... INFORMATION CONTAINED HEREIN CONCERNING ECONOMIC TRENDS ... UNCERTAINTIESâ OF THE COMPANY'S HALF YEAR 2016 BUSINESS AND ...
2016.10
INVESTOR PRESENTATION October 2016
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Disclaimer Important information and forward looking statements • THIS PRESENTATION HAS BEEN PREPARED BY GENFIT AND IS FOR INFORMATION PURPOSES ONLY. • THE INFORMATION AND OPINIONS CONTAINED IN THIS PRESENTATION SPEAK ONLY AS OF THE DATE OF THIS DOCUMENT, UNLESS OTHERWISE INDICATED HEREIN. 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 IS SUBJECT TO CHANGE WITHOUT NOTICE. • 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, CBP 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, CBPAND BIOMARKERS, THE SUCCESS OF ANY INLICENSING STRATEGIES, 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 (WWW.GENFIT.COM) AND ON THE WEBSITE OF THE AMF (WWW.AMFFRANCE.ORG). OTHER THAN AS REQUIRED BY APPLICABLE LAW, GENFIT DOES NOT UNDERTAKE ANY OBLIGATION TO UPDATE OR REVISE ANY FORWARD-LOOKING INFORMATION OR STATEMENTS. • NOTHING IN THE PRESENTATION CONSTITUTES AN OFFER OF SECURITIES FOR SALE IN THE UNITED STATES OR ANY OTHER JURISDICTION WHERE IT IS UNLAWFUL TO DO SO.
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GENFIT A BIOPHARMACEUTICAL COMPANY FOCUSED ON GLOBAL MANAGEMENT OF NASH PATIENTS
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GENFIT: Innovative Company in Diagnostic & Treatment of Metabolic & Inflammatory Diseases • Public company focused on metabolic diseases & associated complications, including liver related disorders › ›
Elafibranor (GFT505) lead program Phase 2b completed, first-in-class PPAR α/δ candidate for NASH Biomarker program in NASH/NAFLD: diagnostic, disease progression, and companion tool
• World-leading expert in nuclear receptor based drug discovery ›
Revenue-generating alliances with multiple major pharmaceutical companies
• Founded in 1999 (Lille, France – Cambridge, US) – 110 employees • Since 2006, Euronext Paris - compartment B (GNFT) – Market capitalisation of €700m • Lead program in NASH: Elafibranor, first-in-class molecule, Fast-track designation, Accelerated approval Subpart H (FDA) and Conditional approval (EMA) • Rich pipeline addressing other key unmet needs: PBC, fibrosis, auto-immune diseases
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GENFIT’s Pipeline is Well-diversified, With R&D Efforts Well Distributed between Late Stage and Early Stage Programs Indication
NASH
Lead Programs
Research Programs
Inlicensing Program
Program
MOA
Elafibranor (GFT505)
PPAR α/δ agonist
Biomarker Diagnostic
Program Maturity Phase 3
End of Enrollment H1 2017 Validation Steps Q1 2017
PBC
Elafibranor (GFT505)
PPARα/δ agonist
Phase 2-ready Q4 2016
NASH Pediatric, NASH Cirrhosis, etc.
Elafibranor (GFT505)
PPAR α/δ agonist
Different Phases
NASH
Combo therapy
Multiple
Undisclosed
Repositionning
Undisclosed
Phase 2-ready H1 2017
Hit-to-lead TGFTX4
Undisclosed
Preclinical-ready H1 2017
Auto immune diseases
TGFTX1
RoRγ inverse agonist
Preclinical-ready Q4 2016
Gastroenterology indications
Undisclosed
Undisclosed
Undisclosed
Liver fibrosis/ cirrhosis
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NASH, the Severe Form of NAFLD, Leads to Liver Fibrosis, Cirrhosis & HCC ›
NASH is the underlying cause of progressive fibrosis resulting from necroinflammation, and leads to cirrhosis
›
Estimated 20 millions US adult patients with NASH & advanced fibrosis
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 2015
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NASH, the Severe Form of NAFLD, Leads to Liver Fibrosis, Cirrhosis & HCC
Waitlist Registrations for Liver Transplantation
New HCC Cases US
Wong, 2015 Reported HCC cases were derived from reported liver cancer cases – SEER database http://seer.cancer.gov/data/
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Elafibranor, First-in-class, has Pluripotent Activities 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
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)
FIBROSIS LIVER DYSFUNCTION
LIPID METABOLISM
CVD RISK
PPARα/δ INFLAMMATION GLUCOSE HOMEOSTASIS
i Atherogenic lipid profile i Endothelial dysf. (ET-1, RGS5, Nox) i Vessel Ox stress (CAT, GPx1, HO1) i Vessel inflam (ICAM1, MCP1)
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 8
Rationale for Treating NASH With Elafibranor, a Dual PPARα/δ Agonist With Multiple Activities
Cariou et al. 2011, Diabetes Care, 34(9):2008-2014 - Cariou et al. 2013, Diabetes Care, 34(9):2008-2014 - Staels et al. 2013, Hepatology, 58(6):1941-1952 9
Phase 2b GFT505 Trial Results GOLDEN-505: The first international clinical trial with “Resolution of NASH without worsening of fibrosis” as the Primary endpoint (56 centers, 9 countries, 52 weeks) • The publication in Gastroenterology highlights the resolution of NASH without fibrosis worsening with 120mg Elafibranor • This result is confirmed both in intention-to-treat population as well as in subgroups of moderate/severe NASH patients, based on the recommended definition of “NASH resolution” now used for clinical trials • In addition, the publication confirms that Elafibranor significantly improves the cardiometabolic risk profile and is safe, well-tolerated • Phase III trial initiated in November 2015 with first patient enrollment in March 2016
(ITT)
GOLDEN-505 study, 2015 10
Phase 3 Trial RESOLVE-IT: Expected Readout in H2 2018 •
•
Study population: High-risk patients › › ›
NASH with a NAS ≥4 Fibrosis stage F2 and F3 (F1 + cardiometabolic risk)
Subpart H (interim analysis) ›
•
Histological primary endpoint: › NASH resolution, corresponding to ballooning=0, inflammation=0-1, without worsening of fibrosis (1 point increase) › Central reading for all biopsies (inclusion & follow-up) › Key secondary endpoint: improvement of histological fibrosis, to be considered as an additional labeling claim › Duration 18 months of treatment › All patients followed until the occurrence of a pre-defined number of progressions to cirrhosis and other liver related events
General design › ›
Approximately 1,000 patients in interim analysis (total of ~2000 patients) 2 arms: Elafibranor 120mg & Placebo SUBPART H ANTICIPATED MARKET AUTHORIZATION
250 centers
Approx 2,000 patients
~1,000 patients FIRST TREATMENT PERIOD
EXTENSION PERIOD
Placebo
Placebo
Elafibranor 120mg
Elafibranor 120mg
2:1 TRIAL INITIATION Q1 2016
2:1 72-WEEK INTERIM ANALYSIS PRIMARY ENDPOINT: NASH RESOLUTION WITHOUT WORSENING OF FIBROSIS
END OF STUDY Occurrence of a pre-defined number of events including progression to cirrhosis
Prevention of NASH associated clinical events, including cirrhosis resulting from progressive fibrosis
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IP Overview Overview 2016
• 407 patent applications/patents
• • •
9 patent families 72 patents (39 allowed/granted) Related to : RORgt, Repositioning, Rev-Erb
• Biomarkers / theranostic patents • • •
4 patent families 12 patents (10 granted) Major patent on biomarker programme
200 150
280
theranostics & technology patents (2% )
100 50
43
33
39
2
10 theran. & technol. allowed/granted
• Patents covering other NCEs
other GFTs patents (18% )
theran. & technol. -pending
Elafibranor in NASH: protection possible until 2035 (with extensions) in US/EU/Japan and others
250
others GFTs - allowed/granted
• •
12 patent families (composition of matter, synthetic processes, therapeutic applications) 323 patents (280 allowed/granted) 49 countries covered
others GFTs - pending
•
300
0 GFT505-related patents allowed/granted
• Elafibranor patent portfolio
GFT505-related patents
GFT505-related patents - pending
A strong protection for all assets in portfolio
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GENFIT’s Current Cash Position • The capital raise of €49.6m at the end of February allowed the Company to increase its cash position to €94.6m as of June 30, 2016 ›
Cash and cash equivalents and current financial instruments of €94.6m at June 30, 2016 (€60.1m at December 31, 2015)
›
Financial liabilities of €6m (€5.7m at December 31, 2015)
• This cash position does not cover GENFIT’s mid-term financing needs to reach 2019, date at which the Company would anticipate receiving marketing authorization for elafibranor in NASH
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PROFILE OF ELAFIBRANOR & RECENT RESULTS
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Angulo 2015 Study Indicates NASH and Hepatocyte Ballooning as Relevant Targets to Prevent Long Term Outcomes
NASH
Ballooning
› NASH and hepatocyte ballooning identified as histological features correlated with clinical outcomes and mortality. › In-line with the clinical use of Elafibranor. Angulo, Gastroenterology 2015 15
Elafibranor Responders have Significant Histological Responses Elafibranor 120mg Responders vs Elafibranor 120mg Non-Responders 1
Mean change versus baseline
0.5 0 -0.5 -1 #
-1.5 ###
-2
Patients who resolved their NASH showed significant reduction in liver fibrosis while non-responders did not show any change from baseline
-2.5 -3 -3.5
###
#
###
NAS
Steatosis
Ballooning
Inflammation
Fibrosis
NASH components Elafibranor 120 mg Responders
Elafibranor 120 mg Non responders
#: p
