Disease-modifying candidate UB-312 demonstrated target engagement of aggregated alpha-synuclein in cerebrospinal fluid of Parkinson’s patients
Data provide validation of the Vaxxinity platform’s ability to selectively target aggregated, toxic forms of neurodegenerative proteins
CAPE CANAVERAL, Fla., July 17, 2023 (GLOBE NEWSWIRE) — Vaxxinity, Inc. (NASDAQ:VAXX), a U.S. company pioneering the development of a new class of medicines, today announced new data from a Phase 1 clinical trial demonstrating that antibodies derived from its investigational immunotherapeutic for Parkinson’s disease (PD), UB-312, slows seeding of alpha-synuclein (aSyn) in cerebrospinal fluid (CSF) of patients with PD as demonstrated using multiple target engagement assays. These data signify that UB-312 has established clear target engagement in PD patient CSF, and provides further validation of Vaxxinity’s platform technology in neurodegenerative disease.
“This is a major milestone for Vaxxinity in our quest to help Parkinson’s patients. Our candidate has shown target engagement of the toxic species of alpha-synuclein in patients, demonstrating not only proof of our technology platform, but also proof of the mechanism of our vaccine-derived antibodies specifically engaging with the toxic target in vivo,” said Mei Mei Hu, CEO of Vaxxinity. “Showing target engagement has always been a key challenge to overcome in neurodegeneration, and is of critical importance when demonstrated – a milestone worth celebrating. It is beyond our expectation to see this in our Phase 1 trial. We are endlessly grateful to the patients who participated, and to The Michael J. Fox Foundation and our collaborators for their work on these cutting-edge assays that supported this breakthrough.”
UB-312 is designed to target aggregated forms of aSyn, the toxic species that underlies Parkinson’s disease and other synucleinopathies. Last month, Vaxxinity announced clinical data from Part B of its Phase 1 clinical trial of UB-312 demonstrating that UB-312 was well-tolerated and induced anti-aSyn antibody responses in participants with early PD, and that antibodies were detectable in the CSF. As part of this 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 characterize the anti-aSyn antibodies produced after UB-312 administration and assess target engagement.
Analyses from this and related research yielded insights about the pharmacodynamic effects of anti-aSyn antibodies generated by UB-312 in the Phase 1 trial.
- UB-312-derived antibodies show preferential binding to aggregated aSyn isolated from patients with PD and Multiple System Atrophy (MSA), 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 demonstrate inhibition of aggregation of aSyn in both a seed amplification assay (SAA) and a protein misfolding cyclic amplification assay (PMCA). These techniques can potentially be used to identify people with PD, and also to measure the treatment response and pharmacodynamic properties of UB-312-derived antibodies from subjects in clinical trials.
- Importantly, aSyn aggregation was slowed down in CSF samples from PD patients who received UB-312, as compared to those who received placebo, in the Phase 1 trial.
Vaxxinity plans to continue analyses of the clinical data as part of the collaborative project with MJFF, in addition to completing other target engagement assays and additional antibody characterization studies for binding kinetics and specificity. Mark Frasier, Ph.D., Chief Scientific Officer of MJFF, commented, “Integration of critical biomarker insight into therapeutic development programs is essential for building confidence in the treatment approach, and for designing informative trials. We’re pleased to support efforts of this kind that can have major impact for people with Parkinson’s disease.”
More information about the Phase 1 trial is available at https://clinicaltrials.gov/ct2/show/NCT04075318.
