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Malam Aboubakar Alexia Dumoulin Hortense Masias Diane-Laurène Smal. Faculty of Pharmacy, Lille 2 _ March 2009. Safe harbor. This is an independent study performed by students from the Faculté des Sciences Pharmaceutiques de Lille
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MalamAboubakar Alexia Dumoulin Hortense Masias Diane-Laurène Smal Faculty of Pharmacy, Lille 2 _ March 2009
Safeharbor This is an independent study performed by students from the Faculté des Sciences Pharmaceutiques de Lille The opinions expressed are our own and not necessarily those of Genfit
Creation in 1999 A team consists of 130 people driven by : • Jean-Charles Fruchart: ExecutiveScientificAdvisor, • Bart Staels : president of the ScientificAdvisoryBoard, • Jean-François Mouney : chairman and chiefexecutive officier SCIENTIFIC & FINANCIAL EXPERTISE
Location and subsidiaries Parc Eurasanté 245, First Street Lille Metropole 18th floor, office 1806 885, av. Eugène Avinée Cambridge MA 02142 59 120 LOOS – France USA
A unique business modele VISION: DEVELOP TOMORROW’S MEDICINES • Valuing partnerships • A thorough clinical knowledge of the disease • Staying at the edge of innovation • Focusing on patients needs
Focuses on Cardiometabolicdisease • Scientific background from Pasteur Institute : PPAR knowledge • Cardiometabolicdiseasesleaded to 17,5 million deathsor 30% of global mortality in 2005 • In 2007, the cardiovasculardisordersmarketwasestimatedat$143.940m (growth rate of 3.9% in 2006-07) • Limitation of currenttherapies
Activityfield : a pluripotent market GENFIT’S PURPOSE : discovery and development of drugs for prevention and treatment of common risk factors associated with cardiovascular and metabolicdisorders
Strongemphasis on partnerships • Since its inception, Genfit has strongly valued the importance of partnerships with pharmaceutical and biotechnology companies for collaborative researchagreements. • Genfit's balanced business model of internally funded programs and partner supported programs allows the company to manage the risks associatedwithsuch programs OPTIMIZATION OF RESOURCES
creation of GENFIT 4 first alliances And then 2 new Headquarters and laboratories in Lille History Alliances renewal Phase II clinical trials for GFT 505 Increase of screening and proteomic capacities New or renewal of alliances 1999 2005 2009 2002 2006 2 new alliances First GENFIT drug enters preclinical studies Creation of GENFIT corp GENFIT listed on Euronext Alliances renewal Phase I clinical tests for GFT505/ launch of phase IIa
Scientific expertise A long-standing knowledge of gene regulation Solid experience in the family of 'Nuclear Receptors‘ Nuclear receptors form a specific family of transcription factors involved in the regulation of many physiological processes. Over 10% of the world's 100 best selling drugs are targeting nuclear receptors.
Genfit’stherapeuticapproach Year 1990’s Year 2000’s Tomorrow 1 pill, 1 risk factor 1 active substance per pill 1 pill, several risk factors several active substances per pill 1 pill, several risk factors 1 active substances per pill • Reduced treatment efficacy and compliance • Durg interactions generated by combination therapies possibly leading to complication • Complex Pharmaceutical development and registratione • Durg interactions possibly leading to complications • Maximised compliance and efficacy of treatments • No drug interactions • Patentable • Attractive therapeutic solution for multifactorial deseases
Illustration in the case of cardiometabolicdisease TTomorow Tomorow
The beginning… LXR PPAR FXR
PPAR : PeroxisomeProliferator-ActivatedReceptors A nuclearreceptoractivated by endogenousmolecules : fattyacids, insulin… PPARα: regulates the expression of genesinvolved in lipidmetabolism. PPARγ: regulates the expression of Genesinvolved in glucidmetabolism
Efficience of this activation pathway Glc TG PPAR HDL Chol LDL
How to act on the transcription ? Glc TG PPAR HDL Chol LDL
SNuRMs : Selective Nuclear Receptor Modulators A new generation of safer medicines targeting nuclear receptors : • nuclear receptor ligands having cell or tissue specific activities • selected as compounds with an optimum efficacy/safety ratio. Which interest ? Ligand’s chemistry Receptor conformation Coactivator recruitment Pharmacological effect
SPPARM : the selective PPAR modulator • SNuRM concept adapted to PPARs used to select and to develop new PPAR- activators • The technologic SPPARM platform : • in vitro pharmacologic assays (cofactor recruitment properties such as GST pull-down,fluorescence resonance energy transfer assays), • activation of the transcription of genes in target cells and tissues (gene profiling and microarray) • in vivo assays (lipid and glucose metabolism, anti-inflammatory, vascular effects, and side effects).
An added value for drug discovery SNuRM & Analysis of differential co-factor recruitment to develop selective compounds for nuclear receptors which optimised pharmacological effects and less side-effects
The technologicalplatform How to apply the knowledge ? Glc TG PPAR HDL Chol LDL
Technologicplatform Optimisation Chemicalanalysis Modelisation Discover and select the best drug candidate Genomics Proteomics Bioinformatics
Technologicalplatform vs Cardiometabolicdisease Concentratedevelopment efforts on 3 main programs: G800, TGFTX1 and TGFTX2: • G800: evaluesSPPARMs, property of Genfit, on cardiometabolicdisease • TGFTX1: evaluesorphannuclearreceptors on atherosclerosis, inflammation and otherneurodegenerativedisorders • TGFTX2is about an enzyme fromlipidmetabolism in tratment of obesity and insulinoresistance
Developtomorrow’smedicines • Leading technologies for innovative therapeutic solutions • Genfit’s drug development strategy is based on the proven combination of leading edge in-house science complimented by Naturalpha’s optimized clinical research expertise. Glc TG PPAR HDL Chol LDL
1. Research for partners Genfit rents its technological platform to international pharmaceutical groups thanks to : • High scientific value-added • Constant innovation • Mainly with valided targets or with products which had in vivo approval Genfit income = a stable financial situation Glc TG PPAR HDL Chol LDL €
GFT 505 A Pluripotent Drug Candidate for Treatment of Global Cardiometabolic Risk • Oral treatment acting on the 2 sub-types of PPAR receptors : - PPARα(preferential action) Atherogenicdyslipidemia ↓TG, ↓LDL-C, ↑HDL-C - PPARγInsulinresistance • Indications :Treatment of micro and macro-vascular events on overweight patients with or without diabetes
GFT 505 : Preclinical Trials • Doses study : in dyslipidemic mice during 8 days GFT505 potently reduces plasma triglycerides and LDL-C
GFT 505 : Preclinical Trials • Doses study : in transgenic mice for human ApoA-I (HDL) during 7 days GFT505 increases plasma hApoA-I concentration
A milestone in 2005… Own drug candidates Clinical Trials Glc TG PPAR HDL Chol LDL € 10,000,000
… and an IPO in 2006 A raise fund ….
GFT 505 : Clinical Trials Phase I : 14 days at 30mg/day (July 2006 to March 2007) - excellent tolerance on 48 healthy volunteers Phase IIa : GFT505 vs placebo during 28 days with 30mg/day 37 patients :limits the statistical power with type IIb dyslipidemia; completed in March 2008 - broad profile of activity : ↓TG; LDL-C and the levels of ApoC3, ApoB and ApoE (VLDL & LDL) ↑ the levels of ApoA1 and ApoA2 (HDL) Encouraging preliminary efficacy results + absence of any adverse effects
GFT 505 : Clinical Trials Additional Phase I and Phase IIa studies in order to measure the product efficacy at up to 100mg/day Phase I : 14 days at 100mg/day (2008) Excellent tolerance : no side effects on healthy voulunteers Phase IIa : GFT505 vs placebo during 28 days Efficacy ‘s endpoints evaluated with : plasma lipids, glucose metabolism and on markers combined with a microcirculatory malfunction Results are expected before the end of 2009
But since the ENHANCE study… • Ezetimibe shows a reduction of LDL-C • But the effect of Ezetimibe on the progression of atherosclerosisremainsunknown • And the onlycriteria to rememberisa morbi-mortalitystudy
GFT 14…A drug candidate to target mixed type IIbdyslipidemia Structurally very close to natural triglycerides • Phase I trial: single dose (50 – 500mg) or repeated dose over 14 days (50-300 mg/day): (initiated in March 2005) over 100 healthy volunteers Very good tolerance + Excellent security profile + No risk of drug-drug interaction • First Phase IIa pilot (initiated in May 2006) 128 patients Excellent safety profile BUT Compared to fenofibrate:not competitive in terms of lowering triglycerides (250 mg/day) They gave up their product !
GenfitOperational and Net result 2007 2003 2004 2005 2006 10 • Sub contracting fees • Status changement
12770 12410 10810 10510 9477 9260 6600 2560 2000 2001 2002 2004 2003 2005 2006 2007 Genfit net turnover evolution In million euros (in 000 euros) Year
Strategy for future Advance the clinical development of GFT505 & New drugsdiscovery Out-license our lead clinical compound to a pharmaceutical partner after completion of Phase II clinical trials. Maintain, renew, strenghtenpartnerships Diversify therapeutic interest by exploring neurodegenerative indications Proactively and selectively explore in-licensing.opportunities
Last news fromGenfit… • Alliance withServierextendedthrough 2010 • Alliance with Sanofi-Aventis extendedthrough 2010 SAVX1 program turnstowardsneurodegenerativediseasesafterdiabetes and vascular inflammation • GenfitunveilsitsTheranosticStrategy Biomarker programs developed in the field of cardiometabolic and neurodegenerativediseases • BMGFT01 isdedicated to earlydetection of artherosclerosis • BMGFT03 focuses on neurodegenerativediseases