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Apr 11, 2022, 14:30 ET
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SAN DIEGO, April 11, 2022 /PRNewswire/ — Kintara Therapeutics, Inc. (NASDAQ: KTRA) (“Kintara” or the “Company”), a biopharmaceutical company focused on the development of new solid tumor cancer therapies, today announces that it has presented data at the 2022 American Association for Cancer Research (AACR) Annual Meeting.
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.
Located in San Diego, California, Kintara is dedicated to the development of novel cancer therapies for patients with unmet medical needs. Kintara is developing two late-stage, Phase 3-ready therapeutics for clear unmet medical needs with reduced risk development programs. The two programs are VAL-083 for GBM and REM-001 for Cutaneous Metastatic Breast Cancer (CMBC).
VAL-083 is a “first-in-class,” 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 (e.g., NSCLC, bladder cancer, head and neck) in U.S. clinical trials sponsored by the National Cancer Institute (NCI). Based on Kintara’s internal research programs and these prior NCI-sponsored clinical studies, Kintara is currently advancing VAL-083 in the GBM AGILE study to support the development and commercialization of VAL-083 in GBM.
Kintara is also advancing its proprietary, late-stage photodynamic therapy platform that holds promise as a localized cutaneous, or visceral, tumor treatment as well as in other potential indications. REM-001 therapy has been previously studied in four Phase 2/3 clinical trials in patients with CMBC who had previously received chemotherapy and/or failed radiation therapy. With clinical efficacy to date of 80% complete responses of CMBC evaluable lesions, and with an existing robust safety database of approximately 1,100 patients across multiple indications, Kintara is advancing the REM-001 CMBC program to late-stage pivotal testing.
For more information, please visit www.kintara.com or follow us on Twitter at @Kintara_Thera, Facebook and LinkedIn.
SAFE HARBOR STATEMENT
Any statements contained in this press release that do not describe historical facts may constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995, including statements regarding the status of the Company’s clinical trials and the GBM AGILE study. Any forward-looking statements contained herein are based on current expectations but are subject to a number of risks and uncertainties. The factors that could cause actual future results to differ materially from current expectations include, but are not limited to, risks and uncertainties relating to the impact of the COVID-19 pandemic on the Company’s operations and clinical trials; the Company’s ability to develop, market and sell products based on its technology; the expected benefits and efficacy of the Company’s products and technology; the availability of substantial additional funding for the Company to continue its operations and to conduct research and development, clinical studies and future product commercialization; and, the Company’s business, research, product development, regulatory approval, marketing and distribution plans and strategies. These and other factors are identified and described in more detail in the Company’s filings with the SEC, including the Company’s Annual Report on Form 10-K for the year ended June 30, 2021, the Company’s Quarterly Reports on Form 10-Q, and the Company’s Current Reports on Form 8-K.
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