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

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


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Developing breakthrough therapies in NASH and mucopolysaccharidosis

Corporate Presentation

November 2019

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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

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

Inventiva: 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 A clinical stage partnership with AbbVie – ABBV-157 RORg program with potential in several auto-immune indications: first phase I completed and second one in 60 healthy volunteers and patients with chronic plaque psoriasis ongoing Compelling early stage pipeline – YAP-TEAD program in late pre-clinical stage, clinical candidate selection expected in 2019 State of the art R&D capabilities including wholly owned ‘pharma scale’ discovery facilities Strong US and European shareholder base and experienced senior management team with a track record of operational and scientific excellence Cash position allowing a runway until end of Q3 2020 post Phase IIb results in NASH

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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 ~70 people
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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

 Next milestone: H1 2020 Hippo

Non-small cell lung cancer and mesothelioma

 Candidate Selection: 2019 TGF-β

Idiopathic pulmonary fibrosis (IPF)

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

YAP/TEAD

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

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Non-confidential – Property of Inventiva │ 6

Key financials and shareholder base

ISIN code FR0013233012 Market Euronext Paris Shares outstanding 26.846.112 Market cap

(Nov. 4 2019)

€77m Cash position

(September 30 2019)

35,3m compared to €56,7m as

  • f December 2018. Runway to

end of Q3 2020 post NASH phase IIb results Revenues in H1 2019

(September 30, 2019)

€3,4m compared to €2,2m in 2018 (9 months period) R&D expenditures in H1 2019

(June 30, 2019)

€19,6m compared to €15,9m in H1 2018

Key financials Shareholder base Analyst coverage

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

Free float* 13,3% BVF 20,2% NEA 11,6% [NOM DE CATÉGO RIE] [VALEUR] [NOM DE CATÉGO RIE] [VALEUR] Employee s & others [VALEUR] Founders 36,4%

* Including Perceptive Advisors Corporate Presentation | 2019

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Lanifibranor in Nonalcoholic Steatohepatitis (NASH)

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

Corporate Presentation | 2019

Compound PPARa EC50 (nM) PPARd EC50 (nM) PPARg 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

hPPARa hPPARd hPPARg

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

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Favorable safety profile differing from previously developed PPARs

Corporate Presentation | 2019

Organ PPAR isoforms activated Reported PPAR liabilities

Lanifibranor effects

Heart  PPARg  Fluid retention  Cardiac hypertrophy

Not observed

Skeletal muscle  PPARa  Myofiber degeneration

Not observed

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

Not observed

Urinary bladder  PPARg  Proliferative changes in bladder epithelium

Not observed

Source: Company data

Lanifibranor not associated with typical single or dual PPAR liabilities

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Lanifibranor favorable safety profile supported by long and extensive studies

Corporate Presentation | 2019

6 month tox in rodents 6 month tox data in primates 12 month tox data in primates 2 year carcinogenicity studies in rats and mice 200+ healthy volunteers treated in Phase I trials 47 T2DM patients treated in Phase IIa study 97 SSc patients treated in a Phase IIb

Safety package Recently generated safety data

    Fourth and last DSMB for NATIVE trial in NASH recommending to continue the trial as planned based on safety data from 228 patients, including 139 patients treated for the whole study period After review of carcinogenicity studies, FDA has lifted PPAR class clinical hold and allowed long-term clinical studies in NASH with lanifibranor     

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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 (PPARg)

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 (PPARa/d)

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 (PPARa/d)

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%

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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%

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

Corporate Presentation | 2019

Insulin sensitivity HDLc TG

PPARa,d,g Metabolism

FA uptake FA catabolism Lipogenesis

PPARg Steatosis Inflammation and Ballooning

NFkB-dependent gene activation Inflammasome Ballooning

PPARa,d,g

Stellate cell proliferation and activation Collagen and fibronectin production

PPARg Fibrosis Vascular

Portal pressure LSEC capillarization Intrahepatic vascular resistance

PPARa,g

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Lanifibranor shows consistent improvements in metabolic parameters and histology while displaying anti-fibrotic activity

Corporate Presentation | 2019

Methionine Choline Deficient diet (MCD) Choline-deficient amino-acid and high fat diet Foz / Foz Carbon tetrachloride (CCL4) Thiocetamide (TAA) Diet induced obesity high fat / high sucrose HSC biology Macrophages biology Hepatoma and muscle cells biology Endothelial biology

Metabolic models NASH & NAFLD models Fibrosis models Cirrhosis models

Lanifibranor improves  Insulin resistance  Non fasting glucose  Homa-IR  Lipid profile Lanifibranor maintains body weight Lanifibranor reduces  Steatosis  Inflammation  Ballooning Lanifibranor improves NAS score Lanifibranor reduces fibrosis Lanifibranor inhibits stellate cell activation Lanifibranor reverses NASH Lanifibranor reduces  Portal pressure  Established fibrosis

In Vivo In Vitro

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Pioglitazone PPARg 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), corporate presentation March 2019 page 14 ; Aramchol Arrest Phase II study (600 mg, 12 months) – press release June 12, 2018

pbo

[VALEUR]

pbo

[VALEUR]

pbo

[VALEUR]

pbo

[VALEUR]

pbo

[VALEUR]

pbo

[VALEUR] 51% 12% 19% 8% 25% 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

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NATIVE phase IIB study

Corporate Presentation | 2019

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

Trial design 225 patients treated for 24 week + 4 week safety follow-up 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 Screening

 Liver biopsy

Principal investigators

 Prof. Sven Francque (Antwerp University, Belgium)  Prof. Manal Abdelmalek (Duke University, USA)

Randomisation

 1/1/1, stratification on T2DM patients  Study powered with 75 patients per group  Central reading

Status

Recruitment completed with 247 patients randomized 4 positive DSMB reviews recommending to continue the study without any changes

Clinicaltrials.gov identifier

 NCT03008070

Inclusion criteria

 Liver biopsy  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

Key secondary endpoints

 Decrease of at least 2 points in NAS  Resolution of NASH (to NAFLD: steatosis ± mild inflammation)  Change in fibrosis score  Change in liver enzymes, inflammatory markers, glucose metabolism parameters, plasma lipids parameters, adiponectin, …  Safety

 

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NATIVE trial in NASH is fully recruited and results are expected for first-half 2020

Corporate Presentation | 2019

17 countries ►13 in EU ►United States ►Canada, Australia ►Mauritius >70 sites recruited patients 14 sites in the United-States

247 patients randomized, exceeding the initial target of 225 patients  Patients with moderate/severe NASH recruited: ~72% with NAS ≥ 6 and ~76% F2 or F3  ~40% have type 2 diabetes allowing to conduct the planned sub-analyses  167 patients(1) had already completed the six-month study confirming that the treatment is well tolerated  Results expected first-half 2020

(1) Database extraction October 8 2019

Country Patients randomized Europe 183 (74%) US 36 (15%) Australia 13 (5%) Canada 8 (3%) Mauritius 7 (3%) Total 247 (100%)

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NATIVE trial: baseline characteristics

Corporate Presentation | 2019

Parameters Patients without diabetes (N = 148 ; 60%) Patients with diabetes (N = 99 ; 40%) Total (N = 247 ; 100%)

Gender Female 57% 60% 58% Male 43% 40% 42% Age Mean ± SD 51.8 ± 13.5 56.3 ± 10.4 53.6 ± 12.5 Median 54.0 57.0 55.0 Min ; Max 20 ; 76 28 ; 77 20 ; 77 Weight (kg) Mean ± SD 93.5 ± 19.0 92.8 ± 18.8 93.2 ± 18.9 Median 91.0 90.0 91.0 Min ; Max 51 ; 142 55 ; 145 51 ; 145 BMI (kg/m²) Mean ± SD 32.8 ± 5.5 33.0 ± 5.3 32.9 ± 5.4 Median 32.2 32.9 32.4 Min ; Max 21 ; 45 23 ; 44 21 ; 45 Male waist circumference (cm) Mean ± SD 109.6 ± 12.6 112.2 ± 12.2 110.6 ± 12.4 Median 108.0 110.0 110.0 Min ; Max 88 ; 134 89 ; 142 88 ; 142 Female waist circumference (cm) Mean ± SD 104.8 ± 13.5 105.7 ± 12.0 105.2 ± 12.9 Median 106.0 106.0 106.0 Min ; Max 76 ; 139 75 ; 138 75 ; 139 Fibrosis Score (%) F0 – F1 27% 20% 24% F2 44% 36% 41% F3 29% 43% 35%

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Non-confidential – Property of Inventiva │ 19 Corporate Presentation | 2019

Parameters DSMB # 1 DSMB # 2 DSMB # 3 DSMB # 4 Date of DSMB meeting June 2018 October 2018 March 2019 September 2019 # patients reviewed / % of total patients in the study 52 / 21% 94 / 38% 156 / 63% 227 / 92% # patients having finished the study / % of total patients in the study 18 / 7% 36 / 15% 86 / 35% 139 / 57% DSMB conclusion: continue study as planned

NATIVE trial: lanifibranor is well tolerated and safe as confirmed by four positive DSMBs

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Ongoing Phase II trial in type 2 diabetes patients with NAFLD evaluating the effect of lanifibranor on hepatic insulin sensitivity

(1) Intrahepatic triglycerides (2) Magnetic resonance elastography (3) De-novo lipogenesis ; (4) Levin J., EASL 2018. Bril, F & Cusi, K, 2017 Diabetes Care, 40:419-430. Younossi, Z., et al, 2018. Nat Rev Gastroenterol Hepatol, 15(1): 11-20

Lanifibranor could be the drug of choice for NASH patients with TD2M: ~48% of NASH patients have TD2M(4)

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  Randomized (1:1), double-blind, placebo-controlled  Non-obese subject control group for the metabolic and imaging procedures  N=64 calculated assuming a 35% relative reduction

  • f IHGT(1)

Status IND approved First Patient First Visit: August 2018  Results expected second-half of 2020 Primary endpoint  Change from baseline to week 24 in IHTG Key secondary endpoints  Proportion of responders (IHTG, NAFLD resolution)  Change in hepatic fibrosis (MRE(2), biomarkers)  Change in metabolic outcomes (insulin sensitivity, DNL(3), glycemic control, lipids)  Safety Clinicaltrials.gov identifier: NCT03459079

Trial design

 

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Odiparcil – MPS

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Non-confidential – Property of Inventiva │ 22

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)   

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Unique mechanism of action potentially synergistic with ERT

Corporate Presentation | 2019

Odiparcil diverts endogenous protein-bound GAG synthesis to soluble odiparcil-bound chondroitin sulfate (CS) and dermatan sulfate (DS) synthesis

Galactosyl transferase I (GTI)

Synthesis of proteoglycans (HS, CS, DS) Synthesis

  • f soluble

DS and CS

Odiparcil

Odiparcil

Galactosyl transferase I (GTI)

Normal GAGs level Healthy Patient Normal GAG degradation Odiparcil GAGs level reduction Intracellular GAGs reduction MPS GAGs accumulation GAG degradation is defective Normal GAGs level

Odiparcil original mechanism of action could provide additive benefit to enzyme replacement therapies (ERT) in MPS I, II, IVA, VI and VII patients

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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

MPS 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

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Odiparcil decreases intracellular GAG accumulation in vitro in MPS VI patient cells

Corporate Presentation | 2019

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

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

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Non-confidential – Property of Inventiva │ 26

Odiparcil decreases GAG accumulation and restores mobility in a mouse model of established MPS VI disease

Corporate Presentation | 2019

Source: Company data

Odiparcil decreases GAG accumulation in tissues Odiparcil restores mobility

Whole eye Liver Knee (Distal femoral growth plate)

Odiparcil decreases knee cartilage thickness

Decrease of GAG accumulation was also observed in spleen, kidney, and heart

Age at treatment onset: 12 weeks Treatment duration: 6 months

5 10 15 20 ***

WT MPS VI MPS VI + Odi

*

GAG in liver [Area * Index]

10 20 30 40 50 ***

WT MPS VI MPS VI + Odi

**

time on pole [sec]

5 1 1 5 2 2 5 * * *
  • 3
2 % W T M P S V I * * * M P S V I + O d i D t h [ µ
  • 40%
  • 66%

1 2 3 4 5

p<0.001

Sulfated GAG (µg/mg of wet tisues) WT MPS VI MPS VI + Odi

p<0.001

  • 67%

p<0.001 p<0.05 p<0.001 p<0.01 p<0.001 p<0.001

Wild-type and MPS VI mice

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Non-confidential – Property of Inventiva │ 27

Odiparcil decreases GAG accumulation in leukocytes which are excreted through the urine

Corporate Presentation | 2019

Source: Company data

Odiparcil decreases intracellular GAG levels in leukocytes Soluble GAG produced from Odiparcil are excreted in urine

2000 4000 6000 p<0.0001

WT MPS VI MPS VI + Odi

Sulfated GAG (µg/mg of creatinine)

Wild-type and MPS VI mice

20 40 60 80 %cells with > 10 GAG granules

p<0.001 p<0.001

MPS VI MPS VI+Odi WT

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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)

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iMProveS Phase IIa trial of odiparcil in MPS VI

Corporate Presentation | 2019

More information on: http://www.improves-mpsvi-trial.com/

End of treatment 4 weeks Placebo + ERT Odiparcil, 250 mg bid + ERT Odiparcil, 500 mg bid + ERT Odiparcil, 500 mg bid and no ERT Follow up 15 patients double blind + 5 patients open label 26 week treatment 4 weeks

Screening, baseline and randomization

6 weeks

Screening (4w) and preliminary safety assessment (2w)

Safety  Clinical and biological assessments (standard tests) Pharmacokinetics  Odiparcil plasma levels Efficacy  Leukocyte, skin and urinary GAG content  Activity and mobility tests (6 minute walk test, upper limb function, shoulder mobility range)  Cardiac, vascular and respiratory functions  Eye impairment, hearing capacity, pain assessment, quality of life questionnaires

Endpoints

≥ 16yo

Phase IIa

► Phase III enabling study with evidence for dose selection and PK / PD response characterization ► Clinicaltrials.gov identifier: NCT03370653

Population Status

1st DSMB (Oct 2018): no safety concerns; recommendation to initiate the core study Four centers selected: UK, Germany, France, Portugal Recruitment completed  Results expected second-half of 2019 15 patients 5 patients

  

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SLIDE 30

ABBV-157

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Non-confidential – Property of Inventiva │ 31

Key validating collaboration with AbbVie

Corporate Presentation | 2019

Successful first Phase I and launch of a new clinical study

(1) Source: clinicaltrial.gov

Inventiva eligible to future milestone payments and sales royalties: next milestone payment is expected for the first half of 2020

 Target Product Profile: Humira in a pill + oral + better safety  Single ascending dose Phase I completed and second clinical study initiated: a randomized, double-blind, placebo-controlled, multiple-dose study in 60 healthy volunteers and patients with chronic plaque psoriasis (clinicaltrials.gov identifier: NCT03922607): start date May 2019 and completion September 2020(1)

RORg is a master regulator of Th17 differentiation and IL-17 expression

 ABBV-157, a potent RORg, addresses large markets dominated by biologics

  • Psoriasis, Rheumatoid Arthritis, Multiple Sclerosis,

IBD, Uveitis, …

RORgt = Retinoic acid-related Orphan Receptor, gamma (thymus)

IL approach has been validated by several successful biologics ABBV-157 could target several diseases

Brand Name Company Target Sales (2018, B€) Stelara Janssen IL-12 and IL-23 4,7 Cosentyx Novartis IL-17A 2,5 Actemra Genentech IL-6 1,9 Taltz Eli Lilly IL-17A 0,8

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SLIDE 32

Upcoming catalysts

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SLIDE 33

Non-confidential – Property of Inventiva │ 33

Three transformational clinical outcomes expected in the short-term

Corporate Presentation | 2019

 Results phase IIa in MPS VI - H2 2019  ABBV-157 milestone when first psoriatic patient is treated - H1 2020  Results: phase IIb NASH - H1 2020

Lanifibranor Odiparcil ABBV-157

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SLIDE 34

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