CAMBRIDGE, Mass., Nov 13, 2024 — Insilico Medicine (“Insilico”), a clinical-stage generative artificial intelligence (AI)-driven biotechnology company, today announced positive topline results from the Phase IIa trial of ISM001-055, the novel drug candidate developed in-house using generative AI to target TNIK (Traf2- and NCK- interacting kinase) for the treatment of idiopathic pulmonary fibrosis (IPF). The results demonstrate that ISM001-055 is safe, well-tolerated, exhibits a favorable pharmacokinetics (PK) profile, and has encouraging clinical efficacy as measured by improvement in forced vital capacity (FVC) at 12 weeks.

“I am very impressed by the positive results observed in IPF patients treated with ISM001-055, particularly the encouraging improvement in FVC. It not only reflects ISM001-055’s potential to slow disease progression but also suggests its capability to stop or even reverse it,” said Zuojun Xu, M.D., Professor of Peking Union Union Medical and the principal investigator in the Phase IIa trial of ISM001-055 in IPF patients. “AI, as an advanced technology, is already playing a crucial role in many aspects of medical practice, including drug discovery and clinical research, and we expect to see the real clinical benefits it brings to patients.”

ISM001-055’s Phase IIa study (NCT05938920) was a double-blind, placebo-controlled trial that enrolled 71 patients with IPF across 21 sites in China. Patients were randomized to receive either placebo, 30 mg once daily (QD), 30 mg twice daily (BID), or 60 mg QD for 12 weeks. Key findings from the ISM001-055 Phase IIa clinical trial topline results include:

ISM001-055 was well-tolerated across all dosing groups. The majority of the drug-related adverse events were mild or moderate in severity. The most common ISM001-055-related adverse events were diarrhea (14.8%) and abnormal liver function (14.8%).

The PK profile of ISM001-055 in IPF patients was in line with the results of Phase I studies in healthy subjects with a half-life of 7-12 hours. In addition, a higher proportional exposure was observed at 60 mg QD compared with 30 mg BID.

Patients who received ISM001-055 demonstrated a dose-dependent improvement in lung function for all doses by the 12 weeks of the trial, with a 98.4 mL mean improvement in forced vital capacity (FVC) from baseline at the highest dose of 60 mg QD as compared to a mean decline in FVC change from baseline of -62.3 mL for patients in the placebo group.

Patients who received ISM001-055 also showed a similar dose-dependent trend in percent predicted forced vital capacity (ppFVC), with a 3.05% mean improvement in ppFVC from baseline at the highest dose of 60 mg QD as compared to a mean decline in ppFVC of -1.84% for patients in the placebo group.

Improvement in quality of life (QoL) and functional measures were also evaluated by change in Leicester Cough Questionnaire (LCQ) score from week 0 to week 12, with a meaningful 2-point improvement in LCQ total score in the highest dose of 60 mg QD group compared to the placebo group by week 12. The other two doses (30 mg QD and 30 mg BID) did not show meaningful improvement.

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, scarring lung disease characterized by a progressive and irreversible decline in lung function. Affecting approximately 5 million people worldwide, IPF carries a poor prognosis, with a median survival of 3 to 4 years. Current approved treatments, including antifibrotic drugs, can slow disease progression but do not stop or reverse it, leaving a significant unmet need for more effective, disease-modifying therapies.

ISM001-055 is a potentially first-in-class small molecule targeting TNIK developed utilizing generative AI. In IPF, the activation of TNIK drives pathological fibrosis in the lungs, contributing to the progressive decline in lung function. By inhibiting TNIK, ISM001-055 aims to halt or reverse fibrotic processes, offering a disease-modifying treatment for patients with IPF. Its early development was published in a Nature Biotechnology article in March 2024.

Insilico will be initiating discussions with regulatory bodies based on these encouraging results and will be pursuing a pivotal trial of ISM001-055 in IPF patients. In addition, complete Phase IIa data from this study will be presented at an upcoming medical conference and published in reputable medical journals.

“We are thrilled with the positive results from this Phase IIa clinical trial, which underscore the potential of AI to facilitate the development of innovative therapies and improve patient outcomes,” said Alex Zhavoronkov, Ph.D., Founder and CEO of Insilico Medicine. “We aim to set industry benchmarks for drug discovery and development using generative AI and commit to pioneering innovative solutions for complex medical challenges.”

Recently, Insilico announced the appointment of Dr. Carol Satler, MD, PhD, as Vice President of Clinical Development responsible for advancing the development of non-oncology programs. Dr Satler is a seasoned physician executive with over 20 years of experience across drug discovery, development, and lifecycle planning in the industry. In her new role, Dr. Satler will play a pivotal role in the further clinical validation of Insilico’s leading program ISM001-055.

In 2016, Insilico first described the concept of using generative AI for the design of novel molecules in a peer-reviewed journal, which laid the foundation for the commercially available Pharma.AI platform. Since then, Insilico has continued to integrate technical breakthroughs into the Pharma.AI platform, which is currently a generative AI-powered solution spanning biology, chemistry and clinical development. Powered by Pharma.AI, Insilico has nominated 20 preclinical candidates in its comprehensive portfolio of over 30 assets since 2021 and has received IND approval for 9 molecules.