Replay and MD Anderson announce FDA clearance of IND application for first-in-class PRAME-targeted T-Cell Receptor Natural Killer Cell Therapy for Myeloid Malignancies

San Diego, California, London, UK, and Houston, Texas – Replay, a genome writing company reprogramming biology by writing and delivering big DNA, 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.

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 natural killer 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 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. 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.

Adrian Woolfson, Executive Chairman, President, and Co-Founder of Replay, said: “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. 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.”

Lachlan MacKinnon, CEO and Co-Founder of Replay, said: “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. 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.”

Dr Arun Balakumaran, Chief Medical Officer of Replay, said: “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. This dichotomous expression pattern and its ability to elicit spontaneous humoral and cellular immune responses render it a promising target for cancer immunotherapy.”

Dr Katy Rezvani Professor of Stem Cell Transplantation & Cellular Therapy at MD Anderson said: “This is an exciting milestone in the development of ‘off-the-shelf’ engineered TCR-NK cell therapies to address significant unmet medical needs. 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.”


About Replay

Replay is a genome writing company, which aims to define the future of genomic medicine through reprogramming biology by writing, designing, and delivering big DNA. The Company has assembled a toolkit of platform technologies, including a high payload capacity HSV platform, to address the challenges that currently limit clinical progress and prevent genomic medicine from realizing its full potential.

The Company’s hub-and-spoke business model separates technology development within Replay from therapeutic development in a portfolio of product companies that leverage its technology platforms. Replay’s first-in-class engineered TCR-NK cell therapy product company, Syena, uses technology developed by Katy Rezvani, M.D., Ph.D., at The University of Texas MD Anderson Cancer Center in Houston, Texas. Replay’s high payload capacity HSV vector capable of delivering up to 30 times the payload of AAV, is utilized by Replay’s gene therapy product companies, bringing big DNA treatments to diseases affecting the skin, and eye. Replay is led by a distinguished team of academics, entrepreneurs, and seasoned industry experts.

The Company raised $55 million in seed financing in July 2022 and is supported by an international syndicate of investors including: KKR, OMX Ventures, ARTIS Ventures, and Lansdowne Partners.


About MD Anderson

The University of Texas MD Anderson Cancer Center in Houston ranks as one of the world’s most respected centers focused on cancer patient care, research, education and prevention. The institution’s sole mission is to end cancer for patients and their families around the world. MD Anderson is one of only 53 comprehensive cancer centers designated by the National Cancer Institute (NCI). MD Anderson is No. 1 for cancer in U.S. News & World Report’s “Best Hospitals” rankings and has been named one of the nation’s top two hospitals for cancer since the rankings began in 1990. MD Anderson receives a cancer center support grant from the NCI of the National Institutes of Health (P30 CA016672).




Dr Adrian Woolfson/Lachlan MacKinnon

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ICR Consilium – media relations

Amber Fennell/ David Daley

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MD Anderson

Clayton Boldt, Ph.D.

[email protected]