Month: October 2024
Remix Therapeutics™ Announces Publication in Science that Reveals Unprecedented Insights into Spliceosome Regulation and Alternative Splicing
Watertown, Mass. (October 31, 2024) – Remix Therapeutics (Remix), a clinical-stage biotechnology company developing small molecule therapies to modulate RNA processing and address underlying drivers of disease, today announced the publication of a collaborative research study with Prof. Juan Valcárcel at the Center for Genomic Regulation in Barcelona, Spain in the prestigious journal Science.
The research article, titled “Transcriptome-wide splicing network reveals specialized regulatory functions of the core spliceosome,” represents a significant advancement in understanding the complexities of RNA splicing regulation.
The study, conducted by the Valcárcel lab in collaboration with Remix Therapeutics, unveils distinct regulatory networks within the spliceosome and sheds light on how its intricate structural and conformational complexity modulates splice site selection. By knocking down the expression of 305 spliceosome components and regulators in human cancer cells and employing deep RNA sequencing, the researchers monitored over 250,000 alternative splicing events across all classes of splice site selection modes.
“This groundbreaking research provides mechanistic insights into the intricate workings of the spliceosome and its regulatory functions,” said Dom Reynolds, CSO at Remix Therapeutics. “The findings not only advance our understanding of RNA processing but also open new avenues for therapeutic interventions in diseases associated with splicing dysregulation.”
This collaborative effort led to several significant discoveries, including the unexpected finding that different protein components of the U1 snRNP complex, a well-studied ribonucleoprotein complex of the spliceosome, are differentially required for two classes of alternative splicing decisions, revealing an unprecedented division of labor in a core spliceosome component. This publication serves as a valuable resource for exploring targets of spliceosome components and associated regulatory factors, identifying modulators of alternative splicing events, and unraveling the complex regulatory relationships within one of the most intricate molecular machineries in eukaryotic cells.
“Our study uncovered complex networks within the spliceosome that control how genes are spliced. Unexpectedly, we found that different parts of a key spliceosome component, the U1 snRNP complex, have distinct roles in alternative splicing decisions. The precise topological arrangement of snRNP complexes involved in spliceosome assembly occurring after initial splice site recognition, determines their activities in splice site selection, uncovering the extensive regulatory potential of this complex machinery” said Prof. Juan Valcárcel. “Our research with Remix substantially advances our understanding of the space and provides the foundation for leveraging RNA processing to develop novel therapeutics across a wide spectrum of human diseases.”
The full article, “Transcriptome-wide splicing network reveals specialized regulatory functions of the core spliceosome” can be found here: https://www.science.org/doi/10.1126/science.adn8105
Additionally, Remix Therapeutics, in collaboration with Prof. Aaron Hoskins at the University of Wisconsin-Madison, recently published a mechanistic study on human U1 snRNP in Nature Communications. This publication sheds light on the binding mechanism of U1snRNP to 5’-splice sites and how small molecules can influence alternative splicing. The full article “A sequential binding mechanism for 5′ splice site recognition and modulation for the human U1 snRNP” can be found here: https://www.nature.com/articles/s41467-024-53124-5.
About Remix Therapeutics
Remix Therapeutics is a clinical-stage biotechnology company developing novel small molecule therapies designed to reprogram RNA processing and treat disease. The REMaster™ technology platform facilitates RNA processing pattern identification, leveraging these learnings to modulate gene expression. Remix’s innovative therapeutic approach has the potential to alter the way genes are read from the genome, to correct, enhance, or eliminate the gene message, thereby addressing disease drivers at their origin. For more information visit www.remixtx.com.
Remix™ Therapeutics Announces Participation in Jefferies London Healthcare Conference
Cambridge, Mass. (October 29, 2024) – Remix Therapeutics (Remix), a clinical-stage biotechnology company developing small molecule therapies to modulate RNA processing and address the underlying drivers of disease, today announced that its management team will host one-on-one meetings with investors at the Jefferies London Healthcare Conference on Tuesday, November 19, 2024 in London, UK.
For those investors interested in scheduling a one-on-one meeting with the Remix management team, please contact your Jefferies representative.
About Remix Therapeutics
Remix Therapeutics is a clinical-stage biotechnology company developing novel small molecule therapies designed to reprogram RNA processing and treat disease. The REMaster™ technology platform facilitates RNA processing pattern identification, leveraging these learnings to modulate gene expression. Remix’s innovative therapeutic approach has the potential to alter the way genes are read from the genome, to correct, enhance, or eliminate the gene message, thereby addressing disease drivers at their origin. For more information visit www.remixtx.com.
Remix Therapeutics™ to Present Preclinical Data Demonstrating Tumor Regressions Induced by REM-422 in Adenoid Cystic Carcinoma Patient-Derived Xenograft Models at the 2024 EORTC-NCI-AACR Symposium
REM-422, a first-in-class MYB mRNA degrader, induces regression across multiple preclinical models of ACC
Watertown, Mass. (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, 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 Symposium on Molecular Targets and Cancer Therapeutics being held on October 23-25, 2024 in Barcelona, Spain.
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.
About Remix Therapeutics
Remix Therapeutics is a clinical-stage biotechnology company developing novel small molecule therapies designed to reprogram RNA processing and treat disease. The REMaster™ technology platform facilitates RNA processing pattern identification, leveraging these learnings to modulate gene expression. Remix’s innovative therapeutic approach has the potential to alter the way genes are read from the genome, to correct, enhance, or eliminate the gene message, thereby addressing disease drivers at their origin. For more information visit www.remixtx.com.