Boundless Bio Announces First Patient Dosed in First-in-Human Phase 1/2 Clinical Trial of BBI-825 in Cancer Patients with Resistance Gene Amplifications - Seite 2

“Advancing our second ecDTx into clinical development is an important milestone for Boundless Bio and underscores the power of our Spyglass platform to identify synthetic lethal targets essential to ecDNA formation and function in oncogene amplified cancers,” said Zachary Hornby, President and Chief Executive Officer at Boundless Bio. “We are excited to enroll patients in this first-in-human Phase 1/2 study, focused initially on patients with KRAS^G12C and BRAF^V600E mutated colorectal cancer with resistance gene amplifications. If data are supportive, we may have the opportunity to expand into broader patient populations, including pan-tumor, pan-RAS, and pan-RAF indications, potentially addressing these populations of cancer patients with very high unmet need.”

About the STARMAP Trial

STARMAP (“Study Treating Acquired Resistance: MAPK Amplifications”) is an open-label, non-randomized, three-part Phase 1/2 clinical trial to evaluate the safety, pharmacokinetics, pharmacodynamic biomarkers, preliminary antitumor activity, and identify the maximum tolerated dose and recommended Phase 2 dose (RP2D) of BBI 825 administered as a single agent or in combination with select targeted therapies (NCT06299761). Part 1 is a dose escalation of BBI-825 as a monotherapy in patients with solid tumors. Part 2 is a combination dose escalation of BBI-825 and targeted therapies, encorafenib and cetuximab, or adagrasib and cetuximab, in patients with advanced or metastatic colorectal cancer with BRAF^V600E or KRAS^G12C mutations, respectively, and co-occurring resistance gene amplifications. Part 3 is a combination dose expansion to evaluate preliminary anti-tumor activity at the RP2D of BBI-825 and each targeted therapy combination from Part 2.

About BBI-825

Boundless Bio’s second ecDNA-directed therapy (ecDTx), BBI-825, is a novel, oral, selective small molecule inhibitor of ribonucleotide reductase (RNR) being studied in the currently enrolling, first-in-human, Phase 1/2 STARMAP trial in cancer patients with resistance gene amplifications. In preclinical studies, BBI-825 demonstrated low double digit nanomolar RNR inhibition and tumor growth inhibition, including regressions, in both the prevention and treatment of amplification-mediated resistance in mitogen-activated protein kinase (MAPK) pathway-activated tumors. RNR is a rate-limiting enzyme responsible for cellular de novo synthesis of deoxynucleotide triphosphates (dNTPs), the building blocks of DNA, and is essential to the assembly and repair of ecDNA. BBI-825 was shown to starve ecDNA-reliant cancer cells of dNTPs, deplete ecDNA, and was synthetic lethal in multiple oncogene amplified preclinical cancer models.