Novartis and Monte Rosa Therapeutics Form $2.1 Billion Global License Agreement for MGD-based Therapeutics

Editor's note: this story was originally published on BioPharmInternational.com.

Monte Rosa Therapeutics, a Boston, Mass.-headquartered clinical-stage biotechnology company specializing in novel molecular glue degrader (MGD)-based medicines, announced on Oct. 28, 2024, that it entered into a global exclusive development and commercialization license agreement with Novartis. The agreement is worth potentially up to $2.1 billion and aims to advance vav guanine nucleotide exchange factor 1 (VAV1) MGDs, including MRT-6160, a drug candidate being evaluated in an ongoing Phase I single ascending dose (SAD)/multiple ascending dose (MAD) healthy volunteer study for immune-mediated conditions.

Under the agreement, Novartis will pay Monte Rosa $150 million up front in exchange for exclusive worldwide rights to develop, manufacture, and commercialize MRT-6160 and other VAV1 MGDs. Monte Rosa is eligible to receive up to $2.1 billion in development, regulatory, and sales milestones, starting with the initiation of Phase II clinical studies of MRT-6160. Monte Rosa is also eligible to receive tiered royalties on ex-US net sales.

Novartis will be responsible for all clinical development and commercialization of MRT-6160, starting at the Phase II clinical phase. Monte Rosa, meanwhile, will remain responsible for completing the ongoing Phase I clinical study for the drug candidate. In addition, Monte Rosa will co-fund any Phase III clinical development. The company will also share any profits and losses associated with the manufacturing and commercialization of MRT-6160 in the United States.

“We are thrilled to announce this agreement with Novartis, a key player in immune-mediated conditions, and we are excited about the transformative potential it provides for Monte Rosa and MRT-6160. We expect this will accelerate and broaden the scope of clinical development of MRT-6160 to advance this unique, orally bioavailable modality while retaining substantial value for Monte Rosa. We believe the transaction validates our unique and industry leading QuEEN discovery engine, and it further increases our conviction to rationally design and develop highly selective and safe MGDs for undruggable targets, including in the areas of immunology and inflammation, metabolism, and genetic diseases,” said Markus Warmuth, MD, chief executive officer, Monte Rosa Therapeutics, in a company press release. “The financial resources provided by this agreement are expected to extend our operational runway, enable us to advance our pipeline to potential value-creating milestones and anticipated proof-of-concept readouts, and further leverage our QuEEN discovery engine.”

MRT-6160 is a potent, highly selective, and orally bioavailable investigational degrader of VAV1, which is known as a key signaling protein found downstream of both T- and B-cell receptors. According to preclinical studies, MRT-6160 demonstrated deep degradation of VAV1, which resulted in a significant decrease in cytokines linked to immune-mediated conditions. It also showed no detectable effects on other proteins. The candidate has shown promising activity in preclinical models of multiple immune-mediated conditions (1,2).

"Novartis has had a long-standing interest in molecular glue degraders, which offer the potential to tackle challenging biological targets. We are excited about their application in immunology and the early progress we have seen by Monte Rosa in this space and with MRT-6160. We look forward to advancing MRT-6160 and learning more about its potential to provide a new therapeutic option for people living with a range of immune-mediated conditions,” said Fiona Marshall, president, Biomedical Research, Novartis, in the press release. “Novartis is committed to bringing forward new therapeutic options for these patients, and we are happy to be working with Monte Rosa to harness the potential of this approach to address unmet medical needs.”

References

1. Cartwright, A.; Desai, F.; Vora, S.; et al. MRT-6160, a VAV1-Directed Molecular Glue Degrader, Reduces Joint Inflammation and Autoantibody Production in a Collagen-Induced Arthritis Autoimmune Disease Model. Poster presented at Digestive Disease Week 2024, Washington, DC, May 21, 2024.
2.Cartwright, A.; Vora, S.; Gyger, L.; et al. MRT-6160, a VAV1-Directed Molecular Glue Degrader, Inhibits Disease Progression in a T-cell Transfer Mediated Colitis Model Concomitant with Reduced Calprotectin Expression. Poster presented at EULAR 2024—Annual European Congress of Rheumatology, Vienna, Austria, June 14, 2024.

Source: Monte Rosa Therapeutics