TSC-101

Trial 2: NCT05473910 (TSCAN-001, TScan Inc.) is a multi-arm non-randomized controlled Phase 1 study evaluating the safety and efficacy of TScan's TSC100 and TSC101 - allogeneic T-cell receptor-engineered T cells that target haematopoietically restricted antigens HA-1 and HA-2 respectively, both presented on HLA-A*02:01, in mismatched reduced-intensity conditioning (RIC)-haplo donor HCT recipients. Additionally, where MRD results were available, AH CD33 iMC was associated with MRD (p=0.019, N=79) (Table 3). These interim results suggest a potential utility of MC measured by AlloHeme, an ultra-sensitive NGS-based chimerism monitoring solution, as a non-invasive predictive biomarker for treatment response and relapse in post allo-HCT patients.

The prognostic value of complete donor chimerism by AlloHeme was evaluated in the ACROBAT study (NCT04635384) in which 73 patients achieved >99.9% chimerism in CD33+ cells and, after median follow-up of 9 months/ 270 days (range 72-608 days), 3 relapsed (4%), comparing favorably with 18-20% 6-month relapse rates in CIBMTR data. In summary, TSC-100 and TSC-101 post-HCT induce MRD negativity and complete donor chimerism which may be associated with substantially reduced relapse rates.

Targeting MiHAs HA-1 or HA-2 with TSC-100/ 101 following HCT shows early safety and biomarker evidence of efficacy by completing elimination of all detectable patient hematopoietic cells, normal or malignant, thereby reducing relapse risk. Updated results will be presented at the meeting.

Patients undergo RIC, peripheral blood stem cell infusion followed by post-transplant cyclophosphamide. T-cell activation markers on TSC-100/ 101 are measured by flow cytometry, cytokine profiling and single-cell RNA sequencing. Together these translational assays measure elimination of the target hematopoietic cell population, malignant or normal, and provide evidence of potential biological activity well before frank clinical relapses occur.

P1, N=63, Recruiting, TScan Therapeutics, Inc.

Early readouts of biological activity include monitoring for minimal residual disease and kinetics of donor chimerism. Recruitment begins in Q1 2022 and after the recommended Phase 2 dose has been identified, the study will transition to a Phase 2 study to assess relapse rates of TSC-100- and TSC-101-treated patients versus the control arm.

Based on these results, TSC-101 has been advanced to IND-enabling activities to prepare for first-in-human testing in 2022. To our knowledge, this is the first clinical grade HA-2-specifc TCR being developed for immunotherapy for liquid tumors.