INSILICO (03696) has announced that its lead artificial intelligence-powered investigational drug, Rentosertib (also known as ISM001-055/INS018_055), has achieved a significant clinical milestone with the first patient successfully enrolled and dosed in the Phase 3 trial (GENESIS-IPF-3) at Peking Union Medical College Hospital.
On the same day, Shanghai Pulmonary Hospital also completed enrollment of its first patient in the same study. GENESIS-IPF-3 is a Phase 3 clinical trial (NCT07687459, CTR20262475) designed to evaluate Rentosertib in patients with idiopathic pulmonary fibrosis (IPF). This prospective, randomized, multicenter, double-blind, placebo-controlled, parallel-group study spans 52 weeks and is expected to recruit a total of 320 participants across 47 clinical centers in China.
The primary endpoint of the study is the annual rate of decline in forced vital capacity (FVC) over the 52-week period, while the key secondary endpoint is the time to first occurrence of disease progression events. This trial aims to determine whether Rentosertib can deliver clinically meaningful benefits across a broader patient population and over a longer treatment duration compared with the findings from the Phase 2a study.
The Phase 3 trial is led by Professor Xu Zuojun from Peking Union Medical College Hospital as the lead investigator, with renowned respiratory expert Academician Zhong Nanshan from the Chinese Academy of Engineering and Dean Chen Chang from Shanghai Pulmonary Hospital serving as co-lead investigators.
Rentosertib is a potential first-in-class small molecule inhibitor targeting TNIK, discovered and developed through INSILICO's proprietary generative artificial intelligence platform, Pharma.AI. In IPF, activation of TNIK drives pathological fibrosis in the lungs, leading to progressive decline in pulmonary function. By inhibiting TNIK, Rentosertib aims to block or reverse the fibrotic process, offering IPF patients a treatment option with disease-modifying potential.
In the GENESIS-IPF Phase 2a clinical trial, Rentosertib demonstrated a favorable safety profile along with dose-dependent efficacy trends, establishing an industry-first milestone in validating the concept of AI-driven drug discovery. The research findings were published in the journal Nature Medicine in June 2025.
IPF is a chronic, progressive fibrotic lung disease characterized by irreversible and progressive deterioration of lung function. The condition affects approximately 5 million people globally and carries a poor prognosis, with a median survival of only 3 to 4 years. Currently approved treatments, including antifibrotic agents, can slow disease progression but cannot halt or reverse the disease process, underscoring the urgent need for more effective disease-modifying therapies.