Mapi Pharma Value-Added High-Barrier to Entry Pharmaceuticals Q4 2015

Transcription

1 Mapi Pharma Value-Added High-Barrier to Entry Pharmaceuticals Q

2 Experienced Management Team Ehud Marom, CEO & Chairman of the Board of Directors Teva VP Tapi, head of the Copaxone global operation team Makteshim (Makhteshim-Agan now ADAMA-ChemChina) CEO Gamida Cell CEO Peptor (DeveloGen) President Pharma Two B Chairman Roy Cohen, CPA, CFO Lundbeck Israel Ltd. Finance Manager Deloitte, San Jose, CA, USA Audit Manager Deloitte, Tel Aviv, IL Senior Auditor Uri Danon, Executive VP Teva Projects manager including Copaxone in a solution in pre-filled syringes Atox Bio Chairman & CEO BioCancell President & CEO Dr. Shai Rubnov, VP R&D NasVax Manager QA and regulatory affairs Peptor (DeveloGen) Director of CMC Alex Mogle, VP Corporate Development Makhteshim-Agan Head of supply chain, investor relations director, Company Secretary NICE System BD Director DVR Ministry of Finance Safi Landskroner, VP Business Development Meuhedet Sick Fund Head of Procurement Dexcel Pharma VP BD & RA Neopharm VP BD Therapix Biosciences Director Dr. David Leonov, Head of API Development Teva Senior research positions Makhteshim-Agan Chief Scientist Dr. Yoram Sela, Head of Formulations Teva Manager controlled-release unit Karma-Pharm Founder LycoRed (now Makhteshim-Agan) VP R&D Nesher Solutions VP R&D Nir Bernstein, CPA, VP Finance Ampal Inc. VP Accounting & Control PwC Senior Manager 2

3 Expert Scientific Advisory Board Prof. Jerry S. Wolinsky, MD Interim Chair, Dept. of Neurology, The University of Texas Medical School at Houston Certified by the National Board of Medical Examiners and the American Board of Psychiatry and Neurology Led clinical trials, including Copaxone clinical trials Recognized in The Best Doctors in America and America's Top Doctors lists Dr. Ben-Zion Weiner, PhD Head of Global Research and Development at Teva Pharmaceutical Industries Ltd. for over three decades as Chief R&D Officer and as a member of Teva Executive Committee Twice been the recipient of the Rothschild Prize for Industrial Innovation, including for the development and commercialization of Copaxone for the treatment of Multiple Sclerosis Currently serves on the Mesoblast Board of Directors Ph.D. degree in Chemistry at the Hebrew University, Jerusalem, and conducted his post-doctorate research at Schering-Plough Corporation in the United States Prof. Tamir Ben-Hur, MD PhD Chairman, Department of Neurology, Hadassah University Medical Center, Jerusalem Research focused on regenerative medicine and cell therapy for the brain, CNS, neuroimmunlogy of Multiple Sclerosis and experimental autoimmune encephalomyelitis MD and PhD degrees from the Hebrew University, Jerusalem Prof. Yaakov Naparstek, MD Prof. of Internal Medicine in the Hebrew University, Jerusalem Chairman of Medicine in the Hadassah University Hospital for 13 years as well as the Senior Deputy Director General for Research & Academic Affairs at the Hadassah University Hospital Founder and chief scientist of Verto Medical and Protab Therapeutics biotechnological companies Recipient of national and international awards, including the 2011 Elkeles Prize in Medicine A graduate of the Hadassah-Hebrew University Medical School in Jerusalem, Israel 3

4 Lead Products 505(b)(2) Pathway Compound (Brand) Indication Preclinical (2014 Branded Product Sales*) Human PK Phase 2 Phase 3 and Registration GA Depot (Copaxone ) Pregabalin ER (Lyrica ) RRMS Neuropathic Pain In global co-development US$4.2B discussions 2018 Two Regional Agreements signed US$5.2B 2018 Risperidone LAI+ (Risperdal Consta ) Schizophrenia US$1.19B First Regional Agreement signed ANDA Pathway Compound (Brand) Indication Pre-Clinical (2014 Branded Product Sales*) Human PK Registration Darunavir (Prezista ) HIV US$1.8B Global Generic Agreement signed Fingolimod (Gilenya ) RRMS US$2.5B Generic Agreement signed GA API (Copaxone ) RRMS US$4.2B DMF 2016 Risperidone LAI Depot (Risperdal Consta ) Schizophrenia US$1.19B First Regional Agreement signed Remarks: * 2014 sales based on Thomson Reuters, Cortellis platform Not all regular development phases are applicable for 505(b)(2) regulatory filings Current Sales Ongoing Planned 4

5 Focused on Glatiramer Acetate Lead product GA Depot: A monthly depot injection vs. the daily / thrice-weekly Copaxone injection in the market today The next Copaxone lifecycle management product Registration via FDA 505(b)(2) pathway: Expect 2019 launch Patent protection in the U.S. until 2030 Ongoing open-label Phase II clinical trial In preparations for a single pivotal Phase III clinical trial Pre-IND meeting held in March 2015 Generic GA: First sales of GA API expected in

6 Multiple Sclerosis Market The 2014 MS therapeutics global market* is estimated at over $18 billion Average annual cost of MS treatment estimated at ~59K per diagnosed individual in the US in 2004 when converted to 2010 $s (Kobelt et al., 2006) MS effects 400K individuals in the US and M worldwide (Oleen-Burkey et al., 2011) 34% (136K) of the 400K diagnosed MS patients in the US, are prescribed GA as a first-line therapy (Margolis et al., 2011) GA is a very safe and well tolerable drug compared to Tysabri, Fingolimod and Tecfidera that have been associated with lethal PML and safety issues Biogen Plegridy $44 0.2% Genzyme Lemtrada $45 0.2% Biogen Avonex $3, % Biogen Tecfidera $2,909 16% Teva Copaxone $4, % Biogen Tysabri $1, % Merck Serono Rebif $2, % Novartis Gilenya $2, % Bayer Betaseron $1, % * 2014 sales ($m) based on Thomson Reuters Cortellis Platform 6

7 GA Depot Developed by Mapi GA in Mapi s PLGA formulation based on all approved FDA compounds Monthly injection, instead of Teva s current once-daily and thrice-weekly treatment Mapi s U.S. Patents titled Depot Systems 1 week to 6 months Comprising GA, expires August 2030 In vitro release profile indicates linear release over 30-day period Phase II ongoing Increased patient compliance and convenience Reduced burden of treatment 7

8 GA Depot: Formulation and Safety Product: GA long-acting injection Formulation: based on GA-loaded PLGA microspheres Microspheres, ~10 microns, are made of Poly (lactide-co-glycolide) (PLGA), a bio-degradable polyester, used in FDA-approved drugs: Lupron, Risperdal Consta and Vivitrol Microspheres encapsulate the GA; there is no chemical connection to GA (hence, GA is unchanged) Safety: 80 mg is the highest immediate-release GA dose administrated in patients (unintentionally) (Source: Copaxone prescribing information) 8

9 GA Depot: Dosing & Compliance Reduced number of injection site reactions Change of Copaxone daily to thrice-weekly reduced the annualized rate of moderateto-severe injection-related adverse events by 60%* GA Depot once every four weeks is expected to further reduce number of injection site reactions (among Copaxone s most common adverse reactions) Reduced compliance burden IM injection by healthcare professional; may be done at patient s home Dose pack: Vial containing 80 mg GA (4 ml to be injected) 10 ml ampoule containing water-for-injection (WFI) Syringe Reconstitution needle (18G) Injection needle (choice of 23G, 21G and 20G needles) Planned reduction of injection volume ~2 ml, 40 mg Storage: 2-8ºC Lyophilized GA Depot & Water for Injection ampule * Presented in ACTRIMS-ECTRIMS, Sept. 2014, titled: GLATIRAMER ACETATE (40 MG/ML, TIW) IN RRMS PATIENTS: FEWER INJECTIONS FOR A FAVORABLE TREATMENT OPTION 9

10 Precedent for Conversion Acceptance Existing evidence of switching from daily longer acting injections: Copaxone 40 mg conversion rate from 20 mg at ~67%* (~12 months from launch) Case study: Risperidone, an oral drug that came off patent in 2007 converted into a long acting Depot every two weeks, sustaining the market for the product at per annum treatment cost of $370 and $8,520 respectively Company survey among Copaxone treated patients: Satisfaction from treatment will increase if frequency is reduced to once-monthly from once-daily Willing to switch to GA Depot although it may cause increased injection site adverse events No Yes (70%) No Yes (76%) * Teva Pharma Fact Sheet May

11 % Content of GA GA Depot Formulation In Vitro Release Profile In Vitro Release Profile - GA Depot Days Total released (day 30) = 90.6% In Vitro release test content % of GA was determined using GPC (gel permeation chromatography) 11

12 GA Depot Activity MOG EAE: Mean Clinical Score in Mice Indication of improved efficacy * P<0.05 compared with untreated control, single factor ANOVA followed by one-tail two-sample T test, assuming unequal variances, n=10 / group, +/- standard error 12

13 FDA Validated Clinical Trials & Regulatory Strategy Regulatory pathway: development of GA Depot under 505(b)(2) Positive FDA Pre-IND meeting on March 10, 2015: We discussed the required steps for initiation of a single pivotal phase III clinical trial Ongoing non-ind Phase II: open label study to evaluate safety, tolerability, and efficacy of switching to GA Depot from Copaxone Planned Pivotal Phase III: Placebo-controlled study of GA Depot in patients with RRMS, for efficacy, safety and tolerability (n=920); Submit IND for Phase III study in Q

14 Ongoing Phase II Synopsis Title: a prospective 1-year, open-label, multicenter, Phase II study to assess safety, tolerability, and efficacy of once-a-month long-acting IM injection of 80 mg glatiramer acetate (GA Depot) in patients with RRMS Number of Centers: 4, in Israel Investigational Product: GA Depot 80 mg, every four weeks Study Objectives to Evaluate: Primary: safety and tolerability Secondary: changes in MRI, Expanded Disability Status Scale (EDSS) and relapse rate from baseline Study Duration: 1 year per patient; overall 5 quarters to results Population and Sample Size: 20 patients with RRMS, treated with Copaxone for at least 12 months prior Final enrollment expected by YE2015. Interim data H2/

15 Planned Phase III Study Title: a multinational, multicenter, randomized, Phase III, placebo controlled in subjects with RRMS for efficacy, safety and tolerability of GA Depot, a long acting IM injection of GA Number of Centers: 160, worldwide Investigational Product: GA Depot 80 mg every four weeks, IM Primary Endpoint: Efficacy as measured by ARR Study Duration: treatment of 1 year / patient; overall 2.5 years to results Population and Sample Size: 920 subjects diagnosed with RRMS; subjects will be randomized into GA Depot and placebo groups File IND in 1Q/2016 Data expected in

16 Generic Copaxone Develop the API for GA Depot, for use as a generic form of Copaxone Favorable regulatory and IP environment: Approval and launch of Momenta s generic GA U.S. courts ruled that Teva s patent is no longer in force Engaged with discussions with companies for supply of GA as API for their needs Neot Hovav facility advantage: Significant favorable tax advantages as it was granted a Preferred Enterprise status allowing governmental cash grants of 20% and reduced tax rate of 9% Anticipated first sales of our generic GA API in

17 Pipeline of API & Finished Dosage Forms Glatiramer Acetate Darunavir (Para. IV) Fingolimod HCl Risperidone LAI Depot Dapagliflozin (Para. IV) Abiraterone Acetate Perampanel (Para. IV) Lurasidone HCl Dronedarone HCl Febuxostat Deferasirox Indacaterol Maleate Tapentadol HCl Alogliptin Benzoate (Para. IV) API Medical Indication Branded Drug and Sales in 2014* RRMS HIV RRMS Schizophrenia Type 2 Diabetes Prostate Cancer Epilepsy Schizophrenia Atrial Fibrillation Chronic Hyperuricemia Chronic Iron Overload Chronic obstructive pulmonary disease Acute pain Diabetes Copaxone (Teva) $4.23 B Prezista (J&J) $1.83 B Gilenya (Novartis) $2.51 B Risperdal Consta (J&J) $1.19 B Forxiga (BMS & AstraZeneca) $138 M Zytiga (J&J) $2.237 B Fycompa (Eisai) $40 M Latuda (DSP) $791 M (Forecast) Multaq (Sanofi) $385 M Uloric (Takeda) $455 M Exjade (Novartis) $926 M Onbrez, Arcapta (Novartis) $220 M Nucynta, Palexia (J&J) $220 M Nesina (Takeda) $421 M Earliest date of off-patent development (relevant territory) MAPI Asset 2015 (U.S.) API 2017 (U.S.), 2019 (U.S. label patent + Ritonavir) API & FDF MAPI IP Processes (US/EP Granted) Polymorphs US Granted 2017 (Israel) 2019 (U.S., E.U., Australia) API & FDF Processes US Granted 2013 (U.S.) 2021 (EU) FDF 2020 (U.S.) API & FDF CO-CRYSTALS US Granted 2017 (Israel) 2016 (U.S.) API Processes US Ganted 2021 (Canada) 2022 (U.S. and E.U.) API & FDF Polymrphs US Allowed 2018 (U.S.) API Processes US Granted 2019 (E.U.) 2016 (U.S.) API 2019 (U.S.) API 2017 (Canada) 2019 (U.S.) API 2020 (RU, China, L-America, Turkey) 2021 (Canada) 2024 (E.U.) 2025 (U.S.) API & FDF Processes (PCT) Polymorphs (PCT) Processes & Polymophs US Granted EP Allowed 2022 (U.S.) API Processes US Granted 2024 (E.U.) 2028 (U.S.) API Processes US Granted * 2014 Sales based on Thomson Reuters Cortellis platform Partnered 17