Cancer Stem Cell Interception with Rebecsinib: A First-in-Class ADAR1 Inhibitor

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Grant Application Details

Application Title:

Cancer Stem Cell Interception with Rebecsinib: A First-in-Class ADAR1 Inhibitor

Public Abstract:
Therapeutic Candidate or Device

Rebecsinib is a novel small molecule inhibitor of ADAR1 splicing that selectively eradicates therapy-resistant cancer stem cells in blood cancers.


The target indication is relapsed/refractory secondary acute myeloid leukemia (sAML), or int-2 or high-risk myelofibrosis (MF).

Therapeutic Mechanism

Rebecsinib therapy for patients with relapsed/refractory sAML, or int-2 or HR MF could eradicate therapy-resistant cancer stem cells thereby preventing relapse and improving overall survival. Splice isoform and editing biomarkers of cancer stem cell response (e.g., ADAR1 and MCL-1 splicing inhibition) to Rebecsinib have been identified in pre-clinical models. We can modify responses to Rebecsinib to provide a companion diagnostic for proof-of-concept studies in future clinical trials.

Unmet Medical Need

Despite advances in molecularly targeted and immunotherapeutic strategies, sAML and int-2 or HR-MF patients have a 5-year life expectancy of 25% due to high relapse rates fueled by cancer stem cells harboring splicing-mediated ADAR1 activation; this underscores the unmet medical need for Rebecsinib.

Project Objective

GMP, definitive tox, IND, Ph1 start-up completion

Major Proposed Activities

  • Manufacture Rebecsinib to complete IND studies and GMP manufacturing of Rebecsinib sufficient for clinical trials.
  • Complete toxicological, pharmacokinetic and pharmacodynamic studies in rats and rabbits as well as genotoxic and ADME studies.
  • Submission of IND and completion of Phase 1 clinical trial start-up activities with Rebecsinib for relapsed/refractory myeloid malignancies.
Statement of Benefit to California:
Cancer is the second leading cause of death with sAML and high-risk MF being among the most rapidly fatal. Relapse-related mortality rates remain exceedingly high because of ADAR1p150-induced malignant regeneration and immune checkpoint inhibitor resistance. While current therapies reduce some symptoms, a cancer stem cell inhibitor, Rebecsinib, offers a novel therapeutic approach for myeloid malignancies and many other ADAR1p150 activated cancers that afflict Californians.