TScan Therapeutics reaches agreement with US FDA on pivotal study design for TSC-101 and announces strategic prioritization to advance TSC-101

TScan Therapeutics, Inc., a clinical-stage biotechnology company focused on the development of T cell receptor (TCR)-engineered T cell (TCR-T) therapies for the treatment of patients with cancer,  announced regulatory and clinical programme updates, implementation of a workforce reduction of approximately 30%, and extension of its cash runway into the second half of 2027.

Following a productive end-of-phase 1 meeting with the US Food and Drug Administration (FDA), the company has reached alignment on the registrational path forward for the TSC-101 programme as a treatment for acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). The pivotal study will mirror TScan’s ongoing phase 1 study, using a biologically assigned internal control arm to support relapse-free survival as the primary endpoint. Through a strategic prioritization, the company will advance clinical development of its heme programme, pause further enrollment in its solid tumour phase 1 trial, and focus preclinical efforts on developing in vivo-engineered TCR-Ts for solid tumours and on target discovery for autoimmunity. In connection with this strategy, the Company’s workforce is being reduced by approximately 30%, or 66 employees.

“We are encouraged by the positive feedback from the FDA on our heme programme and our pivotal trial design for TSC-101. In preparation for the pivotal study, we developed a commercial-ready manufacturing process that shortens the manufacturing time by five days. This results in substantially lower cost of goods and reduces the need for high levels of ex vivo T cell expansion that we believe may be associated with decreased T cell activity in patients. The strength of our long-term data, together with our improved commercial-ready manufacturing process, validates our decision to focus resources on the heme program,” said Gavin MacBeath, Ph.D., chief executive officer. “In our solid tumour programme, we have successfully dosed our first two patients with multiplex TCR-T and plan to share data in the first quarter of 2026. With our new strategic focus on clinical execution within the heme programme, we are pausing further enrollment in the PLEXI-T trial and shifting efforts to the preclinical development of an in vivo engineering platform for solid tumours.”

Dr. MacBeath continued, “We have a unique opportunity to develop and potentially commercialize a compelling program for patients with heme malignancies and are well positioned to develop the first in vivo-engineered TCR-T programme for patients with solid tumours. This prioritization best enables TSC-101 to be developed as quickly and efficiently as possible. Unfortunately, these strategic measures impact a number of our talented TScanners. I am deeply grateful for their commitment to TScan’s mission and their dedication to the patients with serious diseases that we aim to treat and ultimately cure.”

“By focusing clinical development on heme and rightsizing the organization accordingly across all functions, we expect to realize annual cost savings of approximately $45.0 million in 2026 and 2027,” said Jason A. Amello, chief financial officer. “This achieves our goal of preserving capital while continuing to build shareholder value. As a result of these efforts, we have extended our cash runway into the second half of 2027.”

Hematologic malignancies program:

• In October 2025, the company met with the FDA regarding a pivotal trial design for TSC-101, which is designed to treat residual disease and prevent relapse in patients with AML or MDS undergoing allogeneic hematopoietic cell transplantation (HCT) with reduced intensity conditioning (RIC). The interaction was productive and the FDA has agreed to a study design that mirrors the current phase 1 ALLOHA trial (NCT05473910).
• The updated pivotal trial design now includes a biologically assigned internal control arm instead of an external control arm using the CIBMTR registry. In the pivotal trial design, patients who are HLA-A*02:01-positive with an HLA-A*02-negative donor will be assigned to the investigational arm of the study, and patients who are HLA-A*02-01-negative or patients for which an HLA-mismatched donor cannot be found will be assigned to the control arm. This trial design will enable efficient enrollment and streamlined assessment of study endpoints.
• A fixed dosing regimen was introduced into the ALLOHA trial in 2025 and, in agreement with the FDA, the company plans to dose approximately five more patients at this dose level to support the upper end of their proposed recommended dose range prior to initiating the pivotal trial. The company now expects the pivotal trial for TSC-101 to begin in Q2 2026.
• The company recently observed instances of relapse or prolonged incomplete chimerism using a high sensitivity assay in TSC-101 patients who were enrolled in the phase 1 study in 2025. These cases appear to be associated with products that had higher levels of T cell expansion in the manufacturing process. The company has now implemented an improved, commercial-ready manufacturing process that is shorter (12 days vs. 17 days) and requires less T cell expansion. An initial technology transfer of this process to an external contract development and manufacturing organization has been completed. The commercial-ready process will be used to dose the additional patients requested by the FDA in the ongoing phase 1 and registrational studies.
• Data from the ALLOHA phase 1 trial, including two-year relapse data on initial patients treated with TSC-101, will be presented at the 67th American Society of Haematology (ASH) Annual Meeting and Exposition.

• In October 2025, the first two patients were dosed with multiplex TCR-T therapy candidates in the PLEXI-T solid tumour trial. In addition, seven patients have been treated to date with singleplex TCR-T at dose level 3 or higher.
• The company is pausing further enrollment on the study and proceeding with preclinical development of in vivo engineering to treat solid tumours. The Company has recently partnered with a third party specializing in the development of a lentiviral-based platform for in vivo engineering of T cells. The company believes that this approach represents a promising and cost-efficient way to deliver off-the-shelf, multiplexed TCR-T for solid tumours.
• The company expects to share initial safety and efficacy data from the PLEXI-T trial in Q1 2026.

• In October 2025, the company presented initial data from their autoimmunity programs at the American College of Rheumatology Conference 2025, held in Chicago, IL.
• The company continues to identify novel targets in prioritized autoimmune diseases such as ankylosing spondylitis, systemic sclerosis, ulcerative colitis, and birdshot uveitis. In addition, the company is continuing to discover targets for Crohn’s disease in partnership with Amgen.

• The strategic prioritization is expected to produce annual cost savings of $45.0 million in 2026 and 2027, and will impact approximately 30% of the company’s workforce, or 66 employees. The company expects to record a one-time charge of up to approximately $2.3 million in the fourth quarter of 2025 for severance-related benefits and other costs.
• The company’s cash runway is now extended into the second half of 2027.