Insilico Medicine is advancing to Phase III human trials for testing a drug identified by AI targeting idiopathic pulmonary fibrosis (IPF). This progression supplies the computational drug discovery sector with empirical test cases, advancing an AI medicine past early safety evaluations into late-stage efficacy validation.

IPF destroys respiratory capacity through severe lung tissue scarring. Patients typically present a median survival rate reaching two to four years post-diagnosis. The AI-identified drug, rentosertib, inhibits the TRAF2- and NCK-interacting kinase to address underlying disease mechanisms when administered orally.

A randomised trial evaluated 71 patients across 22 Chinese clinical sites, separating participants into placebo and active treatment cohorts. Investigators administered 30 mg or 60 mg daily doses over a 12-week observation window.

Patients assigned to the 60 mg once-daily regimen demonstrated a mean forced vital capacity gain of +98.4 mL, contrasting sharply with the 20.3 mL capacity loss recorded in the placebo group. Safety profiles remained manageable, with adverse events mirroring expected baseline rates across all trial arms. Regulatory authorities at the U.S. Food and Drug Administration (FDA) granted ‘Orphan Drug Designation’ to the asset in February 2023.

Algorithmic target prioritisation through multi-omics

The development relies entirely on Pharma.AI, the proprietary computational pipeline operating at Insilico Medicine. The workflow segments into distinct engines handling specific biological and chemical engineering tasks.

PandaOmics executes the initial target discovery phase. The system ingests vast biological datasets, processing genomics, clinical trial outcomes, academic literature, and patent intelligence to construct comprehensive biological network models. The algorithms apply causal inference mechanisms to identify novel disease links hidden within the data architecture.

PandaOmics isolated TNIK as the primary biological target regarding IPF intervention. The computational system bypassed the receptor tyrosine kinase pathways targeted by existing antifibrotic medications.

The software mapped TNIK as a central node regulating fibrosis and inflammation via Wnt, TGF-β, Hippo/YAP-TAZ, JNK, and NF-κB signalling channels. The target selection process integrated a hallmarks-of-aging framework, scoring biological targets based on their implication in multiple aging mechanisms, chronic inflammation, and extracellular matrix remodelling.

Feng Ren, PhD, Co-CEO and Chief Scientific Officer of Insilico Medicine, said: “IPF is one of the clearest clinical examples of an age-related disease in which fibrosis, chronic inflammation, extracellular matrix remodeling, and cellular senescence intersect.

“Rentosertib was not discovered by starting from a conventional target and simply screening more compounds. It came from a biology-first, ageing-informed AI workflow that connected TNIK to fibrotic and inflammatory disease mechanisms, and then used generative chemistry to create a drug candidate with the properties required for clinical development.”

Read More: Insilico Medicine advances AI drug for IPF to Phase III trials