INVESTOR PRESENTATION

Transcription

1 SEPTEMBER 2018 INVESTOR PRESENTATION September 2018 I. PIPELINE II. INTRODUCTION TO NASH III. GENFIT ASSETS IN NASH IV. BEYOND NASH V. MOVING FORWARD VI. CORPORATE HIGHLIGHTS 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. ALTHOUGH THE COMPANY BELIEVES ITS EXPECTATIONS ARE BASED ON REASONABLE ASSUMPTIONS, THESE FORWARD-LOOKING STATEMENTS 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 ON APRIL 27, 2018 UNDER N 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. NOTHING IN THE PRESENTATION CONSTITUTES AN OFFER OF SECURITIES FOR SALE IN THE UNITED STATES OF AMERICA, CANADA, JAPAN, THE UNITED KINGDOM, AUSTRALIA OR ANY OTHER JURISDICTION WHERE IT IS UNLAWFUL TO DO SO. 2

3 SEPTEMBER 2018 I. PIPELINE 3

4 GENFIT Pipeline Rich Pipeline, Targeting Unmet Needs in Liver & Autoimmune Diseases Targeting Unmet Needs in Liver and Autoimmune Diseases PROGRAM INDICATION TARGET DEVELOPMENT STAGE TIMELINE (E) ADULT NASH PPAR α/δ PHASE 3 Data readout End of 2019 Elafibranor PEDIATRIC NASH PPAR α/δ PHASE 2 Phase 2 Program In progress ADULT NASH (COMBO) PPAR α/δ + others Undisclosed Diagnostic NASH Composite score Elafibranor PBC PPARα/δ DEVELOPMENT PHASE 2 Regulatory approval 2020/21 Data readout End of 2018 Nitazoxanide FIBROSIS, CIRRHOSIS Stellate cell activation PHASE 2 Phase 2 start 2018 TGFTX4 FIBROSIS, CIRRHOSIS Undisclosed TGFTX1 AUTO-IMMUNE DISEASES RORγt Lead Optimization In progress Pre-IND* studies In progress (psoriasis) Pre-clinical Clinical * IND = Investigational New Drug 4

5 II. INTRODUCTION TO NASH Unmet needs Treatment paradigm 5

6 Three Major Unmet Needs in NASH: Considered Top Priority by Regulators and Healthcare Providers 1. TREATMENT Targeting the UNDERLYING CAUSE 2. DIAGNOSTIC Identifying PATIENTS 3. AWARENESS Optimizing STANDARD of CARE 6

7 NASH the Underlying Cause of Progressive Fibrosis Resulting from Necroinflammation Leads to Cirrhosis and HCC Leading cause of liver disease in developed countries; ~20mn in US suffer from NASH & advanced fibrosis Cardiovascular events are the leading cause of death in NASH Multifaceted disease 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

8 NASH and Ballooning are Correlated to Long Term Outcomes NASH Ballooning n= 619 n= 619 NASH and hepatocyte ballooning identified as histological features correlated with clinical outcomes and mortality *: Angulo et al., Gastroenterology 2015 Aug; 149 (2): e10. doi: /j.gastro Epub 2015 Apr 29. 8

9 % 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 Worsening Ballooning & Inflammation GOLDEN505 dataset / P-value derived from Khi2 after grouping of extreme with low counts 9

10 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

11 III. GENFIT ASSETS IN NASH Elafibranor Phase 2 data: a competitive advantage Diagnostic and disease awareness programs 11

12 GENFIT s Approach to NASH: Comprehensive Clinical Management of NASH Patients 1. TREATMENT ELAFIBRANOR Phase 3 NASH resolution & progression to cirrhosis CVD benefit Safety High tolerability Backbone for combination therapy 12

13 Elafibranor, First-in-class, has Pluripotent Activities: PPARα/δ Regulate Multiple Pathways Essential in NASH PPARa and d Regulate Multiple Pathways Essential in NASH 13

14 GOLDEN-505 Elafibranor Phase in NASH 2 Results: A Solid Ground for RESOLVE-IT Phase 3 trial GOLDEN-505 Phase 2 Results* Elafibranor met the Resolution of NASH without worsening of fibrosis endpoint, recommended as primary endpoint for pivotal trials in NASH: Ballooning = 0; Inflammation = 0 (or 1); No worsening of fibrosis (1 stage) Elafibranor confirmed in NASH patients the improved cardiometabolic risk profile: Reduce LDLc, TGs Increase HDLc Improve insulin sensitivity Elafibranor was safe and well tolerated Data published in peer-review journal 14

15 Competitive Landscape on "NASH Resolution": Clinical Evidence from Phase 2 Supporting Phase 3 Designs Evidence from Phase 2 clinical trial supporting Phase 3 design with the approved registrational endpoint of "NASH Resolution without worsening of fibrosis" Duration Design Population Groups "NASH Resolution without worsening of fibrosis" p-value Elafibranor GENFIT 52 weeks R, DB, PBO NAS 4; F0-3 PBO 120mg 5% (1) 26% (1) 0.02 PHASE 3 Programs Ocaliva INTERCEPT GS-4997 GILEAD 72 weeks R, DB, PBO NAS 4; F0-3 PBO 25mg 6% (2) 20% (2) 0.03 N/A : no conclusive data on "NASH resolution" in Phase 2 no focus on "NASH resolution" in Phase 3 Cenicriviroc ALLERGAN N/A : no conclusive data on "NASH resolution" in Phase 2 no focus on "NASH resolution" in Phase 3 MGL-3196 MADRIGAL 36 weeks R, DB, PBO NAS 4; F0-3 PBO 80±20mg 6% (2,3) 27% (2, 3) 0.02 PHASE 2 Programs Aramchol GALMED 52 weeks R, DB, PBO NAS 4; F1-3 PBO 600mg 5% (2) 17% (2) > 0.05 NGM-282 NGM 12 weeks Open label NAS 4; F 1 3mg 11% (2,3,4) 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 (3) Results provided for NASH Resolution only, i.e. not for NASH Resolution without the worsening of fibrosis (4) No placebo arm 15

16 Effect size vs placebo (Absoute change - mmol/l) Effect size vs placebo (% of baseline) Effect size vs placebo (%) Elafibranor Phase in NASH 2 Trial: 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 16

17 RESOLVE-IT 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 Placebo Elafibranor 120mg 2:1 EXTENSION PERIOD 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

18 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 18

19 GENFIT s Approach to NASH: Comprehensive Clinical Management of NASH Patients 2. DIAGNOSTIC IVD BIOMARKER Non-invasive Easy-to-access Best performance vs existing scores Including mi-rna Entering Development phase 19

20 Diagnosis of NASH: a Key Unmet Need Recognized by the FDA BIOPSY IMAGING TECHNIQUES Imperfect "Gold Standard" Non-invasive, but limited alternative Current bottleneck Invasive ; discomfort Costly; Access Issues; Limited to specialized settings Limited to hepatologists and specialized settings Currently best prognostic test available Costly; Access Issues; Limited to specialized settings General tools, not accurate for assessing NASH Non invasive Good patient compliance 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 Ideal for large scale adoption into the clinic and early detection Non invasive; Follows clinical workflow Cost-Effective: Accessible; No capital requirements Disease-specific diagnostic 20

21 GENFIT s Approach to Non-invasive IVD NASH Diagnostic 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 Simple workflow, blood-based, and accurate test for routine clinical use Corporate Strategy for a global In Vitro Diagnostic NASH test FDA-approval (2020/2021) / CE-marking (2021) Global Partner(s): Assay kit development, manufacturing, and commercialization Intended use To identify patients who should be considered for therapeutic intervention 1 if suspected of NASH Monitoring disease evolution: Patients under treatment or patients at risk of progression (e.g. F1) Test should be used in conjunction with other clinical findings and/or laboratory parameters Expected market launch (US, EU): 2020/2021 (1) Patients with NAS Score >4 and fibrosis stage >2 as defined FDA/EMA/KOL s consensus on the histological scoring 21

22 NIS4 Training and Validation Receiver Operating Characteristic Analysis NIS4 combines circulating levels of mir-34a & A2M & HbA1c & YKL-40 (CHI3L1) Training set : GOLDEN (220 pts) Validation set: RESOLVE-IT-DIAG (467 pts) Optimization set: MERGED (687 pts) AUROC 0.81 Accuracy 79 % AUROC 0.81 Accuracy 72 % AUROC 0.82 Accuracy 75 % -Trained (logistic regression) and validated NIS4 in independent, multi-center cohorts of patients with suspected NASH who were prospectively screened for inclusion into interventional trials. - Diagnostic performances not influenced by: T2D status, obesity, ethnicities, gender, age 22

23 % population NIS4 Diagnostic Performance vs Other Scores ROC NIS4 vs Other Scores Distibution of Patients According to Fibrosis Stage and NIS4 Range Retest Retest and/or consider biopsy Consider intervention low medium low medium high high NIS4 risk category Figure 1. NIS4 outperforms existing blood-based scores to identify patients with active NASH and significant fibrosis (NAS>4/F 2). Figure 2. NIS4 scores above the high cut-off identified NAS 4/F 2 patients with an associated PPV >80%. Use of NIS4 would have led to the avoidance of >75% of liver biopsies in this patient population. LDT released by early 2019 FDA approval / CE-marking by 2020 with subsequent world-wide launch Intended population: adults suspected of having NASH (AASLD Practice Guidelines) 23

24 Our Vision of the Future Patient Journey with IVD Test (Adoption phase): Facilitate Initial Screening for Better Clinical Management 24

25 Our Vision of the Future Patient Journey with IVD Test (Post-adoption): Facilitate Initial Screening for Better Clinical Management 25

26 GENFIT s Approach to NASH: Comprehensive Clinical Management of NASH Patients 3. AWARENESS 26

27 The NASH Education Program TM : a GENFIT but Non-Partisan Initiative to Address a Key Unmet Need For BETTER CARE NASH (Non-Alcoholic SteatoHepatitis) PHYSICIANS Beyond hepatology PATIENTS Indidivuals 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 UNACCEPTABLE situation The NASH Education Program TM 27

28 Bringing Together a Large and Diversified Coalition of Key Stakeholders Non- profit, patient advocacy groups, learned societies Benefactors 28

29 Ultimately Leading to a Large Success, on a Worldwide Scale 29

30 IV. BEYOND NASH Elafibranor addressing unmet needs in a rare disease: Primary Biliary Cholangitis (PBC) 30

31 Elafibranor Ideally Positioned to Address Important Unmet Needs in a Rare but Severe Chronic Liver Condition HIGH UNMET NEEDS Cholestatic chronic autoimmune disease Affecting intrahepatic bile ducts Rare but 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 well-identified mechanism of action Significant proportion of non/partial responders with current treatments in PBC patient population + Recent evidence showing the potential of PPARα to alleviate pruritus, a major symptom of PBC Major symptom in PBC is pruritus and is not addressed by current PBC therapies 31

32 Phase 2a Sudy with Elafibranor in PBC (Primary Biliary Cholangitis) 1 st Patient enrolled May WEEK ANALYSIS TREATMENT PERIOD 12 WEEKS Placebo Elafibranor 80mg Elafibranor 2:1 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 32

33 V. MOVING FORWARD Market Access Commercialization 33

34 A Relevant Market Access Strategy: Considering Patient Needs and Pharmacoeconomics 4. MARKET ACCESS 34

35 Commercialization: Maximizing Sales Uptake while Transforming the Company Objective: transform GENFIT into a biopharma, with a mix revenue stream from: Direct sales of elafibranor Royalties from licensing deal Commercialization: Development of a global alliance with a large pharmaceutical company with a solid footprint in metabolic diseases Keep rights in some territories Keep some rights in some clinical settings Stand alone deal in Asia Organizational ramp-up: US/EU Market Access and Marketing teams 35

36 VI. CORPORATE HIGHLIGHTS Company profile Key takeaways Financial highlights 36

37 Company Profile (1/3) Overview Public company focused on metabolic diseases & associated complications, including liver related disorders World-leading expert in nuclear receptor based drug discovery Founded in 1999 (Lille, Paris, France Cambridge, US) 130 employees Since 2006, Euronext Paris compartment B (GNFT) Market capitalization of ~ 800M Lead program in NASH: Nonalcoholic Steatohepatitis Actively enrolling Phase 3 with elafibranor: First-in-class molecule, fast-track designation, accelerated approval Subpart H (FDA) and Conditional approval (EMA) Biomarker program in NASH/NAFLD* for non invasive and easy-to-access IVD (In-Vitro Diagnostic) Rich pipeline addressing other key unmet needs: PBC, fibrosis, auto-immune diseases *: Nonalcoholic Fatty Liver Disease **: In-Vitro Diagnotic 37

38 GENFIT Pipeline Company Profile (2/3): Rich Pipeline, Targeting Unmet Needs in Liver & Autoimmune Diseases Targeting Unmet Needs in Liver and Autoimmune Diseases PROGRAM INDICATION TARGET DEVELOPMENT STAGE TIMELINE (E) ADULT NASH PPAR α/δ PHASE 3 Data readout End of 2019 Elafibranor PEDIATRIC NASH PPAR α/δ PHASE 2 Phase 2 Program In progress ADULT NASH (COMBO) PPAR α/δ + others Undisclosed Diagnostic NASH Composite score Elafibranor PBC PPARα/δ DEVELOPMENT PHASE 2 Regulatory approval 2020/21 Data readout End of 2018 Nitazoxanide FIBROSIS, CIRRHOSIS Stellate cell activation PHASE 2 Phase 2 start 2018 TGFTX4 FIBROSIS, CIRRHOSIS Undisclosed TGFTX1 AUTO-IMMUNE DISEASES RORγt Lead Optimization In progress Pre-IND* studies In progress (psoriasis) Pre-clinical Clinical * IND = Investigational New Drug 38

39 Company Profile (3/3): A Comprehensive Strategy in NASH 1. TREATMENT Targeting the UNDERLYING CAUSE 2. DIAGNOSTIC Identifying PATIENTS 3. AWARENESS Optimizing STANDARD of CARE 39

40 Key takeaways 11. NASH: LARGE AND UNTAPPED MARKET OPPORTUNITY NASH is a therapeutic area with high unmet needs but no available treatment 22. GENFIT NASH PROGRAM: LEADING THE WAY Elafibranor First-in-class molecule World leader with one of the very few Phase 3 currently in progress Strong competitive profile based on efficacy + safety + tolerability + other benefits Diagnostic At the forefront of R&D for an easy-to-access solution 33. CATALYSTS : HIGH POTENTIAL VALUE Phase 2 data in PBC (rare disease) Phase 3 data in NASH (accelerated approval process) Regulatory and partnering/industrial milestones for NASH diagnostic Pediatric program in NASH Combination therapy in NASH 44. COMPANY PROFILE: STRONG NETWORK & EXPERTISE, RELEVANT FOOTPRINT Euro-American biotechnology company based in Lille, Paris and Boston, with a solid expertise in liver and metabolic diseases, and a strong network in NASH 40

41 Financial Highlights Cash position 255 million (Q1 2018) Last fund raisings -March 2016: private placement 50 million -October 2016: private placement 34 million -October 2016: rights issue 45 million -October 2017: convertible bonds 180 million Market cap -GNFT: 800M (Euronext) 41

42 END 42