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

Phase III NATiV3 trial design and expectations

• NATiV3 is modeled after the successful phase II NATIVE2 trial, focusing on a combined primary endpoint of fibrosis improvement and NASH resolution, with readout expected later this year.

• The trial excludes F1 patients, includes F2 and F3, and has a longer duration than phase II, aiming for a strong competitive profile if similar or better results are achieved.

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

• The trial is powered conservatively at over 90% for the primary endpoint, using higher placebo and lower treatment effect assumptions than phase II.

• Guidance on data timing will be narrowed after the midpoint of the 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; monitoring was increased and no further major safety issues have arisen.

• The Data Monitoring Committee meets every six months, with no significant safety concerns reported since the event.

• Weight gain and edema are known tolerability issues; in phase II, 50% had no weight gain, 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 GLP-1 or SGLT2 therapies, and subgroup data will be included in future analyses.

Commercial and market strategy

• Pre-commercialization efforts include hiring experienced leadership and expanding medical affairs to engage KOLs and prepare for market access.

• Differentiation is based on intra- and extrahepatic effects, including anti-fibrotic action, triglyceride and HDL improvement, and insulin sensitization.

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

• Market research is ongoing, with a focus on both diabetic and non-diabetic NASH populations, and commercial strategy will adapt based on upcoming data.