BioVaxys Company Update: Stock Soars Upon Positive FDA Feedback for COVID T Cell Diagnostic Test

T cells and Immunity

The COVID-19 pandemic may as well be called the COVID-21 plague, as hospitalizations and death toll continue to skyrocket due to the emergence of new SARS-CoV-2 variants around the world. Our body’s immune systems are adaptive, capable of creating an army of pathogen-fighting scouts and foot-soldiers to locate and eradicate the viral insurgents. To continue the military analogy, viruses engage in guerilla warfare and adapt quickly to the counter-insurgency’s weapons and tactics (the immune system) by way of natural mutation. The Catch-22 of a strong immune response is that the weak virions are eliminated while the better-equipped continue to infect human host cells and replicate exponentially. The insanely fast rate of viral mutation is responsible for creating these better-equipped “super soldiers.” To put this in perspective, the estimate of mutation for HIV-1 predicts that any single mutation conferring drug resistance should occur within a single day of infection [1]. Mutation rates are expressed in units of substitutions per nucleotide per cell infection, which translates to the rate that the DNA (randomly) mutates per the number of infected cells. Both HIV-1 and influenza have similar mutation rates (~2.4 x 10^-5). Luckily, SARS-CoV-2 mutates almost 10x slower (~10^-6) than these two viruses due to its molecular “proofreading” mechanism [2]. This slower mutation rate implies that vaccines developed against the original SARS-CoV-2 virus could have long-lasting effects compared to the flu, which quickly becomes obsolete due to quick influenza strain mutation. 

To investigate the possibility that SARS-CoV-2 variants might escape the adaptive immune system response, created by either prior infection or vaccination, researchers at the National Institute of Allergy and Infectious Diseases (NIAID, part of the National Institutes of Health), analyzed the immune cells found in the blood of 30 patients that were infected but then recovered from COVID-19. The purpose of this study was to identify immune cells (if any) that remain active against SARS-CoV-2 variants. The research team, led by NIAID’S Andrew Redd, PhD, concluded that the cytotoxic T cells (CD8+ T cells) found in previously-infected patient’s blood remain active against three SARS-CoV-2 variants (B.1.1.7, B.1.351, and B.1.1.248). Previous research has shown that the neutralizing antibodies (Nab) response to different variants are variable, so measuring antibody levels in previously-infected patient’s blood is unlikely to indicate whether that patient will be immune to other variants. Immunity against SARS-CoV-2 variants is most likely conferred by T cell activity; identifying the presence of these T cells targeted against SARS-CoV-2 will inform clinicians and patients about their likelihood of contracting newly mutated strains [3].

BioVaxy’s CoviDTH® Diagnostic

The majority of current COVID-19 tests only measure antibodies, ignoring the powerful, broad-spectrum T cell effect.  Although some significantly more expensive T-cell tests are available, they require a blood draw to be sent to a specially equipped centralized laboratory.   

BioVaxy’s CoviDTH  is a cost efficient and fast turn-around diagnostic that is based on the principle of Delayed-Type Hypersensitivity (DTH).  DTH is known to be a measure of T cell activity and has been used for many years for other infectious diseases (tuberculosis, fungal diseases, mumps). Similar to an allergy skin test, CoviDTH works by placing a small amount of synthesized test material (recombinant SARS-Cov-2 s-protein) intradermally and inspecting the site for redness and minor swelling similar to a mosquito bite 24-48 hours later. CoviDTH is a patent-pending, disposable syringe with ~ 3mm micro needle and ~100mcg of fully-characterized, purified, non-infectious, synthesized SARS-CoV-2 s-1 protein in liquid suspension. The test results can be measured with a ruler or a cell phone app that BioVaxys is developing. By adding the spike proteins from other SARS-CoV-2 variants, CoviDTH has the potential for detecting T-cell responses related to emerging variants such as the B.1.1.7 and 501Y.V2, as well as others such as the delta and lambda variants

The CoviDTH® diagnostic is superior to antibody tests because…

• Antibody levels decline over time, while T cell responses are long-lasting.
• T cells may recognize different patterns of antigens (viral proteins) than antibodies recognize.
• The precise antigens used in antibody tests are poorly characterized, so it is not possible to know whether those antibodies being measured have a neutralizing effect on the virus.
• The FDA has not recommended that antibody tests be used to assess immunity , implying that the antibodies being measured may or may not kill the virus.
  

CoviDTH® is ready for primetime.

BioVaxys received word from the FDA that the company’s clinical plan is adequate to file an Investigational new Drug (IND) application to enter a combined Phase I/II safety and dosing/efficacy study without needing to perform an animal toxicity study. The Agency also concluded that the Chemistry, Manufacturing and Controls section of their application is acceptable, meaning that the manufacturing process is well-defined and ready to be produced at scale (Learn more about BioVaxy’s manufacturing agreement for SARS-CoV-2 vaccine and OVID-T diagnostic program).

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"With the guidance we received from this FDA review, BioVaxys is now able to begin preparing its IND. Although the FDA has indicated that our planned animal tox study is discretionary, we will likely continue with the animal tox study of CoviDTH as it does not interfere with the development time frame and may in fact provide useful data."

~ Ken Kovan, BioVaxys President and Chief Operating Officer

Next Steps

BioVaxys intends to complete the animal toxicity study (even though it is not required) to glean more information about the CoviDTH test, and is now currently preparing the IND application to support the combined Phase I/II study in humans. 

BioVaxys is well positioned to continue advancing its multi-pronged approach that includes Covid-DTH, its SARS-CoV-2 vaccine based on its haptenized viral protein technology, and BioVaxys' BVX-0918A ovarian cancer vaccine candidate.

BIOV shares have been trading in a range-bound accumulation pattern in the last few months, a pattern that appears to be on the verge of resolving to the upside:

BIOV.CA (Daily)

With the TSI (True Strength Index) on the verge of crossing into bullish territory and the RSI (Relative Strength Index) in bullish territory pointing higher, all that's left is for a weekly close above $.30 for BIOV shares to target the next resistance zone between $.45 and $.50.

References

[1] Sanjuán Rafael, Nebot, M. R., Chirico, N., Mansky, L. M., & Belshaw, R. (2010). Viral Mutation Rates. Journal of Virology, 84(19), 9733–9748. https://doi.org/10.1128/jvi.00694-10

[2] Manzanares-Meza, L. D., & Medina-Contreras, O. (2020). SARS-CoV-2 and influenza: a comparative overview and treatment implications. SARS-CoV-2 e influenza: revisión comparativa e implicaciones del tratamiento. Boletin medico del Hospital Infantil de Mexico, 77(5), 262–273. https://doi.org/10.24875/BMHIM.20000183.

[3] AD Redd et al. CD8+ T cell responses in COVID-19 convalescent individuals target conserved epitopes from multiple prominent SARS-CoV-2 circulating variants. Open Forum Infectious Diseases DOI: 10.1093/ofid/ofab143 (2021).

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Disclosure

Author owns BIOV.CA shares at the time of publishing and may choose to buy or sell at any time without notice. Author has been compensated for marketing services by BioVaxys Technology Corp.