REM-422 / Remix Therap - LARVOL DELTA

REM-422, A SMALL MOLECULE MYB MRNA DEGRADER, DEMONSTRATES ANTI-LEUKEMIC ACTIVITY AS A MONOTHERAPY AND IN COMBINATION WITH STANDARDS OF CARE IN PRECLINICAL MODELS OF AML (EHA 2025) - P1 | "REM-422's anti-proliferative activity was unchanged in the resistant models, which is consistent with the differentiated mechanism of action of REM-422 compared to these standards of care.The activity of REM-422 was assessed in vitro in combination with AML standards of care by co-treating leukemia cell lines with REM-422 and other agents including venetoclax, gilteritinib, revumenib, and azacitidine. These data support the therapeutic potential for REM-422 in AML patients both as monotherapy and in combination therapy."

Combination therapy • Monotherapy • Preclinical • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • ANXA5 • CD14 • FLT3 • ITGAM • KMT2A • MYB

REM-422, a first-in-class mRNA degrader of the MYB oncogene, demonstrates anti-tumor activity in xenograft models of adenoid cystic carcinoma and acute myeloid leukemia (AACR 2025) - P1 | "Immunohistochemistry staining confirmed the reduction of MYB protein in the bone marrow of treated animals. Flow cytometry analysis of bone marrow and whole blood demonstrated that REM-422 treatment led to an increase in blasts expressing CD14 and CD11b, known myeloid differentiation markers, as well as an increased frequency of Annexin V+ blasts, a marker of early apoptosis.These data illustrate the potential for REM-422 as an investigational agent for the treatment of a variety of solid tumor and hematological malignancies."

Preclinical • Acute Myelogenous Leukemia • Adenoid Cystic Carcinoma • Colorectal Cancer • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Solid Tumor • ANXA5 • CD14 • ITGAM • MYB

REM-422, a Small Molecule MYB mRNA Degrader, Demonstrates Anti-Leukemic Activity As Monotherapy and in Combination with Standards of Care in Preclinical Models of AML (ASH 2024) - P1 | "The activity of REM-422 was assessed in vitro in combination with AML standards of care by co-treating leukemia cell lines with REM-422 and other agents including venetoclax, gilteritinib, revumenib, and azacitidine. The REM-422 and revumenib combination arm demonstrated more durable activity with delayed tumor regrowth kinetics after cessation of dosing compared to the monotherapy arms. Altogether, these data support the therapeutic potential for REM-422 in AML patients both as monotherapy and in combination therapy."

Combination therapy • IO biomarker • Monotherapy • Preclinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Adenoid Cystic Carcinoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Oncology • ANXA5 • BCL2 • CD14 • FLT3 • ITGAM • KMT2A • MYB

Remix Therapeutics to Present Preclinical Data Demonstrating Anti-Leukemic Activity of REM-422 in AML at the 66th American Society of Hematology Annual Meeting and Exposition (ASH) (PRNewswire) - "Remix Therapeutics...announced an upcoming oral presentation at the 66th ASH Annual Meeting taking place from December 7-10, 2024, in San Diego, CA. Results demonstrate oral dosing of REM-422, a selective mRNA degrader of the MYB oncogene, leads to robust anti-leukemic activity observed both as a monotherapy and in combination across a genetically diverse set of preclinical models of acute myeloid leukemia (AML), including eradication of AML blasts in engrafted patient-derived xenograft (PDX) models of AML."

Preclinical • Acute Myelogenous Leukemia

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 (EORTC-NCI-AACR 2024) - P1 | "These data demonstrate that REM-422 monotherapy treatment leads to degradation of MYB mRNA and protein resulting in tumor regressions in preclinical PDX models of ACC and supports the therapeutic potential for REM-422 in ACC patients."

Preclinical • Acute Myelogenous Leukemia • Adenoid Cystic Carcinoma • Hematological Malignancies • Leukemia • Oncology • MYB • NFIB

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 (PRNewswire) - "Remix Therapeutics...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....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."

Preclinical • Adenoid Cystic Carcinoma

Tempus Announces Expanded Data and Sequencing Collaboration with Remix Therapeutics (Businesswire) - "Tempus AI, Inc...announced an expanded collaboration with Remix Therapeutics, a clinical-stage biotechnology company developing small molecule therapies to modulate RNA processing and address underlying drivers of disease. The collaboration between Remix and Tempus began with the licensing of specific, de-identified data cohorts and has since expanded into a broader, strategic alliance. Remix is leveraging Tempus’ multimodal data to interrogate specific cohorts, including Adenoid Cystic Carcinoma (ACC) and Acute Myeloid Leukemia (AML) with Tempus’ data analytics platform, Lens. The newly expanded scope of work also includes next-generation sequencing support for Remix’s Phase I trial for REM-422, the company’s potent, selective, oral small molecule messenger RNA (mRNA) degrader."

Diagnostic • Licensing / partnership • Acute Myelogenous Leukemia • Adenoid Cystic Carcinoma • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Solid Tumor

REM-422, A POTENT, SELECTIVE, ORAL SMALL MOLECULE MRNA DEGRADER OF THE MYB ONCOGENE, DEMONSTRATES ANTI-TUMOR ACTIVITY IN MOUSE XENOGRAFT MODELS OF AML (EHA 2024) - "These data demonstrate that REM-422 treatment leads to degradation of MYB mRNA in preclinical models ofAML and supports the therapeutic potential for REM-422 in AML patients."

IO biomarker • Preclinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Adenoid Cystic Carcinoma • Brain Cancer • CNS Tumor • Glioma • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Pediatrics • Solid Tumor • T Acute Lymphoblastic Leukemia • BCL2 • FLT3 • MYB

Remix Therapeutics to Present Preclinical Data Demonstrating Anti-Tumor Activity of REM-422 in AML at the European Hematology Association (EHA) 2024 Congress (PRNewswire) - "Remix Therapeutics (Remix)...will deliver a poster presentation demonstrating the therapeutic potential of REM-422...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."

Preclinical • Acute Myelogenous Leukemia

Study of REM-422 in Patients With AML or Higher Risk MDS (clinicaltrials.gov) - P1 | N=100 | Recruiting | Sponsor: Remix Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Remix Therapeutics Announces First Patients Dosed in Two Phase 1 Clinical Trials Investigating REM-422 for Treatment of Adenoid Cystic Carcinoma (ACC) and Acute Myeloid Leukemia/Myelodysplastic Syndromes (AML/MDS) (PRNewswire) - "Remix Therapeutics...announced the first patients enrolled and dosed in two Phase 1 clinical trials assessing REM-422, a first-in-class MYB mRNA degrader, as a potential treatment for recurrent or metastatic adenoid cystic carcinoma (ACC) and acute myeloid leukemia/high-risk myelodysplastic syndromes (AML/MDS). Additionally, the company also announced that REM-422 has received Orphan Drug Designation from the FDA for the treatment of ACC and AML."

Orphan drug • Trial status • Acute Myelogenous Leukemia • Adenoid Cystic Carcinoma • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Solid Tumor

Study of REM-422 in Patients With AML or Higher Risk MDS (clinicaltrials.gov) - P1 | N=100 | Not yet recruiting | Sponsor: Remix Therapeutics

New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Study of REM-422 in Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma (clinicaltrials.gov) - P1 | N=65 | Recruiting | Sponsor: Remix Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Adenoid Cystic Carcinoma • Oncology

Remix Therapeutics Closes $60 Million Financing to Advance REM-422, Pipeline of Small Molecule Therapies Designed to Reprogram RNA Processing to Treat Disease (PRNewswire) - "Remix Therapeutics...announced the close of a $60 million financing led by The Column Group. The financing includes participation from existing investors Atlas Venture, Foresite Capital, Alexandria Venture Investments, Arch Venture Partners, Casdin Capital, and Surveyor (a Citadel company) along with new investors WTT Investment, Willett Advisors, and others. The funds will support clinical development of the company's lead program, REM-422, and further advancement of a pipeline of RNA processing targeted therapeutics....Remix's lead candidate, REM-422, is expected to enter two Phase 1 clinical studies for the treatment of recurrent or metastatic adenoid cystic carcinoma and acute myeloid leukemia/myelodysplastic syndromes in 2024."

Financing • New P1 trial • Acute Myelogenous Leukemia • Adenoid Cystic Carcinoma • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Solid Tumor

REM-422, a Potent, Selective, Oral Small Molecule mRNA Degrader of the MYB Oncogene, Demonstrates Anti-Tumor Activity in Mouse Xenograft Models of AML (ASH 2023) - "Flow cytometry analysis of bone marrow and peripheral blood samples demonstrated that REM-422 led to the eradication of human leukemia cells from both compartments (Figure 1 right). Together, these data demonstrate that REM-422 treatment leads to degradation of MYB mRNA in preclinical models of AML and supports the therapeutic potential for REM-422 in AML patients."

IO biomarker • Preclinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Adenoid Cystic Carcinoma • Brain Cancer • CNS Tumor • Glioma • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Pediatrics • Solid Tumor • T Acute Lymphoblastic Leukemia • BCL2 • FLT3 • MYB

Remix Therapeutics to Present Preclinical Data Demonstrating MYB mRNA Degradation in AML at the 65th American Society of Hematology Annual Meeting and Exposition (ASH) (PRNewswire) - "Remix Therapeutics...today announced an upcoming presentation introducing REM-422, the Company's potent, selective, oral small molecule messenger RNA (mRNA) degrader, as a potential treatment for MYB-driven cancers. Data describing the activity of REM-422 in AML xenograft models will be highlighted at the 65th American Society of Hematology Annual Meeting and Exposition (ASH), taking place from December 9-12, 2023 in San Diego. Results demonstrate oral dosing of REM-422 degrades MYB mRNA, inducing anti-leukemic activity in multiple xenograft models."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Oncology