CORPORATE PRESENTATION

Transcription

1 NOVEMBER 2018 CORPORATE PRESENTATION November 2018 I. CORPORATE HIGHLIGHTS II. LEADERSHIP IN NASH & PBC APPENDIX 1

2 Disclaimer Important Information and Forward Looking Statements THIS PRESENTATION HAS BEEN PREPARED BY GENFIT AND IS FOR INFORMATION PURPOSES ONLY. CERTAIN OF THE INFORMATION CONTAINED HEREIN CONCERNING ECONOMIC TRENDS AND PERFORMANCE IS BASED UPON OR DERIVED FROM INFORMATION PROVIDED BY THIRD-PARTY CONSULTANTS AND OTHER INDUSTRY SOURCES. WHILE GENFIT BELIEVES THAT SUCH INFORMATION IS ACCURATE AND THAT THE SOURCES FROM WHICH IT HAS BEEN OBTAINED ARE RELIABLE, GENFIT HAS NOT INDEPENDENTLY VERIFIED THE ASSUMPTIONS ON WHICH PROJECTIONS OF FUTURE TRENDS AND PERFORMANCE ARE BASED. IT MAKES NO GUARANTEE, EXPRESS OR IMPLIED, AS TO THE ACCURACY AND COMPLETENESS OF SUCH INFORMATION. THIS PRESENTATION CONTAINS CERTAIN FORWARD-LOOKING STATEMENTS OR INFORMATION. ALTHOUGH THE COMPANY BELIEVES ITS EXPECTATIONS ARE BASED ON REASONABLE ASSUMPTIONS, THESE FORWARD-LOOKING STATEMENTS OR INFORMATION ARE SUBJECT TO NUMEROUS RISKS AND UNCERTAINTIES, WHICH COULD CAUSE ACTUAL RESULTS TO DIFFER MATERIALLY FROM THOSE EXPRESSED IN, OR IMPLIED OR PROJECTED BY, THE FORWARD-LOOKING STATEMENTS. THESE RISKS AND UNCERTAINTIES INCLUDE AMONG OTHER THINGS, THE UNCERTAINTIES INHERENT IN RESEARCH AND DEVELOPMENT, INCLUDING RELATED TO BIOMARKERS, PROGRESSION OF, AND RESULTS OF CLINICAL DATA FROM, THE RESOLVE-IT TRIAL, REVIEW AND APPROVALS BY REGULATORY AUTHORITIES, SUCH AS THE FDA OR THE EMA, REGARDING IN PARTICULAR, ELAFIBRANOR IN NASH AND PBC, AS WELL AS OTHER DRUG CANDIDATES IN OTHER INDICATIONS, AND BIOMARKERS, THE SUCCESS OF ANY INLICENSING STRATEGIES, THE COMPANY S CONTINUED ABILITY TO RAISE CAPITAL TO FUND ITS DEVELOPMENT, AS WELL AS THOSE DISCUSSED OR IDENTIFIED IN THE COMPANY S PUBLIC FILINGS WITH THE AMF, INCLUDING THOSE LISTED UNDER SECTION 4 MAIN RISKS AND UNCERTAINTIES OF THE COMPANY S 2017 REGISTRATION DOCUMENT REGISTERED WITH THE FRENCH AUTORITÉ DES MARCHÉS FINANCIERS (AMF) ON APRIL 27, 2018 UNDER NO. R , WHICH IS AVAILABLE ON GENFIT S WEBSITE ( AND ON THE WEBSITE OF THE AMF ( OTHER THAN AS REQUIRED BY APPLICABLE LAW, THE COMPANY DOES NOT UNDERTAKE ANY OBLIGATION TO UPDATE OR REVISE ANY FORWARD-LOOKING INFORMATION OR STATEMENTS. THE INFORMATION, OPINIONS AND FORWARD LOOKING INFORMATION CONTAINED IN THIS PRESENTATION SPEAK ONLY AS OF THE DATE OF THIS DOCUMENT, UNLESS OTHERWISE INDICATED HEREIN. OTHER THAN AS REQUIRED BY APPLICABLE LAW, GENFIT IS NOT UNDER ANY, AND UNDERTAKES NO OBLIGATION TO, UPDATE OR KEEP CURRENT THE INFORMATION CONTAINED IN THIS PRESENTATION AND ANY OPINIONS EXPRESSED THEREIN ARE SUBJECT TO CHANGE WITHOUT NOTICE. NO REPRESENTATION OR WARRANTY, EXPRESS OR IMPLIED, IS MADE AS TO, AND NO RELIANCE SHOULD BE PLACED UPON, THE FAIRNESS, ACCURACY, COMPLETENESS OR CORRECTNESS OF THE INFORMATION OR OPINIONS AND NONE OF THE COMPANY, ITS SUBSIDIARIES, ITS SHAREHOLDERS, OR ITS RESPECTIVE DIRECTORS, OFFICERS, ADVISORS, AGENTS, EMPLOYEES, AGENTS AND REPRESENTATIVES ACCEPTS ANY RESPONSIBILITY OR ANY LIABILITY (IN NEGLIGENCE OR OTHERWISE) WHATSOEVER FOR/OR MAKES ANY REPRESENTATION OR WARRANTY, EXPRESS OR IMPLIED, AS TO THE TRUTH, FULLNESS, ACCURACY OR COMPLETENESS OF THE INFORMATION (OR WHETHER ANY INFORMATION HAS BEEN OMITTED FROM THE INFORMATION) OR ANY OTHER INFORMATION RELATING TO THE COMPANY, ITS SUBSIDIARIES OR ASSOCIATED COMPANIES, WHETHER WRITTEN, ORAL OR IN A VISUAL OR ELECTRONIC FORM, AND HOWSOEVER TRANSMITTED OR MADE AVAILABLE OR FOR ANY LOSS ARISING FROM ANY USE OF THIS PRESENTATION OR ITS CONTENTS OR OTHERWISE IN CONNECTION WITH THIS PRESENTATION OR THE INFORMATION. THIS PRESENTATION SHALL NOT CONSTITUTE AN OFFER TO SELL OR THE SOLICITATION OF AN OFFER TO BUY SECURITIES, NOR SHALL THERE BE ANY SALE OF THESE SECURITIES IN ANY STATE OR JURISDICTION IN WHICH SUCH OFFER, SOLICITATION OR SALE WOULD BE UNLAWFUL PRIOR TO REGISTRATION OR QUALIFICATION UNDER THE SECURITIES LAWS OF ANY SUCH STATE OR JURISDICTION. IT DOES NOT CONSTITUTE ANY FORM OF COMMITMENT ON THE PART OF THE COMPANY OR ANY OTHER PERSON. ANY SUCH OFFERING OF SECURITIES WILL ONLY BE MADE BY MEANS OF A REGISTRATION STATEMENT (INCLUDING A PROSPECTUS) FILED WITH THE SEC, AFTER SUCH REGISTRATION STATEMENT IS DECLARED EFFECTIVE. NO SUCH REGISTRATION STATEMENT HAS BEEN DECLARED EFFECTIVE, AS OF THE DATE OF THIS PRESENTATION. 2

3 I. CORPORATE HIGHLIGHTS 3

4 Company Profile BACKGROUND Public company focused on metabolic diseases and associated complications, including liver related disorders World-leading expert in nuclear receptor based drug discovery Lead drug candidate discovered in-house Founded in 1999 (Lille, Paris, France Cambridge, United States) 150 employees Since 2006, Euronext Paris compartment B (GNFT) Market capitalization of ~ 700M 220 million cash balance (Q3 2018) MAIN PROGRAMS Elafibranor: First-in-class molecule NASH Phase 3 enrolled (Subpart H), accelerated approval process (Subpart H with FDA; Conditional approval with EMA) and fast-track designation PBC Phase 2 (12-week treatment period completed for the last patient) Biomarker program in NASH for non invasive and easy-to-access IVD (In-Vitro Diagnostic) Strong IP protection with full worldwide rights 4

5 Experienced Management Team and Highly Respected Advisory Board Jean-François Mouney, Chief Executive Officer, co-founded the company in 1999 The executive team and board of directors have a deep experience at leading biotech companies, large pharmaceutical companies and academic institutions Pr. Bart Staels, chair of the scientific advisory board and co-founder of the company, is a world-renowned expert in nuclear receptors The scientific advisory board is comprised of internationally recognized key opinion leaders in the field of metabolic and inflammatory diseases, with a particular focus on the liver and gastroenterology The expertise, leadership and strength of the company s relationships within the academic and clinical communities are critical to its ability to execute on its mission as it progresses its development pipeline 5

6 A Comprehensive Strategy in Liver and Metabolic Healthcare 1. TREATMENT Providing THERAPEUTIC SOLUTIONS 2. DIAGNOSTIC Identifying PATIENTS ELIGIBLE FOR TREATMENTS 3. AWARENESS Optimizing STANDARD of CARE 4. MARKET ACCESS Preparing for COMMERCIALIZATION 6

7 Robust Pipeline Focused on Liver and Metabolic Diseases With Near-Term Clinical Milestones 7

8 Upcoming Expected Catalysts PBC (elafibranor) PHASE 2 DATA READOUT NASH (elafibranor) PHASE 3 DATA READOUT NASH Pediatric (elafibranor) PHASE 2 1st PATIENT NASH Fibrosis (nitazoxanide) PHASE 2 POC START NASH Diagnostic (biomarkers) PARTNERSHIP 8

9 NOVEMBER 2018 II. LEADERSHIP IN NASH AND PBC 9

10 A Potential to Become a Leader in NASH and PBC 1. TREATMENT ELAFIBRANOR NASH PBC 10

11 NASH, a Disease Leading to Cirrhosis and HCC, Represents a Large and Untapped Market Leading cause of liver disease in developed countries; ~20 million in the United States suffer from NASH and advanced fibrosis Cardiovascular events are the leading cause of death in NASH Multifaceted disease Market estimations: up to $20bn by 2025 Matteoni, Gastro 1999 Adams, Gastro 2005 Ekstedt, Hepatol 2006 Ong, J Hepatol 2008 Dunn, AJG 2008 Sorderberg, Hepatol 2010 Targher, NEJM 2010 Williams, Gastro 2011 Chalasani, Gastro 2012 Torres, Clin Gastro Hepatol 2012 Wree, Nat. Rev Gastroenterol Hepatol 2013 Rinella, JAMA 2015 Bazick, Diabetes Care

12 Elafibranor, Elafibranor, First-in-class, has Pluripotent Activities Activities: PPARα/δ Regulate Multiple Pathways Essential in NASH PPARa and d Regulate Multiple Pathways Essential in NASH 12

13 SECOND wave candidates FIRST wave candidates Elafibranor Is One of the Most Advanced NASH Product Candidate PHASE 3 interim DATA READOUT Elafibranor (Genfit) Ocaliva (Intercept) Selonsertib (Gilead) Cenicriviroc (Allergan) Potential NDA Submission PHASE 2 DATA READOUT MGL-3196(Madrigal) Aramchol (Galmed) NGM-282 (NGM) VK2809 (Viking) 13

14 Evidence from Phase 2 NASH Trials Elafibranor is the only product candidate from the first wave in NASH to have demonstrated all four of (i) EFFICACY ON "NASH RESOLUTION WITHOUT WORSENING OF FIBROSIS" (ii) IMPROVEMENT OF LIPID PROFILE (iii) IMPROVEMENT OF METABOLIC PROFILE (iv) TOLERABILITY TOP LINE COMPARISON on EFFICACY for "NASH RESOLUTION without worsening of fibrosis" (approved/relevant endpoint for Phase 3 trials and market approval) 1 st wave candidates Elafibranor 1 (GENFIT) 26% vs 5% (p-value 0.02) Ocaliva 2 (INTERCEPT) 20% vs 6% (p-value 0.03) Selonsertib (GILEAD) N/A Cenicriviroc (ALLERGAN) N/A 2 nd wave candidates MGL (MADRIGAL) 25% vs 6% (p-value 0.03) Aramchol 2 (GALMED) 17% vs 5% (p-value >0.05) NGM (NGM) 11% (no placebo) VK (VIKING) N/A (1) Ratziu et al, 2016 Gastroenterology (centers with randomization in all arms, to take into account the well known heterogeneity in the standard of care of NASH patients in different centers) (2) Source: Corporate publications/presentations. Data not published in peer-reviewed scientific journals 14

15 Elafibranor Elafibranor Phase in NASH 2b Results: A Solid Ground for RESOLVE-IT Phase 3 trial GOLDEN-505 Phase 2 Results* Data published in peer-review journal Elafibranor resolved NASH without worsening of fibrosis, which has been recommended as primary endpoint for Phase 3 pivotal trials in NASH: Ballooning = 0; Inflammation = 0 (or 1); No worsening of fibrosis (1 stage) Elafibranor confirmed it can improve the cardiometabolic risk profile of NASH patients Elafibranor was safe and well tolerated 15

16 Elafibranor Elafibranor Phase in NASH 2b Results: Additional Key Benefits for NASH Patients GOLDEN-505 Phase 2 Results* Beneficial effect on Lipid Markers in NASH patients Beneficial effect on - Glucose Homeostasis - Insulin Sensitivity in T2D NASH Patients Clean - Safety profile - Tolerability profile ON TOP OF STANDARD of CARE LDL-c ("bad cholesterol) TG (triglycerides) HDL-c ( good cholesterol) ON TOP OF STANDARD of CARE HbA1c (glucose homeostatis) HOMA-IR (insulino resistance) Crucial for a chronic and silent disease SAFETY clinical outcomes It is imperative that any drug developed for NASH be at least neutral from a cardiovascular risk perspective and ideally also reduce cardiovascular risks (Hepatology 2015) Even using a low assumption for NAFLD prevalence in T2D patients, it is estimated that 84MM people in the U.S. live with prediabetes or T2D and NAFLD. Moreover, the coexistence of NAFLD and T2DM results in a worse metabolic profile and a higher cardiovascular risk. (Bril, Cusi, Diabetes Care 2017) TOLERABILTY compliance efficacy in real world 16

17 Elafibranor Phase 3 Design: Details and Timing > 250 centers (worldwide) ~ 1000 patients ACCELERATED MARKET AUTHORIZATION SUBPART H (FDA) CONDITIONAL APPROVAL (EMA) ~ 2000 patients FIRST TREATMENT PERIOD 18 MONTHS EXTENSION PERIOD Placebo Elafibranor 120mg 2:1 Placebo Elafibranor 120mg 2:1 TRIAL INITIATION Q WEEK INTERIM ANALYSIS END OF STUDY Study population: patients at risk of progression to clinical events NASH with a NAS 4 Fibrosis stage F2 and F3 (F1 + cardiometabolic risk) End of enrollment first ~1000 patients for Subpart H: April 2018 Histological primary endpoint NASH RESOLUTION WITHOUT WORSENING OF FIBROSIS (central reading for all biopsies): Ballooning = 0 Inflammation = 0 (or 1) Without worsening fibrosis (1 stage) Histological key secondary endpoint improvement of histological fibrosis (to be considered as an additional labeling claim) Prevention of NASH associated clinical events, including cirrhosis resulting from progressive fibrosis Read-out ~2000 patients: based on occurrence of a pre-defined number of events Read-out first ~1000 patients: End of

18 Clinical Requirements for Future Combinations: Elafibranor Well Positioned as Backbone Therapy ANTI-NASH drug candidates PURE ANTI-FIBROTIC drug candidates 1 2 Addressing NASH (the underlying cause) Addressing FIBROSIS (the consequence) Among product candidates in Phase 3, only ELAFIBRANOR and OCALIVA have the potential to address both NASH and fibrosis 3 Ensuring a clean SAFETY/TOLERABILITY ELAFIBRANOR has demonstrated a favorable safety and tolerability profile based on Phase 1 and Phase 2 clinical trials 18

19 Proactive Evaluation of Potential "Add-on" Drug Candidates for Elafibranor in NASH BACKBONE Add-On ELAFIBRANOR DRUG X ELAFIBRANOR ELAFIBRANOR ELAFIBRANOR NTZ FXR ACC ELAFIBRANOR + ANTI-T2D 19

20 PBC (Primary Biliary Cholangitis): Elafibranor Well Positioned to Address Unmet Needs in this Severe Chronic Liver Condition HIGH UNMET NEEDS Cholestatic chronic autoimmune disease Affecting intrahepatic bile ducts Severe liver disease Prevalence in the general population: 0.05% Patient profile: women years old RATIONALE for ELAFIBRANOR Elafibranor consistently showed positive effects on ALP in all studied populations + Clinical evidence of beneficial effects induced by PPARα and PPARδ in PBC populations, supported by a pluripotent mechanism of action + Significant proportion of non/partial responders with current treatments in PBC patient population Major symptom in PBC is pruritus and is not addressed by current PBC therapies Recent evidence showing the potential of PPARα to alleviate pruritus, a major symptom of PBC 20

21 Phase 2a Study with Elafibranor in PBC (Primary Biliary Cholangitis) 1 st Patient enrolled May WEEK ANALYSIS TREATMENT PERIOD 12 WEEKS Placebo Elafibranor 80mg 2:1 Elafibranor 120mg Study population adult patients with PBC and inadequate response to ursodeoxycholic acid (UDCA) Primary endpoint effect of daily oral administration of elafibranor on serum alkaline phosphatase (ALP) End of enrollment 45 patients: July 2018 Read-out 45 patients: End 2018 Secondary endpoints include: ALP < 1.67 upper limit of normal (ULN) and total bilirubin within normal limit and > 15% decrease in ALP Paris, Toronto, UK PBC scores Pruritus and QoL (Quality of Life) Safety of elafibranor in a PBC population 21

22 A Pioneering & Proactive Approach to Unlock the NASH Market 2. DIAGNOSTIC Towards a large scale industrial solution 22

23 NASH Diagnosis: A Need for Simple Blood-based Solutions Current bottleneck BIOPSY IMAGING TECHNIQUES Imperfect "Gold Standard" Non-invasive, but limited Ideal situation there is an urgent unmet need to develop biomarkers that facilitate the diagnosis, identification of populations at risk, assessment of disease progression or regression, and/or response to treatment. Page 1401 BLOOD TEST Potential for large scale adoption in the clinic 23

24 GENFIT s Approach Designed to Ensure the NASH Market Can Reach its Full Potential Focus on a specific and relevant clinical question: HEALTHY NAFLD CIRRHOSIS NO NASH NASH NO TO BE TREATED Steatosis 1 Ballooning 1 Inflammation 1 NAS 4 F2 or higher LDT release in 2019 Regulatory submission for approval anticipated in 2020 (US, EU) 24

25 The Future Patient Journey with IVD Test, for Better Clinical Management of NASH Patients 25

26 A Pioneering & Proactive Approach to Unlock the NASH Market 3. AWARENESS 26

27 The NASH Education Program TM For BETTER CARE NASH (Non-Alcoholic SteatoHepatitis) PHYSICIANS Incl. DIABETOLOGISTS, ENDOCRONOLOGISTS, CARDIOLOGISTS, GPs PATIENTS Individuals at risk, Families 1 2 Serious liver condition Unprecedented rise in prevalence Sub-Optimal PATIENT CARE 3 Yet still little known, because Silent, by nature Diagnostic = bottleneck No approved treatment yet HIGH UNMET NEEDS The NASH Education Program TM 27

28 A Worldwide Success for the Inaugural Edition of International NASH Day, in 25+ Countries A large coalition of 20+ stakeholders, across the United States, Europe, and LATAM, including: Patient associations Learned societies Companies 28

29 A Relevant Approach to Market Access to Prepare for Commercialization 1. TREATMENT Ideal drug profile 1st line treatment monotherapy Cornerstone combination therapies 2. DIAGNOSIS Market Enabler (patient identification) 4. MARKET ACCESS 3. AWARENESS Market Enabler (physicians knowledge) 29

30 A Strategy to Maximize Sales Uptake and Transform the Company Elafibranor: uniquely positioned in the first wave of NASH products Objective: transform GENFIT into a biopharma, with a mixed revenue stream from: Direct sales of elafibranor Royalties from potential licensing deal World class launch plan Currently recruiting a team of experienced pharma leaders in the field of marketing and market access People who have joined the team have worked on several global launches and have years of combined experience in big pharma in Europe and the US Commercialization strategy Open to explore potential alliance with large pharma company, preferably with a solid footprint in metabolic diseases 30

31 APPENDIX 31

32 Financial Highlights Successul track record in fund raisings March 2016: private placement 50 million October 2016: private placement 34 million November 2016: rights issue 45 million October 2017: convertible bonds 180 million 32

33 % patients Ballooning and Inflammation (NASH Activity Index ) are Correlated with Fibrosis Reducing Ballooning & Inflammation correlates with Fibrosis improvement Worsening Ballooning & Inflammation correlates with Fibrosis worsening N=7 N=39 N=77 N=82 N=27 N=5 Fibrosis Improvers Fibrosis Worseners p< Reducing Ballooning & Inflammation Change in Activity Index (Ballooning + Inflammation) = NASH disease activity GOLDEN505 dataset / P-value derived from Khi2 after grouping of extreme with low counts / full study population Worsening Ballooning & Inflammation 33

34 NASH and Fibrosis: Two Simple Analogies to Understand the Disease Paradigm UNDERLYING CAUSE = Primary Target for Pharmaceutical Drugs Measure of Progression Clinical Outcome HIV HCV Abacavir, dolutegravir, etravirine, rilpivirine, etc. Sofosbuvir, simeprevir, dasabuvir, etc. FIBROSIS CIRRHOSIS NASH Elafibranor, first drug that targets NASH resolution CIRRHOSIS F4 Arun Paris NASH Symposium

35 Effect size vs placebo (Absoute change - mmol/l) Effect size vs placebo (% of baseline) Effect size vs placebo (%) Elafibranor Elafibranor Phase in NASH 2 Results: A Closer Look at Cardiometabolic Data GOLDEN-505 Phase 2 Results* Elafibranor 120mg vs Placebo on Lipid Markers Elafibranor 120mg vs Placebo on Glucose Homeostasis and Insulin Sensitivity in T2D NASH Patients 0,2 0,1 0-0,1-0,2-0,3-0,4-0,5-0,6-0,7-0,8 *** *** *** *** ** *** # # # ## ## # 0-0,1-0,2-0,3-0,4-0,5-0,6-0,7-0,8-0.46% # HbA1c -0,0 GFT ** : p<0.01 *** : p<0.001 # : p<0.05 ## : p<0.01 Significant decrease in HbA1c vs placebo 35

36 Elafibranor: Potential for First-Line Standalone Monotherapy, and also a Strong Foundation for Combination Therapy Favorable efficacy/safety/tolerability profile (phase 2b) Proactively identify the most effective combination therapies which: Reinforce elafibranor s demonstrated efficacy on NASH resolution Reinforce elafibranor s activity on fibrosis improvement ELAFIBRANOR (PPARa/d) DRUG X Example #1: Elafibranor + FXR Insulin sensitivity Plasma TGs, LDLc HDLc Steatosis Inflammation/Ox stress Hepatocyte damage NAS score Fibrosis (for patients resolving NASH) + Additionnal activity based on a complementary mechanism of action CSAA Example #2 : Elafibranor + NTZ CDAA/c control CDAA/c ELA 1mpk CDAA/c NTZ 100mpk CDAA/c ELA+NTZ 36