Odyssey's OD-001-Vedolizumab Combo Advances to Phase 2a in UC

Odyssey Therapeutics (Odyssey) announced October 12, 2026, that it is presenting the design of a randomized, double-blind phase 2a trial evaluating OD-001 in combination with vedolizumab (Entyvio) in patients with moderate-to-severe ulcerative colitis (UC) at the American College of Gastroenterology (ACG) 2026 Annual Scientific Meeting, occurring October 9-14 in Nashville, Tennessee.¹ The trial is expected to enroll up to 146 patients globally, combining OD-001 and vedolizumab during a 12-week induction period and then continuing with OD-001 monotherapy through week 52. Odyssey expects topline induction results in the second half of 2027.¹

What is the rationale for combining OD-001 and vedolizumab?

OD-001 is an oral receptor-interacting protein kinase 2 (RIPK2) scaffolding inhibitor designed to block upstream, innate immune activation, while vedolizumab, an approved gut-selective integrin antagonist, limits adaptive immune cell trafficking to the intestine.¹ By targeting innate immunity ahead of the adaptive-immune and cell-trafficking pathways that current UC therapies target, Odyssey positions OD-001 as a potential combination backbone rather than a standalone replacement. The new trial is the company's first clinical test of pairing innate- and adaptive-immunity-targeted drugs in this disease.¹

What has OD-001 shown as a monotherapy so far?

The new trial builds on an earlier phase 2a, signal-seeking monotherapy study of OD-001, registered on ClinicalTrials.gov under an earlier compound code, OD-07656, as a 2-part trial in an estimated 57 patients with moderate-to-severe UC who had an inadequate response to at least 1 prior therapy.² Odyssey reported topline results from that trial in June 2026. Among 49 patients who completed 12 weeks of treatment, using both naive and experienced to advanced therapies, 27% achieved clinical remission and 61% achieved clinical response. OD-001 was well tolerated at both doses tested, though the company released no comparator or placebo data.³

Why are companies combining mechanisms in inflammatory bowel disease?

Odyssey's approach reflects a broader shift toward dual-mechanism strategies in inflammatory bowel disease. Johnson & Johnson, for instance, is developing an engineered antibody combining guselkumab and golimumab to inhibit interleukin-23 and tumor necrosis factor-alpha simultaneously; in phase 2b trials presented in 2026, the combination antibody produced higher clinical remission rates than either biologic alone in Crohn's disease.⁴ Such combination strategies aim to help patients who do not achieve adequate, durable control on a single-mechanism biologic or small molecule. Current UC therapies, including biologics and oral small molecules, can lose effectiveness over time or fail to induce remission in many patients, which is part of what has pushed developers toward pairing mechanisms rather than relying on any one pathway.¹^,⁴

What are the limitations?

The company's announcement describes only the new trial's design and does not report efficacy or safety data for the OD-001-vedolizumab combination itself. Topline induction results are not expected until the second half of 2027.¹ The OD-001 monotherapy data cited above are topline, signal-seeking results from a small trial that included an open-label arm, not peer-reviewed or fully placebo-controlled findings, and they have not been independently replicated.²^,³ The ClinicalTrials.gov record for that earlier trial also does not explicitly confirm that OD-07656 and OD-001 refer to the same compound, though the sponsor, disease, phase, and timeline all match.²

References

1. Odyssey Therapeutics. Odyssey Therapeutics to present design of phase 2a study evaluating OD-001 in combination with vedolizumab at ACG 2026. Press release. Published October 12, 2026. Accessed October 12, 2026. https://investors.odysseytx.com/news-releases/news-release-details/odyssey-therapeutics-present-design-phase-2a-study-evaluating-od
2. Safety and efficacy of OD-07656 and of subsequent vedolizumab therapy in moderately to severely active ulcerative colitis. ClinicalTrials.gov; NCT06850727. Updated February 11, 2026. Accessed October 12, 2026. https://clinicaltrials.gov/study/NCT06850727
3. Odyssey Therapeutics. Odyssey Therapeutics reports first quarter 2026 financial results and provides corporate update. Press release. Published June 17, 2026. Accessed October 12, 2026. https://investors.odysseytx.com/news-releases/news-release-details/odyssey-therapeutics-reports-first-quarter-2026-financial
4. Johnson & Johnson. Investigational co-antibody therapy JNJ-4804 shows potential in refractory inflammatory bowel disease. Press release. Published May 5, 2026. Accessed October 12, 2026. https://www.jnj.com/media-center/press-releases/johnson-johnson-investigational-co-antibody-therapy-jnj-4804-shows-potential-to-raise-the-bar-for-clinical-efficacy-in-treating-refractory-inflammatory-bowel-disease