Insilico reports rentosertib Phase 2a gains

Insilico Medicine’s rentosertib story rests on a specific clinical result, not on a broad claim about artificial intelligence. In a Phase 2a trial published in *Nature Medicine* on June 3, 2025, the company and collaborators reported that patients with idiopathic pulmonary fibrosis, or IPF, who received the highest tested dose of rentosertib had a mean gain in forced vital capacity, or FVC, of 98.4 mL after 12 weeks, while the placebo group showed a mean decline of 20.3 mL. The paper also reported similar rates of treatment-emergent adverse events across active and placebo arms. That matters because the social-media version of the story has circulated with a key error. The 98.4 mL figure refers to FVC, a standard lung-function measure used in IPF studies, not FEV1, which is more commonly emphasized in obstructive lung diseases such as asthma and chronic obstructive pulmonary disease. The primary endpoint in the Phase 2a paper was safety, defined as the proportion of patients with at least one treatment-emergent adverse event. (insilico.com) ### What exactly did the Phase 2a trial test? The GENESIS-IPF study enrolled 71 patients across 22 sites in China, according to Insilico and related materials on the publication. Patients were randomized to placebo, 30 mg once daily, 30 mg twice daily, or 60 mg once daily for 12 weeks. (nature.com) The *Nature Medicine* paper described the trial as multicenter, double-blind, randomized and placebo-controlled. In the intention-to-treat population, 55 of 71 patients completed the 12-week placebo-controlled period, according to the paper summary returned in search results. ### What was the main efficacy signal? The 60 mg once-daily arm produced the clearest lung-function result. (bio-itworld.com) The paper reported a mean FVC change of +98.4 mL for that group, with a 95% confidence interval of 10.9 to 185.9 mL, compared with -20.3 mL for placebo, with a 95% confidence interval of -116.1 to 75.6 mL. Insilico’s June 2025 release said exploratory biomarker analyses supported the biological mechanism around TNIK, the target the company says it identified through its AI platform. (nature.com) The company’s rentosertib program page describes the molecule as a potentially first-in-class small molecule aimed at fibrosis-related disease by inhibiting TNIK. (nature.com) ### Did the study meet its primary endpoint? The primary endpoint was safety and tolerability, not a lung-function efficacy endpoint. The paper said the percentage of patients with at least one treatment-emergent adverse event was 72.2% in the 30 mg once-daily group, 83.3% in the 30 mg twice-daily group, 83.3% in the 60 mg once-daily group, and 70.6% in the placebo group. (insilico.com) The same paper said treatment-related serious adverse event rates were low and comparable across groups. The most common events leading to discontinuation were related to liver toxicity or diarrhea. ### Why are people calling this an AI-discovered drug? The paper and company materials make a narrower claim than many online posts. *Nature Medicine* described rentosertib as a first-in-class small-molecule inhibitor of TNIK, with the target discovered using generative AI and the molecule generated using AI-driven methods. (nature.com) Insilico says both target identification and molecular design were powered by its Pharma.AI platform. That does not by itself establish a commercial or regulatory outcome. What it does establish is that a drug Insilico says was discovered and designed with AI-generated methods produced mid-stage human data in IPF and was published in a peer-reviewed journal. ### What happens next for rentosertib? On April 28, 2026, Insilico said China’s Center for Drug Evaluation cleared an inhaled formulation of rentosertib for a Phase 1 study in healthy volunteers and IPF patients, with about 80 subjects expected to enroll. (nature.com) The company said the inhaled version is designed for direct lung delivery and lower systemic exposure. In the same April 2026 release, Feng Ren, Insilico’s co-chief executive and chief scientific officer, said the company remained on track to initiate Phase III trials for the oral rentosertib program in the second half of 2026. Insilico’s investor-relations site separately lists the April 29, 2026 voluntary announcement on the inhaled program. (insilico.com)