Monte Rosa Therapeutics Refocuses MRT-2359 Development on Prostate Cancer

Monte Rosa Therapeutics has announced a strategic shift in the development of its molecular glue degrader MRT-2359, narrowing its focus to prostate cancer following unexpected biomarker expression results across various tumor types. The decision comes as the company continues to advance its partnership with Novartis on another promising candidate.

Biomarker Challenges Reshape Clinical Strategy

Monte Rosa's phase 1/2 trial for MRT-2359, designed to target MYC-driven tumors by degrading the translation termination factor GSPT1, has encountered a significant obstacle. Analysis of tissue samples from 46 patients revealed lower-than-anticipated expression of L- or N-MYC in several tumor types, particularly in non-small cell lung cancer, where no patients exhibited high expression levels.

The biotech has responded by deprioritizing expansion arms for non-small cell lung cancer, small cell lung cancer, and high-grade neuroendocrine tumors. Instead, Monte Rosa will concentrate on prostate cancer, where the relevant biomarker is believed to be sufficiently prevalent to proceed without a companion diagnostic.

Prostate Cancer: A New Focus with Broad Potential

Dr. Filip Janku, Chief Medical Officer at Monte Rosa, outlined the company's revised strategy during a recent earnings call. He suggested that second-line use and combinations with established drugs like Astellas and Pfizer's Xtandi could serve as "a good starting point" for MRT-2359 in prostate cancer.

The potential patient population for MRT-2359 in prostate cancer is substantial, potentially matching that of Xtandi, which is used in both castrate-resistant and castrate-sensitive prostate cancers. Early data from three patients who received both MRT-2359 and Xtandi showed promise, with one patient experiencing a confirmed partial response.

Novartis Partnership Advances Amid Setback

While refocusing efforts on MRT-2359, Monte Rosa continues to make progress on other fronts, notably its collaboration with Novartis. The partnership, which began with a $150 million upfront payment in October, centers on the development of MRT-6160, a molecular glue degrader targeting immune diseases.

CEO Markus Warmuth expressed optimism about the program's future, stating, "These data are mapping a clear path ... to phase 2 studies." While specific timelines for phase 2 initiation were not disclosed, Warmuth emphasized the company's commitment to advancing the program efficiently in collaboration with Novartis.