AltruBio Phase 2a UC data show dose-response signal for ALTB-268

AltruBio has reported Phase 2a data from its ASCEND UC2a trial of ALTB-268 in patients with moderately to severely active ulcerative colitis who had previously failed at least one advanced therapy, including biologics, JAK inhibitors, or S1P receptor modulators. The data were presented in an oral session at United European Gastroenterology Week 2026 on 20 October.

The open-label, dose-exploration study enrolled patients sequentially into two cohorts receiving different doses of the subcutaneously administered candidate over a 12-week induction period. Clinical remission at Week 12 was achieved by 11.4% of patients (4 of 35) in the lower-dose Cohort 1 and 23.1% (3 of 13) in the higher-dose Cohort 2. Clinical response rates were more pronounced: 34.3% in Cohort 1 and 53.8% in Cohort 2. Endoscopic improvement tracked the same direction, at 17.1% and 23.1% respectively.

Exposure-response signal

An exploratory pooled analysis of participants who achieved a Day 29 trough drug concentration at or above the prespecified target level (18 patients across both cohorts) produced notably higher efficacy figures. Within this pharmacokinetically defined subgroup, 38.9% achieved both clinical remission and endoscopic improvement at Week 12, and clinical response reached 55.6%. AltruBio described preliminary modelling as confirming a positive relationship between drug exposure and remission, which the company characterises as supporting the validity of ALTB-268's mechanism.

ALTB-268 is a tetravalent agonist antibody targeting PSGL-1, a cell-surface molecule involved in T-cell trafficking and activation. The proposed mechanism selectively downregulates chronically activated late-stage T effector cells, aiming to restore immune balance rather than broadly suppress the immune system. AltruBio says an earlier-generation asset with a similar mechanism produced positive Phase 2 signals in UC, psoriasis, psoriatic arthritis, and steroid-refractory graft-versus-host disease, though ALTB-268 is a distinct, next-generation molecule.

Safety data from ASCEND UC2a showed ALTB-268 was well tolerated. Treatment-emergent adverse event rates were comparable across both cohorts despite the two-fold dose difference. Injection site reactions were the most frequently reported adverse event but resolved with repeated dosing and were absent by the end of induction. One serious adverse event was recorded in Cohort 1; no deaths were reported.

"The observed relationship between drug exposure and clinical remission provides further validation of ALTB-268's unique mechanism of action," said Judy Chou, President and Chief Executive Officer of AltruBio. David Rubin of the University of Chicago, who presented the data at UEG Week, described the signals as "important initial" findings in a population with long-standing disease and prior treatment failure.

Market context and next steps

The refractory UC segment is a competitive but commercially significant space. Approved advanced therapies include anti-TNF agents, anti-integrin biologics such as vedolizumab, IL-12/23 inhibitors, selective JAK inhibitors, and the sphingosine-1-phosphate receptor modulator ozanimod. Despite this breadth of options, a meaningful proportion of patients fail or lose response to multiple mechanisms, creating durable unmet need. AltruBio's positioning of ALTB-268 as a tolerability-preserving immune restorer, rather than a broad immunosuppressant, is a differentiation argument that resonates with prescribers wary of infection risk and malignancy signals associated with some existing classes.

AltruBio is preparing the global Phase 2b ASCEND UC2b study, which it expects to initiate in 2027. That placebo-controlled trial will evaluate two active dose levels, enrol both advanced therapy-experienced and therapy-naive patients, and assess both induction of remission and durability during maintenance. Investors will be watching Phase 2b enrolment timelines and the company's ability to optimise dosing based on the exposure-response data now disclosed.