Novartis and Monte Rosa Therapeutics have announced a global agreement focused on the development and commercialization of molecular glue degraders targeting VAV1, including Monte Rosa’s MRT-6160. This collaboration aims to address immune-mediated conditions by leveraging a novel approach to protein degradation.
Agreement Details
Under the terms of the agreement, Monte Rosa will receive an upfront payment of $150 million. Additionally, the company is eligible for up to $2.1 billion in development, regulatory, and sales milestone payments, starting upon the initiation of Phase II studies. The agreement also includes tiered royalties on net sales outside the U.S. Monte Rosa will co-fund Phase III clinical development and share profits/losses associated with manufacturing and commercialization of MRT-6160 in the U.S.
MRT-6160: A Novel VAV1 Degrader
MRT-6160 is described as a potent, highly selective, and orally bioavailable investigational degrader of VAV1, a key signaling protein downstream of both T- and B-cell receptors. Preclinical studies have demonstrated that MRT-6160 achieves deep degradation of VAV1, leading to a significant reduction in cytokines associated with immune-mediated conditions, without detectable effects on other proteins. These preclinical results have shown promising activity in models of multiple immune-mediated conditions.
Clinical Development and Future Plans
Currently, MRT-6160 is undergoing a Phase I clinical study involving single ascending dose (SAD) and multiple ascending dose (MAD) evaluations in healthy volunteers. This study is designed to assess the safety and tolerability of the drug. Following the completion of the Phase I study by Monte Rosa, Novartis will assume responsibility for all subsequent clinical development and commercialization activities, commencing with Phase II clinical studies.
Strategic Rationale
Fiona Marshall, president of biomedical research at Novartis, stated that MRT-6160 could "provide a new therapeutic option for people living with a range of immune-mediated conditions.” Markus Warmuth, MD, CEO of Monte Rosa Therapeutics, added that the deal validates their QuEEN™ discovery engine and increases their conviction to develop highly selective and safe MGDs for undruggable targets in immunology, inflammation, metabolism, and genetic diseases.
Molecular Glue Degraders: A Promising Therapeutic Modality
Molecular glue degraders represent an emerging class of therapeutics capable of targeting proteins previously considered undruggable. These molecules work by inducing interactions between a target protein and an E3 ubiquitin ligase, leading to ubiquitination and subsequent degradation of the target protein via the proteasome pathway. This approach holds promise for addressing a wide range of diseases, including those driven by dysregulation of the immune system.
