AI-designed PHD 1/2 inhibitor for bowel disease enters human trials


Insilico Medicine has initiated the first-in-human study for ISM5411, a poly hydroxylase domain (PHD) 1/2 inhibitor for the treatment of inflammatory bowel disease (IBD) designed by its generative AI platform.

The company also plans to conduct global, multicentre 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,” said Sujata Rao, 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. 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.

Analysts GlobalData predict that the total sales of IBD drugs will reach approximately $10.2 billion in the US in 2023.

Innovative clinical options for IBD

Research shows that PHD 1/2 plays a critical role in regulating the stability and transcriptional activity of the hypoxia-inducible factor-1α (HIF-1α), which drives the expression of barrier protective genes. PHD 1/2 is significantly up-regulated in IBD patients, and shows strong correlation with the expression of inflammatory cytokines and the apoptosis marker, suggesting that PHD 1/2 is a potential target for IBD treatment.

“The rising incidence of IBD places a heavy burden on healthcare systems globally,” said Feng Ren, co-CEO and Chief Scientific Officer of Insilico Medicine. “Designed by AI from scratch, ISM5411 targets mucosal healing with the unique mechanism of barrier protection enhancement, which could potentially lead to innovative clinical options for IBD patients. We are committed to accelerating ISM5411 clinical trials to reach unmet clinical needs as soon as possible.”

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