What is the problem?
Idiopathic pulmonary fibrosis (IPF) is an age-related disease: lung tissue scars and stiffens, and breathing gets harder and harder. The authors point out that no current therapy reverses the course of the disease.
Meanwhile, despite much progress in AI for chemistry, few AI-designed drugs have reached human trials. This trial is presented as the first randomised phase 2a trial of such a drug.
IPF is described as progressive, and the authors stress there is no therapy that reverses its degenerative course.
What did the researchers do?
They tested rentosertib, a small molecule that blocks a protein called TNIK, a target discovered with generative AI. The trial was multicentre, double-blind (neither patients nor doctors knew who got what) and placebo-controlled.
Four groups were formed: 30 mg once a day (18 patients), 30 mg twice a day (18), 60 mg once a day (18) and placebo (17), for 12 weeks. The main goal was safety.
Secondary goals included how the drug moves through the body (pharmacokinetics), lung function measures such as forced vital capacity and the lung's ability to transfer carbon monoxide, a cough questionnaire score, walking distance over 6 minutes, and the number and length of hospital stays for acute flare-ups. The trial is registered as NCT05938920.
What were the results?
At least one adverse event occurred in 72.2%, 83.3% and 83.3% of patients depending on the dose, and in 70.6% of those on placebo. Serious treatment-related events were rare and similar across groups; the most common reasons for stopping were liver toxicity or diarrhoea.
For breathing, forced vital capacity (the volume of air you can blow out with force) rose by 98.4 ml on average in the 60 mg a day group, against a fall of 20.3 ml on placebo. The confidence intervals are wide.
The authors say these results suggest that targeting TNIK is safe and well tolerated and warrants larger trials of longer duration. The confidence interval for the placebo change (-116.1 to 75.6 ml) includes zero, so the two groups cannot be told apart with certainty.
Key figures
- +98.4 mlforced vital capacity at 60 mg a day, against -20.3 ml on placebo
- 70.6% vs 72.2 to 83.3%of patients with at least one adverse event, on placebo and on rentosertib
- 12 weeksof treatment in this phase 2a trial
What does this change for patients?
It is an encouraging first signal: the drug seems well tolerated and first signs on lung function are favourable, though not yet proven. The authors conclude it deserves larger and longer trials.
It is not an available treatment, and nothing yet proves it brings a lasting benefit.
A first-in-class target means a protein that no approved drug has aimed at before, so this trial also tests the idea itself.
What are the limits?
With 17 to 18 patients per group over 12 weeks, the trial is small and short. The changes in breathing could partly be down to chance: the confidence interval for the 60 mg group runs from 10.9 to 185.9 ml.
The liver and the gut need watching, since they were the main reasons for stopping. Only phase 3 trials can say whether rentosertib really helps patients.
Because the main goal was safety, the trial was not designed to prove that the drug works.
Clinical trials: talking about them with your doctor, with Mima
Rentosertib is not an approved medicine. It is at a phase 2a trial, a first signal to be confirmed by larger studies. It reminds us that tomorrow's treatments go through trials.
If your lung condition worries you, Mima helps you note your breathlessness day by day and prepare your questions. A question to ask: "Is there a clinical trial I could take part in?"
Frequently asked questions
What is rentosertib?
It is a small molecule that blocks the protein TNIK, a target discovered and designed with the help of generative AI. It is being tested against idiopathic pulmonary fibrosis.
Does this AI-designed drug work?
In this 12-week trial it was generally well tolerated and forced vital capacity rose at 60 mg a day. The trial is small, so effectiveness remains to be confirmed.
What is idiopathic pulmonary fibrosis?
It is an age-related lung disease in which lung tissue gradually stiffens, making breathing harder.
What is a phase 2a trial?
It is an early test in patients that mostly checks safety and looks for first signs of benefit before larger trials.
The original study
Xu Z, Ren F, Wang P, Zhavoronkov A, et al. “A generative AI-discovered TNIK inhibitor for idiopathic pulmonary fibrosis: a randomized phase 2a trial.” Nature Medicine, 3 June 2025. DOI : 10.1038/s41591-025-03743-2
Read the full study in Nature MedicineThis article summarises a scientific study and is not medical advice.