Novartis Inks Potential $2.2B Molecular Glue Deal With Monte Rosa

Pictured: Novartis' logo outside its building in S

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The Swiss pharma is paying $150 million upfront to gain rights to Monte Rosa’s VAV1-targeting molecular glue degraders, led by a Phase I candidate which holds therapeutic promise for immune-mediated diseases.

Novartis on Monday became the latest Big Pharma player to jump into the molecular glue space. The Swiss drugmaker signed an exclusive development and commercialization agreement with Monte Rosa Therapeutics, as it eyes the immune diseases market.

Under the agreement, Novartis will pay the Boston biotech $150 million upfront and will pledge up to $2.1 billion in development, regulatory and sales milestones, starting in Phase II development. Monte Rosa will also be eligible for tiered royalties on sales outside the U.S.

Novartis will be able to take charge of the development of Monte Rosa’s molecular glue degraders targeting the VAV1 protein. These include the early-stage candidate MRT-6160, which is currently undergoing Phase I single-ascending and multiple-ascending dose studies in healthy volunteers.

As part of the agreement, Novartis will only assume responsibility over MRT-6160 starting in Phase II. Monte Rosa will still need to complete its Phase I study of MRT-6160 and the biotech will also co-fund the candidate’s Phase III clinical development. Profits and losses associated with the manufacturing and sale of MRT-6160 in the U.S. will be shared between the two companies.

Fiona Marshall, president of biomedical research at Novartis, said in a statement that the pharma is “excited” about the Monte Rosa partnership—and about the “early progress” that the biotech has demonstrated in applying molecular glue degraders in the field of immunology.

“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,” Marshall said.

Molecular glues are a rapidly emerging class of therapies that work by binding to enzymes called ubiquitin ligase, which functions to tag specific proteins for degradation. The molecular glue also seeks out and binds to its target protein. This mode of action brings the ligase closer to the specific disease-causing protein, which is in turn destroyed by the cell’s internal machinery.

In the case of MRT-6160, the target protein is VAV1 which according to Monte Rosa’s website is a key signaling protein involved in T- and B-cell cascades. Preclinical studies have shown that deactivating VAV1 leads to a significant reduction in the secretion of cytokines, which are central to the immune response. MRT-6160’s mechanism of action gives it therapeutic potential for immune-mediated and autoimmune conditions.

Several other Big Pharma players have recently jumped into the molecular glue space. This includes Takeda, which in May 2024, signed a potential $1.2 billion deal with China’s Degron Therapeutics for molecular glues for cancer, neuroscience and inflammatory disease targets.

Roche in September 2023 bet up to $2 billion in Orionis Biosciences’ pipeline of investigational glues to target “challenging targets” in cancer and neurodegeneration.

Novo Nordisk is also investing in molecular glues, putting nearly $1.5 billion on the line in February 2024 to gain access to Neomorph’s platform to advance therapies for cardiovascular and rare diseases.

Tristan is an independent science writer based in Metro Manila, with more than eight years of experience writing about medicine, biotech and science. He can be reached at tristan.manalac@biospace.com, tristan@tristanmanalac.com or on LinkedIn.
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