Corporate Presentation January 2017

Transcription

1 Corporate Presentation January 2017

2 2 Disclaimer References herein to this presentation (the Presentation ) shall mean and include this document, any oral presentation accompanying this document provided by Pharnext (the "Company") and any further information that may be made available in connection with the subject matter contained herein. This Presentation has been prepared by the Company and is provided for information purposes only. This document does not purport to contain comprehensive or complete information about the Company and is qualified in its entirety by the business, financial and other information that the Company is required to publish in accordance with the rules, regulations and practices applicable to companies listed on the Alternext Market of Euronext Paris, including, in particular, the risk factors set out in the Company s document de base registered by the French Financial Markets Authority (Autorité des marchés financiers) on June 2, 2016 under number I Information and other data appearing in such publications, and certain figures and numbers appearing in this document have been rounded. Consequently, the total amounts and percentages appearing in tables and elsewhere may not necessarily equal the sum of the individually rounded figures, amounts or percentages. No representation, warranty or undertaking, express or implied, is made as to the accuracy, completeness or appropriateness of the information and opinions contained in this Presentation, or its use for any purpose, and no reliance should be placed on any information or opinions contained herein. The Company, its subsidiaries and representatives accept no responsibility for and shall not, under any circumstance, be held liable for any loss or damage that may arise from the use of this document or the information or opinions contained in it. In particular, this document contains information on the Company s markets and competitive position, and more specifically, on the size of its markets. This information has been drawn from various sources or from the Company s own estimates which may not be accurate and thus no reliance should be placed on such information. The information and opinions contained in this document are provided as of the date of this document only and may be updated, supplemented, revised or amended, and thus such information is subject to change at any time. The Company is not under any obligation to update the information, statements or opinions contained in this Presentation. All statements in the Presentation other than statements of historical fact are or may be deemed to be forward-looking statements. These forwardlooking statements are not guarantees of future performance and involve a number of known and unknown risks and uncertainties. These risks and uncertainties, and other factors, could adversely affect the outcome of the forward looking statements, and actual results could differ materially from those contemplated in the statements. As a result, you are cautioned not to rely on such forward-looking statements. Forward-looking statements speak only as of the date of this document and the Company expressly disclaims any obligation or undertaking to update or re-issue any forward-looking statements contained in this Presentation. This Presentation does not constitute or form any part of any offer to sell, or the solicitation of an offer to buy or subscribe for, any shares or securities in the Company, in the United States or in any other jurisdiction. All persons accessing this document are deemed to agree to all the limitations and restrictions set out above.

3 3 Company Overview Public biopharmaceutical company (Alternext : ALPHA) leader in synergistic combinatorial medicine Late stage pipeline focused on neurodegenerative diseases (orphan & common) with 2 clinical-stage products respectively in Phase 2 and Phase 3 clinical trials PXT3003 in pivotal Phase 3 for treatment of an orphan peripheral neuropathy: Charcot-Marie- Tooth Disease Type 1A (CMT1A) PXT864 in Phase 2 for treatment of Alzheimer s Disease and with high potential in other major neurodegenerative indications such as Parkinson s and ALS Universal R&D platform: PLEOTHERAPY to identify and develop synergistic combinations of repositioned drugs at low doses More efficient, safer, faster and affordable drug development process, compared to monotherapy Potentially applicable to any diseases in any geographical areas Founded and led by a deeply experienced management team with the support of first class science and clinical advisors (3 Nobel prizes winners)

4 4 Robust Late-Stage Development Pipeline PHASE OF DEVELOPMENT PRODUCT INDICATION PRECLINICAL PHASE 1 PHASE 2a PHASE 2b PHASE 3 EXPECTED NEXT EVENT PXT3003 CMT1A Adults CMT1A Children (no Phase 1 required) a Results expected in Q Other peripheral neuropathies PXT864 Alzheimer s Disease Parkinson s Disease Results of Phase 2a presented at CTAD* Launch of Phase 2b in H Results expected in 2019/2020 Amyotrophic Lateral Sclerosis b Note (a): The CMT program went through Phase 2 directly after the preclinical results. Phase 1 was not required by French health authorities (ANSM) Note (b): Amyotrophic Lateral Sclerosis is also called Charcot Disease *9th Clinical Trials on Alzheimer's Disease (CTAD) Conference on December 8-10, 2016 in San Diego, CA

5 Pleotherapy Platform

6 6 Novel Multi-Target Approach to Address Diseases with No Treatments CLASSICAL APPROACH MONOTHERAPY Monomolecule PHARNEXT APPROACH PLEOTHERAPY Synergistic combination of repositioned drugs at low dose Lower than combinations EFFICACY More responders and higher response per responder Difficult to predict SAFETY Likely higher (already approved drugs at low dose) 15 years / high attrition rate DEVELOPMENT TIME 10 years / low attrition rate because of higher safety & efficacy Composition of matter on a new molecule IP Composition of matter on new combinations of off-patent drugs High / challenged TARGET PRICE Lower / affordable

7 7 We Build Map of the Disease Network and Identify the Best Lower Dose Combinations to Treat the Disease Monotherapy One drug at high dose for one therapeutic target Pleotherapy Synergistic low-dose combination of drugs for any indication Drug A Drug C Drug B Drug A

8 8 Faster, Safer, More Efficient and Affordable Drug Development Process Discovering the complex molecular network of a disease => inventory of all possible therapeutic targets Screening and repositioning approved drugs at low-dose in order to identify synergistic combinations Protein A Drug A >2,000 available drugs In Silico Screening 50 candidate drugs In Vitro Protein C Protein B Drug B Drug C 25 positive drugs In Vivo 4 synergistic combos 1 PLEODRUG In Human

9 9 Our R&D Process is 5 Years Faster Classical Model: A long and expensive process lasting 15 years with high attrition rates RESEARCH PHASE DEVELOPMENT PHASE Target Identification Drug Identification Preclinical Development In human 6 years 9 years Pharnext Model: A faster development of effective and safe drugs at reduced cost lasting 10 years RESEARCH PHASE DEVELOPMENT PHASE Network Mapping In vitro In vivo In human In silico screening (no Phase 1 required) 3 years 7 years

10 10 High-Value Opportunities in a Broad Spectrum of Diseases 26 disease networks already mapped, many of which await therapeutic targeting CMT MULTIPLE SCLEROSIS ASTHMA PSORIASIS DIABETIC NEUROPATHIES DOWN S SYNDROME CANCER (2) RHEUMATOID ARTHRITIS TOXIC NEUROPATHIES AXONAL GROWTH CORONARY DISEASE SLE (3) NEUREGULIN SIGNALING MYOPATHIES CROHN S DISEASE TYPE 2 DIABETES ALZHEIMER S DISEASE SCHIZOPHRENIA HIGH BLOOD FATS ULCERATIVE COLITIS PARKINSON S DISEASE STROKE HYPERTENSION PXT3003 ALS (1) MEMORY POLYCYSTIC KIDNEY PXT864 Preclinical pipeline Note 1: ALS = Amyotrophic Lateral Sclerosis Note 2: Includes glioma, hepatoma, melanoma, lung cancer, prostate cancer Note 3: SLE = Systemic Lupus Erythematosus

11 PXT3003

12 12 Overview of Charcot Marie Tooth Disease Type 1A Characteristics / Symptoms Chronic, severe, debilitating inherited neuropathy leading to muscle atrophy in extremities: walking and hand disabilities up to handicap Population ~100,000 people affected with mild to moderate CMT1A in US and EU5 Treatment Options No drug approved or in clinical development, only supportive care Barriers to entry Outcome Expected Peak Sales In addition to robust IP until at least 2030, orphan drug status in US and EU5 provides market exclusivity In most patients, disease is stabilized while a fair proportion is even improved Approx. > $ 1 billion (US +EU5)

13 13 Targeting the Cause of the Disease with PXT3003 Disease at a glance Schwann cells constitute myelin which isolates and nurtures axons CMT 1A is due to overexpression of PMP22 protein in Schwann cells that are impaired Schwann cell Opioid receptor GABA receptor Network analysis The CMT network Muscarinic receptor Design of PXT3003 Naltrexone Opioid receptor Baclofen GABA receptor Myelin Sheath Cell Body Basement membrane Myelin Sheath Normal Myelin Impairment Suffering Death 1 Lowers expression of PMP22 gene 2 Improves myelination 3 Preserves axons 4 Improves motor function Sorbitol Muscarinic receptor Axon Muscle

14 14 Phase 2 Trial Overview Assessment Measures 1/1000 PXT3003: Naltrexone + Baclofen + Sorbitol Efficacy Safety and tolerability Low dose n=21 1/200 1/ endpoints including Overall Neuropathy Limitation Scale (ONLS)* No Phase 1 needed Phase 2 Trial Design 12-month treatment 6 reference centers in France Placebo-controlled, randomized and double-blind Oral liquid formulation given twice daily Dosing Same fixed ratio of 3 different doses ranging from 1/1,000 to 1/20 of approved drugs 80 mild-tomoderate adult patients with CMT1A 4-arm study Naltrexone Naltrexone Baclofen Baclofen Sorbitol Intermediate Dose n=21 High Dose n=19 Placebo n=19 1/500 1/100 1/125 1/100 1/20 1/25 0,7 mg 6 mg 210 mg *ONLS is a scale for doctor investigation assessing disability

15 15 Promising and Significant Phase 2 Efficacy Results Improvement on ONLS recommended by FDA/EMA as primary endpoint for Phase 3 ONLS improvement sufficient by FDA/EMA for approval if reproduced in Phase % improvement vs. placebo (p=0.04) in ONLS Main Efficacy Criteria (ONLS) P HD M12 vs. Plb M12 <0.05 P Dose Effect <0.01 P HD M12 vs. Baseline M12 = 0.06

16 16 Ongoing Phase 3 Trial in North America and Europe Endpoints defined with FDA & EMA Primary endpoint: ONLS Secondary endpoints: clinical, functional, electrophysiological and quality of life Phase 3 Trial Design Pivotal, randomized, double blind, placebo-controlled, three arms International study in 30 centers across North America and Europe 15-month double blind + 9-month extension study Naltrexone Baclofen Baclofen Sorbitol 323 mild-tomoderate patients (age >16) with CMT1A and PMP22 gene duplication Phase 2 high dose n=108 2 x Phase 2 high dose n=108 Placebo n= mg 6 mg 210 mg 1.4 mg 12 mg 420 mg 1st patient recruited Q4 2015, last Q Adaptive design analysis at 80 patients in Q Futility analysis at 100 patients to be completed in Q Results expected Q2:2018 Potential market approval in first FDA exemption from single drug testing in man in a combination therapy Formulation: oral liquid solution given twice a day

17 PXT864

18 18 Alzheimer s Disease Overview Characteristics / Symptoms Population Irreversible, progressive neurodegeneration leading to a state of dementia 1 in 8 people 65+ suffer from Alzheimer s disease ~100 million cases expected by 2050 unless effective treatments discovered Seventh leading cause of death in USA Treatment Options Poorly efficient on symptoms with frequent side effects and tolerability issues Barriers to entry IP including composition of matter patents for PXT864 Outcome Any better symptomatic relief or disease-modifying effects would be a success Expected Peak Sales An efficient treatment could be a $5-$20 billion market opportunity Significant co-prescription opportunities with potentially competitive treatments

19 19 Targeting to Restore the Disrupted Excitatory-Inhibitory Balance Design of PXT864 Network analysis Healthy brain Glu No Aβ Disease at a glance GABA Alzheimer s brain Glu Glutamate and GABA are the major excitatory and inhibitory neurotransmitters of the brain Glutamate neuron Aβ GABA neuron GABA Network analysis implicates glutamate/gaba imbalance in Alzheimer s disease GABA receptor Baclofen Acamprosate Increased Aβ toxicity and level GABA receptor Glutamate receptor Breaking the vicious circle Disrupted Excitatory- Inhibitory balance Increased Aβ toxicity and level Disrupted Excitatory- Inhibitory balance Glutamate receptor

20 20 Poly-Efficacy of PXT864 Protects neurons against Aβ toxicity Preserves synaptic integrity Pharnext Pleodrug PXT864 Synergistic with standard of care Protects vessels against Aβ toxicity Baclofen Acamprosate Alleviates cognitive deficits in Alzheimer animals Decreases inflammation Reduces Aβ levels

21 21 Highly Promising Phase 2a Results To Be Presented at 2016 CTAD Meeting Design Phase 2a trial completed end patients with mild Alzheimer s Disease 5 French memory centers Single-blind crossover study 12-week duration 6-month follow-up for safety 3 doses tested Formulation: pill given twice daily Outcome Significant improvement in cognitive function measured by ADAS-cog during active treatment PLEODIAL I Month 1 Month 2 Month 3 PLEODIAL II Month 3 to 9 PXT864 placebo PXT864 PXT864 +/- Aricept T Challenge challenge De-challenge de-challenge Re-challenge re-challenge Combine with Aricept

22 22 Potential in Other Neurodegenerative Diseases Networks suggest similar imbalance in Parkinson s and ALS Publication of Preclinical Results in Parkinson s in Nature Scientific Reports (2015) PXT864 could be developed in Parkinson s disease and Amyotrophic Lateral Sclerosis (ALS)

23 Corporate Summary

24 24 Deeply Experienced Management Team Prof. Daniel Cohen, MD, PhD CEO & Founder Catherine Chalandon VP Operations & Strategy Pierre Schwich Chief Financial Officer René Goedkoop, MD Chief Medical Officer Serguei Nabirotchkin, PhD Chief Biology Officer & Co-Founder Xavier Paoli Director of Commercialization Strategy

25 25 Unparalleled Scientific Advisory Board Ilya Chumakov, PhD, D-Sc Chairman, Co-founder Pioneer in genetics, genomics and molecular pharmacology Prof. David Cornblath, MD Expert in peripheral nerve disorders Chief editor of Journal of the Peripheral Nervous System and of Journal of the Peripheral Nerve Prof. Wally Gilbert, PhD Nobel Prize in Chemistry 1980 Prof. Eric R. Kandel, MD Nobel Prize in Chemistry 2000 Prof. Jean-Marie Lehn, PhD Nobel Prize in Chemistry 1987 Innovator in supramolecular chemistry Prof. Richard Lewis, MD Expert in inflammatory and hereditary neurological diseases, discoverer of the Lewis-Summer syndrome Prof. Anthony Schapira, MD Expert in Parkinson s disease Prof. Michael Sereda, MD, PhD Expert in hereditary neuropathies, creator of the PMP22 transgenic rat model

26 26 Financial Summary Operating Expenses (6 months) Revenues (6 months) Cash Equity Financial Liabilities Data (pro-forma post IPO) in K as of June 30, 2016 Listed on Euronext Alternext Stock Exchange in Paris (ISIN code: FR ) 10,784,615 Shares Outstanding and 11,817,940 Fully Diluted (as of 10/31/16)

27 27 Shareholdings Shareholding Structure as of December 2016 Outstanding Shares : Shareholding Structure fully diluted ( ) 4% 18% 13% 4% 16% 18% 16% 31% 17% 29% 18% 16% Managers & advisers Truffle Capital Managers & advisers Truffle Capital Pierre Bastid Other historical shareholders Pierre Bastid Other historical shareholders Corporate investors Other Corporate investors Other

28 28 Newsflow Upcoming Milestones Realized To come PXT3003 in CMT1A Q4: Last patient enrolled in Phase 3 trial H2: Interim analysis Q2: Final results of Phase 3 trial Submission for marketing approval (FDA + EMA) E 2018E 2019E PXT864 in Alzheimer s H2: Final results of Phase 2a trial H2: Initiation of Phase 2b trial H2: Initiation of PXT864 new formulation study Final results of Phase 2b trial

29 Corporate Presentation January Appendix

30 Very Strong Patentability and Enforceability 340+ patent applications and ~100 granted patents across 13 diseases worldwide PXT3003 PXT864 Composition of matter granted in EU, pending in US Method of use granted in both EU and US Formulation claims pending in both EU and US Composition of matter pending in EU and granted in US Method of use granted in both EU and US Compounding not authorized in US / major EU countries when alternative product approved Program Patent PCT Number Scope Filing Date Expiry Date Status PXT-3003 CMT2 WO Composition of matter for binary compositions covering PXT-3003 Method of use for binary compositions covering PXT-3003 Nov 2008 EU Nov 2028 US Jul 2031 CMT4 WO Composition of matter and method of use for PXT-3003 May 2010 May 2030 Granted EU Granted EU/US Granted EU, Pending US CMT7 WO Formulation for PXT-3003 June 2014 June 2034 Pending EU/US PXT-864 AD2 WO Method of use for baclofen Apr 2009 Apr 2029 Pending EU/US AD7 WO Composition of matter and method of use for PXT Composition of matter for PXT-864 combined with donepezil Mar 2012 Mar 2032 Granted EU (1) /US PXT-864 PD1 WO Method of use for PXT-864 in Parkinson s Feb 2013 Mar 2032 Pending EU/ Granted US 30 (1) Except composition of matter for PXT-864 which is pending in EU