Monte Rosa and Novartis Partner to Target Undruggable Immunology Pathways with Degraders

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Monte Rosa Therapeutics (Monte Rosa), a US-based clinical-stage biotechnology company specializing in novel molecular glue degrader (MGD)-based medicines, announced a second collaboration on Sept. 15, 2025 with Novartis focused on developing novel degraders for immune-mediated diseases (1). This newer partnership builds on the companies’ initial 2024 licensing agreement (2,3) for vav guanine nucleotide exchange factor 1 (VAV1) degraders, including MRT-6160, a candidate advancing toward multiple Phase II studies.

The new agreement aims to accelerate the development of degraders against difficult-to-drug immunology targets. Under the deal, Monte Rosa will apply its proprietary quantitative and engineered elimination of neosubstrates (QuEEN) product engine, which integrates artificial intelligence (AI) and machine learning (ML) with chemical biology and proteomics, to design highly selective MGDs. Novartis will assume responsibility for later-stage development and commercialization.

“We are extremely excited to extend our relationship with Novartis beyond our previously announced VAV1 agreement given the strong progress made to advance MRT-6160 toward initiation of multiple Phase II studies in immune-mediated diseases,” said Markus Warmuth, MD, chief executive officer, 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.”

How is AI driving discovery for new MGDs?

MGDs are a class of small molecules designed to reprogram cellular protein degradation machinery, enabling the elimination of disease-causing proteins that have been historically considered undruggable. For immunology applications, these degraders hold particular promise in modulating complex pathways associated with Th1, Th2, and Th17-driven autoimmune conditions (4).

Monte Rosa’s QuEEN discovery engine applies AI/ML to identify and optimize degrader candidates with high selectivity. This approach combines computational modeling with structural biology and chemical library design, enabling the rational development of degraders that target immune pathways with precision, according to the company in its release.

“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,” Warmuth said in the release. “This new collaboration allows us to expedite the development of certain of those programs with Novartis, leveraging their recognized development and commercialization capabilities.”

Meanwhile, Fiona Marshall, PhD, president of Biomedical Research at Novartis, highlighted the scientific rationale behind expanding the collaboration. She stated in the release, “We are pleased to expand our collaboration with Monte Rosa Therapeutics, building on the strong foundation and progress established through the VAV1 program. This new agreement underscores our commitment to advancing targeted protein degradation as a promising approach to address immune-mediated diseases with high unmet need. 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.”

What does the deal specifically involve, and what are the broader implications for drug development?

Under the agreement, Novartis will pay an upfront payment of $120 million to Monte Rosa, along with option maintenance payments. If fully executed, the partnership could be worth up to $5.7 billion through option exercise fees, preclinical and clinical milestones, regulatory and sales-based payments, and tiered royalties on future global net sales.

Importantly for biopharmaceutical development, the extended financial runway allows Monte Rosa to continue advancing its internal immunology and inflammation portfolio, including undisclosed preclinical programs and upcoming Phase II readouts for candidates MRT-8102, MRT-6160, and MRT-2359. While the specific programs included in this agreement remain undisclosed, Monte Rosa’s other publicly disclosed pipeline assets are not covered under the collaboration.

For biopharmaceutical researchers and developers, this partnership reflects the growing momentum behind protein degradation strategies as a means of tackling immune-mediated diseases. The integration of AI-driven design with traditional drug development pipelines could accelerate the transition from preclinical exploration to clinical testing, broadening the therapeutic landscape for diseases with significant unmet need (5).

References

1. Monte Rosa Therapeutics. Monte Rosa Therapeutics Announces Collaboration with Novartis for Degraders to Treat Immune-mediated Diseases. Press Release. Sept. 15, 2025.
2. Monte Rosa Therapeutics. Monte Rosa Therapeutics Announces Global License Agreement with Novartis to Advance T and B Cell-modulating VAV1-directed Molecular Glue Degraders. Press Release. Oct. 28, 2024.
3. Monte Rosa Therapeutics. Monte Rosa Therapeutics Announces Closing of Global License Agreement with Novartis to Advance T and B Cell-modulating VAV1-directed Molecular Glue Degraders. Press Release. Dec. 11, 2024.
4. Tan, X.; Huang, Z.; Pei, H.; Jia, Z.; Zheng, J. Molecular Glue-Mediated Targeted Protein Degradation: A Novel Strategy in Small-Molecule Drug Development. iScience 2024, 27 (9), 110712. DOI: 10.1016/j.isci.2024.110712
5. Ferreira, F. J. N.; Carneiro, A. S. AI-Driven Drug Discovery: A Comprehensive Review. ACS Omega 2025, 10 (23), 23889-23903. DOI: 10.1021/acsomega.5c00549