Monte Rosa Therapeutics Presents Preclinical Data Highlighting Potential of GSPT1-directed Molecular Glue Degrader MRT-2359 to Target Myc-driven Cancers at AACR Annual Meeting 2022

Rhea-AI Summary

Monte Rosa Therapeutics (NASDAQ: GLUE) announced preclinical data highlighting the role of GSPT1 in Myc-driven tumors and the potential of MRT-2359, a GSPT1-directed molecular glue degrader (MGD). Presented at the AACR Annual Meeting, findings demonstrate that MRT-2359 effectively degrades GSPT1, which is crucial for the growth of Myc-driven tumors. This discovery supports the clinical development of MRT-2359, particularly in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), with an IND submission anticipated in mid-2022.

Positive

• MRT-2359 effectively degrades GSPT1, leading to reduced N-Myc expression.
• Demonstrated anti-tumor activity in lung cancer cell lines with high Myc expression.
• Plans to submit IND for MRT-2359 in mid-2022, advancing clinical development.

Negative

• Limited activity of MRT-2359 in low L-Myc or N-Myc NSCLC models.
• Dependence on the successful outcome of ongoing clinical trials.

– Data Highlight Essential Role of GSPT1 in Sustaining Myc-induced Translational Addiction in Solid Tumors –

BOSTON, April 08, 2022 (GLOBE NEWSWIRE) -- Monte Rosa Therapeutics, Inc. (NASDAQ: GLUE), a biotechnology company developing novel molecular glue degrader (MGD)-based medicines, today announced preclinical data underscoring the role of GSPT1 as a key regulator of protein translation in Myc-driven tumors and highlighting MRT-2359 as a potent and selective GSPT1-directed MGD. The data will be presented in a poster presentation titled, “Identification of MRT-2359, a Potent, Selective and Orally Bioavailable GSPT1-directed Molecular Glue Degrader (MGD) for the Treatment of Cancers with Myc-induced Translational Addiction,” at the American Association for Cancer Research (AACR) Annual Meeting in New Orleans.

“Myc transcription factors are well-established drivers of human cancers, and our analyses of real-world molecular and genomic data of more than 3,000 lung cancer samples continue to underscore their role as some of the most frequently mutated, translocated and overexpressed oncogenes,” said Owen Wallace, Ph.D., Chief Scientific Officer of Monte Rosa. “To sustain uncontrolled cell proliferation and tumor growth, Myc-driven tumors hijack critical components of the translational machinery – including the translational termination factor GSPT1 – providing, in turn, a unique opportunity for therapeutic intervention. Our presentation at AACR represents the culmination of extensive and compelling preclinical in vivo data demonstrating the therapeutic potential of MRT-2359 as a potent, highly selective degrader of GSPT1. We look forward to submitting our IND for MRT-2359 in mid-2022.”

Summary of Findings
The data being presented at the AACR meeting are based on preclinical studies and analyses of real-world data derived from patient tumor samples. Findings include the following:

• MRT-2359 induces degradation of GSPT1 and associated downregulation of N-Myc and its transcriptional output, leading to preferential anti-proliferative activity in lung cancer cell lines with high L-Myc and N-Myc mRNA expression.
• MRT-2359, when administered orally, demonstrates anti-tumor activity in xenograft and patient-derived xenograft (PDX) models of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) with high L-Myc and/or N-Myc mRNA expression levels or neuroendocrine features.
• MRT-2359 had limited activity in low L-Myc or N-Myc NSCLC models, further corroborating the selective vulnerability of Myc-driven tumors to GSPT1 degradation.
• Analyses of real-world data indicate that approximately 15% of NSCLC and 70% of SCLC have high L-Myc and/or N-Myc mRNA expression.
• Collectively, these data support the clinical development of MRT-2359 in Myc-driven solid tumors, with an initial focus on NSCLC and SCLC.
  

About Monte Rosa
Monte Rosa Therapeutics is a biotechnology company developing a portfolio of novel molecular glue degrader 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. For more information, visit www.monterosatx.com. 

Forward-Looking Statements
This communication includes express and implied “forward-looking statements,” including forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include all statements that are not historical facts, and in some cases, can be identified by terms such as “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “objective,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “continue,” “ongoing,” or the negative of these terms, or other comparable terminology intended to identify statements about the future. Forward-looking statements contained herein include, but are not limited to, statements about our product development activities, including our expectations around the ongoing development of our QuEEN™ platform, the advancement of our pipeline and the various products therein, including our expectations of timing for filing our IND for our GSPT1-directed molecular glue degrader, MRT-2359, the advancement of additional programs including NEK7 and CDK2, the expansion of our compound and degron libraries, our ability to initiate at least one additional lead optimization programs, our ability to identify additional molecular glue degraders, our scientific predictions around clinical opportunities for our programs, including for MRT-2359, and any of our statements about the progress, results, costs, predictions, and our expectations for our molecular glue degraders, including for MRT-2359. By their nature, these statements are subject to numerous risks and uncertainties, including the impact that the current COVID-19 pandemic will have on our development activities and operations, as well as those risks and uncertainties set forth in our Annual Report on Form 10-K for the fourth quarter and full year ended December 31, 2021, filed with the US Securities and Exchange Commission on March 29, 2022, and any subsequent filings, that could cause actual results, performance or achievement to differ materially and adversely from those anticipated or implied in the statements. You should not rely upon forward-looking statements as predictions of future events. Although our management believes that the expectations reflected in our statements are reasonable, we cannot guarantee that the future results, performance or events and circumstances described in the forward-looking statements will be achieved or occur. Recipients are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date such statements are made and should not be construed as statements of fact. We undertake no obligation to publicly update any forward-looking statements, whether as a result of new information, any future presentations or otherwise, except as required by applicable law. Certain information contained in these materials and any statements made orally during any presentation of these materials that relate to the materials or are based on studies, publications, surveys and other data obtained from third-party sources and our own internal estimates and research. While we believe these third-party studies, publications, surveys and other data to be reliable as of the date of these materials, it has not been independently verified and makes no representations as to the adequacy, fairness, accuracy or completeness of any information obtained from third-party sources. In addition, no independent source has evaluated the reasonableness or accuracy of our internal estimates or research and no reliance should be made on any information or statements made in these materials relating to or based on such internal estimates and research. 

Contacts:

Investors
Michael Morabito, Solebury Trout
ir@monterosatx.com

Media
Dan Budwick, 1AB
dan@1abmedia.com

FAQ

What is MRT-2359 and its significance for GLUE investors?

MRT-2359 is a GSPT1-directed molecular glue degrader being developed by Monte Rosa, expected to target Myc-driven solid tumors, with potential implications for treatment efficacy and market appeal.

What were the results of the preclinical studies for MRT-2359?

The preclinical studies indicated that MRT-2359 induces degradation of GSPT1 and reduces tumor proliferation in specific lung cancer cell lines with high Myc expression.

When will Monte Rosa submit the IND for MRT-2359?

Monte Rosa plans to submit the IND for MRT-2359 in mid-2022, which is a key step in advancing its clinical development.

What types of cancers is MRT-2359 targeting?

MRT-2359 is focused on treating non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), particularly those driven by Myc oncogenes.

How prevalent are Myc-driven tumors in NSCLC and SCLC?

Real-world data suggests that approximately 15% of NSCLC and 70% of SCLC cases exhibit high levels of L-Myc or N-Myc mRNA expression.