Vaxxinity Confirms Target Engagement of Toxic Alpha-Synuclein in Parkinson's Patients

Tuesday, July 18, 2023

Vaxxinity, Inc a pioneering U.S. company developing a new class of medicines, has announced positive results from a Phase 1 clinical trial of its investigational immunotherapeutic, UB-312, for Parkinson's disease (PD). The trial demonstrated that antibodies derived from UB-312 slow down the seeding of toxic alpha-synuclein (aSyn) in the cerebrospinal fluid (CSF) of PD patients, as evidenced by multiple target engagement assays. These findings provide strong evidence of UB-312's effective target engagement in PD patients' CSF and validate Vaxxinity's platform technology in the field of neurodegenerative diseases.

Mei Mei Hu, CEO of Vaxxinity, expressed excitement about this significant milestone, which brings hope to Parkinson's patients. The Phase 1 trial successfully demonstrated target engagement with the toxic species of alpha-synuclein in patients, providing proof not only of their technology platform but also of their vaccine-derived antibodies' ability to engage with the toxic target in vivo. Target engagement has been a crucial challenge in neurodegeneration research, making this milestone worth celebrating, and exceeding their expectations for the Phase 1 trial. She expressed gratitude to the patients who participated in the study, as well as to The Michael J. Fox Foundation (MJFF) and their collaborators for their work on the advanced assays that supported this breakthrough.

UB-312 is designed to target aggregated forms of aSyn, the toxic species associated with Parkinson's disease and other synucleinopathies. In a previous announcement, Vaxxinity shared clinical data from Part B of the Phase 1 trial, showing that UB-312 was well-tolerated and induced anti-aSyn antibody responses in early PD patients, with detectable antibodies found in the CSF. As part of the trial, the MJFF funded a collaborative project between Vaxxinity, the Mayo Clinic, and UTHealth Houston to analyze CSF collected from patients and conduct exploratory research on the anti-aSyn antibodies produced after UB-312 administration to assess target engagement.
The analyses from the trial provided valuable insights into the pharmacodynamic effects of UB-312-derived antibodies:

UB-312-derived antibodies displayed a preference for binding to aggregated aSyn isolated from PD and Multiple System Atrophy (MSA) patients, as measured by dot blot. Preclinical data published in Alzheimer's Research & Therapy in 2020 showed similar characteristics of UB-312-derived antibodies.
UB-312-derived antibodies successfully inhibited aSyn aggregation in both a seed amplification assay (SAA) and a protein misfolding cyclic amplification assay (PMCA). These techniques hold promise in identifying PD patients and measuring the treatment response and pharmacodynamic properties of UB-312-derived antibodies during clinical trials.

Notably, aSyn aggregation was significantly slowed down in CSF samples from PD patients who received UB-312, compared to those who received a placebo during the Phase 1 trial.

Vaxxinity plans to continue analyzing the clinical data in collaboration with the MJFF, in addition to conducting further target engagement assays and antibody characterization studies to understand binding kinetics and specificity. Mark Frasier, Ph.D., Chief Scientific Officer of MJFF, highlighted the importance of integrating critical biomarker insights into therapeutic development programs to build confidence in the treatment approach and design informative trials, offering significant impact to individuals living with Parkinson's disease.

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