Remix Therapeutics to Present Preclinical Data on REM-422 Tumor Regressions in Adenoid Cystic Carcinoma at 2024 EORTC-NCI-AACR Symposium

REM-422, a pioneering MYB mRNA degrader, shows promise in preclinical ACC models

WATERTOWN, Mass., Oct. 16, 2024 – Remix Therapeutics, a clinical-stage biotech firm, is set to present significant findings on their lead compound, REM-422, at the upcoming 2024 EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona. The presentation will highlight REM-422's potential as a groundbreaking treatment for acute myeloid leukemia (AML) and adenoid cystic carcinoma (ACC).

MYB, an oncogenic transcription factor, is implicated in various cancers, including ACC. ACC tumors often feature a hallmark t(6:9) rearrangement, leading to a MYB::NFIB fusion oncogene. The presented research will detail how REM-422 suppresses MYB mRNA and protein expression by promoting the inclusion of a poison exon into the MYB mRNA transcript. This action effectively degrades the mRNA, preventing the production of the MYB protein, which is crucial for tumor growth.

In preclinical studies, REM-422 demonstrated potent anti-tumor activity in ACC patient-derived xenograft (PDX) mouse models. These models, which harbor the MYB::NFIB fusion oncogene, showed significant tumor regressions upon treatment with REM-422. The compound's efficacy was notable even in models with co-occurring Notch pathway mutations, which often signify more aggressive ACC cases. The anti-tumor effects were linked to the reversal of gene transcriptional programs associated with ACC, as evidenced by comprehensive genome-wide RNA sequencing.

Peter Smith, Ph.D., Co-Founder and CEO of Remix Therapeutics, expressed optimism about the preclinical data, stating that REM-422 has shown substantial promise in treating ACC and other cancers driven by MYB dysregulation. These findings support the ongoing clinical development of REM-422 for ACC patients.

REM-422 is being studied in phase 1 clinical trials as a potential treatment for both ACC and AML/HR-MDS (High-Risk Myelodysplastic Syndromes). The poster presentation at the symposium, titled "REM-422, a potent, selective, oral small molecule mRNA degrader of the MYB oncogene, induces regressions in mouse patient-derived xenograft models of adenoid cystic carcinoma," will feature contributions from several researchers at Remix Therapeutics.

ACC is a rare cancer typically affecting glandular tissues in the head and neck, often linked to genetic mutations that result in the overexpression of the MYB protein. Current treatments include surgery, radiation, and chemotherapy, but new therapeutic options are needed.

AML, a rare blood and bone marrow cancer, is the most common type of acute leukemia in adults. It results from genetic mutations in bone marrow cells, leading to the production of leukemic white blood cells that crowd out healthy cells, causing complications like bleeding, infection, and anemia. High-risk myelodysplastic syndromes (HR-MDS) are disorders that often progress to AML, necessitating novel treatment approaches.

Remix Therapeutics aims to address these challenges through their innovative small molecule therapies designed to modulate RNA processing. Their REMaster™ technology platform identifies RNA processing patterns and leverages these insights to modulate gene expression, potentially revolutionizing treatment by targeting disease drivers at their origin.

REM-422 represents a significant advancement in the field of cancer therapeutics, offering hope for more effective treatments for ACC, AML, and other MYB-dysregulated cancers. The upcoming presentation at the EORTC-NCI-AACR Symposium is anticipated to shed further light on its therapeutic potential and pave the way for future clinical applications.