Boundless Bio (BOLD) 2024 Cantor Fitzgerald Global Healthcare Conference summary

Company overview and scientific focus

• Focuses on precision oncology for oncogene amplified cancers, representing about 25% of all cancers and a high unmet need population.

• Targets extrachromosomal DNA (ecDNA), a cancer-specific phenomenon driving oncogene amplification and resistance to standard therapies.

• Developed a platform to identify and drug synthetic lethalities in ecDNA-reliant cancer cells.

• Three active oral small molecule programs, with two in clinical trials and one in preclinical development.

• Created ECHO, a diagnostic assay using standard sequencing data to detect ecDNA, recently validated with ~90% accuracy.

Clinical programs and mechanisms

• BBI-355 is a selective CHEK1 inhibitor targeting replication stress in ecDNA-driven cancers, with clinical trials in combination with targeted therapies.

• BBI-825 is an oral ribonucleotide reductase (RNR) inhibitor, exploiting cancer cells' reliance on de novo dNTP synthesis, especially in MAP kinase-activated and ecDNA-high tumors.

• A third program targets a novel kinesin essential for ecDNA localization during mitosis, causing cytotoxic aggregation when inhibited.

• Combination strategies aim to block both the primary oncogenic driver and ecDNA-mediated resistance, with preclinical synergy observed.

• Clinical studies are designed to stratify patients by ecDNA status and amplification, with efficacy data expected in the second half of next year.

Diagnostic and biomarker development

• ECHO assay co-developed with SOPHiA GENETICS, uses NGS data to identify ecDNA, its amplified genes, and copy numbers.

• Validated against gold standards like FISH and whole genome sequencing, showing high sensitivity and specificity.

• Enables patient stratification in clinical trials and supports the biomarker-driven approach for targeted therapy development.