Odyssey Therapeutics Highlights OD-001 Phase IIa UC Data, Sets 2027 Trial Readouts

Key Points

• OD-001 showed dose-dependent activity in a 61-patient Phase IIa ulcerative colitis trial, with the 20 mg twice-daily dose producing 27% clinical remission, nearly 50% symptomatic remission and over 60% clinical response at week 12. The lower 10 mg dose appeared less active.
• Odyssey reported no serious adverse events, serious infections, liver-safety signals or drug-related discontinuations. Biopsy analyses indicated reduced RIPK2, inflammatory and cytokine signaling, alongside improved epithelial-homeostasis signatures among responders.
• The company plans to start placebo-controlled Phase IIb monotherapy and vedolizumab-combination Phase IIa trials in the second half of 2026, with induction readouts expected in the second half of 2027. Odyssey reported $433 million in cash, projected to fund operations into the second half of 2028.

Odyssey Therapeutics NASDAQ: ODTX presented additional data from its open-label Phase IIa trial of OD-001, an oral RIPK2 scaffolding inhibitor for moderate-to-severe ulcerative colitis, during its UEG Week 2026 investor webcast. The company said the complete induction dataset, biomarker findings and mucosal biopsy transcriptomics reinforced its selection of a 20 mg twice-daily dose for further development.

The trial enrolled 61 patients across 18 sites in seven countries, with 56 evaluable at week 12: 15 received OD-001 at 10 mg twice daily and 41 received 20 mg twice daily. The study permitted patients with up to three prior advanced therapies and required active rectal bleeding and an endoscopic subscore of at least 2 at entry. Odyssey emphasized that the active-only study was intended as proof of concept and was not designed to establish placebo-adjusted efficacy.

20 mg Dose Showed Stronger Clinical and Biomarker Results

Gary Glick, Odyssey’s founder and CEO, said the company had previously reported a 27% clinical-remission rate at the 20 mg twice-daily dose. The full dataset showed a mean 2.4-point reduction in modified Mayo score across the study, meeting the primary endpoint, according to the company.

At 20 mg twice daily, Odyssey reported clinical remission of 27%, symptomatic remission of nearly 50%, and clinical response of more than 60% at week 12. The company said symptomatic remission was observed in approximately one in five patients by week two, rose to 37% by week eight and reached 49% by week 12.

The lower 10 mg dose appeared less active in the expanded cohort. Of seven additional evaluable patients added to the 10 mg arm, Odyssey said one achieved clinical remission, one had endoscopic improvement and five did not respond.

Tony Opipari, Odyssey’s chief medical officer, said the higher dose also produced stronger changes in objective inflammatory measures. At 20 mg, the company reported declines in high-sensitivity C-reactive protein and neutrophils, along with a downward trend in fecal calprotectin. Serum albumin increased significantly at both dose levels, Odyssey said.

“The greatest efficacy is at the dose that maximally inhibits RIPK2, 20 mg BID,” Opipari said, adding that the company views 20 mg as the lowest maximally effective dose.

In a subgroup of patients with more severe endoscopic disease, defined as a Mayo Endoscopic Score of 3, Odyssey reported no clinical remissions among eight patients receiving 10 mg, compared with a 16% remission rate at 20 mg. Among patients with prior advanced-therapy exposure, the company reported clinical-remission rates of 23% at 20 mg, compared with 29% among advanced-therapy-naive patients. Odyssey cautioned that the advanced-therapy-experienced subgroup included 13 patients and had wide confidence intervals.

Safety and Tissue Analyses

Across all 61 enrolled patients, Odyssey reported no serious adverse events, serious infections, liver safety signals or discontinuations due to drug-related adverse events. The company said the most common treatment-related events were fever and headache, which resolved without patients stopping treatment. Opipari said two Grade 1 fever events reached maximum temperatures of 38.1 and 38.6 degrees Celsius and lasted from hours to about a day.

Glick said paired biopsies from 40 patients treated with 20 mg twice daily showed reductions in RIPK2 signaling, innate immune response pathways, cytokine signaling involving IL-23, TNF and TL1A, and T-cell signatures. The company also reported reduced fibrosis-related gene signatures and increased epithelial-homeostasis signatures among clinical remitters and responders.

Odyssey compared certain transcriptomic findings with published datasets involving infliximab, vedolizumab and mirikizumab. Glick said OD-001 appeared to reduce AP-1-related inflammatory genes that were not reduced among endoscopic responders in the published infliximab and vedolizumab datasets. He said these analyses were intended to support a pharmacologic effect of OD-001 beyond general mucosal improvement, though he did not characterize AP-1 as a proven driver of clinical benefit.

Next Studies Planned for 2027 Readouts

Odyssey plans to begin both its placebo-controlled Phase IIb monotherapy study and a randomized, double-blind Phase IIa combination study with vedolizumab in the second half of 2026. The company expects induction readouts from both trials in the second half of 2027.

The monotherapy study will test multiple doses against placebo, while the combination trial will compare OD-001 plus vedolizumab with vedolizumab plus placebo. During the question-and-answer session, Glick confirmed that the combination study will use OD-001 at 20 mg twice daily rather than 10 mg.

Glick said the company expects 20 mg to remain its top dose because Phase I ex vivo data indicated that higher doses did not produce additional RIPK2 inhibition. He also said Odyssey will seek to manage placebo response in future studies through contemporary enrollment and monitoring practices, including close oversight of corticosteroid use.

Beyond OD-001, Odyssey said it expects to file a clinical trial application this year for OD-002, an oral SLC15A4 inhibitor, and plans to begin dosing healthy participants in the first half of 2027. The company also said its TNFR2 antagonist program, OD-003, is expected to complete IND-enabling studies in the first quarter of 2027.

Odyssey reported $433 million in cash as of June 30 and said it expects that capital to fund operations into the second half of 2028, including planned OD-001 trial readouts and the Phase I readout for OD-002.

About Odyssey Therapeutics (NASDAQ:ODTX)

Odyssey Therapeutics is a clinical-stage biotechnology company focused on discovering and developing precision medicines for immune-mediated diseases and cancer. The company combines computational biology, functional genomics, and experimental drug discovery to identify therapies directed at disease-driving biological pathways.

Its research programs are centered primarily on small-molecule medicines and other targeted approaches intended to modulate the immune system or address vulnerabilities in cancer cells.

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