BioPharma, Pharma

Roche Deal Aims to Get Molecular Glues to Stick to Elusive Cancer, Neuro Targets

Roche is paying $50 million up front to begin a drug R&D alliance with Monte Rosa Therapeutics, a biotech whose molecular glue technology could address targets previously deemed undruggable. It’s Roche’s second such deal in the past month.

Roche’s presence in neuroscience is overshadowed by the company’s large cancer portfolio and pipeline. The Swiss pharmaceutical giant is positioning itself to expand in both therapeutic areas through a new partnership with Monte Rosa Therapeutics aiming to discover and develop drugs for disease targets thought to be undruggable.

The targets of interest were not disclosed. But the alliance announced Tuesday starts with Roche making a $50 million upfront payment to Monte Rosa, a clinical-stage biotech whose research focuses on molecular glues. These glues are small molecules that bring together two proteins that normally do not interact. Fostering that interaction enables a disease-causing protein to be marked for disposal using a built-in cellular system for getting rid of old or damaged proteins.

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This emerging therapeutic modality is called targeted protein degradation. For some targets, it relies on the proximity induced by a molecular glue. Proximity also featured in the leadup to the new collaboration between Roche and Monte Rosa, which is based in Boston but also has operations in Basel, Switzerland.

“When you have an office in Basel, almost in walking distance to Roche, it’s almost natural for, at some point, these conversations to happen,” Monte Rosa CEO Markus Warmuth said during a conference call Tuesday. “There’s many other reasons of course, not just the short commute, why we are excited.”

Warmuth declined to go into detail about the targets covered by the new alliance, other than to say it is a “limited number.” This discovery collaboration does not affect Monte Rosa’s internally discovered and wholly owned programs (lead program MRT-2359, which addresses the elusive cancer-driving protein MYC, posted encouraging interim Phase 1 data on Tuesday), but these programs do have the opportunity to become the basis of future partnerships, Warmuth said. Monte Rosa remains free to pursue other targets in other therapeutic indications, including those in oncology and neuroscience not covered by the Roche agreement.

Under the new partnership, Monte Rosa will lead discovery and preclinical work against the cancer and neurological disease targets up to a certain point. Roche has the right to exclusively pursue further preclinical and clinical development of the compounds. Milestone payments tied to the progress of this research could bring Monte Rosa $2 billion or more, plus royalties if the research leads to any commercialized products.

The Monte Rosa pact is Roche’s second molecular glue partnership in the past month. In September, the pharma giant’s Genentech subsidiary paid Orionis Biosciences $47 million up front to begin an alliance focused on developing small molecule monovalent glues for use in disease areas that include oncology and neurodegeneration.

Similar to Monte Rosa, Orionis has a platform technology that discovers small molecules suitable for use as glues. In addition to degradation, Orionis says its approach can also lead to modulation of its target. The disease targets of this deal were not disclosed, but milestone payments for this Orionis deal could top $2 billion.

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