INVESTOR PRESENTATION

Transcription

1 INVESTOR PRESENTATION APRIL

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 GENFIT BELIEVES ITS EXPECTATIONS REFLECTED IN SUCH FORWARD-LOOKING STATEMENTS 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 INFORMATION AND STATEMENTS. THESE RISKS AND UNCERTAINTIES INCLUDE AMONG OTHER THINGS, THE UNCERTAINTIES INHERENT IN RESEARCH AND DEVELOPMENT, IN PARTICULAR IN ELAFIBRANOR, PBC AND RELATED TO BIOMARKERS, PROGRESSION OF, RESULTS OF CLINICAL DATA FROM, THE RESOLVE-IT TRIALS, REVIEW AND APPROVALS BY REGULATORY AUTHORITIES, SUCH AS THE FDA OR THE EMA, INCLUDING REGARDING ELAFIBRANOR, PBC AND BIOMARKERS, THE SUCCESS OF ANY IN-LICENSING STRATEGIES, AND GENERALLY GENFIT S CONTINUED ABILITY TO RAISE CAPITAL TO FUND ITS DEVELOPMENT, AS WELL AS THOSE DISCUSSED OR IDENTIFIED IN THE PUBLIC FILINGS WITH THE AMF MADE BY GENFIT, INCLUDING THOSE LISTED UNDER SECTION 7 MAIN RISKS AND UNCERTAINTIES OF THE COMPANY S HALF YEAR 2016 BUSINESS AND FINANCIAL REPORT WHICH IS AVAILABLE ON GENFIT S WEBSITE ( ) AND ON THE WEBSITE OF THE AUTORITE DES MARCHES FINANCIERS ( 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 GENFIT: Introduction 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 ~ 1bn 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* Rich pipeline addressing other key unmet needs: PBC, fibrosis, auto-immune diseases *: Nonalcoholic Fatty Liver Disease 3

4 GENFIT Pipeline: Targeting Unmet Needs in Liver and Autoimmune Diseases NASH Programs PHASE 2 Programs OTHER RESEARCH Programs PROGRAM OBJECTIVE DETAILS PROGRAM MATURITY TIMELINE (E) ELAFIBRANOR in NASH 1 st LINE TREATMENT PEDIATRIC, ANCILLARY, etc. COMBO THERAPY BIOMARKERS DIAGNOSTIC mirnas ELAFIBRANOR in PBC FIBROSIS, CIRRHOSIS FIBROSIS, CIRRHOSIS AUTO-IMMUNE DISEASES TREATMENT REPURPOSING MARKETED DRUG HIT-to-LEAD (TGFTX4) (TGFTX1) PPAR α/δ agonist (First-in-class) PPAR α/δ agonist (First-in-class) PPAR α/δ agonist and other MoAs PPARα/δ agonist Nitazoxanide Undisclosed RORγT Inverse agonist PHASE 3 PHASE 2 PHASE 2 PHASE 2 End of enrollment Q PK/PD H Undisclosed Start development H st patient Q IND filing Phase 2a H Preclinical regulatory Q Pre-IND studies On-going (psoriasis) 4

5 NASH: Underlying Cause of Progressive Fibrosis that Results 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

6 NASH and Hepatocyte Ballooning are Relevant Targets to Prevent Long Term Outcomes* NASH Ballooning n= 619 n= 619 NASH and hepatocyte ballooning identified as histological features correlated with clinical outcomes and mortality Strongly supports clinical development and use of elafibranor *: Angulo et al., Gastroenterology 2015 Aug; 149 (2): e10. doi: /j.gastro Epub 2015 Apr 29. 6

7 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

8 The Rising Prevalence of NASH is a Major Health Concern Waitlist Registrations for Liver Transplantation New HCC Cases US Wong, 2015 Reported HCC cases were derived from reported liver cancer cases SEER database 8

9 PROFILE OF ELAFIBRANOR & CLINICAL RESULTS 9

10 Elafibranor, First-in-class, has Pluripotent Activities: PPARa and d Regulate Multiple Pathways Essential in NASH PPARa and d Regulate Multiple Pathways Essential in NASH i Fibrogenesis (TGFβ1, αsma, Col1α1) i Oxidative stress (CAT, SOD) i Inflammation(MCP-1, IL-6, TNFα) i steatosis (h lipid utilization) i Oxidative stress (CAT, SOD) i ALT, GGT, ALP h Hepatic hemodynamics LIVER DYSFUNCTION FIBROSIS CVD RISK i Atherogenic lipid profile i Endothelial dysf. (ET-1, RGS5, Nox) i Vessel Ox stress (CAT, GPx1, HO1) i Vessel inflam (ICAM1, MCP1) h Triglyceride clearance (APOC3) i VLDL-APOB & ildl-apob i sd-ldl cholesterol level h HDL cholesterol level (APOA1/A2) h NEFA utilization (ACOX, CPT1, EHHADH) i NEFA level (lipolysis, β-oxidation) LIPID METABOLISM PPARα/δ GLUCOSE HOMEOSTASIS INFLAMMATION i NF-κB, i TLRs i TNFα, IL-1β i IL-6, CRP, SAA, HG, fibrinogen i Kupffer cell activation (BCL6) h Insulin sensitivity (Fgf21) i Hepatic glucose output (PEPCK, FAS, ACC, PDG, G6PDH) i insulin 10

11 Rationale for Treating NASH With Elafibranor, a Dual PPARα/δ Agonist With Multiple Activities Cariou et al. 2011, Diabetes Care, 34(9): Cariou et al. 2013, Diabetes Care, 34(9): Staels et al. 2013, Hepatology, 58(6):

12 Elafibranor in NASH: GOLDEN-505 Phase 2 Results¹ GOLDEN-505 Phase 2 Results* Elafibranor is safe, well tolerated and significantly improves cardiometabolic risk profile Elafibranor meets the re-defined 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) Results on histology after 12 months Elafibranor 120mg vs placebo on NASH resolution Elafibranor 120mg Responders vs Non responders on Fibrosis (ITT) ¹: Ratziu et al., Gastroenterology 2016; 150: ; Elafibranor 120mg, n= 94; Elafibranor 80mg, n=93; placebo, n= 92; NASH Resolution at 12 months. 12

13 Mean change versus baseline GOLDEN-505 Phase 2 Results* Elafibranor Responders have Significant Histological Responses 1 Elafibranor 120mg Responders vs Elafibranor 120mg Non-Responders 0,5 0-0,5-1 -1,5 # # ### -2-2,5-3 -3,5 ### ### #: p<0.05 ###: p<0.001 Patients who resolved their NASH* showed significant reduction in liver fibrosis while non-responders did not show any change from baseline NAS Steatosis Ballooning Inflammation Fibrosis NASH components Elafibranor 120 mg Responders Elafibranor 120 mg Non responders *: Ratziu et al., Gastroenterology 2016; 150: Analysis with the re-defined and currently recommended NASH resolution endpoint for pivotal trials in NASH 13

14 % patients Changes in Hepatocyte Ballooning and Lobular Inflammation Drive Fibrosis Response % patients % patients Ballooning Inflammation Steatosis Fibrosis Improvers Fibrosis Worseners Fibrosis Improvers Fibrosis Worseners Fibrosis Improvers Fibrosis Worseners N=7 N=78 N=129 N= N=9 N=72 N=138 N=18 p= p< Change in ballooning score Change in lobular inflammation score N=4 N=49 N=128 N=56 NS Change in steatosis score In GOLDEN-505 after only 1 year: Changes in hepatocyte ballooning and lobular inflammation are associated with fibrosis response (% of patient who improved or worsened their fibrosis score) No association between change in steatosis score and fibrosis response P-value derived from Khi2 after grouping of extreme with low counts 14

15 Activity Index Correlates With Change in Fibrosis Score and Response: NASH Resolution Induces Fibrosis Improvement % patients Activity Index = Ballooning Score + Inflammation Score fibrosis score Fibrosis Improvers Fibrosis Worseners Mean±SE 1,5 70 N=7 N=39 N=77 N=82 N=27 N= p< Change in activity Index (Ballooning + Inflammation) 1 R² = 0,946 0,5 Activity Index ,5-1 -1,5 In GOLDEN-505 after only 1 year: Changes in in Activity Index is highly correlated with changes in fibrosis P-value derived from Khi2 after grouping of extreme with low counts 15

16 Effect size vs placebo (Absolute change) Elafibranor has Efficacy on Composites Scores, Liver and Inflammatory Markers Effect size vs placebo (U/L) Effect size vs placebo (g/l or log- HsCRP) Elafibranor 120mg vs Placebo on Composite Scores Elafibranor 120mg vs Placebo on Liver Markers Elafibranor 120mg vs Placebo on Inflammatory Markers FIBROTEST *** STEATOTEST *** NAFLD-Fibrosis score p= ,1-0, ** *** *** ALT AST GGT ALP -0,3-0,4 p=0.09 *** ** Fibrinogen Haptoglobin HsCRP (log) The effect size vs placebo was calculated and expressed as LSMean±Standard Error. ** : p< *** : p<

17 CVD Risk in NASH Patients is Under High Scrutiny by Regulatory Agencies and Experts Alike FDA/AASLD recommendation (Hepatology 2015): NASH is associated with type II diabetes, increased cardiovascular risk and cancer-related mortality (74-76). For this reason, it seems important to monitor LDL- and HDL-cholesterol, triglycerides, and diabetes control (e.g. hemoglobin A 1c) in phase 2b and 3 NASH trials. It is imperative that any drug developed for NASH be at least neutral from a cardiovascular risk perspective and ideally also reduce cardiovascular risks. Elafibranor has beneficial effects on top of standard of care (statins, anti-diabetic drugs, etc.) 17

18 Cardiovascular Diseases, Leading Cause of Death in NASH Patients Angulo et al., Gastroenterology 2015 Aug; 149 (2): e10. doi: /j.gastro Epub 2015 Apr 29 18

19 Effect size vs placebo (Absoute change - mmol/l) Elafibranor Improves CV Risk Factors: TG, Cholesterol, LDL-C, Remnant-C, HDL-C 0,2 Elafibranor 120mg vs Placebo on Lipid Markers *** 0,1 0-0,1-0,2-0,3-0,4 *** ** -0,5-0,6-0,7-0,8 *** *** *** TG Total-Chol Non-HDL-Chol LDL-Chol Remnant-Chol VLDL-Chol HDL-Chol The effect size vs placebo was calculated and expressed as LSMean±Standard Error. ** : p<0.01 *** : p<

20 Effect size vs placebo (% of baseline) Elafibranor Improves Glucose Homeostasis / Insulin Sensitivity in Type 2 Diabetic NASH Patients Effect size vs placebo (%) Elafibranor 120mg vs Placebo Elafibranor 120mg vs Placebo 0 0-0, ,1-20 ## -0,2-0,3-30 # -0, , # ## # -0,6-0,7-0,8 # HbA1c GFT # FPG Insulin HOMA-IR FFA Fructosamine C-peptide Significant decrease in HbA1C vs placebo The effect size vs placebo was calculated and expressed as LSMean±Standard Error. # : p<0.05 ## : p<

21 Elafibranor Improves NASH by Acting on All Cell Types Involved in NASH Parenchymal Cells KC Elafibranor EC HSC PPRE FAO decreases Liver fat NFkB AP-1 decreases Inflammation Fibrosis increases Insulin Sensitivity Elafibranor decreases Fibrosis Elafibranor improves Vaso-reactivity E T -1 Elafibranor decreases Inflammation 21

22 Elafibranor has Very Good Safety and Tolerability Profiles, Essential for a Long-term Treatment Very good tolerance confirmed after one year of treatment in Phase 2b No Death and no Major Cardiovascular Events (MACE) No effect on body weight No signal on cancer No meaningful change in safety markers and hematology No signal for pruritus Elafibranor 80mg Elafibranor 120mg Placebo Total Adverse event N=93 N=89 N=92 N=274 Nausea Vomiting Diarrhoea Headache Fatigue/asthenia Creatinine increase Abdominal pain Myalgia Decreased appetite Rash Pruritus

23 Elafibranor in NASH: RESOLVE-IT Phase 3 Design Details and Timing > 250 centers (worldwide) ~ 1000 patients ANTICIPATED MARKET AUTHORIZATION SUBPART H (FDA) CONDITIONAL APPROVAL (EMA) ~ 2000 patients FIRST TREATMENT PERIOD 18 MONTHS EXTENSION PERIOD Placebo Elafibranor 120mg Placebo Elafibranor 120mg 2:1 2:1 TRIAL INITIATION Q 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: ~Q WEEK INTERIM ANALYSIS 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) END OF STUDY 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: ~Q

24 GENFIT: Addressing Key Unmet Needs in NASH TREATMENT Elafibranor currently evaluated in RESOLVE-IT Phase 3 trial Resolution of histological NASH Safe and well tolerated for long term treatment Beneficial cardiometabolic profile for global management of NASH patients DIAGNOSIS Biomarker program to unlock market potential Liver biopsy, the standard for diagnosis of NASH is invasive and costly NASH remains significantly under-diagnosed and in need of non-invasive diagnostics as alternative to liver biopsy GENFIT is amongst the leaders developing non-invasive blood based biomarkers for identification of NASH patients for treatment 24

25 GENFIT s Biomarker Program Exploiting in-house expertise in mirnas, biostatistics and unique database in NASH Goal: Identification of NASH patients who should receive treatment Healthy NAFLD CIRRHOSIS No NASH NASH NO TO BE TREATED Steatosis 1 Ballooning 1 Inflammation 1 NAS 4 F2 or higher Patients at risk to be treated are defined according to FDA/EMA/KOL s consensus on the histological scoring Discovery: Highly predictive 5 biomarker algorithm derived by two independent approaches Clinical data: Phase 2 GOLDEN-505 Cohort Biostatistical analysis mir-200a mir-34a A2M HbA1c P3NP 25

26 GENFIT s Proprietary Algorithms More Predictive Than Existing Scores to Identify NASH Patients for Treatment ¹, ² Identification of NASH patients with NAS 4 with F2 or F3 fibrosis Important for the patient: non-invasive diagnosis for treatment Important for the physician: facilitated diagnosis of patients to treat Important for the NASH market: to meet full potential GENFIT is developing proprietary biomarker algorithms to identify, diagnose and follow-up patients Innovation with bioinformatics and mirnas FDA position on NASH diagnosis 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 ¹ Sanyal. AJ et al. 2016, Hepatology, Volume 64- Number 1 (SUPPL): 327A. ² Sanyal et al., EASL ILC 2016: A new method including the quantification of circulating mirnas allows the efficient identification of NASH patients at risk who should be treated 26

27 The NASH Education Program TM A GENFIT initiative The NASH The Education NASH Program TM A GENFIT initiative

28 The NASH Education Program TM A GENFIT initiative NASH is the result of modern lifestyles, and is closely related to the triple epidemic of: Obesity Diabetes Pre-diabetes The NASH Education Program TM is a public health initiative aimed at producing and disseminating essential medical knowledge, towards a targeted audience All physician specialties within the medical community that will be in charge of NASH patients, as soon as diagnostic and therapeutic solutions are made available Patients and their families who also have to understand causes, mechanisms, and consequences of the disease, in order to fully appreciate the importance of an early diagnosis and the usefulness of a treatment well-suited to their condition. The NASH Education Program TM is an endowment fund created by GENFIT to design, finance and manage relevant disease awareness activities in the NASH space Contact us and find out more about The Nash Education Program TM The NASH Education Program TM A GENFIT initiative 28