Nature Medicine Publishes Vaxxinity UB-312 Parkinson's Trial Results

Vaxxinity, Inc., an American biotechnology company specializing in active immunotherapy medicines (AIMs), has announced that Nature Medicine has published significant findings from its Phase 1 clinical trial of UB-312, targeting Parkinson's disease (PD). This trial, pioneering new treatments for PD, assessed both clinical efficacy and exploratory research funded by The Michael J. Fox Foundation (MJFF) in collaboration with the Mayo Clinic and UTHealth Houston.

In the study, UB-312-induced antibodies were found to significantly reduce levels of aggregated alpha-synuclein (αSyn), a protein implicated in PD pathology, using a seed amplification assay (SAA). This reduction suggests that UB-312 may help eliminate harmful αSyn protein aggregates in the brain. Patients with detectable UB-312-induced antibodies in cerebrospinal fluid (CSF) showed marked improvement in motor experiences of daily living, as measured by the MDS-UPDRS Part II scale, indicating potential clinical benefits.

The Phase 1 trial successfully achieved its primary outcomes, showing UB-312 was generally well-tolerated and effective in inducing anti-αSyn antibody responses in both healthy volunteers and PD patients. Out of 13 PD patients who completed dosing, 12 developed anti-αSyn antibodies.

Lou Reese, Co-Founder and Executive Chairman of Vaxxinity, emphasized the importance of these findings, suggesting a promising future for Parkinson's treatment. He described the publication as a significant milestone toward changing the status quo in PD care.

Parkinson’s disease is a progressive neurodegenerative disorder without currently approved disease-modifying treatments. Alpha-synuclein pathology, characterized by the formation of Lewy bodies, is central to PD's progression. UB-312 is designed to induce a targeted immune response against these pathological αSyn forms to potentially slow or halt disease progression.

Highlights from the exploratory Phase 1 data published in Nature Medicine include:

1. Promising results from two exploratory CSF biomarkers indicating target engagement:
- Aggregated αSyn, as measured by SAA.
- Phosphorylated αSyn (pS129-αSyn).

2. PD patients with UB-312-induced antibodies in CSF had significantly lower levels of αSyn aggregation and pS129-αSyn compared to those without detectable CSF antibody titers.

3. PD patients with UB-312-induced antibodies also showed significant improvement in MDS-UPDRS Part II motor experiences compared to those without detectable antibodies.

In vitro studies demonstrated that UB-312-induced antibodies preferentially bind to aggregated forms of αSyn, slowing its aggregation process.

Professor Geert Jan Groeneveld, neurologist and principal investigator of the Phase 1 trial, remarked on the potential of UB-312 to become a significant disease-modifying therapy for Parkinson’s disease, envisioning a future where vaccination against PD could be possible.

The publication in Nature Medicine follows the completion of Part B of the Phase 1 trial, which involved 20 early-stage PD patients and included 24 weeks of observation. Vaxxinity is committed to further development of UB-312 as a promising candidate for PD treatment. Results from Part A of the trial, involving 50 healthy volunteers, were published in Movement Disorders in 2022.

The exploratory biomarker and target engagement research were funded by The Michael J. Fox Foundation, marking a collaborative effort between Vaxxinity, the Mayo Clinic, and UTHealth Houston.

UB-312 is an AIM designed to address the root cause of Parkinson's by safely inducing antibodies against toxic αSyn aggregates. It is the first active immunotherapy to demonstrate target engagement in patient CSF using the αSyn seed amplification assay.

Vaxxinity is dedicated to democratizing healthcare with its innovative AIM technology platform, aiming to revolutionize the treatment of chronic diseases such as Alzheimer’s, Parkinson’s, migraines, and hypercholesterolemia. The platform is also applied in a COVID-19 vaccine program, striving for a global impact on human health.