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CORPORATE PRESENTATION
March 2019
MAR
CH20
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II. LEADERSHIP IN NASH & PBC
I. CORPORATE HIGHLIGHTS
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Disclaimer Important Information and Forward Looking Statements
IMPORTANT NOTICE - YOU MUST READ THE FOLLOWING BEFORE CONTINUING •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 OR INFORMATION. ALTHOUGH THE COMPANY BELIEVES ITS EXPECTATIONS ARE BASED ON REASONABLE ASSUMPTIONS, THESE FORWARD-LOOKING STATEMENTS OR INFORMATION 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 2018 REGISTRATION DOCUMENT REGISTERED WITH THE FRENCH AUTORITÉ DES MARCHÉS FINANCIERS (AMF) ON FEBRUARY 27, 2019 UNDER NO. D.19-0078, WHICH IS AVAILABLE ON GENFIT’S WEBSITE (WWW.GENFIT.COM) AND ON THE WEBSITE OF THE AMF (WWW.AMF-FRANCE.ORG) OTHER THAN AS REQUIRED BY APPLICABLE LAW, THE COMPANY DOES NOT UNDERTAKE ANY OBLIGATION TO UPDATE OR REVISE ANY FORWARD-LOOKING INFORMATION OR STATEMENTS. •WE HAVE FILED A REGISTRATION STATEMENT WITH THE SECURITIES AND EXCHANGE COMMISSION ("SEC") IN CONNECTION WITH THE OFFERING TO WHICH THIS PRESENTATION RELATES. BEFORE YOU INVEST, YOU SHOULD READ THE REGISTRATION STATEMENT, THE PRELIMINARY PROSPECTUS INCLUDED WITHIN THE REGISTRATION STATEMENT, AND OTHER DOCUMENTS WE HAVE FILED WITH THE SEC FOR MORE COMPLETE INFORMATION ABOUT US AND THIS OFFERING. YOU CAN OBTAIN THESE DOCUMENTS FOR FREE BY VISITING EDGAR ON THE SEC WEBSITE AT WWW.SEC.GOV. ALTERNATIVELY, COPIES OF THE PRELIMINARY PROSPECTUS MAY BE OBTAINED BY CONTACTING SVB LEERINK LLC, ATTENTION: SYNDICATE DEPARTMENT, ONE FEDERAL STREET, 37TH FLOOR, BOSTON, MA 02110, OR BY TELEPHONE AT (800) 808-7525, EXT. 6132, OR BY EMAIL AT [email protected]; OR FROM BARCLAYS CAPITAL INC., C/O BROADRIDGE FINANCIAL SOLUTIONS, ATTENTION: PROSPECTUS DEPARTMENT, 1155 LONG ISLAND AVENUE, EDGEWOOD, NY 11717, OR BY TELEPHONE AT (888) 603-5847, OR BY EMAIL AT [email protected].
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I. CORPORATE HIGHLIGHTS
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Company Profile
BACKGROUND
• Public company focused on metabolic diseases and associated complications, including liver related disorders • World-leading expert in nuclear receptor based drug discovery • Lead drug candidate discovered in-house • Founded in 1999 (Lille, Paris, France – Cambridge, United States) – 150+ employees • Since 2006, Euronext Paris – compartment B (GNFT) – Market capitalization of ~€700M • €207 million cash balance (End of Year 2018) MAIN PROGRAMS • Elafibranor: First-in-class molecule
• NASH – Phase 3 enrolled (Subpart H), accelerated approval process (Subpart H with FDA; Conditional approval with EMA) and fast-track designation
• PBC – 12-week Phase 2 trial completed with positive top line results • In-Vitro Diagnostic (IVD) for non-invasive diagnosis of NASH • Strong IP protection with full worldwide rights
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Experienced Management Team and Highly Respected Advisory Board
• Jean-François Mouney, Chief Executive Officer, co-founded the company in 1999
• The executive team and board of directors have a deep experience at leading
biotech companies, large pharmaceutical companies and academic institutions
• Pr. Bart Staels, chair of the scientific advisory board and co-founder of the company, is a world-renowned expert in nuclear receptors
• The scientific advisory board is comprised of internationally recognized key opinion leaders in the field of metabolic and inflammatory diseases, with a particular focus on the liver and gastroenterology
• The expertise, leadership and strength of the company’s relationships within the academic and clinical communities are critical to its ability to execute on its mission as it progresses its development pipeline
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A Comprehensive Strategy in Liver and Metabolic Healthcare
1. TREATMENT 2. DIAGNOSIS
3. AWARENESS
Providing THERAPEUTIC SOLUTIONS
Identifying PATIENTS ELIGIBLE FOR TREATMENTS
Optimizing STANDARD of CARE
4. LAUNCH EXCELLENCE Preparing for COMMERCIALIZATION
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Robust Pipeline Focused on Liver and Metabolic Diseases With Near-Term Clinical Milestones
• License agreement with LabCorp – January 2019 • LDT anticipated release in 2019 • Regulatory submission for IVD in 2020
• Currently finalizing analytical and clinical study designs • 2018: alignment with FDA on path forward to validate NIS4 • Discovery of two key miRNA biomarkers in 2015
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Upcoming Expected Catalysts
2019 2018
PBC (elafibranor) PHASE 2 – DATA READOUT
NASH (elafibranor) PHASE 3 – INTERIM DATA READOUT
NASH Diagnostic (biomarkers) PARTNERSHIP
NASH Pediatric (elafibranor) PHASE 2 – 1st PATIENT
2020
NASH Fibrosis (nitazoxanide) PHASE 2 – POC START
PBC (elafibranor) PHASE 3 – LAUNCH
NASH Diagnostic (biomarkers) NIS4 – START COMMERCIALIZATION (LDT)
for ACCELERATED MARKET APPROVAL
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II. LEADERSHIP IN NASH AND PBC
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A Potential to Become a Leader in NASH and PBC
1. TREATMENT NASH & FIBROSIS Elafibranor Combinations Nitazoxanide PBC Elafibranor
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NASH, a Disease Leading to Cirrhosis and HCC, Represents a Large and Untapped Market
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
› Leading cause of liver disease in developed countries; ~20 million in the United States suffer from NASH and advanced fibrosis › Cardiovascular events are the leading cause of death in NASH › Multifaceted disease › Market estimations: up to $20bn by 2025
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Elafibranor, First-in-class, has Pluripotent Activities
PPARα and δ Regulate Multiple Pathways Essential in NASH
Elafibranor, First-in-class, has Pluripotent Activities: PPARα/δ Regulate Multiple Pathways Essential in NASH
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Elafibranor Is One of the Most Advanced NASH Product Candidates
2021 2020 2019
PHASE 3 interim DATA READOUT
• Elafibranor (Genfit) • Ocaliva (Intercept) • Selonsertib (Gilead) • Cenicriviroc (Allergan)
Potential NDA Submission
2018
PHASE 2 DATA READOUT
• MGL-3196 (Madrigal) • Aramchol (Galmed) • NGM-282 (NGM) • VK2809 (Viking)
FIRS
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Evidence from Phase 2 NASH Trials
Elafibranor1
(GENFIT) Ocaliva2
(INTERCEPT) Selonsertib
(GILEAD)
N/A 20% vs 6%
(p-value 0.03) 26% vs 5%
(p-value 0.02)
Cenicriviroc (ALLERGAN)
N/A
MGL-31962
(MADRIGAL) Aramchol2
(GALMED) NGM-2822
(NGM)
TOP LINE COMPARISON on EFFICACY for "NASH RESOLUTION without worsening of fibrosis"
(approved/relevant endpoint for Phase 3 trials and market approval)
11% (no placebo)
17% vs 5% (p-value >0.05)
25% vs 6% (p-value 0.03)
VK28092 (VIKING)
N/A
1st wave candidates
2nd wave candidates
(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
Elafibranor is the only product candidate from the first wave in NASH to have demonstrated all four of (i) EFFICACY ON "NASH RESOLUTION WITHOUT WORSENING OF FIBROSIS" (ii) IMPROVEMENT
OF LIPID PROFILE (iii) IMPROVEMENT OF METABOLIC PROFILE (iv) TOLERABILITY
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Elafibranor in NASH GOLDEN-505 Phase 2 Results*
› Data published in peer-review journal
› Elafibranor resolved NASH without worsening of fibrosis, which has been recommended as primary endpoint for Phase 3 pivotal trials in NASH1: Ballooning = 0; Inflammation = 0 (or 1); No worsening of fibrosis (1 stage)
› Elafibranor showed improvement in the cardiometabolic risk profile of NASH patients
› Elafibranor showed favorable safety and tolerability results
Elafibranor Phase 2b Results: A Solid Ground for RESOLVE-IT Phase 3 trial
(1) Draft guidance presented by the FDA on 12/3/18
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Elafibranor in NASH GOLDEN-505 Phase 2 Results*
Elafibranor Phase 2b Results: Additional Key Benefits for NASH Patients
Beneficial effect on Lipid Markers
in NASH patients
Beneficial effect on - Glucose Homeostasis
- Insulin Sensitivity in T2D NASH Patients
ON TOP OF STANDARD of CARE
LDL-c ("bad” cholesterol) TG (triglycerides) HDL-c (“good” cholesterol)
ON TOP OF STANDARD of CARE
HbA1c (glucose homeostatis) HOMA-IR (insulino resistance)
“It is imperative that any drug developed for NASH be at least neutral from a cardiovascular risk perspective and ideally also reduce cardiovascular risks” (Hepatology 2015)
“Even using a low assumption for NAFLD prevalence in T2D patients, it is estimated that 84MM people in the U.S. live with prediabetes or T2D and NAFLD. Moreover, the coexistence of NAFLD and T2DM results in a worse metabolic profile and a higher cardiovascular risk.“ (Bril, Cusi, Diabetes Care 2017)
Favorable - Safety profile
- Tolerability profile
Crucial for a chronic and silent
disease
SAFETY clinical outcomes TOLERABILTY compliance efficacy in real world
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Elafibranor 120mg Placebo
FIRST TREATMENT PERIOD 18 MONTHS
Elafibranor Phase 3 Design: Details and Timing
2:1
> 250 centers (worldwide)
TRIAL INITIATION Q1 2016
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
Read-out first ~1000 patients: End of 2019
72-WEEK INTERIM ANALYSIS
Histological key secondary endpoint improvement of histological fibrosis (to be considered as an additional labeling claim)
ACCELERATED MARKET AUTHORIZATION • SUBPART H (FDA) • CONDITIONAL APPROVAL (EMA)
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)
~ 1000 patients
EXTENSION PERIOD
Elafibranor 120mg Placebo
~ 2000 patients
2:1
Prevention of NASH associated clinical events, including cirrhosis cancer, all cause mortality
Read-out ~2000 patients: based on occurrence of a pre-defined
number of events
END OF STUDY
DSMB 18-month DSMB 24-month DSMB 30-month
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Clinical Requirements for Future Combinations: Elafibranor Shows Potential as Backbone Therapy
ANTI-NASH drug candidates
PURE ANTI-FIBROTIC drug candidates
Addressing NASH (the underlying cause)
Addressing FIBROSIS (the consequence)
Ensuring a clean SAFETY/TOLERABILITY
Among product candidates in Phase 3, only ELAFIBRANOR and OCALIVA have the potential to address both NASH and fibrosis
ELAFIBRANOR has demonstrated a favorable safety and tolerability profile
in Phase 1 and Phase 2 clinical trials
1
2
3
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Proactive Evaluation of Potential "Add-on" Drug Candidates for Elafibranor in NASH
ELAFIBRANOR DRUG X BACKBONE Add-On
ELAFIBRANOR FXR
ELAFIBRANOR ACC
+
+
ELAFIBRANOR NTZ +
ELAFIBRANOR ANTI-T2D +
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Nitazoxanide (NTZ): GENFIT’s Pure Anti-Fibrotic Drug Candidate
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› A new anti-fibrotic drug candidate, part of GNFT’s discovery program › Currently approved as an anti-parasitic › Early pre-clinical studies have shown promising anti-fibrotic activity › A wholly owned IP position in NASH-related fibrosis › Currently being evaluated in a Phase 2a investigator-led study
Nitazoxanide (NTZ)
CSAA CDAAc NTZ 30mpk NTZ 100mpk Preventive protocol in the CDAA/c model (12 wks)
EASL 2017
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Nitazoxanide (NTZ): Investigator-initiated Phase 2a
Evaluate the safety and efficacy of NTZ
NASH patients with fibrosis Stage 2 (significant fibrosis) or 3 (severe fibrosis)
Non-invasive readout related to fibrosis to assess the changes from baseline to the end of treatment:
de novo collagen synthesis through Fractional Synthesis Rate of circulating plasma proteins circulating markers of fibrosis fibrosis scores based on circulating markers imaging techniques
OBJECTIVE
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PBC (Primary Biliary Cholangitis): Elafibranor Well Positioned to Address Unmet Needs in this Severe Chronic Liver Condition
HIGH UNMET NEEDS
Significant proportion of non/partial responders with current treatments in PBC patient population Major symptom in PBC is pruritus and is not addressed by current PBC therapies
• Cholestatic chronic autoimmune disease • Affecting intrahepatic bile ducts • Severe liver disease • Prevalence in the general population: 0.05% • Patient profile: women 40-60 years old
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 pluripotent mechanism of action
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Recent evidence showing the potential of PPARα to alleviate pruritus, a major symptom of PBC
RATIONALE for ELAFIBRANOR
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Phase 2a Study with Elafibranor in PBC (Primary Biliary Cholangitis)
UDCA + Elafibranor 80mg UDCA + Placebo
TREATMENT PERIOD 12 WEEKS
2:1
1st Patient enrolled May 2017
End of enrollment 45 patients: July 2018
Study population
adult patients with PBC and inadequate response to
ursodeoxycholic acid (UDCA)
Primary Endpoint achieved: December 2018
12-WEEK ANALYSIS
UDCA + Elafibranor 120mg
Primary endpoint
effect of daily oral administration of elafibranor on
serum alkaline phosphatase (ALP) from baseline
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
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Elafibranor in NASH GOLDEN-505 Phase 2 Results*
› Elafibranor successfully meets PRIMARY ENDPOINT (“change at week 12 in serum alkaline phosphatase (ALP) from baseline”) with:
› High statistical significance (p<0.001) › Substantial reductions in alkaline phosphatase in patients receiving elafibranor
› -52% (80 mg) and -44% (120 mg) when compared to placebo
› Significant response rate on COMPOSITE ENDPOINT previously used for REGULATORY APPROVAL of existing PBC therapies (“Serum ALP<1.67xULN, an ALP >15% from baseline, and total bilirubin (TB)< ULN”) with:
› High statistical significance (p<0.001) › 67% (80 mg) and 79% (120 mg) responders vs. 6.7% for placebo
Elafibranor Phase 2 Results: Positive Data Readout in PBC – Key Takeaways
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Elafibranor in NASH GOLDEN-505 Phase 2 Results*
Elafibranor Phase 2 Results: A Highly Competitive Profile
Elafibranor1
(GENFIT) Ocaliva2
(INTERCEPT) Seladelpar3 (CYMABAY)
TOP LINE COMPARISON EFFICACY in PHASE 2 (12-week data)
ALP (% change vs baseline)
% responders ALP<1.67ULN; Bili<ULN
and Delta ALP<-15%
-48%
80mg 120mg pbo 10mg pbo 5mg 10mg pbo
-41% +3% -24% +3%
1. Company press release 2. Hirshfield et al. 2015 Gastroenterology 148:751-761 3. Poster Ap. 2018 - EASL-Hirshfield at al. (Pres Nov 2017 AASLD, Hirshfield et al.)
-33% -45% N/A
67% 79% +6.7% 23% +10% N/A
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Elafibranor in NASH GOLDEN-505 Phase 2 Results*
Elafibranor Phase 2 Results: Positive Data Readout in PBC – Additional Key Benefits
Improvements in: Markers of PBC › Gamma-glutamyl
transferases (GGT)
Beneficial effect: › Early indication of
improvement in pruritus to be confirmed in a longer study
Favorable: › Safety profile › Tolerability profile
Clear clinical evidence to further advance Elafibranor in PBC
Metabolic Markers › Total cholesterol, low-
density lipoprotein-C, and triglycerides.
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A Pioneering & Proactive Approach to Unlock the NASH Market
2. DIAGNOSIS Towards a large scale industrial solution
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Non-invasive, but limited
Imperfect "Gold Standard"
NASH Diagnosis: A Need for Simple Blood-based Solutions
BIOPSY
IMAGING TECHNIQUES
Current bottleneck
“…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
Ideal situation
BLOOD TEST Potential for large scale adoption in the clinic
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GENFIT’s Approach Designed to Ensure the NASH Market Can Reach its Full Potential
HEALTHY CIRRHOSIS
NO NASH NASH
TO BE TREATED N/A NAS ≥ 4 F2 or higher
Steatosis ≥1 Ballooning ≥1 Inflammation ≥1
NAFLD
Focus on a specific and relevant clinical question:
LDT anticipated release in 2019 Regulatory submission for approval anticipated in 2020 (US, EU)
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NIS4 Commercialization: Planned Strategy and Objectives
2021 2020
Prepare IVD for FDA Submission
2019
• LDT for Clinical Research • Expansive Research
PART
NER
SHIP
RE
GU
LATO
RY
• IVD Approval
U.S. Commercial Licensing Agreement
E.U. Commercial
Licensing Agreement
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The Future Patient Journey with IVD Test, for Better Clinical Management of NASH Patients
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A Pioneering & Proactive Approach to Unlock the NASH Market
3. AWARENESS
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The NASH Education ProgramTM
www.the-nash-education-program.com The NASH Education ProgramTM
NASH (Non-Alcoholic
SteatoHepatitis)
Serious liver condition
Unprecedented rise in prevalence
Sub-Optimal PATIENT CARE
Silent, by nature
Diagnostic = bottleneck
No approved treatment yet
Yet still little known, because… HIGH UNMET NEEDS
1
2
3
PHYSICIANS Incl. DIABETOLOGISTS, ENDOCRONOLOGISTS, CARDIOLOGISTS, GPs
PATIENTS Individuals at risk, Families
For BETTER CARE
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A Worldwide Success for the Inaugural Edition of International NASH Day, in 25+ Countries
A large coalition of 20+ stakeholders, across the United States, Europe,
and LATAM, including:
• Patient associations • Learned societies • Companies
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ROADMAP 2019
New and larger leadership
Focus on education
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A Relevant Approach to Market Access to Prepare for Commercialization
1. TREATMENT Ideal drug profile 1st line treatment monotherapy Cornerstone combination therapies
2. DIAGNOSIS Market Enabler (patient identification)
3. AWARENESS Market Enabler (physicians’ knowledge)
4. LAUNCH EXCELLENCE
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A Strategy to Maximize Sales Uptake and Transform the Company
Elafibranor: uniquely positioned in the first wave of NASH products Objective: transform GENFIT into a biopharma, with a mixed revenue stream from:
Direct sales of elafibranor Royalties from potential licensing deal
World class launch plan
Currently recruiting a team of experienced pharma leaders in the field of marketing and market access
People who have joined the team have worked on several global launches and have years of combined experience in big pharma in Europe and the US
Commercialization strategy
Open to explore potential alliance with large pharma company, preferably with a solid footprint in metabolic diseases