RGT-61159 / Rgenta Therap - LARVOL DELTA

RGT-61159, Best-in-Class Small Molecule Inhibitor of MYB Via Selective RNA Splicing Alteration, Showed Robust Anti-Tumor Activity across AML Tumor Models Harboring Common Genetic Lesions (ASH 2024) - P1 | "In summary, MYB oncogene represents a therapeutic target of relevance to AML and other hematological malignancies. RGT-61159 is a potent and selective oral small molecule inhibitor of MYB RNA and protein and an attractive therapeutic avenue to treat cancers overexpressing the oncogenic MYB protein."

IO biomarker • Preclinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Adenoid Cystic Carcinoma • Colorectal Cancer • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Solid Tumor • T Acute Lymphoblastic Leukemia • Targeted Protein Degradation • T-cell Acute Lymphoblastic Lymphoma • BCL2 • NPM1 • TRB

A phase I trial of RGT-61159, an oral MYB transcription factor inhibitor, for patients with relapsed/refractory (R/R) adenoid cystic carcinoma (ACC) and colorectal cancer (CRC) (ESMO 2025) - P1 | "Legal entity responsible for the study Rgenta Therapeutics. Funding Rgenta Therapeutics."

Clinical • P1 data • Adenoid Cystic Carcinoma • Colorectal Cancer • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

Rgenta Therapeutics Receives Orphan Drug Designation from the U.S. FDA for RGT-61159 for the Treatment of Adenoid Cystic Carcinoma (ACC) (GlobeNewswire) - "RGT-61159...is currently being evaluated in a Phase 1a/b clinical trial in patients with advanced relapsed or refractory ACC or colorectal cancer....'We also plan to broaden this program and initiate a new Phase 1/2 study of RGT-61159 in adults with AML/high risk myelodysplastic syndromes.'"

New P1/2 trial • Orphan drug • Trial status • Acute Myelogenous Leukemia • Adenoid Cystic Carcinoma • Colorectal Cancer • Myelodysplastic Syndrome

RGT-61159, A POTENT AND SELECTIVE SMALL MOLECULE MYB RNA INHIBITOR, SHOWED SIGNIFICANT ANTI-TUMOR ACTIVITY AS MONOTHERAPY OR IN COMBINATION WITH STANDARDS OF CARE IN SEVERAL LEUKEMIA DISEASE MODELS HARBORING AML MOST COMMON GENETIC LESIONS (EHA 2025) - P1 | "Significant synergistic cell killing activity was observed when RGT-61159 was combined with Flt3 inhibitors (e.g. gilteritinib and midostaurin) in MOLM-13 and MV4.11 cell lines harboring Flt3 ITD mutation, and with menin inhibitors (e.g. KO-539, revemenib) in AML cell lines with NPM1 mutation or MLL-fusion. Finally, RGT-61159 in combination with a Bcl2 inhibitor (venetoclax) resulted in synergistic cell killing activity in AML cell lines carrying NPM1 mutations or AML-1-ETO fusion protein... In summary, MYB oncogene represents a therapeutic target of relevance to AML and other hematological malignancies. RGT-61159 is a potent and selective oral small molecule inhibitor of MYB RNA and protein and an attractive therapeutic avenue to treat cancers overexpressing the oncogenic MYB protein as single agent or in combination with SoC. A phase 1 study of RGT-61159 in AML / high risk MDS is planned in addition to the ongoing phase 1 study in adults with relapsed/​refractory..."

Combination therapy • IO biomarker • Monotherapy • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Targeted Protein Degradation • ABL1 • BCR • FLT3 • IDH1 • NPM1

Rgenta Therapeutics Presents Preclinical Data from Lead Program, RGT-61159, a Potent and Selective Small Molecule Inhibitor of MYB RNA, Supporting its Application in the Treatment of Acute Myeloid Leukemia (AML) (GlobeNewswire) - "Data are being presented at the 30th Annual Congress of the European Hematology Association 2025 (EHA2025)....RGT-61159 demonstrated potent dose-dependent cell killing of AML derived cell lines that overexpressed MYB, while sparing normal cells. Importantly, the data show a correlation between the elimination of MYB RNA and protein by RGT-61159 and its potent killing activity. RGT-61159 also induced a robust increase in expression of CD11b and CD14 cell differentiation markers and downregulation of the expression of master oncogenes controlled by MYB, including MYC, BCL2, FLT3 and IDH1 supporting the hypothesis that RGT-61159 anti-tumor activity is driven by MYB signaling inhibition and illustrating MYB dependency across a broad AML patient population."

Preclinical • Acute Myelogenous Leukemia

Rgenta Therapeutics Announces Presentation of Preclinical Data from Lead Program, RGT-61159, a Potent and Selective Small Molecule Inhibitor of MYB RNA, at the European Hematology Association (EHA) 2025 Congress (PRNewswire) - "Rgenta Therapeutics...announced today that preclinical data will be presented on its lead program, RGT-61159, at the European Hematology Association (EHA) 2025 Congress, which will be held from June 12-15, 2025, in Milan, Italy."

Preclinical • Acute Myelogenous Leukemia

RGT-61159, best-in-class oral small molecule inhibitor of MYB via selective RNASplicing alteration, synergistic anti-tumor aActivity when combined with standards of care in leukemia disease models harboring AML common genetic lesions and with NOTCH inhibitors in ACC disease models (AACR 2025) - P1 | "The data revealed synergistic cell killing activity when RGT-61159 was combined with Flt3 inhibitors (e.g. gilteritinib and midostaurin) in MOLM-13 and MV4.11 cell lines harboring Flt3 IDT mutation, and with menin inhibitors (e.g. KO-539, revemenib) in AML cell lines with NPM1 mutant) or MLL-fusion. Finally, RGT-61159 combination with a Bcl2 inhibitor (venetoclax) resulted in synergistic cell killing activity in AML cell lines carrying NPM1 mutations or AML-1-ETO fusion protein. These studies provide compelling supportive evidence for combining RGT-61159 with standards-of-care for AML treatment in the relevant population of patients with AML. ."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • NPM1

Rgenta Therapeutics Presents Preclinical Data on RGT-61159, a Potent, Selective Oral Small Molecule Inhibitor of MYB, Demonstrating Robust Anti-Tumor Activity in Several Monotherapy Models of AML and Synergistic Activity when Combined with Standard of Care for AML (PRNewswire) - "The data demonstrate robust anti-tumor activity of RGT-61159 in several cell-derived xenograft (CDX) models of AML and synergistic benefit when combined with standard of care for AML highlighting the potential of RGT-61159 to treat a broad AML patient population...'initiating a new Phase 1/2 study of RGT-61159 in adults with AML/high risk myelodysplastic syndromes the second half of 2025.'....RGT-61159 also inhibited AML cell proliferation and downregulated the expression of master oncogenes controlled by MYB, including MYC, BCL2, FLT3 and IDH1. Data from several CDX models of AML with genetic alterations seen commonly in AML, demonstrated the robust anti-tumor activity of tolerated doses of RGT-61159 and synergistic activity both in vitro and in vivo when administered in combination with agents used in AML standard of care."

New P1/2 trial • Preclinical • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

Rgenta Therapeutics Announces Presentation at the American Association for Cancer Research (AACR) 2025 Annual Meeting (PRNewswire) - "Rgenta Therapeutics...announced today that preclinical data will be presented on its lead program, RGT-61159, at the American Association for Cancer Research (AACR) 2025 Annual Meeting..."

Preclinical • Acute Myelogenous Leukemia • Adenoid Cystic Carcinoma

Rgenta Therapeutics Presents Preclinical Data Demonstrating Anti-Tumor Activity of Oral Small Molecule MYB Inhibitor, RGT-61159, in Multiple Models of AML at the 66th American Society of Hematology (ASH) Annual Meeting (PRNewswire) - "The data presented at ASH demonstrate that RGT-61159 potently eliminates MYB RNA and protein in a dose-dependent manner in AML cancer cell lines. As a single agent, RGT-61159 showed significant anti-tumor activity in several AML cell line-derived xenograft (CDX) models that harbor the most prevalent genetic alterations found in patients. In addition, RGT-61159 driven MYB inhibition led to a robust, dose-dependent increase in the differentiation markers CD11b and CD14 on the surface of THP-1 AML cells..."

Preclinical • Acute Myelogenous Leukemia

Rgenta Therapeutics Announces Presentation at the 66th American Society of Hematology (ASH) Annual Meeting (PRNewswire) - "Rgenta Therapeutics...announced today that preclinical data will be presented from its lead program, RGT-61159, at the 66th American Society of Hematology Annual Meeting and Exposition being held December 7-10, 2024, in San Diego, CA."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Rgenta Therapeutics Announces First Patients Dosed in Phase 1a/b Clinical Trial of RGT-61159, an Oral Small Molecule Targeting MYB, in Adenoid Cystic Carcinoma (ACC) and Colorectal Cancer (CRC) (PRNewswire) - "Rgenta Therapeutics...announced today that the first patients have been dosed in the Phase 1a/b clinical trial of RGT-61159....Rgenta's Phase 1a/b clinical trial of RGT-61159 is a multi-center, open-label study dose escalation and expansion study in patients with advanced relapsed or refractory ACC or CRC."

Trial status • Adenoid Cystic Carcinoma • Colorectal Cancer

Rgenta Therapeutics Announces FDA Clearance of IND Application for RGT-61159, an Oral Small Molecule RNA Modulator Designed to Halt Disease-Driver MYB Production in Adenoid Cystic Carcinoma (ACC) and Colorectal Cancer (CRC) (PRNewswire) - "Rgenta Therapeutics...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)....'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'."

IND • Adenoid Cystic Carcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Study of Safety and Efficacy of RGT-61159 in Adults With Relapsed/Refractory Adenoid Cystic Carcinoma (ACC) or Colorectal Carcinoma (CRC) (clinicaltrials.gov) - P1 | N=105 | Recruiting | Sponsor: Rgenta Therapeutics Inc | Not yet recruiting ➔ Recruiting

Enrollment open • Adenoid Cystic Carcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Effect of RGT-61159 on inhibition of oncogene c-MYB synthesis and tumor growth inhibition in a broad range of ACC PDX models, at well tolerated doses in rodents and non-human primates. (ASCO 2024) - "Finally, we showed that the combination of RGT-M001, an analog of RGT-61159, with the NOTCH Inhibitor AL-101 resulted in significant tumor regression at well tolerated doses. Altogether, these data demonstrated that RGT-61159 efficiently and safely targets the undruggable oncogenic transcription factor c-MYB. Down-regulation of c-MYB by the RGT-61159 RNA-targeting small molecule is a very promising therapeutic strategy to treat ACC and other cancers driven by c-MYB dysregulation."

Preclinical • Adenoid Cystic Carcinoma • Oncology

Study of Safety and Efficacy of RGT-61159 in Adults With Relapsed/Refractory Adenoid Cystic Carcinoma (ACC) or Colorectal Carcinoma (CRC) (clinicaltrials.gov) - P1 | N=105 | Not yet recruiting | Sponsor: Rgenta Therapeutics Inc

New P1 trial • Adenoid Cystic Carcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Rgenta Therapeutics Presents Preclinical Data from Lead Program RGT-61159, a Potent Inhibitor of Oncogenic MYB Synthesis, at the American Society of Clinical Oncology Annual Meeting (ASCO 2024) (PRNewswire) - "Rgenta Therapeutics...today announced the presentation of preclinical data at ASCO 2024 from its lead program, 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)...'We look forward to advancing this novel therapeutic in a first-in-human Phase 1a/1b clinical study in adults with ACC and CRC this year.'....'The data demonstrate that daily, single agent treatment with RGT-61159 results in significant anti-tumor activity at tolerated doses in all four ACC patient derived xenograft (PDX) models evaluated.'"

New P1 trial • Preclinical • Adenoid Cystic Carcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor