Inventiva SA · EURONEXT:IVA
Inventiva SA — Investor Presentation (March 2024)
82 slides from Inventiva SA's investor presentation, March 2024
Slide 1: Developing innovative therapies in NASH
Developing innovative therapies in NASH Corporate Presentation March 2024
Slide 2: Disclaimer
DISCLAIMER This presentation contains “forward-looking statements” within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, included in this presentation are forward-looking statements. These
Slide 3: Key take-aways
Key take-aways A Phase III asset in NASH A Phase III ready program in R&D Capabilities and Cash MPS(1) Position Lanifibranor: only pan-PPAR agonist in Odiparcil: a GAG reduction therapy to R&D capabilities including wholly- clinical development for NASH potentially treat several forms of MPS owned ‘
Slide 4: Management team with extensive global experience across all stages of drug development
Management team with extensive global experience across all stages of drug development and commercialization Frédéric Cren, MA/MBA, CEO and Co- Pierre Broqua, Ph.D., CSO and Co-Founder Founder Successfully managed numerous research programs Wide expertise within the areas of R&D, marketing, lead
Slide 5: Oral small molecule-focused discovery engine targeting nuclear receptors
Oral small molecule-focused discovery engine targeting nuclear receptors, transcription factors and epigenetic modulation Expertise: nuclear receptors, transcription factors, epigenetic Library of ~240,000 Wholly-owned targets compounds of which 129,000 square 60% proprietary foot pharma-like R&D
Slide 6: Deep pipeline
Deep pipeline Program Indication Discovery IND Enabling Phase I Phase II Phase III Lanifibranor NASH pan-PPAR Odiparcil MPS VI GAG clearance Yap-Tead Oncology TGF-β Fibrosis Corporate Presentation | 2024 Property of Inventiva │ 6
Slide 7: Key financials and shareholder base
Key financials and shareholder base Key financials Shareholder base Free Float Founders 25.2% 18.4% Employees & BVF ISIN code FR0013233012 / US46124U1079 Others… 16.2% Yiheng 7.4% Market Euronext Paris / Nasdaq GM Sofinnova NEA 9.8% 10.8% Qatar Holding LLC Shares outstanding 52,115, 807 9.9% Analyst
Slide 8: Lanifibranor in Nonalcoholic Steatohepatitis (NASH)
Lanifibranor in Nonalcoholic Steatohepatitis (NASH)
Slide 9: Lanifibranor: a pan-PPAR agonist in phase III development in NASH
Lanifibranor: a pan-PPAR agonist in phase III development in NASH LANIFIBRANOR Moderate and balanced pan-PPAR agonist activity Small molecule that activates all three PPAR isoforms in humans PPARα Differentiated chemical structure: not a fibrate or a TZD Once daily oral administration Positi
Slide 10: Lanifibranor: licensing and commercialization agreement in Greater China, Japan and South Korea
Lanifibranor: licensing and commercialization agreement in Greater China, Japan and South Korea Licensing agreement in Greater China Licensing agreement in Japan / South Korea Agreement with CTTQ an affiliate of Sino Biopharm one of Licensing agreement with Hepalys Pharma, Inc. backed by the lar
Slide 11: Lanifibranor is a differentiated pan-PPAR agonist
Lanifibranor is a differentiated pan-PPAR agonist with moderate and well balanced activity on the three PPAR isoforms LANIFIBRANOR Differentiated oral small molecule … … that binds differently than glitazone to PPARγ Small molecule that activates all three PPAR isoforms Differentiated chemical R
Slide 12: Lanifibranor's activation of the three PPAR isoforms addresses key features of NASH
Lanifibranor’s activation of the three PPAR isoforms addresses the key features of NASH LANIFIBRANOR Pan-PPAR activity expected to ensure improved efficacy INFLAMMATION AND METABOLISM STEATOSIS BALLOONING PPARα PPARδ PPARγ PPARγ PPARα PPARδ PPARγ Insulin sensitivity FA uptake NFkB-dependent PPARα ge
Slide 13: Adverse events and toxicity seen in other PPAR agonists not observed with lanifibranor
Adverse events and toxicity previously seen in other single and dual PPAR agonists have not been observed to date with lanifibranor SAFETY Organ Isoforms activated Reported PPAR side effects lanifibranor effects Fluid retention HEART PPARγ Cardiac hypertrophy SKELETAL PPARα Myofiber degenerati
Slide 14: Phase I and IIa trials in T2D patients: beneficial changes in metabolic markers
Phase I and Phase IIa clinical trials* in type 2 diabetes (T2D) patients: beneficial changes in key metabolic markers PHASE I AND IIa Lanifibranor metabolic markers in patients with T2D Adiponectin (PPARγ)** HDL Cholesterol (PPARα/δ)^ Triglycerides (PPARα/δ) ^^ 300 baseline baseline baseline p=0.05
Slide 15: Improvements in metabolic parameters and liver histology demonstrated in animal models
Improvements in metabolic parameters and liver histology with anti- fibrotic activity have been demonstrated in animal models LANIFIBRANOR ANIMAL MODELS, BY MODEL TYPE METABOLIC NASH & NAFLD FIBROSIS CIRRHOSIS Diet induced obesity high Methionine Choline Carbon tetrachloride fat / high sucrose Thioc
Slide 16: NASH is a chronic progressive disease with no approved treatment options
NASH is a chronic progressive disease with no currently approved treatment options NASH OVERVIEW Chronic disease that may progress to cirrhosis Reversible Severe liver damage HEPATOCELLULAR -CARCINOMA HEALTHY CIRRHOSIS* DEATH** LIVER LIVER NAFLD NASH NASH with fibrosis TRANSPLANT c.25% of global c.2
Slide 17: Lanifibranor: comprehensive impact on the histology and biology of NASH
Lanifibranor: comprehensive impact on the histology and biology of NASH HISTOLOGY AND MARKERS 1 Fibrosis Regression Fibrosis NASH & Lanifibranor: statistically significant Regression Resolution NASH Resolution effects after 24 weeks Healthy liver Steatosis Steatohepatitis Liver fibrosis Cirrhosis St
Slide 18: Phase IIb NATIVE trial design versus placebo in 247 patients
The Phase IIb NATIVE trial evaluated 800 mg and 1200 mg once-daily lanifibranor versus placebo in 247 patients PHASE IIb DESIGN OVERVIEW 24-week treatment + 4-week follow-up Screening Double blind, randomized, placebo-controlled End of treatment Liver biopsy Liver biopsy Placebo lanifibranor, 80
Slide 19: 247 patients randomised across sites worldwide
247 patients were randomised across 71 sites worldwide, with the majority of patients based in Europe PHASE IIb DESIGN SITE SELECTION 4 sites in 49 sites in Canada Europe Patients Country randomized Europe 183 (74%) U.S. 36 (15%) Australia 13 (5%) 12 sites in the Canada 8 (3%) United States Mauritiu
Slide 20: Majority of patients completed the 24-week treatment
The majority of patients successfully completed the 24-week treatment PHASE IIb DESIGN TREATMENT ARMS 247 patients randomised and treated Placebo lanifibranor 800 mg/day lanifibranor 1200 mg/day N = 81 N = 83 N = 83 74 (91%) patients completed 77 (93%) patients completed 77 ( 93%) patients completed
Slide 21: Patient population baseline characteristics
Patient population included 58% of female and 42% of patients with T2D PHASE IIb DESIGN BASELINE Placebo lanifibranor lanifibranor Overall Parameters (unit) - 800 mg/day 1200 mg/day - n (%) or mean ± SD N = 81 N = 83 N = 83 N = 247 Demographics Female 41 (51%) 54 (65%) 49 (59%) 144 (58%) Age (years)
Slide 22: Liver tests and lipid and glucose markers recorded
Several liver tests and markers of lipid and glucose metabolism were recorded PHASE IIb DESIGN BASELINE Placebo lanifibranor lanifibranor Parameters (unit) - 800 mg/day 1200 mg/day mean ± SD N = 81 N = 83 N = 83 Liver enzymes Alanine aminotransferase, ALT (UI/L) 56.9 ± 31.6 64.1 ± 41.4 63.6 ± 43.4 A
Slide 23: Statistical significance on all histological endpoints in ITT and PP populations
Lanifibranor demonstrated statistical significance on all histological endpoints in both ITT and PP populations PHASE IIb EFFICACY KEY ENDPOINTS xx Statistically significant xx Non-statistically significant Key Phase IIb results by endpoint N = 247 ITT population N = 197 PP population Placebo 800 mg
Slide 24: Significance in patients with F2-F3 fibrosis stage
Statistical significance was also demonstrated for the main key histological endpoints in patients with F2-F3 fibrosis stage PHASE IIb EFFICACY F2-F3 POPULATION xx Statistically significant xx Non-statistically significant Key secondary endpoints in FAS F2-F3 patients (N=188) lanifibranor Placebo Pl
Slide 25: Effect on histological endpoints in overall and F2-F3 population
Effect of lanifibranor therapy on histological endpoints, in the overall population and the subgroup with F2-F3 fibrosis stage Reduction of 2 points of SAF Activity Score and Fibrosis improvement w/o worsening of NASH no worsening of fibrosis All F2-F3 48% 49% 51% N=247 N=188 42% 41% 43% 30% 32% 28%
Slide 26: Statistically significant decrease in liver enzymes
A statistically significant decrease in liver enzymes was observed PHASE IIb EFFICACY OTHER Other secondary endpoints in ITT (N = 247) Absolute change from baseline in ALT Absolute change from baseline in AST 10 10 Mean absolute change (UI/L) Mean absolute change (UI/L) 0 0 -10 -10 -20 ** * ** ** *
Slide 27: Change in HDL-cholesterol and triglycerides
A statistically significant change in HDL-cholesterol and triglycerides was seen, without a change in LDL-cholesterol PHASE IIb EFFICACY OTHER Other secondary endpoints in ITT (N = 247) * p<0.01 **p<0.001 Absolute change from baseline in HDL-C Absolute change from baseline in triglycerides SECONDARY
Slide 28: Reductions of fasting glucose, insulin, HbA1c in NASH and T2D
In patients with NASH and T2D, statistically significant reductions of fasting glucose and insulin, HbA1c were observed PHASE IIb EFFICACY OTHER Secondary endpoints in patients with NASH and T2D (N = 103) Absolute change from baseline in HbA1c Absolute change from baseline in fasting glucose 0.5 Mea
Slide 29: Significant decrease in circulating biomarkers after 24 weeks
A significant decrease in circulating biomarkers was observed under lanifibranor treatment after 24-weeks PHASE IIb EFFICACY OTHER lanifibranor Median relative change (%) Placebo Pvalue (Two doses pooled) Pro-C3 (4.1%) (13.9%) p= 0.005* OTHER OUTCOME MEASURES Pro-C3 >14 at Fibrosis (12.8%) (20.5%) p
Slide 30: Additional NATIVE analyses: improved cardiometabolic health markers
Additional analyses of NATIVE results: lanifibranor improved markers of cardiometabolic health Clinical data demonstrating a robust beneficial effect on markers of cardiometabolic health Correlation between severity of hepatic steatosis and markers of cardiometabolic health, and effect of lanifibr
Slide 31: Lanifibranor has a favourable safety profile
Lanifibranor has a favourable safety profile PHASE IIb SAFETY OVERALL Placebo 800 mg 1200 mg N (%) patients reporting Adverse Event (AE) (N = 81) (N = 83) (N = 83) Any Treatment-Emergent AE (TEAE) 50 (61.7%) 59 (71.1%) 62 (74.7%) Drug-related TEAE 19 (23.5%) 25 (30.1%) 23 (27.7%) Any TEAE leadin
Slide 32: A limited number of serious TEAEs occurred
A limited number of serious TEAEs occurred PHASE IIb SAFETY SERIOUS TEAE Patients reporting treatment-emergent Placebo 800 mg 1200 mg Serious AE (SAE); N (%) (N = 81) (N = 83) (N = 83) Total 3 (3.7%) 3 (3.6%) 7 (8.4%) Treatment-Emergent Serious AE linked to biopsy procedure Post-procedural haematoma
Slide 33: Modest weight increase with no impact on efficacy
Phase II results have demonstrated modest weight increase with no impact on efficacy PHASE IIb SAFETY WEIGHT GAIN CONSISTENT WITH KNOWN INSULIN-SENSITIZING PHARMACOLOGY, a mean weight increase from baseline of 2.4 kg (2.6%) at the 800 mg/day dose and 2.7 kg (3.1%) at the 1200 mg/day dose was obser
Slide 34: Adipose tissue health and cardio-metabolic markers (I/II)
Improvement of adipose tissue health and cardio-metabolic markers following a 24-weeks treatment with lanifibranor (I/II) PHASE IIb SAFETY WEIGHT GAIN NATIVE enrolled 247 patients with SAF activity score 3-4 and fibrosis stage F0-F3 in 3 arms: lanifibranor 800, 1200 mg/d and placebo for 24 weeks
Slide 35: Adipose tissue health and cardio-metabolic markers (II/II)
Improvement of adipose tissue health and cardio-metabolic markers following a 24-weeks treatment with lanifibranor (II/II) Adiponectin Stable weight, Moderate weight increase, Weight Increase CAP, HOMA-IR, ALT and DBP Lanifibranor Lanifibranor Placebo 25 25 6060 2020 20 CAP (dB.m-1) 20 Mean absolute
Slide 36: Improvements of cardio-metabolic health markers at 24 weeks
Improvements of markers of cardio-metabolic health (CMH) at 24- weeks of treatment with lanifibranor Weight change Change from baseline in CMH parameters at EOT Lanifibranor Placebo Moderate Mean (standard deviation) Stable Increase Stable Increase increase N = 73 N = 48 N = 61 N = 12 N = 23 Lipids
Slide 37: Lanifibranor is designed to address all key features of NASH
Lanifibranor is designed to address all key features of NASH ORAL INJECTABLE Lanifibranor Resmetirom Efruxifermin Pegozafermin Semaglutide (pan-PPAR) (THR-β) (FGF) (FGF) (GLP-1) STATUS Phase III Phase III Phase III Phase III Phase III ROUTE OF Oral Oral Injectable Injectable Injectable ADMINISTRATIO
Slide 38: NASH competitive landscape
NASH competitive landscape Resolution of NASH and improvement of fibrosis of at least 1 stage ORAL INJECTABLE Lanifibranor Resmetirom Efruxifermin Pegozafermin Phase II Phase III Phase IIb Phase II 6 months 12 months 6 months 6 months N=247 N=955 N=128 N=222 ITT population ITT population ITT populat
Slide 39: NASH competitive landscape: fibrosis improvement
NASH competitive landscape ≥1 Stage Fibrosis improvement and no worsening of NASH ORAL INJECTABLE Lanifibranor Resmetirom Resmetirom Efruxifermin Semaglutide Pegozafermin Phase II Phase III Phase II Phase IIb Phase II Phase II 6 months 12 months 9 months 6 months 18 months 6 months N=247 N=955 N=125
Slide 40: NASH competitive landscape: NASH resolution
NASH competitive landscape NASH resolution and no worsening of fibrosis ORAL INJECTABLE Lanifibranor Resmetirom Resmetirom Efruxifermin Semaglutide Pegozafermin Phase II Phase III Phase II Phase IIb Phase II Phase II 6 months 12 months 9 months 6 months 18 months 6 months N=247 N=955 N=125 N=128 N=3
Slide 41: Lanifibranor clinical trial in patients with NAFLD and T2D
Lanifibranor clinical trial in patients with NAFLD and T2D PHASE II NAFLD T2D TRIAL Objective of investigator-initiated trial: Establish safety, efficacy and mechanism of action of lanifibranor in patients with T2D and NAFLD. Specifically determine if lanifibranor decreases IHTG(1), improves hepatic
Slide 42: Lanifibranor significantly reduces liver fat and resolves NAFLD
Lanifibranor significanty reduces liver fat and resolves NAFLD LS means relative percent change Percentage of patients achieving Percentage of patients achieving from baseline in liver fat (IHTG) at liver fat reduction ≥30% at week 24 NAFLD resolution at week 24 week 24 (FAS N=38) (FAS N=38) (FAS N=
Slide 43: Treatment effects on liver fat reduction: competitive landscape
Treatments effects on liver fat reduction: competitive landscape Lanifibranor Efruxifermin Pegozafermin Resmetirom Semaglutide T2D/NAFLD NASH (F2-F3) NASH (F2-F3) NAFLD NAFLD Phase II Phase IIb Phase IIb Phase III Phase I 24 weeks* 24 weeks 24 weeks** 52 weeks 24 weeks 48 weeks 30mg 44mg Pbo 800mg P
Slide 44: Improvements in hepatic and muscular insulin sensitivity
Lanifibranor leads to significant improvements in hepatic and muscular insulin sensitivity LS mean absolute change from LS mean absolute change from LS mean absolute change from baseline to week 24 in baseline to week 24 in baseline to week 24 in endogenous glucose production hepatic insulin resista
Slide 45: Lanifibranor increases HDL and adiponectin levels
Lanifibranor treatment increases HDL and adiponectin levels LS Mean absolute change from baseline to week LS Mean absolute change from baseline to week 24 in HDL cholesterol (completers N=28) 24 in adiponectin (completers N=28) 9 pa<0.001 9.0 pa=0.016 7.5 7 6.3 7.0 5 mg/dl 5.0 μg/mL 3 3.0 1 1.0 -1 -
Slide 46: Key take-aways
Key take-aways Lanifibranor met the primary efficacy endpoint by inducing a liver fat reduction of 44% in patients with T2D and NAFLD treated for 24 weeks. – 65% of patients with T2D and NAFLD treated with lanifibranor achieved a greater than 30% liver triglyceride reduction and 25% achieved NAFLD
Slide 47: Physicians positive about lanifibranor's value proposition
Physicians are positive about lanifibranor's value proposition, noting its ability to target both fibrosis and NASH resolution EFFICACY The benefits of a pan-PPAR targeting multiple isoforms are clear to most physicians, who comment positively on lanifibranor's efficacy on fibrosis and NASH resolu
Slide 48: Physicians perceive weight gain as manageable
Physicians perceive weight gain due to lanifibranor as manageable, with the risk profile viewed positively SAFETY Physician express differing views on the importance of weight gain – the majority of physicians believed that given lanifibranor's efficacy profile the risk-benefit ratio was acceptabl
Slide 49: FDA's recent thinking on NASH
FDA’s recent thinking on NASH “The Division of Hepatology and Nutrition (DHN) at the FDA views NASH with liver fibrosis as a serious and life-threatening condition.” (May 2021) “Patients with NASH are also vulnerable to other diseases, and the investigational drugs should not worsen other comorbidit
Slide 50: Phase III NATiV3 should allow accelerated approval filing (I/II)
Phase III NATiV3 should, if positive, allow to file for accelerated approval (I/II) A randomized, double-blind, placebo-controlled, multicenter, Phase III study evaluating long-term efficacy and safety of lanifibranor in adult patients with NASH with liver fibrosis Main Cohort Accelerated 72 weeks t
Slide 51: Phase III NATiV3 should allow accelerated approval filing (II/II)
Phase III NATiV3 should, if positive, allow to file for accelerated approval (II/II) PRINCIPAL INVESTIGATORS: ► Dr. Sven Francque & Dr. Arun Sanyal for the main cohort Potential regulatory approval based on: ► Dr. Stephen Harrison for the exploratory cohort PRIMARY ENDPOINT at week 72 on c.950 patie
Slide 52: Over 400 sites and 24 countries involved in NATiV3
Over 400 sites and 24 countries involved in NATIV3 PHASE III DESIGN SITE SELECTION ► 24 countries ► 468 sites activated in 24 countries (status as of December 20, 2023) ► Target to achieve LPFV H1 2024 NATiV3 countries Corporate Presentation | 2024 Property of Inventiva │ 52
Slide 53: Phase III confirmatory trial design to support full approval
Phase III NATiV3 clinical trial confirmatory trial: anticipated expected design to support broader “full approval” PHASE III OVERVIEW Anticipated event driven trial in patients with NASH compensated cirrhosis Phase 3: event driven N~ 800 EoT Patients with NASH and Lanifibranor: Once daily Potential
Slide 54: Key milestones of the Phase III study in NASH
Key milestones of the Phase III study in NASH PHASE III MILESTONES 2023 2024 2025 2026 F2-F3 Phase III H1 2024 Q1 2026 H1 2026 Part 1: Last Patient Part 1: Last Part 1: Topline First Visit target Patient Last results Visit target H2 2026 NDA submission Corporate Presentation | 2024 Property of Inven
Slide 55: Lanifibranor can be evaluated in combination with other therapies
Lanifibranor can be evaluated in combination with other therapies to further strengthen its value proposition OUTLOOK Combination therapies Examples and potential benefits of combination therapies GLP-1 Potential complementary effects on the multistep disease biology of NASH (disturbances of lipid
Slide 56: SGLT2i with pioglitazone combination benefits
Combination of SGLT2i with pioglitazone has shown additional metabolic health benefits and favorable weight management OUTLOOK SGLT2 combination study Lanifibranor and SGLT2 inhibitor rationale Four randomized trials – Pioglitazone alone vs pioglitazone + sGLT2i – N = 1411 T2D patients • Centers w
Slide 57: LEGEND Study Design
LEGEND Study Design Lanifibranor in Combination with the SGLT2 Inhibitor empagliflozin in patients with NASH and Type 2 Diabetes LEGEND Study Principal investigator Inclusion criteria Prof. M. Lai, gastroenterologist-hepatologist, Adult patients with diabetes and NASH associate professor of medi
Slide 58: Odiparcil in mucopolysaccharidosis (MPS)
Odiparcil in mucopolysaccharidosis (MPS)
Slide 59: MPS VI is a devastating rare lysosomal storage disorder
MPS VI is a devastating rare lysosomal storage disorder Potential for Market Rare, Hereditary Lysosomal Storage Disorder Currently Treated Population Expansion • Mucopolysaccharidoses (MPS) is an inherited disorder characterized Oral therapy would significantly There are ~1,000 patients treated by t
Slide 60: Despite ERT success, many unmet medical needs remain
Despite enzyme replacement therapies (ERT) being commercially successful, many unmet medical needs remain Enzyme replacement therapies are standard of care in MPS Recombinant human enzymes, requiring a once a week intravenous infusion over 4 hours Limited penetration into protected or poorly vas
Slide 61: Odiparcil: oral small molecule GAG reduction therapy for several forms of MPS
Odiparcil: an orally available small molecule GAG reduction therapy designed to potentially treat several forms of MPS Odiparcil reduces GAG accumulation in multiple organs in both developing and established disease MPS VI models Penetrates and clears GAGs from difficult-to-reach tissues, including
Slide 62: Odiparcil key highlights
Odiparcil key highlights We believe odiparcil has the potential to be a differentiated treatment addressing unmet needs for a life-threatening condition • Potential game changer as the first product candidate with the ability to broadly address a wide range of clinical manifestations in MPS VI Oral
Slide 63: MPS VI treatment paradigm
MPS VI treatment paradigm Odiparcil aims at improving the treatment options for both ERT eligible and ineligible patients Current MPS VI Treatment Paradigm ERT-eligible ERT-ineligible 1st Line Naglazyme Palliative Care 2nd Line No Approved Treatments Potential Treatment Paradigm with odiparcil ERT-e
Slide 64: Differentiated mechanism of action potentially synergistic with ERT
Differentiated mechanism of action potentially synergistic with ERT Odiparcil acts to divert endogenous protein-bound GAG synthesis to soluble odiparcil- bound chondroitin sulfate (CS) and dermatan sulfate (DS) synthesis Galactosyl transferase I (GTI) Galactosyl transferase I (GTI) Synthesis of prot
Slide 65: Mechanism relevant to MPS subtypes with excess DS and CS
Odiparcil mechanism of action potentially relevant to MPS subtypes with excess DS and CS MPS Type Frequency DS CS HS(1) KS(2) MPS I-H MPS I-S 1/100,000 MPS I-H/S MPS II Types A & B 1/100,000 1/40,000 to MPS IV Type A 1/200,000 1/240,000 to MPS VI 1/400,000 MPS VII Very rare
Slide 66: Odiparcil GAG clearance mechanism observed in MPS VI mice
Odiparcil GAG clearance mechanism of action observed in MPS VI mice Odiparcil and GAG accumulation in livers tissues 40 GAG in liver [Area * Index] p<0.001 p<0.001 Soluble GAGs produced from 30 odiparcil are excreted in urine 20 Sulfated GAG (µg/mg of creatinine) 6000 p<0.0001 10 0 4000 WT MPS VI MP
Slide 67: Odiparcil penetrates tissues where ERT has limited efficacy
Odiparcil penetrates tissues where ERT has limited efficacy Odiparcil observed to be well distributed in tissues and organs poorly penetrated by recombinant enzymes Heart Bone Cornea Cartilage Odiparcil(1) rhASB(2) Not tested Not detected Not detected Meaningful concentrations of odiparcil observed
Slide 68: Odiparcil reverses corneal impairment in MPS VI mice
Odiparcil reverses corneal impairment in MPS VI mice Odiparcil administration observed to affect corneal structure and corneal GAG storage epithelium stroma WT MPSVI MPS VI + Odi Odiparcil effect on corneal Odiparcil effect on number Odiparcil effect on GAG storage in corneal stroma epithelium thick
Slide 69: iMProveS Phase 2a study design
iMProveS PHASE 2a STUDY DESIGN iMProves Phase 2a Study iMProveS Endpoints and Patient Population IMProveS Phase 2a in MPS VI patients was designed and executed in Phase 2a Patient collaboration with leading MPS VI experts and patient organizations Safety and efficacy of two doses of Population odi
Slide 70: Clinical proof of concept: GAG clearance
Clinical Proof of Concept: GAG clearance Daily oral odiparcil regimen in the IMProveS trial resulted in significant clearance of urinary GAGs Total Urinary GAG 2,000 1,500 Μg/mg creatinine 1,000 500 0 0 0.25 1 3 6 Treatment duration (months) ERT-PLB ERT + ODI - 500 mg ERT + ODI - 1,000 mg ODI - 1,00
Slide 71: Efficacy endpoints assessed in the iMProveS trial
Efficacy endpoints assessed in the iMProveS trial Efficacy endpoints assessed span beyond functional parameters addressed by ERTs Partially addressed by ERT Not addressed by ERT (hard-to-reach tissues) • 6-minute walk test (6MWT) • ECG, Echocardiogram • 9-hole peg test (9HPT) Cardiac and • Carotid i
Slide 72: Clinical proof of concept: functional parameters
Clinical Proof of Concept: functional parameters Improvement on 6MWT and respiratory function (FVC) in adult patients with established disease 6 Minute Walking Test (6MWT) Forced Vital Capacity (FVC) Patients with normal value at baseline (>450m) ERT-PLB -123 4.5 ERT-PLB mg -150 15 ERT + ODI-500 mg
Slide 73: Functional evaluation of individual evaluable patients
Functional evaluation of individual evaluable patients Odiparcil improves key organ function in difficult-to-reach tissues that ERT does not address Improvements in the ERT Combination cohort (N=10) Number of improved patients Outcomes Improvement threshold ERT-Placebo ERT-odiparcil (n=6) (n=4) Opht
Slide 74: Patient improvements with odiparcil / ERT combination
Patient improvements with odiparcil / ERT combination 5 out of 6 patients in the odiparcil + ERT group improved on parameters not addressed by ERT • Slightly improved on respiratory function (FVC: +9%) • Improved on COM (+13 on non-transplanted eye) • Slightly improved on respiratory function (FVC:
Slide 75: Safety and tolerability
Safety and tollerability Odiparcil has robust safety data from extensive studies Safety Summary Adverse Events in MPS Trial Placebo odiparcil Odiparcil has been tested for safety in over Number of clinical SAEs N=5 N = 15 1,900 patients through trials done by GSK1 at doses up to 1500 mg Bronchopneum
Slide 76: Overview of odiparcil regulatory status
Overview of odiparcil regulatory status EUROPE USA • EMA Scientific Advice Meeting – Jul 2020 • Type C Meeting – August 2022 Overview of • ANSM Scientific Advice Meeting – Apr 2019 • Type C Meeting – Nov 2020 Discussions • MHRA Scientific Advice Meeting – Mar 2019 • P-IND Meeting – Mar 2018 • EMA Sc
Slide 77: Odiparcil potential path to regulatory submission
Odiparcil potential path to regulatory submission The proposed clinical trial design contemplates to enroll 50 pediatric patients for 12 months, potentially leading to filing for odiparcil’s approval as ERT combination therapy in patients 5 y/o to adults Part 1 Potential FDA Approval iMProveS Study
Slide 78: YAP-TEAD and TGF-β programs
YAP-TEAD and TGF-β programs
Slide 79: YAP-TEAD and TGF-β programs
YAP-TEAD and TGF-β programs YAP-TEAD program Hippo signalling pathway is potentially implicated in the process of cell differentiation and proliferation, tissue growth and organ size Inventiva compounds observed to disrupt interaction between YAP and TEAD along the pathway Potentially relevant
Slide 80: Recent and upcoming catalysts
Recent and upcoming catalysts
Slide 81: Catalysts
Catalysts 2024 2025 2026 Lanifibranor H1 2024 Q1 2026 H1 2026 H2 2026 Last Patient Last Patient Topline New Drug First Visit Last Visit results Approval filing with FDA Q1 2024 Topline results Odiparcil Review potential options to further develop odiparcil for the treatment of MPS VI, which may incl
Slide 82: Contacts
Contacts Inventiva Brunswick Westwicke, an ICR Company Pascaline Clerc Tristan Roquet Montégon Patricia L. Bank Executive VP Aude Lepreux Investor relations Strategy and Corporate Affairs Julia Cailleteau Media relations [email protected] [email protected] patti.bank@wes