Inventiva (IVA) TD Cowen 46th Annual Health Care Conference summary

Phase III NATiV3 trial design and expectations

• NATiV3 is designed similarly to the successful phase II NATIVE2, focusing on F2 and F3 patients, with a longer duration and a combined primary endpoint of fibrosis improvement and NASH resolution.

• Achieving a 20% placebo-adjusted effect on fibrosis would be highly competitive, potentially doubling current market effect sizes and expanding use to earlier-stage, non-diabetic patients.

• The dual endpoint is seen as a strong differentiator, offering both fibrosis and NASH resolution in the same patient, which is compelling for physicians and payers.

• Powering assumptions for NATiV3 are conservative, with over 90% power on the primary endpoint, using higher placebo and lower treatment effect estimates than phase II.

• Guidance on data timing will be narrowed after mid-year, with operational factors influencing final timelines.

Safety and tolerability profile

• A hepatic SUSAR event occurred in early 2024 in a patient with autoimmune hepatitis, but did not meet full Hy's Law criteria; enhanced monitoring was implemented.

• Ongoing safety monitoring by the DMC has not raised further concerns, and meetings occur every six months.

• Weight gain and edema are recognized tolerability issues; in phase II, 50% had no weight gain, and one-third had >5% gain, but this did not impact efficacy.

• Weight gain is considered modest and manageable, with dose adjustments possible; effect size is not dependent on weight change.

• Less than 15% of patients are on background GLP-1 or SGLT2 therapies, and subgroup data will be analyzed post-topline.

Commercial and strategic planning

• Pre-commercialization efforts include hiring a chief commercial strategy officer and expanding medical affairs to engage KOLs.

• Messaging emphasizes intra- and extrahepatic benefits, including anti-fibrotic effects, triglyceride and HDL improvement, and insulin sensitization.

• The drug is positioned as the only oral agent addressing all three NASH drivers: unhealthy adipose, glycemic control, and direct liver histology benefits.

• The diabetic NASH population is a key commercial opportunity, given the drug’s HbA1c-lowering effect and high diabetes prevalence in advanced NASH.