Inventiva SA · EURONEXT:IVA
Inventiva SA — Investor Presentation (January 2025)
50 slides from Inventiva SA's investor presentation, January 2025
Slide 1: Corporate Presentation
Corporate Presentation January 2025
Slide 2: Disclaimer
Disclaimer This presentation contains “forward-looking statements” within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, included in this presentation are forward-looking statements. These
Slide 3: Management team with extensive global experience
Management team with extensive global experience across all stages of drug development and commercialization Frédéric Cren, MA/MBA, CEO and Co-Founder Pierre Broqua, Ph.D., CSO and Co-Founder Wide expertise within the areas of R&D, marketing, Successfully managed numerous research programs strat
Slide 4: Lanifibranor well positioned to treat MASH patients with advanced fibrosis and T2D
Lanifibranor well positioned to treat MASH patients with advanced fibrosis and T2D Best in Class Oral Efficacy Data Differentiated pan-PPAR Agonist Phase IIb demonstrated 18% fibrosis placebo- adjusted improvement at 6 months Balanced pan-PPAR agonist activity, once-daily Differentiated profile that
Slide 5: Clinicians and industry have recognized the value of PPAR agonists
Clinicians and industry have recognized the value of PPAR agonists Prescriptions and M&A support the potential of this class of drugs Physicians continue to prescribe pioglitazone In 2024, the FDA liver division has approved with over 6M scrips written in 2023 in the U.S. two PPARs in PBC Pioglitazo
Slide 6: Lanifibranor: a pan-PPAR agonist with differentiated profile
Lanifibranor: a pan-PPAR agonist with differentiated profile A new chemical entity: not a fibrate, not a TZD Moderate and balanced pan-PPAR agonist activity 150 PPARα Small molecule that activates all three PPAR isoforms in humans 125 hPPARα Balanced activity across the three human PPAR isoforms
Slide 7: Balanced PPAR activity with differential binding/target engagement
Balanced PPAR activity with differential binding/target engagement Lanifibranor did not lead to the adverse events and toxicity previously seen in single/dual PPAR agonists Moderate pan-PPAR agonist activity… … that engages PPARγ differently PPARα PPARδ PPARγ Compound EC50 (nM) EC50 (nM) EC50 (nM) L
Slide 8: NATIVE Phase II Study of lanifibranor in MASH
NATIVE Phase II Study of lanifibranor in MASH
Slide 9: The Phase IIb NATIVE trial published in NEJM
The Phase IIb NATIVE trial published in NEJM Evaluated 800 and 1200mg, oral, once-daily, 247 patients 24-week treatment + 4-week follow-up Screening Double blind, randomized, placebo-controlled End of treatment Liver biopsy ITT: 247 Patients Randomized Patients Liver biopsy Placebo • Randomizati
Slide 10: Patient population (I/II)
Patient population (I/II) 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 52.2 ± 13.8 53.6 ± 12.5 White 74 (91%) 80 (96%
Slide 11: Patient population (II/II)
Patient population (II/II) 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 (UI/L) 43.3 ± 24.1 53.9 ± 43.4 43.9 ± 24.8 Gam
Slide 12: Resolution of MASH and fibrosis improvement ≥1 stage
Resolution of MASH and fibrosis improvement ≥ least 1 stage Compares favourably to other oral and injectable compounds ORAL INJECTABLE PPARs THR-β FGF-21 GLP1-RA and GLP1-RA dual agonists Lanifibranor Resmetirom** Efruxifermin Pegozafermin Semaglutide Survodutide Tirzepatide Phase II Phase III Phase
Slide 13: Fibrosis improvement ≥1 stage with no worsening of MASH
Fibrosis improvement ≥ 1 stage with no worsening of MASH Compares favourably to other oral and injectable compounds ORAL INJECTABLE PPARs THR-β FGF-21 GLP1-RA and GLP1-RA dual agonists Lanifibranor Resmetirom** Efruxifermin Pegozafermin Semaglutide Survodutide Tirzepatide Phase II Phase III Phase II
Slide 14: MASH resolution with no worsening of fibrosis
MASH resolution with no worsening of fibrosis Compares favourably to other oral and injectable compounds ORAL INJECTABLE PPARs THR-β FGF-21 GLP1-RA and GLP1-RA dual agonists Lanifibranor Resmetirom** Efruxifermin Pegozafermin Semaglutide Survodutide Tirzepatide Phase II Phase III Phase IIb Phase IIb
Slide 15: Reduction in Steatosis measured by MRI-PDFF
Reduction in Steatosis measured by MRI-PDFF Compares favourably to other oral and injectable compounds Lanifibranor Efruxifermin Pegozafermin Resmetirom* Survodutide Tirzepatide Semaglutide T2D/NAFLD T2D NASH (F2-F3) NASH (F2-F3) NAFLD NASH (F1-F3) NASH NAFLD Phase II Phase II Phase IIb Phase IIb Ph
Slide 16: Statistically significant decrease in liver enzymes
Statistically significant decrease in liver enzymes Liver biomarkers show rapid and sustained improvement 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
Slide 17: Statistically significant change in lipid profile
Statistically significant change in lipid profile Improvements in HDL-cholesterol & triglycerides without a change in LDL-cholesterol Other secondary endpoints in ITT (N = 247) * p<0.01 **p<0.001 Absolute change from baseline in HDL-C Absolute change from baseline in triglycerides SECONDARY ENDPOINT
Slide 18: Clear benefit in MASH patients with T2D, across multiple studies
Clear benefit in MASH patients with T2D, across multiple studies Significant reductions in HbA1c and fasting glucose Secondary endpoints in patients with NASH/MASH and T2D (N = 103) Absolute change from baseline in HbA1c Absolute change from baseline in fasting glucose 0.5 Mean absolute change (%) 0
Slide 19: Significant improvements in hepatic and muscular insulin sensitivity
Significant improvements in hepatic and muscular insulin sensitivity(1) Strong benefit has been observed across multiple studies LS mean absolute change from baseline LS mean absolute change from baseline to LS mean absolute change from to week 24 in week 24 in baseline to week 24 in endogenous gluc
Slide 20: Lanifibranor observed to induce a decrease in serum biomarkers
Lanifibranor observed to induce a decrease in serum biomarkers Increasing use of biomarkers to measure MASH/fibrosis in clinical practice Data from Phase IIb NATIVE clinical trial evaluating lanifibranor (800mg/day and 1200mg/day) in patients with MASH for 24 weeks lanifibranor Median relative cha
Slide 21: Lanifibranor has a favourable safety profile
Lanifibranor has a favourable safety profile 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%) Any TEAE leading to drug withdrawal 3 (3
Slide 22: A limited number of serious TEAEs occurred
A limited number of serious TEAEs occurred 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-procedural haematoma/haemorrhage - 1 (1.2%) 1 (1.2
Slide 23: Weight gain is observed in ~50% of patients
Weight gain is observed in ~50% of patients Weight changes at end of treatment (week 24) in patients treated with lanifibranor versus placebo Lanifibranor Placebo 100% N=144 N=73 84%, N=61 80% 60% 51%, N=73 33%, 40% N=48 16%, 20% N=23 11%, N=8 6%, N=4 0% Stable Moderate Weight Stable Moderate Weight
Slide 24: Weight gain comes with improvements in metabolic, cardiometabolic, or liver markers (I/II)
Weight gain comes with improvements in metabolic, cardiometabolic, or liver markers (I/II) Stable weight (≤2.5%) Moderate weight gain (2.5%-5%) Weight gain (>5%) Stable weight (≤2.5%) Weight gain (>5%) Fasting HOMA-IR ALT Mean absolute change at Week 24 from baseline Mean absolute change at Week 24
Slide 25: Weight gain comes with improvements in metabolic, cardiometabolic, or liver markers (II/II)
Weight gain comes with improvements in metabolic, cardiometabolic, or liver markers (II/II) Stable weight (≤2.5%) Moderate weight gain (2.5%-5%) Weight gain (>5%) Stable weight (≤2.5%) Weight gain (>5%) APO-C3 APO-B Mean absolute change at week 24 from baseline (μg/ml) Mean absolute change at week 2
Slide 26: Lanifibranor alone and with empagliflozin shifts towards metabolically healthy adipose tissue
Lanifibranor alone and in combination with empagliflozin leads to a shift towards metabolically healthy adipose tissue Ratio VAT/SAT, N=23 LS Mean Relative change (%) from Baseline to Week 24 10 5 2 0 -5 -5 * -10 -15 -20 -17 ** Placebo Lani Lani + Empa n= 7 n= 9 n= 7 SAT=Subcutaneous Adipose Tissue,
Slide 27: Lanifibranor has a differentiated weight gain profile relative to pioglitazone
Lanifibranor has a differentiated weight gain profile relative to pioglitazone Weight gain plateaus with lanifibranor after 24-36 weeks Lanifibranor Pioglitazone 4.0 D Weight Abs Chg +/- 95%CI Weight (kg) mean 2.3 2.4 1.9 2.1 5.0 2.0 Change from baseline (kg) 1.0 Pioglitazone 0.4 0.0 0.0 2.5 Vitamin
Slide 28: SGLT2 inhibitor empagliflozin mitigates lanifibranor weight gain
SGLT2 inhibitor empagliflozin mitigates lanifibranor weight gain Meta-analysis data suggest that GLP-1s have a similar effect when combined with PPARs Lanifibranor + empagliflozin Pioglitazone + GLP1 or SGLT2i Baseline 63-137 kg Week 24 n=9/12/10 Placebo 5 Absolute change from baseline (kg) Week 12
Slide 29: LEGEND Study of lanifibranor in Combination with SGLT2 inhibitor
LEGEND Study of lanifibranor in Combination with SGLT2 inhibitor
Slide 30: LEGEND, a study of lanifibranor in combination with empagliflozin
LEGEND, a study of lanifibranor in combination with empagliflozin Strong mechanistic rationale for combination of lanifibranor with an SGLT2 inhibitor agent Lanifibranor in Combination with the SGLT2 Inhibitor empagliflozin in patients with MASH and Type 2 Diabetes LEGEND Trial • Clinical data sugge
Slide 31: Patient population (I/II)
Patient population (I/II) Lanifibranor Lanifibranor + Parameters (unit) Placebo Total 800 mg Empagliflozin n (%) or mean ± SD N=14 N=39 N=12 N=13 Disposition 24-week completed 12 (100%) 12 (92%) 9 (64%) 33 (85%) Prematurely discontinued 0 (0%) 1 (8%) 5 (36%) 6 (15%) Demographics Female 6 (50%) 8 (62
Slide 32: Patient population (II/II)
Patient population (II/II) Lanifibranor Lanifibranor + Parameters (unit) Placebo Total 800 mg Empagliflozin mean ± SD N=14 N=39 N=12 N=13 Liver enzymes Alanine aminotransferase, ALT (UI/L) 54.0 ± 36.9 54.8 ± 40.5 38.9 ± 22.2 48.8 ± 33.7 Aspartate aminotransferase, AST (UI/L) 37.3 ± 24.8 35.2 ± 20.5
Slide 33: Primary endpoint was met
Primary endpoint was met Statistically significant reduction in HbA1c with lanifibranor alone and in combination HbA1c absolute HbA1c (%) – FAS HbA1c < 6.5% decrease ≥1% N=37 Completers, N=30 Completers, N=30 LS Mean Absolute Change from Baseline to Week 24 Percentage of responders at Week 24 Week 1
Slide 34: Insulin sensitivity was improved, consistent with other studies
Insulin sensitivity was improved, consistent with other studies Additional improvement was observed in combination with empagliflozin Insulin – FAS HOMA-IR – FAS N=37 N=37 LS Mean Relative change (%) from Baseline to Week 24 LS Mean Relative change (%) from Baseline to Week 24 Baseline 54-586 pmol/L
Slide 35: Markers of liver injury were significantly improved
Markers of liver injury were significantly improved Improvement was solely driven by lanifibranor; empagliflozin did not add any additional benefit ALT – FAS AST – FAS N=38 N=38 LS Mean Relative change (%) from Baseline to Week 24 LS Mean Relative change (%) from Baseline to Week 24 Baseline 14-163
Slide 36: Hepatic steatosis measured by MRI-PDFF was reduced significantly
Hepatic steatosis measured by MRI-PDFF was reduced significantly Improvement was observed with lanifibranor alone and in combination with empagliflozin Liver fat measured by MRI-PDFF, N=32 from Baseline at Week 24 LS Mean Relative change (%) Individual Relative changes (%) Baseline 9.7-31.4% 20 0 -5
Slide 37: Markers of inflammation and fibrosis measured by cT1 were improved
Markers of inflammation and fibrosis measured by cT1 were improved Improvement were similar with lanifibranor alone or in combination with empagliflozin Changes in Inflammation and Fibrosis measured by cT1, cT1 Absolute Reduction of >80 ms N=31 Percentage of responders at Week 24 LS Mean Absolute ch
Slide 38: HDL-C and adiponectin improved
HDL-C and adiponectin improved Improvement were similar with lanifibranor alone or in combination with empagliflozin HDL-C, N=38 Adiponectin, N=37 LS Mean Relative change (%) from Baseline to Week 24 LS Mean Fold change from Baseline to Week 24 Baseline 0.6 – 2.0 mmol/L Baseline 0.8-11.5 mg/L 20 4 1
Slide 39: SGLT2 inhibitor empagliflozin mitigates lanifibranor weight gain
SGLT2 inhibitor empagliflozin mitigates lanifibranor weight gain Meta-analysis data suggest that GLP-1s have a similar effect when combined with PPARs Lanifibranor + empagliflozin Pioglitazone + GLP1 or SGLT2i Baseline 63-137 kg Week 24 n=9/12/10 Placebo 5 Absolute change from baseline (kg) Week 12
Slide 40: Lanifibranor alone and with empagliflozin shifts towards metabolically healthy adipose tissue
Lanifibranor alone and in combination with empagliflozin leads to a shift towards metabolically healthy adipose tissue Ratio VAT/SAT, N=23 LS Mean Relative change (%) from Baseline to Week 24 10 5 2 0 -5 -5 * -10 -15 -20 -17 ** Placebo Lani Lani + Empa n= 7 n= 9 n= 7 SAT=Subcutaneous Adipose Tissue,
Slide 41: Lanifibranor for the Treatment of MASH
Lanifibranor for the Treatment of MASH
Slide 42: MASH with advanced fibrosis represents a high unmet medical need
MASH with advanced fibrosis represents a high unmet medical need Patients with MASH and type 2 diabetes are at higher risk MASH U.S. Prevalence and Progression Estimates by Fibrosis Stage Millions 30.0 (US, 2030) 27.0 3.1 25.0 ► 22% of patients with F3 fibrosis 9.0 liver-related mortality 20.0 progr
Slide 43: Lanifibranor is well-positioned in the MASH market
Lanifibranor is well-positioned in the MASH market Multiple competitive advantages vs. other therapies pan-PPAR THR-β FGF-21 GLP-1 Route of administration Oral Oral Injectable Injectable Indirect Direct activity Indirect Direct activity seen with sema. after 18 Fibrosis improvement seen at 6 months
Slide 44: Lanifibranor could play a key role in several high unmet need segments in MASH
Lanifibranor could play a key role in several high unmet need segments in MASH Priority patient segment based on KOL feedback at time of lanifibranor launch F2 (~25%) F3 (~27%) F4cc (~10%) “Lean” Pan-PPAR agonists have strong MASH antifibrotic and insulin sensitivity (~10%) THR-β FGF21 profile, and
Slide 45: Lanifibranor: well positioned in MASH, especially in patients with T2D
Lanifibranor: well positioned in MASH, especially in patients with T2D Based on patient type, can be used as a monotherapy or in combination with anti-diabetic agents Lanifibranor Profile Improvements Superior fibrosis improvement to RezdiffraTM* Comprehensive observed in Oral dosing differentia
Slide 46: NATiV3 Phase III Study of lanifibranor in MASH
NATiV3 Phase III Study of lanifibranor in MASH
Slide 47: NATiV3 recruitment is nearly complete
NATiV3 recruitment is nearly complete Trial design mirrors the successful Phase IIb study Main Cohort Accelerated 72 weeks treatment Approval N~ 950 Lanifibranor: 1200 mg once daily Non-cirrhotic MASH & Lanifibranor: 800 mg once daily F2-F3 fibrosis Active Treatment Extension Trial Placebo: Once dai
Slide 48: Baseline characteristics of NATiV3 versus NATIVE Phase IIb are aligned with expectations
Baseline characteristics of NATiV3 versus NATIVE Phase IIb are aligned with expectations Status September 10, 2024 Exploratory Main Randomized NATIVE Exploratory Main Randomized NATIVE N=261 N=798 N=1059 N=247 N=261 N=798 N=1059 N=247 Actual N 259 795 1054 247 Weight (kg) N 261 798 1059 247 Diabet
Slide 49: NATiV3 data is expected in 2026
NATiV3 data is expected in 2026 Lanifibranor could be the second oral liver-directed agent for the treatment of MASH if approved Targeted timeline for anticipated catalysts 2025 2026 2027 2028 Lanifibranor H1 2025 H2 2026 2027 Last Patient Last Patient New Drug Randomized Last Visit and Approval fil
Slide 50: Contacts
Contacts Inventiva Brunswick Westwicke, an ICR Company Pascaline Clerc Tristan Roquet Montégon Patricia L. Bank Executive VP Aude Lepreux Investor relations Strategy and Corporate Affairs Julia Cailleteau Media relations [email protected] [email protected] patti.bank@icr