Vaxart is a clinical-stage biotechnology company focused on developing oral recombinant vaccines. They are working on an oral COVID-19 vaccine candidate called VXA-CoV2-1. Vaxart’s vaccine is a room temperature stable tablet, rather than an injectable like the currently approved mRNA vaccines from Pfizer/BioNTech and Moderna. Vaxart’s oral tablet vaccine works by delivering vaccine antigens to the immune cells in the lining of the intestines to generate an immune response. This could offer potential advantages over injectable vaccines including easier administration, better efficacy against mucosa transmitted viruses like SARS-CoV-2, and potentially enabling mucosal immunity. However, Vaxart’s COVID-19 vaccine candidate is still in early clinical trials and is not yet approved.
Vaxart’s Technology
Vaxart specializes in oral recombinant protein vaccines. Their proprietary oral vaccine platform uses adenovirus type 5 (Ad5) vectors to deliver protein antigens to immune cells in the lining of the intestines. This triggers both systemic immunity through antibody generation, as well as mucosal immunity by activating intestinal lymphocytes. Vaxart believes their oral tablets may have several advantages over injectable vaccines:
- Needle-free administration could improve uptake and coverage
- Oral delivery enables activation of mucosal immunity in the intestines
- Tablets are room temperature stable for easy storage and distribution
- May be manufactured more easily and at lower cost than injectables
In addition to COVID-19, Vaxart is also developing oral tablet vaccine candidates for norovirus, seasonal flu, respiratory syncytial virus (RSV), and human papillomavirus (HPV).
VXA-CoV2-1 COVID-19 Vaccine
VXA-CoV2-1 is Vaxart’s lead COVID-19 vaccine candidate. It contains adenovirus vectors engineered to express the SARS-CoV-2 spike protein antigen. In phase 1 clinical trials, two doses of VXA-CoV2-1 generated immune responses against SARS-CoV-2 comparable to levels associated with protection in convalescent sera. Vaxart has also reported that VXA-CoV2-1 vaccination resulted in IgA responses in the mucosal linings of the airways, indicating activation of mucosal immunity.
In June 2021, Vaxart initiated a phase II study evaluating the efficacy of VXA-CoV2-1 against COVID-19 infection compared to placebo. The phase II trial plans to enroll ~800 participants across multiple study sites in the US and assess immune responses as well as protection against SARS-CoV-2 infection. Results from the phase II trial are expected in 2022 and will provide important efficacy data on VXA-CoV2-1 compared to placebo.
Phase I Clinical Trial Results
In Vaxart’s phase I trial, the VXA-CoV2-1 vaccine candidate demonstrated:
- Robust SARS-CoV-2 specific antibody responses after 2 doses
- Comparable antibody titers to convalescent sera from COVID-19 patients
- Activation of mucosal IgA antibody secreting cells
- Favorable safety profile with mainly mild adverse events like headache, fatigue, and injection site pain
These results supported advancing VXA-CoV2-1 into phase II efficacy trials. However, the phase I study was small (n=35) and did not include a placebo control arm, so efficacy could not be assessed. The phase II trial will provide much more definitive efficacy data.
Phase II Efficacy Trial
- Randomized, placebo-controlled trial in ~800 participants
- Will evaluate two dose vaccination regimen of VXA-CoV2-1
- Primary endpoint is prevention of symptomatic COVID-19 infection
- Secondary endpoints include immune responses and safety monitoring
Results from the phase II trial are expected in 2022 and will indicate whether VXA-CoV2-1 provides protection against COVID-19 compared to placebo.
Status of Vaxart’s COVID-19 Vaccine
As of October 2022, Vaxart’s VXA-CoV2-1 COVID-19 vaccine candidate is still in phase II clinical trials. It is not yet approved for use by any regulatory agencies. The vaccine cannot be administered to people outside of clinical trials.
Based on the phase I results, VXA-CoV2-1 appears to generate robust immune responses against SARS-CoV-2. However, efficacy data is still needed from the ongoing phase II trial before VXA-CoV2-1 could be considered for emergency use authorization or approval.
Vaxart will need to successfully complete phase II and III trials demonstrating VXA-CoV2-1 is safe and effective. The company will then need to apply for regulatory approval from agencies like the FDA and EMA. This approval process typically takes many months to years after efficacy is proven in late stage trials.
In summary, Vaxart is developing an oral COVID-19 vaccine candidate, but it remains in clinical testing at this time. More data on its efficacy is expected in 2022 from the phase II trial. Approval would only be possible after completing additional clinical studies.
Advantages of Vaxart’s Approach
Vaxart’s oral tablet vaccine may offer some potential benefits over the currently approved mRNA and viral vector injectable COVID-19 vaccines:
Needle-Free Administration
An oral tablet vaccine eliminates the need for injections and could help improve vaccine uptake. Some people have a fear of needles or are uncomfortable receiving shots. An oral tablet is easier to administer and could improve coverage.
Activation of Mucosal Immunity
Oral vaccination can stimulate immune cells within the mucosa or lining of the intestines. This may provide better protection against SARS-CoV-2 since it primarily infects and replicates in the respiratory mucosa. Having IgA antibodies in the mucosa could block viral entry and replication.
Room Temperature Stable
Vaxart’s vaccine tablets are designed to be stable at room temperature for months. This could eliminate the need for freezer storage and complex cold chains required for mRNA vaccines and make distribution much simpler, especially to low and middle income countries.
Potentially Lower Manufacturing Costs
As a protein subunit vaccine, VXA-CoV2-1 may be simpler and less expensive to manufacture at scale compared to more complex mRNA or viral vector vaccines. However, real cost comparisons are difficult to make at this early stage.
Protection Against Emerging Variants
The adenovirus vector vaccines appear to maintain efficacy against some SARS-CoV-2 variants like Omicron with spike protein mutations. Vaxart has also reported on preliminary research indicating VXA-CoV2-1 maintained antibody responses against Alpha, Beta, Gamma, and Delta variants in animals. Further clinical data is needed on protection across emerging variants.
Disadvantages and Challenges
While Vaxart’s oral vaccine approach offers some potential benefits, there are also disadvantages and challenges:
Unproven Efficacy Against COVID-19 Infection
The biggest disadvantage currently is that VXA-CoV2-1’s efficacy against COVID-19 infection is still unknown. The phase II trial results expected in 2022 will provide the first efficacy data. In contrast, the approved mRNA vaccines have proven >90% effective in large clinical trials.
Adenovirus Vector Immunity
Pre-existing immunity to the adenovirus type 5 vector in some people could reduce VXA-CoV2-1 immune responses. This has been observed with other Ad5-vectored vaccines. Strategies like using alternative rarer adenovirus serotypes could potentially overcome this issue.
Oral Vaccine Unfamiliarity
Clinicians and the public lack familiarity with oral vaccines compared to standard shots. This could present an initial adoption challenge if approved. Demonstrating comparable efficacy and safety to existing vaccines will be critical for acceptance.
Potential Gastrointestinal Side Effects
Delivering antigens directly to the intestines could cause temporary GI side effects like diarrhea, nausea, or abdominal pain more frequently than injectable vaccines. The phase II trial will provide more safety data.
Refrigeration Likely Still Required
While room temperature stable initially, Vaxart’s vaccine will likely still require refrigerated storage for long term shelf life similar to other oral vaccines. However, this should still provide advantages over mRNA vaccines requiring deep freezing.
Investment and Funding
As a clinical stage biotechnology company, Vaxart requires significant ongoing investment and funding to support its vaccine development programs. Some key sources of Vaxart’s financing include:
Stock Offerings
Vaxart has periodically issued new stock through public offerings to raise operating capital. For example, in June 2020 Vaxart raised $90 million by issuing new shares.
Government Funding
Vaxart has received some government funding support including:
- $4.7 million from NIH and BARDA for oral flu vaccine development
- $8.9 million from CARB-X for norovirus and RSV vaccine development
- Over $9 million from DHHS for its oral coronavirus vaccine candidates
Licensing Deals and Royalties
Vaxart can generate revenue by licensing their proprietary oral vaccine platform technology to other pharmaceutical companies, as well as through royalties on any approved products. For example, they receive royalties from Emergent BioSolutions for their approved oral adenovirus vaccine.
Strategic Partnerships
Vaxart has partnered with companies like KindredBio to help advance their vaccine candidates, providing funding support. Partnerships with contract manufacturing organizations are also critical for vaccine production.
Investor Funding
Various institutional and individual investors have provided private capital. As of mid-2021, Vaxart had raised over $200 million from investors and financial groups like Armistice Capital.
Manufacturing
To bring an oral COVID-19 vaccine successfully to market, Vaxart needs to demonstrate the ability to manufacture the vaccine reliably at scale. Some key aspects of Vaxart’s manufacturing include:
Vaccine Production
The vaccine antigen is produced using a recombinant protein manufacturing process, likely involving fermentation in engineered bacteria or yeast. The adenovirus vector is also produced separately in cell culture.
Tableting
The bulk vaccine proteins and vectors are then formulated and processed into stable oral vaccine tablets using pharmaceutical grade equipment and standard tableting methods.
Fill/Finish
The vaccine tablets are filled into bottles, labeled, packaged, and stored ready for distribution. Fill/finish for oral tablets is less complex than vials of injectable vaccines.
External Manufacturing Partners
Vaxart will likely rely on contract manufacturing partners to produce bulk vaccine antigens and drug product. They have existing partnerships with Catalent, Lonza, and KindredBio.
Scalability
Switching between clinical to commercial scale manufacturing can present challenges. Vaxart will need to demonstrate the vaccine production processes and supply chains can be scaled up to produce hundreds of millions of doses annually.
Regulatory Compliance
All contract manufacturing partners must have facilities that meet strict cGMP and regulatory guidelines enforced by FDA/EMA. Vaxart’s manufacturing will face intensive oversight and inspection.
Vaccine Component | Production System |
SARS-CoV-2 Spike Antigen | Recombinant protein/fermentation |
Adenovirus 5 Vector | Cell culture |
Formulation | Tableting/fill-finish |
Manufacturing Partners | Catalent, Lonza, KindredBio |
Intellectual Property Protection
Vaxart relies on patents, trade secrets, and proprietary know-how to protect its oral vaccine platform technology. Some key elements of its intellectual property portfolio include:
Oral Vaccine Delivery Platform Patents
Vaxart has over 150 issued and pending patents covering:
- Methods of oral vaccination with adenovirus vectors
- Novel adenovirus constructs and genetic modifications to vectors
- Production and manufacturing methods
- Formulation and stabilization of oral adenovirus tablets
These platform technology patents provide broad protection for Vaxart’s oral vaccine approach using adenovirus vectors.
COVID-19 Vaccine Candidate Patents
Vaxart has filed for patents specifically on the composition and methods of use for their VXA-CoV2-1 construct.
Other Product Specific Patents
The company has additional pending and issued patents for their other pipeline vaccine candidates targeting HPV, flu, RSV, and norovirus.
Trade Secrets
Key proprietary methods and know-how in areas like production cell lines, quality control assays, and manufacturing processes are also trade secrets retained by the company.
Company Financials and Stock Performance
As a publicly traded company, Vaxart’s financial results and stock price performance provides insight into investor sentiment on the company’s vaccine programs.
Overall Financial Results
Vaxart does not currently generate product revenue, with all funding coming from investors and licensing/grants. Some key financial metrics from 2020 results:
- Net loss of $35.9 million
- $126.2 million in cash and equivalents
- R&D expenses of $20.1 million
- G&A expenses of $15.4 million
- Revenue of $4.0 million (grants)
These results show Vaxart’s heavy spending on R&D and reliance on capital raising to fund operations. Revenue growth requires successful product development.
Stock Price and Valuation
Vaxart’s stock price saw significant volatility since 2020, driven by COVID-19 vaccine news. Key trends:
- Spiked from $1.25 to $17.49 in January 2021 on COVID-19 program news
- Traded between $5-10 range through most of 2021
- Currently around $3.00 per share (October 2022)
- Market capitalization around $400 million
Vaxart’s valuation rose dramatically during periods of optimism around its COVID-19 program before retreating. Continued volatility is likely until definitive efficacy data readout.
Management and Leadership
Vaxart’s executive management team includes:
- Andrei Floroiu – President and CEO
- Sean Tucker – Chief Scientific Officer
- James Cummings – Chief Medical Officer
- Margaret Echerd – Vice President of Corporate Communications
Other key leaders include long-time board member Michael Finney and directors with pharmaceutical industry experience like Anne VanLent and Todd Davis.
The management team brings experience in viral vector vaccines, drug development, corporate strategy, and communications to support bringing Vaxart’s oral vaccine platform to market.
Conclusion
In summary, Vaxart has developed an oral recombinant adenovirus vector COVID-19 vaccine, VXA-CoV2-1, which is currently in phase II efficacy trials. The oral vaccination approach could offer advantages including easier administration, potential mucosal immunity, and better storage stability compared to injectable vaccines. However, Vaxart’s candidate remains early stage and still requires successful phase III trials and regulatory approval before widespread use. Efficacy results from the ongoing phase II study expected in 2022 will provide the first definitive indication whether VXA-CoV2-1 can protect against COVID-19 compared to placebo. Vaxart’s oral vaccine platform also faces challenges like unproven large scale manufacturing and potential pre-existing adenovirus immunity effects. But if the efficacy and safety data holds up, Vaxart’s easy to take oral tablet could become a useful alternative COVID-19 vaccine option. The company has accumulated significant losses and relies on stock issuances and licensing deals for funding. Vaxart’s stock has been volatile based on COVID-19 program news. Vaxart has an experienced management team to guide development, but faces risks inherent to clinical stage biotechnology companies.