First-in-Human Trial of BBI-825 Begins with Patient Dosing for Cancer Resistance Gene Amplifications

Boundless Bio, a clinical-stage oncology firm, has initiated a Phase 1/2 clinical trial for BBI-825, a new oral medication targeting ribonucleotide reductase (RNR), in patients with cancer that has become resistant to standard treatments. This marks the second extrachromosomal DNA (ecDNA)-directed therapy (ecDTx) from the company to enter clinical trials, following the premise that ecDNA plays a pivotal role in the high copy number amplification observed in many cancers.

BBI-825 is a novel, selective inhibitor of RNR, an enzyme critical for the synthesis of DNA's building blocks. The drug has shown promise in preclinical studies, where it was able to inhibit tumor growth and even induce regression in tumors that have developed resistance through the MAPK pathway.

The STARMAP trial is designed to assess the safety, pharmacokinetics, and preliminary antitumor effects of BBI-825. It will involve three stages: a dose escalation as a monotherapy, a combination dose escalation with targeted therapies for colorectal cancer patients with specific mutations and resistance gene amplifications, and a dose expansion to evaluate the anti-tumor activity of the drug in combination with targeted therapies.

The first patient has already been dosed in this trial, which is a significant step forward in the development of therapies for hard-to-treat cancers. Boundless Bio's approach focuses on the unique characteristics of ecDNA and its role in the survival and resistance of certain cancer cells, offering a new avenue for cancer treatment.

The company's Spyglass platform has been instrumental in identifying synthetic lethal targets essential for ecDNA formation and function in cancers with amplified oncogenes. This platform has allowed Boundless Bio to advance its drug candidates, including BBI-825, into clinical development.

Boundless Bio is committed to developing transformative therapies for patients with oncogene amplified cancers, a significant unmet need in oncology. The company's pipeline includes additional programs in preclinical development, all aimed at targeting ecDNA to treat cancers that have proven difficult to manage with existing therapies.

While the trial is in its early stages, the dosing of the first patient is an encouraging milestone. If the trial results are positive, there is potential for BBI-825 to be expanded to treat a broader range of patient populations, including those with pan-tumor, pan-RAS, and pan-RAF indications, which could greatly benefit patients with high unmet needs.