Slide 1: First-Half 2018 Financial Results
First-Half 2018 Financial Results September 27, 2018
Slide 2: Disclaimer
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
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 Jean Volatier, MA, CFO H1 2018 Presentation Property of Inventiva │ 3
Slide 4: Summary
Summary First-Half 2018 highlights Pipeline update Financials Near-term catalysts H1 2018 Presentation Property of Inventiva │ 4
Slide 5: First-Half 2018 Highlights
First‐Half 2018 Highlights
Slide 6: First-Half 2018 Highlights
First-Half 2018 Highlights Lanifibranor program Continuation of the clinical development of lanifibranor and confirmation of its good safety profile Increased and extended protection of lanifibranor with the grant of a new patent in the United States Decision to open new clinical sites in the
Slide 7: Pipeline update
Pipeline update
Slide 8: Lanifibranor: Recent achievements and upcoming milestones
Recent achievements and upcoming milestones 2018 2019 2 year carcinogenicity study results Lanifibranor Results Phase IIb SSc US fibrosis indication patent Last patient Phase IIb NASH US IND Last patient Pr Cusi study in NAFLD patients with First patient in NAFLD Phase II TD2M MPS VI
Slide 9: Lanifibranor – Systemic Sclerosis (SSc) and NASH
Lanifibranor – Systemic Sclerosis (SSc) and Nonalcoholic steatohepatitis (NASH) A new generation pan-PPAR agonist for a safe and efficacious treatment of fibrotic conditions
Slide 10: Lanifibranor: increased and extended protection
Lanifibranor: increased and extended protection Previous IP Composition of matter patent protecting lanifibranor in 59 countries including US, Europe, Japan , China,… – Limit of exclusivity August 2031 including 5-year extension Newly granted patent Use patent granted in the United States countr
Slide 11: Lanifibranor: a strengthened safety profile
Lanifibranor: a strengthened safety profile Safety package 6 month tox in rodents 6 month tox data in primates 12 month tox data in primates 100 healthy volunteers treated in Phase I trials and 56 patients treated in Phase IIa study Recently generated data First DSMB for NATIVE trial in NA
Slide 12: Update on FASST Phase IIb study in SSc
Update on FASST Phase IIb study in SSc Trial design Principal investigator Inclusion criteria Principal investigators: Pr Allanore (Hôpital Cochin, MRSS (Modified Rodnan Skin Score) between 10 and 25 Paris) and Pr Denton (University College of London ) SSc diagnosed from less than 3 years Ot
Slide 13: Update on NATIVE Phase IIb study in NASH (I/III)
Update on NATIVE Phase IIb study in NASH (I/III) Trial design Principal investigator Inclusion criteria Pr Francque (Universitair Ziekenhuis, Antwerpen, Belgium) Liver biopsy Status Moderate to severe patients with an inflammation and Trial enrolling ballooning score of 3 or 4 Results expe
Slide 14: NATIVE: update on actions implemented to secure recruitment (II/III)
NATIVE: update on actions implemented to secure recruitment (II/III) Status at end of : December 2017 June 2018 September 2018 # of sites activated at the 36 66 71 end of the period # of sites screening at the 17 49 57 end of the period # of patients screened 51 186 106 over the period # of patients
Slide 15: NATIVE: update on actions implemented to secure recruitment (III/III)
NATIVE: update on actions implemented to secure recruitment (III/III) To secure patient recruitment, the Company has decided to open several sites in the United States, to transform it into a global study and increase its visibility in the United-States. We believe the opening of new sites in th
Slide 16: Update on US investigator-initiated Phase II study in T2DM patients with NAFLD (I/II)
Update on US investigator-initiated Phase II study in T2DM patients with NAFLD (I/II) Nonalcoholic fatty liver disease (NAFLD) develops in ~70% of patients with type 2 diabetes mellitus (T2DM): ► Diabetes becomes more difficult to control and often needs more medication ► About 40% develop the more
Slide 17: Update on US investigator-initiated Phase II trial in T2DM patients with NAFLD (II/II)
Update on US investigator-initiated Phase II trial in T2DM patients with NAFLD (II/II) Trial design Principal investigator Primary endpoint Pr. Kenneth Cusi (University of Florida) Change from baseline to week 24 in IHTG Randomisation Key secondary endpoints Randomized (1:1), double-blind, pla
Slide 18: PanNASH initiative: international experts promoting NASH and PPARs approach
PanNASH initiative: a group of well recognized international experts working to promote NASH and PPARs approach Creation of panNASH™, a committee of international independent experts aiming to play an active role in developing and disseminating their NASH expertise among the scientific community,
Slide 19: Odiparcil
Odiparcil The first oral therapy to treat five forms of mucopolysaccharidosis (MPS): MPS I, II, IV, VI and VII
Slide 20: Odiparcil: clinical strategy update
Odiparcil: clinical strategy update Development of a promising biomarker approach to support odiparcil’s development and registration in MPS VI Continued progress of the Phase IIa iMProveS study for the treatment of MPS VI Evolution of the development plan to shorten time to market H1 2018 Pre
Slide 21: Development of a promising biomarker for MPS VI
Development of a promising biomarker for MPS VI confirming the limited efficacy of ERT in reducing leukoGAGs Leukocytes are promising cells: low invasiveness of collection procedure and intracellular glycosaminoglycans (GAG) levels are increased in animal model of MPS where Odiparcil decreases intra
Slide 22: Update on iMProveS Phase IIa study in MPS VI patients
Update on iMProveS Phase IIa study in MPS VI patients Phase IIa Population ► Phase 3 enabling study with evidence for dose selection ► Receiving ERT (N=18) and PK / PD response characterization ► Not receiving ERT (N=6) ► Clinicaltrials.gov identifier: NCT03370653 ≥ 16yo 18 patients double blind + 6
Slide 23: Odiparcil: evolution of the development plan
Odiparcil: evolution of the development plan In July 2018 FDA published a draft guidance(1) on the evidence necessary to demonstrate the effectiveness of new drugs intended for slowly progressive low-prevalence rare diseases that are associated with substrate deposition and caused by single enzyme
Slide 24: Collaborations with AbbVie and Boehringer Ingelheim
Collaborations with ‘e\e) bovi =) fi Boehringer V Ingelheim
Slide 25: Update on collaborations with AbbVie and Boehringer Ingelheim
Update on collaborations with AbbVie and Boehringer Ingelheim RORγ collaboration Fibrosis collaboration RORγ program addresses large markets currently Multi-year R&D collaboration and licensing partnership dominated by biologics and could prove to be superior to biologics Joint team until pre-
Slide 26: Yap-Tead program
Yap-Tead program
Slide 27: YAP-TEAD: update on program progress
YAP-TEAD: update on program progress The Hippo pathway: a newly discovered oncogenic signaling pathway, where Inventiva has established a leading position The program addresses both rare cancers (malignant mesothelioma, uveal melanoma, …) as well as large cancers (NSCLC, TNBC, hepatoblastoma, hepa
Slide 28: Financials
Financials
Slide 29: Strong cash position and shareholder base
Strong cash position and shareholder base Key financials Shareholder base Free Float* 22,1% ISIN code FR0013233012 Founders 43,9% Market Euronext Paris BVF 15,0% Shares outstanding 22.257.277 Market cap €174m (September 25 2018) Novo 8,8% €75.9m compared to €59.0m in Employees & Others Sofinnova Dec
Slide 30: H1 2018: financial position
H1 2018: financial position Income Statement Highlights First half First half ► Revenues of €1.3M compared to €2.7M in H1 17 In thousands of euros 2018 2017 • Significant progress in the collaborations with AbbVie and Revenue 1,301 2,658 Boehringer Ingelheim leading to lower resources Other recurrin
Slide 31: Near-term catalysts
Near-term catalysts
Slide 32: Recent achievements and upcoming milestones
Recent achievements and upcoming milestones 2018 2019 2 year carcinogenicity study results Lanifibranor Results Phase IIb SSc US fibrosis indication patent Last patient Phase IIb NASH US IND Last patient Pr Cusi study in NAFLD patients with First patient in NAFLD Phase II TD2M MPS VI
Slide 33: Q&A
Q&A
Slide 34: Contacts
Contacts Inventiva Brunswick LifeSci Advisors Frédéric Cren Julien Trosdorf / Yannick Tetzlaff Chris Maggos CEO Media relations Investor relations info@inventivapharma.com inventiva@brunswickgroup.com chris@lifesciadvisors.com +33 (0)3 80 44 75 00 + 33 1 53 96 83 83
Slide 35: Lanifibranor: a next generation panPPAR agonist for fibrotic conditions
Lanifibranor: a next generation panPPAR agonist for a safe and efficacious treatment of fibrotic conditions Unprecedented chemical structure with moderate and balanced panPPAR agonist activity (PPAR, PPAR and PPAR Oral administration Efficacy demonstrated in preclinical models of insulin r
Slide 36: Systemic sclerosis overview
Systemic sclerosis overview A severe disease with no approved treatment (1) SSc is an autoimmune disease with microvascular damage and progressive fibrosis of the skin and visceral organs There are two subtypes: − Limited cutaneous (lcSSc; ~60% of patients): restricted skin involvement, but with
Slide 37: Lanifibranor inhibits TGF signaling in fibroblasts from SSc patients
Lanifibranor inhibits TGF signaling in fibroblasts from SSc patients TGF Fibroblast to myofibroblast differentiation drives effective fibrosis across multiple organs and tissues and is largely regulated by TGF-β through the SMAD2/3 pathway Lanifibranor blocks pSMAD2/3 accumulation in the nucle
Slide 38: Lanifibranor has demonstrated anti-fibrotic activity in multiple models
Lanifibranor has demonstrated anti-fibrotic activity in multiple models and several organs that are relevant to SSc Lanifibranor positively impacts the most relevant clinical features of SSc Lanifibranor reduces Lanifibranor reduces Lanifibranor reduces Lanifibranor restores established skin fibrosi
Slide 39: Lanifibranor: a mechanism of action addressing all key features of NASH
Lanifibranor: a mechanism of action addressing all the key features of NASH PPAR PPAR, Metabolism Steatosis Insulin sensitivity FA uptake HDLc FA catabolism Lanifibranor TG Lipogenesis Moderate and balanced panPPAR agonist activity regulating genes in: • PPAR: hepatocytes • PPAR: kuppfer cell
Slide 40: Lanifibranor reduces steatosis, inflammation, ballooning and fibrosis in preclinical models
Lanifibranor significantly reduces steatosis, inflammation, ballooning and fibrosis in preclinical models Lanifibranor inhibits steatosis Lanifibranor significantly and inflammation in the MCD reduces ballooning and the Lanifibranor reverses model NAS score in the foz/foz model established liver fib
Slide 41: MPS are devastating diseases with high unmet medical needs
MPS are devastating diseases with high unmet medical needs MPS diseases are inherited lysosomal storage diseases Autosomal recessive disorder characterized by accumulation of glycosaminoglycan(s) (GAG) due to lack of an enzyme Seven distinct clinical types based on the enzyme affected Odiparcil coul
Slide 42: Odiparcil, the first orally available therapy to treat several forms of MPS
Odiparcil, the first orally available therapy to treat several forms of MPS Mechanism of action via modulation of GAG synthesis which accumulation triggers MPS Oral administration Odiparcil reduction of GAG intracellular accumulation demonstrated in in vitro and in vivo relevant models Activit
Slide 43: Odiparcil has the potential to differentiate versus current enzyme replacement therapies
Odiparcil has the potential to positively differentiate versus current enzyme replacement therapies Aldurazyme, Elaprase, Odiparcil Naglazyme, Vimizim, Mepsevii HSCT (Hematopoietic stem cell transplantation) Effect on mobility Eye, cartilage, bones, heart valves, spinal cord compression Safety Dose