Background:

  • Acute Myeloid Leukemia (AML) remains a highly aggressive disease with frequent relapse and limited durable responses.
  • AML cells rely on oncogenic transcriptional programs and anti-apoptotic buffering (e.g., MCL-1) to survive therapy.
  • Combination therapies targeting complementary survival pathways are increasingly needed to improve treatment outcomes.

Our Innovation:

  • A51 is an oral small-molecule multi-kinase inhibitor designed for rational AML combination therapy.
  • Dual mechanism: inhibition of CK1α stabilizes and activates p53, while inhibition of CDK7/9 suppresses oncogenic transcription.
  • Super-enhancer transcription collapse leads to suppression of key survival drivers including MYC, MDM2, and MCL-1.
  • The convergence of p53 activation and transcriptional shutdown drives cancer cell death, providing strong rationale for AML combination strategies.
  • Early Phase 1 clinical experience in AML/MDS and advanced solid tumors supports clinical feasibility.

Advantages:

  • Combination-ready mechanism targeting transcriptional regulation and apoptosis.
  • Oral capsule formulation suitable for outpatient combination regimens.
  • Clinical exposure in >100 patients across early studies.
  • Manageable safety profile, mainly nausea and vomiting.
  • No major toxicities observed compared with related drugs targeting MDM2, CDK7, CDK9, or MCL-1.
  • Preclinical efficacy, including PDX activity in solid tumors such as dedifferentiated liposarcoma.

Development Plan

  • Primary focus – AML combination therapy: finalize an investigator-initiated trial combining A51 with a novel leukemia drug and biomarker strategy.
  • Generate translational biomarkers and apoptosis signatures to guide clinical expansion and partnering.
  • Secondary program: expand preclinical work in KRAS-mutant PDAC as an additional partnering opportunity.

Scientific and Clinical Environment

  • Strong KOL endorsement from leading oncology experts.
  • Clinical work supported by collaborators at Dana-Farber Cancer Institute, Memorial Sloan Kettering Cancer Center, and NYU Langone Health.
  • Significant institutional interest in advancing A51 into further clinical trials.

Commercial Opportunity

  • We are seeking collaboration with pharmaceutical and biotechnology companies developing AML combination therapies.
  • Seed financing target:$2M–$3M to establish a new company and fund:
    • AML investigator-initiated combination study
    • Supporting translational program
    • Focused PDAC preclinical work

Contact in Yissum: Ariela Markel