World's First Generative AI-Discovered Drug Enters Phase III: Insilico Doses First Patient with Rentosertib

GENESIS-IPF-3, the Phase III trial of Rentosertib (ISM001-055) in idiopathic pulmonary fibrosis (IPF), has dosed its first patient at Peking Union Medical College Hospital, with Shanghai Pulmonary Hospital enrolling its first patient the same day. The 52-week study plans to enroll 320 patients across 47 centers in China — the first drug with both an AI-identified target and an AI-designed molecule to reach Phase III.

Insilico Medicine (HKEX: 3696) announced that it has dosed the first patient with Rentosertib (also known as ISM001-055 / INS018_055) in GENESIS-IPF-3, a Phase III clinical trial, at Peking Union Medical College Hospital, while Shanghai Pulmonary Hospital enrolled its first patient on the same day.

Trial Design: 320 Patients, 47 Centers, 52 Weeks

GENESIS-IPF-3 is a Phase III trial (NCT07687459, CTR20262475) evaluating Rentosertib in patients with idiopathic pulmonary fibrosis (IPF). The 52-week, prospective, randomized, multi-center, double-blind, placebo-controlled, parallel-group study is expected to enroll a total of 320 participants across 47 centers in China. The primary endpoint is the annual rate of decline in forced vital capacity (FVC) over 52 weeks; the key secondary endpoint is time to first occurrence of any disease progression event.

The study is led by Professor Zuojun Xu of Peking Union Medical College Hospital as Leading Principal Investigator, with Academician Nanshan Zhong of the Chinese Academy of Engineering and President Chang Chen of Shanghai Pulmonary Hospital as Co-Leading Principal Investigators.

Professor Xu commented: "TNIK, the target driven by AI, had never previously been linked to fibrosis. This perhaps indicates that AI is carving out a path distinct from traditional research paradigms in target discovery for complex diseases." He noted that from initiating Phase III to final regulatory approval would take three to four years under favorable conditions.

From Phase IIa to Phase III: A Dose-Dependent Efficacy Trend

Rentosertib is a potentially first-in-class small molecule targeting TNIK, developed using generative AI. In IPF, TNIK activation drives pathological fibrosis in the lungs, contributing to progressive decline in lung function; by inhibiting TNIK, Rentosertib aims to halt or reverse fibrotic processes.

In the Phase IIa GENESIS-IPF study (results published in Nature Medicine), patients in the 60 mg once-daily arm showed a mean FVC change of +98.4 mL at 12 weeks, versus -20.3 mL in the placebo group. The study met its primary safety and tolerability endpoint. Phase III is designed to validate these efficacy and safety signals in a larger population over a longer treatment period.

R&D Efficiency and Commercial Validation

Compared with traditional paths, Rentosertib's early discovery took only 18 months and fewer than 80 molecules screened to identify the candidate. The drug has received Orphan Drug Designation from the US FDA (February 2023) and Breakthrough Therapy Designation from China's CDE (May 2025).

Insilico also reported total revenue of approximately US$106 million for H1 2026, up 287% year on year, achieving its first profitable half-year since listing with adjusted net profit exceeding US$51 million. Total contract value of transactions announced in 2026 reached approximately US$7.3 billion, pushing cumulative collaboration value since 2021 to roughly US$11 billion. As of late August, Insilico had nominated nine development candidates within the first eight months of 2026, a company record for annual pipeline productivity, alongside eight clinical milestones.