Slide 1: Full Year 2018 Financial Results
Full Year 2018 Financial Results February 27, 2019
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 Marie-Paule Richard, MD, CMO Jean Volatier, MA, CFO Full Year 2018 Presentation Property of Inventiva │ 3
Slide 4: Summary
Summary Full year 2018 highlights Pipeline update Financials Near-term catalysts Full Year 2018 Presentation Property of Inventiva │ 4
Slide 5: Full Year 2018 Highlights
Full Year 2018 Highlights
Slide 6: Full Year 2018 Highlights
Full Year 2018 Highlights Lanifibranor program Successful extension of the NASH Native trial which is now running in Europe, Australia, Canada and the US: 70% of patients randomized. Results expected first-half 2020 Decision to stop development in systemic sclerosis following the results of the
Slide 7: Pipeline update
Pipeline update
Slide 8: Lanifibranor
Lanifibranor A new generation pan-PPAR agonist for a safe and efficacious treatment of fibrotic conditions
Slide 9: Systemic sclerosis overview
Systemic sclerosis overview A severe orphan disease with no approved treatment (1) SSc is a rare autoimmune rheumatic disease characterized by microvascular damage, vascular leakage and progressive fibrosis of the skin and visceral organs There are two principal forms: − Limited cutaneous (lcSSc
Slide 10: Update on FASST Phase IIb study in SSc
Update on FASST Phase IIb study in SSc Study design Principal investigator Inclusion criteria Principal investigators: Prof. Allanore (Hôpital Cochin, MRSS (Modified Rodnan Skin Score) between 10 and 25 Paris) and Prof. Denton (University College of London ) SSc diagnosed less than 3 years ago
Slide 11: Demographics and Baseline characteristics – mITT (N=145)
Demographics and Baseline characteristics – mITT (N=145) 800 mg 1200 mg Placebo Overall (N=49) (N=48) (N=48) (N=145) Female Gender 45 (91.84%) 40 (83.33%) 35 (72.92%) 120 (82.76%) N (%) Mean (SD) Age 46.4 (11.4) 49.0 (11.5) 49.0 (11.1) 48.1 (11.3) years Mean (SD) 18.0 (12.0) 17.0 (11.7) 16.2 (10.4)
Slide 12: Primary Endpoint MRSS not met – mITT (N=145)
Primary Endpoint MRSS not met –– mITT (N=145) Primary objective: provide evidence of the efficacy of lanifibranor at week 48 through the dose response relationship, using absolute MRSS change from baseline. Descriptive analysis over time of the absolute change in MRSS from baseline to W48 (Primary I
Slide 13: Secondary Endpoint: %pFVC – mITT (N=145)
Secondary Endpoint: %pFVC – mITT (N=145) Descriptive analysis over time of the absolute change in %pFVC from baseline to W48 (Primary Imputation Method) Results from the statistical model (Mixed 2 Model Repeated Mean +/- 95% CI Measures) 0 Effect of lanifibranor versus placebo at week 48 through the
Slide 14: Secondary Endpoint: VAS Physician, VAS Patient – mITT
Secondary Endpoint: VAS Physician, VAS Patient – mITT (N=145) Descriptive analysis over time of the absolute change in VAS from baseline to W48 through the dose response relationship (Primary imputation method) VAS Physician – p: 0.4198 VAS Patient – p: 0.0859 0 0 -5 Mean +/- 95% CI -5 -10 -10 -15 -
Slide 15: Summary of Overall TEAEs
Summary of Overall TEAEs 800 mg 1200 mg Placebo (N=49) (N=48) (N=48) At least one … n (%) TEAE 44 (89.8%) 41 (85.4%) 43 (89.6%) TEAE related to treatment 32 (65.3%) 31 (64.6%) 11 (22.9%) Severe TEAE related to treatment 3 (6.1%) 1 (2.1%) 0 TESAE related to treatment 0 1 (2.1%)* 0 Severe TESAE relate
Slide 16: Fluid Retention AEs
Fluid Retention AEs 800 mg 1200 mg Placebo (N=49) (N=48) (N=48) At least one … n (%) Fluid retention TEAE related to treatment 17 ( 34.7% ) 17 ( 35.4% ) 0 Severe fluid retention TEAE related to treatment 0 1 (2.1%)* 0 Fluid retention TESAE related to treatment 0 1 (2.1%)* * 0 Severe fluid retention
Slide 17: Circulating adiponectin levels indicate strong PPAR target engagement
Circulating adiponectin levels indicate strong PPAR target engagement in lanifibranor-treated SSc patients possibly due to twice daily dosing Mean adiponectin Lanifibranor Baseline Population Duration fold increase vs dosage adiponectin level baseline SSc 400 mg twice daily 3 Months 7.1 µg/ml 4.8 S
Slide 18: Adiponectin response in NATIVE NASH patients lower than in SSc patients
Adiponectin response in NATIVE NASH patients significantly lower than in systemic sclerosis patients with fluid retention Description of mean folds of adiponectin over time – mITT population with FRAE(1) over time Fold-increase adiponectin levels in NATIVE NASH patients treated with lanifibranor s
Slide 19: No cardiac or renal safety concern observed in the FASST study
No cardiac or renal safety concern observed in the FASST study after one year of treatment Description of fold in creatinine over time – observed Description of fold in NT-ProBNP over time– cases under treatment - mITT population observed cases under treatment - mITT population Full Year 2018 Presen
Slide 20: Conclusion of the FASST study
Conclusion of the FASST study Well conducted clinical trial in early dcSSc adult patients Little or no progressors and strong placebo effect, possibly due to background therapy The primary endpoint on skin score was not met, nor secondary efficacy endpoints Lanifibranor showed a favorable tr
Slide 21: NATIVE Phase IIb study in NASH
NATIVE Phase IIb study in NASH Study design Principal investigator Inclusion criteria Prof. Sven Francque (Universitair Ziekenhuis, Antwerpen, Liver biopsy Belgium) Severe patients with an inflammation and ballooning score Prof. Manal Abdelmalek (Duke University, USA) of 3 or 4 Status Stea
Slide 22: NATIVE: 70% of patients randomized and trial enrolling also in the US
NATIVE: 70% of patients randomized and trial enrolling also in the US 17 countries worldwide ► 13 in EU ► United States ► Canada ► Australia ► Mauritius 14 sites selected in the United-States 91 sites involved 76 sites activated 64 sites screening Status February 27, 2019: 556 patients screened, 1
Slide 23: NATIVE study backed by Phase II trial in T2DM patients with NAFLD
NATIVE study results will also be backed by the Phase II trial in T2DM patients with NAFLD Investigator initiated study design Principal investigator Primary endpoint Prof. Kenneth Cusi (University of Florida) Change from baseline to week 24 in IHTG Randomisation Key secondary endpoints Random
Slide 24: Odiparcil – MPS
Odiparcil – MPS
Slide 25: iMProveS Phase IIa study of odiparcil in MPS VI
iMProveS Phase IIa study of odiparcil in MPS VI Study design Population ► Phase III 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 26: BM6 study to evaluate leukoGAGs in MPSVI patients receiving ERT
BM6 study to evaluate leukoGAGs in MPSVI patients receiving ERT – study concluded Population 6 patients with MPS VI (7y+) receiving enzyme replacement therapy (mean treatment duration: 10 y ± 3.1 [6 – 14 y]) 6 control subjects not affected with MPS (age matched with MPS VI patients) Investigatio
Slide 27: BM6 extension study to evaluate skinGAGs and leukoGAGs after ERT infusion
BM6 extension study to evaluate skinGAGs and leukoGAGs after ERT infusion Objectives Determine the time course of the effect of ERT on leuko GAG levels and LeukoASB activity Evaluate skinGAG levels in MPS VI ERT receiving patients compared to control subjects Population Same patients as for BM6
Slide 28: Safe-KIDDS phase Ib/II study of odiparcil in MPS VI children
Safe-KIDDS phase Ib/II study of odiparcil in MPS VI children A Phase Ib/II safety, pharmacokinetics, pharmacodynamics and efficacy, dose- ranged, three-period, randomized, double-blind, placebo-controlled study of odiparcil as add-on to ERT in a pediatric population with MPS type VI from 5 to 15 yea
Slide 29: R&D collaborations and Hippo pathway program update
R&D collaborations and Hippo pathway program update
Slide 30: Significant progresses achieved, especially with phase I initiation of ABBV-157
Significant progresses achieved, especially with phase I initiation of ABBV-157 RORγ collaboration in inflammatory disease Fibrosis collaboration RORγ program addresses large markets currently Multi-year R&D collaboration and licensing partnership dominated by biologics and could prove to be sup
Slide 31: YAP-TEAD program: significant progress and clinical candidate selection in 2019
YAP-TEAD program: significant progress achieved and clinical candidate selection planned in 2019 Novel cancer pathway involved in drug Proprietary chemistry resistance, immune evasion, tumor progression and metastases Lead and back-up compounds available Relevant in multiple, commercially attractive
Slide 32: Inventiva lead compounds inhibit YAP/TEAD interaction in mesothelioma cells
Inventiva lead compounds inhibit YAP/TEAD interaction in malignant mesothelioma H2052 cells Inhibition of proliferation and YAP-TEAD target genes is due to inhibition of YAP-TEAD interaction Inhibition of proliferation (2D) PLA 100 DMSO DMSO IVA Lead Compound 3µM IV 3µM Proliferation % 50 0 6.782e-0
Slide 33: Inventiva lead compounds inhibit malignant mesothelioma H2052 spheroid growth
Inventiva lead compounds inhibit malignant mesothelioma H2052 spheroid growth SOC1 3µM H2052 spheroid model DMSO 0,5% IVA 0.3µM SOC1 + IVA 0.3µM IVA 1µM SOC1 + IVA 1µM H2052 150 IVA 3µM SOC1 + IVA 3µM ► Hippo pathway gene mutation: NF2, LATS2 ► YAP dependent model 100 Growth % ► IVA compounds inhibi
Slide 34: Lead compounds re-sensitize NSCLC resistant cell lines to chemotherapy
Inventiva lead compounds re-sensitize NSCLC resistant cell lines to chemotherapy with standard of care Standard of care resistant cell line (acquired resistance) Parental Resistant ++ IVA Resistant IV1612112 3µM Lead Compound 3µM HCC827 Resistant 150 100 % Proliferation % Proliferation 100 50 50 0 0
Slide 35: Activity demonstrated in vivo in relevant mesothelioma model
Activity demonstrated in vivo in relevant mesothelioma model Vehicle Vehicle p.op.o QD QD H2052 Xenograft model IV1612640 IVA 1 mg/kg Lead 1 mg/kg p.o QD p.o QD Cellular model: H2052 RelativeTumor volume Relative Tumor Volume Mice: female CB17-SCID (means ±± SEM) (means SEM) 3.0 Read out: Tumo
Slide 36: Financials
Financials
Slide 37: Strong cash position and shareholder base
Strong cash position and shareholder base Key financials Shareholder base ISIN code FR0013233012 Market Euronext Paris Shares outstanding 22.294.677 Market cap €84m (February 26 2019) €56,7m compared to €59.1m as of December 2017. *Including Perceptive Advisors Cash position Successful €48.5m Eurone
Slide 38: Full year 2018: a solid financial position and sustained R&D efforts
Full year 2018: a solid financial position and sustained R&D efforts Income Statement ► Revenues of €3.2m, in line with expectations, vs €4.8m in 2017 • First-time application of IFRS 15 Key figures December 31, December 31, • ABBV-157’s entry into Phase I, a clinical program resulting from (in thou
Slide 39: Near-term catalysts
Near-term catalysts
Slide 40: Recent achievements and upcoming milestones
Recent achievements and upcoming milestones 2018 2019 2 year carcinogenicity study results Lanifibranor Last patient Phase IIb NASH US fibrosis indication patent Last patient Prof. Cusi study in NAFLD patients US IND with TD2M First patient in NAFLD Phase II MPS VI biomarker study resu
Slide 41: Q&A
Q&A
Slide 42: Contacts
Contacts Inventiva Brunswick LifeSci Advisors Frédéric Cren Julien Trosdorf / Yannick Tetzlaff Monique Kosse CEO Media relations Investor relations info@inventivapharma.com inventiva@brunswickgroup.com monique@lifesciadvisors.com +33 (0)3 80 44 75 00 + 33 1 53 96 83 83