Rentosertib Enters Phase III for Idiopathic Pulmonary Fibrosis

Rentosertib—also known as ISM001-055 or INS018_055—has reached pivotal Phase III testing in idiopathic pulmonary fibrosis (IPF). Insilico Medicine says it is the first drug candidate to reach this stage after generative AI was used to identify both its biological target and its small-molecule design. That is a meaningful development milestone for AI-enabled drug discovery, not evidence that the medicine works or that it will be approved. 32732

First patient dosed in GENESIS-IPF-3

Insilico reported first-patient enrollment and dosing in the GENESIS-IPF-3 trial at Peking Union Medical College Hospital in September 2026. Shanghai Pulmonary Hospital also enrolled its first patient that day. The study is listed as NCT07687459 and CTR20262475. 34

GENESIS-IPF-3 is a prospective, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial in China. It is planned to enroll 320 adults with IPF across 47 centers and follow them for 52 weeks. Its primary efficacy endpoint is the annualized rate of decline in forced vital capacity (FVC), a standard measure of lung function in IPF studies. 46

That design matters: a larger, year-long blinded comparison is intended to determine whether the earlier signal holds up and whether the safety profile remains acceptable over a clinically relevant period.

What rentosertib targets—and where AI fits

Rentosertib is an oral small-molecule inhibitor of TNIK, short for TRAF2- and NCK-interacting kinase. A 2024 Nature Biotechnology paper described the use of Insilico's generative-AI workflow to identify TNIK inhibition as a potential antifibrotic strategy and to develop INS018_055; it reported selective antifibrotic activity in mouse and rat models as well as Phase I safety and tolerability data. 27

The distinction is important. AI can prioritize targets and generate or optimize candidate structures, but laboratory experiments, manufacturing, toxicology, and human trials still determine whether a candidate becomes a medicine. The Phase III trial—not the design method—will decide whether rentosertib has demonstrated clinical value for people with IPF.

The Phase IIa result that prompted Phase III

The randomized Phase IIa study treated participants for 12 weeks. In the 60 mg once-daily group, mean FVC change from baseline was +98.4 mL; in the placebo group, it was −20.3 mL. The trial included 18 participants in the 60 mg once-daily arm and 17 in the placebo arm. 2649

Those findings were encouraging enough to justify a pivotal program, but they should be interpreted cautiously:

• The study was short—12 weeks rather than a year.
• Each dose group was small.
• A difference in mean FVC over that period does not establish sustained efficacy, an effect on survival, or superiority to other IPF treatments.

The Phase IIa publication characterized the study as a randomized, placebo-controlled evaluation of safety and efficacy; the Phase III endpoint will provide a more rigorous test of the lung-function finding. 2649

Who is leading the trial

Professor Zuojun Xu of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, is the leading principal investigator for GENESIS-IPF-3. Insilico named Academician Nanshan Zhong and Chang Chen, president of Shanghai Pulmonary Hospital, as co-leading principal investigators. 11

Xu has described TNIK as an AI-driven target not previously linked to fibrosis and framed the larger Phase III study as a way to validate the preliminary Phase IIa findings. 50

Regulatory designations and the inhaled program

Rentosertib received U.S. FDA Orphan Drug Designation for IPF in February 2023 and was included in China's Breakthrough Therapy Designation list in May 2025. These designations may support development and regulatory interactions, but they do not establish efficacy and do not guarantee approval. 47

Insilico is also developing an inhaled solution of rentosertib. China's Center for Drug Evaluation approved its investigational new drug application in 2026, allowing the inhaled formulation to enter clinical development as a separate program from the oral Phase III study. 41

What to watch next

Rentosertib's progress is a high-profile test of whether a program built with generative AI can deliver a late-stage clinical success. The immediate questions are more conventional than the technology headline: Can GENESIS-IPF-3 show a convincing reduction in annual FVC decline over 52 weeks, and can it do so with acceptable safety?

Any estimate of approval timing remains conditional. Before an application could succeed, the program would need timely enrollment and follow-up, positive pivotal results, a sufficient safety package, regulatory agreement, and manufacturing readiness. For now, rentosertib is an investigational drug in Phase III—not an approved treatment. 34