Recently, the molecular glue star company Monte Rosa Therapeutics announced that it has reached a global exclusive development and commercialization license agreement with Novartis to advance the development of molecular glue protein degraders targeting VAV1, including the research therapy MRT-6160.

Under the terms of the agreement, Novartis agreed to pay Monte Rosa an advance payment of US$150 million. In addition, Monte Rosa is eligible to receive up to US$2.1 billion in development, regulatory and sales milestone payments (US$2.25 billion is approximately RMB 16 billion).

Monte Rosa Therapeutics is headquartered in Boston, USA. The company was founded in 2018 and is a biotechnology company focusing on the development of molecular glue drugs. Its core technology platform is the QuEEN platform, which is mainly dedicated to the discovery and development of molecular glue drugs.

Under the terms of the agreement, Monte Rosa will continue to be responsible for completing the ongoing Phase 1 clinical study of MRT-6160, and Novartis will be responsible for all clinical development and commercialization starting from the Phase 2 clinical study. Monte Rosa will co-fund the Phase 3 clinical development of MRT-6160 in the United States and share any gains and losses associated with production and commercialization.

According to the information, MRT-6160 is a VAV1 molecular glue degrader under investigation. VAV1 is a key signaling protein downstream of T cell and B cell receptors. Preclinical studies have shown that deep degradation of VAV1 leads to a significant reduction in cytokines associated with immune-mediated disorders, while there is no detectable effect on other proteins. The drug has shown promising activity in preclinical models of multiple immune-mediated diseases, including multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease and other diseases.

In fact, this is not the first time that Novartis and molecular glue have "touched". As early as July this year, the latest research on Novartis' molecular glue protein degrader was published in Science, establishing WIZ degradation as a new treatment strategy for sickle cell disease that is globally accessible.

As we all know, sickle cell anemia (SCD) is a common, life-threatening blood disease that can be attributed to genetic mutations in β-hemoglobin. Although the first approved CRISPR/Cas9 gene editing therapy is available to treat the disease, it involves editing DNA and costs millions of dollars. SCD is in urgent need of a new and more accessible therapy.

Novartis researchers published a research paper titled "A molecular glue degrader of the WIZ transcription factor for fetal hemoglobin induction" in the journal Science. The research team used a molecular glue chemical library targeting Cereblon to explore the reactivation of HbF.

The study describes a molecular glue protein degrader targeting WIZ, which can also upregulate the expression of HbF by degrading WIZ, thereby achieving the effect of treating sickle cell anemia (SCD). First, the molecular glue-related research appeared in Science, and then there was a molecular glue-related collaboration worth more than $2 billion. All signs indicate that Novartis is strengthening its pipeline layout in the field of molecular glues and adding "new weapons" to it.

Molecular glue drugs are a class of small molecule compounds that can induce or stabilize protein-protein interactions. Their mechanism of action is different from that of traditional drugs. Molecular glues achieve therapeutic effects by specifically regulating the functions and interactions of proteins, mediating the degradation or functional modification of target proteins. This mechanism provides a new way to target "undruggable" proteins, greatly expanding the scope and application prospects of drug design, and molecular glue drugs have gradually become the focus of major pharmaceutical giants.

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