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Putting the BiTE on cancer
THOUSAND OAKS, Calif.—Amgen and Tuebingen, Germany-based Immatics Biotechnologies GmbH have announced a research collaboration and license agreement to develop next-generation, T cell-engaging bispecific immunotherapies targeting multiple cancers. Under this arrangement, Amgen will employ proprietary and tumor-specific peptide antigens discovered by Immatics’ target and T cell receptor (TCR) discovery platform XPRESIDENT to provide targets for its bispecific T cell engager (BiTE) technology with the aim of creating novel oncology drugs.
As part of the arrangement, Immatics will receive an upfront fee of $30 million and up to $500 million in development, regulatory and commercial milestone payments for each program. Amgen will be responsible for the programs’ worldwide clinical development, manufacturing and commercialization.
“We are very pleased to be entering this strategic collaboration with Amgen, which is contributing its bispecific T cell engagers expertise, as together we look to develop novel immunotherapies that will deliver a step change in the treatment of several cancers,” said Dr. Carsten Reinhardt, managing director and chief medical officer at Immatics. “This collaboration also demonstrates Amgen’s confidence in Immatics’ world-leading immune-oncology target and TCR discovery capabilities.”
Tumor cells contain proteins which are broken down inside the cell into fragments, called tumor-associated peptides (TUMAPs). Class-I major histocompatibility complex (MHC) molecules bring these peptides to the surface of the cell, providing a picture of the cell’s interior. Cytotoxic T cells roam the blood, tissue, and lymph of the body looking for cells which express these peptides and attack them. They are activated when their T cell receptors (TCR) and a co-stimulatory molecule (like CD3) are engaged with the TUMAPs and co-stimulatory molecules on the target cell. Once activated, the T cells release perforins which form pores in the membrane of the cancer cell, and granzymes to destroy the cell structures.
For this engagement to occur, cytoxic T cells need to be present and need to be able to perceive the TUMAPs. Malignant cells can evade these T cells through a variety of mechanisms, including masking of the antigen presentation or the blocking the T cell signaling process that leads to cell lysis. Amgen’s BiTE technology overcomes those mechanisms by acting as a tether, with one arm binding to specific antigens on the cancer cell, and the other recruiting and activating T cells by recognizing the T cell activator. This approach allows every T cell to become activated and able to attack the tumor, independent of the T cells’ intrinsic specificity. Through this bispecific approach, the immunotherapies’ ability to eradicate malignant cells is improved, while damage to healthy tissues is avoided.
BiTE has already deployed in Amgen’s Blincyto (blinatumomab) which was approved by the U.S. Food and Drug Administration in 2014 for treatment of relapsed/refractory acute lymphoblastic leukemia, and forms the basis of solitomab, which is currently in preclinical study in uterine and ovarian cancer. Amgen also has three therapies in stage one trials, including AMG 330, which is being investigated as a treatment for acute myeloid leukemia, and AMG 420 for multiple myeloma.
Immatics’ XPRESIDENT TCR discovery platform has allowed the company to identify several hundred thousand TUMAPs per year. TUMAPs are not limited to surface proteins, which are the targets of classical antibodies or CAR-T therapies, and so can significantly expand the target space for immuno- oncology as they are not limited to surface proteins. The company maintains that XPRESIDENT is to date the only known high-throughput research technology to directly identify, quantitate and prioritize naturally presented TUMAPs/T cell targets recognized by T cells.
Immatics partnered in 2013 with Roche to develop and commercialize a number of new cancer peptide antigen-based immunotherapies, targeting primarily gastric, prostate and non-small cell lung cancer. In 2015, the company signed a strategic alliance with MorphoSys to develop novel antibody-based therapeutics against these targets in a number of solid and hematological cancers. Immatics’ pipeline includes several TCR-bispecifics and T cell therapy programs such as ACTolog and ACTengine developed in collaboration through Immatics U.S. with the University of Texas M. D. Anderson Cancer Center in Houston and co-funded by the Cancer Prevention and Research Institute of Texas.
“The intersection of immunology and oncology represents a promising and rapidly developing approach that can have a significant impact for patients with cancer,” said Dr. Sean E. Harper, executive vice president of research and development at Amgen. “We look forward to collaborating with Immatics to translate their unique target and TCR discovery capabilities combined with Amgen’s validated BiTE technology into novel therapies.”