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Novartis, Monte Rosa Launch Up-to-$2.1B Molecular Glue Collaboration
Novartis will apply Monte Rosa Therapeutics’ target discovery platform to develop its T and B cell-modulating molecular glue degraders targeting the VAV1 protein—starting with its Phase I autoimmune disease candidate MRT-6160—through a collaboration that could
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Novartis will apply Monte Rosa Therapeutics’ target discovery platform to develop its T and B cell-modulating molecular glue degraders targeting the VAV1 protein—starting with its Phase I autoimmune disease candidate MRT-6160—through a collaboration that could generate more than $2.1 billion for the Boston biotech.
Monte Rosa’s Quantitative and Engineered Elimination of Neosubstrates (QuEEN™) discovery engine is designed to identify degradable protein targets and rationally design molecular glue degraders with what the company calls unprecedented selectivity, through the platform’s combination of AI-guided chemistry, diverse chemical libraries, structural biology, and proteomics.
QuEEN is designed to enable access to a wide-ranging and differentiated variety of well-validated targets across multiple therapeutic areas. Using QuEEN, Monte Rosa has developed a pipeline of six disclosed molecular glue degrader programs in therapeutic areas that include oncology, autoimmune, and inflammatory disease.
“Novartis has had a long-standing interest in molecular glue degraders, which offer the potential to tackle challenging biological targets,” Fiona Marshall, Novartis’ President of Biomedical Research, said in a statement. “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.”
MRT-6160 is now under study in a first-in-humans Phase I single ascending dose/multiple ascending dose healthy volunteer trial (NCT06597799) designed to assess the drug for immune-mediated conditions.
MRT-6160 is a highly selective oral investigational degrader of VAV1, a key signaling protein downstream of both the T- and B-cell receptors. According to Monte Rosa, preclinical studies have shown MRT-6160 to cause “deep” degradation of VAV1, resulting in a significant decrease in cytokines linked to immune-mediated conditions, with no detectable effects on other proteins. MRT-6160 has also shown promising activity in preclinical models of multiple immune-mediated conditions.
Investors roared their approval of the collaboration by sending Monte Rosa’s shares on NASDAQ more than doubling, surging 135% as of 2:45 p.m. today, from $4.89 to $11.49. Novartis shares on the SIX Swiss Exchange rose 1% to CHF 99.81 ($115.36).
Through the collaboration, Novartis has received exclusive worldwide rights to develop, manufacture, and commercialize MRT-6160 and other VAV1 molecular glue degraders. Novartis has agreed to oversee all clinical development and commercialization, starting with Phase II trials, while Monte Rosa remains responsible for completion of the ongoing Phase 1 trial of MRT-6160.
Novartis has agreed to pay Monte Rosa $150 million upfront, plus up to $2.1 billion in payments tied to achieving development, regulatory, and sales milestones, starting with the start of Phase II studies. The pharma giant has also agreed to shell out tiered royalties on net sales outside the U.S. for products covered by the collaboration.
The $150 million upfront is the second highest upfront payment among more than 30 molecular glue degrader collaborations tracked by Jefferies over the past three years
“We think this high upfront payment indicates NVS [Novartis’] confidence [in] MRT-6160 in achieving clinical & commercial success in autoimmune,” Jefferies equity analyst Kelly Shi, PhD, wrote today in a research note.
“Retaining substantial value”
“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,” stated Monte Rosa CEO Markus Warmuth, MD. “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 [molecular glue degraders] for undruggable targets, including in the areas of immunology and inflammation, metabolism, and genetic diseases.”
MRT-6160 is one of two clinical candidates in Monte Rosa’s pipeline. The other is MRT-2359, a wholly owned GSPT1-targeting molecular glue degrader being developed for non-small cell lung cancer, small cell lung cancer, and other MYC-driven malignancies. MRT-2359 is under study in a Phase I/II trial (NCT05546268) designed to determine safety, tolerability, maximum tolerated dose and/or recommended Phase II dose (RP2D).
Novartis is not the first pharma giant with which Monte Rosa is partnering in developing molecular glue degraders.
A year ago this month, Monte Rosa joined with Roche to launch a strategic collaboration aimed at discovering and developing molecular glue degraders against targets in cancer and neurological diseases previously considered impossible to drug. Roche paid Monte Rosa $50 million upfront and agreed to pay up to $2 billion in preclinical, clinical, commercial, and sales milestone payments, as well as tiered royalties.
Growing numbers of biopharma giants have focused on developing molecular glues over the past year. Two weeks ago, Pfizer agreed to apply Triana Biomedicines’ target-first and proximity-first discovery platform to discover molecular glue degraders for unspecified “multiple” targets in oncology and several other disease areas, through a collaboration that could generate more than $1.5 billion for the Lexington, MA, biotech.
Takeda Pharma inked an up-to-$1.2 billion, plus royalties, partnership with Degron Therapeutics in May to develop molecular glue-based therapies in oncology, neuroscience, and inflammation, using Degron’s GlueXplorer® platform. And in February, Novo Nordisk launched an up-to-$1.46 billion partnership with San Diego-based Neomorph to discover, develop, and commercialize molecular glue degraders for unspecified targets in cardiometabolic and rare diseases.
Monte Rosa said it planned to provide information about its updated cash position and financial runway following the collaboration when it releases third quarter earnings, something expected next month. The company reported $108.847 million in cash and cash equivalents as of June 30, down 15% from $128.101 million on December 31, 2023.
“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.” Warmuth added.
The collaboration agreement is subject to regulatory clearance and other customary closing conditions.
“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 added.