IPF treatment ISM001-055 safe, improves lung function, data show
Top-line data from Phase 2a trial encouraging, researchers say
Insilico Medicine’s ISM001-055 was generally safe and improved lung function in people with idiopathic pulmonary fibrosis (IPF), according to top-line data from a Phase 2a trial.
The trial (NCT05938920) enrolled 71 patients with IPF across 21 sites in China who were randomly assigned to receive one of two doses of ISM001-055 (30 mg once or twice daily, or 60 mg once daily), or a placebo, for 12 weeks. Improvements in lung function were demonstrated by a dose-dependent increase in forced vital capacity (FVC), which measures the total amount of air that can be forcibly exhaled from the lungs after a deep breath.
A parallel Phase 2a trial (NCT05975983) is ongoing and recruiting patients at several sites in the U.S.
“I am excited to see that ISM001-055 demonstrated obvious clinical efficacy in IPF patients in only 3-months treatment,” Feng Ren, PhD, Insilico’s co-CEO and chief scientific officer, said in a company press release. “While preliminary, this clinical data is certainly encouraging, and provides the clinical validation of AI-powered drug [research and development] for both novel target and novel molecule.”
The IPF treatment’s dose-dependent response in FVC was “particularly” encouraging, said Toby M. Maher, MD, PhD, an investigator in the trial and a professor of clinical medicine at Keck Medicine of the University of Southern California. “Seeing improvements in lung function over just 12 weeks of treatment is a promising indication that ISM001-055 may provide a new therapeutic option for patients,” Maher said.
IPF treatment target identified with AI
Pulmonary fibrosis is characterized by inflammation and progressive scarring, or fibrosis, in the lungs, making it difficult for patients to breathe. In IPF, the exact underlying cause of fibrosis is unclear.
ISM001-055, also known as INS018_055, is an oral small molecule designed to block TNIK (Traf2- and NCK-interacting kinase), a therapeutic target identified using Pharma.AI, Insilico’s artificial intelligence-driven drug discovery and development platform. After identifying targets, the company virtually designs small molecules directed at the selected candidate.
The detailed process of identifying TNIK as a therapeutic target and designing ISM001-055 was described in the study, “A small-molecule TNIK inhibitor targets fibrosis in preclinical and clinical models,” published in Nature Biotechnology.
In a mouse model of lung fibrosis, ISM001-055 was found to significantly reduce lung fibrosis and inflammation, and improve lung function.
The treatment was also found to be safe and well tolerated, displaying pharmacological properties that were in line with its design, including good oral availability and dose-proportional pharmacokinetics (movement into, through, and out of the body) in healthy volunteers who participated in two Phase 1 trials, one in New Zealand (NCT05154240) and the other in China (CTR20221542).
Complete top-line data from the Phase 2 trial will be presented at a medical conference, and trial results will be submitted for publication, according to Insilico.
“While we expected the drug to be safe, we did not expect to see such a clear dose-dependent efficacy signal after such a short dosing period,” said Alex Zhavoronkov, PhD, Insilico’s co-CEO.
The fact that ISM001-055 “demonstrated efficacy in addition to safety in a Phase IIa study is extraordinary and represents a true first in this new era of AI-powered drug discovery,” said Michael Levitt, PhD, a professor of cancer research at Stanford Medicine.
Insilico said it will engage with regulatory authorities to discuss the design of a future Phase 2b trial. The company also plans to test the IPF treatment in larger groups of patients, and to explore the possibility of extended treatment durations.
ISM001-055 received U.S. Food and Drug Administration (FDA) orphan drug designation to treat IPF. The designation provides certain incentives to therapy developers, including a guarantee of seven years of market exclusivity upon approval and tax credits for clinical trials.
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