Vaccinex Secures $60 Million to Advance Phase 2b Trial of Alzheimer's Drug Pepinemab
Key Insights
Vaccinex announced a $60 million revenue sharing agreement with Pepinemab Development Venture to fund an enlarged Phase 2b clinical trial of pepinemab for Alzheimer's disease treatment.
The anti-SEMA4D (search) antibody pepinemab demonstrated promising results in early trials, blocking harmful brain inflammation and preserving vascular integrity while reducing disease-related proteins in cerebrospinal fluid.
Recent genetic research identified the SEMA4D (search)-PLXNB1 (search) signaling pathway as a key regulator of Ast10 astrocytes, which correlate with cognitive decline in Alzheimer's patients.
Vaccinex, Inc. has secured $60 million in funding to advance its experimental Alzheimer's disease treatment pepinemab into an enlarged Phase 2b clinical trial. The clinical-stage biotechnology company announced the revenue sharing agreement with Pepinemab Development Venture, LP (PDV), an investment entity established by existing investor FCMI (search).
Under the agreement, PDV will receive 50% of future economic proceeds from pepinemab related to neurological indications and 25% for other indications in exchange for the funding commitment. Albert Friedberg, who chairs both FCMI (search) and the Vaccinex Board, facilitated the partnership.
Novel Mechanism Targets Brain Inflammation
Pepinemab represents a differentiated approach to treating Alzheimer's disease by inhibiting semaphorin 4D (SEMA4D (search)), a biological effector that triggers pathogenic events downstream of astrocyte reactivity. Previous studies in animal disease models and the early-stage SIGNAL-AD phase 1/2a clinical trial demonstrated that pepinemab treatment produces multiple beneficial effects in the brain.
The antibody blocks crosstalk between reactive astrocytes and microglia that amplifies glial reactivity, leading to inflammation and glial scars. Additionally, pepinemab preserves vascular integrity in the brain and downregulates expression of Alzheimer's disease-related proteins in cerebrospinal fluid (CSF), including SNAP25 (search) associated with synaptic loss and GAP-43 (search) that promotes tau spreading and accumulation.
Clinical Evidence Supports Continued Development
Data from a randomized Phase 2 study in Huntington's disease involving 179 patients, as well as the completed SIGNAL-AD phase 1/2a study in mild cognitive impairment and mild Alzheimer's disease with 50 participants, suggest that pepinemab was well-tolerated. Treatment early in disease showed favorable effects on biomarkers related to disease progression and appeared to slow cognitive decline.
Genetic Research Validates Target
Recent research led by Dr. Philip De Jager, Professor of Neurology and Chief of the Division of Neuroimmunology at Columbia University Medical Center, provided additional validation for Vaccinex's approach. The large investigator group identified a genetic signature associated with a unique subset of astrocytes termed Ast10, whose representation in the brain correlates with cognitive decline in Alzheimer's disease.
Critically, the SEMA4D (search)-PLXNB1 (search) signaling pathway was identified as a top ligand-receptor pair that strongly regulates Ast10 representation in brain tissue. Based on information shared by Dr. De Jager and colleagues, Vaccinex determined that pepinemab treatment reduced representation of Ast10 cells in the brain, and this reduction appeared to be associated with slowing of cognitive decline relative to placebo controls.
These results were presented at the Clinical Trials on Alzheimer's Disease (CTAD) Conference in San Diego on December 3, 2025. The company believes the combination of biological, clinical and genetic evidence for the important role of the SEMA4D (search)-PLXNB1 (search) signaling pathway in Alzheimer's disease progression provides compelling rationale to continue development of pepinemab as a potentially novel and effective therapeutic.
Broader Neurodegenerative Applications
Vaccinex is pioneering the inhibition of SEMA4D (search) as a treatment approach for slowly progressive neurodegenerative diseases beyond Alzheimer's, including Huntington's disease. The company's lead drug candidate pepinemab blocks SEMA4D, which the company believes triggers a chain of pathogenic events downstream of astrocyte reactivity that drive disease progression in both conditions.