RARE Daily

Replay and MD Anderson Form Syena to Pioneer First-in-Class TCR-NK Cell Therapy

February 14, 2023

Rare Daily Staff

Genome writing biotech Replay and The University of Texas MD Anderson Cancer Center have launched Syena, a new oncology-focused product company pioneering T-cell receptor natural killer cell therapies.

Building on the intellectual property and technology from MD Anderson and Replay, the partners say Syena has the potential to create the next generation of cell therapy, combining the safety, potency, and scalability of natural killer (NK) cells with the ability of T-cell receptors (TCRs) to target intracellular tumor antigens. The new company’s TCR-NK cell platform is based upon the scientific discoveries of Katy Rezvani, professor of Stem Cell Transplantation and Cellular Therapy at MD Anderson.

“This first-in-class TCR-NK technology provides an opportunity for Replay to disrupt the existing cell therapy paradigm and positions Syena to become a leader in this space,” said Adrian Woolfson, executive chairman, president, and co-founder of Replay. “While clinical successes in hematological malignancies have demonstrated the transformative potential of engineered cell therapies, these successes have not yet been realized in solid tumors. NK cells offer distinct advantages over T-cells and building on Dr. Rezvani’s research to arm them with TCRs has the potential to significantly impact oncology cell therapy.”

Based on the contributions of Replay and MD Anderson, Syena will build a pipeline of engineered cell therapies using its novel TCR-NK cell platform, licensed exclusively from MD Anderson. It is targeting a selection of validated cancer neoantigens, including NY-ESO-1, and additional undisclosed TCRs. The NY-ESO-1 program in hematological malignancies and solid tumors is anticipated to enter the clinic in Q2 2023 and will enroll patients with multiple myeloma and sarcoma.

Syena’s TCR-NK cell therapy platform will combine the advantages of engineered TCR cancer therapy with those of NK cells, offering the possibility of improved safety and efficacy through a multi-armored approach incorporating natural and artificial mechanisms. Unlike chimeric antigen receptor (CAR)-based therapies, which recognize specific surface proteins, TCR therapies are engineered to recognize proteins normally found inside the cell. The use of a TCR allows the NK cell to recognize externalized protein fragments presented by the cell’s surface immune proteins.

“NK cells play a pivotal role in anticancer immunity and, following the successes of CAR T-cell therapy, and the potential for CAR-NK therapies, TCR-NK cells are positioned to be a next-generation agent for cancer therapy,” said Rezvani. “We believe that the TCR-NK cell approach will allow targeting of a broad range of tumor antigens, including cancer-specific neoantigens, and could pave the way for potentially safe and efficacious ‘off-the-shelf’ cell therapies for hematological malignancies and solid tumors.”

Rezvani’s work at MD Anderson has explored the role of NK cells in mediating innate immunological activity against human malignancies, as well as strategies to enhance their killing function. She was the first investigator to conduct a clinical trial with cord blood derived CAR-NK cells, and has successfully advanced 11 cell therapies into the clinic through MD Anderson’s institutional support and commitment to advance innovative science.

Syena will receive licenses to various Replay cell and genome engineering platform technologies.

Replay, which raised $55 million in seed financing in July 2022, employs a hub-and-spoke business model that separates technology development within Replay from therapeutic development in product companies that leverage its toolkit of technology platforms, including a high payload capacity HSV vector capable of delivering up to 30 times the payload of AAV that is utilized by Replay’s four gene therapy product companies to develop treatment for diseases affecting the skin, eye, brain, and muscle.

Photo: Adrian Woolfson, executive chairman, president, and co-founder of Replay

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