472P - Comprehensive quinomics assessment of BPM31510IV treatment in advanced glioblastoma multiforme patients

Background

BPM31510IV is a drug-lipid conjugate nanodispersion comprised of oxidized Coenzyme Q10 (CoQ10, a predominant quinone metabolite) in clinical development for glioblastoma multiforme (GBM). A completed Phase I single agent BPM31510IV study (NCT03020602) provided positive results on safety and tolerability in recurrent GBM.

Methods

Longitudinal pharmacodynamic samples during a 28-day cycle were collected at various times timepoints in patient’s undergoing BPM31510 dose escalation, which allows us the opportunity to investigate quinone metabolites in the presence of superphysiological concentrations of CoQ10. Fifteen (15) patients were evaluable, receiving BPM31510 infusion at 110 mg/kg, 137 mg/kg, and 171 mg/kg. A quinomics workflow (broad bioanalysis of quinones comprised of metabolites predominantly characterized by the classical phenolic ring structure similar to CoQ10) was added to the conventional plasma pharmacodynamic using multiomic analysis to allow for comprehensive dynamics of CoQ10 and its subsequent metabolites.

Results

Quinomics analysis was performed using high resolution LC MS/MS analysis (Thermo Q-Exactive+ and Bruker TIMSTOF Flex) through a parallel reaction monitoring (PRM) method to quantify around 20 precursor, oxidized/reduced states, and metabolic breakdown analytes of CoQ10, in addition to an untargeted metabolomic/lipidomic workflow. In parallel, spatial quinomics assessment of brain tissue in mice treated with BPM31510 is presently being evaluated to determine regional organization and distribution of quinone metabolites using the Bruker TIMSTOF Flex workflow. This approach will facilitate single cell resolution of analytes.

Conclusions

Integrated systemic and tissue distribution quinomics profiling offers novel insights into the pharmacodynamics of BPM31510, both clinically and experimentally, providing valuable biological insights on the therapeutic intervention of GBM with BPM31510 as well as association with clinical outcomes.

Clinical trial identification

NCT03020602.

Editorial acknowledgement

Legal entity responsible for the study

BPGbio, Inc.

Funding

BPGbio, Inc.

Disclosure

J.J. Henao, B. Greenwood, S. Karmacharya, M. Nastke, S. Gesta, V. Modur, M.A. Kiebish: Financial Interests, Personal, Full or part-time Employment: BPGbio. N.R. Narain: Financial Interests, Personal, Full or part-time Employment: BPGbio; Financial Interests, Personal, Stocks/Shares: BPGbio. All other authors have declared no conflicts of interest.