Inventiva updates on NATiV3 clinical program for lanifibranor in MASH/NASH and financial status

Inventiva, a clinical-stage biopharmaceutical company specializing in the development of oral small molecule therapies for metabolic dysfunction-associated steatohepatitis (MASH/NASH) and other diseases with unmet medical needs, has provided updates on its clinical program for lanifibranor and its financial status.

Frederic Cren, Chairman, CEO, and co-founder of Inventiva, expressed optimism about the recruitment progress in the Phase III clinical trial, NATiV3. The trial continues to see strong engagement from clinical sites. Notably, the patient characteristics in the main cohort of NATiV3 mirror those in the previous Phase IIb trial. Importantly, data suggests that weight gain plateaus between weeks 24 and 36 of treatment, highlighting the potential of lanifibranor compared to single PPAR gamma compounds like pioglitazone. Cren emphasized lanifibranor’s differentiated profile and potential to address the broad spectrum of MASH/NASH, further supported by recent data presented at the EASL Liver Congress. Inventiva is actively evaluating financing options to sustain its activities and advance lanifibranor to market, aiming to provide a new treatment for MASH patients.

Recruitment for NATiV3 is progressing well, with screening ongoing at 347 sites in 19 countries. As of July 5, 2024, 1,027 patients have been randomized, with 784 in the main cohort, meeting 82% of the target. North America and Western Europe are leading in patient recruitment, contributing 67% and 21% respectively, while China has made a minor contribution of 2%. The exploratory cohort has surpassed its target with 243 patients randomized, yet recruitment will continue until the main cohort is complete.

Given the current screening numbers, Inventiva estimates needing an additional 165 patients for the main cohort. Despite a recruitment delay of 3 to 5 months, the company targets the last patient visit for the second half of 2024 and expects topline results by early 2026.

The baseline characteristics of patients in the main cohort align with those from the NATIVE Phase IIb trial. Notably, 13% of patients were on a stable dose of GLP1 receptor agonist and 9% on SGLT2 inhibitors at baseline. This could provide insights into the benefits of combining these treatments with lanifibranor.

A blinded review of 780 patients in the main cohort indicates similar weight gain patterns observed in the NATIVE Phase IIb trial, stabilizing after 24 to 36 weeks. This suggests a unique profile for lanifibranor, particularly compared to single PPAR gamma compounds like pioglitazone.

Inventiva continues to strengthen its patent portfolio, currently comprising 20 patent families directed at various aspects of lanifibranor, including product, treatment method, combination therapy, and diagnostics. The patent family for crystalline forms of lanifibranor is expected to extend the product’s protection until at least 2043.

Financially, Inventiva estimates that its cash, cash equivalents, and deposits will fund operations through the second half of July 2024. As of May 31, 2024, the company reported €9.6 million in cash and cash equivalents, €0.1 million in short-term deposits, and €10 million in long-term deposits. To finance ongoing activities and development goals, Inventiva is exploring additional funding options, including debt and equity instruments. A royalty-based financing deal is anticipated to extend the company's cash runway through mid-2024, although further funds will be required.

Lanifibranor, Inventiva’s lead candidate, is unique in its ability to activate all three PPAR isoforms, showing a favorable tolerability profile in trials. It has received Breakthrough Therapy and Fast Track designation from the FDA for MASH/NASH treatment. The NATiV3 trial, conducted across 24 countries, aims to recruit 900 patients to assess lanifibranor’s effects over 72 weeks, with results expected by mid-2026.

Inventiva remains dedicated to developing lanifibranor and exploring additional therapeutic opportunities, backed by a highly experienced scientific team and an extensive library of pharmacologically relevant molecules. The company continues to advance its pipeline and explore strategic options to bolster its financial standing.