Inventiva (IVA) investor relations material

Phase III trial design and clinical development

• Lanifibranor is a pan-PPAR agonist developed for MASH, designed to avoid liabilities of earlier PPARs by balancing receptor activity and moderating gamma binding.

• Extensive toxicology studies required by FDA showed a favorable safety profile, enabling progression to clinical trials.

• The Phase III NATiV3 trial builds on a successful Phase IIb (NATIVE 2), using a composite primary endpoint of both NASH resolution and fibrosis improvement in the same patient over 18 months.

• The study is powered above 90% for the co-primary endpoint, with conservative assumptions and over-enrollment to account for high dropout rates.

• Patient baseline characteristics in Phase III include a higher proportion of diabetics (55%) and F3 patients, reflecting contemporary practice and increased GLP-1 use.

Market landscape and positioning

• The MASH market is at an early stage, with multiple drug classes emerging and about 375,000 F2/F3 patients as the initial target population.

• Lanifibranor is positioned as an oral therapy to be layered on top of GLP-1s, especially for F3 diabetic patients where fibrosis risk is highest.

• FGF-21s are expected to remain in the F4 segment due to pricing, administration, and safety concerns, while lanifibranor and Rezdiffra will compete in F2/F3.

• Market segmentation is based on fibrosis stage and diabetes status, with lanifibranor favored for F3 diabetics and potentially expanding as efficacy data matures.

• Prescriber focus will initially be on hepatologists and gastroenterologists, with potential expansion to endocrinologists as familiarity with PPARs grows.

Safety profile and tolerability

• Lanifibranor was designed to minimize traditional PPAR risks, with toxicology and clinical data showing reduced cancer, muscle, and kidney risks.

• Adverse events in trials show a unique profile, with muted gamma effects compared to pioglitazone, including less weight gain and edema.

• About 50% of Phase II patients did not gain weight; 20% gained 2.5–5%, and 30% gained more than 5%, but weight gain was often not recorded as an adverse event.

• Peripheral edema and heart failure signals are lower than with traditional PPARs, and the risk profile may support a differentiated label, pending FDA review.

• The drug is not a TZD and has a novel scaffold, which may help avoid class-based warnings if supported by trial data.