Insilico’s AI-designed IPF drug rentosertib reverses biological age by 3–6 years in Phase IIa trial

The study analysed 42 IPF patients over 12 weeks using six biological age models developed by researchers from Harvard, Oxford, Peking University, and Insilico.

All six models showed a reduction in biological age among patients treated with rentosertib. The strongest effects were seen at week four, with biological age appearing to reverse by around three to four years.

The drug also improved lung function. Patients taking 60 mg of rentosertib daily showed an average FVC improvement of 98.4 mL, compared with a 20.3 mL decline in patients who received a placebo.

Read More:Frazier & Deeter Appoints Jeremy Jacobs as Partner

Published in Nature Biotechnology, the study is the first clinical evaluation of a drug candidate that combines an AI-discovered target linked to ageing and disease with an AI-designed molecule. Unlike repurposed drugs such as rapamycin or metformin, the candidate was developed using AI from the early stages.

The findings also show how biological ageing markers could be included in clinical trials to help speed up the development of new treatments for ageing-related diseases and longevity.

Insilico Medicine used its AI platform to identify TNIK as a potential target linked to ageing, fibrosis, and idiopathic pulmonary fibrosis (IPF). TNIK showed strong links to six key ageing-related biological processes, leading the company to select it as a target for both ageing and IPF.

Insilico then used its generative AI chemistry platform, Chemistry42, to design rentosertib, a small-molecule drug candidate targeting TNIK.

The programme moved from target discovery to selecting a preclinical candidate in about 18 months. Preclinical findings were published in Nature Biotechnology in 2024.

"Six proteomic clocks from six independent groups, applied to the same 42 patients, all reported a younger biological age in the treated arms. What convinces me is not the size of the effect but the agreement, because these models share neither their features nor their training data." said Michael Levitt, PhD, 2013 Nobel Prize laureate in Chemistry.

"In this study, we evaluated clinical trial data to compare the blood proteomic profiles of pulmonary fibrosis patients treated with Rentosertib versus placebo", said Ludger Goeminne, Research Fellow in Medicine at Harvard Medical School, and co-author of the paper.

About Insilico Medicine

Founded in 2014 by Alex Zhavoronkov, Insilico Medicine is a global biotechnology company that uses artificial intelligence and automation to speed up drug discovery, advance life sciences, and support healthy longevity.

Read More:Digital Realty opens 6.4 MW Nairobi data centre as iColo rebrands