MD Anderson and Syena’s Sarcoma TCR NK Cell Therapy Gets IND Clearance


A phase 1/1b clinical trial is planned to evaluate the safety and efficacy of the therapy.

The University of Texas MD Anderson Cancer Center (MD Anderson) and Syena, a subsidiary of Replay, have received clearance of an investigational new drug (IND) application for their T-cell receptor natural killer (TCR NK) cell therapy NY-ESO-1 TCR/IL-15 NK, which is intended to treat advanced synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCL).1

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. 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. A phase 1/1b clinical trial is planned to evaluate the safety and efficacy of the therapy. The study will seek to enroll approximately 44 patients with SS or MRCL. Patients will undergo lymphodepletion via fludarabine/cyclophosphamide, which will be administered in standard doses, before being treated with NY-ESO-1 TCR/IL-15 NK. The development of NY-ESO-1 TCR/IL-15 NK was informed by research and discoveries made by Katy Rezvani, MD, PhD, a professor of Stem Cell Transplantation & Cellular Therapy at MD Anderson.

“SS and MRCL 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,” Rezvani said in a statement.1 “I am delighted with the team's progress and look forward to initiating the Phase 1/1b study later this year.”

Replay originally launched in July 2022 with $55 million in funding obtained through a round of seed financing.2 Among the contributors were KKR, OMX Ventures, and ARTIS Ventures. Replay launched Syena in February 2023. Syena is the latest in a line of several product companies launched by Replay over the past year and the first to be focused on cell therapy and an oncology indication.3 Replay’s first product company, Eudora, was launched in October 2022.4 Eudora is focused on the development of gene therapies for indications including retinitis pigmentosa, Stargardt disease, and Usher syndrome type 1B that will utilize a high payload capacity herpes simplex virus (HSV) delivery vector. The HSV vector is intended to enable the delivery of genes that are too large to be delivered by adeno-associated virus vectors. In November 2022, Replay launched Telaria, another HSV gene therapy company.5 Telaria is focused on the development of HSV gene therapies for rare skin diseases; its initial lead program is intended for the treatment of recessive dystrophic epidermolysis bullosa. Later, in December 2022, Replay launched Kaleibe.6 Kaleibe is focused on developing HSV gene therapies for genetic brain disorders. Kaleibe’s pipeline includes programs for genetic Parkinson disease and Friedreich ataxia.

"Syena is leveraging the scalability and allogeneic nature of engineered cord blood-derived NK cells to democratize cell therapy for cancer treatment,” Adrian Woolfson, executive chairman, president and co-founder of Replay, added to the statement.1 “The recent FDA IND clearance of the first-in-human TCR NK protocol is a significant milestone for Syena. Syena is now 1 step closer to bringing its first-in-class, ‘off-the-shelf’ engineered TCR NK therapy to patients with solid tumors.”

1. 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 June 22, 2023.
2. Replay launches with $55 million seed to reprogram biology by writing and delivering big DNA. News release. Replay. July 25, 2022. Accessed June 22, 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 June 22, 2023.
4. Replay launches its first HSV gene therapy company, Eudora, focused on retinal eye disease. News release. Replay. October 31, 2022. Accessed June 22, 2023.
5. Replay launches big DNA HSV gene therapy company, Telaria, focused on rare skin diseases. News release. Replay. November 21, 2022. Accessed June 22, 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 June 22, 2023.
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