MD Anderson and Replay announce FDA clearance of IND application for first-in-class PRAME-targeted TCR NK cell therapy for hematological malignancies

Phase I/II study in patients with relapsed/refractory AML and MDS anticipated to commence Q3 2024

The University of Texas MD Anderson Cancer Center and Replay 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.

PRAME TCR/IL-15 NK (SY-307) is being developed by Syena, an oncology-focused product company launched by Replay and MD Anderson based on the scientific discoveries of Katy Rezvani, M.D., Ph.D., professor of Stem Cell Transplantation & Cellular Therapy at MD Anderson. Syena has an exclusive license to Miltenyi Biotec’s PRAME (PReferentially expressed Antigen in MElanoma) T cell receptor (TCR). The engineered PRAME-targeted TCR NK cell therapy is developed from cord blood-derived NK cells that express a high affinity TCR targeting the PRAME tumor-associated neoantigen.

PRAME is highly immunogenic and expressed on numerous different cancer types, including hematologic malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), and solid tumors such as melanoma, sarcoma, and ovarian, endometrial, lung and breast cancer. The ability of PRAME to elicit humoral and cellular immune responses, along with its restricted tissue expression, establishes it as a compelling target for cell therapy-mediated cancer immunotherapy.

The Phase I/II 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. It will be administered following lymphodepletion with standard doses of fludarabine/cyclophosphamide (Flu/Cy) and decitabine. Up to 44 patients will be enrolled into the study, which is anticipated to commence in Q3 2024.

"PRAME is expressed at high levels in multiple different tumor types, making it a compelling target for engineered TCR NK cancer immunotherapy. The recent IND clearance of our PRAME TCR/IL-15 NK (SY-307) program for AML and MDS represents a significant expansion of Syena’s growing pipeline of “off-the-shelf" engineered TCR NK therapies and complements our existing NY-ESO-1 targeted programs in myeloma and sarcoma,” said Adrian Woolfson, executive chairman, president and co-founder of Replay. “This diversification of Syena’s TCR NK portfolio takes us a step closer to democratizing cell therapy for cancer patients with high unmet medical needs and limited treatment options.”

“The recent FDA IND clearance of our PRAME TCR/IL-15 NK (SY-307) cell therapy is demonstrative of the growing momentum at Syena, as the second program enters the clinic,” said Lachlan MacKinnon, chief executive officer and co-founder of Replay. “This is illustrative of the strength of our business model to rapidly progress the development of a commercial-scale supply of cell therapy products with significant potential for patients.”

“PRAME is a well-known cancer-testis antigen with re-expression in multiple cancer types, including AML and solid tumors, and restricted expression on normal tissues,” said Arun Balakumaran, M.D., Ph.D., chief medical officer at Replay. “This dichotomous expression pattern and its ability to elicit spontaneous humoral and cellular immune responses render it a promising target for cancer immunotherapy.”

“This is an exciting milestone in the development of 'off-the-shelf' engineered TCR NK cell therapies to address significant unmet medical needs,” Rezvani said. “Our hope is the PRAME studies, initially in hematological malignancies and then in solid tumors, will further advance our understanding of the potential for engineered TCR-modified NK cells to benefit patients with relapsed/refractory myeloid malignancies.”


MD Anderson has an institutional conflict of interest with Replay and Syena, and MD Anderson has implemented an Institutional Conflict of Interest Management and Monitoring Plan to manage these relationships.