Boundless Bio Presents Preclinical and Clinical Pharmacodynamic Data on its Lead Extrachromosomal DNA (ecDNA)-Directed Therapy, BBI-355, at the American Association for Cancer Research Annual Meeting 2024

Boundless Bio (Nasdaq: BOLD), a clinical-stage oncology company interrogating extrachromosomal DNA (ecDNA) biology to deliver transformative therapies to patients with previously intractable oncogene amplified cancers, presents preclinical and clinical pharmacodynamic data on its lead ecDNA-directed therapy (ecDTx), BBI-355, and research on ecDNA-mediated acquired resistance to chemotherapy at the American Association for Cancer Research (AACR) Annual Meeting 2024. BBI-355 is a novel, oral, selective inhibitor of checkpoint kinase 1 (CHK1) being studied in the ongoing, first-in-human, Phase 1/2 POTENTIATE clinical trial in patients with oncogene amplified cancers.

“Extrachromosomal DNA afford unique advantages to tumors, typically rendering existing therapies ineffective and correlating with poor patient outcomes,” said Chris Hassig, Ph.D., Chief Scientific Officer of Boundless Bio. “Our first poster presented this year at AACR demonstrated that BBI-355 overcame ecDNA-mediated targeted therapy resistance in preclinical tumor models by leveraging the enhanced reliance of ecDNA-driven tumor cells on CHK1 for survival. BBI-355 showed substantial antitumor activity, including complete and durable regressions, in preclinical oncogene amplified models.

Dr. Hassig continued, “Today we present preclinical and preliminary clinical pharmacodynamic biomarker assay data that showed detection of CHK1 inhibition-associated replication stress in both patient skin and tumor tissue following administration of BBI-355. In addition, we report a possible role for ecDNA in acquired resistance to chemotherapy observed in preclinical models, extending the potential applicability of ecDNA-directed strategies beyond targeted therapy resistance. We are encouraged by these findings as we continue to advance BBI-355 through the ongoing Phase 1/2 POTENTIATE clinical trial.”

Details of the presentations are as follows:

Title: Oral CHK1 inhibitor BBI-355 allows flexibility of dose and schedule with demonstration of monotherapy and combinational antitumor activity in extrachromosomal DNA (ecDNA)-driven oncogene amplified preclinical models
Abstract Number: 613
Session Category: Experimental and Molecular Therapeutics
Session Title: Kinase and Phosphatase Inhibitors 1
Session Date and Time: Sunday Apr 7, 2024, 1:30 PM – 5:00 PM PT
Location: Poster Section 25
Poster Board Number: 23

BBI-355 showed inhibition of CHK1 in a host of tumor cell lines and demonstrated in vivo single agent tumor growth inhibition, including complete tumor regressions, across a range of tumor models representing multiple different oncogene amplifications and tumor types. BBI-355 also demonstrated synergistic tumor growth inhibition, including durable regressions, when combined with targeted therapies across multiple oncogene amplified tumor models.