Edgewood Oncology Unveils Compelling Preclinical Data Supporting BTX-A51 in Liposarcoma at AACR Annual Meeting 2025
Edgewood Oncology, a clinical-stage biotechnology company dedicated to advancing targeted cancer therapies, today announced new preclinical efficacy data for BTX-A51 in liposarcoma (LPS). The data, presented at the 2025 American Association for Cancer Research (AACR) Annual Meeting held April 25–30 in Chicago, reinforces the scientific rationale for targeting a novel set of key regulatory kinases involved in cancer cell proliferation and survival.
The findings were shared by researchers from Dana-Farber Cancer Institute and Hebrew University-Hadassah Medical School, who are currently leading an investigator-sponsored Phase 1 clinical trial evaluating BTX-A51 in patients with liposarcoma. This study builds on an evolving body of evidence supporting BTX-A51’s unique mechanism of action and broad therapeutic potential.
A New Class of Targeted Therapy
BTX-A51 is a first-in-class, orally available small molecule kinase inhibitor designed to simultaneously inhibit casein kinase 1 alpha (CK1α) and cyclin-dependent kinases 7 and 9 (CDK7 and CDK9). These kinases are considered master regulators of transcriptional control and cellular survival pathways—processes that are frequently dysregulated in various cancers.
While many kinase inhibitors target single nodes in oncogenic signaling pathways, BTX-A51 takes a multi-pronged approach. By co-targeting CK1α, CDK7, and CDK9, the compound aims to disrupt core mechanisms essential to the growth and survival of genetically defined tumor types. This includes malignancies marked by gene amplifications or transcriptional dependencies, such as liposarcoma.
“BTX-A51 is designed to hit multiple critical pressure points in cancer biology,” said Dr. David N. Cook, Chief Executive Officer of Edgewood Oncology. “The combination of CK1α and CDK7/9 inhibition addresses both upstream and downstream drivers of tumor growth and transcriptional addiction, offering a powerful tool in the fight against hard-to-treat cancers.”
Presentation Highlights: Mechanistic Insights and Efficacy in Liposarcoma
The AACR presentation, titled “Therapeutic potential of combined targeting of casein kinase 1 alpha (CK1α) and CDK7/9 with the inhibitor BTX-A51 in human liposarcomas,” delivered fresh preclinical insights into BTX-A51’s activity in models of well-differentiated and dedifferentiated liposarcoma (WD/DDLPS).
Using patient-derived cell lines and xenograft models, researchers evaluated the impact of BTX-A51 on cell viability, gene expression, and tumor growth. Notably, the study included genome-scale RNA interference (RNAi) perturbation analysis to identify genes essential to liposarcoma survival. This analysis revealed that CK1α plays a critical role in tumor cell growth, emerging as a potentially targetable vulnerability in LPS.
Researchers then confirmed the importance of CK1α, CDK7, and CDK9 through RNAi knockdown studies and the application of selective small-molecule inhibitors. These experiments showed that inhibiting these targets—especially in combination—induced synergistic anti-tumor effects in LPS models.
As a single agent, BTX-A51 demonstrated the ability to downregulate MDM2—a key oncogene frequently amplified in liposarcoma—and upregulate the tumor suppressor protein P53. This resulted in robust activation of apoptotic pathways and inhibition of tumor growth in vivo. In patient-derived xenografts, BTX-A51 significantly suppressed tumor progression at well-tolerated dose levels, supporting its potential utility in clinical settings.
A Critical Need in Liposarcoma Treatment
Liposarcoma, a rare and heterogeneous type of soft tissue sarcoma, poses substantial challenges to treatment. Well-differentiated and dedifferentiated liposarcomas are the most common subtypes and are often characterized by amplifications in MDM2, which contributes to tumor growth and resistance to traditional therapies. Treatment options for recurrent or metastatic LPS are limited, with modest clinical outcomes from current chemotherapies and radiation.
“WD/DDLPS remain among the most difficult sarcomas to manage due to their aggressive nature and limited treatment responsiveness,” said Dr. Geoffrey I. Shapiro, M.D., Ph.D., Professor of Medicine at Harvard Medical School and Director of the Early Drug Development Center at Dana-Farber Cancer Institute. “This preclinical study identifies novel, targetable molecular vulnerabilities in liposarcoma and builds a strong rationale for the continued clinical evaluation of BTX-A51 in this patient population.”
Phase 1 Clinical Trial Ongoing at Dana-Farber
The promising preclinical findings support the rationale for an ongoing investigator-initiated Phase 1 clinical trial of BTX-A51 in patients with metastatic and/or recurrent liposarcoma. This open-label pilot study is currently being conducted at Dana-Farber Cancer Institute and focuses on individuals whose tumors harbor MDM2 gene amplifications—a common genetic alteration in WD/DDLPS.
The study aims to evaluate the safety, tolerability, and preliminary efficacy of BTX-A51, as well as identify biomarkers associated with response. Initial results are expected to inform further development and potential expansion into larger, multi-center studies. Full details on the clinical trial are available at clinicaltrials.gov under the identifier NCT06414434.
Broader Implications for Genetically Defined Tumors
Beyond liposarcoma, the mechanism of action behind BTX-A51 may be applicable to a wide range of genetically defined cancers. The dual inhibition of CK1α and CDK7/9 offers a versatile strategy to disrupt transcriptional dependencies found in hematologic malignancies, MYC-driven cancers, and tumors with MDM2 or other amplification-driven oncogenic programs.
BTX-A51 is also being studied in other cancer types where these molecular signatures play a dominant role in disease progression. Previous preclinical work has demonstrated the compound’s activity in models of acute myeloid leukemia (AML), mantle cell lymphoma, and triple-negative breast cancer, further supporting its potential across oncology indications.
“These new findings in liposarcoma align well with our broader development strategy,” added Dr. Cook. “BTX-A51 targets the molecular underpinnings of cancer cell survival in a precise and multi-faceted way. This approach is especially promising in tumor types with clear genetic drivers, where targeted therapies have historically shown the greatest clinical success.”
The presentation of these data at AACR 2025 underscores Edgewood Oncology’s commitment to translating cutting-edge science into meaningful clinical solutions for patients with challenging cancers. With encouraging efficacy results in preclinical liposarcoma models and a Phase 1 study underway, BTX-A51 is well positioned to advance into subsequent stages of development.
In the coming months, Edgewood Oncology expects to continue generating data that will further elucidate BTX-A51’s therapeutic potential, refine its clinical strategy, and explore opportunities for combination therapies. As precision oncology continues to evolve, agents like BTX-A51 that exploit fundamental transcriptional dependencies may help shift the paradigm in cancer treatment.
