Vaccinex Unveils New SIGNAL-AD Trial Findings at CTAD Conference in Madrid

Vaccinex has shared the outcomes of its SIGNAL-AD Phase 1b/2 trial of the pepinemab antibody, highlighting significant findings in the treatment of Alzheimer’s disease. The recent clinical evidence underscores the beneficial effects of pepinemab on biomarkers and cognitive functions in patients at the early stages of Alzheimer’s, specifically those with Mild Cognitive Impairment (MCI) and mild dementia.

The primary goal of the SIGNAL-AD study was to assess the impact of pepinemab starting from the initial diagnostic phase of MCI, through to the later stages marked by mild dementia. The traditional treatments for Alzheimer’s disease focus on reducing the expression of Abeta amyloid, which only moderately slows cognitive decline. In contrast, Vaccinex aims to intervene early using pepinemab to inhibit astrocyte activation and inflammation, thus seeking a more significant reduction in disease activity.

The study reported that biomarkers such as plasma Glial Fibrillary Acidic Protein (GFAP) and p-tau 217, which increase predominantly during MCI, were effectively inhibited by pepinemab treatment. GFAP is a marker of astrocyte reactivity, while p-tau 217 is associated with toxic tau tangles in neurons. Without effective treatment, patients typically progress to mild dementia, with Mini-Mental State Examination (MMSE) scores ranging from 22 to 26. Pepinemab treatment demonstrated potential in slowing further cognitive decline at this stage, with positive trends observed across multiple cognitive measures.

Further supporting the potential benefits of pepinemab, the study included a proteomic analysis of cerebrospinal fluid (CSF) from patients treated with either pepinemab or a placebo. This analysis revealed that several proteins, known to increase during normal Alzheimer’s progression, were inhibited by pepinemab treatment, further substantiating its positive impact.

Additionally, concerns regarding potential vascular damage and inflammation due to antibody treatments targeting Abeta amyloid were addressed. The study reported no such adverse effects with pepinemab. Utilizing a human Brain-Chip model, the researchers demonstrated that pepinemab could inhibit or reverse damage inflicted by toxic alpha synuclein aggregates. This model showed that treatment with pepinemab significantly inhibited the harmful effects of alpha synuclein and even reversed damage when administered later. Similar analyses regarding Abeta amyloid-related damage will be shared soon.

The broader context of this study includes previous findings from a randomized phase 2 study in Huntington’s disease, which showed significant benefits of pepinemab on disease-specific biomarkers and cognitive measures. The SIGNAL-AD study aimed to validate whether these effects are consistent in another common neurodegenerative disease. Additionally, new findings indicate that pepinemab can counteract the damaging effects of alpha synuclein, a key component of Lewy bodies seen in diseases such as Dementia with Lewy Bodies, Parkinson’s disease, and in about 50% of Alzheimer’s cases. This suggests that pepinemab could have broader applications across various neurological diseases.

Vaccinex’s current strategy focuses on treating patients with MCI or mild dementia due to Alzheimer’s disease with pepinemab, aiming to slow or halt disease progression and prevent further pathological changes. The company plans to pursue partnerships to continue the development of pepinemab in Alzheimer's disease, Huntington’s disease, and potentially other neurological conditions.