
•	Phase 1/2 study in patients with relapsed/refractory AML and MDS, anticipated to commence Q3 2024

•	PRAME is Syena’s second TCR-NK target and follows the NY-ESO-1-targeted TCR-NK program, which has an ongoing clinical study in multiple myeloma with a clinical study in advanced synovial sarcoma, and myxoid/round cell liposarcoma anticipated to commence imminently 

__San Diego, California, London, UK, and Houston, Texas, April 30, 2024__ – 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.”

__Ends__

__Disclosure__

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.

__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.

Replay is headquartered in San Diego, California. For further information please visit [www.replay.bio](https://www.replay.bio) and follow us on LinkedIn and X.

__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).

__Contacts:__

__Replay__

Dr Adrian Woolfson/Lachlan MacKinnon

info@replay.bio

__ICR Consilium – media relations__

Amber Fennell/ David Daley

replay@consilium-comms.com 

__MD Anderson__

Clayton Boldt, Ph.D.

CRBoldt@MDAnderson.org


Syena

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

nature.com

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Safety, efficacy and determinants ofresponse of allogeneic CD19-specific CAR-NKcells in CD19+ B cell tumors: a phase 1/2 trial

•	Phase 1/2 clinical study of NY-ESO-1 TCR/IL-15 NK for relapsed or refractory multiple myeloma commences on track

•	NY-ESO-1 TCR/IL-15 NK is the lead clinical program of Syena, a Replay and MD Anderson cell therapy company based on the scientific discoveries of Professor Katy Rezvani, M.D., Ph.D.

•	Syena is Replay’s first product company to enter clinical development

__San Diego, California, London, UK, and Houston, Texas, March 11, 2024__ – Replay, a genome writing company reprogramming biology by writing, designing, and delivering big DNA, today announced that the first patient has been dosed in the Phase 1/2 study of NY-ESO-1 TCR/IL-15 NK, an engineered T-Cell Receptor Natural Killer (TCR-NK) cell therapy for relapsed or refractory multiple myeloma. 

NY-ESO-1 TCR/IL-15 NK is being developed by Syena, an oncology-focused product company [launched](https://replay.bio/news/kkr-backed-replay-and-md-anderson-form-syena) by Replay and The University of Texas MD Anderson Cancer Center,, based on the scientific discoveries of [Katy Rezvani, MD, PhD](https://faculty.mdanderson.org/profiles/katy_rezvani.html), Professor of [Stem Cell Transplantation & Cellular Therapy](https://www.mdanderson.org/research/departments-labs-institutes/departments-divisions/stem-cell-transplantation.html) at MD Anderson. Syena has an exclusive licensing agreement for MD Anderson’s TCR-NK technology platform. This first-in-class engineered cell therapy comprises cord blood-derived natural killer cells that express an affinity-enhanced TCR targeted against the NY-ESO-1 antigen. NY-ESO-1 is highly immunogenic and expressed on numerous cancer cell types. The ability of NY-ESO-1 to elicit humoral and cellular immune responses along with its restricted tissue expression makes it a compelling target for cancer immunotherapy. 

The Phase 1/2 clinical study will assess the safety and efficacy of NY-ESO-1 TCR/IL-15 NK in patients with relapsed or refractory multiple myeloma. It will be administered following lymphodepletion with standard doses of fludarabine/cyclophosphamide (Flu/Cy). The study will enrol up to 44 patients in total.

__Adrian Woolfson, Executive Chairman, President, and Co-Founder of Replay, said:__ “The dosing of the first patient in Syena’s NY-ESO-1 TCR-NK clinical study represents a major step forward in addressing the significant unmet medical need for ‘off-the-shelf’ cell therapies. I am delighted with the rapid progress that we have made to date. NY-ESO-1 is highly expressed in poor-prognosis multiple myeloma, making this a suitable indication for demonstrating proof of concept for Syena’s TCR-NK technology platform. We believe that the use of optimally selected cord blood donors is likely to translate into improved patient outcomes. We are grateful to the patients, clinical sites, and development teams for their ongoing commitment and efforts to advance this new technology into the clinic.”

__Lachlan MacKinnon, CEO and Co-Founder of Replay, commented:__ “This Phase 1/2 clincial study will be key to further understanding the potential of our TCR-NK platform, with Syena making significant strides towards delivering its pioneering first-in-class TCR-NK cell therapy to patients with relapsed or refractory multiple myeloma. We look forward to enrolling further patients and evaluating the safety and efficacy outcomes as the study progresses.”

For more information please visit [ClinicalTrials.gov](https://clinicaltrials.gov/study/NCT06066359?term=NY-ESO-1%20TCR%2FIL-15%20NK&rank=1) and reference identifier NCT06066359.

__Ends__

__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 disruptive platform technologies — including a high payload capacity HSV delivery platform — to address the challenges currently limiting clinical progress and preventing genomic medicine from realizing its 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. The Company recently incorporated a first-in-class engineered TCR-NK cell therapy product company, Syena, using technology developed by Katy Rezvani, MD, PhD, at The University of Texas MD Anderson Cancer Center in Houston, Texas. Replay’s synHSV™ technology, a high payload capacity HSV vector capable of delivering up to 30 times the payload of AAV, is used by Replay’s gene therapy product companies, bringing big DNA treatments to monogenic diseases impacting the skin, and eye. Replay is led by a distinguished team of academics, entrepreneurs, and industry experts. 

The Company has raised $85 million to date and is supported by an international syndicate of investors including: KKR, OMX Ventures, ARTIS Ventures, Lansdowne Partners and the Bill and Melinda Gates Foundation. 

Replay is headquartered in San Diego, California. For further information please visit www.replay.bio and follow us on LinkedIn and Twitter.  

__About NY-ESO-1 TCR/IL-15 NK__
NY-ESO-1 TCR/IL-15 NKs are adoptive Natural Killer (NK) cells expressing an affinity-enhanced T-cell receptor (TCR) directed against NY-ESO-1-specific cord blood-derived NK cells. The cells are engineered to express the CD3 and TCR signalling complex and IL-15, and use the same manufacturing method as engineered CAR-NKs, which have demonstrated safety and efficacy in lymphoma (Liu et al, NEJM 2020 and Marin et al Nature Medicine 2024). 

NY-ESO-1 (New York Esophageal Squamous cell carcinoma 1) is an cancer-testis antigen with re-expression in multiple cancer types, and restricted expression in healthy tissues. This expression pattern and its ability to elicit humoral and cellular immune responses makes it a compelling target for TCR-T cell therapy. TCR-engineered NK cells retain their capacity to target tumor cells through their native receptors. The ability of NK cells to target tumor cells that down-regulate or lack MHC through the ‘missing self’ mechanism, may make disease escape through the most common mechanism of acquired resistance, less likely. IND-enabling studies have confirmed that NY-ESO-1 TCR/IL-15 NK cells do not kill healthy human cell lines derived from organs including the heart, lungs, liver, and kidneys. 

__Contacts:__

__Replay__

Dr. Adrian Woolfson/Lachlan MacKinnon

info@replay.bio

__ICR Consilium – media relations__

Amber Fennell/Tracy Cheung/David Daley 

replay@consilium-comms.com 


Replay’s cell therapy product company Syena announces first patient dosed in Phase 1/2 study of TCR-NK cell therapy for multiple myeloma

GEN Biotechnology

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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

Safety, efficacy and determinants ofresponse of allogeneic CD19-specific CAR-NKcells in CD19+ B cell tumors: a phase 1/2 trial

Replay’s cell therapy product company Syena announces first patient dosed in Phase 1/2 study of TCR-NK cell therapy for multiple myeloma

Defining the Rules of Biology in the Age of Genome Writing