Insilico Medicine published a paper on Sept. 7 in Nature Biotechnology titled Integration of proteomic aging clocks in a phase 2a clinical trial supports simultaneous geroprotective assessment, reporting that six independently developed proteomic aging clocks all showed lower biological age readings in blood samples from 42 patients with idiopathic pulmonary fibrosis.
The largest change appeared in the 30 mg twice-daily arm. According to the paper, biological age in that group moved back by about three to four years at week four, and one clock showed a six-year reversal. The study described this as the first time multiple proteomic aging clocks had been compared within a clinical trial involving a drug intervention.
Insilico Medicine founder Alex Zhavoronkov said on X that this was the most important paper of his career so far. He also said the study was first presented on Sept. 8 at a Nature conference at Sorbonne University in Paris.
AI was used to choose the target and generate the molecule
The drug candidate is called rentosertib. Its starting point was a protein known as TNIK. Insilico said it used its PandaOmics platform to scan gene, protein, disease and aging data, and TNIK matched six items on its aging-feature list while also being linked to pulmonary fibrosis, leading the company to select it as the target.
After that, a second system, Chemistry42, generated molecular structures. Chemists then selected several computer-generated candidates for laboratory testing.
Earlier clinical data highlighted lung function, not aging clocks
This development path had already produced clinical data before the new paper. A Nature Medicine paper published on June 3, 2025, said 128 people were screened and 71 were randomized into four groups: 30 mg once daily, 30 mg twice daily, 60 mg once daily and placebo, for 12 weeks.
In that study, forced vital capacity increased by an average of 98.4 mL in the 60 mg once-daily group, while the placebo group fell by 20.3 mL. The source text said idiopathic pulmonary fibrosis currently has no drug that can reverse disease progression, making an increase in lung capacity itself an unusual result. It also said the Chinese post circulating earlier was actually referring to the Nature Medicine paper.
The best lung-function arm was not the same as the best aging-clock arm
The two papers did not point to the same dose group as the strongest performer. The clearest improvement in lung function came from the 60 mg once-daily group, while the largest reversal in biological age appeared in the 30 mg twice-daily group. As presented in the source, if the drop in biological age were only a byproduct of better lung function, the strongest signal would be expected to show up in the same arm.
The six clocks used in the analysis were ProtAge, two versions of OrganAge, PAC, ipfP3GPT and PAOPAC. Michael Levitt, who won the 2013 Nobel Prize in Chemistry, said what persuaded him was not the size of the effect but the consistency across the models, because they shared neither features nor training data.
The paper also spells out the limits and safety issues
The authors were explicit about the study’s limitations. At this stage, the trial cannot distinguish between slower aging and an effect driven by improved lung disease. The 42 patients included in the aging-clock analysis were only the subset of the 71-patient trial who had blood samples available, so the work was exploratory. The official press release also did not provide p-values or confidence intervals.
On safety, 16 of the 71 phase 2 participants discontinued treatment. The most common reasons for discontinuation were hepatotoxicity and diarrhea.
Phase 3 has started in China with a 320-patient target
Rentosertib received U.S. Food and Drug Administration orphan drug designation in February 2023. A phase 3 trial started in China on July 7, 2026, across 47 centers, with a planned enrollment of 320 patients and a 52-week treatment period. The primary endpoint is the annual rate of decline in lung capacity.
The principal investigator is Xu Zhuojun of Peking Union Medical College Hospital. Zhong Nanshan of the Chinese Academy of Engineering and Chen Chang of Shanghai Pulmonary Hospital are serving as co-deputy principal investigators.
The source text said the 52-week phase 3 study is four times as long as the 12-week phase 2 trial and should also generate more blood samples that can be used to repeat this kind of analysis. Whether biological age changes track with improved lung function may not be clearer until then.
Company background and listing details
Insilico Medicine was founded in 2014 and listed in Hong Kong on Dec. 30, 2025, under stock code 3696. Its IPO was priced at HK$24.05 per share and opened at HK$35. Cornerstone investors included Eli Lilly, Tencent and Temasek.
According to the company’s own description, it has nominated 31 preclinical drug candidates, 13 of which have received clinical trial clearance, while eight are in phase 1 studies.
What the paper does and does not answer
As described in the source, rentosertib is an oral small-molecule inhibitor for idiopathic pulmonary fibrosis, with TNIK identified through PandaOmics and the molecular structure generated through Chemistry42. As for the claim that biological age moved back by three to four years, the result currently rests on an exploratory analysis of 42 patients. The paper says the trial cannot yet tell whether aging slowed or whether the finding reflects treatment of lung disease, while Levitt said the agreement across six different models was more convincing than the effect size alone.