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Takeda has inked an exclusive license agreement with Shanghai-based Degron Therapeutics to discover and develop novel molecular glue degraders targeting oncology, neuroscience and inflammation. Under the terms of the deal, Degron will receive an upfront payment and potential milestone payments totaling up to $1.2 billion.The collaboration will leverage Degron's GlueXplorer platform to identify, validate, and optimize molecular glue degraders for therapeutic targets selected by Takeda. Projects that reach a certain stage of advancement will be transitioned to Takeda for further development and commercialization. Takeda will also make an equity investment in Degron, which retains full ownership of its pipeline programs. The agreement includes options to expand the collaboration to more targets. Founded in 2021, Degron uses its proprietary GlueXplorer platform to develop molecular glue degraders for previously undruggable disease targets. The platform includes a diverse compound library, screening approaches, and extensive validation assays, supported by an AI algorithm to predict novel targets and accelerate discovery. The industry has shown a rising interest in molecular glues. Back in February, BMS teamed with generative AI company VantAI to find new molecular glues for targeted therapeutic purposes. Weeks later, Neomorph and Novo Nordisk announced a potential $1.46 billion collaboration to develop molecular glue degraders targeting cardiometabolic diseases and rare conditions. Last year, Austria-based biotech Proxygen signed a research collaboration and license agreement with Merck to jointly develop molecular glue degraders for therapeutic targets. Currently, only thalidomide and its analogues have been approved by the FDA. But with key players entering the ring and many clinical trials underway, the molecular glue garden sector is bound to bloom soon.

Pictured: Facade of Takeda's office in Massachusetts/iStock, hapabapa Takeda Pharmaceuticals has inked an exclusive licensing deal with China-based Degron Therapeutics to develop novel molecular glue degraders for various oncology, neuroscience and inflammatory disease targets, the Chinese biotech announced Thursday. The partners did not disclose the specific financial breakdown of the agreement, only revealing that Takeda will make an upfront payment and will pledge potential preclinical, clinical, development and commercial milestones, all of which could reach $1.2 billion. Meanwhile, Degron will be eligible for tiered royalties on sales of any commercialized product as a result of the partnership. Takeda will also make an equity investment in Degron as part of the agreement. In return, the Japanese multinational will gain access to Degron’s proprietary GlueXplorer discovery platform, which makes use of the biotech’s “unique and expanding library of structurally differentiated molecular glue degraders,” which are subjected to various assays and screening techniques to validate their mechanism and therapeutic potential, according to the announcement. Degron also uses artificial intelligence to supplement its GlueXplorer approach, using proprietary data and algorithms to predict novel glue targets and accelerate the discovery of potential compounds. Takeda CSO Chris Arendt said in a statement that its collaboration with Degron will add “an innovative new platform to our drug discovery toolbox,” adding that molecular glue degraders could give the company access to targets that have been “previously inaccessible or inadequately modulated by other treatment modalities.” Takeda and Degron will retain the option to expand the partnership to include additional targets. Molecular glue degraders are an emerging class of potentially therapeutic compounds that work by facilitating the interaction between two molecules, typically two proteins, inside a cell. This mechanism of action allows the molecular glues to tag previously undruggable disease-causing proteins for destruction. Several Big Pharma players have recently ramped up investments in molecular glues. In February 2024, Novo Nordisk put $1.46 billion on the line to team up with San Diego biotech Neomorph to develop and commercialize novel molecular glues. The partners have yet to reveal what cancers they will prioritize, only indicating that the collaboration will cover multiple targets. Neomorph will handle discovery and preclinical activities and then Novo will take over clinical development. Also betting on the molecular glue space is Roche. In September 2023, its subsidiary Genentech paid $47 million upfront and pledged up to $2 billion in a multi-year collaboration with Orionis Biosciences to develop therapies for “challenging targets in major disease areas” such as cancer and neurodegeneration. In April 2023, Merck also jumped into the hot molecular glue space with a potential $2.55 billion deal with Vienna-based Proxygen. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

C4 Therapeutics has inked a potentially lucrative deal with Merck KGaA to discover two targeted protein degraders against undisclosed oncogenic proteins. The collaboration adds to Merck's growing portfolio of protein degradation projects as it expands its presence in the space.Under the agreement, C4 will receive an upfront payment of $16 million from Merck, which will help cover the costs of discovery research efforts for the two programmes. In turn, Merck will be responsible for developing and commercialising any drug candidates emerging from the partnership.C4 is eligible to receive up to approximately $740 million in combined discovery, development, and commercial milestones across the two programmes. It will also be able to pocket mid-single to low-double digit tiered royalties on potential future sales of any approved products.Merck's protein powerplayThe deal marks Merck's fourth collaboration in the protein degradation space, following agreements inked in 2022 with Amphista potentially worth over €932 million ($1 billion), Proxygen for up to €495 million ($537 million), and Celeris Tx. The German pharma giant has been actively pursuing partnerships to bolster its pipeline of targeted protein degraders, a modality that has drawn interest from a number of other major players, including Novo Nordisk (for more, see – Spotlight On: Targeted protein degradation grows up).For the collaboration, C4T will leverage its proprietary TORPEDO platform. According to the company, the platform allows it to create both molecular glue degraders, or so-called MonoDACs, and heterobifunctional degraders, referred to as BiDACs, providing the capability to target "almost any disease-causing protein."CEO Andrew Hirsch said the deal "highlights [our] differentiated approach to targeted protein degradation science and our strong track record of designing novel targeted protein degrader medicines with desirable drug-like properties."C4 is also partnered with Merck & Co. to develop degrader-antibody conjugates in a deal potentially worth $600 million.However, Monday’s alliance comes on the heels of a corporate restructuring at C4, which recently cut 30% of its workforce, or about 45 positions, to extend its cash runway into 2027. The layoffs followed the company's decision to discontinue development of its BRD9-targeted degrader, CFT8634, due to insufficient efficacy in a Phase I trial.