TSC-101 Eliminates Recipient Hematopoietic Cells and Demonstrates Potential for Improved Relapse-Free Survival in Patients with AML, ALL, or MDS Undergoing Allogeneic HCT (Allo-Hct) with Reduced Intensity Conditioning (RIC): Updated Results from the Phase 1 (ALLOHA) Trial

Introduction Disease relapse is the leading cause of death in patients after allo-HCT for AML, ALL and MDS. TSC-101is a donor-derived TCR-T cell product targeting HA-2 on HLA-A*02:01 positive hematopoietic cells. Objective Pairing A*02:01 positive patients with A*02:01 negative donors should allow TSC-101 (TSC) to eliminate only residual patient blood cells post-HCT, thus preventing relapse. Methods ALLOHA is a multi-center, biologically controlled, Phase 1 dose escalation study evaluating TSC in adults with AML, ALL or MDS undergoing RIC-HCT. HA2-positive subjects receive either one or two infusions of TSC after count recovery (∼days 21 and 61 post-HCT). Control subjects receive RIC-HCT per standard of care. Primary endpoints are dose limiting toxicities and safety; other endpoints are efficacy, chimerism and minimal residual disease (MRD). Results As of 18 Jul 2025, endpoints were evaluated in 31 subjects (17 TSC and 14 control) without early post-HCT complications. Median follow-up (range) was 9.6m (2-29m) for the TSC arm and 11.9m (1-33m) in control. Baseline prognostic features were similar, including age and disease type. High-risk features were found in both arms including mutated TP53 (TP53m) in 4 TSC vs 2 controls, and pre-HCT MRD positivity in 10/15 TSC vs 8/14 control subjects.There were no DLTs after TSC. Safety was similar in both arms and included expected post-HCT adverse events. Acute graft-versus-host-disease of any grade occurred in 10/17 TSC vs 7/14 control subjects. Chronic GvHD occurred in 1 TSC and 2 controls. Following TSC, cytokine release syndrome occurred in 2/17 subjects (grade 1 and 2) and neurotoxicity in 1 subject (grade 1). There were no TSC-related deaths or graft failures.Efficacy analyses showed reduced relapses with TSC 3/17 vs control 5/14, with improved relapse-free survival (hazard ratio (HR) 0.48), relapse probability (HR 0.43) and overall survival (HR 0.44). Event-free survival, including clinical interventions, also improved (HR 0.41). Among mTP53, relapses occurred in 2/2 control vs. 1/4 TSC and 1 TP53m TSC subject was disease-free >2 years.Translational analysis showed complete donor chimerism in all cells (whole blood, CD33+, or CD3+) at ≥1 timepoint after TSC-101 in 15 evaluable subjects. In contrast, complete chimerism ≥1 timepoint after HCT occurred in 8/14 of controls. Bone marrow biopsies ∼Day 63 post-HCT, showed 0/13 TSC compared to 3/10 control subjects were MRD+. TCR-T cells were detectable in all TSC subjects at last follow-up (f/u) including 7 subjects with ≥ 1y post-infusion. Conclusions The safety seen with HCT followed by TSC-101 is generally consistent with post-HCT safety. Preliminary analyses show early elimination of residual recipient cells in all evaluable subjects and support the potential of TSC-101 to reduce relapses and improve relapse-free survival in RIC-HCT patients. Updated data will be presented.