MD Anderson and Syena’s TCR NK Cell Therapy Gets Another IND Clearance for Multiple Myeloma


NY-ESO-1 TCR/IL-15 NK previously received clearance of an IND for advanced synovial sarcoma and myxoid/round cell liposarcoma in June 2023.

The University of Texas MD Anderson Cancer Center (MD Anderson) and Syena, a subsidiary of Replay, have received clearance of a new investigational new drug (IND) application for their T-cell receptor natural killer (TCR NK) cell therapy NY-ESO-1 TCR/IL-15 NK.1 The IND clears the therapy for a trial in multiple myeloma.

NY-ESO-1 TCR/IL-15 NK consists of cord blood-derived NK cells that have been engineered to express a TCR directed at the NY-ESO-1 cancer-associated antigen.2 The antigen was chosen as a target based on its high immunogenicity and the fact that it is expressed on many types of cancer cells, with limited expression in healthy tissue. Notably, in preclinical IND-enabling studies, NY-ESO-1 TCR/IL-15 NK did not kill healthy human cells in cell lines derived from the heart, lungs, liver, and kidneys.1 Replay anticipates the initiation of a clinical trial in multiple myeloma within the third quarter of 2023. The IND is sponsored by MD Anderson.

“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,” Katy Rezvani, MD, PhD, a professor of Stem Cell Transplantation & Cellular Therapy at MD Anderson, whose research and discoveries informed the development of NY-ESO-1 TCR/IL-15 NK, said in a statement.1 “I look forward to the study beginning later this year.”

The new IND is the second the FDA has cleared for NY-ESO-1 TCR/IL-15 NK. Previously, in June 2023, the agency cleared an IND for the evaluation of the therapy in advanced synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCL).2 At the time of the previous IND clearance, MD Anderson announced that NY-ESO-1 TCR/IL-15 NK will be evaluated in a phase 1/1b clinical trial that will seek to enroll approximately 44 patients with SS or MRCL.

"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, signaling the rapid advancement of our TCR-NK program into the clinic and the breadth of our engineered TCR-NK cell therapy’s potential," Adrian Woolfson, the executive chairman, president, and co-founder of Replay, added to the statement.1

Syena was launched by Replay in February 2023 and is the most recent product company to be launched under Replay’s “hub-and-spoke" business model.1,3 It is the only of Replay’s subsidiaries to be focused on cell therapy and oncology indications. Replay, which itself launched in July 2022 with $55 million in seed financing, has previously launched 3 other product companies.1,4 Each of these 3 companies are focused on the development of gene therapies that use Replay’s synHSV technology, a high payload capacity herpes simplex virus (HSV) delivery vector intended to enable the delivery of genes that are too large to be delivered by adeno-associated virus vectors. The companies include Eudoara, which is developing gene therapies for retinitis pigmentosa, Stargardt disease, and Usher syndrome type 1B; Telaria, which is developing gene therapies for rare skin diseases; and Kaleibe, which is developing gene therapies for genetic Parkinson disease and Friedreich ataxia.4-6

“With clinical studies in 2 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,” Lachlan MacKinnon, the CEO and co-founder of Replay, added to the statement.1

1. 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. News release. Replay. July 24, 2023. Accessed July 25, 2023.
2. MD Anderson and Replay announce FDA clearance of IND application for first-in-class TCR NK cell therapy for sarcoma. News release. The University of Texas MD Anderson Cancer Center. June 20, 2023. Accessed July 25, 2023.
3. KKR-backed Replay and MD Anderson form new product company Syena to pioneer first-in-class TCR-NK cell therapy. News release. Replay. February 14, 2023. Accessed July 25, 2023.
4. Replay launches its first HSV gene therapy company, Eudora, focused on retinal eye disease. News release. Replay. October 31, 2022. Accessed July 25, 2023.
5. Replay launches big DNA HSV gene therapy company, Telaria, focused on rare skin diseases. News release. Replay. November 21, 2022. Accessed July 25, 2023.
6. Replay targets genetic brain disorders with new gene therapy company, Kaleibe, utilising big DNA HSV technology. News release. Replay. December 13, 2022. Accessed July 25, 2023.
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