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

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

• Phase 1 study of NY-ESO-1 TCR/IL-15 NK for relapsed or refractory multiple myeloma, first TCR-NK clinical study in hematological malignancies, anticipated to commence Q3 2023
• Follows earlier IND clearance for solid tumor study in synovial sarcoma and myxoid/ round cell liposarcoma received in June 2023

San Diego, California, London, UK, and Houston, Texas, July 24, 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, a first-in-class engineered T-Cell Receptor Natural Killer (TCR-NK) cell therapy for relapsed or refractory multiple myeloma. 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.

A study in patients with synovial sarcoma and myxoid/round cell liposarcoma received IND clearance from the FDA in June 2023.

“This IND clearance of Syena’s engineered TCR-NK cell technology in hematological malignancies swiftly follows the FDA’s clearance of our solid tumor study in sarcoma, signalling the rapid advancement of our TCR-NK program into the clinic and the breadth of our engineered TCR-NK cell therapy’s potential,” said Adrian Woolfson, Executive Chairman, President, and Co-Founder of Replay.

Lachlan MacKinnon, CEO and Co-Founder of Replay, commented: “With clinical studies in two indications, spanning solid tumors and hematological malignancies, we are excited for the potential of Syena’s first-in-class ‘off-the-shelf’ engineered TCR-NK platform to address multiple unmet clinical needs.”

“NY-ESO-1 is highly expressed in certain patients with multiple myeloma and associated with a poor prognosis, so this clinical study will be key to further understanding the potential of our TCR-NK platform in hematological malignancies,” said Dr Katy Rezvani. “I look forward to the study beginning later this year.”

Ends

Disclosure

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, 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 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 www.replay.bio 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 multiple myeloma

Multiple myeloma is a common hematological malignancy, with an estimated 34,920 new cases diagnosed in the United States in 2021, accounting for 1.8% of all new cases of cancer in the country. There has been a steady increase in the available treatment options for these patients, including proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and monoclonal antibodies. More recently, two separate autologous chimeric antigen receptor T (CAR-T) cells, and bispecific targeting BCMA have also been approved for the treatment of multiple myeloma. They have shown impressive response rates and duration of response but are associated with serious toxicity, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, pancytopenia, prolonged hypogammaglobulinemia, immunodeficiency and delayed-onset progressive movement disorders. There are no approved therapies for patients who have failed the BCMA targeting therapies and the outcome of relapsed/refractory multiple myeloma, especially the triple-class refractory multiple myeloma patients, who are refractory to a PI, an IMiD, and an anti-CD38 monoclonal antibody has been poor.

Contacts:

Replay

Dr Adrian Woolfson/Lachlan MacKinnon

info@replay.bio

Consilium Strategic Communications – Media relations

Amber Fennell/David Daley /Isabelle Abdou

replay@consilium-comms.com