BPGbio Presents AI-Guided Immune-Modulating Therapeutics at SITC 2024

BPM31510, currently in a Phase 2b trial for glioblastoma, targets mitochondrial biology to modulate the tumor microenvironment, increasing reactive oxygen species (ROS) within cancer cells, which promotes cell death and enhances cytotoxic lymphocyte activity while lowering markers of T cell exhaustion. This compound is being evaluated for potential effectiveness in "immunologically cold" tumors, including glioblastoma and pancreatic cancer.

BRG399 is a novel oral microtubule-binding agent that showed 100% tumor regression in a glioblastoma model, attributed to immune memory responses and an alteration in immune cell profiles within the tumor environment. The treatment led to survival in all tested rats, with findings indicating immune memory retention, which prevented tumor recurrence when re-challenged with glioma cells. BRG399 has demonstrated potential as both a direct tumor ablator and an immune-modulating agent, suggesting further investigation for use in combination therapies.

Technology

BPGbio’s NAi Interrogative Biology Platform, a causal AI-driven tool, underpins these studies, utilizing a biobank of clinically annotated patient samples and the Frontier supercomputer at Oak Ridge National Laboratory. This platform identifies biological signals within complex datasets, isolating causal relationships in patient biology to guide therapeutic target discovery, biomarker identification, and clinical safety assessments.

NAi combines data from tissue, blood, and urine samples, as exemplified in its use for BPM31510’s mechanism analysis, where patient-specific genomic profiles helped narrow clinical indications and optimize trial design.

In drug repurposing efforts, NAi has identified mitochondrial dysregulation as a therapeutic target across various diseases, leading to the adaptation of BPM31510 from a topical wound treatment to an IV and oral formulation in trials for conditions including glioblastoma, pancreatic cancer, and sarcopenia.

Additionally, the platform identified an E2 ubiquitin-conjugating enzyme as a viable drug target, traditionally considered undruggable due to binding challenges. Through structural modifications and targeted ligands, BPGbio established E2-based targeted protein degradation (TPD) approaches, which have demonstrated effects in Huntington’s disease and oncology applications, distinguishing it from the more common E3-based TPD.

See also: Protein Degraders Take Industry By Storm

NAi’s high-resolution causal mapping has enabled BPGbio to advance targeted therapies in oncology, neurology, and rare diseases, supported by multiomic analysis and extensive computational resources. These findings highlight the NAi platform’s role in refining drug development and trial methodologies through predictive modeling and biologically relevant target identification.