Replay Secures IND Approval for PRAME T Cell Therapy

The U.S. Food and Drug Administration (FDA) has approved an investigational new drug (IND) application from Replay Bio, a genome writing company, allowing them to proceed with a clinical trial of their T cell therapy for haematological malignancies. The trial, a Phase I/II study, will explore the efficacy of T cell receptor natural killer (TCR-NK) cell therapy in patients suffering from relapsed or refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).

The engineered therapy, identified as PRAME TCR/IL-15 NK (SY-307), targets preferentially expressed antigens in melanoma (PRAME). This treatment is being developed in collaboration between Syena, a company formed by Replay and MD Anderson, and the University of Texas MD Anderson Cancer Center.

The clinical trial aims to recruit 44 patients who will undergo a process known as lymphodepletion. This procedure involves the use of chemotherapy to reduce lymphocyte levels. In this trial, standard chemotherapies such as fludarabine/cyclophosphamide (Flu/Cy) and decitabine will be utilized for the lymphodepletion process, with the trial anticipated to start in the third quarter of 2024.

This PRAME-directed TCR-NK cell therapy marks Syena’s second venture into clinical trials. Their initial program, NY-ESO-1 TCR/IL-15 NK, is a first-in-class cell therapy for patients with relapsed or refractory multiple myeloma and is currently in a Phase I/II study that began in November of last year. Furthermore, another study involving patients with synovial sarcoma and myxoid/round cell liposarcoma is planned to commence, following FDA's IND clearance in June 2023.

Syena’s efforts in developing advanced therapies have been bolstered by collaborations, including a research partnership with JURA Bio to create TCR-based therapies. PRAME is a highly immunogenic antigen found in various cancer cell types, making it a prime target for cell therapy-driven cancer immunotherapy.

In February 2024, Immunocore and Bristol Myers Squibb (BMS) announced a collaboration to evaluate a PRAME-targeted candidate IMC-F106C as a first-line treatment for melanoma. Additionally, Adaptimmune, after regaining rights to its preclinical PRAME-targeted program from GlaxoSmithKline (GSK) last year, plans to move its therapy ADP-600 into clinical trials this year following promising preclinical data.

Replay Bio made its entry into the cell therapy market with a $55 million seed financing round in July 2022, supported by global investment firm KKR and OMX Ventures. Other participants included Artis Ventures, Lansdowne Partners, SALT, DeciBio Ventures, and Axial.

Professor Katy Rezvani, who specializes in stem cell transplantation and cellular therapy at MD Anderson, highlighted the significance of this development. She expressed optimism about the potential of “off-the-shelf” engineered TCR-NK cell therapies to address significant unmet medical needs. Rezvani noted, “Our hope is the PRAME studies, initially in haematological 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.”

This Phase I/II clinical trial represents a crucial step forward in developing innovative treatments for difficult-to-treat cancers, leveraging the potential of advanced genetic engineering and cell therapy technologies to bring new hope to patients facing these challenging conditions.