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

developing breakthrough therapies in nash and
SMART_READER_LITE
LIVE PREVIEW

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

Developing breakthrough therapies in NASH and mucopolysaccharidosis Corporate Presentation April 2019 DISCLAIMER This document has been prepared by Inventiva (the "Company") solely for the purpose of this presentation. This


slide-1
SLIDE 1

Developing breakthrough therapies in NASH and mucopolysaccharidosis

Corporate Presentation

April 2019

slide-2
SLIDE 2

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

slide-3
SLIDE 3

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 in phase I with AbbVie, Phase I data due in 2019 – YAP-TEAD program in late pre-clinical stage, clinical candidate selection expected in 2019 Strong balance sheet and experienced senior management team with a track record of

  • perational and scientific excellence
slide-4
SLIDE 4

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 of 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
slide-5
SLIDE 5

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

Phase I results: 2019 Hippo

Non-small cell lung cancer and mesothelioma

Candidate Selection: 2019 TGF-β

Idiopathic pulmonary fibrosis (IPF)

Lead Op(1) GAG clearance ROR pan-PPAR

YAP/TEAD

(1) Lead optimization means refining molecules in advance of selecting candidates

slide-6
SLIDE 6

Non-confidential – Property of Inventiva │ 6

Strong cash position and shareholder base

ISIN code FR0013233012 Market Euronext Paris Shares outstanding 22.294.677 Market cap

(February 26 2020)

€84m Cash position

(December 31 2018)

€56,7m compared to €59.1m as of December 2017. 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

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

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

slide-7
SLIDE 7

Lanifibranor in Nonalcoholic Steatohepatitis (NASH)

slide-8
SLIDE 8

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

slide-9
SLIDE 9

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 Plasma volume and heart weight after administration of PPAR agonists

Source: Company data

Plasma Volume Heart Weight

20 40 60

* * * *

Rosi Mura IVA337 Tesa Plasma volume (mL)

0.0 0.2 0.4 0.6

* * * *

Rosi Mura IVA337 Tesa Heart weight (% BW)

Control Rosi (3 mg/kg/d) Rosi (10 mg/kg/d) Mura (10 mg/kg/d) Mura (100 mg/kg/d) IVA337 (100 mg/kg/d) IVA337 (1000 mg/kg/d) Tesa (1 mg/kg/d) Tesa (10 mg/kg/d)

Lani Lani

Lani Lani

mg/kg/day; 9 W rat study

Single PPAR  Dual PPAR  Dual PPAR  Pan PPAR  Single PPAR  Dual PPAR  Dual PPAR  Pan PPAR 

Lanifibranor not associated with plasma volume expansion or heart weight increase

slide-10
SLIDE 10

Non-confidential – Property of Inventiva │ 10

Phase IIb study in systemic sclerosis confirmed favorable safety profile of lanifibranor

 Well conducted 48 week phase IIb clinical trial in early diffuse systemic sclerosis adult patients  The primary endpoint on skin score was not met, nor secondary efficacy endpoints  Lanifibranor showed a favorable trend in patients’ global assessment of disease activity indicating a perceived benefit by patients  Within this fragile and poly-medicated population, lanifibranor was observed to be associated with a favorable safety profile without apparent adverse interactions with immunosuppressive background therapies, and no cardiac or renal safety concerns  Presence of mostly mild or moderate edema maybe due to twice daily administration of lanifibranor possibly leading to higher PPAR pathway activation reflected by high adiponectin levels in a systemic sclerosis population prone to present edema  Adiponectin levels in NATIVE NASH patients significantly lower compared to FASST systemic sclerosis patients

Corporate Presentation | 2019

slide-11
SLIDE 11

Non-confidential – Property of Inventiva │ 11

No cardiac or renal safety concern observed in the phase IIb study in systemic sclerosis study after one year of treatment

Corporate Presentation | 2019

Description of fold in creatinine over time – observed cases under treatment - mITT population Description of fold in NT-ProBNP over time– observed cases under treatment - mITT population

Value (Mean ± 95% CI) Week 12 Week 24 Week 48 Week 12 Week 24 Week 48 Value (Mean ± 95% CI)

slide-12
SLIDE 12

Non-confidential – Property of Inventiva │ 12

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

Corporate Presentation | 2019

 Insulin resistance (HOMA-IR, adiponectin)  Dyslipidemia (increase in HDL-C, reduction of TG) Lanifibranor metabolic markers in type II diabetic patients  Good overall tolerance and no major safety findings  No increases of creatinine, LFTs, or CPK  No changes in blood pressure  No signal of fluid overload or hemodilution  No clinically relevant weight gain 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

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

slide-13
SLIDE 13

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%

slide-14
SLIDE 14

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

slide-15
SLIDE 15

Non-confidential – Property of Inventiva │ 15

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

slide-16
SLIDE 16

Non-confidential – Property of Inventiva │ 16

Overview of NATIVE trial design (II/II)

Corporate Presentation | 2019

17 countries worldwide ► 13 in EU ► US ► Canada ► Australia ► Mauritius 92 sites involved 78 sites activated 68 sites screening  Status March 23, 2019: 594 patients screened, 164 patients randomized  3 positive DSMB reviews  Results expected first-half 2020 14 sites selected in the US

slide-17
SLIDE 17

Non-confidential – Property of Inventiva │ 17

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

 

slide-18
SLIDE 18

Odiparcil – MPS

slide-19
SLIDE 19

Non-confidential – Property of Inventiva │ 19

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: – MPS I: 1/100,000(1) – MPS II: 1/100,000(1) – MPS IV type A: 1/40,000 to 1/200,000(1) – MPS VI: 1/240,000 to 1/400,000 (1) – MPS VII: very rare (1)

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)   

slide-20
SLIDE 20

Non-confidential – Property of Inventiva │ 20

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

slide-21
SLIDE 21

Non-confidential – Property of Inventiva │ 21

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

slide-22
SLIDE 22

Non-confidential – Property of Inventiva │ 22

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

slide-23
SLIDE 23

Non-confidential – Property of Inventiva │ 23

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]

In vivo in MPS VI affected mice  Odiparcil decreases GAG accumulation in various tissues and intracellular GAG accumulation in lymphocytes  Odiparcil decreases GAG accumulation in cornea, restores corneal structure and decreases GAG accumulation in cartilage  Odiparcil restores mobility

GAG Granules: 1 -1 0 > 1 0 WT 40.4 45.8 9.4 MPS VI 15.1 32.6 51.3 MPS VI + Odi 19.7 47.4 21.5

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 old ►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

  • 100%

Odiparcil decreases intra-cellular GAG Odiparcil improves animal mobility

Chow diet Odiparcil : 4.5 g/kg in food Chow diet Odiparcil : 4.5 g/kg in food

slide-24
SLIDE 24

Non-confidential – Property of Inventiva │ 24

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

slide-25
SLIDE 25

Non-confidential – Property of Inventiva │ 25

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

slide-26
SLIDE 26

Non-confidential – Property of Inventiva │ 26

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)

slide-27
SLIDE 27

Non-confidential – Property of Inventiva │ 27

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
slide-28
SLIDE 28

R&D collaborations and Hippo pathway program update

slide-29
SLIDE 29

Non-confidential – Property of Inventiva │ 29

Key validating collaborations with AbbVie and Boehringer Ingelheim

Corporate Presentation | 2019

ABBV-157: Phase I studies initiated RORγ collaboration in inflammatory disease  RORγ program addresses large markets currently dominated by biologics and could prove to be superior to biologics  AbbVie has started Phase I study with ABBV-157  Inventiva remains eligible to future milestone payments and sales royalties on all ROR molecules identified during the collaboration 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  Inventiva eligible to up to ~€170m in milestones plus royalties Program progressing as planned with first screening performed

slide-30
SLIDE 30

Non-confidential – Property of Inventiva │ 30

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

slide-31
SLIDE 31

Near-term catalysts

slide-32
SLIDE 32

Non-confidential – Property of Inventiva │ 32

Recent achievements and upcoming expected milestones

Corporate Presentation | 2019

2018

Lanifibranor Odiparcil Collab.

 Phase IIa MPS VI results - H2 2019  Launch Phase Ib/II in children – H2 2019 Rare pediatric disease designation MPS VI

Discovery Finance

 Last patient Phase IIb NASH  Last patient Prof. Cusi study in NAFLD patients with TD2M

2019

 Start Phase I with ABBV-157  Clinical candidate selection

 MPS VI biomarker study results

Juvenile tox results Capital increase

YAP/TEAD: In vivo POC

   2 year carcinogenicity study results

US fibrosis indication patent US IND First patient in NAFLD Phase II

  

 Phase I ABBV-157 results - 2019

 

slide-33
SLIDE 33

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