Just WHO is TSCAN?

You’ve seen us post about them on social media, perhaps seen they have screening sites open for their clinical trial – but just who are they as a company? And why should you, someone in the omie community, care?

Check out a summary of a recent interview with Debora Barton, Chief Medical Officer at TSCAN Therapeutics and be sure to tune into the podcast episode, linked at the button below:

Getting to Know TSCAN Therapeutics:

Tell us a little about yourself, your career – specifically what fuels your passion for what you do?

Starting at a very young age I have always been curious about cancer – what it is, where does it come from, how come some of them spread, and how some people have very good outcomes while others do not? With that curiosity I went to medical school, where I was taught about the amazing systems that compose the human body, and the ways it slides into all different types of diseases, including cancer. Back then, cancer treatment options were very limited, and I continued with my questioning, which transitioned into how come there are only these few treatment options? And with that, I dove headfirst into clinical research. In the beginning of my oncology career as an investigator, I would enroll patients in clinical trials while in clinic. Fast forward to now, I write and manage the clinical trial protocols, which guide the clinics as to how to go about giving innovative therapies to their cancer patients through clinical research. Fairly recently, one of the clinical trials that I worked on, was so beneficial to patients, that it got a new drug approved for the treatment of a specific type of cancer called neuroendocrine tumors, in the USA and in Europe. That is the ultimate goal – to run a clinical trial utilizing a new technology or platform, that hopefully will bring more benefit to patients versus the current standard of care – that ultimately it can become an approved therapy available to all patients with that type of cancer. 

What is your role at TSCAN Therapeutics and why did you become a part of their team?

At TScan I am the Chief Medical Officer, which means I work with a team of very capable clinicians, scientists and clinical operations professionals to ensure the cellular therapy products that TScan has discovered and is developing, goes to the right patient, at the right time, that a complete data package is collected in order for us to fully understand the true benefits and any potential risks of these innovative therapies. I ensure every and any safety finding is fully understood, and hopefully, if the benefits outweigh the risks, we can, in the future, get a new therapy approved for all patients with certain tumor types.

Can you please give us an overview of TSCAN as a company, their mission, and what you do within the group?

TScan Therapeutics is a clinical-stage biopharmaceutical company focused on the development of T cell receptor (TCR)-engineered T cell therapies (TCR-T) for the treatment of patients with cancer. The company was founded on the premise that we can learn from patients winning their fight against cancer to treat those who are not. We currently have two clinical-stage programs across hematologic malignancies (heme) and solid tumors. Our heme program consists of two lead TCR-T cell therapy candidates, TSC-100 and TSC-101. TSC-100 and TSC-101 are designed to target minor histocompatibility antigens HA-1 and HA-2, respectively, to treat residual disease and prevent relapse in patients with acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), and myelodysplastic syndromes (MDS) undergoing allogeneic haploidentical hematopoietic cell transplantation (HCT) with reduced intensity conditioning (RIC). It is a mouthful, but in short, patients with various hematological malignancies, or what people call “blood cancers”, who undergo a certain type of transplant, would receive our innovative cell therapy product to avoid the cancer from coming back.

For solid tumors, TScan is populating its ImmunoBank, a repository of therapeutic TCRs that recognize diverse tumor cell targets and are associated with multiple HLA types, to provide customized multiplexed TCR-T therapies for patients with head and neck, cervical, anal, non-small cell lung, melanoma (including uveal melanoma), and ovarian cancers. Solid tumors are notoriously heterogenous, meaning tumors often express more than one target. To overcome this, TScan has designed its clinical trial to support the administration of two to three TCRs based on the targets expressed and intact HLAs in a patient’s tumor. In the solid tumor clinical trial, we will get a patient’s tumor sample through either a biopsy, or via a recent archival sample, and check for how many targets that tumor expresses – and we intend to aim at 2 to 3 of them, not only one, based on the biopsy findings. We feel that through multiplexing we can increase response rates as well as duration of response in these patients. 

What led TSCAN Therapeutics to work in the space of our rare disease, Metastatic Uveal Melanoma?

TScan has chosen indications with targets that are frequently co-expressed in prevalent solid tumors to enable multiplexed therapy. For example, within melanoma, 50% of them are expected to express MAGE-C2, 90% to express PRAME, and 50% to express MAGE-A1, all of which are targets of TCRs from our ImmunoBank. We believe that with a well-populated ImmunoBank, we will be able to treat a substantial amount of patients with melanoma, including uveal melanoma, in the U.S.

What is HLA typing and how is the HLA typing needed for your protocol different than that of tebe? How does the results of the HLA typing come in to play in your development of your treatment protocol? 

HLA typing, also known as human leukocyte antigen (HLA) typing, is a process used to identify the specific HLAs present in an individual. HLAs are proteins found on the surface of most cells in the body, this is why we can test HLA with a simple buccal swab, the cells in the oral mucosa will have the same HLAs as any other cells in the body. HLAs play a crucial role in the immune system by helping the body to recognize foreign substances such as bacteria. The ImmunoBank is being filled with TCRs that aim at targets presented by different HLAs, not only A*02:01 (the same HLA as required for the treatment with tebentafusp), but also by B*07:02, C*07:02, A*01:01 and others in the future. Having a wider range of HLAs in the ImmunoBank enables more patients to potentially be a match to receive at least one of the TCR-T cell therapy products being developed by TScan. HLA loss is a known mechanism of resistance in cancer and can lead to resistance against immunotherapies. To overcome this, TScan is prospectively screening patients for intact HLAs in order to allow T cells to accurately identify and attack a patient’s cancer.

Why is the prescreening for your trial an important thing for patients, physicians, and doctors to be aware of?  

Our solid tumor program consists of two separate protocols: a screening protocol and a treatment protocol. The goal of the screening protocol is to test for target expression and the presence of HLA genes in patients’ tumors. This information is then used to determine eligibility for enrollment into the treatment protocol and the guide selection of which TCR-Ts to administer to the patient. The advantage of having these two steps separately, is that patients can be screened while they are receiving another therapy, even if they are stable or responding to such therapy. This way, we can understand if they may be eligible to join the treatment study if and when they experience disease progression. If progression occurs and they already know their target expression and HLAs, we can rapidly initiate the treatment protocol with very simplified blood and scan testing. 

Can you summarize some of the critical research areas you are focused on in addition to metastatic uveal melanoma?

We have prioritized targets that are frequently co-expressed in prevalent solid tumors. Our current pipeline focuses on head and neck cancer, cervical cancer, anal cancer, NSCLC, and ovarian cancer, in addition to melanoma. Separately, we have entered into a collaboration with Amgen to harness TargetScan to identify the antigens recognized by T cells in patients with Crohn’s disease. Our TargetScan platform can be applied to virtually any TCR that plays a role in the cause or prevention of disease and we have developed this technology to be extremely versatile and applicable across multiple therapeutic areas, including cancer, autoimmune disorders, and infectious diseases.

What is your vision for the future of uveal melanoma?

Our vision at TScan is to bring forward innovative and effective cellular therapies where there remains an unmet need, such as uveal melanoma. We hope our therapies will bring clinical benefit in the form of tumor responses, to improve the quality of life and prolong the life for these patients, as well as in patients across other prevalent solid tumors and heme malignancies. 

If patients wanted to learn more about TSCAN and current trial sites, current screening sites, and/or research for uveal melanoma, where would be the best sources for that information?

The best place to find up-to-date scientific and clinical trial information is both through our website at www.tscan.com, or by looking up our open studies on clinicaltrials.gov. We encourage you to view our clinical trial site listings up-to-date information at NCT05812027 (screening protocol) and NCT05973487 (treatment protocol).