Rgenta Therapeutics Shows RGT-61159's Anti-Tumor Effects in AML at ASH Meeting

Rgenta Therapeutics, a biotechnology firm immersed in the clinical development of RNA-targeting small molecule drugs, is making significant strides in the fight against certain cancers. The company is focusing on a groundbreaking oral treatment, RGT-61159, which targets the MYB oncogene—a critical regulator in various malignancies, particularly in acute myeloid leukemia (AML) and other cancers. The data supporting the drug's efficacy was recently unveiled at the 66th American Society of Hematology Annual Meeting.

RGT-61159 operates by manipulating MYB RNA transcripts to activate the nonsense-mediated decay pathway. This process leads to the depletion of MYB mRNA and subsequent degradation of the MYB protein. During preclinical trials, RGT-61159 demonstrated potent anti-tumor activity in numerous AML cell lines, including those with genetic mutations typically linked to resistance against current treatments. This highlights the potential of RGT-61159 in treating AML, as well as adenoid cystic carcinoma (ACC) and colorectal cancer (CRC).

The preclinical trials revealed significant results, showing that RGT-61159 could effectively decrease both MYB RNA and protein levels in a dose-dependent manner. Additionally, the drug exhibited notable anti-tumor activity in AML cell line-derived xenograft (CDX) models. Further positive outcomes were observed with RGT-61159 inhibiting the MYB pathway, leading to increases in differentiation markers CD11b and CD14 on THP-1 AML cells, and the reduction of oncogenes like MYC and BCL2 across diverse AML cell lines. These findings suggest a robust rationale for its development as a treatment for AML.

Travis Wager, Ph.D., co-founder and president of Rgenta, emphasized the importance of these findings. He noted how genomic analyses of AML cell lines treated with RGT-61159 elucidated the regulation of oncogenes BCL2 and MYC via MYB inhibition, which underscores the drug's potential as a novel therapeutic approach. This reinforces the idea of MYB as a crucial dependency across AML tumors, advocating for RGT-61159's role as a pioneering MYB inhibitor in cancer treatment.

RGT-61159 is currently undergoing evaluation in a multi-center, open-label Phase 1a/b clinical trial. This study aims to assess the drug's safety, tolerability, pharmacokinetics, and efficacy in patients with advanced ACC or CRC. The trial, registered under ClinicalTrials.gov (NCT06462183), is designed to gather essential data to support the drug's further development.

Acute myeloid leukemia (AML) is a rapid-growing blood cancer, commonly diagnosed in adults, with approximately 20,000 new cases annually in the United States. Despite high initial remission rates, long-term survival remains low, emphasizing the need for novel treatments like RGT-61159. Allogeneic hematopoietic cell transplantation is currently the most effective curative strategy, yet relapse rates and subsequent survival remain challenging.

Rgenta Therapeutics, based in Woburn, Massachusetts, continues to advance its pipeline of RNA-targeting small molecule medicines. Their proprietary platform leverages extensive genomics data to identify actionable RNA processing events, crafting small molecules to modulate interactions within the spliceosome and regulatory proteins. This innovative approach is unlocking new therapeutic possibilities for diseases previously considered undruggable. As Rgenta progresses with their clinical trials, RGT-61159 represents a promising beacon of hope for patients battling AML and other MYB-dependent malignancies.