Insilico Medicine plans to push its computer-designed drug into pivotal clinical trials after a phase 2a study demonstrated improvements in a respiratory health measure for patients with idiopathic pulmonary fibrosis (IPF).
The study centers around Insilico’s ISM001-055, a small molecule developed using generative AI to target TNIK (Traf2- and NCK- interacting kinase). The midstage trial enrolled 71 patients across 21 sites in China, with patients randomized to receive either placebo, 30 mg of ISM001-055 once daily (QD), 30 mg twice daily (BID) or 60 mg once a day for three months.
The top-line results reveal a dose-dependent improvement in an efficacy endpoint measuring the change in forced vital capacity (FVC) at 12 weeks, according to a Nov. 12 release shared with Fierce Biotech. FVC is a common measure of respiratory health that quantifies the maximum amount of air a person can let out after inhaling deeply.
Patients who received 60 mg of ISM001-055 once daily saw a 98.4 mL mean improvement in FVC compared to baseline, versus a mean decline of -62.3 mL for participants receiving placebo.
ISM001-055 was found to be safe and well tolerated, according to Insilico. The study’s main endpoint measured the percentage of patients with at least one treatment-emergent adverse event, according to ClinicalTrials.gov. Specific data were not shared in the Nov. 12 release.
The company did say that “the majority of the drug-related adverse events were mild or moderate in severity,” with diarrhea (14.8%) and abnormal liver function (14.8%) being the most common ISM001-055-related adverse events reported, according to the release.
Investigators also measured improvement in functionality and quality of life using a chronic cough scale known as the Leicester Cough Questionnaire. Insilico reported a two-point improvement in total score for the 60-mg once-daily group compared to placebo by Week 12. The other two dose groups did not show meaningful improvement.
The complete data set will be shared at an undisclosed upcoming medical conference and published in unnamed medical journals, according to Insilico.
“I am very impressed by the positive results observed in IPF patients treated with ISM001-055, particularly the encouraging improvement in FVC,” Zuojun Xu, M.D., a professor at Peking Union Medical College and the trial’s principal investigator, said in the company release. “It not only reflects ISM001-055’s potential to slow disease progression but also suggests its capability to stop or even reverse it.”
To further advance the program, Insilico has welcomed Carol Satler, M.D., Ph.D., on board as vice president of clinical development. Satler joins the company from Respira Therapeutics, where she served as chief medical officer and president, and will be responsible for the development of Insilico’s non-oncology programs including lead asset ISM001-055.
Based on the results, the Cambridge, Massachusetts-based biotech plans to meet with regulatory agencies about launching a pivotal trial in the indication.
IPF is a chronic disease that causes the lungs to scar and makes it more difficult to breathe. Existing treatments can slow disease progression but cannot stop or reverse it.
Just a few weeks ago, Big Pharma Amgen discontinued an IPF program after its investigational small molecule failed to hit any of the primary or secondary endpoints in a phase 2 study. The primary goal of that trial was to improve the maximum amount of air patients could forcefully exhale after 52 weeks of treatment.
German drugmaker Boehringer Ingelheim has seen better luck, reporting in September that its IPF candidate nerandomilast was tied to FVC improvement at 52 weeks in a late-stage trial. The pharma plans to seek approval for nerandomilast, with work on a second phase 3 study, this time in progressive fibrosing interstitial lung disease, ongoing.