Kintara Therapeutics (KTRA) Presents Additional VAL-083 Data

Kintara Therapeutics, Inc. (NASDAQ: KTRA) today announces that it has presented data at the 2022 American Association for Cancer Research (AACR) Annual Meeting.

Data Presentation:

Track 24: Experimental and Molecular Therapeutics

Session PO.ET02.01 - Mechanisms of Drug Action 1

1843 / 15 - Dianhydrogalactitol (VAL-083) for the Treatment of Glioblastoma Multiforme (GBM): Impact of Glucose Transporters for Crossing the Blood Brain Barrier (BBB)

(Presentation Time: Monday, April 11, 2022 - 1:30 p.m. to 5:00 p.m. CT)

Enhanced drug concentrations of VAL-083 in the brain and GBM brain tumors in comparison to circulating plasma concentrations have been observed in human clinical trials. Most therapeutic agents targeting brain tumors have very limited access to primary brain tumors due to the protective nature of the BBB that limits access for most chemical structures.

VAL-083 shares structural and molecular similarities to glucose including low molecular weight and high water solubility. Glucose transporters, in particular GLUT1, are overexpressed by the BBB since the brain requires very high concentrations of glucose for metabolism. Laboratory studies presented at the meeting assessed whether glucose transporters are involved in the ability of VAL-083 to cross the BBB.

Three glucose transporters were studied in vitro including SGLT1, SGLT2 and GLUT1. For all three transporters VAL-083 was not a substrate for these active transport systems. This suggests that VAL-083 may be crossing the BBB by passive diffusion rather than facilitated active transport.

VAL-083 has some physical chemical parameters that differ from glucose. These include increased lipophilicity (log P) and a significantly lower polar surface area (PSA) (lower surface charge) which may allow for relatively unencumbered passive diffusion across the lipid cell membranes of the BBB as well as GBM tumor cells. This independence for the need for specific active drug transporters may help to explain the enhanced drug concentrations of VAL-083 observed clinically in GBM.

"These results are extremely important," said Dennis Brown, Ph.D., Kintara's Chief Scientific Officer. "We thought that since there were numerous structural similarities between VAL-083 and glucose that perhaps a specialized glucose transporter could explain the favorable brain concentration demonstrated clinically for VAL-083. It appears that other molecular features like PSA and log P may account for the very unique pharmacologic properties we are observing. This suggests that the clinical pharmacokinetics of VAL-083 would result in less inter- and intra-patient variability in CNS penetration and, therefore, greater precision of drug dosing to the brain.

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