Unbound by convention, bound to save lives
While traditional precision oncology companies advance marginally superior targeted therapies against mutations of known cancer targets, Boundless Bio has a distinct mission to aid a neglected group, patients with oncogene amplification. Cancers with oncogene amplification have been historically challenging and targeted therapies have struggled to demonstrate efficacy for these patients. Cancer-wide studies show that patients with oncogene amplification have significantly worse survival than the general cancer patient population, and those with ecDNA-driven amplification fare even worse. Boundless Bio is the only company dedicated to therapies for amplification patients via insight into ecDNA.
The only therapy that has been shown to be effective in gene amplified cancers is antibodies against HER2 in breast and gastric cancers. All other targeted therapies (e.g., erlotinib, infigratinib) tested across tumor types have failed to show sufficient efficacy. We have found that ecDNA explains the lack of responses and short durations associated with treatment of gene amplified cancers with targeted therapies in the clinic. The results from our AACR 2021 study show the resistance of SNU16 cells to infigratinib is driven by the heterogeneity of oncogenes residing on ecDNA. First, low doses of infigratinib led to additional amplification of FGFR2 on ecDNA to levels that outcompeted the drug. High doses of infigratinib resulted in amplification of EGFR on ecDNA. Infigratinib resistant cells (now with EGFR amplification on ecDNA) treated with the EGFR inhibitor, erlotinib, again became resistant, and switched back to FGFR2 dependency, again on ecDNA. Lastly, the study tested dual upfront of both infigratinib and erlotinib. Although initial cytotoxicity was robust, the cell population inevitably became resistant, again mediated by ecDNA, with amplification of various oncogenes, including MET and KRAS. The inability to a priori predict which new oncogenes would amplify on ecDNA as a mechanism of resistance to single-agent or multi-target inhibition suggest that both sequential and combination approaches of oncogene targeted therapies are suboptimal, if not largely ineffective, and akin to attempting to play a game of clinical “whack-a-mole”. For these reasons, a new therapy targeting ecDNA is desperately needed for patients with oncogene amplification.
BBI licensed foundational ecDNA intellectual property from its academic founders’ institutions at University of California San Diego, Ludwig Cancer Research Institute, and Stanford University and has assembled a robust intellectual property portfolio based on its own innovations around ecDNA cancer pathways, methods of ecDNA detection, ecDNA diagnostic signatures, and novel drug compositions. Though many large pharma are interested in partnering with BBI, the team has been currently focused in developing the current programs towards the clinic.