Data Demonstrate Novel Link Between GSPT1 and Myc-induced Transcription and Protein Translation

BOSTON, MA, USA I October 07, 2021 I 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

About Monte Rosa
Monte Rosa Therapeutics is a biotechnology company developing a portfolio of novel molecular glue degrader precision medicines. These medicines are designed to employ the body’s natural mechanisms to selectively eliminate therapeutically relevant proteins. The company has developed a proprietary protein degradation platform, called QuEEN™ (Quantitative and Engineered Elimination of Neosubstrates), that enables it to rapidly identify protein targets and molecular glue degrader, or MGD, product candidates that are designed to eliminate therapeutically relevant proteins in a highly selective manner. The company’s drug discovery platform combines diverse and proprietary chemical libraries of small molecule protein degraders with in-house proteomics, structural biology, AI/machine learning-based target selection and computational chemistry capabilities to predict and obtain protein degradation profiles. Monte Rosa was launched from founding investor Versant Ventures’ Ridgeline Discovery Engine and is headquartered in Boston, Mass., with research operations in both Boston and Basel, Switzerland. 

SOURCE: Monte Rosa Therapeutics