Edgewood Oncology: Promising BTX-A51 Study Results in Liposarcoma Preclinical Models

Edgewood Oncology, a biotech company specializing in BTX-A51 treatments for hematologic malignancies and solid tumors, has revealed fresh preclinical findings. The study, conducted by Dana-Farber Cancer Institute and Hebrew University-Hadassah Medical School, explores BTX-A51’s potential in human liposarcoma (LPS). These results will be presented at the AACR Annual Meeting 2024 in San Diego.

BTX-A51, a pioneering small molecule, acts as a multi-selective kinase inhibitor targeting casein kinase 1 alpha (CK1α), along with cyclin-dependent kinases 7 and 9 (CDK7 and CDK9), pivotal transcriptional regulators. By simultaneously addressing these cancer master regulators, BTX-A51 aims to induce programmed cell death (apoptosis).

The presentation (Abstract 604) at the AACR Annual Meeting 2024 shed light on BTX-A51’s potential in treating human liposarcomas (LPS) through preclinical models. Results showcased BTX-A51’s efficacy in patient-derived LPS cell lines and xenograft models, highlighting its ability to inhibit both casein kinase 1 alpha (CK1α) and transcriptional cyclin-dependent kinases 7 and 9 (CDK7/9) synergistically.

George Demetri, M.D., Professor of Medicine and director of the Sarcoma Center at Dana-Farber, emphasized the urgent need for improved therapies for metastatic dedifferentiated liposarcomas (DDLPS), given their life-threatening nature. Based on the promising data, plans are underway to initiate clinical trials with BTX-A51 for LPS patients.

The study illustrated that liposarcomas are marked by MDM2 gene amplification, resulting in abnormal p53 suppression. BTX-A51 effectively countered MDM2 overexpression, leading to p53 upregulation and subsequent apoptosis in multiple LPS cell lines. Moreover, BTX-A51 demonstrated tolerability and efficacy in patient-derived xenograft models.

David N. Cook, Ph.D., CEO of Edgewood Oncology, expressed satisfaction with Dana-Farber’s interest in BTX-A51. He also highlighted its potential in cancers with MDM2 amplifications, hinting at broader therapeutic applications.

Further insights from the study revealed that CDK9 inhibition, combined with CK1α depletion, significantly suppressed LPS cell growth and induced apoptosis. BTX-A51, known for its nanomolar efficacy in AML models, effectively targeted CK1α, CDK9, and CDK7, leading to apoptosis in LPS cells. Notably, in vivo data from patient-derived xenograft models affirmed BTX-A51’s tolerability and its ability to inhibit tumor growth.

About Edgewood Oncology: Edgewood Oncology is a clinical-stage biotech company dedicated to advancing BTX-A51 for patients with hematologic malignancies and genetically-defined solid tumors. BTX-A51, a novel multi-kinase inhibitor, holds promise in activating apoptosis in acute myeloid leukemia and genetically-defined solid tumors, forming the cornerstone of ongoing clinical endeavors.

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