Last Friday, MedicalGold sat down with Kenneth Kovan and Dr. David Berd, the COO and CMO of BioVaxys, respectively, to discuss the company’s recent headlines. What we anticipated would be a high-level overview of the company’s positive news regarding their COVID-19 vaccine platform and CoviDTH diagnostic turned into a much more detailed discussion about their upcoming in vitro study, cancer vaccine program, and the ingenuity of their haptenized antigen approach to vaccine development. It turned out to be an illuminating, fascinating discussion about a topic not being given enough coverage by the media.
Let me begin by congratulating you on your progress over the last few months. The positive news concerning the human studies of your CoviDTH diagnostic was groundbreaking. This T cell immunity diagnostic has been flying under the radar for so long, and only recently has the scientific community been vocal about the importance of T cells in giving people durable, long-lasting immunity to SARS-CoV-2. Yesterday’s announcement of the in vitro study you plan on conducting for your COVID vaccine caused quite a stir in the investment community, and we expect to see some clear results that demonstrate the superiority of your haptenized antigen approach to vaccine development. What’s very interesting to me is the claim that your approach will make a safer vaccine than the ones currently in the market. I know that myocarditis and thrombocytopenia are some significant concerns and are making people wary of getting vaccinated. It’s obvious that creating a vaccine that eliminates those side effects will lead to greater vaccine adoption. So, let’s start the discussion by explaining how haptenized antigens can generate a stronger and safer immune response than the current vaccines.
First of all, great interpretation of our research. You hit the nail on the head. Hapten modification (“haptenization”) is a very old immunological trick. It was discovered by a researcher named Landsteiner who won the Nobel Prize because he also discovered the ABO blood groups. A hapten is a small molecule, of which there are tens of thousands to choose from, that trigger the immune system when they are bound to a larger molecule. The key property of haptens is that they have a very strong affinity for proteins, so it was easy for us to modify the “spike” protein (s-protein) that is introduced to the immune system by our COVID vaccine. Our theory is that a haptenized s-protein will elicit a stronger immune response than the natural s-protein alone, meaning that we could create a stronger COVID vaccine using this simple chemical modification. These haptens are basically signals to the immune system that say “hey, you need to pay extra attention to the protein I am bound to. It’s up to no good.” There have been animal studies that show that you can haptenize a naturally-found protein that would never, under normal circumstances, be recognized as dangerous by the immune system, and elicit a strong immune response against that innocuous protein. Clearly this is a very powerful way of enhancing immune responses and creating more powerful vaccines.
One very important thing to note… haptenization augments both the antibody responses and T cell-mediated responses. Our company is quite interested in the latter, but both are important. With our cancer program, we don’t know what specific piece of the tumor cell (antigen) is reactive, so we must use the whole cancer cell to prime the immune system to fight. However, with the COVID program we can select our antigen, and we chose an antigen that is a piece of the SRS-CoV-2 spike protein. Many other groups (Pfizer, Moderna, J&J, AstraZeneca) are targeting this same antigen for good reason [it’s the most mutable region of the virus, so you can create vaccines that are specifically for SARS-CoV-2 and do not have off-target effects].
So, what you’re saying is that a haptenized s-protein results in an increase in neutralizing antibodies and T cells?
Well, what we’ve done with our vaccine, called “BVX-0320”, is prepare the haptenized s-protein and tested it in mice using four ascending doses. Virtually all the mice developed a high antibody titer that bind to the virus. And a dose response was clearly demonstrated. We also tested the T cell response in vitro by measuring the production of cytokines, which are inflammatory molecules that indicate that the immune system is gearing up for attack. In a select number of mice, we were able to show that the antibodies produced actually neutralized the virus.
And does the data support the idea that the vaccine could work against multiple SARS-CoV-2 variants? Does your haptenized spike protein offer a durable, long-lasting immunity?
Well, durable, long-lasting immunity depends on the type of immune response that you generate. So, for example, the antibody responses that are generated by most people are transient, meaning that they go up rapidly but then quickly fall back down. In my opinion, we are not sure how quickly those antibody levels drop down below an effective level. And this is very controversial. People are arguing this out. But it’s a pretty good assumption that a haptenized protein would produce an antibody response of similar duration. Now, where our vaccine differs significantly is in the T cell immunity response. As opposed to the short half-lives of antibodies, T cells are virtually forever. So, when you induce a T cell response against a viral protein, it lasts for a very long time. There is abundant evidence to support what I just said. For example, there are people who recovered from SARS-CoV-1 in 2003, and they still have a potent T cell response against the virus to this day. There have been some people who have been studied in old age, their late 80s, who were infected by measles in their youth and still have T cell responses against the measles virus. The power of the T cell response can not be understated, and we are on the forefront of this research.
We believe that our BVX-0320 vaccine will induce a durable T cell response in addition to the short antibody response. We do not yet know the exact duration of the T cell response, maybe it will last a lifetime. But all the current data clearly shows that T cell responses are long-lasting.
Why do you think so much attention has been focused on the antibody response to COVID and not the T cell activity?
Well, it’s a pretty simple answer. It is a lot easier to measure antibody response, not only for COVID but for other viruses like influenza. There’s a lot of research out there on antibody responses, and any reasonably equipped lab can run these experiments. It’s also relatively inexpensive. T cell responses are more difficult to measure. These experiments require a lot of blood from the subject, and you must isolate the T cells and then incubate the T cells in a tissue culture to get a readout. Experimenting with live cells is much more delicate than conducting a simple antibody binding assay. Not to say that it hasn’t been done before, it is just much more tedious. So far, there are only two laboratories (to our knowledge) in the United States that have commercialized T cell response assays. Both require a blood draw and cost a minimum $300 per test. It’s just not feasible to run these experiments on hundreds or thousands of subjects, like in the vaccine clinical trials. BioVaxys is about to change that with our CoviDTH diagnostic, an incredibly simple test that requires no blood draw and is analogous to a simple skin allergy test.
Another reason is that it is simply harder to understand and communicate to the public. It’s easier for science reporters to talk about antibodies, which is basically common parlance at this point. Their choice is not based on science, it’s based on their own convenience.
I’m glad you brought up your COVID T cell diagnostic, the “CoviDTH” test, designed to detect the T cell responses in patients exposed to the virus. If the BioVaxys COVID vaccine [BVX-0320] works against multiple SARS-CoV-2 variants, then does it stand to reason it can detect infection of emerging variants?
Yes. Well, the CoviDTH diagnostic is a T cell test, and T cells are more broadly reactive than antibodies. We already know that the antibody tests are reacting against almost all of the variants that have been tested so far. So, we are quite certain that the CoviDTH diagnostic will determine immunity to multiple variants. The difference is that we will be able to determine this immunity months and even years after infection. Antibodies will not give us that information. And if it turns out that another variant emerges that is not cross-reacting, then we could easily modify the test material just as everybody else in the industry does. So far that hasn’t happened yet.
The simplicity of the test is that if there was a new variant that the CoviDTH, in its current configuration, couldn’t detect, then it would be very easy for us to modify the test. Both our vaccine and diagnostic programs are platform technologies, which can easily adapt to new viruses.
That makes sense. Does the CoviDTH test require a doctor or nurse to administer?
No, it doesn’t have to be a nurse, but just a paramedical person that is licensed with the state. So, a pharmacist can administer it, just like with the vaccines.
The key thing to remember is that this is very similar to an allergy test. It’s a very miniscule, intradermal application, almost identical to the tuberculosis tests of years past. The CoviDTH does not require a specialized facility and could be performed in a CVS or Rite Aid.
Could the CoviDTH also be performed in an airport or train station?
Yes, exactly. All it requires is minimal training on how to use a short needle to inject the tiny bit of s-protein material under the skin. Any doctor, nurse, paramedic, or trained pharmacist could do this. So far, the CoviDTH test is pretty much idiot-proof. As soon as the s-protein is injected into the skin a T cell response is detected by a small bit of redness and swelling. Either you react or you do not. It’s a binary answer that requires no special knowledge or training to interpret.
Very interesting. So, getting back to the COVID vaccine… one of the major concerns of the medical community is that the currently available vaccines won’t be as effective against future viral variants. Is BioVaxy’s vaccine development platform more efficient at generating new s-protein variants than the mRNA approach being used by Pfizer and other large pharmaceutical companies?
It’s fairly easy to synthesize new pieces of mRNA to vaccinate against new variants, but the difficulty is in the regulatory process. So, the question is whether it is faster and cheaper to develop a brand-new piece of RNA or a new haptenized protein from a variant. We think that our process is simpler and cheaper, and we can get it through the regulatory process faster. Time will tell whether we are right.
We have been receiving a lot of questions about the upcoming in vitro study in which you will measure the binding of the haptenized s-protein to the AEC2 receptor, which should inform us about the toxicity of your vaccine. Our understanding is that the hapten molecule attached to your s-protein, in addition to creating a heightened immune response, prevents the binding of that s-protein to the ACE2 receptor located on human cells, which should reduce the likelihood of deadly side effects associated with current vaccines [e.g., myocarditis and blood clotting disorders]. What’s the timeline look like, and can you provide us with any additional details of the study?
We plan on initiating the study within six to eight weeks, once we finalize our academic partners. The entire study should not take more than two to three months. Given the high antibody response, robust T-cell activation, and neutralizing antibody response that we have already confirmed with BVX-0320, we do not see this ACE2 binding study to be pivotal for our planned IND for next year. However, a positive outcome as we anticipate would significantly differentiate the benefit of haptenization from others such as the mRNA and adenoviral vector vaccines.
Now on the study itself… we are working with a synthesized S1 subunit of the spike protein (s-protein) that is found in the SARS-CoV-2 virus. In Nature, the s-protein is responsible for binding to the ACE2 receptors found on human cells, allowing the virus to infect those cells. The ACE2 receptor is found on many types of human cells, including lung cells, heart cells and platelets. All the available vaccines (whether they are mRNA or adenovirus-based) are using a s-protein to “prime” the immune system and induce an immune response against the SARS-CoV-2 virus. The issue is that introducing “extra” s-protein into the body via vaccine can have off-target effects since the synthesized s-protein is free to bind to ACE2 receptors on heart cells and platelets (leading to heart inflammation and blood clotting disorders). We believe that our novel, haptenization approach inhibits the binding of the haptenized s-protein to the ACE2 receptors. In theory, this would prevent the life-threatening side effects seen with the other vaccines by Pfizer, Moderna, and J&J. We are going to test this theory in a variety of cell lines that express the ACE2 receptor and compare the binding ability of our haptenized s-protein against the natural s-protein.
Very interesting. A side-effect free vaccine would be a total game changer. I’m sure that vaccine adoption will go up dramatically if the public’s perception of the negative side effects, no matter how rare, are ameliorated. Have you given any thought to partnerships or deals with governments and healthcare organizations? In particular, the CoviDTH diagnostic test seems like it would be very attractive to governments or healthcare institutions.
While we do not have any definitive agreements inked, we are in serious discussions with various government agencies and a global health organization on rolling out the CoviDTH. Without saying too much, we are getting extremely strong receptivity to this particular product and its anticipated use and benefit. The timing is great because we are currently putting together an IND package to submit to the FDA. Given the simplicity of the CoviDTH test, and the positive human data we have already gathered, we believe that the pathway to approval is going to be relatively straightforward.
That’s great news! One final question. Do you think that there is anything important that investors should know about the BioVaxys opportunity that we have not covered here?
Yes! The discussion today revolved heavily around our COVID vaccine and diagnostic platforms, which are relevant due to the leaps forward we have made on both fronts in the last few months. However, let’s not forget that BioVaxys has a major cancer vaccine program advancing under all the COVID hype. We are planning on starting a Phase 1 trial in Europe next year for our ovarian cancer vaccine. Remember, both the viral and cancer programs are platform technologies, meaning they can be adapted to different viruses and different types of cancers.
To add to David’s response, we are in the process of preparing a Clinical Trial Application (CTA) in Europe for a Phase 1 study that we will begin in early 2022. We have already begun selecting the contract research organizations to conduct the trials, recruitment strategy is being developed, and we are currently preparing and validating the bioproduction process of our tumor cancer vaccine for the study. As you can see, there is a lot going on behind the scenes that is not reflected in the news on a day-to-day basis. Investors need to know that we are continuously operating on all our projects, and value is being created without sexy headlines following it up. The market will catch up to our level of excitement once the CoviDTH diagnostic is approved and we start the clinical trials for the COVID and cancer vaccines!
Gentlemen, it was a privilege speaking with you both this morning. MedicalGold has been covering the BioVaxys story since November of 2020, and it has been a pleasure to follow BIOV as it has advanced its viral and oncological vaccine platforms.
I’m glad you get it. At the end of the day, we are trying to save lives here. Both Dr. Berd and I receive messages from patients with stage 3/4 ovarian cancer, pleading for help. These people are not going to survive much longer. I’m not a clinician, and it can be hard to handle. Thankfully, Dave’s bedside manner is much better than mine! Our mission is simple, our vision is clear. Now all that’s left is to execute. And that’s where we excel.
Here’s to curing COVID and cancer!
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.
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