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 by Replay and The University of Texas MD Anderson Cancer Center,, based on the scientific discoveries of Katy Rezvani, MD, PhD, Professor of Stem Cell Transplantation & Cellular Therapy 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.”
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.
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
ICR Consilium – media relations
Amber Fennell/Tracy Cheung/David Daley