Vaccinex to Present New Biomarker Data Supporting Expanded Phase 2b Trial of Pepinemab in Early Alzheimer's Disease
核心洞察
Vaccinex will present new biomarker data from its Phase 1b/2 SIGNAL-AD study at the Alzheimer's Association International Conference in London on July 13, 2026.
The data support plans for an enlarged randomized Phase 2b "SIGNAL-AD2" trial of pepinemab, a SEMA4D-blocking monoclonal antibody, in early Alzheimer's disease (搜索).
Pepinemab targets a novel mechanism involving reactive astrocytes and neuroinflammation, distinct from amyloid-focused approaches.
Vaccinex, Inc. announced it will present promising new biomarker data from its Phase 1b/2 SIGNAL-AD study at the Alzheimer's Association International Conference (AAIC) in London, United Kingdom, on July 13, 2026. The data support the company's plans to advance pepinemab, its lead drug candidate, into an enlarged randomized Phase 2b trial — dubbed SIGNAL-AD2 — for the treatment of early Alzheimer's disease (搜索) (AD).
Elizabeth Evans, PhD, Chief Operating Officer and Senior VP of Discovery and Translational Medicine at Vaccinex, will chair the Featured Research Session entitled "Alzheimer's therapy: mechanisms beyond amyloid" and present the novel results. The presentation, titled "Glial Biomarkers Associated With Disease Progression Are Regulated By SEMA4D Blocking Antibody Pepinemab in Patients with Early-stage AD," is scheduled for Monday, July 13, 2026, from 9:00 AM to 10:30 AM London time at Excel London.
A Differentiated Mechanism Targeting Astrocyte Reactivity
Pepinemab is a humanized IgG4 monoclonal antibody designed to block Semaphorin 4D (搜索) (SEMA4D), a molecule that Vaccinex scientists discovered is highly upregulated on stressed or damaged neurons during Alzheimer's disease (搜索) progression. SEMA4D binds to plexin-B1 (搜索) receptors expressed on astrocytes in the brain, and this signaling is believed to trigger the collapse of the actin cytoskeleton, leading to loss of homeostatic functions of astrocytes and other glial cells.
The company's central hypothesis — currently being tested in the Phase 1b/2 SIGNAL-AD study — is that pepinemab can block SEMA4D signaling through astrocyte plexin-B1 (搜索) receptors and thereby slow or prevent the damaging consequences of astrocyte activation. This approach represents a departure from amyloid-targeting strategies that have dominated Alzheimer's drug development.
Collaborative Discovery of Key Biomarkers
An independent transcriptomic meta-analysis led by Dr. Philip De Jager at Columbia University Medical Center previously identified a unique reactive astrocyte subset strongly associated with cognitive impairment and Alzheimer's disease (搜索) progression. Through a collaboration between Vaccinex and Dr. De Jager's team, scientists discovered key biomarkers of reactive astrocytes and dynamic disease processes — including synaptic loss, cognitive decline, and neuroinflammation — that appear to be regulated by pepinemab treatment.
Evidence from these studies, according to the company, supports and informs the design of the enlarged randomized Phase 2b SIGNAL-AD2 trial for people living with early Alzheimer's dementia.
Funding and Broader Development Program
The SIGNAL-AD study was funded in part by a grant from the Alzheimer's Association as well as by investments from the Alzheimer's Drug Discovery Foundation (ADDF). Pepinemab appears to be well-tolerated with a favorable safety profile across multiple clinical trials in different neurological and cancer indications, according to Vaccinex.
Beyond Alzheimer's disease (搜索), pepinemab is being evaluated in oncology settings, including in combination with KEYTRUDA in the Phase 1b/2 KEYNOTE-B84 study for recurrent or metastatic head and neck cancer, and in combination with BAVENCIO in a Phase 1b/2 study for metastatic pancreatic adenocarcinoma. The company has also previously published promising Phase 2 data for pepinemab in Huntington's disease. Vaccinex holds global commercial and development rights to pepinemab.