AltruBio Inc. presented compelling new preclinical data for its lead immune checkpoint enhancer ALTB-268 at the Federation of Clinical Immunology Societies (FOCIS) 2025 Annual Meeting in Boston, demonstrating the drug's therapeutic potential in T cell-mediated inflammatory diseases. The data reinforce ALTB-268's mechanism of action and support its ongoing clinical development in ulcerative colitis and potential expansion into other inflammatory conditions.
Preclinical Efficacy Across Multiple Disease Models
The preclinical studies evaluated ALTB-268's activity in both colitis and graft-versus-host disease (GvHD) models, providing evidence for its broad therapeutic potential. In vitro studies showed that ALTB-268 effectively downregulated T cell activation, including reduced CD25 expression, diminished T cell proliferation, and decreased secretion of key inflammatory cytokines such as IFN-γ, IL-2, TNFα, IL-6, and IL-12.
In a human-mouse xenogeneic GvHD model, ALTB-268 demonstrated significant therapeutic benefits. The treatment improved survival rates, reduced disease severity scores and body weight loss, and decreased both human CD4+ and CD8+ T cells while increasing apoptotic T cells in the spleen. The drug also significantly inhibited T cell expansion and CD25 expression in vivo, confirming its immune-modulating effects.
Colitis Model Results Support UC Development
The DSS-induced colitis studies using human PSGL-1 knock-in mice provided particularly relevant data for ALTB-268's development in ulcerative colitis. Treatment with ALTB-268 reduced Disease Activity Index scores, colon weight/length ratio, and histopathologic inflammation scores. The drug also decreased colonic infiltration of CD8+ T cells and led to marked reductions in pro-inflammatory cytokines and leukocyte infiltration in colon tissue.
"These findings presented at FOCIS 2025 further validate ALTB-268's therapeutic potential as a differentiated immune checkpoint enhancer," said Dr. Judy Chou, President and Chief Executive Officer of AltruBio. "By demonstrating anti-inflammatory effects in both GvHD and colitis models, this data adds to the growing body of evidence supporting ALTB-268's development in ulcerative colitis and other immunological diseases."
Clinical Program Advancement and Funding
ALTB-268 is currently being evaluated in a Phase 2a exploratory biomarker study in biologics-refractory ulcerative colitis patients (NCT06109441). The company expects to report primary endpoint data for clinical remission per modified Mayo score in the first half of 2025. A larger, randomized global Phase 2b study open to both advanced therapy experienced and naïve patients is planned for initiation in 2026.
The clinical development program is supported by AltruBio's recent Series B financing of up to $225 million, which was oversubscribed. The funds will advance the clinical development of ALTB-268 and support the planned Phase 2 trials in ulcerative colitis.
Novel Mechanism of Action
ALTB-268 is a subcutaneously administered, tetravalent agonist antibody targeting PSGL-1, a key immune checkpoint regulator. The drug acts as an immune checkpoint enhancer, preferentially downregulating chronically activated late-stage T effector cells and leading to their exhaustion and apoptosis. This mechanism represents the same approach as AltruBio's earlier candidate ALTB-168, which demonstrated promising Phase 2 results across multiple inflammatory conditions including ulcerative colitis, psoriasis, psoriatic arthritis, and steroid-refractory acute graft-versus-host disease.
The enhanced potency of ALTB-268 enables subcutaneous administration, offering potential advantages in patient convenience and treatment compliance. Previous Phase 1 data showed that ALTB-268 was well tolerated with no serious adverse events across all subject cohorts, with substantially greater biological activity than the first-generation molecule ALTB-168.
Pipeline-in-a-Product Potential
Given that T-cell modulation is key in managing multiple immunological diseases, ALTB-268 has broad indication expansion potential. The company describes it as a promising "pipeline-in-a-product" that could address a range of inflammatory diseases beyond ulcerative colitis. The preclinical data presented at FOCIS 2025 support this potential by demonstrating efficacy across different inflammatory disease models.
