EXECUTIVE INTERVIEW - TC BioPharm: Developing Platform Allogeneic Gamma-Delta T Cell Therapies for Cancer

TC Biopharm (Holdings) PLC (NASDAQ: TCBP) (NASDAQ: TCBPW) is a clinical-stage biotechnology company developing platform allogeneic gamma-delta T cell therapies for cancer. Established in 2013 and based in Scotland, TC BioPharm is currently conducting its Phase 2B trials of its proprietary therapeutic, OmnImmune®, an allogeneic unmodified cell therapy consisting of activated and expanded gamma delta T cells. The trial is for the treatment of patients suffering from relapse/refractory Acute Myeloid Leukemia (AML).

OmnImmune comprises gamma-delta T cells sourced from healthy donors, expanded, and activated in large numbers before being purified and formulated for infusion into patients. It is a frozen and thawed allogeneic product, now “banked” from donor derived cells.

Gamma-delta T (GDT) cells are naturally occurring immune cells that embody properties of both the innate and adaptive immune systems and can intrinsically differentiate between healthy and diseased tissue. The GDT cells are activated via their T-cell receptor (TCR) after recognizing molecules that are only present on stressed, virally infected or cancer cells. The activated GDT cells can then use a variety of mechanisms to kill cancer cells and virally infected cells. This includes direct killing via perforin and granzymes, or indirectly through cytokine production. The molecules, which activate GDT cells, are shared by a variety of stressed and tumor cells, making it possible for GDT cells to target a broad range of different tumors. TC BioPharm uses an allogeneic approach in both unmodified and CAR-modified gamma delta T cells to effectively identify, target, and eradicate both liquid and solid tumors.

TC BioPharm is the leader in developing banked allogeneic gamma-delta T cell therapies, and the first company to conduct International Conference on Harmonisation (ICH) compliant Phase 2/pivotal clinical studies in oncology. Previous clinical results have enabled TC BioPharm to obtain FDA orphan drug status for its method of treatment of AML. Orphan drug status is a designation granted by the FDA for therapies targeting rare diseases. The status allows for a 7-year exclusive marketing window post approval of the drug, certain lowered application fees and tax incentives.

The company’s primary goal is to develop safer, less-expensive CAR-T products that can target a broad range of cancers and save more lives. TC BioPharm does this using its integrated model that drives the development of products through preclinical testing to the clinic.

Drug Development & Delivery recently interviewed Bryan Kobel, CEO of TC BioPharm, to discuss the company’s upcoming plans, therapeutic, clinical trials, and the biotech landscape.

Q: What are gamma-delta T cells, and what is their role in supporting our immune system?

A: Gamma-delta T (GDT) cells are a functionally distinct component of the lymphocytes (white blood cells) present within all humans, representing approximately 1%-5% of the circulating population. They are naturally occurring immune cells that embody properties of both the innate and adaptive immune systems and can intrinsically differentiate between healthy and diseased tissue. Tumor recognition and killing is not dependent on the expression of a single antigen, therefore enabling GDT cells to recognize a broad spectrum of antigens on different cancer cells. GDT cells have been termed “unconventional” T cells as they recognize different antigens without presentation by Major Histocompatibility Complex (MHC) molecules. Given their ability to bridge the innate and adaptive immune system, GDT cells have been shown to play a key role to interact directly and indirectly with different immune cells to orchestrate the immune response. As part of the immune system’s innate and adaptive response, their natural properties make them promising therapeutic candidates.

Q: How is TC BioPharm using gamma-delta T cell therapies for the treatment of cancer?

A: GDT cells constantly monitor the body for signs of biological stress, such as cancerous or infected cells, and are one of the first lines of defense against disease. TC BioPharm’s therapies are focused on leveraging the inherent biological capabilities of GDT cells together with an integrated cell engineering approach.

TC BioPharm collects cellular material from healthy donors as a source to manufacture next-generation allogeneic “off-the-shelf” GDT cell therapies for clinical development. To achieve this, we currently use a proprietary media formulation to support the selective expansion of unmodified and CAR GDT cells. This media yields a high number and high purity of GDT cells at the end of the expansion process. Our cell banks have enabled the generation of cost-effective, safe, and efficacious therapeutic treatments that allows us to treat more patients.

OmnImmune is our unmodified allogeneic GDT cell product, being initially used for the treatment of AML, aiming to treat patients who have not responded well to first-line therapy and preventing the need for a bone-marrow transplant.

Q: You recently initiated Phase 2b/3 gamma-delta T cell therapy clinical trials of OmnImmune. Can you discuss the early results?

A: The early results are very encouraging. We have positive safety findings from the first cohort of the clinical trial; the drug was well-tolerated and safe in R/R AML patients, with no dose-limiting toxicities. Furthermore, no signs of acute or chronic graft-versus-host disease (GvHD) nor organ injury were reported. Preliminary safety data shows that our allogeneic cell therapy is safe and well-tolerated, which has enabled the company to progress OmnImmune to Phase 2b/3 clinical trials.

Q: TC BioPharm went public in February of this year. What are your goals as a public company?

A: Our key goal as a public company is to gain more access to capital to help expedite the next phase of our clinical trials and bring OmnImmune to market. We believe this is a truly revolutionary product that will positively impact not only AML treatment but cancer therapies in general.

We also have stealth programs being developed for additional next-gen cell therapy treatments. The capital from going public will help our extremely talented and dedicated staff to develop these treatments.

Q: Can you expand on the opportunities there are to using combination therapies/approaches with OmnImmune for the treatment of solid tumors?

A: A number of other companies have recognized the huge potential of GDT in cancers and are developing non-cell-based therapeutic approaches to enhance GDT function for the treatment of solid tumors. Our therapeutic approach is based upon the infusion of a healthy effector population of GDT and CAR-GDT cells into the patient to target and eradicate the tumor. Our clinical experience has demonstrated that GDT populations in patients with late-stage disease are anergic and exhausted. An opportunity therefore exists as a combination approach to combine these non-cell-based approaches with OmnImmune to augment the clinical response.

In addition, we have a number of in-house and partner programs at the preclinical stage focused on developing CAR modified allogeneic gamma delta T cell products targeting solid and hematological indications.

Q: What are the key trends you are seeing in the solid-tumor CAR-T therapy space?

A: Chimeric antigen receptor (CAR) T cell therapy has made an impact on the treatment of certain blood cancers. Previously, in many clinical studies, the cellular therapy was not as successful for patients with solid tumors. A number of challenges remain for the treatment of solid tumors, including CAR-T function on the immunosuppressive tumor microenvironment, identification of CAR targets selectively expressed on the tumor, lack of tumor target expression in target tissues, CAR T cell trafficking, tumor infiltration, and persistence. The other issue with standard CAR T-cell therapies has been on-target, off-tumor toxicity caused by CAR antigen expression on normal calls.

Different CAR-T approaches are currently under active investigation by CAR-T companies to address these challenges. Today, we are seeing them branch out aggressively into solid tumors as the efficacy data rolls in, especially the gamma-delta companies. Several of these companies are using different CARs to enhance the cell therapy in their indication of choice and can do so while still showing very little of the previously associated toxicity with CAR technologies. There are many CAR-T approaches targeting solid tumors in early clinical development, and many of these are addressing key challenges, such as infiltration, persistence, and exhaustion. It is an exceptionally exciting time to be developing next-gen approaches as we anticipate emerging efficacy data.

Q: Can you provide insight into next steps with OmnImmune and when it will be commercially available?

A: TC BioPharm plans to expand the Phase 2/3 study to the US in the fourth quarter of 2022 or early 2023. Currently, we are in conversations with the US FDA regarding the final trial protocol in conjunction with our US clinical partner.