Insilico Medicine (HKEX: 3696) has dosed the first patient in GENESIS-IPF-3, the Phase III trial of rentosertib (ISM001-055 / INS018_055) in idiopathic pulmonary fibrosis (IPF). First dosing occurred at Peking Union Medical College Hospital on September 9, 2026, with Shanghai Pulmonary Hospital enrolling its first patient on the same day. Insilico describes rentosertib as the first drug with both an AI-identified target and an AI-generated molecule to advance into Phase III development.
The 52-week, prospective, randomized, double-blind, placebo-controlled study is designed to enroll 320 IPF patients across 47 centers in China. The primary endpoint is the annual rate of decline in forced vital capacity (FVC) over 52 weeks — the standard registrational measure in IPF. The key secondary endpoint is time to first disease progression event. Insilico said the trial is intended to determine whether the efficacy and safety signals from the earlier Phase IIa study hold in a larger cohort over a longer treatment period.
Rentosertib inhibits TNIK (TRAF2- and NCK-interacting kinase), a serine/threonine kinase implicated in fibrosis-driving pathways including Wnt, TGF-β, and NF-κB signaling. Insilico identified TNIK as a high-priority fibrosis target through its AI-powered platform, PandaOmics, which integrates multi-omics data from fibrotic tissues with aging-relevant target scoring — a target class not previously associated with IPF. The US FDA granted rentosertib Orphan Drug Designation for IPF in February 2023, and China's Center for Drug Evaluation (CDE) granted Breakthrough Therapy Designation in May 2025.
The Phase IIa GENESIS-IPF results, published in Nature Medicine in June 2025 and presented at the American Thoracic Society 2025 International Conference, provided the basis for Phase III advancement. In the 60 mg once-daily arm, patients demonstrated a mean FVC change of +98.4 mL at 12 weeks, compared with -20.3 mL in the placebo group. The study met its primary safety and tolerability endpoint, with treatment-emergent adverse event rates similar across all treatment arms. The Phase IIa enrolled 71 patients across 22 sites in China over 12 weeks — a substantially smaller and shorter dataset than the Phase III is designed to generate.