Welcome. January 10 th, 2014

Transcription

1 Welcome January 10 th,

2 Welcome UP1 LC-MS - proteomic UP2 screening 2 in vivo facility cell biology molecular biology biochemistry/ chemistry 2

3 GENFIT as of Today A Biopharmaceutical Company Public company focused on metabolic disorders & associated complications, incl. liver related disorders (NAFLD, NASH, Fibrosis) World-leading expert in nuclear receptor based drug discovery Founded in 1999 (Lille, France Cambridge, US) 80 employees Listed on the Alternext market (ALGFT) of Euronext (NYSE, Paris) since

4 Challenges in Metabolic Diseases GFT505, A Therapeutic Solution for NASH RISK FACTORS Altered glucose metabolism Lipid Disorders Overweight, obesity Pro-inflammatory & oxidative stress Hypertension Liver Dysfunction Glucose reduction is not sufficient to avoid Type II diabetes complications PREDIABETES Organ Defects High need for products to treat complications and comorbid diseases associated with diabetes OADS METFORMIN SULFONYLUREAS GLITAZONES DPP-IV DIABETES Insulin Resistance Hyperglycemia COMPLICATIONS Retinopathy / Blindness Nephropathy Diabetic Foot NASH GFT505 CV Events 4

5 GFT505 in NASH A Pluripotent Product Is Needed, GFT505 Can Meet the Need GFT505, New dual PPARα/δ non PPARγ product Over 600 patients or healthy volunteers treated with GFT505 to date Beneficial properties for NASH Improvement of glucose homeostasis & insulin sensitivity Improvement of markers of liver dysfunction Favorable effects on plasma lipids Efficacy on histological NASH parameters in disease models (fibrosis, steatosis, ) Absence of safety concern, Absence of PPAR deleterious effect Anti-inflammatory properties 5

6 GFT505 Development Plan in NASH Aligned to Register GFT505 Among the 1st Approved Drugs for NASH Proof of Safety & Efficacy Package COMPLETED Pivotal Phase IIb Ready for Phase III package Phase III Pivotal phase IIb in Europe & US 1-year treatment liver biopsy-based trial 270 patients / 70 centers 2 doses (80mg & 120mg) + placebo FDA IND approval: OK EMA Scientific Advice: OK DSMB approval for second recruitment phase Submission US & Europe June-Oct 2012 First patient, First Visit... Sept 2012 End of treatment analysis. Dec

7 GFT505 Development Plan in NASH Data Safety Monitoring Board recommendation (Oct 25, 2013) DSMB is: an independent committee of international experts set up to ensure patient safety data for patients that have been treated for more than 6 months with GFT505 at 80mg/day DSMB unanimous conclusions: GFT505 shows no safety issue that compromise the continuation of the phase IIb study Unrestricted approval to continue the Phase IIb study according to the planned protocol the next patients that are randomized to receive GFT505 in the trial will be treated at 120mg/day for 12 months 190m 1355m 1735m 7

8 GFT505 Development Plan in NASH Pivotal Phase IIb Progress (275 patients randomized) As of Jan 10,2014 : 194 patients with more than 2 months of treatment 134 patients with more than 4 months of treatment 129 patients with more than 6 months of treatment 100 patients with more than 8 months of treatment 29 patients with more than 10 months of treatment 14 patients has completed treatment (V8) 8

9 GFT505 Development Plan in NASH AASLD-FDA Public Workshop (Sept 5-6, 2013) NASH recognized as a high unmet need indication NASH rapidly becoming the leading cause of liver transplantation New data on Nash Prevalence in US: between 12 and 17% of the general population 15-25% of NASH patients can progress to cirrhosis Fibrosis worsens the prognosis: Cirrhosis develops in 13.3% of NASH patient with mild to moderate fibrosis (F1-F2) Cirrhosis develops in 50% of NASH patient with advanced fibrosis (F3) Registration in US: Reversal of NASH without worsening of fibrosis is an acceptable clinical endpoint for Phase III trials Eligible to subpart H procedure (hard clinical end-points -> post marketing studies) Phase III trials should address high risk patients: NASH + advanced 1355m fibrosis 1735m 190m 590m 9

10 NASH Competitive Landscape Lack of Products for the Treatment of NASH No approved curative treatment for NASH Developments of products in NASH GENFIT GFT505 Dual PPAR α/δ Phase IIb INTERCEPT PHARMACEUTICALS INT747 FXR agonist Phase IIb GILEAD GS-6624 MAb against LOXL2 Phase IIb RAPTOR PHARMACEUTICALS Cysteamine Antioxidant Phase IIb PHENEX PHARMACEUTICALS PX-102 FXR agonist Phase I GALECTIN THERAPEUTICS GR-MD-02 Target galectin-3 Phase I Poor efficacy of marketed drugs and development failure: Glucophage (generics) -> weak efficacy on steatosis but no activity on NASH Glitazones (PPARγ Pioglitazone) -> moderate efficacy on steatosis and NASH but safety concerns (NEJM, 2006 & 2010) Vitamin E -> moderate efficacy on steatosis and NASH (N Engl J Med, 2010) Ursodiol (UDCA) -> weak efficacy on steatosis but no activity on NASH (J Hepatol, 2011) GS.9450 (Caspase Inhib) -> stopped in Phase IIb (adverse effects) (J Hepatol, 2010 & Hepatology, 2012) 10

11 GENFIT, From 2000 To : Reinforcement of Pipeline is ongoing GFT505 dual PPARα/δ non PPARγ Phase IIB ongoing in NASH NASH CV Prevention Liver fibrosis TGFTX1 RORγt Hit to Lead Autoimmune diseases (including IBD) 2015 TGFTX3 Reverbα Lead Optimization Diabetes, NASH RTK Other fibrotic disorders and Liver Cancer New Molecules Development BMGFT02 Prediabetes / Diabetes BMGFT03 NASH 2000 Biomarker Candidate Biomarker Candidate 11

12 Making the transition to a specialty biopharma for the metabolic related liver and GI diseases A strong R&D to develop innovative treatments and diagnostic tools A network of renowned KOLs, clinicians, experts in Europe, North America and Asia Addressing Market Access, Pharmaco-economy, Regulatory in EU & NA markets GFT505, an innovative treatment for NASH To be out-licensed in 2015 at the latest Either on a worldwide basis Or on selected markets, while Genfit could retain rights on chosen territories (China, some European countries) Biomarkers / companion tool Drug candidate programs for autoimmune and fibrotic diseases in the Liver/GI area Positioned to evolve progressively into a business model combining R&D and products on selected markets, alone or with strategic partners 12

13 Stock Historic Stock Lookup (one year) Share price: st Jan: +37% 3 months: +29% 6 months : +178% 1 Year: +262% Market cap.: M

14 Stock 2013 Performance: +184% TOP 50 (46 th ) of approximately 750 Major Public Biotech Company performance in the world TOP 15 (15 th ) of approximately 200 Major Public Biotech Company performance in the Cardiometabolic/GI/Liver TOP 5 (5 th ) of approximately 120 Major Public Biotech Company performance in Europe ( Zone + Great Britain + Nordic countries + Switzerland) 14

15 Vie Boursière Forum Boursorama 15

16 Opération financière en cours Augmentation de Capital de 5M Procédure : Augmentation de capital portant sur un maximum de 5M avec maintien du droit préférentiel de souscription par offre au public Intérêts pour nos actionnaires : Offrir la possibilité aux actionnaires existants de participer à l opération Privilégier la participation des actionnaires existants par rapport à de nouveaux investisseurs Un prix de souscription attractif, inférieur d un peu plus de 20% par rapport aux cours de bourse de référence précédant la décision de lancement de l opération (moyenne des 10 derniers cours de clôture de 2013) L opération est «sécurisée» par l engagement de Biotech Avenir à couvrir jusqu à hauteur de 75% du montant pour assurer la réalisation de l opération Modalités : Prix de souscription par action : 6,98 Droit préférentiel de souscription (DPS) : 1 action donne droit à 1 DPS Parité de souscription : 33 DPS (33 actions anciennes) donnent droit à 1 action nouvelle 16

17 Opération financière en cours Comment Souscrire Souscrire à titre irréductible : L actionnaire a le droit de souscrire à hauteur de tous les droits de souscription qu il détient au dernier jour de la souscription, sans qu il soit possible de réduire sa demande. Souscrire à titre réductible L actionnaire peut déposer une demande de souscription au-delà des droits qu il détient. Si les demandes à titre réductible excèdent le nombre d actions offertes, une réduction sera appliquée à chaque demande au prorata des droits présentés 17

18 Opération financière en cours Comment Souscrire Pour un actionnaire au moment du lancement de l émission, faculté de : souscription irréductible à concurrence de ses droits achat ou vente de droits (DPS) en bourse pour ajuster sa souscription demande d une souscription à titre réductible (sera servie suivant la part irréductible et dans la limite de sa demande effective) ne pas souscrire et vendre l intégralité de ses DPS pour compenser financièrement sa dilution La banque teneur du compte titre de l actionnaire l informe de ses droits et lui demande ce qu il souhaite faire Pour un non actionnaire au moment du lancement de l émission : Achat de droits en bourse pour une souscription à titre irréductible et demande à titre réductible 18

19 Opération financière en cours Calendrier 2 janvier 2014 : Directoire ayant décidé des modalités de l émission 9 janvier 2014 : Ouverture de la période de souscription et début de la cotation des droits préférentiels de souscription 23 janvier 2014 : Clôture de la période de souscription et fin de cotation des droits préférentiels de souscription 4 février 2014 : Publication du résultat de l opération 7 février 2014 : Règlement livraison des actions nouvelles 10 février 2014 : Cotation des actions nouvelles 19

20 Next Events First Quarter 2014 Key pharma business, partnering & scientific conferences JP Morgan & Biotech Showcase 2014 January 13-16, 2014 (San Fransisco USA) BIO CEO & Investors Conference February 10-11, 2014 (New-York USA) Inflammatory Bowel Diseases February 20, 2014 (Copenhagen Denmark) Future Leaders in the Biotech Industry March 28, 2014 (New York - USA) EASL April 9, 2014 ( London, Great Britain) 20

21 x UMR1011 Une Approche Public-Privé Complémentaire et Synergique UMR1011 «Récepteurs nucléaires, maladies cardiovasculaires et diabète»

22 UMR1011 «Récepteurs nucléaires, maladies cardiovasculaires et diabète» Directeur : Bart Staels Professeur CE, Univ. Lille 2 Co-fondateur de Genfit Président du SAB de Genfit Co-fondateur d EGID

23 Une réputation internationale basée sur une recherche d excellence Entre Oct Dec 2013: 224 publications, including 42 reviews, 2 book chapters and 14 letters or editorials large number of publications between >2 teams of the unit >180 invited (inter)national lectures >200 abstracts in (inter)national meetings Annual citation number of UMR1011 publications

24 The Obesity Epidemic: caloric intake vs energy expenditure

25 The Metabolic Syndrome Obesity (waist circ.: men>103; women>88 cm) I n s u l i n r e s i s t a n c e - g l u c o s e i n t o l e r a n c e D y s l i p i d e m i a (FPG: >110 mg/dl) (TG: >150 mg/dl; HDL men<40; women<50 mg/dl) H e m o s t a t i c & c o a g u l a t i o n d i s t u r b a n c e s H y p e r t e n s i o n & h e m o d y n a m i c d i s t u r b a n c e s (SBP: >130 mmhg; DBP: >85 mmhg) Atherosclerosis NCEP ATPIII Guidelines, 3 of 5 Inflammation

26 Clinical Complications of Obesity and the Metabolic Syndrome The metabolic syndrome is a predictor of Type 2 Diabetes The metabolic syndrome is a CV risk factor NAFLD is the liver phenotype of the metabolic syndrome

27 Non-Alcoholic Fatty Liver Disease (NAFLD) 25% of the general population 70% in diabetic and obese patients STEATOSIS 5-7 % of the general population in western countries 45M people in North America & Europe 25-30% in diabetic & obese patients HEALTHY LIVER Hepatocellular Carcinoma Liver Transplantation Death (cardiovascular&liver-related) NASH (Non-alcoholic Steatohepatitis) CIRRHOSIS

28 Le Syndrome Métabolique Obesity Team 1: I n s u l i n r e s i s t a n c e - g l u c o s e i n t o l e r a n c e D y s l i p i d e m i a H e m o s t a t i c & c o a g u l a t i o n d i s t u r b a n c e s Team 4: Molecular mechanisms H y p e r t e n s i o n & h e m o d y n a m i c d i s t u r b a n c e s Cardiovascular Disease Teams 2 & 3: Immuno-inflammation Atherosclerosis

29 L Institut Européen de Diabète EGID FR 3508 European Genomic Institute for Diabetes (E.G.I.D.) UMR 8199 Integrative genomics and metabolic diseases modelling U 1011 Nuclear receptors, cardiovascular diseases and diabetes U 859 Translational research and Diabetes Genomics and epigenomics of metabolic diseases Molecular basis and obesity and diabetes modelling Nuclear receptors in the metabolic syndrome Molecular control of monocyte/ macrophage functions in cardiometabolic syndrome Nuclear receptors, immunoinflammation and cardiometabolic diseases Molecular analysis of gene regulation in cardiometabolic diseases Biotherapy Experimental diabetes

30 The EGID project and laboratories UMR1011

31 Genfit x EGID: Active Collaborations in the Fields of Obesity, Diabetes and its Complications R & D DIAGNOSTIC THERAPY MONITORING Valorisation of research tools Diagnostic tools Therapeutic compounds: Innovating compounds

32 10. GFT505 Pres. Investors v22 aug 2013 Thank you 32