MYB

REM-422, a first-in-class MYB mRNA degrader, induces regression across multiple preclinical models of ACC WATERTOWN, Mass., Oct. 16, 2024 /PRNewswire/ -- 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 . SOURCE Remix Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

First-in-human Phase 1a/1b clinical trial will evaluate orally available, RGT-61159 designed to selectively target MYB RNA and inhibit oncogenic MYB protein production Preclinical data supporting the clinical trial were recently presented at the American Society of Clinical Oncology Annual Meeting (ASCO 2024) WOBURN, Mass., July 10, 2024 /PRNewswire/ -- Rgenta Therapeutics, a biotechnology company pioneering the development of a new class of oral small molecules targeting RNA and RNA regulation for oncology and neurological disorders, announced the clearance of its Investigational New Drug application (IND) by the U.S. Food and Drug Administration (FDA) for RGT-61159, which is being developed for the potential treatment of adenoid cystic carcinoma (ACC), colorectal cancer (CRC) and other solid tumors as well as acute myeloid leukemia (AML). "Clearance of our first IND application is a significant milestone in Rgenta's mission to develop oral, small molecule RNA-targeting medicines to treat previously incurable diseases," said Simon Xi, Ph.D., co-founder and chief executive officer of Rgenta. "We look forward to initiating clinical studies of RGT-61159 with a first-in-human Phase1a/1b clinical study in adults with ACC and CRC to potentially provide a new therapeutic option for patients with these difficult-to-treat cancers." "Development of small molecule drugs targeting oncogenic drivers such as MYB, has proven challenging in the past," said Travis Wager, Ph.D., co-founder, president and chief scientific officer. "RGT-61159 demonstrates potent inhibition of oncogenic MYB protein production and significant inhibition of tumor growth at tolerated doses in preclinical models of ACC and other cancers, and we are excited to move this novel therapeutic into clinical evaluation." About RGT-61159 RGT-61159 is an orally available small molecule designed to specifically modulate splicing of the transcription factor MYB resulting in the inhibition of oncogenic MYB protein production, which has the potential to inhibit proliferation or induce cell death of cancer cells that overexpress MYB protein. MYB acts as a master regulator of cell proliferation differentiation processes and its aberrant expression has been demonstrated in multiple forms of human cancer including adenoid cystic carcinoma (ACC), acute myeloid leukemias (AML), T-cell acute lymphoblastic leukemias (T-ALL), colorectal cancer (CRC), small cell lung cancer (SCLC) and breast cancer. Additional information on the planned Phase 1a/1b clinical trial can be accessed at clinicaltrials.gov (NCT06462183). About Adenoid Cystic Carcinoma (ACC) It is estimated that approximately 200,000 people are living with ACC throughout the world including 11,000 in the US. While it is a rare cancer, ACC is the second most common cancer type arising in the salivary gland and is an aggressive malignancy with a tendency to infiltrate surrounding nerves and metastasize to distant sites. Overactivation of the MYB oncogene has been described as a hallmark of ACC and is noted in over 90% of ACC. Treatment for ACC is extremely challenging and may include surgery and/or radiation, which often fails to control local tumor recurrence and distant metastases. There are no effective targeted therapies available for patients with recurrent and/or metastatic disease. There is thus an unmet medical need for new therapeutic targets and treatment strategies for patients with this fatal cancer. About Colorectal Cancer (CRC) CRC is the third most prevalent cancer and the second leading cause of cancer-related mortality worldwide. According to the World Health Organization, in 2022, more than 1.9 million cases of CRC were diagnosed. Despite the improved early detection of CRC and the recent success of targeted therapeutics, approximately 15%-30% of patients present with metastases and 20%-50% of patients with initially localized disease will develop metastases. Patients with relapsed or refractory CRC who have exhausted all the available standard of care therapy options, have a very poor prognosis. MYB is significantly overexpressed in 80-85% of CRC and has been frequently found to be a predictive biomarker of tumor aggressiveness and poor prognosis. Developing novel therapies to treat patients with metastatic CRC remains a major unmet medical need. About Rgenta Therapeutics Rgenta Therapeutics is developing a pipeline of oral, small-molecule RNA-targeting medicines with an initial focus on oncology and neurological disorders. Our proprietary platform mines the massive genomics data to identify targetable RNA processing events and design small-molecule glues to modulate the interactions among the spliceosome, regulatory proteins, and RNAs. Our lead programs and unique approach are unlocking the therapeutic potential of historically undruggable targets in human diseases. Learn more at . Contacts Investors: Sylvia Wheeler Wheelhouse Life Science Advisors [email protected] Elizabeth Wolffe, Ph.D. Wheelhouse Life Science Advisors [email protected] Media Aljanae Reynolds Wheelhouse Life Science Advisors [email protected] SOURCE Rgenta Therapeutics

REM-422, a first-in-class MYB mRNA degrader, induces anti-tumor activity across multiple preclinical models of AML WATERTOWN, MA, USA I June 13, 2024 I 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), at the European Hematology Association (EHA) 2024 Hybrid Congress in Madrid, Spain. The poster presentation will include preclinical data from MYB-dependent AML cell lines and human leukemia xenograft models showing REM-422 is broadly active across various AML models. Furthermore, REM-422 induces tumor regressions in cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models of AML at well-tolerated doses. In vitro and in vivo studies show that REM-422 functions by inducing incorporation of a poison exon into the MYB mRNA transcript resulting in mRNA degradation and inhibition of MYB protein expression. “We’ve built a robust package of preclinical data across various models that reinforces the therapeutic potential of REM-422 for the treatment of AML and other MYB-dysregulated cancers,” said Peter Smith, Ph.D., Co-Founder and Chief Executive Officer of Remix Therapeutics. “The ability to successfully target a previously undruggable transcription factor is encouraging as we continue to investigate REM-422 in our ongoing clinical trials.” The dysregulation of MYB, an oncogenic transcription factor, has been linked to numerous cancers including AML, myelodysplastic syndromes (MDS) and lymphoma.  REM-422 is a potent, selective, and oral small molecule mRNA degrader that induces the reduction of MYB mRNA and subsequent protein expression, resulting in antitumor activity in MYB-dependent human tumor models. REM-422 is currently being investigated as a potential treatment for AML/HR-MDS and adenoid cystic carcinoma (ACC) 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, demonstrates anti-tumor activity in mouse xenograft models of AML Abstract Number: P531 Session Date and Time: June 14 at 6:00 PM CEST Session Location: Poster Hall 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. Depending on the location of the tumor, symptoms may include numbness of the face, difficulties swallowing, changes in vision, or difficulty breathing, among others. 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 . SOURCE: Remix Therapeutics