AI-designed drug for lung fibrosis passes phase 2a and enters phase 3

Insilico Medicine's rentosertib, described by its developers as a first-in-class AI-generated small-molecule inhibitor of TNIK, improved lung function against placebo in a phase 2a trial in idiopathic pulmonary fibrosis (IPF). The results were published in Nature Medicine on 3 June 2025 by Zuojun Xu of Peking Union Medical College Hospital, Alex Zhavoronkov of Insilico Medicine and colleagues ¹.

What the trial found

The GENESIS-IPF trial was a multicentre, double-blind, randomised, placebo-controlled study of 71 patients across 22 sites in China, treated for 12 weeks ². Patients received 30 mg once daily (18 patients), 30 mg twice daily (18), 60 mg once daily (18) or placebo (17) ¹.

In the 60 mg once-daily group, forced vital capacity (FVC) changed by +98.4 ml (95% confidence interval 10.9 to 185.9) over 12 weeks, against -20.3 ml (95% confidence interval -116.1 to 75.6) on placebo ¹. Treatment-emergent adverse events occurred in 72.2% of the 30 mg once-daily group, 83.3% of the 30 mg twice-daily group, 83.3% of the 60 mg group and 70.6% of the placebo group ¹. Seven patients discontinued because of liver injury or dysfunction, four of them while also taking nintedanib, and 12 of the 18 patients (67%) completed the high-dose arm, against 88% on placebo ³.

The authors list as limitations "the small cohort size of each arm, the geographical and demographic homogeneity of the participants (all were residents of China of similar race) and a short period of follow-up" ³. Alex Zhavoronkov, Insilico's founder and chief executive, said: "These results not only suggest that Rentosertib has a manageable safety and tolerability profile, but also warrants further investigation in larger-scale clinical trials" ².

The target was identified and the molecule designed with Insilico's Pharma.AI platform. The discovery history was published in Nature Biotechnology in March 2024 ².

What it means for the market

The authors note that "few novel AI-discovered or AI-designed drugs have reached human clinical trials" ¹. For pharma R&D leaders weighing generative chemistry, the evidence here is a 12-week lung-function signal in 71 patients, with a manageable but not clean safety record, and the question of clinical benefit now passes to phase 3.

On 7 July 2026 Insilico announced a phase 3 trial of 320 patients across 47 centres in China over 52 weeks, with the annual rate of FVC decline as the primary endpoint and time to first disease progression event as the key secondary endpoint ⁴. Carol Satler, Insilico's senior vice president for clinical development, non-oncology, said: "The Phase III study is designed to determine whether the safety profile and lung-function signal observed in Phase IIa can translate into clinically meaningful benefit" ⁴. The US Food and Drug Administration granted rentosertib orphan drug designation in February 2023 ⁴.

The phase 3 trial, registered as NCT07687459, started on 9 September 2026 and is recruiting, with primary completion estimated for 30 October 2029 ⁵.