An Innovative Solution To An Intractable Problem: Immunotherapy For Ovarian Cancer

Upshot

Our coverage of BioVaxys over the last year has largely focused on their universal SARS vaccine, which the company is developing with it’s research collaborators at The Ohio State University . Now that the COVID hype is dying down, biotechs that pivoted all their resources toward COVID initiatives may be found high and dry, lacking both funds and investor interest. BioVaxys is not one of these companies. Throughout the pandemic, BioVaxys has made steady progress on their core initiative: developing immunotherapeutic vaccines for ovarian cancer, colorectal cancer, and a range of other solid tumors. The company’s unique approach to a universal SARS virus dominated headlines, stealing focus from the drug development programs that are central to their operation. Now, it's time to revisit the status of BioVaxys’ anti-cancer vaccine development program.

In recent months, the company has made some significant strides towards a Phase 1 safety and efficacy study for BVX-0918, one of their lead cancer vaccines, as a treatment for late-stage, platinum-resistant ovarian cancer. We can expect the company to make three big announcements later this year as the BVX-0918 GMP* bioproduction  process is finalized, the Clinical Trial Application (CTA) is filed in Europe, and they begin recruiting for their Phase 1 clinical trial. The company has confirmed participation of two well-published clinical investigators from the Hospice Civils de Lyon, France’s premier site for clinical studies in the EU, to participate in the Phase I study. With shares hovering around $0.11 CAD (market cap $11M CAD), BioVaxys may be poised for turnaround catalyzed by shifting investor sentiment (biotech is poised for a run after months of slaughter) and their material advancements along the drug approval process.

*Good Manufacturing Practices (GMP): an FDA standard that ensures that biologics and pharmaceuticals intended for human use are produced in compliant facilities and under specific manufacturing conditions that reproducible and well-documented, resulting in uncontaminated, consistent product with little batch-to-batch variation.

The Science

Anti-cancer vaccines

The potential for vaccines to treat cancer has been explored over the last 30 years. Conceptually, an anticancer vaccine functions just like an antiviral: the vaccine primes the body’s immune system to recognize cancerous cells and, in a highly-specific manner, eliminate them. Unfortunately, the development of anticancer vaccines has not been straightforward, and many issues must be addressed, such as antigen-specificity, delivery methods, combination immunotherapies, and issues surrounding the tumor “microenvironment” and immunosuppression. Identification of tumor-specific antigens* is extremely important to ensure that the vaccine directs cytotoxic (“cell killing”) immune cells directly to the tumor and away from normal, healthy cells. Once a suitable antigen is selected and an immune response induced, the immune cells must be able to reach the tumor site and perform their function without inhibition. Improving T cell access into the tumor and combating the immunosuppressive tumor microenvironment are critical aspects to developing a successful anticancer therapy.

*antigen: a toxin or other foreign substance (often a protein) which induces an immune response in the body, especially the production of antibodies.

Biovaxys has surmounted the antigen specificity problem by using whole tumor cells as the inoculating agent, exposing the immune system to cancer cells excised from the patient’s own tumor. When injected into the bloodstream, the immune system recognizes these cells as foreign agents and begins ramping up antibody and immune cell (T and B cells) production against proteins “visible” on the surface of the cancerous cells.

BioVaxys’ second piece of ingenuity lies employs a tweak of chemistry to prime the cancer cells to invoke a “super immune” response.

“Super immune” response

The core of BioVaxy’s innovation is the attachment of a “hapten” protein to cancer antigens.  Haptens are molecules that induce an immune response only when attached to a large carrier protein, such as the proteins found on the surface of excised tumor cells. The hapten-antigen complex can increase the targeted immune response beyond naturally occurring levels. Once the haptenized cancer antigens are recognized by the immune system, antibodies are generated against the hapten-antigen conjugate and T cells begin destroying the cancer cells.

In the context of developing antiviral or anticancer vaccines, a hapten “teaches” the patient’s immune system to recognize and target a virus or tumor by making the hapten-modified (“haptenized”) antigen more “visible” to the immune system (more so than if the antigen alone was presented to the immune system).

Read MedicalGold’s primer on the immune system.

De-risked development

From our original article: Biovaxy’s antiviral and anti-cancer vaccine development platform is an extension of the protein haptenization and vaccine development efforts by Dr. David Berd, Chief Medical Officer of Avax Technologies (while at Thomas Jefferson University). Avax technologies invested over $100M in research and development of haptenized antigens for antiviral and antitumor vaccine development and patented the MVax® and OVax® vaccines for melanoma and ovarian cancer, respectively. Both vaccines were in clinical trials but were halted for financial reasons, but not before promising clinical data was generated (see Ovarian Cancer and Melanoma sections below). Biovaxys licensed the Avax vaccine development with the mission of enhancing the core technology through state-of-the-art protein chemistry and leveraging the core science of the existing platform to expand their drug development pipeline.

The legacy of haptenized vaccines is well-established, and the positive Phase 1/2 data for MVax®/OVax® are a testament to the safety, efficacy, and clinical study design and manufacturing protocols of the haptenized tumor cell vaccine development platforAvax technologies invested over $100M in research and development of haptenized antigens for antiviral and antitumor vaccine development and patented the MVax® and OVax® vaccines for melanoma and ovarian cancer, respectively.

Ovarian cancer vaccine

BVX-0918A

Ovarian cancer is an extremely fatal disease (3x that of breast cancer) that affects ~300,000 women worldwide per year. It is considered the deadliest gynecologic malignancy in developed countries, and the majority of Stage III/Stage IV disease will ultimately be recurrent and resistant to chemotherapy. Clearly, new treatment modalities are needed. Biovaxys’ BVX-0918A vaccine for ovarian cancer is based on the single-hapten OVax® therapy developed by Avax.

Recently, Biovaxys entered into a partnership with Hospices Civils de Lyon ("HCL"), a public hospital and France's premier site for clinical studies in the EU, to conduct the Phase 1 clinical study and supply the surgically debulked tumor cells for late-stage ovarian cancer. From the press release: Access to surgically removed ovarian cancer tumor cells is a critical step enabling BioVaxys to validate the manufacturing process for BVX-0918. BioVaxys recently entered a similar collaboration with Deaconess Research Institute in the United States to provide the Company with surgically debulked tumors from Stage III/Stage IV ovarian cancer patients. Tumor samples from both hospitals are being used to validate the tumor collection protocol, cryopackaging, cryopreservation, and supply chain logistics for BVX-0918 bioproduction for prospective patients in the US and EU. Tumor samples from HCL will also be used for process testing and manufacturing "dry runs" of BVX-0918, a major step leading to the completion of Good Manufacturing Process ("GMP") production, a requirement for the planned CTA with the EMA.

The company has also entered into a contract with BioElpida, a France-based bioproduction organization, to produce their BVX-0918A autologous cellular vaccine. Cell banks (OVCAR-3) have been created and stored for creating identity assays which will have to be performed on every batch of ovarian cancer vaccine to ensure reproducibility of the manufactured product.

"Completion of OVCAR-3 cell banks is another step towards our ability to produce GMP yields of BVX-0918, and brings us closer to our Phase I study in the EU planned for later this year."

~ Kenneth Kovan, BioVaxys President and Chief Operating Officer

BioVaxys is preparing to file a Clinical Trial Application ("CTA") with the European Medicines Agency ("EMA") later in 2022 and begin the Phase 1 study of BVX-0918A for late-stage ovarian cancer in early 2023.

Market Conditions

Market conditions in the biotech sector are among the worst I have ever seen in any sector in my 20-year trading and investment career. However, we are beginning to see signs of insider buying activity picking up and M&A activity in the biotech sector.

BioVaxys shares have not been spared the destruction across the biotech sector and broader market.

BIOV.CA (Daily)

The $.10 area is important support from which BIOV will need to build out a base as it advances its ovarian cancer vaccine to a phase 1 trial in France early next year. The market pendulum has swung from optimism and excitement to fear and pessimism. Astute long-term investors know that the best times to accumulate investment positions are during times pervasive pessimism and depressed share prices.

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.