The collaboration will focus on expanding targeted protein degradation therapies through the discovery of previously unrecognized molecular glues or monovalent degraders.
California-based companies Amgen and Plexium, Inc. announced Thursday that they are entering an exclusive, worldwide, multi-year research collaboration and license agreement. The collaboration will focus on expanding targeted protein degradation therapies through the discovery of previously unrecognized molecular glues or monovalent degraders.
Protein degradation therapies work by utilizing the cell’s natural system for clearing damaged proteins to target disease-causing proteins for annihilation. Plexium uses molecular glues, small molecules that stabilize the interaction between two proteins that normally don’t interact and monovalent degraders, which bind to a target protein of interest and modify its surface to become recognizable to the cellular mechanisms for degradation. In this collaboration, Amgen will focus on two programs using Plexium’s comprehensive targeted protein degradation platform to create novel therapeutics to meet unmet medical needs in patients suffering from severe illnesses.
Plexium will be eligible to receive over $500 million in success-based target access, pre-clinical, clinical, regulatory and commercial milestones, and tiered single-digit royalty payments if all options are exercised. Amgen will maintain a commercial license to each of its two programs that advance to a predefined preclinical stage of development and will hold responsibility for global development and commercialization.
“We are on the cusp of a new era of drug discovery where medicines could function very differently than conventional ones do today,” said Ray Deshaies, Ph.D., senior vice president of global research at Amgen in a press release. “Collaborating with Plexium and leveraging their innovative technology to identify molecular glue degraders can help tackle some of the most challenging protein targets to address serious disease.”
The draw of protein degradation therapeutics is exciting in the field of oncology. Currently, many therapeutics focus on targeting pathogenic proteins in malignant tumors with small-molecule inhibitors (SMIs) that impede the enzymatic actions of target proteins. Treatment with SMIs can pose certain challenges though due to the lack of active sites in intracellular proteins. Protein degradation therapies can overcome this obstacle because they do not need continuous exposure to binding sites of the proteins. Leukemia, lymphoma, lung and breast cancers all have the potential to be treated with a protein degradation therapy using proteolysis-targeting chimeras (PROTAC) that induce degradation of malignant cells.
“Amgen is a globally recognized pharmaceutical company that shares our commitment to pushing the boundaries of modern drug discovery and we’re thrilled to announce our collaboration today,” said Percival Barretto-Ko, president and chief executive officer at Plexium. “This partnership leverages and expands our drug discovery capabilities and will further demonstrate the power of our platform to unlock the potential of protein degradation. We look forward to working with Amgen to accelerate the discovery of the next generation of targeted protein degraders to improve patients’ lives around the globe.”
Plexium has several projects in the works involving protein degradation therapies. These projects include a therapy that selectively degrades the undruggable IKZF2 transcription factor, a driver in leukemia stem cell self-renewal, and selective degraders of therapeutically important proteins CDK2 and SMARCA2, of which overexpression is associated with epithelial ovarian cancer.
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