After IPO, AI Drug Developer Insilico Medicine Advances Gut-Restricted PHD Inhibitor Into Phase II IBD Trial

Insilico Medicine reported first patient first dose in a Phase IIa clinical trial of its gut-restricted PHD inhibitor ISM5411, now assigned the generic name garutadustat.

The milestone moves the AI-designed program into mid-stage clinical testing in ulcerative colitis, shortly after the company’s Hong Kong IPO, and adds another clinical datapoint to Insilico’s internal pipeline following its transition to a publicly listed company.

The Phase IIa study, named BETHESDA (Barrier Enhancement Therapy for Healing Enteric Structural Defects & Anomalies), is a multicenter, randomized, double-blind, placebo-controlled trial enrolling around 80 patients with ulcerative colitis. The trial is led by Professor Minhu Chen at the First Affiliated Hospital of Sun Yat-sen University in China. According to the trial design, primary objectives include safety, tolerability, and pharmacokinetics, with exploratory efficacy assessed via clinical remission and response metrics, endoscopy, histopathology, and biomarker analyses.

Garutadustat is positioned as a gut-restricted prolyl hydroxylase (PHD) inhibitor intended to combine anti-inflammatory activity with enhancement of intestinal barrier repair. The compound originated from Insilico’s Pharma.AI (featured in recent Eli Lilly $100M collaboration) platform and Chemistry42 generative chemistry engine, with the company reporting that approximately 115 molecules were synthesized and screened before nomination of the preclinical candidate in January 2022, roughly 12 months after program initiation.

Two Phase I studies conducted in Australia and China have been completed, with Insilico reporting favorable safety and tolerability profiles and pharmacokinetics consistent with gut-restricted exposure across tested dose levels. Preclinical data for ISM5411 were published in Nature Biotechnology in December 2024, outlining the compound’s design rationale and translational profile.

The company frames garutadustat as addressing limitations of existing inflammatory bowel disease therapies, which largely focus on systemic immune modulation and are associated with loss of response over time in a substantial proportion of patients. In contrast, the ISM5411 program is designed to act locally in the gut, targeting epithelial integrity alongside inflammatory pathways, though clinical efficacy remains to be established in Phase II testing.

Beyond ISM5411, Insilico has previously licensed another PHD inhibitor program, ISM4808, to TaiGen Biotechnology for anemia associated with chronic kidney disease. The disclosed deal size was in the double-digit million-dollar range, combining TaiGen’s clinical development capabilities with Insilico’s AI-driven discovery workflows.

The Phase II initiation comes weeks after Insilico Medicine completed its Hong Kong Stock Exchange listing in December 2025, raising more than US$290 million in what became the city’s largest biotech IPO of the year. According to its prospectus, Insilico intends to deploy nearly half of the proceeds toward clinical research and development, alongside continued investment in early discovery and AI model development.

Topic: AI in Bio