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

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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

REFERENCES
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. https://replay.bio/news/replay-and-md-anderson-announce-fda-clearance-of-ind
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. https://www.mdanderson.org/newsroom/novel-tcr-nk-cell-therapy-sarcoma-receives-ind-clearance-fda.h00-159619434.html
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. https://replay.bio/news/kkr-backed-replay-and-md-anderson-form-syena
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. https://replay.bio/news/replay-launches-eudora
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. https://replay.bio/news/replay-launches-eudora
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.https://replay.bio/news/replay-targets-genetic-brain-disorders
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