Replay and MD Anderson announce FDA clearance of IND application for first-in-class T-Cell Receptor Natural Killer (TCR-NK) cell therapy for sarcoma

  • First-in-human Phase 1 study of NY-ESO-1 TCR/IL-15 NK for advanced synovial sarcoma and myxoid/round cell liposarcoma anticipated to commence Q3 2023
  • NY-ESO-1 TCR/IL-15 NK is the lead clinical program of Syena, Replay and MD Anderson’s first-in-class engineered TCR-NK cell therapy company. The Company’s scientific founder is Professor Katy Rezvani, M.D., Ph.D.
  • NY-ESO-1 is an extensively validated tumor-associated antigen that has been successfully targeted by TCR therapies in a range of oncology indications

San Diego, California, London, UK, and Houston, Texas, June 20, 2023 – Replay, a genome writing company reprogramming biology by writing and delivering big DNA, and The University of Texas MD Anderson Cancer Center (“MD Anderson”), today announced that the U.S. Food & Drug Administration (FDA) has issued a ‘safe to proceed’ for the Investigational New Drug (IND) application for NY-ESO-1 TCR/IL-15 NK, an engineered T-Cell Receptor Natural Killer (TCR-NK) cell therapy for advanced synovial sarcoma and myxoid/round cell liposarcoma. MD Anderson is the IND sponsor.

NY-ESO-1 TCR/IL-15 NK is being developed by Syena, an oncology-focused product company launched by Replay and MD Anderson based upon the scientific discoveries of Katy Rezvani, M.D., Ph.D., professor of Stem Cell Transplantation & Cellular Therapy at MD Anderson. Syena has an exclusive licensing agreement for MD Anderson’s TCR-NK platform. This first-in-class engineered cell therapy is comprised of cord blood-derived natural killer cells that express an affinity-enhanced T-cell receptor (TCR) targeted against the NY-ESO-1 cancer-associated antigen, which 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, establishes it as a compelling target for cancer immunotherapy.

The Phase 1/1b study will assess the safety and efficacy of NY-ESO-1 TCR/IL-15 NK in patients with synovial sarcoma and myxoid/round cell liposarcoma. It will be administered following lymphodepletion with standard doses of fludarabine/cyclophosphamide (Flu/Cy). Approximately 44 patients will be enrolled into the study, anticipated to commence in Q3 2023.

"Syena is leveraging the scalability and allogeneic nature of engineered cord blood-derived NK cells to democratize cell therapy for cancer treatment. The recent FDA IND clearance of the first-in-human TCR-NK protocol is a significant milestone for Syena," said Adrian Woolfson, Executive Chairman, President, and Co-Founder of Replay. “Syena is now one step closer to bringing its first-in-class, ‘off-the-shelf’ engineered TCR-NK therapy to patients with solid tumors.”

Lachlan MacKinnon, CEO and Co-Founder of Replay, commented: “Following the FDA IND acceptance, Syena is Replay’s first product company to enter the clinic. The ability to secure rapid FDA IND clearance for our first-in-class TCR-NK program is a testament to the caliber of our team and quality of our science, and continues to validate our business model.”

“Synovial and myxoid/round cell liposarcomas express NY-ESO-1 at high levels and in a high frequency of cells, making them excellent tumor types for establishing proof of concept for the TCR-NK platform,” said Dr. Katy Rezvani. “I am delighted with the team's progress and look forward to initiating the Phase 1/1b study later this year.”



MD Anderson has an institutional conflict of interest with Replay and Syena, and MD Anderson will implement 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 and delivering big DNA. The Company has assembled a toolkit of disruptive platform technologies — including a high payload capacity HSV platform, a hypoimmunogenic cell therapy platform, and a genome writing 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. For example, the Company recently incorporated a first-in-class engineered TCR-NK cell therapy product company using technology developed by Katy Rezvani, M.D., Ph.D., 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 utilized by Replay’s four gene therapy product companies, bringing big DNA treatments to diseases affecting the skin, eye, brain, and muscle. Replay is led by a distinguished team of academics, entrepreneurs, and 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 and follow us on LinkedIn and Twitter.

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).

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) reactive directed against the 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 that used for the engineered CAR-NKs, which have demonstrated safety and efficacy in lymphoma (Liu et al, NEJM 2020).

NY-ESO-1 (New York Esophageal Squamous cell carcinoma 1) is an established 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 intrinsic capacity to target tumor cells through their native receptors. The fact that NK cells kill tumor cells that down-regulate or lack MHC through the ‘missing self’ mechanism, may make disease escape through the most common primary 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.

About Synovial Sarcoma

Synovial Sarcoma is an aggressive and rare human malignancy that accounts for approximately 5-10% of all soft-tissue sarcomas. The peak incidence is in the third decade of life. It typically presents at extremities, but any serosal surface may be involved. The 5-year overall survival is 50-60% in adult patients. Most patients with localized synovial sarcoma can be cured using multimodality treatment, but in the case of patients with advanced disease, the treatment options are more limited, and the prognosis poor. Liposarcomas (LPS) are the commonest subtype of adult soft tissue sarcomas. There are multiple histological subtypes of LPS with different natural histories, treatment, and prognosis. Myxoid/round cell liposarcoma (MRCLS) accounts for ~40% of liposarcomas. MRCLS typically arises at the extremity of young adults but may also present in the retroperitoneum. The prognosis for patients with metastatic MRCLS is poor.



Dr Adrian Woolfson/Lachlan MacKinnon

Consilium Strategic Communications – Media relations

Amber Fennell/David Daley /Melissa Gardiner

MD Anderson

Clayton Boldt, Ph.D.

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