AI-designed drug shows promise in reversing biological aging markers in clinical trial

Sep 7, 2026

An analysis published in Nature Biotechnology reveals that Insilico Medicine's AI-designed drug rentosertib, originally developed for idiopathic pulmonary fibrosis, reduced biological age markers by 3 to 4 years in a 42-patient clinical trial. Six independent proteomic aging clocks consistently showed age reversal, particularly in the 30 mg twice-daily cohort. While the drug demonstrated lung function improvements, experts caution that the study cannot yet separate systemic anti-aging effects from localized lung healing, and proteomic age is not currently a recognized regulatory endpoint.

Rentosertib clinical trial results

▪The peak biological age reversal of approximately 3 to 4 years, and up to 6 years on one clock, occurred at Week 4 in patients receiving 30 mg of rentosertib twice daily.
▪The biological age analysis evaluated serum proteome profiles from 42 of the 71 participants who consented to profiling during rentosertib's Phase IIa clinical trial.
▪A study published in Nature Biotechnology on September 7, 2026, showed that the experimental drug rentosertib reduced predicted biological age across six independent proteomic aging clocks.

AI-driven drug discovery process

▪Insilico Medicine used its AI-powered target discovery platform to identify TNIK as a dual-purpose target implicated in both aging biology and idiopathic pulmonary fibrosis.
▪Insilico Medicine deposited the trial's proteomic data with the China National Center for Bioinformation and released its analysis pipelines as an open-source Python library on GitHub.
▪Insilico Medicine deployed its generative chemistry platform, Chemistry42, to design the small-molecule candidate rentosertib targeting TNIK in approximately 18 months.

Proteomic aging clock methodology

▪Researchers evaluated 2,841 proteins from patient blood samples against six independently developed proteomic aging clocks, including ProtAge, OrganAge, PAC, ipfP3GPT, and PAOPAC.
▪The study compared patient proteomic profiles with 55,319 UK Biobank profiles to validate that rentosertib reversed typical age-related protein-expression trajectories.
▪The six proteomic aging clocks used in the study utilize diverse methodologies ranging from traditional machine learning to deep learning, trained on chronological age or mortality risk.

Idiopathic pulmonary fibrosis treatment

▪Rentosertib entered a Phase III clinical trial in July 2026 to evaluate its efficacy in treating idiopathic pulmonary fibrosis.
▪In a Phase IIa trial of rentosertib for idiopathic pulmonary fibrosis, patients in the 60-mg once-daily group experienced a mean forced vital capacity improvement of +98.4 mL compared to a -20.3 mL decline for placebo.
▪Seven patients discontinued the Phase IIa trial of rentosertib due to liver toxicity, with four of those patients also taking the standard-of-care drug nintedanib.

Regulatory approval challenges

▪The published study cannot yet definitively separate slower biological aging from the localized physiological improvements of treating a diseased lung.
▪No medicines regulator currently licenses drugs based on changes in proteomic age, meaning rentosertib remains years away from regulatory approval.