FDA Clears IND of PRAME TCR-IL-15 NK Program for R/R Myeloid Malignancies

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The FDA issued a ‘safe to proceed’ for the investigational new drug application for PRAME TCR/IL-15 NK for relapsed or refractory myeloid malignancies.

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  • An investigational new drug (IND) application for PRAME TCR/IL-15 NK (SY-307) has been cleared by the FDA for the treatment of patients with relapsed/refractory myeloid malignancies.
  • PRAME TCR/IL-15 NK is an engineered T-cell receptor natural killer (TCR-NK) cell therapy.
  • A phase 1/2 open-label study will assess PRAME TCR/IL-15 NK in patients with relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).

The FDA has cleared the IND application for PRAME TCR/IL-15 NK, an engineered TCR-NK cell therapy for the treatment of patients with relapsed/refractory myeloid malignancies.1

“This is an exciting milestone in the development of 'off-the-shelf' engineered TCR-NK cell therapies to address significant unmet medical needs. Our hope is the PRAME studies, initially in hematological malignancies and then in solid tumors, will further advance our understanding of the potential for engineered TCR-modified NK cells to benefit patients with relapsed/refractory myeloid malignancies.” said Katy Rezvani, MD, PhD, professor of stem cell transplantation and cellular therapy at MD Anderson Cancer Center, the IND sponsor, in a press release.

With this clearance, a phase 1/2 study evaluating the safety, tolerability, and preliminary efficacy of PRAME TCR/IL-15 NK in patients with relapsed/refractory AML and MDS will begin. The study is anticipated to start in Q3 of 2024.

3D illustration of AML cells: © LASZLO - stock.adobe.com

3D illustration of AML cells: © LASZLO - stock.adobe.com

In the study, PRAME TCR-IL-15 NK will be administered to patients following lymphodepletion with standard doses of fludarabine/cyclophosphamide and decitabine. Investigators plan to enroll approximately 44 patients.

“PRAME is expressed at high levels in multiple different tumor types, making it a compelling target for engineered TCR-NK cancer immunotherapy. The recent IND clearance of our PRAME TCR/IL-15 NK program for AML and MDS represents a significant expansion of Syena’s growing pipeline of ‘off-the-shelf’ engineered TCR-NK therapies and complements our existing NY-ESO-1-targeted programs in myeloma and sarcoma,” said Adrian Woolfson, executive chairman, president, and cofounder of Replay, in the press release.

“This diversification of Syena’s TCR-NK portfolio takes us a step closer to democratizing cell therapy for cancer patients with high unmet medical needs and limited treatment options,” continued Woolfson.

PRAME TCR/IL-15 NK is made from cord blood-derived NK cells that express a high affinity TCR targeting the PRAME tumor-associated neoantigen, which is highly immunogenic and expressed on various types of cancers. These include hematologic malignancies like AML, MDS, and solid tumors such as melanoma, sarcoma, ovarian, endometrial, lung, and breast cancer.

Through its ability to elicit a humoral and cellular immune response, PRAME is a compelling target for cell therapy-mediated cancer immunotherapy. PRAME also has restricted tissue expression.

PRAME TCR/IL-15 NK is being developed by Syena. This is the second TCR-NK target from Syena following the NY-ESO-1-targeted TCR-NK program. This program currently has an ongoing clinical study in multiple myeloma, and a study in advanced synovial sarcoma and myxoid/round cell liposarcoma is expected to begin shortly, following its IND clearance from the FDA in June 2023.2

“PRAME is a well-known cancer-testis antigen with reexpression in multiple cancer types, including AML and solid tumors, and restricted expression on normal tissues,” said Arun Balakumaran, MD, PhD, chief medical officer at Replay, in a press release.1 “This dichotomous expression pattern and its ability to elicit spontaneous humoral and cellular immune responses render it a promising target for cancer immunotherapy.”

REFERENCE:
1. Replay and MD Anderson announce FDA clearance of IND application for first-in-class PRAME-targeted T-Cell receptor natural killer (TCR-NK) cell therapy for hematological malignancies. News release. Replay. April 30, 2024. Accessed April 30, 2024. https://tinyurl.com/yjyfwrfd
2. MD Anderson and Replay announce FDA clearance of IND application for first-in-class TCR NK cell therapy for multiple myeloma. News release. MD Anderson Cancer Center. April 30, 2024. Accessed April 30, 2024. https://tinyurl.com/2y8enmfx
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