AltruBio has reported Phase 2a results for ALTB-268 in patients with moderate to severe ulcerative colitis who had not responded adequately to previous advanced therapies.

The open-label ASCEND UC2a study found clinical remission rates of 23.1% with the higher dose and 11.4% with the lower dose after 12 weeks of treatment. The trial included 48 participants and had no placebo group, meaning the findings are preliminary and require confirmation in a controlled study.

ALTB-268 is an investigational subcutaneous antibody targeting P-selectin glycoprotein ligand-1 (PSGL-1), an immune modulator involved in regulating T-cell activity. AltruBio is developing the treatment for inflammatory and immune-mediated diseases.

Higher dose cohort had a higher remission rate

At Week 12, four of 35 participants in the lower-dose Cohort 1 achieved clinical remission, compared with three of 13 participants in the higher-dose Cohort 2. These results correspond to remission rates of 11.4% and 23.1%, respectively.

Clinical response was reported in 34.3% of participants receiving the lower dose and 53.8% of those receiving the higher dose. Endoscopic improvement, which assesses changes visible during endoscopic examination, was recorded in 17.1% and 23.1%, respectively.

Improvements in patient-reported quality of life, measured using the Inflammatory Bowel Disease Questionnaire, were reported in 51.4% of Cohort 1 and 53.8% of Cohort 2.

An exploratory analysis examined participants whose Day 29 drug trough concentration met or exceeded a target level. Among these 18 participants, seven (38.9%) achieved clinical remission and seven (38.9%) achieved endoscopic improvement at Week 12. Clinical response and quality-of-life response were each reported in 55.6%.

AltruBio said preliminary exposure-response modelling showed a positive relationship between drug concentration at Day 29 and clinical remission at Week 12. The subgroup analysis is exploratory and does not establish that reaching the target concentration causes remission.

Safety findings and trial limitations

The company reported that ALTB-268 was well tolerated, with similar overall proportions of treatment-emergent adverse events in both cohorts despite a two-fold difference in dose.

The most common adverse event was an injection-site reaction. These reactions decreased with repeat administration and were not observed in either cohort by the end of the 12-week induction period. One serious adverse event occurred in Cohort 1, and no deaths were reported.

The study enrolled patients with moderately to severely active ulcerative colitis who had an inadequate response to at least one previous advanced therapy, including biologics, Janus kinase (JAK) inhibitors or sphingosine-1-phosphate (S1P) receptor modulators.

The small sample size, sequential enrolment of the two cohorts and absence of a placebo comparator limit the conclusions that can be drawn from the results. Larger controlled trials will be needed to assess the treatment’s efficacy and safety more reliably.

Phase 2b trial planned for 2027

AltruBio is preparing the global Phase 2b ASCEND UC2b trial, which is expected to start in 2027. The placebo-controlled study will evaluate two active dose levels and assess both induction of clinical remission and the durability of response during maintenance treatment. It is planned to include patients who have and have not previously received advanced therapies.

Judy Chou, president and chief executive officer of AltruBio, said: “The remission rates observed in this trial are highly encouraging, particularly in this advanced therapy-refractory UC population, and support further evaluation in a randomized study.”

David Rubin, professor of medicine at the University of Chicago and the study’s presenter at UEG Week 2026, said: “The benefits of this novel treatment in the complex patients with long-standing disease who had not adequately responded to other advanced therapies are important initial signals.”

The Phase 2b study should help determine whether the early clinical activity observed with ALTB-268 translates into a meaningful treatment benefit compared with placebo.