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).
Contents
Clinical Milestone
| Item | Detail |
|---|---|
| Study | BETHESDA Phase IIa (NCT07265570) |
| Design | Multicenter, randomized, double‑blind, placebo‑controlled |
| Population | ~80 ulcerative colitis patients |
| Primary Endpoints | Safety, tolerability, pharmacokinetics (PK) |
| Secondary Endpoints | Clinical remission/response, endoscopic improvement, histopathology, biomarkers |
| Status | First patient dosed November 2025 |
| Next Milestone | Topline data expected Q4 2026 |
Drug Profile & Mechanism of Action
- 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 |
| PK Profile | Plasma Cmax < 5 ng/mL; fecal concentrations > 1,000× higher than plasma |
| PD Marker | 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
