Replay Signs Exclusive Licensing Agreements with NIH and Miltenyi Biotec for Cell Therapy Development and Manufacturing

On Dec. 18, 2023, Replay, a genome writing company, announced that it has entered into separate agreements with the National Institutes of Health (NIH) and Miltenyi Biotec, a provider of products and services for biomedical research and cellular therapy, that will lead to the development and manufacture of T-cell receptor (TCR) and natural killer (NK) cell-based cell therapies.

Under an exclusive, worldwide license agreement with NIH, Replay will have access to intellectual property (IP) related to a library of TCRs directed against multiple cancer neoantigens. Replay’s oncology-focused product company, Syena, will develop and thus expand its pipeline of engineered TCR–NK cell therapies based on this IP.

The TCR library includes TCRs that target the cancer neoantigens KRAS, p53, HPV16, and MAGE. These TCRs were discovered by Steven Rosenberg, MD, PhD, chief of the Surgery Branch at the NIH National Cancer Institute’s (NCI) Center for Cancer Research. Rosenberg was a pioneer of immunotherapies and gene therapies for advanced cancers, according to a company press release.

Preclinical development of the new TCR–NK programs will be advanced in parallel to the clinical development of Syena’s lead engineered TCR–NK cell therapy candidate, which targets New York esophageal squamous cell carcinoma 1 (NY-ESO-1), and the preferentially expressed antigen in melanoma (PRAME) program, for which Replay has formed the collaboration with Miltenyi Biotec.

First-in-human Phase I studies of NY-ESO-1 TCR/interleukin-15 NK in patients with advanced synovial sarcoma, myxoid/round cell liposarcoma, and relapsed or refractory multiple myeloma started in the 2023 fourth quarter. Under the NIH agreement, Replay gets worldwide rights to develop, manufacture, and commercialize NIH’s TCR library within Syena’s engineered TCR–NK cell platform. Replay will pay NIH an undisclosed upfront payment. NIH will also be eligible for certain clinical, regulatory, and sales milestone payments as well as royalties on the net sales of products that are covered by the license.

Under the Miltenyi Biotec licensing and manufacturing agreement, Replay will have an exclusive license to Miltenyi Biotec’s PRAME TCR. Miltenyi Biotec will use its closed and automated cell processing platform, CliniMACS Prodigy, to manufacture a scalable, good manufacturing practice-compliant, PRAME-targeted, TCR–NK cell therapy product. Miltenyi Biotec will supply material for clinical development and future commercial supply.

Researchers have been investigating PRAME as a target for cancer immunotherapy, according to a company press release. PRAME has been shown to be highly expressed across a broad range of tumor types and shows minimal expression in healthy tissue.

“The TCRs licensed from NIH address several cancer neoantigens of medical importance and will significantly expand our … engineered TCR–NK therapy operations. These new targets will help establish TCR-NKs as a transformative ‘off-the-shelf’ engineered cell therapeutic modality with the potential to benefit patients across multiple different solid tumor and hematological malignancy indications,” said Adrian Woolfson, executive chairman, president, and co-founder of Replay, in the press release.

“PRAME is an extensively validated target for immunotherapy in both solid tumors and hematological malignancies. It comprises a compelling addition to our expanding portfolio of targets for our … engineered TCR–NK cord blood-derived cell therapies. We are, additionally, delighted to have Syena partner with Miltenyi Biotec at this early stage to use their CliniMACS Prodigy cell manufacturing system to lock down our GMP commercial supply,” Woolfson stated.

Syena was launched in February 2023 by Replay and The University of Texas MD Anderson Cancer Center.

Source:Replay for NIH agreement and Miltenyi Biotec agreement