities to explore Major Pharma deal or sale of assets post phase 2 US & EU Market Opportunity: €400M OSE PharmaC• 30 EFTA01113768  Management Team Dominique Costantini, M.D. Pres. & CEO o Former Founder and CEO BioAlliance Pharma (1997-2011,publicly traded on the EuroNext) o More than €100M raised, three products approved EU/US supportive care and oncology o Management of drug development and launches (HMR — Sanofi) -M.D, Immunology David Dellamonica, COO o Theralpha founder and CEO, TxCells VP BD Biotech o Sanofi consultant, Patient Solutions i.e. Colitis foundation & PCSK9 o International Marketing experiences Lilly; Ogilvy- ESG Lyon, MBA Switzerland Elisabeth Peyraube, CFO o 15 years experience in international companies of which 5 years in the US. o CFO Metaboli-. CFO ADP GlobalView- USA: SFG, Ubisoft o Arthur Andersen Auditor.- EDHEC accounting and finance • OSE Pharma* 31 EFTA01113769  Consultants and Advisors Jean Bernard Lepecq, Ph.D. Palo Alto Mike Nicolaou, Ph.D. San Diego o Developed Taxotere for Aventis o Former Epimmune Director of Manufacturing o Expertise in cancer vaccines o Expertise in formulation, manufacturing, QA/QC, bioassays (Amylin, Yasoo Health) Alex Sette, Ph.D. La Jolla o Former Epimmune CSO o Developed algorithm programs at Epimmune and currently at La Jolla Institute for Allergy Les Walker, PhD; San Diego o Former Epimmune Director of process, Alain Chatelin, M.D. pneumologist -Altius - Paris o EP-2101 batches for Phase I/I and phase II o Consultant to the Pharma and Biotech o Expertise in vaccine and peptide o Developed products in infectiology, oncology, manufacturing respiratory field. ( HMR) .Altius Pharma CEO o Contributed to orphan status for both OSE products and will be involved in the phase III Fred Bancroft, San Diego coordination program o QA/regulatory (Amylin) Jim Carter, Ph. D. Regulatory compliance Inc Las Vegas o US FDA OSE representative, Consultant to the Pharma and Biotech (IND/registration/API Steve Reich, M.D Oncologist. San Diego o Consultant Pharma and Biotech, dossier). Large FDA regulatory experiences and o involved in EP-2101 phase I and II designs network o Contributing to phase III protocol. OSE Pharmael:?' 32 EFTA01113770  Board of Directors Emile Loria, M.D., Chairman o Former President & CEO of Epimmune (Nasdaq:EPMN), Science and Business expertise o Biotech and Pharma companies (Biovector Therapeutics, Medical Synergy/Cygnus, Sanofi, Ciba-Geigy) Dominique Costantini, M.D., CEO o Founder and CEO of BioAlliance, more than 100M€ raised and products approved in EU/US o HMR, Roussel Guy Chatelain o Attorney at Law, partner Mentha & Associes o Geneva and Swiss Barr association, Geneva association of Business Law Walter Flamenbaum, M.D. o 40 years of healthcare experience in innovation and investments , Paul Capital partner emeritus, Professor of medicine at Mount Sinai University, MD at Columbia University Jean Theron o Founder and Managing Director of JT.Pharma International Consulting o Former President Hoechst Marion Roussel France, o CEO of Hoechst Roussel Diamant, Lutsia, Hoechst Behring OSE Pharma 33 EFTA01113771 Business models and Comparables • Biovex / Amgen acquisition 2011: $425 million cash up to $575 million in additional payments oncolytic vaccine in Phase 3, melanoma/ H&N cancers • Immatics 108M€ Invested in 3 rounds natural peptides from primary tumour tissues/ Phase III in renal cell carcinoma-phase II in colon cancer • Novartis -Transgene Option : 995M$ deal in 2010 Muc tumor antigen/ IL2 recombinant Virus in Phase III - NSCLC/ first line Treatment Deal with Novartis 10M$ upfront in phase Ilb /III • AB Sciences (594M€ Euronext) Masitinib at registration stage in Pancreatic cancer + other indications OSE Pra is EFTA01113772 Value proposition after first private placement Breakthrough products addressing 01.48 markets NSCLC leading cause of cancer mortality/ CF is killing before 40 Milestones targeted after 5M€ 1st round Increasing value in 12/18 months: 0SE 2101 targeted cancer immune therapy phase III in advanced HLA A2+ NSCLC 0SE 1101 H4R agonist Phase II in CF pts — Orphan status for both opportunities — FDA/EMEA protocol acceptance and partnering opportunities — GMP materials Limited risk due to late stage clinical drugs (Phase 3 and Phase 2) OSE P-a 35 EFTA01113773  Next step and exit strategy IPO feasible with these assets and management expertise next 12-18 months 5 IPO done in 2012 with far less advanced portfolio Opportunity as Pre IPO round at attractive valuation Pharma deal/ sale of the assets after clinical data OSE Pna EFTA01113774  Contacts • Dominique Costantini , CEO OSE Phar'na OSE Pharma Pépinière Paris Santé Cochin 29 bis rue du faubourg, Saint Jacques, Paris, 75014 France Phone + Fax + Cell + severe Orphan E mail: lung diseases • Emile Loria, Chairman Cell + E mail: EFTA01113775