Vaxart, Inc. reported positive top-line data from the first part of a planned two-part Phase II study of its Wuhan S-only oral pill COVID-19 vaccine candidate, VXA-CoV2-1.1-S. The data demonstrate that the trial met its primary safety and secondary immunogenicity endpoints and will inform ongoing development of new Omicron-based vaccine constructs. Serum neutralizing antibodies rose after oral vaccination, and the increases were particularly notable in subjects who had previously received an mRNA vaccine. Additionally, all subjects who had a mucosal immune response to the Wuhan-based vaccine had mucosal immune responses that cross-reacted with the Omicron variants, including BA 4/5, as well as other coronaviruses.

Vaxart is the first company to advance an oral pill COVID-19 vaccine to Phase II clinical development. Study Key Findings The VXA-CoV2-1.1-S vaccine construct was safe and well-tolerated. No vaccine-related solicited grade 3 adverse events (AEs) and no vaccine-related serious adverse events (SAEs) were reported.

Vaccination with VXA-CoV2-1.1-S increased levels of SARS-CoV-2-specific serum IgG and IgA antibodies at Days 29 and 57. The geometric mean titer (GMT) increase of SARS-CoV-2-specific serum neutralizing antibodies from Day 1 to Day 57 ranged by cohort between 1.2- and 2-fold, with higher increases for higher doses. Among 18-55 year-old subjects previously vaccinated with mRNA vaccines, the geometric mean titer (GMT) of SARS-CoV-2-specific serum neutralizing antibodies increased 1.6-fold, from 481 AU/ml at Day 1 to 778 AU/ml at Day 57.

The subjects who had lower starting titers showed greater increases after oral boosting. Approximately 50% of all subjects, as well as 50% of subjects that previously received an mRNA vaccine, had at least a 1.5-fold increase in mucosal IgA antibodies. All subjects who had a mucosal response to Wuhan S from VXA-CoV2-1.1-S (a Wuhan-based vaccine) also had mucosal immune responses that cross-reacted with the Omicron variants, including BA 4/5, as well as other coronaviruses.

This includes subjects that had previously received an mRNA-based vaccine. SARS-CoV-2-specific T cell responses were observed in the majority of subjects after the second dose of VXA-CoV2-1.1-S. As previously announced, Vaxart is evaluating new Omicron-based constructs as Omicron-only monovalent vaccine candidates and as bivalent candidates in combination with the Company's Wuhan constructs. Vaxart will also compare the clinical results of its S-only and S+N constructs to determine the best path forward in developing a vaccine that can hinder viral infection and transmission for current and emerging variants.

These constructs are expected to be evaluated in preclinical models this year and to advance to clinical trials in the first half of 2023. The Company expects to move forward with the best possible vaccine constructs for its planned COVID-19 Omicron challenge in the second half of 2023 with hVIVO, as well as larger trials in the U.S. and internationally. Part 1 of the open-label, Phase II study enrolled 66 healthy adult volunteers, including subjects who had or had not received prior mRNA COVID-19 vaccination, ages 18-55 years and 56-75 years.

Subjects were randomized into six cohorts stratified by age, vaccination history and dose. Subjects received either a high or a low dose of VXA-CoV2-1.1-S on Day 1 and Day 29, and immune responses were assessed prior to vaccine administration on Day 1, Day 29 and on Day 57.