Pfizer will apply Triana Biomedicines’ target-first and proximity-first discovery platform to discover molecular glue degraders for unspecified “multiple” targets in oncology and several other disease areas, through a collaboration that could generate more than $1.5 billion for the Lexington, MA, biotech.
Privately held Triana focuses on building a molecular glue pipeline developed through its platform, which is designed to identify small molecules that induce protein:protein interactions between disease targets and a component of the cell’s ubiquitin-proteasome system (UPS), thus altering the fate or function of the disease target protein.
Triana applies its protein:protein pairing engine to identify E3 ligases that are potential matches, then launches a comprehensive glue discovery campaign covering diverse chemical spaces to identify new molecular glues.
The resulting molecular glue degraders eliminate disease-causing proteins by promoting their interaction with the cell’s UPS—namely enhancing binding between a disease-causing protein and an E3 ligase enzyme. According to Triana, the small molecules can effectively promote the formation of a complex between two proteins even with low binding affinity of the molecular glue to either protein partner.
Triana says it applies genomic, functional, and translational data to prioritize disease targets and candidate E3 ligases for molecular glue discovery, creating a short list from the universe of more than 600 E3 ligases. The company’s technologies are designed to identify preferred E3 ligases for a specific disease target, then discover small molecules that directly promote the interaction of the disease target:E3 ligase pair.
Under their strategic collaboration and licensing agreement, Pfizer has agreed to pay Triana $49 million upfront and potentially more than $1.5 billion in payments tied to achieving milestones, plus tiered royalties.
“This collaboration with Triana Biomedicines on molecular glue discovery reflects our commitment to exploring cutting-edge technologies to drive the next wave of potential breakthroughs,” Jeff Settleman, PhD, CSO of Pfizer Oncology.
Growing interest
Pfizer is the latest biopharma giant over the past couple of years to launch a collaboration focused on molecular glues, reflecting a growing interest in the space.
“It has become clear lately that molecular glue type binding can be considered as a new modality option, specifically for otherwise poorly druggable protein targets,” Angela Zhou, PhD, manager of scientific analysis and insights with CAS, a Division of the American Chemical Society, and colleagues concluded in a 2023 paper reviewing developments in molecular glue development.
Takeda Pharma in May inked an up-to-$1.2 billion, plus royalties, partnership with Degron Therapeutics to develop molecular glue-based therapies for unspecified “multiple” indications in glue candidates in oncology, neuroscience, and inflammation, using Degron’s GlueXplorer® platform. Candidates discovered through Degron’s platform would be shifted to Takeda for further development and commercialization.
Additional targets could be added if the companies exercise their option to expand their collaboration. Takeda also agreed at the time to make an equity investment of an unspecified amount in Degron, which will retain full ownership of its pipeline programs. Degron is based in San Diego and Shanghai, China.
Novo Nordisk launched an up-to-$1.46 billion partnership in February with San Diego-based Neomorph to discover, develop, and commercialize molecular glue degraders for unspecified targets in cardiometabolic and rare diseases, tapping into Novo Nordisk’s expertise in both therapeutic areas.
“This collaboration will enable the expansion of our platform into new therapeutic areas, complementing our ongoing efforts in oncology,” Phil Chamberlain, DPhil, co-founder, president, and CEO of Neomorph, stated at the time.
And in September 2023, Genentech, a Member of the Roche Group, committed $47 million upfront, and potentially up-to-$2 billion-plus in milestone payments toward developing small molecule molecular glue therapies for “major disease areas” that include oncology and neurodegeneration, using Orionis’s Allo-Glue™ platform. Orionis agreed to oversee the discovery and optimization of molecular glues for Genentech’s designated targets, while Genentech is taking responsibility for later-stage preclinical, clinical development, regulatory filing, and commercialization.
Bristol Myers Squibb and Merck & Co. have also initiated molecular glue alliances with smaller partners.
“This collaboration agreement signifies an important milestone in the evolution of Triana, as the company advances toward delivering on its product-focused strategy,” added Patrick Trojer, PhD, Triana’s president and CEO.
