Monte Rosa Therapeutics was formed in 2018 by Versant Ventures, Cancer Research UK (via its wholly-owned subsidiary Cancer Research Technology Limited) and The Institute of Cancer Research, London (ICR) from Cancer Research UK-funded science at the ICR. Monte Rosa Therapeutics’ lead programme comes from research geared towards targeting a protein called GSTP1, which was originally initiated by researchers at the Cancer Research UK Cancer Therapeutics Unit at the ICR.
Data Demonstrate Novel Link Between GSPT1 and Myc-induced Transcription and Protein Translation
BOSTON, Oct. 07, 2021 (GLOBE NEWSWIRE) -- Monte Rosa Therapeutics, Inc. (NASDAQ: GLUE), a biotechnology company developing novel molecular glue-based precision medicines, today announced preclinical data describing the potential of the company’s GSPT1-directed molecular glue degraders to address Myc-driven cancers. The data presented demonstrate a novel link between GSPT1 and Myc-induced transcription and protein translation. In this context, GSPT1 degraders work by impairing Myc-oncogenic signaling, leading to the selective induction of cell death in Myc-driven cancer cells. The data were uploaded today as an on-demand late-breaking poster presentation titled, “Identification of GSPT1-mediated molecular glue degraders for the treatment of Myc-driven breast cancer,” for the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics.
“Myc transcription factors are some of the most frequently mutated, translocated and overexpressed oncogenes driving tumorigenesis in human cancers. Despite this, no therapy directly or indirectly targeting the Myc family of transcription factors has been developed, resulting in substantial unmet medical need,” said Owen Wallace, Ph.D., Chief Scientific Officer of Monte Rosa. “In collaboration with the Cancer Research UK Cancer Therapeutics Unit at the Institute of Cancer Research (ICR), as well as using our unique and proprietary QuEEN™ platform, we identified and characterized GSPT1 as a key vulnerability in Myc-driven malignancies, as exemplified in our data using breast cancer cells and other solid and liquid tumor cell lines.”
“The foundational data presented today with our prototypical degrader MRT-048 solidifies GSPT1 as a critical target and has inspired our discovery and development of novel orally available and highly selective GSPT1-directed molecular glue degraders with activity in solid and liquid tumors,” said Markus Warmuth, M.D., CEO of Monte Rosa. “We remain on track to progress a development candidate and initiate IND-enabling studies this year.”
Summary of Findings
The data presented today were based on preclinical studies and include the following:
- Discovered potent and highly selective GSPT1-directed molecular glue degraders, including the prototypical molecular glue degrader MRT-048, differentially induce cell death in Myc-driven cells versus non-Myc expressing control cells
- Discovered correlation between key biomarkers of Myc-activation and sensitivity to GSPT1 degradation in a large panel of solid and hematopoietic cancer cell lines
- Demonstrated GSPT1 degradation leads to anti-tumor activity in vivo in Myc-driven, biomarker-positive breast cancer models
- Demonstrated GSPT1 degradation impairs protein translation and reduces Myc-induced transcription and oncogenic signaling, leading to the selective killing of Myc-driven cancer cells