TScan Therapeutics (NASDAQ:TCRX) said it is shifting its strategic focus toward an in vivo engineered T-cell platform for solid tumors, advancing two product candidates targeting PRAME and MAGE-A4 into investigational new drug, or IND, enabling activities.
Chief Executive Officer Gavin MacBeath said the company had paused its prior solid-tumor program in October 2025 to develop the in vivo approach. The platform uses lentiviral delivery to introduce T-cell receptor, or TCR, genes directly into patients’ T cells, with the aim of creating an off-the-shelf treatment that avoids patient-specific cell manufacturing.
Solid-Tumor Program Advances
TScan plans to present preclinical data on its final PRAME and MAGE-A4 constructs, along with a regulatory update, in the first quarter of 2027. It expects to begin GMP manufacturing of the lentivirus in the second quarter, file its first IND in the third quarter and begin a Phase I trial in the fourth quarter of 2027.
MacBeath said the company’s updated lentiviral construct uses two targeting antibodies intended to direct the vector to cytotoxic and helper T cells, while also activating the cells to support expansion. The vector includes the company’s proprietary TCR genes and CD8 co-receptor components.
In preclinical mouse models using an earlier version of the construct, MacBeath said the in vivo product controlled tumor growth as effectively as an ex vivo engineered treatment targeting MAGE-A4, while using less than 10% of the comparable ex vivo dose. He said forthcoming data are expected to detail T-cell transduction, expansion and tumor-control activity in mouse models.
During the question-and-answer session, MacBeath said TScan intends to move relatively quickly through dose escalation once the Phase I study begins. The company expects imaging every six weeks after treatment and said meaningful preliminary clinical data could potentially be available within six months of trial initiation.
Hematologic Program Paused as Company Seeks Partner
TScan also said it is pausing further development of its Phase III hematologic malignancies program for TSC-101 after being unable to secure sufficient funding to complete the study. The company had reached agreement with the FDA on the pivotal study and enrolled its first seven patients, MacBeath said.
TSC-101 is designed to treat residual disease and prevent relapse following hematopoietic cell transplantation. The company will continue following 14 patients in Cohort C, who received product made with its commercial-ready manufacturing process, as well as the seven patients enrolled in the pivotal trial.
MacBeath said Cohort C included 14 high-risk patients, 12 of whom were minimal residual disease positive before transplant. At a median follow-up of six months, the company reported two relapses and a 79% relapse-free survival rate. It also reported that all 14 patients had reached complete donor chimerism at their most recent assessment.
The company plans to present six-month data from the 14 Cohort C patients in the fourth quarter at a major medical meeting. It expects to provide updated results for all 21 patients in the second quarter of 2027, when all patients are expected to have more than one year of follow-up.
MacBeath said the treatment has been well tolerated to date, with observed adverse events consistent with those typically associated with bone marrow transplantation and no increase in concerning events relative to transplant-only control patients. TScan is seeking a strategic partner to fund continued development of TSC-101.
Autoimmune Work Halted Pending Partnerships
The company is also halting further development of its autoimmune program pending a partnership. TScan previously disclosed targets in HLA-B*27-driven autoimmune diseases, including ankylosing spondylitis.
MacBeath said the company has assembled data supporting the biological relevance of several targets and is working to further assess their prevalence across patients and the potential to eliminate target-reactive T cells. He said much of the data package has already been collected, with the next step focused on finding an appropriate partner.
Reorganization Extends Cash Runway
As part of the strategic shift, TScan is undertaking a reduction in force. MacBeath said the move is expected to save $55 million over approximately the next year and a half and extend the company’s cash runway into the fourth quarter of 2027, when it plans to begin Phase I development of its solid-tumor candidates.
The company said it believes the reorganization will prioritize the advancement of its in vivo PRAME and MAGE-A4 programs while it seeks partnerships for its hematologic and autoimmune assets.
About TScan Therapeutics (NASDAQ:TCRX)
TScan Therapeutics is a clinical-stage biotechnology company focused on the discovery and development of T-cell receptor (TCR) therapies for the treatment of cancer. Leveraging its proprietary T-Scan platform, the company seeks to identify high-affinity TCRs that recognize intracellular tumor antigens presented on the surface of cancer cells. TScan’s approach aims to broaden the reach of immunotherapy beyond current targets by unlocking a wider array of cancer-associated proteins.
The company’s pipeline includes multiple preclinical and early-stage clinical programs in both hematologic malignancies and solid tumors.
