Monte Rosa Therapeutics’ plan to develop a molecular glue degrader in a wide range of cancers has come unstuck. Biomarker-positive patients were rarer than expected in some tumor types, prompting the biotech to focus MRT-2359 development on prostate cancer while continuing to advance its alliance with Novartis toward phase 2.
The wholly owned MRT-2359 is Monte Rosa’s attempt to exploit a vulnerability of MYC-driven tumors. Believing the tumors are dependent on GSPT1, the biotech designed a molecule to drive degradation of the translation termination factor and took the candidate into a phase 1/2 trial in 2022. The study enrolled people with tumors where high L- or N-MYC expression was expected based on preclinical data.
After assessing tissue samples from 46 patients, Monte Rosa said expression was lower than expected in some tumor types. None of the sampled non-small cell lung cancer patients had high L- or N-MYC. Levels were higher in small cell lung cancer, 31%, and high-grade neuroendocrine tumors, 17%, but the figures still fell short of expectations.
Monte Rosa responded to the data by deprioritizing further expansion arms in the three tumor types. Instead, the biotech is focusing on prostate cancer, a tumor where it believes the biomarker is ubiquitous enough for it to proceed without a companion diagnostic, simplifying further clinical development.
Filip Janku, M.D., Ph.D., chief medical officer at Monte Rosa, set out the opportunity in prostate cancer on an earnings call Thursday, telling investors that second-line use and combinations with drugs such as Astellas and Pfizer’s Xtandi are “probably a good starting point.” Janku’s longer-term goals extend beyond that first use case.
The target might be coverage of the same population as Xtandi, Janku said. With Xtandi used in castrate-resistant and castrate-sensitive prostate cancers, Janku said “the ultimate patient population you can target with [MRT-2359] is actually quite broad.” Monte Rosa has data on three people who received MRT-2359 and Xtandi, of which one patient had a confirmed partial response.
MRT-2359 is advancing alongside other Monte Rosa programs including the Novartis-partnered immune disease drug candidate MRT-6160. Novartis paid $150 million upfront for the molecular glue degrader in October. Monte Rosa shared phase 1 data on the drug candidate in its earnings release, and CEO Markus Warmuth, M.D., sketched out the next steps on the call.
“These data are mapping a clear path ... to phase 2 studies. While I can't give you guidance on exact timing for the phase 2 initiation, I can say that we are working with our collaborators at Novartis to advance this program as efficiently as possible, building on the promising data we shared with you today,” Warmuth said.