Insilico Medicine has dosed the first patient in GENESIS-IPF-3, a Phase III clinical trial evaluating the efficacy and safety of Rentosertib, a generative AI-designed investigational drug for idiopathic pulmonary fibrosis (IPF).
The first patient was dosed at Peking Union Medical College Hospital, while Shanghai Pulmonary Hospital enrolled its first patient on the same day.
Rentosertib, also known as ISM001-055 or INS018_055, is a small-molecule inhibitor of TNIK (Traf2- and Nck-interacting kinase) developed using generative artificial intelligence (AI). TNIK activation is implicated in the development of pathological fibrosis in the lungs, contributing to progressive loss of lung function. By targeting TNIK, Rentosertib aims to halt or reverse fibrotic processes, offering a disease-modifying treatment for patients with IPF.
The US Food and Drug Administration granted Rentosertib Orphan Drug Designation for IPF in February 2023.
The Phase III study is a prospective, multicentre, randomised, double-blind, placebo-controlled, parallel-group trial designed to evaluate the efficacy and safety of once-daily Rentosertib over 52 weeks.
The trial is led by Professor Zuojun Xu of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, as the leading principal investigator. Academician Nanshan Zhong of the Chinese Academy of Engineering, a respiratory medicine specialist, and Chang Chen, president of Shanghai Pulmonary Hospital, are serving as co-leading principal investigators.
Prof. Xu said, “Dosing the first patient marks another key clinical milestone for Rentosertib; after preliminary findings in the 12 week duration phase IIa study showed promising results, including improvements in lung function among patients with idiopathic pulmonary fibrosis (IPF). This Phase III study is designed to validate the phase IIa study findings in a larger cohort of idiopathic pulmonary fibrosis patients treated for a longer duration of 52 weeks.”
Xu said it will take three to four years from initiating Phase III to obtaining final regulatory approval, under favourable conditions.
Carol Satler, senior vice-president, Clinical Development, Non-Oncology, at Insilico Medicine, said she believes Rentosertib could be transformative for patient care in the field of IPF, noting that “AI has enabled this breakthrough with higher speed and reduced cost, which could make a lot of difference in the future of drug discovery.”
Idiopathic Pulmonary Fibrosis is a chronic, progressive lung disease characterised by scarring of lung tissue and a decline in lung function. It affects an estimated five million people worldwide and has a poor prognosis, with median survival reported at three to four years. Current approved treatments, including antifibrotic drugs, can slow disease progression but do not stop or reverse it, leaving a significant unmet need for more effective, disease-modifying therapies.
The GENESIS-IPF-3 trial is expected to enrol 320 patients across 47 centres in China. The primary endpoint is the annual rate of decline in forced vital capacity (FVC) over 52 weeks.
The key secondary endpoint is the time to the first occurrence of a disease progression event. The study will assess whether Rentosertib can demonstrate a clinically meaningful benefit in a larger patient population and over a longer treatment period than was evaluated in the Phase IIa study.
The initiation of the Phase III trial marks a further development milestone for Rentosertib. However, the drug remains investigational and has not been approved by any regulatory authority.
