Inventiva Sa · EURONEXT:IVA
Inventiva Sa — Technical Presentation (June 2020)
27 slides from Inventiva Sa's technical presentation, Jun 16, 2020
Slide 1: Lanifibranor in Nonalcoholic Steatohepatitis (NASH): NATIVE Phase IIb Topline Results
Lanifibranor in Nonalcoholic Steatohepatitis (NASH) NATIVE Phase IIb Topline Results June 16, 2020
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 cofounder Pierre Broqua, Ph.D., CSO and cofounder Marie-Paule Richard, MD, CMO Prof. Sven Francque, MD University Hospital Antwerp, Principal Investigator of NATIVE trial Prof. Manal Abdelmalek, MD Division of Gastroenterology and Hepatology
Slide 4: Highlights of topline results
Highlights of topline results ► Lanifibranor (1,200 mg) met the primary endpoint with a statistically significant reduction after 6 months of treatment of the Steatosis Activity Fibrosis score (SAF), which combines assessments of hepatocellular inflammation and ballooning, with no worsening of fibro
Slide 5: Lanifibranor: the only pan-PPAR agonist in clinical development for NASH
Lanifibranor: the only pan-PPAR agonist in clinical development for the treatment of NASH Moderate and balanced pan-PPAR agonist activity PPARa PPARd PPARg Differentiated Compound EC50 (nM) EC50 (nM) EC50 (nM) chemical structure Once daily oral Lanifibranor(1) 1630 850 230 administration Fen
Slide 6: Trial design
Trial design Clinicaltrials.gov identifier: NCT03008070 24-week treatment + 4-week follow-up Screening Double blind, randomized, placebo-controlled End of treatment Liver biopsy Liver biopsy Placebo Lanifibranor, 800 mg once daily • Randomisation 1/1/1 • Stratification on Lanifibranor, 1200 mg o
Slide 7: 247 patients randomized in 71 sites worldwide
247 patients randomized in 71 sites worldwide 4 sites in 49 sites in Canada Europe Patients Country randomized Europe 183 (74%) US 36 (15%) Australia 13 (5%) 12 sites in the Canada 8 (3%) United States Mauritius 7 (3%) 1 site in 5 sites in Total 247 (100%) Mauritius Australia 17 countries worldwide
Slide 8: Efficacy endpoints
Efficacy endpoints Primary endpoint Decrease from baseline to week 24 of at least 2 points of inflammation and ballooning and no worsening of fibrosis (as measured by SAF activity score) Secondary endpoints Resolution of NASH and no worsening of fibrosis Improvement of fibrosis by at least 1 s
Slide 9: NATIVE endpoints use both SAF and NAS scoring
NATIVE endpoints use both SAF and NAS scoring The severity of hepatocellular ballooning and inflammation is a strong predictor for the presence of hepatic fibrosis and the risk for fibrosis progression NATIVE primary endpoint is a reduction of ≥ 2 points of the SAF activity score, which excludes
Slide 10: Patient disposition (N = 247)
Patient disposition (N = 247) 247 patients randomised and treated Placebo Lanifibranor 800 mg/day Lanifibranor 1200 mg/day N = 81 N = 83 N = 83 74 (91%) patients completed 77 (93%) patients completed 77 ( 93%) patients completed the 24-week treatment the 24-week treatment the 24-week treatment 7 (9%
Slide 11: Patient Baseline Demographics and Characteristics (I/II)
Patient Baseline Demographics and Characteristics (I/II) ITT (N = 247) Placebo Lanifibranor Lanifibranor Overall Parameters (unit) - 800 mg/day 1200 mg/day - n (%) or mean ± SD N = 81 N = 83 N = 83 N = 247 Demographics Female 41 (51%) 54 (65%) 49 (59%) 144 (58%) Age (years) 53.4 ± 13.1 55.0 ± 10.4 5
Slide 12: Patient Baseline Demographics and Characteristics (II/II)
Patient Baseline Demographics and Characteristics (II/II) ITT (N = 247) Placebo Lanifibranor Lanifibranor Parameters (unit) - 800 mg/day 1200 mg/day mean ± SD N = 81 N = 83 N = 83 Liver enzymes Alanine aminotransferase, ALT (UI/L) 56.9 ± 31.6 64.1 ± 41.4 63.6 ± 43.4 Aspartate aminotransferase, AST (
Slide 13: Reduction of inflammation and ballooning (SAF Activity Score): primary endpoint
Dose-dependent and statistically significant (1200 mg) reduction of 2 points of inflammation and ballooning (SAF Activity Score) and no worsening of fibrosis Primary Efficacy Endpoint ITT Population (N = 247) Per Protocol Population (N = 194) p=0.015* p=0.004* p=0.058 p=0.061 % patients % patients 5
Slide 14: Resolution of NASH and no worsening of fibrosis
Dose-dependent and statistically significant results in resolution of NASH and no worsening of fibrosis Secondary endpoint ITT Population (N = 247) Per Protocol Population (N = 194) p=0.002* p<0.001* p=0.039* p=0.043* % patients % patients 49% 45% 40% 33% 19% 23% (N= 81) (N= 83) (N= 83) (N= 62) (N=
Slide 15: NASH resolution in F2/F3 patients
Dose-dependent and statistically significant results in resolution of NASH and no worsening of fibrosis in F2/F3 patients in both ITT and PP populations Secondary endpoint in F2/F3 patients ITT Population in F2/F3 (N = 188) Per Protocol Population in F2/F3 (N = 149) p<0.001* p<0.001* p=0.016* p=0.01
Slide 16: Improvement of fibrosis and no worsening of NASH
Dose-dependent and statistically significant (1200 mg) improvement of fibrosis and no worsening of NASH Secondary endpoint ITT Population (N = 247) Per Protocol Population (N = 194) p=0.04* p=0.011* p=0.75 % patients % patients p=0.53 46% 42% 29% 32% 28% 24% (N= 81) (N= 83) (N= 83) (N= 62) (N= 63) (
Slide 17: Resolution of NASH and fibrosis improvement
Dose-dependent and statistically significant results on both resolution of NASH and fibrosis improvement Secondary endpoint ITT Population (N = 247) Per Protocol Population (N = 194) p=0.001* p<0.001* % patients % patients p=0.036* p=0.017* 33% 31% 24% 21% 7% 10% (N= 81) (N= 83) (N= 83) (N= 62) (N=
Slide 18: Statistically significant decrease in liver enzymes
Statistically significant decrease in liver enzymes Other secondary endpoints in ITT (N = 247) Absolute change from baseline in ALT Absolute change from baseline in AST 10 10 Mean absolute change (UI/L) Mean absolute change (UI/L) 0 0 -10 -10 -20 ** * ** ** * ** -30 ** -20 * ** ** * ** 00 4 W4 8 12
Slide 19: Statistically significant change in HDL-cholesterol and triglycerides
Statistically significant change in HDL-cholesterol and triglycerides Other secondary endpoints in ITT (N = 247) Absolute change from baseline in HDL-C Absolute change from baseline in triglycerides 0.25 0.2 Mean absolute change (mmol/L) Mean absolute change (mmol/L) ** ** 0 0.15 ** ** * -0.2 ** 0.0
Slide 20: Reductions of fasting glucose, insulin, HbA1c in T2DM patients with NASH
Statistically significant reductions of fasting glucose and insulin, HbA1c in type 2 diabetes (T2DM) patients with NASH Secondary endpoints in T2DM patients with NASH (N = 103) Absolute change from baseline in fasting Absolute change from baseline in HbA1c glucose 0.5 Mean absolute change (%) 0.5 Me
Slide 21: Lanifibranor: a continued favorable tolerability profile (I/II)
Lanifibranor: a continued favorable tolerability profile (I/II) Safety population N = 247 Placebo 800 mg 1200 mg N (%) patients reporting Adverse Event (AE) (N = 81) (N = 83) (N = 83) Any Treatment-Emergent AE (TEAE) 50 (61.7%) 59 (71.1%) 62 (74.7%) - Drug-related TEAE 19 (23.5%) 25 (30.1%) 23 (27.7
Slide 22: Lanifibranor: a continued favorable tolerability profile (II/II)
Lanifibranor: a continued favorable tolerability profile (II/II) Safety population N = 247 Patients reporting treatment-emergent Placebo 800 mg 1200 mg Serious AE (SAE); N (%) (N = 81) (N = 83) (N = 83) Total 3 (3.7%) 3 (3.6%) 7 (8.4%) Treatment-Emergent Serious AE linked to biopsy procedure - Post-
Slide 23: Lanifibranor NATIVE results and other oral NASH drug candidates (I/II)
Lanifibranor NATIVE results and other oral NASH drug candidates (I/II) Phase II results of orally available drug candidates: NASH resolution without worsening of fibrosis 60% Placebo Active 50% 45% 40% 30% 24.7% 21.3% 19% 19.0% 20% 16.7% 13.3% 12.0% 10% 6.5% 5.0% 0% Ocaliva Aramchol Elafibranor Resm
Slide 24: Lanifibranor NATIVE results and other oral NASH drug candidates (II/II)
Lanifibranor NATIVE results and other oral NASH drug candidates (II/II) Phase II results of orally available drug candidates: fibrosis improvement without worsening of NASH(1) 60% Placebo Active 50% 42% 40% 35.3% 29.5% 28.8% 30% 24% 23.5% 19.3% 20% 17.5% 10% 0% Ocaliva Elafibranor Aramchol Resmetiro
Slide 25: Conclusion
Conclusion ► Lanifibranor (1,200 mg) met the primary endpoint with a statistically significant reduction after 6 months of treatment of the Steatosis Activity Fibrosis score (SAF), which combines assessments of hepatocellular inflammation and ballooning, with no worsening of fibrosis in the Intentio
Slide 26: Lanifibranor: NASH key milestones
Lanifibranor: NASH key milestones Finalization of Phase III synopsis and protocol: ongoing End of Phase IIb meeting with FDA: expected in Q4 2020 Scientific advice meeting with EMA: expected in Q4 2020 Finalization of Phase II trial in NAFLD patients with TD2M conducted by Pr. Cusi Launch
Slide 27: Q&A
Q&A