Abstract 1527: Reversal of the Warburg Effect with BPM31510 treatment in a quinone deficient C6 Glioma resulting in efficacy

Abstract BPM31510-IV is a drug-lipid conjugate nanodispersion comprised of oxidized Coenzyme Q10 (CoQ10) in clinical development for glioblastoma multiforme (GBM). BPM31510 reengineers tumor metabolism, while supporting efficient metabolism of non-tumorigenic tissue. Recent evidence suggests that GBM tumors have a deficiency in quinones, most notable CoQ10, leading to altered mitochondrial function. Additionally, emerging data suggests that the rat C6 glioma also is deficient in quinone metabolites. Herein, we explored the therapeutic MOA of BPM31510 in the treatment of GBM based on twice a day dosing vs intermittent dosing. Survival assessment was performed with untreated, 100 mg/kg BID dosing (IP), 200 mg/kg IV dosing (every other day) and 400 mg/kg IV dosing (every other day) in rats implanted with a C6 glioma. Tumor implantation was confirmed using MRI at day 9 and treatment began at day 11. In a parallel treatment study, rats were treated in a corresponding manner and tissue samples were collected at day 14. Rat brains were immediately frozen and were assessed by spatial metabolomics/lipidomics and quinone assessment (quinomics) to spatially resolve metabolic changes at a single cell level post-treatment. C6 glioma exhibited a deficiency in CoQ9 (dominant CoQ in rats) and treatment with BPM31510 was able to increase CoQ9 in tumors reengineer metabolic activity, thus reversing the Warburg effect. Analysis of BPM31510 treated animals revealed a dose dependent and dosing sequent dependent response impacting survival and tumor resolution as well as an impact on spatial metabolic effect of BPM31510 treatment in brain compared to C6 glioma tissue. Additionally, changes in lactate and citrate were also evident in tumor compared to brain in a dose and cycling dependent manner, which demonstrates reengineering of mitochondrial metabolism in cancer compared to normal brain. These data definitely demonstrate that BPM31510 is capable of entering the brain and tumor, reengineering mitochondrial metabolism resulting in a resolution of the glioma which impacts survival. Both dosing and sequencing of doses impact outcome and metabolic response. Citation Format: Michael A. Kiebish, Abbas Khojasteh, Sylwia Stopka, Juan J. Aristizabal-Henao, Seema Nagpal, Lisa Ghiglieri, Mustafa Kendirli, Maria-D Nastke, Stephane Gesta, Niven R. Narain, Vijay Modur, Lawrence Recht. Reversal of the Warburg Effect with BPM31510 treatment in a quinone deficient C6 Glioma resulting in efficacy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1527.