SY-307 / Syena, UT MD Anderson Cancer Center - LARVOL DELTA

NK-TCR cells: A next-generation platform expanding NK-cell therapeutic potential (AACR 2026) - "NY-ESO-1-TCR NK cells showed potent antigen specific activity, efficiently eliminating Saos-2, A375 and U266B1 cells, with strong cytokine production, sustained serial killing and superior persistence relative to non-transduced NK cells. The PRAME TCR NK cells showed equally strong activity against U266B1, Saos2, and A375 cells. In vivo, NY-ESO-1 TCR NK cells mediated rapid tumor regression and prolonged survival in multiple myeloma xenograft models, with durable persistence and no signs of exhaustion or toxicity."

IO biomarker • Hematological Malignancies • Melanoma • Multiple Myeloma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • Synovial Sarcoma • CTAG1B • HLA-A • IL15 • PRAME

Phase I dose escalation and expansion study of PRAME T-cell receptor (TCR) engineered IL15-transduced cord blood–derived natural killer (NK) cells in patients with recurrent and/or refractory melanoma (PRAMETIME-Mel). (ASCO 2025) - P1 | "Enrolled patients will receive lymphodepletion chemotherapy (fludarabine 30 mg/m2 and cyclophosphamide 500 mg/m2) on days -6 to -3, followed by a single dose of PRAME TCR/IL-15 NK cells on day 0. Longitudinal blood and tissue samples will be collected for correlative immune analysis."

Clinical • P1 data • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • IL15 • IL2 • PRAME

Phase 1 Dose Escalation and Expansion Study of PRAME T Cell Receptor (TCR) Engineered NK Cells in Participants With Recurrent and/or Refractory Melanoma (PRAMETIME-Mel) (clinicaltrials.gov) - P1 | N=39 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Active, not recruiting ➔ Recruiting

Enrollment open • Melanoma • Oncology • Solid Tumor

Phase 1 Dose Escalation and Expansion Study of PRAME T Cell Receptor (TCR) Engineered NK Cells in Participants With Recurrent and/or Refractory Melanoma (PRAMETIME-Mel) (clinicaltrials.gov) - P1 | N=39 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Melanoma • Oncology • Solid Tumor

Phase I dose escalation and expansion study of PRAME T-cell receptor engineered IL15-transduced cord blood-derived natural killer cells in patients with recurrent/refractory melanoma (PRAMETIME-Mel) (SITC 2024) - "Enrolled patients will receive lymphodepletion chemotherapy (fludarabine 30 mg/m2 and cyclophosphamide 500 mg/m2) on days -6 to -3, followed by a single dose of PRAME TCR/IL-15 NK cells on day 0 (figure 1). Longitudinal blood and tissue samples will be collected for correlative immune analysis."

Clinical • P1 data • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • IL15 • IL2 • PRAME

Phase 1 Dose Escalation and Expansion Study of PRAME T Cell Receptor (TCR) Engineered NK Cells in Participants With Recurrent and/or Refractory Melanoma (PRAMETIME-Mel) (clinicaltrials.gov) - P1 | N=39 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center

New P1 trial • Melanoma • Oncology • Solid Tumor

Phase I/II Study of Engineered T Cell Receptor-Modified NK Cells Targeting PRAME in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapse/Refractory Myeloid Malignancies (clinicaltrials.gov) - P1/2 | N=54 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Active, not recruiting ➔ Recruiting

Enrollment open • Oncology

Phase I/II Study of Engineered T Cell Receptor-Modified NK Cells Targeting PRAME in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapse/Refractory Myeloid Malignancies (clinicaltrials.gov) - P1/2 | N=54 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology

Phase I/II Study of Engineered T Cell Receptor-Modified NK Cells Targeting PRAME in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapse/Refractory Myeloid Malignancies (clinicaltrials.gov) - P1/2 | N=54 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Not yet recruiting ➔ Recruiting | Initiation date: Oct 2024 ➔ Jun 2024

Enrollment open • Trial initiation date • Oncology

Phase I/II Study of Engineered T Cell Receptor-Modified NK Cells Targeting PRAME in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapse/Refractory Myeloid Malignancies (clinicaltrials.gov) - P1/2 | N=54 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center

New P1/2 trial • Oncology

Replay and MD Anderson announce FDA clearance of IND application for first-in-class PRAME-targeted T-Cell Receptor Natural Killer (TCR-NK) cell therapy for hematological malignancies (GlobeNewswire) - "Replay...and The University of Texas MD Anderson Cancer Center, today announced that the Food & Drug Administration (FDA) has issued a ‘safe to proceed’ for the Investigational New Drug (IND) application for PRAME TCR/IL-15 NK (SY-307), an engineered T-Cell Receptor Natural Killer (TCR-NK) cell therapy for relapsed/refractory myeloid malignancies. MD Anderson is the IND sponsor....The phase 1/2 open-label study will assess the safety, tolerability, and preliminary efficacy of PRAME TCR/IL-15 NK (SY-307) in patients with relapsed/refractory AML and MDS....Up to 44 patients will be enrolled into the study, which is anticipated to commence in Q3 2024."

IND • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology