Kintara Therapeutics (NASDAQ:KTRA) Inc presented data at the 2022 American Association for Cancer Research (AACR) Annual Meeting.
The San Diego, California-based company is developing novel cancer therapies for patients with unmet medical needs, including VAL-083 for Glioblastoma Multiforme (GBM) and REM-001 for Cutaneous Metastatic Breast Cancer (CMBC).
VAL-083 is a small-molecule chemotherapeutic with a novel mechanism of action that has demonstrated clinical activity against a range of cancers, including central nervous system, ovarian and other solid tumors.
READ: Kintara Therapeutics announces multi-year research grant to support research of its VAL-083 program to treat glioblastoma
Kintara observed enhanced drug concentrations of VAL-083 in the brain and GBM brain tumors in comparison to circulating plasma concentrations in human clinical trials. The company highlighted that 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.
The company presented laboratory studies on three glucose transporters that were studied in vitro, including SGLT1, SGLT2 and GLUT1. For all three transporters VAL-083 was not a substrate for these active transport systems, which Kintara suggests could indicate 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, Kintara said, including increased lipophilicity (log P) and a significantly lower polar surface area (PSA), or a 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, Kintara said.
Kintara’s chief scientific officer Dennis Brown called the results “extremely important.”
"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,” Brown said in a statement.
“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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