pVaccinex Inc has entered into a USD 60 million revenue sharing agreement with Pepinemab Development Venture (PDV), LP to continue advancing development of its pepinemab anti-SEMA4D antibody in an enlarged phase II b clinical trial for treatment of AD.

The agreements provide that in exchange for the commitment of funding, PDV will receive 50 percent of future economic proceeds received by Vaccinex from a development partner or licensee of pepinemab related to neurological indications and 25 percent related to other indications.

This agreement follows on promising data previously reported from studies in animal disease models and in the early stage SIGNAL-AD phase I/IIa clinical trial indicating that treatment with pepinemab antibody blocks crosstalk between reactive astrocytes and microglia that amplifies glial reactivity leading to inflammation and glial scars; preserves vascular integrity in brain and downregulates expression of AD disease-related proteins in Cerebral Spinal Fluid (CSF) including SNAP25 associated with synaptic loss and GAP-43 that promotes tau spreading and accumulation. In addition, data from a randomised phase II study in Huntington’s disease (HD, n=179) as well as the completed SIGNAL-AD phase I/IIa study in Mild Cognitive Impairment (MCI) and mild AD (n=50) suggest that pepinemab was well-tolerated and that treatment early in disease has favourable effects on biomarkers related to disease progression and appears to slow cognitive decline.

More recently, a large group of investigators led by Dr Philip De Jager, Professor of Neurology and Chief, Division of Neuroimmunology, Columbia University Medical Center, identified a genetic signature associated with a unique subset of astrocytes termed Ast10 whose representation in brain correlates with cognitive decline in Alzheimer’s.

Importantly, the SEMA4D-PLXNB1 signaling pathway was identified as a top ligand-receptor pair that strongly regulates Ast10 representation in brain.