Vaxart Reports Positive Clinical Data Demonstrating its Second-Generation Vaccine Technology Produces Much Stronger Antibody Responses Than its First-Generation Technology

Vaxart, Inc. recently reported positive topline results from the Phase 1 clinical trial evaluating its second-generation oral pill norovirus vaccine constructs head-to-head against its first-generation constructs.

The open-label, Phase 1 trial was conducted in 60 healthy volunteers who were randomized to receive the first-generation constructs, an equivalent dose of the second-generation GI.1 and GII.4 constructs, or a lower dose of the second-generation constructs (n=20 for each group). The primary immunological endpoint was norovirus blocking antibody assay (NBAA) titer at Day 0 and Day 28. In a Phase 2 challenge trial of the first-generation vaccine constructs, these functional NBAA titers correlated with protection against norovirus infection. Although the study was not powered to determine superiority by statistical methods, the increase in NBAA titers with the second-generation constructs was sufficiently large (141% for the GI.1 construct and 94% for the GII.4 construct) to demonstrate statistical significance at the higher dose.

“Consistent with what we previously demonstrated in animal models, these clinical data prove that our second-generation constructs increased antibody titers in humans, providing additional compelling evidence of the potential of our oral pill vaccine candidates,” said Sean Tucker, PhD, Vaxart’s Founder and Chief Scientific Officer. “We previously demonstrated that our first-generation construct for the norovirus GI.1 genotype protected against infection and that protection correlated with increased antibody levels detected by our proprietary NBAA assay. The significant increases in NBAA titers reported today give us high confidence that our second-generation constructs will provide even greater protection against infection.”

Key findings from the study show:

• Significantly increased GI.1 NBAA titers in the cohort receiving the high dose of the second-generation constructs compared with an equivalent dose of the first-generation constructs.
  -A 141% increase in GI.1 NBAA titers was observed, which corresponds to a 3.2 increase in Geometric Fold Response (GMFR) from 2.2 to 5.4.
• Significantly increased GII.4 NBAA titers in the cohort receiving the high dose of the second-generation constructs compared with an equivalent dose of the first-generation constructs.
  -A 94% increase in NBAA titers was observed, which corresponds to a 1.8 increase in GMFR from 1.9 to 3.7.
• The low dose of the second-generation constructs produced a numerical increase in NBAA titers compared with the first-generation constructs.
  -129% increase in NBAA titers for GI.1 was observed, which corresponds to a 2.9 increase in GMFR from 2.2 to 5.1.
  -84% increase in NBAA titers for GII.4 was observed, which corresponds to a 1.6 increase in GMFR from 1.9 to 3.5.
• With respect to safety, all norovirus vaccine candidates evaluated in this study were well-tolerated, with no vaccine-related serious adverse events.

Vaxart intends to publish the complete results of this study in a peer-reviewed journal.

“We are very pleased with these results, which exceeded our expectations. With no currently approved vaccine, norovirus causes millions of infections globally resulting in billions of dollars of economic burden,” said Steven Lo, Chief Executive Officer of Vaxart. “We believe that our second-generation norovirus oral pill vaccine candidate has the potential to provide first-in-class or best-in-class protection against this highly contagious virus where there is significant unmet need. We intend to incorporate these compelling new data into our ongoing discussions with potential partners.”

Assuming a partnership or other funding, Vaxart expects to conduct a Phase 2b safety and immunogenicity study that could potentially begin as early as the second half of 2025 followed by an End of Phase 2 meeting with the U.S. Food and Drug Administration (FDA). A Phase 3 trial could then begin as early as 2026.

Vaxart’s oral pill technology works by inducing expression of antigen proteins in the cells of humans’ intestines. Vaxart’s second-generation technology was developed in 2023 and 2024 to achieve two purposes: first, to increase expression levels of the antigen proteins, and thus to greatly increase antibody titers; and second, to improve manufacturability. In pre-clinical experiments, the second-generation constructs substantially improved antibody responses in animal models. The trial reported today, for the updated norovirus vaccine candidate, is the first test in humans of the new technology. Vaxart has also adopted the new technology in its latest COVID-19 vaccine candidate and implemented these improvements throughout its portfolio.

There is no approved vaccine against norovirus, a leading cause of acute gastroenteritis (AGE) worldwide that is responsible for outbreaks of infection and illness globally. Each year there are approximately 685 million norovirus infections globally, with 20 million infections occurring annually in the United States. Due to these high rates of infection, norovirus is believed to cause nearly 20% of diarrheal disease globally. Additionally, the economic burden associated with norovirus infection and AGE is estimated at $60 billion worldwide and $10 billion in the United States.

Vaxart is a clinical-stage biotechnology company developing a range of oral recombinant vaccines based on its proprietary delivery platform. Vaxart vaccines are designed to be administered using pills that can be stored and shipped without refrigeration and eliminate the risk of needle-stick injury. Vaxart believes that its proprietary pill vaccine delivery platform is suitable to deliver recombinant vaccines, positioning the company to develop oral versions of currently marketed vaccines and to design recombinant vaccines for new indications. Vaxart’s development programs currently include pill vaccines designed to protect against coronavirus, norovirus and influenza, as well as a therapeutic vaccine for human papillomavirus (HPV), Vaxart’s first immune-oncology indication. Vaxart has filed broad domestic and international patent applications covering its proprietary technology and creations for oral vaccination using adenovirus and TLR3 agonists.