Enzolytics, Inc., Charles S. Cotropia, Monoclonal Antibodies HIV Treatment

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IN-DEPTH INTERVIEWS WITH Top CORPORATE EXECUTIVES (727) 480-7070 info@ceocfocontact.com

Lynn Fosse, Senior Editor

Steve Alexander, Associate Editor

Bud Wayne, Marketing
& Production Manager

Christy Rivers - Editorial Associate

Enzolytics Technologies Targeting HIV and the CoronaVirus

Charles S. Cotropia

CEO

Enzolytics, Inc.

(OTC PINK: ENZC)

www.bioclonetics.com

Contact:

Charles Cotropia

csc@bioclonetics.com

Interview conducted by:

Lynn Fosse, Senior Editor

CEOCFO Magazine

Published – December 7, 2020

CEOCFO: Mr. Cotropia, what is the concept behind Enzolytics, Inc?

Mr. Cotropia: Enzolytics, Inc. is a drug development company with two separate but complementary therapy platforms for treating infectious diseases, including treatment for HIV. One technology, invented by Harry Zhabilov, the CSO of our company, includes a patented antiviral peptide that has been tested in clinical studies at the National Center of Infectious and Parasitic Diseases in Bulgaria. In these trials, this therapeutic, known as ITV-1, demonstrated effectiveness in the treatment of HIV patients in various stages of the disease. In trials conducted in 31 patients, the therapeutic showed efficacy; specifically, in 68% of those individuals tested, there was an increase in CD4 + T lymphocytes. This increase was accompanied by an increase in the CD4/CD8 index and CD4% in over 50% of those tested. The increase in these parameters demonstrated statistical significance compared to the control group. The absolute number and the relative percent of CD8 + T lymphocytes decreased. And the viral load in 80.5% of those tested was below the threshold of detection.

This Enzolytics anti-HIV treatment is now being advanced through the certification stage to thereafter be made available for patient therapy.

The Company is now combining this technology with recently acquired technology, created by BioClonetics Immunotherapeutics, for creating fully human anti-monoclonal antibodies for treating HIV. Using this technology, the Company has produced a fully human anti-monoclonal antibody that has been tested in 5 international labs where it neutralized over 95% of all strains of the HIV virus against which it was tested. Additional neutralizing antibodies are being produced.

The therapies of Enzolytics’ two technologies, that produced by Enzolytics and that created by BioClonetics, are expected to be synergistic. Additionally, because the HIV virus and the CoronaVirus have correlative structures and with our knowledge of how our monoclonal antibodies neutralize HIV, we are now developing monoclonal antibodies for treating the CoronaVirus.

CEOCFO: Isn’t HIV pretty well taken care of now?

Mr. Cotropia: That is the view, particularly in the U.S., but it is a misconception. There are over 36 million people in the world infected with HIV. There are more than 2 million new infections every year and over one million people die from the virus annually. Ten percent of the HIV deaths are children – amounting to over 300 children deaths per day. That number of children who die from HIV is greater than those that die from cancer.

The reason there is the belief that HIV is no longer a problem is that there is now, and has been for years, a treatment but no cure. The treatment is through administering anti-retrovirals, a treatment that must be taken daily and for life. There is no effective anti-HIV monoclonal antibody on the market for treating HIV and that is the focus of the therapies developed by Enzolytics. In the recent months, the entire world has now come to know “monoclonal antibodies”. This is what was used in a treatment provided to President Trump for the CoronaVirus and now is being development by several companies. In contrast, the current (and for decades) treatment for HIV has been anti-retrovirals, which do not cure HIV patients but rather just keep the virus at bay. Monoclonal antibody therapy offers the promise of total viral neutralization and as a result an effective cure in place of the present anti-retroviral therapy which requires lifelong treatments.

There are several downsides to the use of anti-retrovirals. Because anti-retroviral drugs are a chemotherapy, and not a humoral immunobiological therapeutic such as monoclonal antibodies, long-term side effects of the chemotherapy can result – including kidney problems, involving kidney failure, liver damage (hepatotoxicity), heart disease, osteoporosis, heart disease, diabetes or insulin resistance, an increase in fat levels in the blood (hyperlipidemia), and changes in how the body uses and stores fat (lipodystrophy).

Moreover, the anti-retroviral treatment is only accessible to 40% of the over 36 million people infected in the world – leaving 60% of the 36 million infected HIV patients with no treatment.

Thus, these issues can be resolved by implementation of a better HIV treatment, using immunotherapy with the administration of our technologies including broadly neutralizing monoclonal antibodies.

CEOCFO: I think to a lot of people it seems the crisis is over.

Mr. Cotropia: Your observation is exactly right! The perception is that the HIV crisis is over, but it is a misconception. The extent of the world crisis can be appreciated by the facts I just mentioned, namely, there are over 36 million people in the world infected and only 40% of those have access to the anti-retroviral therapy now used to treat HIV. There are over two million new infections per year and more than one million people die from the virus annually.

The current anti-retroviral therapy is not a cure and as mentioned earlier, the side effects from lifelong use are significant. Also, the yearly average costs of treatment on anti-retrovirals is $14,000 to $20,000 per year and the average lifetime costs is calculated as $379,000. The cost of an anti-HIV therapy we are proposing would be a fraction of this costs since the treatment would be for a limited time and would not require life-long use.

Just as monoclonal antibodies were made available to successfully treat President Trump when he contracted the CoronaVirus, monoclonal antibodies can be made available to treat HIV patients and we believe we are on the verge of providing and validating specific therapies in order to safely and successfully treat HIV.

CEOCFO: From your recent press release, you have a proprietary methodology for producing fully human OGG1 monoclonal antibodies. How is your approach different?

Mr. Cotropia: There are a number of different ways of producing monoclonal antibodies. The procedure is significant and our procedure differs from those used by other pharma companies.

In some cases, other pharma companies produce “humanized” rat and mouse monoclonal antibodies where the original antibody affinity and specificity are not maintained and the chances of immunogenicity are increased. Our methodology also differs significantly from other pharma approaches using the transgenic mouse model, which is a human immune system that has been “grafted” within a mouse model having been "vaccinated" with specific and selected purified virus proteins.

In contrast, our method starts with human "immune-B cells", obtained from convalescent individuals who have recovered from the target virus. The primary distinction of our process for creating fully human monoclonals is the starting point – namely from human “immune-B cells” obtained from humans who have survived successfully from a "natural" infection. From these human “immune-B cells”, we then produce antibodies that target conserved immutable sites (neutralizable epitopes) on the virus’ surface envelope proteins – which will thereby avoid “virus escape”, which has been frequently demonstrated to occur as a consequence of mutations in the HIV virus surface structure.

Additionally, our antibodies retain the original natural antibody affinity and specificity, and have lower risk of immunogenicity when used as a therapeutic. They will provide broad-spectrum coverage against viral variants with increased potency, stability as a single-domain molecule, in what is called the camelid structure form, and, in the recombinant form will have greater accessibility to the virus binding sites not accessible with a whole antibody. We believe that our method is one that produces an antibody which will be more effective with less risk of adverse reaction.

There are an infinite number of distinct anti-HIV and anti-CoronaVirus monoclonal antibodies that can exist – some disease neutralizing, some perhaps of no benefit and some perhaps disease enhancing. Thus, specific antibodies that neutralize are necessary to provide an effective therapy. Enzolytics’ method of producing effective monoclonal antibodies focuses on identifying immutable binding sites on the virus and then creating monoclonal antibodies that bind to such sites and neutralize the virus. In this way, the virus cannot mutate around the therapy. For example, the antibodies administered to President Trump to treat him for the CoronaVirus, may target a site on the virus that will mutate. Thus, the same antibodies may not be effective for you or me later if the CoronaVirus has mutated, changed structure, at this binding site. Our anti-HIV monoclonal antibody binds to a site on the HIV virus that is conserved in 98% of the more than 6000 strains of the HIV-1 viruses now known, sequenced and archived in the Los Alamos National Laboratory HIV Database. The same will have to be achieved for successful anti-CoronaVirus monoclonal antibodies.

CEOCFO: What are you looking at regarding COVID?

Mr. Cotropia: We have produced an HIV monoclonal antibody that had been successfully tested in five international labs where it neutralized 95% of all strains against which it was tested. There are 6000 different strains of the HIV virus now known. We know that that our antibody is effective and we know the target site on the virus resulting in neutralization of the HIV virus. For an antibody to be effective it has to attack a neutralizable site on the virus that is always there, does not mutate from strain to strain. Knowing the binding site of our HIV monoclonal antibody, and then examining the CoronaVirus amino acid sequence, a correlation in the structures has been identified by our CSO, Dr. Joseph Cotropia, between the CoronaVirus and the HIV virus. With knowledge of these homologous viral structures, monoclonal antibodies will be created that target the corresponding “Achilles Heel” site on the CoronaVirus, an expected conserved immutable and neutralizable site on the virus. Additionally, using artificial intelligence, we will examine the numerous different strains of the virus to identify other conserved sites and produce additional monoclonal antibody targeting them. This is for the purpose of producing a “collection” or “cocktail” of antibodies for therapeutic use. We recognize that there are now known over 16,000 different variations or strains of the CoronaVirus, each slightly different due to mutation. A successful monoclonal antibody “cocktail” therapy must include multiple antibodies that specifically target several immutable sites and which results in neutralization.

For example, we all now know that President Trump received a combination of two Regeneron antibodies. Eli Lilly has also produced an anti-CoronaVirus antibody. However, what we do not know is whether those antibodies will be successful as the virus mutates. As I mentioned, there are now known 16,000 different variants to the CoronaVirus and immutable sites must be the targeted in order to be effective in the long run.

Also, as all experts in the field of monoclonal antibodies agree, including Dr. Anthony Fauci, head of the NIAID/NIH, to have an effective therapy, we must have multiple monoclonal antibodies that target various sites on the virus - and in fact, even President Trump was given a cocktail of two. Therefore, it is imperative to identify conserved neutralizing binding sites on the CoronaVirus, and create multiple monoclonal antibodies that target these critical neutralizable and immutable structures. It is like finding a needle in a haystack and retrieving the needle; you must identify the immutable sites on the virus and then create and characterize fully human monoclonal antibodies that target those sites. The process described here will be our focus and for the reason that success has already been achieved with regard to the production of broadly neutralizing antibodies directed against the HIV virus, we expect success will likewise be achieved in production of broadly neutralizing human monoclonal antibodies directed against the CoronaVirus.

CEOCFO: I realize your brother is the medical person behind the company, but what led you to take on this role. You have been a practicing attorney for many years. Why this challenge now?

Mr. Cotropia: Obviously, it is very rewarding to hope that we will produce something that will be so meaningful to so many people. Our initial focus has been on HIV, a still devastating disease which is very much still with us and certainly more so in other counties. That is because in the U.S., the focus is off of HIV; because most U.S. citizens who contract HIV can afford $20,000 a year, through insurance or otherwise, and be treated. Unfortunately, many of those who have taken anti-retroviral for thirty years or less have to suffer side effects caused by the current therapy, so there is a great reward and a great challenge in the hope that we can produce something that is better. We see a better therapy and a therapy that can be produced inexpensively for all, and particularly for the 60% and the 36 million people who have no access to currently available anti-retroviral therapy. In many countries, like the U.S., this situation no longer makes the headlines in the news. For us, we recognize the need for a better therapy.

Now, we turn to the CoronaVirus and that is something that is on the front page of the U.S. and world news. We definitely have taken note of that. How do you address it? The antibodies that are being produced by other pharma companies may very well have initial beneficial effects. However, a solution requires more than one antibody to be effective. If their antibody targets a site that mutates, and that is what has happened to every other monoclonal antibody produced by the NIH and big pharma in their attempts to treat HIV, it is ultimately not going to be effective. The virus will mutate around it. Therefore, what worked, perhaps, for President Trump, will not necessarily work for you or me in the future. Consequently, as the virus mutates over and over again—in order to be therapeutically successful—you have to target a site that is immutable.

We do know that our identified initial target on the CoronaVirus is significantly different from the targets of the antibodies produced by Regeneron and Eli Lily. Thus, with a combination of our proposed broadly neutralizing anti-CoronaVirus antibodies, the administration of a “cocktail” of several antibodies could be expected to produce a more significant neutralizing effect.

If you look back to the history of HIV, the NIH, with Vaccine Research Center and all the other companies that the NIH has supported, they all attempted for forty years to produce an effective anti-HIV monoclonal antibody and the ones that they produced, VRC01 and VRC02, to name just a few, failed in years-long testing because of what is called “virus escape”. Virus escape is a euphemism for the fact that the virus mutated around what they spent decades trying to produce. Hence, there is a challenge to develop a successful therapy. To answer your question more directly, it is the challenge and more than that, it is the hope of having a successful therapeutic that drives us. Also, at Enzolytics we also have a therapeutic which will, we expect, be synergistic with our monoclonal antibodies. It is a peptide that binds to the virus and provides a clinically tested therapeutic effect, which will be examined in combination with our monoclonal antibodies. Again, this combination hopefully will be synergistic and provide a therapeutic that will be highly effective.

CEOCFO: What is your funding position? Development and eventually commercialization are very expensive.

Mr. Cotropia: Yes, that is a very relevant question. We will be securing long term financing for advancing our technology. We have begun the process of producing variants of our existing anti-HIV monoclonal antibodies and identifying target site on the CoronaVirus for producing multiple antibodies against that virus. We are extending our lab capabilities on the Texas A&M University campus at its Institute for Pre-clinical Studies where we will be producing both addition monoclonal antibodies against HIV and the against the CoronaVirus. For HIV, we will be combining the anti-HIV neutralizing antibodies with the anti-HIV peptide—which is also immunomodulating—that has been previously clinically tested by Enzolytics to have beneficial effect in HIV patients. The funding we arrange will take us through that development which will include animal trials to be followed by human clinical trials of these therapeutics.

Success in these steps will bring the necessary funding for success. Demonstrating positive results will translate into the necessary funding due to the dire need for these therapies. As I mentioned, there is not going to be one bullet that fends off either the HIV virus or the CoronaVirus. It will be necessary to have more than one. We welcome Eli Lilly and Regeneron in their initial antibody production and that success is all to be rewarded and celebrated. However, as we have seen in the past with HIV, it is going to be a very difficult to completely control the CoronaVirus and all of its mutated forms. Success will require multiple therapeutics and we know that monoclonal antibodies will certainly be in the picture and in the front line of successful treatments.

Another important aspect of our technology is that identification of a neutralizable binding site on the virus can lead to the creation of a vaccine – one that would be of a different format from the current mRNA vaccines now being produced. Specifically, the vaccine would be based on the known broadly neutralizing antibody and the highly conserved binding site to produce an active immunization that would not comprise nor incorporate an immunization process using nucleic acid constructs. In this process, a protective active immunization would use the neutralizable binding site on the virus as subunit peptide vaccine. Use of peptide sub-unit immunogens in active immunization obviates the concerns for weak humoral immune response, theoretical risks of insertional mutagenesis, and provocation of an autoimmune response, in other words, concerns associated with immune response outcomes that are related to DNA and mRNA vaccination.

Therefore, different vaccines may be produced in very different ways, some of which hopefully will be very effective and very safe as to their long-term effect on the human body. A safe vaccine can be expected, based on a subunit peptide vaccine formulation using the neutralizable bind site on the virus in its development.

CEOCFO: There are so many new ideas, especially around COVID. Why does Enzolytics’s approach stand out?

Mr. Cotropia: We have a patented anti-HIV peptide, ITV-1, that has been tested in clinical studies. It is now being advanced through the next certification stage in preparation for patient application.

As a complementary treatment for HIV, we have created monoclonal antibodies for treating HIV. These antibodies can accurately be identified as being “fully human” broadly neutralizing monoclonal antibodies in that the starting point is from human “immune-B cells” providing the basis for production of the antibodies. Antibodies created in this way retain the original natural antibody affinity and specificity, and have lower risk of immunogenicity when used as a therapeutic. They will provide broad-spectrum coverage against viral variants with increased potency and stability as a single-domain camelid molecule. Our technology then further stands out in that we are able to identify conserved, immutable sites on the targeted virus and we have the ability to specifically create monoclonal antibodies that target these identified sites. The whole process is, in our view, a perfect approach to producing therapeutics that are safe and effective and that address and overcome the effect of virus mutation - all the while being able to be produced inexpensively, so they may be provided throughout the world.

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“There are an infinite number of distinct anti-HIV and anti-CoronaVirus monoclonal antibodies that can exist – some disease neutralizing, some perhaps of no benefit and some perhaps disease enhancing. Thus, specific antibodies that neutralize are necessary to provide an effective therapy. Enzolytics’ method of producing effective monoclonal antibodies focuses on identifying immutable binding sites on the virus and then creating monoclonal antibodies that bind to such sites and neutralize the virus. In this way, the virus cannot mutate around the therapy.” Charles S. Cotropia

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