A secondary analysis of a phase 2a trial of rentosertib, an AI-designed TNIK inhibitor for idiopathic pulmonary fibrosis, found that patients receiving the drug showed a reduction in biological age markers across six independent proteomic ageing clocks.
- Rentosertib reduced biological age markers by 3-6 years in proteomic analysis
- Trial involved 42 patients with idiopathic pulmonary fibrosis receiving the drug or placebo
- Phase 3 trial underway to confirm lung function benefits and safety
What happened
Insilico Medicine conducted a secondary proteomic analysis of blood samples from 42 patients participating in a phase 2a trial of rentosertib, a drug designed using generative AI to target idiopathic pulmonary fibrosis (IPF). Samples taken at baseline and then at two, four, and twelve weeks into treatment were evaluated against six independently developed protein-based ageing clocks. These biological clocks consistently indicated that patients on the 30mg twice-daily dose of rentosertib appeared approximately three to four years younger biologically than expected for their chronological age, with some clocks suggesting up to six years of biological rejuvenation.
The original trial enrolled 71 patients across 21 sites in China, testing different dosages of rentosertib and monitoring safety and lung function outcomes. While the primary focus was safety, the 60mg once-daily group showed a mean forced vital capacity gain—a measure of lung function—significantly higher than placebo. Adverse events, including some liver toxicity cases, were observed. The proteomic data and analysis methods were made publicly available for validation.
Why it matters
Idiopathic pulmonary fibrosis is a progressive and fatal lung disease with limited treatments that only slow decline in lung function. A drug potentially reversing lung damage and improving biological age markers could transform patient outcomes and offer insights into systemic ageing processes. The consistent results across six aging clocks from different research groups strengthen the credibility of the biological age reduction observed.
However, the analysis carefully notes that reduced biological age signals may reflect improved lung health and reduced inflammation rather than a generalized slowing of ageing throughout the body. Proteomic ageing clocks predict mortality and age-related disease risk but are not regulatory endpoints, so further research is necessary to validate these findings beyond lung disease and establish clinical relevance.
What to watch next
The ongoing phase 3 trial of rentosertib will provide critical data on the drug’s efficacy and safety in a larger IPF patient population, mainly focusing on lung function and disease progression endpoints. Success there could establish rentosertib as a superior therapy to existing antifibrotics by demonstrating not just slowed decline but measurable lung function improvements.
Beyond this, continued exploration of proteomic and other biomarker-based ageing clocks will be essential to distinguish direct anti-ageing effects from disease-specific improvements. Independent validation and broader trials could clarify whether rentosertib or similar AI-designed therapies might contribute to extending healthy lifespan on a general level.