BTX-A51

Overview

BTX-A51 is an oral, first‑in‑class small‑molecule inhibitor that co‑targets casein kinase 1α (CK1α) and transcriptional cyclin‑dependent kinases CDK7 and CDK9. It has been evaluated in a first‑in‑human Phase I trial in relapsed/refractory (R/R) acute myeloid leukemia (AML) and high‑risk myelodysplastic syndromes (MDS), with results published July 15, 2025. Additional trials are ongoing in solid tumors, including ER+/HER2‑ metastatic breast cancer and liposarcoma. (jhoonline.biomedcentral.com)

Mechanism of action

• Direct inhibition of CK1α relieves p53 suppression (in part by countering MDM2/MDMX‑mediated regulation), increasing p53 stabilization. Concurrent inhibition of CDK7/9 suppresses RNA polymerase II phosphorylation and super‑enhancer–driven transcription of oncogenes such as MYC and MCL1, producing selective apoptosis of leukemia cells. Pharmacodynamic readouts in patients include increased p53 and reduced MCL1 and RNA Pol II phosphorylation in bone marrow after treatment. (jhoonline.biomedcentral.com)

Efficacy

• Phase I (open‑label, dose escalation) in R/R AML and high‑risk MDS (n=31; doses 1–42 mg, 3 days/week): overall, 3 patients (10%) achieved complete remission with incomplete count recovery (CRi). All responders harbored RUNX1 mutations; among RUNX1‑mutated patients treated at efficacious doses (≥11 mg), the CR/CRi rate was 30%. The study also showed target engagement (p53 upregulation; reduced MCL1 and RNA Pol II phosphorylation). Published July 15, 2025; trial registration reported as NCT04872166 in the manuscript. (jhoonline.biomedcentral.com)

• Earlier interim readouts (2022 conference abstracts) described the same first‑in‑human AML study design and goals (safety, PK/PD, preliminary activity). (ascopubs.org)

• Solid tumors: As of October 2025, there are no peer‑reviewed human efficacy results reported for breast cancer or liposarcoma; clinical work is ongoing (Phase 2a ER+/HER2‑ metastatic breast cancer; investigator‑sponsored Phase 1 in MDM2‑amplified liposarcoma). (edgewoodoncology.com)

Safety

• In the Phase I AML/MDS study (n=31): most common treatment‑emergent adverse events (any grade) were nausea (67%), vomiting/emesis (63%), hypokalemia (53%), and diarrhea (40%). Two patients experienced dose‑limiting hepatic toxicity that resolved with treatment interruption; no treatment‑related deaths occurred. The recommended Phase 2 dose (RP2D) was 21 mg orally, three days per week for 4 weeks of each 28‑day cycle. (jhoonline.biomedcentral.com)

Development status and trials

• Hematologic malignancies: First‑in‑human AML/MDS Phase I published (J Hematol Oncol, July 15, 2025). Site listings note trials under NCT04243785 (AML/MDS) and NCT04872166 (solid tumors/breast cancer). (jhoonline.biomedcentral.com)
• Solid tumors: Phase 2a in ER+/HER2‑ metastatic breast cancer (NCT04872166) and investigator‑sponsored Phase 1 in liposarcoma (NCT06414434) are enrolling. (edgewoodoncology.com)

Further reading

• Journal of Hematology & Oncology (2025): Phase I first‑in‑human study in AML/MDS (open access). (jhoonline.biomedcentral.com)
• PubMed record for the Phase I AML/MDS trial. (pubmed.ncbi.nlm.nih.gov)
• ASCO 2022 abstract: first‑in‑human AML interim results. (ascopubs.org)
• HemaSphere 2022 (EHA abstract): interim AML results. (journals.lww.com)
• Clinical trials listings and program overviews (breast cancer, liposarcoma). (edgewoodoncology.com)

Notes: Company communications indicate active development of BTX‑A51 in genetically‑defined solid tumors (Edgewood Oncology). Scientific claims and clinical outcomes above are based on peer‑reviewed and conference sources; press materials are used only to identify ongoing trials and indications. (edgewoodoncology.com)

Last updated: Oct 2025