Insilico announces first-in-human study for oral PHD inhibitor for IBD

Biotech aims to accelerate clinical trials to reach unmet clinical needs for inflammatory bowel disease.
Insilico Medicine, a generative AI-driven clinical-stage biotech, has announced it has initiated the first-in-human study for ISM5411, a potentially first-in-class PHD inhibitor for the treatment of inflammatory bowel disease (IBD).

Longevity.Technology: Designed and developed by Insilico’s proprietary end-to-end AI drug discovery platform, Pharma.AI, this is Insilico’s fifth AI drug program to enter the clinic. The ongoing Phase I study is designed to evaluate the safety, tolerability, pharmacokinetics and food effects of ISM5411 at increasing oral doses in 76 healthy subjects, with the first dose in healthy volunteers now completed in Australia. To further evaluate ISM5411 in wider populations, Insilico plans to conduct global multi-center Phase Ib trials in patients with ulcerative colitis following the Phase Ia study.

“IBD impacts a large patient population who currently have limited therapeutic options,” says Sujata Rao, MD, Chief Medical Officer at Insilico Medicine who is leading the clinical trial.

“We believe this new treatment – which is potentially first-in-class – could offer a promising alternative.”

IBD is a chronic inflammatory disease of the gastrointestinal tract, including ulcerative colitis (UC) and Crohn’s disease (CD), that affects huge populations globally, and 3 million adults in the US alone. Neither disorder is curable, and they both increase the risk of colorectal cancer up to four times. The current standard of treatment for IBD consists of anti-inflammatory drugs which offer limited improvement in mucosal healing, which is closely correlated to positive prognosis according to genetic and clinical evidence.

The intricate relationship between cellular senescence, characterized by the irreversible cessation of cell division, and the phenomenon of inflammaging plays a pivotal role in the pathogenesis of inflammatory bowel disease (IBD). As aging progresses, heightened senescence-associated secretory phenotype (SASP) contributes to chronic low-grade inflammation, fostering an environment conducive to the development and exacerbation of IBD. The age-related decline in immune regulatory mechanisms further accentuates these processes, underscoring the increased susceptibility of the elderly to inflammatory bowel diseases.

Insilico announces first-in-human study for oral PHD inhibitor for IBD