Insilico Medicine is set to advance its lead drug candidate, ISM001-055, into a potentially pivotal Phase IIb study for idiopathic pulmonary fibrosis (IPF) following positive topline results from a Phase IIa trial. The AI-driven drug demonstrated encouraging clinical efficacy and a favorable safety profile in IPF patients.
The topline data revealed that ISM001-055 improved the forced vital capacity (FVC) of IPF patients 12 weeks post-dosing. The drug also exhibited a favorable pharmacokinetics (PK) profile and was well-tolerated.
Phase IIa Trial Results
The Phase IIa trial, conducted across 21 sites in China (NCT05938920), enrolled 71 IPF patients in a double-blind, placebo-controlled study. Participants were randomized to receive either placebo, 30 mg once daily (QD), 30 mg twice daily (BID), or 60 mg QD for 12 weeks.
Insilico reported that patients receiving ISM001-055 showed dose-dependent improvement in lung function. The most significant results were observed in the 60 mg QD group, with a 98.4 mL mean FVC improvement from baseline, compared to a 62.3 mL mean decline in FVC in the placebo group. Patients in the 60 mg QD group also showed a 3.05% mean improvement in percent predicted forced vital capacity (ppFVC) from baseline, while placebo patients showed a negative 1.84% mean decline.
Furthermore, patients receiving the 60 mg QD dose showed a meaningful two-point improvement in Leicester Cough Questionnaire (LCQ) score compared to the placebo group by week 12, indicating improvement in quality of life (QoL) and functional measures.
Planned Pivotal Trial
"Insilico will very soon be initiating discussions with regulatory bodies based on these encouraging results and will be pursuing a potentially pivotal trial of ISM001-055 in IPF patients," said Insilico founder and co-CEO Alex Zhavoronkov, PhD.
The planned global Phase IIb trial is expected to enroll 90 patients in each of three arms—approximately 270 total—to assess ISM001-055 over longer treatment periods than the Phase IIa study. The company anticipates potentially starting the trial by the second half of 2025.
Ongoing U.S. Trial
In addition to the Phase IIa study in China, Insilico is also conducting a U.S. Phase IIa trial (NCT05975983) of ISM001-055, which is currently enrolling patients. This study aims to enroll a total of 60 patients and is estimated to achieve primary completion in February 2026. "Enrollment in the U.S. has the likely potential to speed up with these positive Phase IIa China results," Zhavoronkov noted.
About ISM001-055
ISM001-055 is an internally developed drug candidate created using generative AI. It targets Traf2- and NCK- interacting kinase (TNIK), a serine/threonine kinase crucial in cellular processes involved in fibrosis development. Insilico utilized its AI platform, Pharma.AI, to identify TNIK as a novel target and design the small molecule structure of ISM001-055.
TNIK's Role in Fibrosis and Aging
Research indicates that TNIK regulates major signaling pathways implicated in IPF and other fibrotic conditions. TNIK inhibition is connected to biological processes important for fibrosis progression, such as focal adhesion signaling, myofibroblast differentiation, and mesenchymal cell migration. Recent studies also suggest TNIK inhibition could potentially treat age-related diseases, including cancer, metabolic disorders, and neuronal dysfunction.
