Insilico Medicine (HKG: 3696) announced that the first patient has been dosed in the BETHESDA Phase IIa trial (NCT07265570) evaluating ISM5411 (generic name: Garutadustat), a gut‑restricted PHD inhibitor developed via its Pharma.AI generative platform, for the treatment of ulcerative colitis (UC), a major form of inflammatory bowel disease (IBD).
Molecule: Novel PHD (prolyl hydroxylase domain) inhibitor with a unique dual mechanism
Dual Action: Combines anti‑inflammatory activity with intestinal barrier repair, addressing both immune dysregulation and epithelial integrity in IBD
AI‑Driven Design: Discovered and optimized using Insilico’s Pharma.AI platform, featuring a novel chemical scaffold not found in existing PHD inhibitors
Gut‑Restriction: Engineered for minimal systemic absorption, potentially reducing off‑target effects (e.g., anemia, cardiovascular risk) seen with systemic JAK or S1P modulators
Phase I Results: Two completed studies in Australia and China demonstrated favorable safety, no Grade ≥ 3 adverse events, and gut‑restricted PK profile with target engagement in colonic tissue
Clinical Evidence – Phase I Summary
Parameter
Result
Safety
100 % of subjects (n = 72) completed dosing; no serious adverse events
Colonic HIF‑1α stabilization confirmed in 95 % of biopsy samples
GI Tolerability
Mild nausea (8 %), no dose‑limiting toxicity up to 200 mg BID
Market Impact & Outlook
Parameter
2025E
2026E
2027E
China UC Prevalence
500,000
520,000
540,000
Moderate‑to‑Severe Cases
200,000
208,000
216,000
ISM5411 Addressable Population
60,000
62,400
64,800
Projected Market Share
0 %
5 %
12 %
Estimated Annual Price
–
¥65,000
¥62,000
Revenue Forecast
–
¥203 million
¥482 million
China IBD Market Landscape: Oral small‑molecule market dominated by tofacitinib (JAK inhibitor) and emerging S1P modulators; unmet need for safer, gut‑targeted therapies remains high
Competitive Differentiation: ISM5411’s gut‑restricted design could minimize systemic immunosuppression, offering a safety profile advantage over systemic JAK/S1P agents
Strategic Partnership Potential: Insilico is in discussions with regional pharma partners for co‑promotion in Southeast Asia and Japan, leveraging PHD inhibition’s novel mechanism
Pipeline Value: Positive Phase IIa data would validate Pharma.AI’s IBD design capability, supporting Insilico’s broader IDP (Intestinal Disease Portfolio) including candidates for Crohn’s disease and celiac disease
Forward‑Looking Statements This brief contains forward‑looking statements regarding clinical timelines, regulatory pathways, and commercial projections for ISM5411. Actual results may differ due to enrollment rates, competitive dynamics, and evolving treatment paradigms in IBD.-Fineline Info & Tech
By Fineline Cube