Insilico Medicine begins late-stage testing of Rentosertib, an oral medication targeting lung scarring and inflammation.
RT’s Three Key Takeaways:
- Late-stage clinical milestone: Insilico Medicine has initiated a Phase III clinical trial for Rentosertib, an oral medication discovered using artificial intelligence to treat idiopathic pulmonary fibrosis (IPF).
- Novel therapeutic target: The drug inhibits the TNIK protein, which is linked to the signaling pathways that drive lung scarring, chronic inflammation, and cellular aging.
- Phase IIa clinical data: Previous study results indicated that patients receiving a 60 mg daily dose of the drug experienced improved lung function compared to those who received a placebo.
Insilico Medicine has started a Phase 3 clinical trial for Rentosertib, an oral small-molecule inhibitor designed to treat idiopathic pulmonary fibrosis (IPF), according to the company.
Rentosertib targets TNIK, a kinase involved in fibrotic and inflammatory pathways. The program is the first from the company’s Ai-driven pipeline to reach late-stage clinical testing. The USFDA previously granted the drug orphan drug designation in February 2023.
“Rentosertib was not discovered by starting from a conventional target and simply screening more compounds,” said Feng Ren, PhD, co-ceo and chief scientific officer of Insilico Medicine. “It came from a biology-first, aging-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.”
IPF is a chronic lung disease characterized by progressive scarring that makes breathing difficult. It affects approximately 5 million people worldwide and has a median survival rate of two to four years after diagnosis, according to the news release. While current antifibrotic therapies can slow the progression of the disease, they do not reverse its course.
The Phase III study is a randomized, double-blind, placebo-controlled trial expected to enroll 320 patients across 47 centers in China. Researchers will evaluate the efficacy and safety of once-daily Rentosertib over a 52-week period. The primary endpoint is the annual rate of decline in forced vital capacity (FVC).
The decision to move to Phase III follows results from a Phase IIa study involving 71 patients. In that trial, patients in the 60 mg once-daily arm showed a mean FVC change of +98.4 mL at 12 weeks, while the placebo group saw a decline of 20.3 mL, according to the company.
“The Phase IIa results gave us the confidence to advance Rentosertib into larger and longer clinical testing,” said Carol Satler, MD, PhD, senior vice president for clinical development, non-oncology at Insilico Medicine. “The Phase III study is designed to determine whether the safety profile and lung-function signal observed in Phase IIa can translate into clinically meaningful benefit for patients with IPF.”
Professor Zuojun Xu, leading principal investigator of the study from Peking Union Medical College Hospital, noted that researchers observed a dose-dependent efficacy trend in the earlier trial.
“For the Phase III study at a larger scale with longer duration, we look forward to enhanced collaboration across all parties regarding study standards, risk mitigation, and cross-center data consistency, so as to realize an objective and comprehensive evaluation of Rentosertib, benefiting patients in need,” said Xu.
The drug remains investigational and has not yet been approved by any regulatory authority for use in healthcare settings.
