Monte Rosa Therapeutics has seen good news for one of its molecular glue degradation candidates and bad news for another with one immunotherapy study showing promising results whilst another in solid tumours falls short.
Based in Boston, US, the company has unveiled new data from two trials of its pipeline of molecular glue degraders, including updates from a Phase I single-ascending dose / multiple-ascending dose (SAD/MAD) study of MRT-6160 (NCT06597799) in healthy volunteers.
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Investigators sought to understand the safety and tolerability of MRT-6160, along with its ability to degrade a nucleotide exchange factor, VAV1.
VAV1 plays a crucial role in several immune processes, as well as T-cell and B cell production. Results saw a sustained, dose-dependent VAV1 degradation of more than 90%.
At the same time, the oral therapy inhibited the secretion of inflammatory cytokines, such as IL-2, by up to 99%. That first-in-human study recruited 79 patients at sites across the US split into five dose cohorts.
Disappointment in solid tumours
Meanwhile, Monte Rosa’s Phase I/II trial examining MRT-235 (NCT05546268) has seen its molecular glue degrader targeting GSPT1 fail to produce the expected biomarker positivity rates intended to support further development in lung cancers and neuroendocrine tumours. As a result, the company will be dropping the investigation of these indications. Favourable signals were detected in patients living with castration-resistant prostate cancer (CRPC) where research will continue.
Monte Rosa Therapeutics CEO Markus Warmuth said: “Our updated MRT-2359 results deepen our understanding of the drug’s clinical profile across several challenging-to-treat solid tumours. We have observed encouraging early signals of clinical response in heavily pretreated CRPC, including a confirmed partial response and two patients with stable disease within the first three patients treated with MRT-2359/enzalutamide combination therapy.
“In light of these data, we plan to focus our ongoing MRT-2359 development efforts in CRPC, with the potential to expand this cohort to 20 to 30 patients while deprioritising other expansion arms except ER-positive breast cancer.”
Research by GlobalData estimates that if MRT-2359 makes it to market, it is likely to bring in approximately $21m for Monte Rosa by the end of 2028.
MRT-6160 is being developed in partnership with pharma giant Novartis, which saw Monte Rosa receiving an upfront payment of $150m last year to develop the immunotherapy candidate. In addition, Monte Rosa has the potential to receive up to $2.1bn in development, regulatory and sales milestones, as well as tiered royalties on sales outside the US.
GlobalData is the parent company of Clinical Trials Arena.
Elsewhere in the space of molecular glue degraders, Novo Nordisk has signed a deal with Neomorph to discover and develop multiple kinds of degraders for cardiometabolic disorders and rare diseases.
