Medical Laboratory Scientist at bench with micropipettes. —
Courtesy U.S. National Institutes of Health (Public Domain)
Innovative medicinal products and healthcare applications are necessary for the advancement of society. Often science and business come together, based around products and ideas. What is it like establishing a rapidly growing business within this dynamic marketplace?
Bryan Kobel is CEO of TC BioPharm (Holdings) PLC (NASDAQ: TCBP), a clinical stage biotechnology company developing platform allogeneic gamma-delta T cell (a subset of T cells that promote the inflammatory responses of lymphoid and myeloid lineages) therapies for cancer and viral indications.
Kobel’s company went public earlier this year and Digital Journal spent some time probing the inner workings of innovative biotechnology.
Digital Journal: Can you provide a brief background on TC BioPharm?
Kobel: TC BioPharm (TCBP) was founded in 2014 by Dr. Mike Leek and Angela Scott, both thought leaders and recognized key opinion leaders in their respective fields of cell therapy. Mike is a self-ascribed “cell therapy junkie” who had stumbled upon a technology in Japan around these really interesting but little discussed or understood T-cells called gamma-deltas.
These cells piqued Mike and Angela’s interest upon deeper review, and Angela developed our gamma-delta T-cell (GDT) manufacturing process and licensing of our plant, while Mike worked on the therapeutic protocols and raising money. The idea was taking these innate killer cells, the first line of defense of the immune system with an inherent ability to locate and kill cancer infected and virally-infected cells, and expand them into the billions and then infuse the unmodified cells into the patient.
Basically, Mike and Angela felt Nature is undefeated, so let’s just provide it the reinforcements the system needs of the soldiers it would normally use, only do it using healthy activated vibrant donor cells allogeneic instead of the tired cells in an autologous approach. Pretty soon, the team had grown exponentially and fast forward to today, we are the leading gamma-delta company in a number of areas, have great clinical data and are looking at multiple clinical and operational inflection points in the next 6-9 months.
DJ: TC BioPharm went public earlier this year, why did the company decide to take this step?
Kobel: There are a number of reasons we chose to go public, but mainly access to capital was the driving force in our decision-making process. TCBP has large clinical trial aspirations relative to the number of indications we are pursuing, our ACHIEVE trial in the UK/EU has launched in acute myeloid leukemia (AML) with Emma Nicholson as the lead chief investigator.
We are looking at an AML trial in the US-where we have Orphan Drug Designation for our OmnImmune product in AML – which would include a wide range of patients, and we are also reviewing an umbrella trial in multiple blood cancers in the US. This is all not to mention the potential angles in sub-indications in AML, where our clinical team has a strong interest, and with our senior clinical director Dr. Sebastian Wanless leading the charge after he spent 20 years at Bristol Meyers Squibb. We believe we have a good chance of success if properly capitalized for these trials. Beyond the immediate trials, our development team, led my Emilio Cosimo, is working on really exciting, cutting-edge things for the next iteration of our gamma-delta therapeutic platform.
These include but are not limited to solid tumor approaches using chimeric antigen receptor (CAR) versions of gammas and the use of gammas in varying combination therapies. We have stealth programs being developed as well for next-gen cell therapy advancements, so we are cash hungry, but also extremely well-positioned to continue to hold our leadership position. We have hired incredibly smart, innovative and self-driven people, and now it’s our job to give them the tools and capital to pursue their efforts with vigor. Of course……it’s always nice to give shareholders and exit too!
DJ: What is allogeneic gamma-delta T-cell therapy and why is it important?
Kobel: An allogeneic gamma-delta T-cell therapy is a therapeutic derived from donor for a patient. In today’s commercial cell therapy approaches like CAR-Ts, the patient – who is extremely sick and has a weakened immune system – is “donating” their blood, having their particular T-cell isolated and expanded and modified, and then receiving that product derived FROM the patient back as the therapeutic.
As you can imagine, with all these steps it’s costly, it can be arduous on the patient and the eligible patient population can be low given you’re product inherently comes from an immune suppressed or immune destroyed patient. The hurdles there are obvious, and we went through an autologous trial and experienced these uphill battles first-hand of trying to create a robust therapeutic out of a very beaten up T-cell population. So the allogeneic approach is where we ended up. We now use donor blood, we freeze it down and bank the starting product, then to create the therapeutic, we thaw, isolate these particular cells – the gamma-deltas – and expand them into the billions.
Once we’ve expanded these cells, we freeze the therapeutic dose down again and store it for use. So it’s truly off the shelf in that regard, we can thaw the product in most hospitals and deliver it to the patient directly. The therapy is important for a number of reason, the most important of which and the main reason the team at TCBP works so fervently, is the benefit we are seeing in patients. It can save lives. Beyond that, the therapeutic has no toxicity due to the innate mechanism of action in the gamma-delta, it only targets sick, unhealthy cells around its antigen trigger.
So the therapeutic can potentially slot into a number of areas in the treatment paradigm without drug on drug interaction and bolster the response from patients. Chemotherapy, bone marrow transplants, CARs, and other therapies are highly toxic, the patient has to survive the disease and the treatment, and if one treatment fails, it’s hard to get that patient healthy enough for the next round of chemotherapy or a new treatment. The gammas have none of those issues, so you could use them to delay the disease, and get the patient stronger for the next step.
You can use them to “clean up” after the more brutal assaults on the system. You can dose patients repeatedly to keep them in a remission state. The possibilities are pretty wide for this therapeutic. And we aren’t asking these cells to change who they are or modifying them. All we’re saying is go do what you do every day, there’s just a lot more of you to go after these “bad” cells like cancer.
DJ: Can you discuss your current clinical trials and their results?
Kobel: We completed our Phase 1b/2a in relapse/refractory AML most recently, showing one stable disease and three complete responses, including one patient who exhibited morphologic leukemia free state (disease -“free”). The patients received one dose of our lead product OmnImmune and the disease state was measured at 14 and 28 days post infusion or the dose. These were palliative care patients with 4-6 weeks to live, if that, who had failed all other treatments available and this was meant as a safety trial for our allogeneic unmodified gamma-deltas. So seeing the responses we did, albeit in a small patient cohort, in such a short time frame of 28 days was quite remarkable.
The average blast count of patients at infusion was 38%, we saw a reduction in blast count in these patients 28 days later to 6%. For reference, anything below 5% is considered to be remission. This all occurred with no adverse events and no signs of toxicity, so it’s quite exciting. Obviously, the regulators were quite pleased and we have moved forward with OmnImmune, now in a Phase 2b/3 pivotal trial dubbed ACHIEVE which has launched.
The protocol is for a second line therapy as a bridge to transplant, patients who have had chemotherapy and failed to see a response will receive our therapeutic to stabilize the disease state and get them to a bone marrow transplant. At the moment we are expecting a data read out on the first cohort of ACHIEVE in Q1 2023.
DJ: What are the main regulatory challenges you have faced and how did you address these?
Kobel: Being the first to do something always presents challenges, especially when you’re talking about a therapeutic being used in humans! The initial regulatory hurdle we faced was convincing the MHRA – the European FDA – to allow us to move into a safety trial without any other animal models, like humanized mice for example. Once we were able to clear that hurdle, founders Dr. Mike Leek and Angela Scott did a phenomenal job presenting a strong case for animal models being difficult to interpret, and that the most prudent approach would be to go directly into humans with some added precautionary safety.
Our next hurdle really is around donor blood restrictions and differences in the US versus the UK/EU. There are so many nuances in cell therapy and it’s still a very young therapeutic area, so I think both companies and regulators are working diligently at each turn to build a formalized process. We’ve been lucky, I think the regulatory agencies recognize the need for these products and the outsized patient benefits we represent, so they’ve continued to work with us at every turn to progress our trials in a reasonable manner.
DJ: What are some of the biggest and most promising trends you are seeing in biotech?
Kobel: For us, the most promising trend is the increased focus on cell therapies and enhancing or engaging the immune system in a more natural approach to fighting disease. The use of gamma-delta t-cells, natural kill cells, macrophages and any number of companies looking to harness and activate the innate immune system without toxic approaches is a huge step forward. Historically the way we’ve fought disease, oncology specifically, has basically been to create a poison that kills the disease before it kills you. This is a pretty brute force approach that gives patients an extended life but at a terrible cost many times. I think the advancement of technology of the last 15-20 years has gotten us to a point where we understand the immune system and the body to a much more detailed degree which has led to significant advancements in our ability to use more “natural” treatments for oncology.
Whether that’s modified cells, like CAR-Ts or gene-edited cells, or unmodified allogeneic approaches like TCBP’s OmnImmune, the promise of efficacious treatments with low-to-no toxicity is a paradigm shift in healthcare. We think cell therapy is the future for treatment in a number of disease verticals, oncology and central nervous system (CNS) diseases jump to the forefront of my mind, and it’s exciting to see so many innovative companies moving quickly into the clinic with strong scientific data. There’s a wave of cell therapies coming into the clinic today and for the foreseeable future, so this could represent a game-changing moment in how these diseases are treated across the board.
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