Boundless Bio, Inc.

• Boundless Bio will not advance BBI-825 into Part 2 of the STARMAP trial due to pharmacokinetic data and the evolving treatment landscape. • The company is prioritizing BBI-355, with initial clinical data expected in the second half of 2025, and a third ecDTx program. • Boundless Bio anticipates nominating a development candidate for its third ecDTx program by mid-2025 and submitting an IND in H1 2026. • Leadership changes include the departure of the CMO and CBO, with James L. Freddo, M.D., appointed as Interim CMO.

• Researchers identified extrachromosomal DNA (ecDNA) in 17.1% of tumors across 39 cancer types, highlighting its role in tumor growth and treatment resistance. • The study suggests that ecDNA fragments carry cancer-driving genes and suppress the immune system, contributing to tumor resilience against therapies. • A CHK1 inhibitor, developed by Boundless Bio, demonstrated potential in reducing tumors and preventing resistance when combined with traditional anti-cancer drugs in mice. • Scientists believe targeting ecDNA could offer a new therapeutic avenue for aggressive cancers by exploiting vulnerabilities created by this unique type of DNA.

• Researchers have discovered that ecDNAs, circular DNA structures in cancer cells, can contain enhancers that drive gene expression on other ecDNAs, promoting cancer cell growth. • Unlike chromosomes, ecDNA transcription continues during cell division, causing advantageous combinations of ecDNAs to segregate together, giving cancer cells a survival advantage. • Blocking the checkpoint protein CHK1 leads to the death of ecDNA-containing tumor cells and tumor regression in mice, suggesting a new therapeutic approach. • A CHK1 inhibitor is currently in early phase clinical trials for cancers with multiple copies of oncogenes on ecDNAs, showing promise for targeted cancer treatment.

• SOPHiA GENETICS and Boundless Bio collaborate with Precision for Medicine to validate a novel clinical trial assay for detecting extrachromosomal DNA (ecDNA). • The ecDNA Solution (ECS) algorithm identifies patients with ecDNA-amplified tumors for Boundless Bio's POTENTIATE Phase 1/2 study of BBI-355. • Precision for Medicine adapts its diagnostic workflow to integrate with the SOPHiA DDM™ Platform, enhancing patient selection for clinical trials. • The collaboration aims to expedite clinical trial enrollment and support the development of new ecDNA-directed therapies for cancer patients.