Vaccinex Updates on SIGNAL-AD Trial Findings and Development Partnership Plans

Vaccinex, a biopharmaceutical company, has shared promising updates from its SIGNAL-AD Phase 1b/2 trial, which investigates the effects of its lead product, pepinemab, on Alzheimer's disease (AD). The study focuses on cognitive impacts and the potential for this treatment to support further development in AD and other neurodegenerative diseases, including Huntington's Disease (HD).

Pepinemab's promising results in the Phase 1b/2 study for early Alzheimer's stages show its efficacy and tolerability. After a successful Phase 2 study in HD, Vaccinex identified Alzheimer's disease as a significant market, prompting further investigation into pepinemab’s effects on AD. The SIGNAL-AD trial was designed to be cost-effective, targeting common disease progression features in HD and AD. A particularly important efficacy endpoint is the decline in brain metabolic activity, measured by FDG-PET signals. The study achieved its goal, demonstrating a statistically significant difference in the medial temporal cortex FDG-PET signal after 12 months of treatment with pepinemab compared to placebo.

During the trial, secondary endpoints were also examined. These included blood-based biomarkers for astrocyte reactivity and neurodegeneration. Previous studies indicated that during the progression of AD and HD, SEMA4D levels increase in neurons. When SEMA4D binds to receptors on astrocytes, it triggers a transformation from a supportive state to a reactive state, causing neuroinflammation. This reaction releases GFAP, a detectable marker in the blood. The study also monitored p-tau 217, a peptide released due to neuronal damage and tau protein accumulation, which is toxic to neurons.

The results from the SIGNAL-AD trial showed a correlation between levels of GFAP and p-tau 217 over the 12-month treatment period, supporting the connection between astrocyte reactivity and neuronal damage. The findings shared at the Alzheimer’s Association International Conference revealed that pepinemab treatment reduces the increase in GFAP levels typically seen in patients with Mild Cognitive Impairment (MCI) due to AD. Similarly, there was an observed effect on p-tau 217 levels in patients with MCI, although this effect was not seen in those with advanced early dementia. These findings are consistent with prior studies on early-stage HD patients.

Cognitive decline is a major concern in AD and HD. The SIGNAL-AD trial utilized different cognitive assessment measures, including the iADRS combination and ADAS-Cog 13. The data suggested a cognitive benefit from pepinemab treatment in MCI patients, contrasting with the lack of effect in early dementia patients. This aligns with previously reported significant cognitive benefits in early-stage HD patients.

Vaccinex aims to report further SIGNAL-AD trial details at upcoming scientific conferences and in medical journals. The company believes that pepinemab treatment can benefit patients with MCI due to AD, highlighting the importance of early identification and treatment to delay the progression to dementia. With MCI affecting an estimated 1 million people with AD in the U.S. alone, pepinemab presents a promising treatment option with significant unmet needs.

Vaccinex asserts that it has gathered compelling evidence of pepinemab’s favorable tolerability and efficacy in early-phase neurodegenerative disease studies. The company plans to pursue a major partnership for further development, reducing operating expenses while progressing with late-stage development. The support from investors has been crucial in achieving these milestones, and the company expresses gratitude for this support as it moves forward with confidence.