Summary of Boundless Bio (BOLD) Update / Briefing May 27, 2025 Company Overview - **Company**: Boundless Bio (BOLD) - **Focus**: Development of therapies for oncogene amplified cancers, particularly through the study of extrachromosomal DNA (e cDNA) biology [5][6] Key Industry Insights - **Industry Context**: The biotechnology sector is facing challenges in securing funding and establishing differentiation due to a proliferation of competitor compounds [38] - **Market Considerations**: The company is prioritizing first-in-class drugs against innovative biological targets to maintain a competitive edge [38] Core Points and Arguments 1. **Portfolio Prioritization**: Boundless Bio has decided to discontinue all current arms of the BBI-355 clinical trial due to clinical observations and market considerations, shifting focus to a new trial arm evaluating BBI-355 in combination with BBI-825 [3][4] 2. **Workforce Reduction**: The company has streamlined operations, reducing its workforce by approximately 20 positions, representing about one-third of its staff, to extend its cash runway into the first half of 2028 [4][36] 3. **Development Candidates**: BBI-940 has been declared a development candidate for the novel kinesin oral degrader program, with an IND filing expected in the first half of 2026 [4][36] 4. **Clinical Findings**: BBI-355 has shown evidence of anti-tumor activity but has a narrow therapeutic index due to on-target hematologic toxicity, leading to the decision not to advance certain clinical arms [12][14] 5. **Combination Therapy Rationale**: The combination of BBI-355 and BBI-825 is believed to provide synergistic anti-tumor activity while minimizing hematologic toxicity, with plans to initiate clinical development in 2025 [28][29] Additional Important Content - **Scientific Basis**: The company has developed a proprietary SpyGlass platform to identify new targets in e cDNA biology, leading to the discovery of three druggable targets that may be synthetic lethal in oncogene amplified tumors [5][6] - **Clinical Strategy**: The combination of BBI-355 and BBI-825 is expected to leverage the unique mechanisms of both drugs, potentially overcoming the limitations observed when each is used independently [20][28] - **Preclinical Data**: BBI-940 has demonstrated potent anti-tumor activity in preclinical models, with favorable pharmacokinetics and oral bioavailability [33][34] - **Future Outlook**: The company is focused on achieving important clinical readout milestones and believes it is uniquely positioned with proprietary selective inhibitors [39][70] Financial Guidance - **Cash Runway**: The changes in operations and portfolio prioritization are expected to extend the company's cash runway into the first half of 2028, aligning with anticipated clinical readouts [36][37]

"IDE849 is a potential first-in-class DLL3 TOP1 ADC, a target antigen that has demonstrated preliminary monotherapy clinical validation in SCLC. In addition, IDE849 aligns with our strategy to develop rational combination therapies, particularly with our potential first-in-class Phase 1 PARG inhibitor IDE161, where we have generated preclinical combination data with TOP1-based ADCs that demonstrates combination synergy and enhanced durability," said Dr. Darrin M. Beaupre, M.D., Ph.D., Chief Medical Officer, ...