TScan Therapeutics, Inc. announced a poster presentation highlighting preliminary data from the Phase 1 umbrella clinical trial evaluating TSC-100 and TSC-101 targeting minor histocompatibility antigens (MiHA) HA-1 and HA-2, respectively, to treat residual disease and prevent relapse following hematopoietic cell transplantation (HCT) using reduced intensity conditioning (RIC) in patients with acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), or acute lymphocytic leukemia (ALL) at the American Society of Gene & Cell Therapy (ASGCT) 26th Annual Meeting 2023. TScan has developed two lead TCR-T cell therapy candidates, TSC-100 and TSC-101, that express TCRs targeting MiHAs HA-1 and HA-2, respectively, both presented by HLA-A*02:01. The goal is to select HCT patients who are HA-1 or HA-2 positive, with donors who are mismatched on either the MiHA or HLA-A*02:01.

In this context, TSC-100 and TSC-101 are designed to eliminate all recipient hematopoietic cells, including malignant cells, that persist post-transplant, while leaving donor-derived cells unaffected. Both products are being developed in patients with AML, ALL, and MDS undergoing allogeneic haploidentical HCT with RIC, with the goal of preventing disease relapse. Approximately 42% of patients with these diseases relapse within two years of RIC transplant, at which point there are limited treatment options and poor prognosis.

The longer-term objective is to enable more patients to maintain prolonged remission after receiving HCT with RIC, which is a more tolerable conditioning regimen than myeloablative conditioning. The Phase 1 umbrella trial is a multi-arm, i3+3 study evaluating TSC-100, TSC-101, and standard of care HCT alone (control arm) in patients with AML, ALL or MDS. Patients enrolled in Dose Level 1 (DL1) receive either TSC-100 or TSC-101 upon count recovery after HCT at approximately day 21.

Patients enrolled in Dose Level 2 (DL2) will receive the same dose of TSC-100 or TSC-101 approximately 21 days post-transplant, followed by a second dose administered 40 days after the initial dose, provided there are no safety issues. The trial design also includes a third dose level (DL3), where the second dose is escalated 4-fold. Key Poster Highlights: Phase 1 umbrella clinical trial evaluating TSC-100 and TSC-101 targeting MiHAs HA-1 and HA-2, respectively, to treat residual disease and prevent relapse following HCT using RIC in patients with AML, MDS or ALL: Two control arm patients have been enrolled and received standard of care (SOC) (HCT alone): Both control arm patients have medium-risk MDS and experienced incomplete donor chimerism (presence of patient-derived cells) following transplant; one patient is now in early stages of relapse: after 100 days, patient-derived cells are still observed and increasing.

TSC-101 treatment arm (n=1 high-risk MDS with p53 mutation): DL1 administered 21 days after transplant; Engineered T cells showed expansion between 14-21 days after infusion; Detectable markers of activation and proliferation observed; Twenty-one days after treatment and 42 days after transplant, donor chimerism was at 100% (no detectable patient-derived hematopoietic cells with sensitivity limit of 0.13%); Minimal residual disease (MRD) assessment: p53 mutation was not detected post-transplant in bone marrow and peripheral blood samples, with sensitivity limit of 0.01%; No DLTs observed; Study advancing to DL2. TSC-100 treatment arm (n=1 T-cell ALL): DL1 administered 28 days after transplant; T cell expansion occurred on Day 7 with detectable markers of T cell activation and proliferation. Two assays are used to detect the action of T cells: MRD: SOC assays measuring remaining malignant cells use flow cytometry, which has a sensitivity of ~0.1%; High sensitivity assay based on next-generation sequencing (NGS) and droplet digital PCR is also used in this study, with a sensitivity of 0.01%; Chimerism: SOC STR assays have ~1% sensitivity; Study is using the high-sensitivity NGS-based Alloheme assay, with a sensitivity of ~0.13%.