Monte Rosa Therapeutics, Inc. (NASDAQ: GLUE) has released an update on the ongoing phase 1/2 open-label, multicenter study of MRT-2359 in patients with myc-driven solid tumors.
The recommended phase 2 dose has been determined as 0.5 mg daily at a 21 days on, 7 days off drug dosing schedule. This schedule enables dosing of MRT-2359 more than twice as frequently per cycle as compared to the previously explored regimen. The safety profile supports further clinical development, with no signs of hypotension, cytokine release syndrome, or clinically significant hypocalcemia observed at any dose level and regimen.
Enrollment highlights show that patients have been dosed with MRT-2359 in 6 dose levels across two dosing schedules. The study has enrolled patients with a diverse set of tumor types, including non-small cell lung cancer, small cell lung cancer, neuroendocrine tumors of the prostate, bladder, and other organs of origin, androgen receptor-positive prostate cancer, and estrogen receptor-positive breast cancer.
Using the 5/9 dosing schedule, doses of 0.5 mg and 1 mg per day were identified as having a generally favorable safety profile, while doses of 1.5 mg or higher were above the maximum tolerated dose with thrombocytopenia being a dose limiting toxicity. Using the 21/7 schedule, both 0.5 and 0.75 mg were identified as having a generally favorable safety profile. 0.5 mg using the 21/7 dose schedule was selected as the recommended phase 2 dose for any expansion cohorts of the study.
Pharmacodynamic effects were assessed utilizing mass spectrometry measurements of gspt1 protein levels from paired tumor biopsies. The target levels of approximately 60% gspt1 degradation were observed in tumor biopsies across all dose levels in relevant tumor types, supporting that the dose of 0.5 mg per day provides optimal degradation consistent with its designed activity based on preclinical studies.
Monte Rosa expects to share updated data, including biomarker and activity data, in Q1 2025.
About MRT-2359, it is described as a potent, highly selective, and orally bioavailable investigational molecular glue degrader that induces the interaction between the e3 ubiquitin ligase component cereblon and the translation termination factor gspt1, leading to the targeted degradation of gspt1 protein.
As for Monte Rosa, it is a clinical-stage biotechnology company developing highly selective molecular glue degrader medicines for patients living with serious diseases in the areas of oncology, autoimmune and inflammatory diseases, and more. The company's Queen™ discovery engine combines AI-guided chemistry, diverse chemical libraries, structural biology, and proteomics to identify degradable protein targets and rationally design medicines with unprecedented selectivity.
Monte Rosa has a global license agreement with Novartis to advance vav1-directed molecular glue degraders and a strategic collaboration with Roche to discover and develop medicines against targets in cancer and neurological diseases previously considered impossible to drug. Following these announcements, the company's shares moved -1.1%, and are now trading at a price of $9.14. For the full picture, make sure to review Monte Rosa Therapeutics's 8-K report.
