Abstract Details

Title UB-313, an Investigational CGRP Vaccine for the Prevention of Migraine

Topic Headache

Presentation(s) ES1 - Emerging Science 1 (11:39 AM-11:45 AM)

Poster/Presentation
Number 005

Background

Monoclonal antibodies against CGRP have demonstrated efficacy for the prevention of migraine. UB-313, a vaccine designed to stimulate the production of endogenous antibodies against CGRP, might provide an attractive new option to prevent migraine.

Objective

Preclinical characterization of UB-313 in support of clinical development

Design/Methods

Immunogenicity studies were conducted in rodents and monkeys. Vaccine-induced serum antibodies were characterized for their binding and functional properties. Efficacy was assessed in a rat capsaicin model and toxicity was evaluated in a repeat-dose GLP study.

Results

Studies in rodents and monkeys demonstrated that immunization with UB-313 induces robust anti-CGRP antibodies across species. Affinity purified antibodies from immunized animals were shown to bind human CGRP with high affinity (KD in the low pM range) and demonstrated a dose-dependent functional inhibition of CGRP (EC₅₀ in the low nM range) in cell-based assays, indicating antibody properties comparable to marketed monoclonal antibodies. Off-target analyses indicated very high specificity of the anti-CGRP antibodies for human CGRP. Interestingly, antibodies induced by UB-313 demonstrate a stronger potency against human CGRP than rat CGRP, despite a single amino acid substitution between species. Importantly, immunization of rats with the murine version of UB-313 prevented the effects of capsaicin on dermal blood flow to a similar extent as treatment with Galcanezumab. Preclinical toxicology studies indicated that UB-313 was safe and well tolerated, with findings limited to injection site reactions. Splenocytes collected after immunization of rats with UB-313 were not responsive to stimulation with the CGRP peptide, suggesting that UB-313 safely overcomes immune tolerance.

Conclusions

UB-313 has now advanced to clinical development: the ongoing Phase 1 trial is designed to assess safety, immunogenicity and target engagement (capsaicin-induced increase in dermal blood flow). As a potentially safe and effective immunotherapy against CGRP, UB-313 may represent an affordable and convenient strategy to prevent migraine.

Authors/Disclosures
Jean-Cosme Dodart, PhD (Vaxxinity) PRESENTER	Dr. Dodart has received personal compensation for serving as an employee of Vaxxinity. Dr. Dodart has stock in Vaxxinity.
Hui Jing Yu, PhD (Vaxxinity, Inc.)	Dr. Yu has received personal compensation for serving as an employee of Vaxxinity, Inc.. Dr. Yu has stock in Vaxxinity, Inc..
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