Monte Rosa, Novartis Target ‘Undruggable’ Proteins in Major Immunology Partnership
A deal worth up to USD 5.7 billion has been unveiled that is aimed at the development of molecular glue degraders for immune-mediated diseases utilizing Monte Rosa’s AI-driven QuEEN platform.
A major collaboration between Monte Rosa Therapeutics and Novartis, focusing on the discovery and development of molecular glue degraders (MGDs) for the treatment of immune-mediated diseases, has been announced (1). As part of the agreement, Novartis will pay Monte Rosa USD 120 million upfront, with the total deal value potentially reaching USD 5.7 billion through a combination of milestone payments, option fees, and tiered royalties on any resulting therapies' global sales. The deal also grants Novartis exclusive rights to an undisclosed discovery target and the option to license two additional programs from Monte Rosa’s preclinical immunology pipeline.
MGDs are small molecules that act by promoting or stabilizing an interaction between a disease-causing protein and the cell’s natural protein degradation machinery — specifically E3 ubiquitin ligases (2). Unlike traditional drugs that inhibit protein function, or PROTACs that physically link the target protein to an E3 ligase, molecular glues induce a direct protein–protein interaction, leading to the selective degradation of the target protein. This mechanism enables the targeting of previously "undruggable" proteins by reshaping protein surfaces to enable new interactions (3), effectively eliminating all functions of the pathogenic protein rather than merely inhibiting it. Recent advances indicate that molecular glues can target a wider variety of proteins than initially thought, expanding therapeutic options for treating diseases such as cancer and immune disorders with higher sensitivity and efficacy at low doses.
To develop the highly selective MGDs, Monte Rosa will leverage its QuEEN drug discovery platform — a proprietary, artificial intelligence (AI)-driven product engine integrating machine learning and proteomics — that targets the difficult-to-drug proteins implicated in immune disorders. The company will further be responsible for discovery and early-stage validation, after which Novartis will assume development and global commercialization for programs it opts to license.
“We are extremely excited to extend our relationship with Novartis… toward initiation of multiple Phase II studies in immune-mediated diseases,” said Markus Warmuth, M.D., Chief Executive Officer of Monte Rosa Therapeutics, in a company press release (1). “We believe this new agreement further strengthens our relationship with Novartis, a recognized global leader in immune-mediated diseases, and reflects the expansive opportunity in the space for our highly selective and potent MGDs. Our AI/ML-enabled QuEEN product engine continues to generate new insights and opportunities, delivering an expanding pipeline of programs directed against a breadth of historically undruggable immunology targets. This new collaboration allows us to expedite the development of certain of those programs with Novartis, leveraging their recognized development and commercialization capabilities.”
“This new agreement underscores our commitment to advancing targeted protein degradation as a promising approach to address immune-mediated diseases with high unmet need,” added Fiona Marshall, Ph.D., President of Biomedical Research at Novartis, in the press release (1). “We believe Monte Rosa’s QuEEN platform has the potential to uncover new insights in this field. We look forward to working together to translate these insights into transformative therapies for patients.”
The alliance comes as pharmaceutical companies race to access new, more effective modalities for immune diseases, targeting proteins long considered “undruggable” using traditional approaches. In addition to expanding Novartis’s strategic push in targeted protein degradation, the partnership gives Monte Rosa the financial resources to progress several internal programs through key clinical milestones, reflecting growing industry validation of molecular glue degrader technology for next-generation immunology therapeutics. This marks the second substantial partnership between the companies, following a 2024 deal for a VAV1-targeted degrader program, including MRT-6160, which is advancing toward multiple Phase II clinical trials.
References
Monte Rosa Therapeutics. Monte Rosa Therapeutics Announces Collaboration with Novartis for Degraders to Treat Immune-mediated Diseases. Press Release, Sep. 15, 2025.
Tan, X.; Huang, Z.; Pei, H.; et al. Molecular glue-mediated targeted protein degradation: A novel strategy in small-molecule drug development. iScience, 2024, 27 (9), 110712.
Sasso, J.M.; Tenchov, R.; Wang, D.; et al. Molecular Glues: The Adhesive Connecting Targeted Protein Degradation to the Clinic. Biochemistry, 2023, 62 (3), 601–623.