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Abstract Details

UB-313, an Investigational CGRP Vaccine for the Prevention of Migraine
Headache
ES1 - Emerging Science 1 (11:39 AM-11:45 AM)
005

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. 

Preclinical characterization of UB-313 in support of clinical development
 

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.

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.

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..
Justin Boyd (Vaxxinity) Justin Boyd has received personal compensation for serving as an employee of Vaxxinity.
Eric Hsieh (Vaxxinity) No disclosure on file
Hanxin Lu (Vaxxinity) No disclosure on file
Shixia Wang, PhD (Vaxxinity Inc.) Dr. Wang has received personal compensation for serving as an employee of Vaxxinity, Inc.. Dr. Wang has stock in Vaxxinity, Inc..
Martina Ramos (Vaxxinity) No disclosure on file
Alanis Sun (Vaxxinity) No disclosure on file
Matthew Longo (Vaxxinity) Mr. Longo has nothing to disclose.
Madeline Vroom (Vaxxinity) No disclosure on file
Shuang Ding (Vaxxinity) Shuang Ding has nothing to disclose.
Brett Thibodeaux, PhD (Vaxxinity) Dr. Thibodeaux has received personal compensation for serving as an employee of Vaxxinity. Dr. Thibodeaux has received intellectual property interests from a discovery or technology relating to health care. Dr. Thibodeaux has received intellectual property interests from a discovery or technology relating to health care. Dr. Thibodeaux has received personal compensation in the range of $50,000-$99,999 for serving as a Scientist with Florida Department of Health.
Jeanne Kaye Brooks (Vaxxinity) Ms. Brooks has nothing to disclose.
Jaya Sahni, PhD Dr. Sahni has received personal compensation for serving as an employee of Vaxxinity. Dr. Sahni has received personal compensation for serving as an employee of Seattle Children's . Dr. Sahni has stock in Vaxxinity. Dr. Sahni has received intellectual property interests from a discovery or technology relating to health care.
Jonathan Wiggins (Vaxxinity) Mr. Wiggins has received personal compensation for serving as an employee of Vaxxinity. Mr. Wiggins has stock in Vaxxinity.
Dario Mirski (Vaxxinity) No disclosure on file