Insilico rentosertib Phase 2a result

Insilico Medicine’s rentosertib result is a mid-stage readout in idiopathic pulmonary fibrosis, or IPF, a progressive lung-scarring disease with limited treatment options. The company’s Phase 2a data, published in *Nature Medicine* on June 3, 2025, came from a 71-patient randomized, double-blind, placebo-controlled study run across 22 sites in China. (insilico.com) In that trial, patients receiving the highest oral dose — 60 mg once daily — posted a mean increase of 98.4 mL in forced vital capacity, a standard measure of lung function, while placebo patients showed a mean decline of 20.3 mL over 12 weeks. Insilico has continued to point to that dataset in 2026 as it advances both oral and inhaled versions of the drug. (insilico.com) ### What exactly did the Phase 2a trial test? The GENESIS-IPF study enrolled 71 patients with idiopathic pulmonary fibrosis and assigned them to placebo, 30 mg once daily, 30 mg twice daily, or 60 mg once daily rentosertib for 12 weeks. The trial’s primary endpoint was safety and tolerability, and Insilico said those endpoints were met with similar rates of treatment-emergent adverse events across groups. (insilico.com) The drug was previously known as ISM001-055 and is now called rentosertib. Insilico describes it as a TNIK inhibitor, referring to TRAF2- and NCK-interacting kinase, the target the company says it identified with its AI platform before designing the molecule itself. ### Why is the 98.4 mL number the figure everyone is using? The 98.4 mL figure comes from the highest-dose cohort, not from the entire study population pooled together. *Nature Medicine* and Insilico’s June 2025 release both said the 60 mg once-daily arm showed the largest mean improvement in forced vital capacity, compared with a mean decline in the placebo arm. (bio-itworld.com) Forced vital capacity, or FVC, is the amount of air a person can forcibly exhale after a deep breath. In IPF trials, changes in FVC are commonly used to track whether lung function is worsening, stabilizing or improving. The topline comparison that has circulated most widely is therefore 60 mg once daily at +98.4 mL versus placebo at -20.3 mL over 12 weeks. (nature.com) ### What makes this drug unusual beyond the trial result? Insilico and its executives have framed rentosertib as an AI-discovered and AI-designed drug, meaning both the biological target and the molecule were generated through the company’s software-driven discovery process. (nature.com) Alex Zhavoronkov, Insilico’s founder and chief executive, said in the company’s June 2025 statement that the paper represented “proof-of-concept clinical validation” for that approach. The company has made that point repeatedly because many AI-drug-discovery groups have produced preclinical candidates, but fewer have reported controlled mid-stage efficacy data in patients. (nature.com) That framing is Insilico’s characterization, not an independent regulatory designation. ### Was this a China-only study, and does that matter for next steps? The 22 study sites were in China, according to the paper and company materials. Insilico has also said a U.S. Phase 2a study has been underway, with Zhavoronkov telling *GEN* in June 2025 that 22 patients had been screened and eight enrolled at that point. (insilico.com) That means the dataset most often cited today is the China Phase 2a result, while broader multinational development is still being assembled. (insilico.com) Insilico has not presented this as a pivotal trial result. ### What happens next for rentosertib? On April 28, 2026, Insilico said Chinese regulators cleared an inhaled rentosertib formulation for a Phase 1 study involving healthy volunteers and IPF patients, with about 80 subjects expected to enroll. (bio-itworld.com) The company said the inhaled program is designed to deliver the drug directly to the lungs while reducing 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 start Phase 3 trials of oral rentosertib in the second half of 2026. That timeline — along with any registration-trial design details — is the next concrete milestone investors and lung-disease specialists will be watching. (bio-itworld.com) (insilico.com)