Slide 1: Full Year 2020 Financial Results
Full Year 2020 Financial Results March 5, 2021
Slide 2: Disclaimer
DISCLAIMER This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this presentation, including statements regarding our future financial condition, results of operations, business s
Slide 3: Today's speakers
Today’s speakers Frédéric Cren, MA/MBA, Chairman, CEO and Co-Founder Pierre Broqua, Ph.D., CSO and Co-Founder Michael Cooreman, MD, CMO Jean Volatier, MA, CFO Full Year 2020 Presentation | 2021 Non-confidential – Property of Inventiva │ 3
Slide 4: Summary
Summary Full year 2020 highlights Clinical pipeline update Financials Near-term catalysts Full Year 2020 Presentation | 2021 Non-confidential – Property of Inventiva │ 4
Slide 5: Full Year 2020 Highlights
Full Year 2020 Highlights
Slide 6: Full year 2020 highlights
Full year 2020 highlights Lanifibranor program in non-alcoholic steatohepatitis (NASH) Launch of collaboration with Pr. Jérôme Boursier, M.D., Ph.D, Professor of Medicine Angers University, to develop biomarkers to identify patients responding to lanifibranor with regards to NASH resolution and fi
Slide 7: Full year 2020 highlights
Full year 2020 highlights Collaboration with AbbVie in auto-immune diseases Completion by AbbVie of the International Nonproprietary Names (INN) process for ABBV-157, now named cedirogant Confirmation by AbbVie of clinical POC in psoriasis with cedirogant in Q2 2021 Other Opening of Inventiva’
Slide 8: Clinical pipeline update
Clinical pipeline update
Slide 9: Lanifibranor
Lanifibranor A new generation pan-PPAR agonist for the treatment of fibrotic conditions
Slide 10: Lanifibranor: the only pan-PPAR agonist in clinical development for NASH
Lanifibranor: the only pan-PPAR agonist in clinical development for the treatment of NASH and improvement in liver fibrosis LANIFIBRANOR Moderate and balanced pan-PPAR agonist activity Differentiated PPARa PPARd PPARg Compound EC50 (nM) EC50 (nM) EC50 (nM) chemical structure Once daily oral Lani
Slide 11: Lanifibranor's activation of the three PPAR isoforms
Lanifibranor’s activation of the three PPAR isoforms designed to address the key features of NASH LANIFIBRANOR INFLAMMATION AND METABOLISM STEATOSIS BALLOONING PPARα PPARδ PPARγ PPARγ PPARα PPARδ PPARγ PPARα Insulin sensitivity FA uptake NFkB-dependent gene activation HDLc FA catabolism Inflammasome
Slide 12: Adverse events and toxicity of other PPAR agonists not observed in lanifibranor
Adverse events and toxicity previously seen in other single and dual PPAR agonists are not observed in lanifibranor SAFETY Organ Isoforms activated Reported PPAR side effects lanifibranor effects Fluid retention HEART PPARγ Cardiac hypertrophy SKELETAL PPARα Myofiber degeneration MUSCLE NOT
Slide 13: Development plan builds on successful NATIVE Phase IIb outcomes
The overall development plan builds on the successful outcomes of the NATIVE Phase IIb trial CLINICAL DEVELOPMENT F2-F3 Phase III Registration Phase I Phase IIa Phase IIb (NATIVE) III OVERVIEW • 72 week Part 1 + Part IIb DESIGN 2 extension period • 24 weeks • Inclusion criteria and Conducted by Abbo
Slide 14: The Phase IIb NATIVE trial across 247 patients
The Phase IIb NATIVE trial studied 800 mg and 1200 mg once-daily lanifibranor across 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, 800 mg once dai
Slide 15: First candidate to achieve significant results on both Phase III primary endpoints
Lanifibranor is the first candidate to achieve statistically significant results on the two Phase III FDA and EMA primary endpoints 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 popul
Slide 16: Secondary endpoints in F2-F3 patients
In F2-F3 patients, statistical significance was demonstrated for the main key histological secondary endpoints 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 Placebo 800 mg 8
Slide 17: 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 Fibrosis Pro-C3 >14 at baseline (12.8%)
Slide 18: 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 19: 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 20: Glycemic improvements in T2DM patients with NASH
In type 2 diabetes (T2DM) patients with NASH, statistically significant reductions of fasting glucose and insulin, HbA1c were observed PHASE IIb EFFICACY T2DM Secondary endpoints in T2DM patients with NASH (N = 103) Absolute change from baseline in HbA1c Absolute change from baseline in fasting gluc
Slide 21: Lanifibranor continued to show a favourable safety profile
Lanifibranor has continued to show 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%)
Slide 22: 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 23: Peripheral oedemas not flagged as a concern by investigators
Peripheral oedemas were not flagged as a concern by study investigators PHASE IIb SAFETY PERIPHERAL OEDEMA Treatment Verbatim of AE Action taken or Corrective Relationship # Intensity group Oedema peripheral treatment to treatment 1 oedema in the lower leg and knees Moderate IMP interrupted + Meloxi
Slide 24: Modest weight increase with no impact on efficacy
Phase II results in NASH 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 w
Slide 25: Weight gain likely related to subcutaneous fat increase
Weight gain is likely related to an increase in subcutaneous fat rather than water retention, while visceral and liver fat may be reduced SAFETY Weight gain Body driven by increase in subcutaneous fat Weight Bodyweight loss Pioglitazone Failed diet Subcutaneous Fat PIOBody BW-loss weightDiet-fail Su
Slide 26: Pan-PPAR activation and a favourable cardio-metabolic profile
Pan-PPAR activation could lead to a favourable cardio-metabolic profile and a reduction in Cardio Vascular Disease (CVD) SAFETY Potential to improve cardio-metabolic profile and to reduce CVD Pioglitazone Failed diet Pioglitazone Excess caloric intake Insulin levels (atherogenic) ↓ ↑ FFA levels (lip
Slide 27: Differentiated potential to address all features of NASH
Lanifibranor has a differentiated potential to address all features of NASH in a safe and efficacious manner EFFICACY AND SAFETY Targeting all features of NASH… … ensures favourable comparison against competitors NASH resolution with no worsening of fibrosis METABOLISM STEATOSIS VASCULAR Fibrosis im
Slide 28: Overall development plan builds on NATIVE Phase IIb outcomes
Lanifibranor’s overall development plan builds on the successful outcomes of the NATIVE Phase IIb trial OVERVIEW Lanifibranor clinical development overview F2-F3 Phase III Registration III OVERVIEW Phase I Phase IIa Phase IIb (NATIVE) III EFFICACY IIb DESIGN Overview III SAFETY Conducted by Abbott S
Slide 29: F2-F3 Phase III inclusion criteria and patient profile
The F2-F3 Phase III inclusion criteria and patient profile are in line with the NATIVE Phase IIb trial PHASE III OVERVIEW A randomized, double-blind, placebo-controlled, multicenter, Phase III study evaluating long-term efficacy and safety of lanifibranor in adult patients with NASH and liver fibros
Slide 30: Part 1 may enable U.S. accelerated and EU conditional approval
Part 1 of the Phase III may enable U.S. accelerated approval and EU conditional approval based on a 72-week histology analysis PHASE III OVERVIEW Part 1 F2-F3 Phase III Part 1: 72 week treatment Screening Placebo Biopsy Eligible for U.S. ACCELERATED Biopsy Part I lanifibranor, 800 mg once daily APPR
Slide 31: Part 2 may allow for broader full approval
Part 2 of the Phase III study may allow for a broader “full approval” of lanifibranor in F2-F3 patients PHASE III OVERVIEW Part 2 F2-F3 Phase III Part 2: Extension period Placebo Biopsy Part II Potential for FULL lanifibranor, 800 mg once daily APPROVAL in U.S. and EU lanifibranor, 1200 mg once dail
Slide 32: Composite endpoint can help differentiate from key competitors
The composite endpoint combining NASH resolution and fibrosis improvement can help differentiate from key competitors PHASE III EFFICACY The primary endpoint “resolution of NASH and improvement of fibrosis” addresses the major pathways of the disease: achieving both of these histological outcomes
Slide 33: Phase III patients randomised across approximately 300 sites
The Phase III patients will be randomised across approximately 300 sites worldwide PHASE III DESIGN SITE SELECTION Nativ3 countries 25 countries worldwide for close to 300 sites expected to participate Full Year 2020 Presentation | 2021 Non-confidential – Property of Inventiva │ 33
Slide 34: Key milestones of the Phase III study in NASH (Part 1)
Key milestones of the Phase III study in NASH (Part 1) PHASE III MILESTONES 2021 2022 2023 2024 F2-F3 Phase III Q3 2021 H2 2022 H1 2024 First Patient Part 1: Last Patient Part 1: Last First Visit First Visit Patient Last Visit (c.900 patients) (c.900 patients) Q2 2021 First Site Active H2 2024 Part
Slide 35: Overall development plan builds on NATIVE Phase IIb outcomes
Lanifibranor’s overall development plan builds on the successful outcomes of the NATIVE Phase IIb trial OVERVIEW F2-F3 Phase III Registration III OVERVIEW Phase I Phase IIa Phase IIb (NATIVE) III EFFICACY IIb DESIGN Overview III SAFETY Conducted by Abbott Site selection prior to Inventiva Treatment
Slide 36: Lanifibranor in T2DM and NAFLD: a profiling study (I)
Safety, efficacy and mechanism-of-action of lanifibranor in patients with T2DM and NAFLD: a profiling study (I) Collaboration with Dr. Ken Cusi, Professor of Medicine and Chief, Division of Endocrinology, Diabetes and Metabolism at the University of Florida, Gainesville, FL (sponsor) – Clinicaltri
Slide 37: Lanifibranor in T2DM and NAFLD: a profiling study (II)
Safety, efficacy and mechanism-of-action of lanifibranor in patients with T2DM and NAFLD: a profiling study (II) Efficacy endpoints Primary efficacy endpoint: decrease of IHTG from baseline to end of therapy, measured by MRS – Responder: ≥ 30% reduction of hepatic fat from baseline – Proportion of
Slide 38: Evaluation of lanifibranor in F4 compensated cirrhotic patients
Evaluation of lanifibranor in F4 compensated cirrhotic patients F4 compensated cirrhotic patients In vivo Thiocetamide (TAA) HSC biology In vitro Endothelial biology PROMISING PRECLINICAL DATA Improved portal hypertension through reduction in intrahepatic vascular resistance Rats exhibited signi
Slide 39: Potential use in combination with other therapies
Lanifibranor has the potential to be used in combination with other therapies to further strengthen its value proposition OUTLOOK COMBINATION THERAPIES Examples of potential combination therapies POTENTIAL BENEFITS OF COMBINATION USE GLP-1 COMPLEMENTARY EFFECTS on the multistep disease biology of
Slide 40: Potential combination therapies: GLP-1, SGLT-2 and ACC inhibitors
Potential combination therapies could include GLP-1 agonists as well as SGLT-2 and ACC inhibitors OUTLOOK COMBINATION THERAPIES Examples of potential combination therapies Weight loss (kg) with exenatide or dulagutide plus pioglitazone PPAR + GLP-1 PPAR + SGLT2 Weight loss (kg) with empagliflozin +
Slide 41: Collaboration with AbbVie in auto-immune diseases: cedirogant (ABBV-157)
Collaboration with AbbVie in auto- immune diseases: cedirogant (ABBV-157)
Slide 42: Cedirogant, a clinical compound co-discovered by Inventiva
Cedirogant, a clinical compound co-discovered by Inventiva, with potential in several auto-immune diseases RORg believed to be a master regulator of IL-17 / 23 approach has been validated by Th17 differentiation and IL-17 expression several successful biologics RORgt = Retinoic acid-related Orphan R
Slide 43: Financials
Financials
Slide 44: Key financials and shareholder base
Key financials and shareholder base Key financials Shareholder base(1) Founders 25% Free Float 31% Employees ISIN code FR0013233012 / US46124U1079 & Others 2% Market Euronext Paris / Nasdaq GM Sofinnova 38,630,261 (incl. 7,478,261 shares of 8% Shares outstanding the July 9 Nasdaq IPO) BVF Euronext P
Slide 45: Full year 2020: Key figures
Full year 2020: Key figures Highlights ► No expected revenues in 2020 vs €3.5m and €2.6m for the collaborations with AbbVie and Boehringer Ingelheim in 20219 ► 29% decrease in R&D investment, €23.7m vs €33.8m in 2019 • Continued efforts dedicated to the development of lanifibranor (NASH) and odiparc
Slide 46: Near-term catalysts
Near-term catalysts
Slide 47: Recent and anticipated key milestones
Recent and anticipated key milestones Lanifibranor Positive topline results of NATIVE Phase IIb trial in NASH Breakthrough Therapy Designation granted by FDA NATIVE Phase IIb meeting with FDA and EMA Scientific Advice Launch of phase III trial with lanifibranor in NASH – H1 2021 Odiparcil
Slide 48: Q&A
Q&A
Slide 49: Contacts
Contacts Inventiva Brunswick Westwicke, an ICR Company Frédéric Cren Yannick Tetzlaff / Tristan Roquet Montégon Patricia L. Bank / Aude Lepreux CEO Investor relations Media relations info@inventivapharma.com inventiva@brunswickgroup.com patti.bank@westwicke.com +33 (0)3 80 44 75 00 + 33 1 53 96 83 8