AltruBio's ALTB-268 Shows Promise in Preclinical Models of Inflammatory Diseases, Supporting Phase 2 UC Trial
核心洞察
AltruBio (搜索) presented new preclinical data at FOCIS 2025 demonstrating ALTB-268's efficacy in murine models of colitis (搜索) and graft-versus-host disease (搜索) through downregulation of T cell effector functions.
The immune checkpoint enhancer significantly improved survival and reduced disease severity in xenogeneic GvHD models while decreasing inflammatory cytokines and T cell infiltration in DSS-induced colitis (搜索) models.
ALTB-268 is currently being evaluated in a Phase 2a biomarker study for biologics-refractory ulcerative colitis (搜索) patients, with a larger Phase 2b randomized trial planned for 2026.
AltruBio (搜索) 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 (搜索) and potential expansion into other inflammatory conditions.
Preclinical Efficacy Across Multiple Disease Models
The preclinical studies evaluated ALTB-268's activity in both colitis (搜索) and graft-versus-host disease (搜索) (GvHD) models, providing evidence for its broad therapeutic potential. In vitro studies showed that ALTB-268 effectively downregulated T cell activation, including reduced CD25 (搜索) expression, diminished T cell proliferation, and decreased secretion of key inflammatory cytokines such as IFN-γ (搜索), IL-2, TNFα (搜索), IL-6, and IL-12 (搜索).
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 (搜索)+ and CD8 (搜索)+ T cells while increasing apoptotic T cells in the spleen. The drug also significantly inhibited T cell expansion and CD25 (搜索) expression in vivo, confirming its immune-modulating effects.
Colitis Model Results Support UC Development
The DSS-induced colitis (搜索) studies using human PSGL-1 (搜索) knock-in mice provided particularly relevant data for ALTB-268's development in ulcerative colitis (搜索). 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 (搜索)+ 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 (搜索). "By demonstrating anti-inflammatory effects in both GvHD and colitis (搜索) models, this data adds to the growing body of evidence supporting ALTB-268's development in ulcerative colitis (搜索) 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 (搜索) 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 (搜索)'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 (搜索).
Novel Mechanism of Action
ALTB-268 is a subcutaneously administered, tetravalent agonist antibody targeting PSGL-1 (搜索), 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 (搜索)'s earlier candidate ALTB-168, which demonstrated promising Phase 2 results across multiple inflammatory conditions including ulcerative colitis (搜索), psoriasis (搜索), psoriatic arthritis (搜索), and steroid-refractory acute graft-versus-host disease (搜索).
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 (搜索). The preclinical data presented at FOCIS 2025 support this potential by demonstrating efficacy across different inflammatory disease models.