Novel, AI-Procured ISM001-055 Demonstrates Great Promise for Treatment of IPF

Today, Insilico Medicine announced encouraging results from their phase 2a trial (NCT05938920) on the use of ISM001-055 for treating patients with idiopathic pulmonary fibrosis (IPF). These results have thus far demonstrated the tolerability and safety of the medication, as well as its efficacy and pharmacokinetic (PK) potential as, after 12 weeks, patients exhibited improvements in their forced vital capacity (FVC).¹

A 2% to 6% decline in FVC is clinically signifiant in patients with IPF. | image credit: Thipphaphone - stock.adobe.com

FVC has long been a key measurement of lung function in IPF, with declining FVC often dictated as the primary endpoint in clinical trials for this patient population. Individual FVC percentage that are lower than normal rates can indicate restrictive lung diseases such as IPF and have proven to be a valuable marker of disease progression. A 2% to 6% reduction in FVC remains generally regarded as clinically significant in patients with IPF.²

ISM001-055 was developed through Insilico Medicine’s generative artificial intelligent (AI) biotechnology and was created to target Traf2- and NCK-interacting kinase (TNIK). "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,” stated Zuojun Xu, MD, professor, Peking Union Medical College, and principal investigator.¹

In total, the phase 2a study featured 71 patients with IPF who were enrolled from 21 different sites in China. The trial was both double-blind and placebo-controlled, with participants being randomized to receive a dose of 30 mg once per day (QD), 30 mg twice per day, or 60 mg QD for the duration of 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 Xu.

Notable findings from the trial showed that ISM001-055 is well-tolerated among patients no matter the dosage. Diarrhea (14.8%) and abnormal liver function (14.8%) were the most prevalent adverse events (AEs) experienced, with all AEs largely classified as mild or moderate to severe.

The researchers observed dose-dependent patient responses, noting an average FVC improvement of 98.4 mL at 12 weeks for those who received the higher 60 mg QD dosing compared with an average FVC decline of –62.3 mL in those who received the placebo.

The Leicester Cough Questionnaire was also implemented to measure quality of life. From baseline to week 12, patients in the 60 mg QD group reported a “meaningful” improvement of 2 points, whereas patients in the other groups did not have meaningful improvements. These findings further support the dose-dependent nature of ISM001-055.

“The results of the Phase IIa study are highly promising. The dose-dependent improvement in FVC in IPF patients treated with ISM001-055 compared to those treated with placebo suggest ISM001-055 may play a role in both the prevention of progression of IPF as well as disease regression, thus highlighting the disease-modifying potential,” said Carol Satler, MD, PhD, vice president of clinical development, Insilico Medicine, as she highlighted the value of future studies to further demonstrate the potential of ISM001-055 to transform the treatment landscape for patients with IPF.

References

1. Insilico Medicine Announces Positive Topline Results of ISM001-055 for the Treatment of Idiopathic Pulmonary Fibrosis (IPF) Developed Using Generative AI. Insilico Medicine. News release. November 12, 2024. Accessed November 12, 2024. https://www.prnewswire.com/news-releases/insilico-medicine-announces-positive-topline-results-of-ism001-055-for-the-treatment-of-idiopathic-pulmonary-fibrosis-ipf-developed-using-generative-ai-302302583.html

2. du Bois RM, Weycker D, Albera C, et al. Forced vital capacity in patients with idiopathic pulmonary fibrosis: test properties and minimal clinically important difference. Am J Respir Crit Care Med. 2011;184(12):1382-9. doi:10.1164/rccm.201105-0840OC