Genfit Sa · EURONEXT:GNFT
Genfit Sa — Investor Day (December 2023)
74 slides from Genfit Sa's investor day presentation, Dec 12, 2023
Slide 1: ACLF Day – Corporate Presentation
ACLF Day DECEMBER 12, 2023 Paris, FRANCE Corporate Presentation
Slide 2: Disclaimer
Disclaimer 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 B
Slide 3: Towards a new GENFIT
Towards a new GENFIT P a s c a l P R I G E N T, C E O ACLF disease state Pr. Richard Moreau, MD, Senior Scientist (Outstanding Grade) at INSERM Q&A GENFIT’s approach to ACLF Dean Hum, Chief Scientific Officer – Meriam Kabbaj, Chief Technology Officer ACLF market opportunity Pascal Caisey, Chief Oper
Slide 4: Towards a new GENFIT
Towards a new GENFIT Today Inception Clinical development Pivoting to rare and life-threatening & early years in chronic liver diseases liver diseases with high unmet needs 1999 2023 A diversified pipeline in ACLF (5 programs) and Development of Research Development of elafibranor in NASH/MASH1 othe
Slide 5: 2024 Outlook Following Acceptance of Elafibranor Filings in PBC in U.S./EU
2024 Outlook Following Acceptance of Elafibranor Filings in PBC in U.S./EU ▪ Regulatory filings U.S. and Europe – <6 months after topline data ▪ Expected launch of elafibranor in the U.S. – Priority Review granted by U.S. FDA – FDA PDUFA set to June 10, 2024 ▪ Financial implications for GENFIT – Exp
Slide 6: Pipeline
Pipeline Preclinical Phase 1 Phase 2 Phase 3 Next expected/targeted steps2 ACLF VS-01 Orphan Drug Designation FDA & EMA Ph2 UNVEIL-ITTM Interim analysis mid-2024 franchise NTZ3 Ph2a POC initiation targeted for 1H25 SRT-0154 First-in-Human study targeted for 2H24 CLM-0225 Preclinical Proof of Concept
Slide 7: ACLF Disease state
Towards a new GENFIT Pascal Prigent, CEO ACLF Disease state P r . R . M o re a u , M D, S e n i o r S c i e n t i s t ( O u t s t a n d i n g G ra d e ) , I N S E R M Q&A GENFIT’s approach to ACLF Dean Hum, Chief Scientific Officer – Meriam Kabbaj, Chief Technology Officer ACLF market opportunity Pa
Slide 8: Professeur Richard Moreau, Founding Member of EF-CLIF and Worldwide Leader in ACLF
Professeur Richard Moreau, Founding Member of EF-CLIF and Worldwide Leader in ACLF 8
Slide 9: Acute-on-Chronic Liver Failure (ACLF)
ACLF Day December 12, 2023 Acute-on-Chronic Liver Failure (ACLF) Richard Moreau, MD, FAASLD,1,2,3 1European Foundation for the Study of Chronic Liver Failure (EF CLIF), Barcelona, Spain; 2Centre de Recherche sur l’Inflammation (CRI), INSERM, Université Paris Cité, CNRS, Paris, France; 3Service d’hép
Slide 10: Outline
Outline • Cirrhosis & ACLF • Defining ACLF • Pathophysiology • Medical management • Liver transplantation • Unmet needs
Slide 11: Cirrhosis
•. Cirrhosis • 11th most common cause of death o 2 million deaths worldwide/year (~4% of deaths worldwide) • 2 billion consume alcohol o At risk for alcohol-associated cirrhosis • 2 billion overweight/obese o At risk for metabolic-associated cirrhosis Asrani et al. J Hepatol 2019;70:151-71. Devarbha
Slide 12: Characteristics of Cirrhosis
Characteristics of Cirrhosis • Chronic liver disease • Compensated for years • Decompensated: ascites, gastrointestinal hemorrhage, hepatic encephalopathy o Recent onset defines acute decompensation • Acute decompensation: often leads to nonelective hospital admission • ACLF: cause of death in acute
Slide 13: Characteristics of ACLF
Characteristics of ACLF • Men ~55 yr • Seen among patients nonelectively admitted for acutely decompensated cirrhosis • Defined by impaired function of major organ systems & intense systemic inflammation • Associated with high short-term mortality (by 28 & 90 days) • Engages health-care system resou
Slide 14: ACLF Burden in Europe
ACLF Burden in Europe • Under evaluation (commissioned by Journal of Hepatology) • Currently estimated to ~150,000 cases/yr (projection from German data).
Slide 15: Evidence-Based Knowledge Produced by EF CLIF
Evidence-Based Knowledge Produced by EF CLIF • Studies in patients nonelectively admitted for acute decompensation: o CANONIC: 1343 European patients o PREDICT: 1273 European patients o ACLARA: 1274 LATAM patients Moreau et al. Gastroenterology 2013;144:1426-37. Trebicka et al. J Hepatol 2020;73:842
Slide 16: Outline
Outline • Cirrhosis & ACLF • Defining ACLF • Pathophysiology • Medical management • Liver transplantation • Unmet needs
Slide 17: Diagnostic Criteria & Prevalence of Organ System Failures (CANONIC Study)
Diagnostic Criteria & Prevalence of Organ System Failures (CANONIC Study) Prevalence Organ system Diagnostic criteria* (%) Liver Bilirubin ≥12 mg/dL 15.4 Kidney Creatinine ≥2 mg/dL or 12.6 RRT Coagulation INR ≥2.5 7.8 Brain Grade 3 or 4 HE 7.4 Circulation Use of vasopressor 4.8 Respiration SpO2/FiO2
Slide 18: The CANONIC Study Defined ACLF
The CANONIC Study Defined ACLF 1343 patients nonelectively admitted for acutely decompensated cirrhosis (new ascites, encephalopathy, infection, GI hemorrhage) 70% 30% Presence of ACLF Absence of ACLF • High-grade systemic inflammation • Low-grade systemic inflammation • Organ failures • No organ fa
Slide 19: Triggers of Inflammation & ACLF (PREDICT Study)
Triggers of Inflammation & ACLF (PREDICT Study) Trigger Prevalence Type: Bacterial infection 44% Alcohol-related hepatitis 44% GI hemorrhage with shock 6% Toxic encephalopathy 6% Number: 1 46% ≥2 25% 0 29% Trebicka, Fernandez, et al. J Hepatol 2021:74;1097-108.
Slide 20: Clinical Course of ACLF Within the 1st Week
Clinical Course of ACLF Within st the 1 Week ACLF Grade at Day 7 Initial Grade 0 1 2 3 % patients ACLF-1 55 24 8 12 ACLF-2 35 15 25 25 ACLF-3 16 4 12 68 Gustot, Fernàndez, et al. Hepatology 2015;62:243-52.
Slide 21: 90-Day Transplantation-Free Survival According to Status at Day 7
90-Day Transplantation-Free Survival According to Status at Day 7 Among 329 Patients Had ACLF on Admission Arroyo, Moreau, Jalan. N Engl J Med 2020;382:2137-45.
Slide 22: ACLF is a Global Disorder
ACLF is a Global Disorder Europe USA Asia Latin America Arroyo, Moreau, Jalan. N Engl J Med 2020;382:2137-45.
Slide 23: Outline
Outline • Cirrhosis & ACLF • Defining ACLF • Pathophysiology • Medical management • Liver transplantation • Unmet needs
Slide 24: Inducers of Inflammation
Inducers of Inflammation • Pathogen-associated molecular patterns (PAMPs) = bacterial byproducts immediately recognized by immune system; induce inflammation • Damage-associated molecular patterns (DAMPs) = intracellular molecules released by dying cells; immediately recognized by immune system; ind
Slide 25: Inducers of Inflammation According to Triggers
Inducers of Inflammation According to Triggers Liver injury Infection (cell death) No apparent trigger PAMPs DAMPs PAMPs Systemic inflammation Organ failures Arroyo, Moreau, Jalan. N Engl J Med 2020;382:2137-45.
Slide 26: Impaired Gut Barrier in Decompensated Cirrhosis
Impaired Gut Barrier in Decompensated Cirrhosis • Changes in gut microbiome (↑ pathobionts = “bad” bacteria) • ↑ Intestinal permeability to bacteria and/or bacterial PAMPs • Translocation of bacteria and/or bacterial PAMPs to blood flowing to the liver • ↓ Function of the “hepatic filter”; bacteria
Slide 27: Outline
Outline • Cirrhosis & ACLF • Defining ACLF • Pathophysiology • Medical management • Liver transplantation • Unmet needs
Slide 28: Key Points
Key Points • Main principle: Diagnose acute precipitants & treat them urgently • Provide supportive therapy in ICU • Objective: Bridge to early liver transplantation • No “pathophysiology-based” therapy available. Arroyo, Moreau, Jalan. N Engl J Med 2020;382:2137-45. EASL CPG. J Hepatol 2023;79:461-
Slide 29: Supportive Therapy
Supportive Therapy • Cardiovascular: vasoconstrictors. • Respiratory: mechanical ventilation. • Brain: protective intubation if necessary; lactulose; albumin dialysis (MARS) if lactulose failure. • Liver: 2 negative RCTs of extracorporeal MARS. Arroyo, Moreau, Jalan. N Engl J Med 2020;382:2137-45. E
Slide 30: Other Interventions
Other Interventions • Granulocyte colony-stimulating factor o No efficacy • Plasma exchange o Trial recruiting • Cell therapy o Under evaluation EASL CPG. J Hepatol 2023;79:461-91.
Slide 31: Outline
Outline • Cirrhosis & ACLF • Defining ACLF • Pathophysiology • Medical management • Liver transplantation • Unmet needs
Slide 32: Survival Among Patients with ACLF-2, -3 with or without Early Liver Transplant
Survival Among Patients with ACLF-2, -3 who Did or Did not Receive Early (<28 days) Liver Transplant Gustot, Fernandez, et al. Hepatology 2015;62:243-52.
Slide 33: Narrow window for liver transplantation
Survival Among Patients with ACLF-2, -3 who Did or Did not Receive Early (<28 days) Liver Transplant Narrow window for liver transplantation Gustot, Fernandez, et al. Hepatology 2015;62:243-52.
Slide 34: Liver Transplantation in Patients with ACLF
Liver Transplantation in Patients with ACLF ACLF-3 only Artru et al. J Hepatol 2017; 67:708-15.
Slide 35: Outline
Outline • Cirrhosis & ACLF • Defining ACLF • Pathophysiology • Medical management • Liver transplantation • Unmet needs
Slide 36: Targeting Bacterial/PAMP Translocation
Targeting Bacterial/PAMP Translocation • Current approaches are based on antibiotics • Restricted to few patients • Major issues with antibiotic use (emergence of multidrug-resistant bacteria) • Alternative approaches: unmet need.
Slide 37: Conclusions
Conclusions • ACLF is the most severe form of acutely decompensated cirrhosis • Bacterial/PAMP translocation & systemic inflammation are key pathogenic mechanisms • There is no “pathophysiology-based” therapy currently available • Liver transplantation is effective but limited due to narrow time, or
Slide 38: Questions & answers
Towards a new GENFIT Pascal Prigent, CEO ACLF disease state Pr. Richard Moreau, MD, Senior Scientist (Outstanding Grade) at INSERM Questions & answers GENFIT’s approach to ACLF Dean Hum, Chief Scientific Officer – Meriam Kabbaj, Chief Technology Officer ACLF market opportunity Pascal Caisey, Chief O
Slide 39: GENFIT's approach to ACLF
Towards a new GENFIT Pascal Prigent, CEO ACLF disease state Pr. Richard Moreau, MD, Senior Scientist (Outstanding Grade) at INSERM Q&A GENFIT’s approach to ACLF Dean Hum, Chief Scientific Officer – Meriam Kabbaj, Chief Technology Officer ACLF market opportunity Pascal Caisey, Chief Operating Officer
Slide 40: Building a targeted portfolio to address the unmet need in ACLF
Building a targeted portfolio to address the unmet need that exists with current (not approved) Standard of Care in ACLF Specific selection of strategic assets: based on pathophysiology1 of ACLF, as defined by liver experts and consortiums such as EF-CLIF (European Foundation for the study of Chroni
Slide 41: 5 assets with complementary mechanisms of action targeting key pathways
5 assets with complementary mechanisms of action targeting key pathways We are developing a diversified pipeline to better address the complexities of ACLF and improve treatment outcomes VS-01-ACLF NTZ SRT-015 CLM-022 VS-02-HE Peritoneal Oral Injectable Oral Liposomal-based Anti-inflammatory ASK1 NL
Slide 42: Patient Journey & Window of Opportunity for Treatment
Patient Journey & Window of Opportunity for Treatment VS-01 NTZ SRT-015 Multiorgan support in the VS-02 early course of ACLF CLM-022 TREATMENT GOALS - DYSBIOSIS - PAMPS - BACTERIAL TRANSLOCATION Recovery ▪ Resolve ACLF ▪ Improve survival ▪ Chance of liver transplant Transplantation (Tx) increased ▪
Slide 43: VS-01 Clinical Stage Program in ACLF
VS-01 Clinical Stage Program in ACLF
Slide 44: Extraction of Metabolites to Reduce Mortality
VS-01 Extraction of Metabolites to Reduce Mortality Standard of care VS-01 in brief Ascites drainage High unmet medical need in ACLF with no approved treatment and 112’000 cases1 Targets first-line treatment for VS-01 VS-01 scavenging liposomes ACLF to reverse the disease Delivered via in-place peri
Slide 45: First in Human Study
VS-01 First in Human Study Part A: Single Ascending Dose (n = 9) Part B: Multiple Doses (n = 3) Cohort 1 Cohort 2 Cohort 3 IDSMB Cohort 4 15 mL/kg 30 mL/kg 45 mL/kg 34-42 mL/kg daily for 4 days DETAILS OUTCOME • Study population (n=12): ✓ Generally safe and well tolerated - Decompensated liver cirrh
Slide 46: Phase 1b Preliminary Efficacy Results on Liver & Brain Function
VS-01 Phase 1b Preliminary Efficacy Results on Liver & Brain Function IMPACT ON OVERALL LIVER DOSE-DEPENDENT AMMONIA IMPROVEMENT IN DISEASE SEVERITY REMOVAL FROM THE BODY PSYCHOMETRIC TESTS FOR HE e.g., assessed by Child-Pugh Score (CPS) Ammonia clearance increased with VS-01 dosage in e.g., number
Slide 47: UNVEIL-ITTM Phase 2a Proof-of-Concept Trial
VS-01 UNVEIL-ITTM Phase 2 Proof-of-Concept Trial Phase 2a Proof Of Concept Study of VS-01 in Patients with Acute-on-Chronic Liver Failure INTERIM ANALYSIS* OPEN-LABEL 1:1 RANDOMIZED CONTROLLED MULTI-CENTER GLOBAL STUDY TARGETED 1H2024 Patient Primary Population Objective Adult patients with Acute-on
Slide 48: NTZ Clinical Stage Program in ACLF
NTZ Clinical Stage Program in ACLF NTZ (Nitazoxanide) is a repositioned molecule
Slide 49: NTZ Impacts Multiple Pathways
NTZ NTZ Impacts Multiple Pathways NTZ antibacterial activity through inhibition of PFOR NTZ anti-inflammatory activity at least through NF-kB/MAPK pathway 49
Slide 50: Activity in Disease Models Support ACLF Clinical Development
NTZ Activity in Disease Models Support ACLF Clinical Development Reduces LPS-induced Beneficial effects on liver Alleviates liver and renal Reduces brain edema, Improves survival in inflammation in function markers (bil, alb) in damages in a model of inflammation markers and reverses treatment model
Slide 51: Completed Ph1 studies in hepatic and renal impairment
Completed Ph1 studies in subjects with NTZ hepatic impairment (HI) and renal impairment (RI) An Open-label, Phase 1, Multiple-dose Study to Evaluate the Pharmacokinetics and Safety of NTZ 500 mg twice daily for 7 days in Adult Subjects with Moderate & Severe Hepatic Impairment and Adult Healthy Cont
Slide 52: Development of a New Formulation ahead of Phase 1b/2a Proof-of-concept
Development of a New Formulation, ahead of a NTZ Phase 1b/2a Proof-of-concept Targeted to Start in 1H25 New formulation under development To permit greater dosing flexibility and ultimately better serve the ACLF patients: ▪ This population is known to have impaired/organs failure, and this new formu
Slide 53: SRT-015 Preclinical stage program in ACLF
SRT-015 Preclinical stage program in ACLF SRT-015 has been in-licensed from Seal Rock Therapeutics
Slide 54: An Injectable Formulation of ASK1 Inhibitor
SRT-015 An Injectable Formulation of ASK1 Inhibitor SRT-015 in brief ASK1 inhibitor in-licensed from Seal Rock Therapeutics in acute liver diseases Injectable formulation Targets inhibition of cellular apoptosis, inflammation and fibrosis Scientific rationale ASK1 inhibition has shown several potent
Slide 55: Target Engagement, MoA, Activity and Data Supporting Development in ACLF
SRT-015 Target Engagement, MoA, Activity and Data Supporting Development in ACLF Inhibits: -ASK-1 -phosphorylation of p38 -phosphorylation of JNK Activity: -Anti-inflammatory -Anti-apoptotic -Anti-fibrotic SRT-015 alleviates hepatic injury in a model of drug-induced liver injury, SRT-015 alleviates
Slide 56: Clinical Data Support Development in Liver Diseases
SRT-015 Clinical Data Support Development in Liver Diseases Multi-organ benefits of ASK1 modulation have been observed in several animal models and clinical trials1 › SRT-015 has demonstrated efficacy in multiple In kidney diseases preclinical models2 of acute and chronic liver => limits renal infla
Slide 57: CLM-022 Preclinical stage program in ACLF
CLM-022 Preclinical stage program in ACLF CLM-022 has been in-licensed from Celloram Inc.
Slide 58: Supporting Evidence and Next Steps
CLM-022 Supporting Evidence and Next Steps Preclinical CLM-022 • Blocks NLRP3 inflammasome activated by ATP and Nigericin • Blocks the endotoxin-induced production of inflammatory cytokines in an LPS sepsis model • Blocks ASC speck formation at nanomolar concentrations Preclinical NLRP3 • Decreases
Slide 59: VS-02-HE Preclinical program in ACLF and its complications
VS-02-HE Preclinical program in ACLF and its complications
Slide 60: Supporting Evidence and Next Steps
VS-02-HE Supporting Evidence and Next Steps About HE VS-02 in Preclinical data ACLF-HE • Superior urease inhibitory activity in vitro - Major complications of • Cytotoxicity and mutagenicity assessment (Ames test) IND enabling advanced liver disease and portal hypertension6 • Reduces plasmatic ammon
Slide 61: ACLF market opportunity
Towards a new GENFIT Pascal Prigent, CEO ACLF disease state MD, Senior Scientist at the National (French) Institute of Health (Inserm) Q&A GENFIT’s approach to ACLF Dean Hum, Chief Scientific Officer – Meriam Kabbaj, Chief Technology Officer ACLF market opportunity Pascal Caisey, Chief Operating Off
Slide 62: Disclaimer
Disclaimer • IQVIA is not an “authorized person” for the purposes of the Financial Services and Markets Act 2000 (“FSMA”) and does not provide investment advice or carry on any other regulated activity under Part II of the FSMA 2000 (Regulated Activities) Order 2001. • Projections and related inform
Slide 63: Secondary market research to assess the commercial opportunity in ACLF
We conducted secondary market research / literature review to assess the commercial opportunity in ACLF SCOPE ACLF disease landscape ACLF addressable market estimation • Performed a literature review and secondary market • Overall ACLF market size estimated based on research to understand: epidemiol
Slide 64: ACLF is a life-threatening disease involving multiple organ failure
ACLF is a life-threatening disease involving multiple organs failure and characterized by short term mortality Acute on chronic liver Life-threating disease characterized by acute decompensation of chronic liver disease associated with multiple organ failures failure and high short-term mortality1 5
Slide 65: Economic burden of ACLF on healthcare systems
Management of ACLF results in significant economic burden on healthcare systems, leading to a high need for innovative therapies The burden of ACLF in numbers 52 000 $ 16 days 6.4 Bn $ Average cost per Average length of hospital Estimated annual cost hospitalization per patient in stay1 burden in US
Slide 66: ACLF has low epidemiology and could be eligible for orphan designation
ACLF has low epidemiology and could be eligible to orphan designation; aging population and launch of targeted Tx can increase diagnosis rate Estimated current prevalence (1:100,000) Overview and future outlook 100 • In 2021, the prevalence of ACLF is 90 estimated to be ~294K across the US, EU4 80 a
Slide 67: Analogues selected to estimate price range of upside potential
Several analogues were selected to estimate price range of upside potential, including one-off therapies for chronic disease and drugs for acute episodes Analogues considered • To identify relevant price range for Analogue MoA Features List Price (US) the ACLF drugs, different analogues Recombinant
Slide 68: Grade 1-2 ACLF may represent a ~4 bn USD addressable market by 2030
Overall, grade 1-2 ACLF may represent a potential ~4 bn USD addressable market opportunity in the US and EU4+UK by 2030 Ballpark overall market size by 2030, bn USD1 Assumptions / considerations 4.0 • Prevalence: 150K (EU4 + UK) / 90k (US) for grade 1-2 ACLF patients2 • Drug price could amount to $3
Slide 69: Detailed overview of assumptions used to estimate addressable market in 2030
Detailed overview of assumptions used to estimate addressable market in 2030 in US & EU4+UK Assumptions / considerations Input Base Upside Rationale / Sources ~100K • US: Hernaez, et al., J of Hepatol (2019) Prevalence ~190 • EU4+UK: Moreau, R., et al., (2013) Table 10; ACLF 1 prevalence 45% 45% • I
Slide 70: ACLF is an attractive market opportunity with upside potential
ACLF is an attractive market opportunity with upside potential given significant unmet need for urgent treatment and easier clinical development Possibility to lead ACLF market growth with therapies being launched at a price fully representing their value ACLF is an attractive opportunity for Biotec
Slide 71: Questions & answers
Towards a new GENFIT Pascal Prigent, CEO ACLF disease state Pr. Richard Moreau, MD, Senior Scientist (Outstanding Grade) at INSERM Q&A GENFIT’s approach to ACLF Dean Hum, Chief Scientific Officer – Meriam Kabbaj, Chief Technology Officer ACLF market opportunity Pascal Caisey, Chief Operating Officer
Slide 72: Highlights on newsflow
Towards a new GENFIT Pascal Prigent, CEO ACLF disease state Pr. Richard Moreau, MD, Senior Scientist (Outstanding Grade) at INSERM Q&A GENFIT’s approach to ACLF Dean Hum, Chief Scientific Officer – Meriam Kabbaj, Chief Technology Officer ACLF market opportunity Pascal Caisey, Chief Operating Officer
Slide 73: Highlights on newsflow
Highlights on newsflow Elafibranor1 Elafibranor1 Regulatory submission (U.S., E.U.) Expected commercialization by partner ✓ second line PBC2 Ipsen, if approved U.S. FDA PDUFA action date: June 10, 2024 Dec 23 2024 2025 VS-01 NTZ Phase 2 UNVEIL-ITTM Interim analysis Phase 2a POC initiation (1H25) SRT
Slide 74: THANK YOU
THANK YOU Corporate Presentation