Vaxxinity, Inc. announced positive clinical data from its UB-312 program in Parkinson?s disease (PD) presented by Jean-Cosme Dodart, PhD, SVP of Research at Vaxxinity in an oral session at the AD/PD? 2024 International Conference on Alzheimer?s and Parkinson?s Disease, held virtually and in Lisbon, Portugal from March 5 to March 9, 2024. UB-312 is the first active immunotherapy candidate to show reduction of pathological alpha-synuclein (aSyn) in cerebrospinal fluid (CSF) of PD patients.

UB-312 is designed to target aggregated forms of aSyn, the toxic species that underlies PD and other synucleinopathies. As part of the randomized, double-blind, placebo-controlled Phase 1 clinical trial, The Michael J. Fox Foundation (MJFF) funded a 2-year collaborative project between Vaxxinity, the Mayo Clinic, and UTHealth Houston to analyze CSF collected from patients, and to conduct exploratory research to assess target engagement. The UB-312-induced antibodies showed preferential binding to aggregated aSyn and almost no binding to normal monomeric aSyn, as measured by dot blot.

After a single priming regimen, those treated with UB-312 in the 300/100/100µg dosing group showed a 20% decrease from baseline in aggregated aSyn in the CSF compared to a 3% increase in the placebo group (p<0.05), as measured by a Seed Amplification Assay (SAA). Further, a post hoc analysis showed that patients with detectable UB-312-induced antibodies in the CSF exhibited improvement in activities of daily living as measured by the MDS-UPDRS II clinical scale (p<0.01). These data also suggest a correlation between reduction in aggregated aSyn in the brain and change in MDS-UPDRS II (R=0.52, p=0.001).

The aforementioned results come from Part B of the Phase 1 clinical trial in 20 PD patients. Vaxxinity expects to publish these results in a peer reviewed scientific journal soon. Results from Part A of the trial in healthy volunteers were published in Movement Disorders in 2022 (Yu et al.).

Both parts of the trial showed UB-312 to be generally well tolerated (most adverse events were mild and transient) and immunogenic, with antibodies detectable in serum and CSF.