GENESIS-IPF-3: the Phase III trial

GENESIS-IPF-3 is the first Phase III trial of rentosertib. It began dosing participants in September 2026, plans to enrol 320 people at 47 centres, and is expected to run until October 2029. Every centre is in China.

The design

The trial is registered as NCT07687459 with ClinicalTrials.gov and as CTR20262475 in China. It compares rentosertib tablets taken once daily against a matching placebo over 52 weeks. It is quadruple-blind, meaning participants, the doctors treating them, the investigators and the people analysing the data all remain unaware of who is taking which.

Insilico Medicine has not disclosed the dose, although 60 mg once daily was the only dose in the Phase 2a trial whose lung function result excluded zero.

As in the Phase 2a trial, people already taking an antifibrotic medicine such as nintedanib or pirfenidone may continue it, provided the dose is stable. So the trial asks whether adding rentosertib to existing treatment does more than adding a placebo to it.

Who can take part

The registry entry sets the main criteria as being aged 40 or over, having a confirmed diagnosis of IPF, and having a forced vital capacity (FVC), a measure of how much air you can breathe out, of at least 45% of the value predicted for someone of the same age, sex and height. Stable use of an existing antifibrotic is permitted.

Recruitment is at 47 centres in China only.

What it is measuring

The primary endpoint is the annual rate of decline in FVC over 52 weeks. In plain terms: everyone with IPF loses lung capacity over time, and the trial is asking whether people taking rentosertib lose it more slowly than people taking placebo. This is the same measure regulators have accepted for nintedanib, pirfenidone and nerandomilast. It is a different question from the one the Phase 2a trial appeared to answer, which was whether FVC rose over 12 weeks.

The key secondary endpoint is time to first progression event, which combines things like a substantial drop in lung function, an acute flare-up of IPF, hospital admission for a lung problem, or death, and records how long it takes before the first of them happens.

Other secondary measures include: changes on HRCT, a detailed CT scan of the lungs analysed by computer to quantify how much scarring there is; the King’s Brief Interstitial Lung Disease questionnaire (K-BILD) and the Living with Pulmonary Fibrosis questionnaire (L-PF), both of which ask people how their symptoms affect daily life; and DLCO, a measure of how well oxygen passes from the lungs into the blood. Blood proteins and the bone markers P1NP and CTX are also being collected.

Who is running it and when

The lead investigators are Professor Zuojun Xu of Peking Union Medical College Hospital, who also led the Phase 2a trial, Academician Nanshan Zhong, and President Chang Chen.

Insilico announced the trial on 7 July 2026. The first participant was dosed on 10 September 2026 at Peking Union Medical College Hospital, with Shanghai Pulmonary Hospital dosing on the same day. The estimated completion date is 30 October 2029.

Professor Xu has estimated that approval could follow 3 to 4 years after the Phase III start, under favourable conditions. That is his estimate, it assumes the trial succeeds, and it refers to Chinese approval. It says nothing about the UK.

What was announced earlier and did not happen

In June 2025, Insilico’s chief executive Alex Zhavoronkov described two late-stage studies due to start in the fourth quarter of 2025: a US Phase 2b of more than 200 people, and a China Phase III of more than 500. Neither materialised as described. The US Phase 2b was never registered and has not been mentioned since. The China Phase III became this 320-person trial.

The Phase 2a authors also said drug-interaction studies were needed. None has been registered.

Why the Phase 2a safety findings matter

Two signals from the Phase 2a trial will be watched closely over 52 weeks.

The first is the liver. Seven of the 12 people who stopped the Phase 2a trial because of a side effect did so with liver injury or abnormal liver function, at rates of 22.2% in the 30 mg twice-daily group and about 17% in the 60 mg once-daily group. All resolved on stopping. A 12-week trial cannot show what happens after a year of continuous dosing.

The second is acute exacerbations, sudden severe worsenings of IPF. There were 3 in the 60 mg once-daily group against 1 on placebo, and all four people were hospitalised, for an average of 23.3 days. The numbers are far too small to be conclusive either way.

There is a recent precedent for why this matters. Bexotegrast, an integrin inhibitor from Pliant Therapeutics, showed a 12-week FVC increase of 72 mL at its 160 mg dose. Its Phase 2b/3 trial, BEACON-IPF, was halted by its safety monitoring board in March 2025 and the programme was discontinued in June 2025, because of an imbalance in IPF progression events, exacerbations, hospital admissions and deaths. It was the first late-stage IPF trial stopped for safety while showing a lung function benefit, and it is the closest available parallel to rentosertib’s combination of an FVC signal with an adverse-event imbalance.

Whether rentosertib follows that path or not will not be known until this trial reports, which on current timelines means 2029 at the earliest.