Boundless Bio (BOLD) Guggenheim’s Inaugural Healthcare Innovation Conference summary

Company overview and scientific foundation

• Focuses on precision oncology for patients with oncogene-amplified cancers, a group underserved by current targeted therapies.

• Amplifications account for about 25% of all tumors, more common than point mutations or fusions.

• Extrachromosomal DNA (ecDNA) is identified as a key driver of poor outcomes in amplified tumors.

• ecDNA leads to tumor heterogeneity and rapid resistance to therapies.

Platform and discovery approach

• Developed the Spyglass platform to characterize hundreds of amplification-driven models and identify ecDNA-specific targets.

• Uses whole genome CRISPR screens to find genes synthetically lethal to ecDNA-positive cells.

• High copy number amplification (≥8 copies) is ecDNA-driven in 54% of cases.

Lead program: BBI-355 (CHK1 inhibitor)

• BBI-355 targets replication stress in ecDNA-positive cancer cells, leading to cell death.

• Prior CHK1 inhibitors failed due to lack of biomarker-driven patient selection and suboptimal drug properties.

• BBI-355 was developed in-house for potency, selectivity, and oral bioavailability.

• Phase I study (POTENTIATE) showed good tolerability up to 60 mg; combination arms with EGFR, FGFR, and CDK4/6 inhibitors are ongoing.

• No emergent combination toxicity observed; data updates expected in the second half of next year.