NEW YORK – Boundless Bio on Thursday said it will not advance its ribonucleotide reductase inhibitor BBI-825 into the second portion of the Phase I/II STARMAP trial, in which the firm was testing the drug in patients with solid tumors, including those with BRAF V600E or KRAS G12C mutated colorectal cancers that have developed oncogene resistance amplifications.
The firm's decision was based on preliminary pharmacokinetic data from the first part of the trial showing a lack of dose-proportional exposure. Boundless Bio said in a statement that due to the unfavorable pharmacokinetics and "the increasing complexity and associated development costs related to the evolving BRAF V600E and KRAS G12C mutated cancer treatment landscape," it made a strategic decision not to advance BBI-825 to the dose-escalation portion of the first part of the trial or proceed to the second part.
Boundless Bio is developing treatments for cancers driven by extrachromosomal DNA (ecDNA). BBI-825 was designed to limit synthesis of deoxyribonucleotide triphosphates, which are required for ecDNA assembly and repair.
The San Diego-based company will continue the POTENTIATE Phase I/II trial of its CHK1 inhibitor BBI-355 in oncogene-amplified cancers and a preclinical program targeting a kinesin protein, within which it plans to choose a development candidate by mid-2025. The company's strategy for BBI-355 is to disrupt the role of CHK1 in regulating replication stress in ecDNA-enabled oncogene-amplified cancer cells. It expects to report preliminary safety and antitumor activity data in the second half of 2025.
This strategic decision "extends our operating runway into 2027, well beyond the anticipated milestones for both BBI-355 and ecDTx 3," Boundless CEO and President Zachary Hornby said in a statement.
Boundless also announced several personnel changes with Chief Medical Officer Klaus Wagner and Chief Business Officer Neil Abdollahian leaving the company at the end of the month. Starting in January 2025, James Freddo, currently an adviser to Boundless, will serve as the firm's interim chief medical officer while it searches for a permanent replacement. Boundless said it will not appoint a new chief business officer at this time.