Pipeline
AVN944
Hematologic Malignancies
The hematologic malignancy Phase I study is a repeat-dose dose escalation trial in patients with advanced hematologic malignancies. Patients are dosed for 21 days on a 28-day cycle. At a minimum, three patients are treated at each dose level. The study is divided into two arms, one for treatment of leukemia patients and the other for the treatment of patients with lymphoma and myeloma.

Interim data indicate that AVN944 is well tolerated, has dose-dependent pharmacokinetics, induces biomarkers of programmed cell death in cancer cells from patients, and demonstrates stabilized disease in both leukemia and multiple myeloma patients.

• Pharmacokinetics measurements indicate dose proportional plasma levels of AVN944 during treatment and sustained plasma concentrations at the dose levels tested thus far.
• Dose dependent MPDH enzyme inhibition and GTP pool depletion have been observed at the dose levels tested thus far.
• The AvalonRx® platform has identified selected biomarkers from patient samples which show a correlation of changes in gene expression in a dose-dependent manner. Importantly, several of these markers display a durable, sustained stress response indicative of cancer cell death, particularly in cancer cells from AML patients. As dose levels increase the biomarkers reflect an even greater impact of AVN944 on the cancer cells. Direct markers of apoptosis are induced at these higher levels, including members of the Bcl2 gene family, which play a critical role in programmed cell death.

For additional information on or participation in this clinical trial, please visit the National Institutes of Health clinical trial database at www.ClinicalTrials.gov (a service of the U.S. National Institutes of Health developed by the National Library of Medicine) and enter AVN944 into the search bar.