On October 16, 2024 Remix Therapeutics (Remix), a clinical-stage biotechnology company developing small molecule therapies to modulate RNA processing and address underlying drivers of disease, reported that it will deliver a poster presentation demonstrating the therapeutic potential of REM-422, a potent, selective, oral small molecule MYB mRNA degrader for the treatment of acute myeloid leukemia (AML) and adenoid cystic carcinoma (ACC), at the upcoming 2024 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics being held on October 23-25, 2024 in Barcelona, Spain (Press release, Remix Therapeutics, OCT 16, 2024, View Source [SID1234647238]).

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MYB is an oncogenic transcription factor that is dysregulated in human malignancies including ACC, where the majority of tumors contain a hallmark t(6:9) rearrangement resulting in a MYB::NFIB fusion oncogene. The poster presentation will include preclinical data from biophysical and cellular assays that demonstrate the mechanism of action of REM-422 in suppressing MYB mRNA and protein expression by promoting inclusion of a poison exon into the MYB mRNA transcript. In vivo studies in ACC patient-derived xenograft (PDX) mouse models harboring the MYB::NFIB fusion demonstrates that REM-422 induces tumor regressions, including in models that harbor co-occurring mutations in the Notch pathway, a profile that represents especially aggressive clinical cases of ACC. Anti-tumor activity of REM-422 in these models is associated with a reversal of gene transcriptional programs that are associated with ACC, as assessed by genome-wide RNAseq experiments.

"We’ve built an exciting package of preclinical data across various models that reinforces the therapeutic potential of REM-422 for the treatment of ACC and other MYB-dysregulated cancers," said Peter Smith, Ph.D., Co-Founder and Chief Executive Officer of Remix Therapeutics. "The preclinical data demonstrated that REM-422 monotherapy treatment leads to tumor regressions in PDX models of ACC and support clinical development in ACC patients."

REM-422 is currently being investigated as a potential treatment for adenoid cystic carcinoma (ACC) and AML/HR-MDS (High-Risk Myelodysplastic Syndromes) in two, phase 1 clinical trials.

Details for the poster presentation are as follows:

Title: 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
Authors: M. Cameron1, S. Levin-Furtney1, A. Harney1, M. Thomas1, J. Maag1, B. Dunyak1, M. Shan1, S. Prajapati1, Y.A. Siu1, D. Nguyen1, S. Buonamici1, M. Seiler1, F. Vaillancourt1, P. Smith1, D. Reynolds1, C. Kung1.

1Remix Therapeutics, Research, Watertown, USA.

Abstract Number: ENA24-0468
Session Date and Time: Wednesday, October 23, 2024 (11:00 AM – 8:00 PM)
Session Location: CCIB Exhibition Hall poster area, Barcelona, Spain

About REM-422

REM-422 is a first-in-class, potent, selective, and oral small molecule mRNA degrader that induces the reduction of MYB mRNA and subsequent protein expression. REM-422 functions by facilitating the incorporation of poison exons within the mRNA transcript, leading to nonsense-mediated decay (NMD) of the transcript. REM-422 addresses MYB dysregulation, a driver of oncogenesis, upstream of protein expression.

About ACC

Adenoid cystic carcinoma (ACC) is a rare cancer that commonly develops in glandular tissues in the head and neck. It is caused by genetic mutations, likely developed over a patient’s lifetime, with the majority of ACC cases linked to an overexpression of the MYB protein. Current treatment solutions include surgery, radiation therapy, and chemotherapy.

About AML/HR-MDS

Acute myeloid leukemia (AML), a rare cancer of the blood and bone marrow, is the most common type of acute leukemia in adults. AML is caused by genetic mutations within bone marrow cells, which in turn causes the production of leukemic white blood cells that crowd out healthy blood cells. This may cause problems with bleeding, infection, and anemia. Myelodysplastic Syndromes (MDS) are disorders of blood-forming units in the bone marrow. High-risk (HR)-MDS patients have a higher percentage of blast cells in the bone marrow and that, in many cases, progresses to AML. There are several approved agents to treat AML, however, many patients relapse after achieving a response, underscoring the need for new therapies.