Acute myeloid leukemia (AML) typically is found in patients older than 60 years of age, and these patients have a 5-year survival rate of 10-15%. Combination therapy using a BCL-2 inhibitor with chemotherapy has improved treatment regimens for patients who cannot tolerate intensive chemotherapy. However, recurrence rates are still high, and new combination therapy regimens are needed to improve the survival rates of AML patients.

There have been several combination therapies that have been tested to improve anti-BCL-2 drug activity while still maintaining low toxicity levels. One such promising combination was the FMS-like tyrosine kinase 3 (FLT3) inhibitor, gilteritinib, which had high response rates. However, it is unclear whether these high response rates will translate into increased patient survival, and clinical toxicity levels are unknown. Derivatives of artemisinins (ARTs) were more recently identified to have antileukemic activity and work synergistically with other currently used antileukemia drugs, suggesting ARTs may be useful in combination therapies to treat AML.

This technology is a novel artemisinin-derived compound, ART714, developed for the treatment of AML as either a monotherapy or in combination with existing therapies. ART714 demonstrates potent antileukemic activity and has been optimized for improved solubility, stability, and pharmacokinetic properties.  This technology offers a potential new therapeutic strategy that combines favorable drug-like properties with strong efficacy and compatibility with clinically relevant AML treatment regimens.

The university is seeking licensing partners and research sponsors to advance the development of this technology. Companies interested in commercializing novel AML therapies or collaborating on the development of artemisinin-derived compounds are encouraged to engage with the university to discuss licensing opportunities, sponsored research agreements, and strategic development partnerships.

Technology Overview

Current Challenges

Although treatments of leukemias and specifically ART compounds have been studied, there are constraints posed by toxicity, poor solubility and stability and limited efficacy of current AML monotherapies and combinations. This invention shows favorable pharmacokinetic properties without toxicity and has demonstrated efficacy by prolonging survival of AML models when combined with a BCL-2 inhibitor and a kinase inhibitor, supporting its potential for clinical development.

Our Innovation

This invention, called ART714, is a new compound derived from artemisinin to use in the treatment of AML. It demonstrates significant antileukemic activity alone and in combination with established drugs such as BCL-2 inhibitors, kinase inhibitors, and anti-neoplastic agents. This novel compound has also been shown to have optimal solubility, stability and efficacy, important for clinical development and offers a method of treating leukemia as a monotherapy or combination therapy to improve patient outcomes.  

Benefits of this Technology

  • Optimal solubility and stability for effective delivery, which may improve treatment response rates.
  • Potent antileukemic efficacy as monotherapy and in combination with other therapies.
  • Synergistic effects when combined with BCL-2 and kinase inhibitors, enhancing their therapeutic efficacy.
  • Favorable pharmacokinetic profile with high systemic exposure.
  • Reduces MCL-1 expression, boosting efficacy of existing BCL-2 inhibitor treatments.

Stage of Development

The inventors have data testing 22 different 2-carbon-linked artemisinin-derived dimers (2C-ART) for potency, stability and solubility compared to a prior 2C-ART that was efficacious but had suboptimal solubility and stability. The inventors identified a lead artemisinin-derived (ART) compound and validated pharmacokinetics, pharmacodynamics, and efficacy in an in vivo model. They additionally demonstrated the compound's cooperativity with venetoclax and sorafenib and with the combination of venetoclax and gilteritinib. Additional efficacy studies with other AML models and using multiple cycles of therapy are planned, as well as further studies to identify the optimal niche for the use of the ART compound in treating AML.