Developing breakthrough therapies in NASH and mucopolysaccharidosis - - PowerPoint PPT Presentation

Developing breakthrough therapies in NASH and mucopolysaccharidosis

Corporate Presentation

June 2019

Non-confidential – Property of Inventiva │ 2

DISCLAIMER

This document has been prepared by Inventiva (the "Company") solely for the purpose of this presentation. This presentation includes only summary information and does not purport to be

• comprehensive. Any information in this presentation, whether from internal or from external sources, is purely indicative and has no contractual value. The information contained in this presentation

are provided as at the date of this presentation. Certain information included in this presentation and other statements or materials published or to be published by the Company are not historical facts but are forward-looking statements. The forward-looking statements are based on current beliefs, expectations and assumptions, including, without limitation, assumptions regarding present and future business strategies and market in which the Company operates, and involve known and unknown risk, uncertainties and other factors, which may cause actual results, performance or achievements, or industry results or other events, to be materially different from those expressed or implied by these forward-looking statements. These risks and uncertainties include those discussed or identified under Chapter “Risk factors” in the Company’s registration document (document de reference) filed with the French Financial markets authority (AMF – Autorité des marchés financiers), available on the Company’s website (www.inventivapharma.com) and on the website of the AMF. The Company may not actually achieve the plans, intents or expectations disclosed in its forward-looking statements and you should not place undue reliance on the forward-looking statements contained herein. There can be no assurance that the actual results of the Company’s development activities and results of operations will not differ materially from the Company’s expectations. Factors that could cause actual results to differ from expectations include, among others, the Company’s ability to develop safe and effective products, to achieve positive results in clinical trials, to obtain marketing approval and market acceptance for its products, and to enter into and maintain collaborations; as well as the impact of competition and technological change; existing and future regulations affecting the Company’s business; and the future scope of the Company’s patent coverage or that of third parties. The information contained in this presentation has not been subject to independent verification. No representation or warranty, express or implied, is made by the Company or any of its affiliates, advisors, representatives, agents or employees as to, and no reliance should be placed on, the fairness, accuracy, completeness or correctness of the information, or opinions contained herein. Neither the Company, nor any of its respective affiliates, advisors, representatives, agents or employees, shall bear any responsibility or liability whatsoever (for negligence or otherwise) for any loss howsoever arising from any use of this presentation or its contents or otherwise arising in connection with this presentation. Such information is subject to modification at any time, including without limitation as a result of regulatory changes or changes with respect to market conditions, and neither the Company, nor any of its affiliates, advisors, representatives, agents or employees, shall, nor has any duty to, update you. Corporate Presentation | 2019

Non-confidential – Property of Inventiva │ 3 Corporate Presentation | 2019

Inventiva investment highlights

Clinical stage biotech with focus on oral small molecules for high unmet need in fibrosis, lysosomal storage disorders and oncology Two unencumbered late stage assets in two high value indications – Lanifibranor – only pan-PPAR agonist in clinical development for NASH, Phase IIb data due H1 2020 – Odiparcil – first orally available therapy for MPS, Phase IIa data due H2 2019 State of the art R&D capabilities including wholly owned ‘pharma scale’ discovery facilities Portfolio underpinned by discovery engine focused on nuclear receptors, transcription factors and epigenetic targets with a 240,000 compound library, 60% of which are proprietary Compelling early stage pipeline leveraging power of discovery engine in fibrotic disease and oncology, supported by validating partnerships with AbbVie and Boehringer Ingelheim – ABBV-157 ROR program: first phase I completed and second one in 60 healthy volunteers and patients with chronic plaque psoriasis due to start in May 2019 – YAP-TEAD program in late pre-clinical stage, clinical candidate selection expected in 2019 Strong US and European shareholder base and experienced senior management team with a track record of operational and scientific excellence

Non-confidential – Property of Inventiva │ 4

Validated oral small molecule-focused discovery engine targeting nuclear receptors, transcription factors and epigenetic modulation

Corporate Presentation | 2019

Power of discovery engine underpins deep pipeline

• f clinical and discovery stage assets

Library of ~240,000 compounds of which 60% proprietary Wholly-owned 129,000 square foot pharma-like R&D facilities Expertise: nuclear receptors, transcription factors, epigenetic targets Strong scientific team

• f ~90 people

Non-confidential – Property of Inventiva │ 5

Deep pipeline approaching major near term value inflection points

Corporate Presentation | 2019

Candidate / Program Indication Discovery IND Enabling Phase I Phase II Phase III Commercial Rights

Lanifibranor NASH

Phase IIb results: H1 2020

Odiparcil

MPS VI Phase IIa results: H2 2019

ABBV-157

Moderate to severe psoriasis

 SAD phase I completed(1)

Hippo

Non-small cell lung cancer and mesothelioma

Candidate Selection: 2019

TGF-β

Idiopathic pulmonary fibrosis (IPF)

Lead Op(2)

GAG clearance ROR pan-PPAR

YAP/TEAD

(1) SAD: Single Ascending Dose; (2) Lead optimization means refining molecules in advance of selecting candidates

Non-confidential – Property of Inventiva │ 6

Key financials and shareholder base

ISIN code FR0013233012 Market Euronext Paris Shares outstanding 22.294.677 Market cap

(May 24 2019)

€54m Cash position

(March 31 2019)

€47,3m compared to €56,7m as of December 2018. Successful €48.5m Euronext IPO (February 2017) and €35.5m private placement (April 2018) Revenues

(December 31 2018)

€3.2m compared to €4.8m in 2017 R&D expenditures

(December 31 2018)

€31,6m compared to €26,7m in 2017

Key financials Shareholder base Analyst coverage

HC Wainwright LifeSci Capital Jefferies KBC Société Générale Gilbert Dupont Kepler Chevreux Ed Arce Patrick Dolezal Peter Welford Lenny Van Steenhuyse Delphine Le Louët Jamila El Bougrini Arsene Guekam

Corporate Presentation | 2019

Free float* 22.1% BVF 15,0% Novo 8,8% Sofinnova 7,1%

Employees & Others 3,1%

Founders 43,9%

*Including Perceptive Advisors

Lanifibranor in Nonalcoholic Steatohepatitis (NASH)

Non-confidential – Property of Inventiva │ 8

Lanifibranor is a differentiated pan-PPAR agonist with moderate and well balanced activity on the 3 PPAR isoforms

Corporate Presentation | 2019

Compound PPAR EC50 (nM) PPAR EC50 (nM) PPAR EC50 (nM)

 Lanifibranor(1) 1630 850 230

 Fenofibrate 2400

•  Pioglitazone
• 263

 Rosiglitazone

• 13

 Elafibranor(2) 10 100

•  Seladelpar(3)
• 2
• Lanifibranor human dose response curves and EC50s for various PPAR agonists
• 10
• 8
• 6
• 4

25 50 75 100 125 150

%Activation

hPPAR hPPAR hPPAR

Lanifibranor (M)

Potency scale: red 10 nM; grey: 500 nM; green 5 000 nM

Lanifibranor binds differently than rosiglitazone to PPARγ inducing different coactivator recruitment(4)

Source: (1) Company data (2) Hanf R et al, Diabetes & Vascular Dis Res 2014 (3) Cymabay company presentation (4) J Med Chem. 2018 Feb 15. doi: 10.1021/acs.jmedchem.7b01285

Non-confidential – Property of Inventiva │ 9

Favorable safety profile differing from previously developed PPARs

Corporate Presentation | 2019

Organ PPAR isoforms activated Reported PPAR liabilities

Lanifibranor effects

Heart  PPAR  Fluid retention  Cardiac hypertrophy

Not observed

Skeletal muscle  PPAR  Myofiber degeneration

Not observed

Kidney  PPAR  > 50% increases in creatinine, degenerative changes in renal tubules

Not observed

Urinary bladder  PPAR  Proliferative changes in bladder epithelium

Not observed

Source: Company data

Lanifibranor not associated with typical single or dual PPAR liabilities

Non-confidential – Property of Inventiva │ 10

In long-term toxicological studies lanifibranor presents a safe and differentiating profile

After review of carcinogenicity studies, FDA has lifted PPAR class clinical hold and allowed long-term clinical studies in NASH with lanifibranor

Corporate Presentation | 2019

 Lanifibranor shows a very favorable profile in 12 month monkey study … − No adverse clinical signs were observed at any dose-level tested − No effects on body weight and heart weight, no haemodilution or creatinine increase − Electrocardiography and clinical pathology investigations did not reveal any undesirable effects  … and in two-year carcinogenicity studies performed in rat and mice − Rat: no neoplastic changes and increase in tumor types commonly associated with single PPAR and dual PPARagonists: liver, adipose, bladder, renal and skin − Mice: no neoplastic changes and increase in tumor types of human relevance No carcinogenic effect relevant to humans, contrasting with some other PPAR and PPARagonists

Non-confidential – Property of Inventiva │ 11

Phase I and Phase IIa clinical studies(1) demonstrated lanifibranor beneficial effects on key metabolic markers

Corporate Presentation | 2019

Lanifibranor has beneficial effects on key metabolic markers in type II diabetic patients

Source: Company data ; (1) Conducted by Abbott (2) A placebo controlled trail of Pioglitazone in subjects with nonalcoholic steatohepatitis Belfort et Al; N Engl J Med 355;22 November 30, 2006; 6 month treatment (3) Effects of the new dual PPAR α/δ agonist GFT505 on lipid and glucose homeostasis in abdominally obese patients with combined dyslipidemia or impaired glucose metabolism ; Diabetes Care. 2011 Sep;34(9):2008-14. doi: 10.2337/dc11-0093. Epub 2011 Aug 4. 4 week treatment study 1 (4) A Novel Peroxisome Proliferator Receptor-δ Agonist: Lipid and Other Metabolic Effects in Dyslipidemic Overweight Patients Treated with and without Atorvastatin The Journal of Clinical Endocrinology & Metabolism, Volume 96, Issue 9, 1 September 2011, Pages 2889–2897, https://doi.org/10.1210/jc.2011-1061; 8 week treament

Placebo 400 mg 800 mg 1400 mg

100 200 300

IVA337 IVA337 IVA337

p=0.08 p=0.05 p=0.05

Percent change of baseline

Adiponectin (PPAR)

Percent change from baseline

lanifibranor lanifibranor lanifibranor

Placebo 400 mg 800 mg 1400 mg

10 20 30 40

IVA337 IVA337 IVA337

p=0.13 p<0.05 p<0.05

Percent change of baseline

HDL Cholesterol (PPAR)

Percent change from baseline

lanifibranor lanifibranor lanifibranor

Placebo 400 mg 800 mg 1400 mg

• 50
• 40
• 30
• 20
• 10

IVA337 IVA337 IVA337

p=0.08 p<0.05 p<0.05

Percent change of baseline

Triglycerides (PPAR)

Percent change from baseline

lanifibranor lanifibranor lanifibranor

HDL increase: Lanifibranor (800/1400mg): +18%/28% Elafibranor(3) (80mg): +7,8% Seladelpar(4) (50mg): +9,9% TG decrease: Lanifibranor (800/1400mg): -24%/28% Elafibranor (80mg)(3): -16,7% Seladelpar(4) (50mg): -32,4% Adiponectin fold:  Lanifibranor (800/1400mg): +2.8/+3.2  Pioglitazone(2) (45mg): +2.3 Homa-IR:  Lanifibranor (800/1400mg): -20%/-44%

Non-confidential – Property of Inventiva │ 12

Phase I and Phase IIa clinical studies(1) confirmed lanifibranor safety

Corporate Presentation | 2019

 Good overall tolerance and no major safety findings – No increases of creatinine, liver function test (LFT) or creatine phosphokinase (CPK) – No changes in blood pressure – No signal of fluid overload or hemodilution – No clinically relevant weight gain  No significant differences in SAE and AE between placebo and lanifibranor in the phase IIa Clinical findings underline the favorable tolerability of lanifibranor

Source: Company data and * Ohashi, Endocr Metab Immune Disord Drug Targets. 2015. Note: (1) Conducted by Abbott ; (2) Pioglitazone data obtained after 6 month treatment (Belfort 2006); elafibranor after 4 week and seladelpar after 8 week

Non-confidential – Property of Inventiva │ 13

NASH overview

Source: NASH Market, Allied Market Research 2016 ; Deutsche Bank Markets Research; Intercept website.; Epidemiology and natural history of non-alcoholic steatohepatitis.Clinical Liver Disease.2009 Nov;13(4):511-31.

Corporate Presentation | 2019

The overall NASH prevalence in the adult population of the United States is believed to be approximately 12% A severe disease with no currently approved treatment

Hepato- carcinoma Death Liver transplant Reversible 40-50% 15-20% Severe liver damage

Healthy Liver NASH NAFLD Cirrhosis

NASH with fibrosis 2-3% per year 30-40%

Non-confidential – Property of Inventiva │ 14

Lanifibranor’s mechanism of action addresses all the key features of NASH

Corporate Presentation | 2019

Insulin sensitivity HDLc TG PPAR Metabolism FA uptake FA catabolism Lipogenesis PPAR, Steatosis Inflammation and Ballooning NFkB-dependent gene activation Inflammasome Ballooning PPAR Stellate cell proliferation and activation Collagen and fibronectin production PPAR Fibrosis

Non-confidential – Property of Inventiva │ 15

Pioglitazone PPAR NASH resolution efficacy results are still unmatched

Corporate Presentation | 2019

Pioglitazone Cusi study (45 mg, 18 month), Annals of Internal Medicine, 2016 ; Ocaliva Regenerate Phase III study (25 mg, 18 months), press release Feb. 19, 2019 CVC Centaur Phase II study (150 mg, 12 months), Hepatology 2017 ; Elafibranor Golden 505 Phase II study (120 mg, 12 months), Gastroenterology. 2016 MGL-3196 Phase II study (100mg, 8 months), press release May 31, 2018 ; Aramchol Arrest Phase II study (600 mg, 12 months) – press release June 12, 2018

pbo

19%

pbo

8%

pbo

12%

pbo

6%

pbo

6%

pbo

7% 51% 12% 19% 8% 27% 19% 0% 10% 20% 30% 40% 50% 60%

Pioglitazone Ocaliva Elafibranor CVC MGL-3196 Aramchol

Patients with improvement, %

Resolution of NASH without worsening of fibrosis

Non-confidential – Property of Inventiva │ 16

Overview of NATIVE trial design (I/II)

Corporate Presentation | 2019

More information on: http://www.native-trial.com/

Trial design 225 patients 24 week treatment Double blind randomized placebo controlled End of treatment  Liver biopsy Placebo, 75 patients Lanifibranor, 800 mg once daily, 75 patients Lanifibranor, 1200 mg once daily, 75 patients Principal investigator  Prof. Francque (Universitair Ziekenhuis, Antwerpen, Belgium)  Prof. Manal Abdelmalek (Duke University, USA) Status  Trial enrolling  Results expected first-half 2020 Clinicaltrials.gov identifier: NCT03008070 Inclusion criteria  Severe patients with an inflammation and ballooning score of 3 or 4  Steatosis score ≥ 1 and fibrosis score < 4 (no cirrhosis) Primary endpoint  Decrease from baseline ≥ 2 points of the inflammation and ballooning score without worsening of fibrosis Screening  Liver biopsy

Non-confidential – Property of Inventiva │ 17

Overview of NATIVE trial design (II/II)

Corporate Presentation | 2019

17 countries worldwide ► 13 in EU ► United States ► Canada ► Australia ► Mauritius 92 sites involved 91 sites activated 82 sites screening 14 sites selected in the United- States Status  756 patients screened and 192 patients randomized (85%) at end of May 2019  3 positive DSMB reviews recommending to continue the study without any changes  Limited number of edema (blinded data): 7 patients treated with placebo or lanifibranor reported mild or moderate edemas of short duration and which did not require treatment discontinuation  Results expected first-half 2020

Non-confidential – Property of Inventiva │ 18

NATIVE study results will also be backed by the Phase II trial in T2DM patients with NAFLD

(1) Intrahepatic triglycerides (2) Magnetic resonance elastography (3) De-novo lipogenesis

A positive study result would further reinforce lanifibranor’s profile in NAFLD and NASH patients with type 2 diabetes

Corporate Presentation | 2019

64 patients 24 week treatment Double blind randomized placebo controlled Healthy non-obese control group, 10 subjects Placebo, 32 patients Lanifibranor, 800 mg once daily, 32 patients Principal investigator  Prof. Kenneth Cusi (University of Florida) Randomisation  N=64 assuming a 35% reduction of IHGT(1) Status IND approved First Patient First Visit: August 2018  Results expected first-half of 2020 Primary endpoint  Change from baseline to week 24 in IHTG Key secondary endpoints  Proportion of responders; change in hepatic fibrosis (MRE(2), biomarkers); change in metabolic outcomes  Safety Clinicaltrials.gov identifier: NCT03459079 Trial design

 

Odiparcil – MPS

Non-confidential – Property of Inventiva │ 20

Mucopolysaccharidoses (MPS) are devastating diseases with high unmet medical need

Corporate Presentation | 2019

Source: (1) Source: Rheumatology 2011 Therapy for mucopolysaccharodises; Vassili Valayannopoulos and Frits A. Wijburg

 Autosomal recessive disorders characterized by accumulation of glycosaminoglycan(s) (GAGs) due to deficient lysosomal enzymes  Seven distinct clinical types based on the enzyme affected: odiparcil could be the first substrate reduction therapy for five forms of MPS with the following incidences:

Kathleen (MPS I) Scotty (MPS II) Karima (MPS VI)

MPS is a group of inherited lysosomal storage disorders MPS has devastating clinical consequences: example MPS I, II and VI

MPS I

 Mental retardation  Coarse facies, short stature  Dysostosis multiplex  Joint stiffness  Spinal cord compression  Organomegaly  Poor vision (corneal clouding)  Hearing loss  Cardiac/respiratory disease

MPS II MPS VI Consequences  

(1) Retinal degeneration with no corneal clouding

 Odontoid hypoplasia  Kyphoscoliosis, genu valgum  Pebbled skin  Diarrhoea

                    (1)   

Non-confidential – Property of Inventiva │ 21

Enzyme replacement therapy (ERT) is commercially successful, but with limited therapeutic efficacy

Source: (1) H. Noh, J. I. Lee; Current and potential therapeutic strategies for mucopolysaccharidoses; Journal of Clinical Pharmacy

Corporate Presentation | 2019

 Recombinant human enzymes, weekly intravenous infusion over 4 hours  Approx. 50% of patients experience infusion reactions initially, some can be life threatening  Limited penetration into protected or poorly vascularized tissues such as cornea or cartilage Product Company MPS

• Est. yearly cost

2018 sales  MPS I  $ 217K  $ 206M  MPS II  $ 522K  $ 616M(1)  MPS IVA  $ 578K  $ 482M  MPS VI  $ 476K  $ 345M  MPS VII  $ 550K  $ 8M ERT is expensive and usually requires outpatient administration. Significant unmet need remains in addressing symptoms in organs where ERT fails to penetrate Enzyme replacement therapies are standard of care in MPS

Source: Sales - Company annual reports 2017; WAC without discounts for a 25-kg patient - BioCentury “Making of MEPSEVII” Dec 11, 2017 ; (1) 2017 sales

Non-confidential – Property of Inventiva │ 22

Unique mechanism of action potentially synergistic with ERT

Corporate Presentation | 2019

Source: H. Noh, J. I. Lee; Current and potential therapeutic strategies for mucopolysaccharidoses; Journal of Clinical Pharmacy, company data

Odiparcil diverts endogenous protein-bound GAG synthesis to soluble odiparcil-bound chondroitin sulfate (CS) and dermatan sulfate (DS) synthesis Odiparcil decreases intracellular GAG accumulation in vitro in MPS VI patient cells

Galactosyl transferase I (GTI)

Synthesis of proteoglycans (HS, CS, DS) Synthesis

• f soluble

DS and CS

Odiparcil

Odiparcil

Galactosyl transferase I (GTI)

MPS VI fibroblasts GAG overloaded cells Intracellular CS storage Extracellular GAG

5 10 15 20 25 10- 8 10- 7 10- 6 10- 5

MPS VI (IC50=3 µM)

Veh.

Odiparcil concentration (M) Total sulfated GAGS (µg/mL)

100000 200000 300000

10- 8 10- 7 10- 6 10- 5

Control (IC50=2.8 µM) MPS VI (IC50=2.7 µM)

Veh.

Odiparcil concentration (M) Fluorescence intensity

Odiparcil observed to reduce GAG accumulation in MPS VI patient cells

Odiparcil

Non-confidential – Property of Inventiva │ 23

By producing soluble dermatan and chondroitin sulfates, odiparcil can address several types of MPS

Source: Rheumatology 2011 Therapy for mucopolysaccharodises; Vassili Valayannopoulos and Frits A. Wijburg

Type Name DS CS HS KS MPS I-H Hurler syndrome



 MPS I-S Scheie syndrome



MPS I-H/S Hurler-Scheie syndrome



 MPS II Types A & B Hunter syndrome



 MPS IV Type A Morquio syndrome



 MPS VI Maroteaux-Lamy syndrome

 

MPS VII Sly syndrome

 



Corporate Presentation | 2019

Non-confidential – Property of Inventiva │ 24

Odiparcil decreases GAG content in vivo and improves mobility in a MPS VI model

Corporate Presentation | 2019

Source: Company data

10 20 30 40 p<0.001

WT MPS VI MPS VI + Odi

p<0.05

time on pole [sec]

10 20 30 40 p<0.001

WT MPS VI MPS VI + Odi

p<0.001

GAG in liver [Area * Index]

± Odiparcil* Given in food 6 months

Wild-type and MPS VI mice Treatment starts when animals are one month

• ld

►Sulfated GAGs in organs/tissues and urine ►Mobility test ►Corneal structure/clouding

* The doses administered provide exposure levels similar to that to be used in clinic

Liver

Odiparcil decreases GAG accumulation in tissues Odiparcil improves animal mobility

Chow diet Odiparcil : 4.5 g/kg in food

Odiparcil decreases intra- cellular GAG

20 40 60 80 %cells with > 10 GAG granules

p<0.001 p<0.001

MPS VI MPS VI+Odi WT

Leukocytes Pole Test

Non-confidential – Property of Inventiva │ 25

Odiparcil penetrates tissues that ERT cannot reach

Meaningful concentrations of odiparcil observed also in tissues that are poorly vascularized or protected by a barrier: bone, corneal tissue and cartilage

Corporate Presentation | 2019

Odiparcil is well distributed in tissues and organs poorly penetrated by recombinant enzymes

Heart Cornea Bone Cartilage

Odiparcil(1) rhASB(2) Not detected Not tested Not detected

Non-confidential – Property of Inventiva │ 26

Odiparcil shows promising results in poorly vascularized tissues not treated by ERT

Corporate Presentation | 2019

Source: Company data

Decreases in GAG accumulation and improvements in corneal structure expected to improve corneal function and ocular impairment

WT control MPSVI

epithelium stroma

MPS VI + Odi

10 20 30 40 p<0.001

WT MPS VI

p<0.0001

MPS VI + Odi thickness (µm)

Odiparcil effect on corneal structure and epithelium thickness

Chow diet Odiparcil : 4.5 g/kg in food

Odiparcil decreases trachea and knee cartilage thickness

20 40 60 80 100 p<0.0001

• 31%

Trachea cartillage thickness in µm

MPS VI MPS VI + Odi WT

Chow diet Odiparcil : 4.5 g/kg in food 100 200 300 p<0.0001

• 26%

WT MPS VI

p<0.0001

MPS VI + Odi Distal femoral growth plate thickness [µm]

Chow diet Odiparcil : 4.5 g/kg in food

By decreasing GAG storage in cartilage, odiparcil improves cartilage- linked disease manifestations

Non-confidential – Property of Inventiva │ 27

Odiparcil has the potential to positively differentiate versus current MPS treatment options

Corporate Presentation | 2019

Source: Company evaluation

Effect on mobility Effect on eye, cartilage, bones, heart valves, spinal cord compression Distribution type Oral Intravenous Infusion Transplantation Odiparcil Aldurazyme, Elaprase, Naglazyme, Vimizim, Mepsevii HSCT (Hematopoietic stem cell transplantation)

Non-confidential – Property of Inventiva │ 28

Odiparcil overall development plan in MPS VI

Corporate Presentation | 2019 (1) leukoGAG: GAG levels in circulating leukocytes; UGAG: urinary GAG)

Biomarker Study 12 MPS VI patients Phase IIa, 6-month treatment 24 MPS VI adults Add on to ERT and Naïve Phase Ib/II, 6-month treatment 9 MPS VI children Add on to ERT Phase III MPS VI (5y-adult)

• Validate LeukoGAG(1) assay in human: potential

efficacy biomarker

• Safety and tolerability
• PK data with pediatric formulation
• PD data, biomarkers (uGAG,

leukoGAG, skin GAG)

• Identify signals of clinical efficacy
• Safety and tolerability
• Identify signals of clinical efficacy and

potential as stand-alone therapy

• PK/PD, biomarkers (uGAG(2),

leukoGAG, skin GAG)

• Safety and Tolerability
• Efficacy

R&D collaborations and Hippo pathway program update

Non-confidential – Property of Inventiva │ 30

Key validating collaborations with AbbVie and Boehringer Ingelheim

Corporate Presentation | 2019

Inventiva eligible to future milestone payments and sales royalties

• n all ROR molecules identified during the collaboration

RORγ collaboration in inflammatory disease  RORγ program addresses large markets currently dominated by biologics and could prove to be superior to biologics  Single ascending dose phase I completed with ABBV-157, the clinical candidate coming from the partnership  Next step: A randomized, double-blind, placebo-controlled, multiple-dose study to evaluate the pharmacokinetics, safety and tolerability of ABBV-157 in 60 healthy volunteers and patients with chronic plaque psoriasis (clinicaltrials.gov identifier: NCT03922607) – Study start date: May 2019 – Study completion: September 2020(1) Inventiva eligible to up to ~€170m in milestones and sales royalties Fibrosis collaboration  Multi-year R&D collaboration and licensing partnership. Joint team until pre-CC stage. BI to take full responsibility of clinical development and commercialization  Program progressing as planned with first screening performed

(1) Source: clinicaltrial.gov

Non-confidential – Property of Inventiva │ 31

YAP-TEAD program: significant progress achieved and clinical candidate selection planned in 2019

The program is expected to enter into Phase I/II enabling preclinical development in 2019

Corporate Presentation | 2019

 Novel cancer pathway involved in drug resistance, immune evasion, tumor progression and metastases  Relevant in multiple, commercially attractive cancer indications  Proprietary chemistry  Lead and back-up compounds available  IP protected  Preclinical candidate screening

• ngoing

 Clinical candidate selection in 2019  Phase I/II start planned in 2020  In vitro evidence for synergies with standard of care and suppression of tumor resistance  In vivo efficacy shown (alone and in combination with standard of care)

First in class YAP-TEAD program

Conclusions

Non-confidential – Property of Inventiva │ 33

Recent achievements and upcoming expected milestones

Corporate Presentation | 2019

2019

Lanifibranor Odiparcil ABBV-157

Rare pediatric disease designation MPS VI  Phase IIa in MPS VI: last patient recruited  Phase IIa in MPS VI results - H2 2019

YAP-TEAD

FDA decision to lift lanifibranor clinical hold  Last patient Phase IIb NASH  Last patient Prof. Cusi study in NAFLD patients with TD2M

2020

 Clinical candidate selection



 ABBV-157 multiple-ascending dose in healthy volunteers and psoriatic patients phase I initiation



SAD(1) Phase I with ABBV-157 completed



(1) SAD: Single Ascending Dose

ABBV-157 development in psoriasis  Phase IIb NASH results – H1 2020  Phase II in NAFLD patients with TD2M results – H1 2020  Launch of phase IB/II in MPS VI children  Launch of Phase I/II in mesothelioma patients

Contacts Inventiva Frédéric Cren CEO info@inventivapharma.com +33 (0)3 80 44 75 00 Brunswick Yannick Tetzlaff / Tristan Roquet Montégon Media relations inventiva@brunswickgroup.com + 33 1 53 96 83 83 LifeSci Advisors Monique Kosse Investor relations monique@lifesciadvisors.com