Slide 1: Unlocking a New Paradigm in Cancer Treatment via ecDNA-Directed Therapies (ecDTx)
Unlocking a New Paradigm in Cancer Treatment via ecDNA-Directed Therapies (ecDTx) Corporate Presentation May 2026 Nasdaq: BOLD @BoundlessBio
Slide 2: Disclaimer: Forward-Looking Statements and Market Data
Disclaimer: Forward-Looking Statements and Market Data We caution you that this presentation contains forward-looking statements about us and our industry. All statements other than statements of historical facts contained in this presentation are forward-looking statements. These statements involve
Slide 3: Boundless Bio (BOLD): clinical-stage company addressing oncogene amplified cancers
Boundless Bio (BOLD): clinical-stage public company establishing a new category in oncology that addresses oncogene amplified cancers Oncogene amplified cancer: • Significant unmet medical need (worse survival) • Generally unresponsive to targeted therapy and immunotherapy • ~1.3M new patients per y
Slide 4: ecDNA are cancer-specific, circular units of DNA driving oncogene amplified cancer
ecDNA are cancer-specific, circular units of DNA that are a frequent driver of oncogene amplified cancer Altered oncogene Mutation Fusion ‣ ~14-18% of cancer patients have mutations or fusions OR ‣ 60+ FDA approved drugs NEXT FRONTIER OF ONCOLOGY ‣ ~$50B in annual sales globally Transformation to ca
Slide 5: Next-generation precision oncology pipeline for oncogene amplified cancer
Next-generation precision oncology pipeline to address high unmet needs in oncogene amplified cancer CIN/ecDNA GLOBAL TARGET ecDTx DISCOVERY IND - ENABLING PHASE 1/2 PHASE 3 INTERVENTION NODES RIGHTS SEGREGATION Kinesin BBI - 940 Patients with ER+/HER2 - BC and TNBC - LAR REPLICATION STRESS CHK1 BBI
Slide 6: Accomplished leadership team has proven experience delivering value
Accomplished leadership team has proven experience delivering value for patients and shareholders 5
Slide 7: Significant unmet need in oncogene amplified cancers
Significant unmet need in oncogene amplified cancers
Slide 8: Cancers with oncogene amplifications: more aggressive, difficult to treat, worse prognosis
Cancers with oncogene amplifications: more aggressive, difficult to treat, and worse prognosis Survival of cancer patients, PFS of cancer patients with FGFR alterations segmented by oncodriver status1 treated with FGFR inhibitors Oncogene amplified cancers • Oncogene amplification is an oncogenic al
Slide 9: Oncogene amplified cancers generally do not respond to targeted therapies
Despite advancements in precision medicine, cancers with oncogene amplifications generally do not respond to targeted therapies TARGETED THERAPY TARGET APPROVED NO APPROVAL CDK4/6 HR+/HER2- breast cancer X Amplification L858R NSCLC T790M NSCLC EGFR Exon 19 deletion NSCLC X Amplification Exon 20 inse
Slide 10: Improvements in cancer drugs drive increased resistance via oncogene amplification
Improvements in cancer drugs drive increased rates of resistance via oncogene amplification Patients with ≥ 1 amplification at resistance Indication Previous-gen inhibitors Next-gen inhibitors References EGFR-mutated non-small cell erlotinib or gefitinib osimertinib Chmielecki et al., Nat Comm (2023
Slide 11: ecDNA: a key driver of oncogene amplifications
ecDNA: a key driver of oncogene amplifications
Slide 12: ecDNA are a primary driver of oncogene amplified cancers and enable resistance
ecDNA are a primary driver of oncogene amplified cancers and enable resistance to targeted therapies ecDNA are circles of DNA, Circular shape of ecDNA enhances ecDNA asymmetrically segregate during mitosis, distinct from chromosomes, transcriptional activity, leading to enabling exponential gene cop
Slide 13: Multiple clinical datasets show ecDNA detected broadly across cancers
Multiple clinical datasets demonstrate that ecDNA are detected broadly across cancers ecDNA are not found in normal tissue or blood ecDNA prevalence across tumor types; early-stage patients Pan-cancer Normal Samples 100 100 • ecDNA are present in 75 75 14-17% of cancer specimens at diagnosis, across
Slide 14: Common high copy number amplifications frequently occur on ecDNA, linked to worse survival
Cancer’s most common high copy number oncogene amplifications frequently occur on ecDNA; when they do, it is associated with worse survival ~54% of high-copy number oncogene Patients with oncogene amplification on amplifications are detected on ecDNA ecDNA have worse survival Most frequently amplifi
Slide 15: ecDNA oncogene amplifications are a frequent mechanism of clinical resistance
Oncogene amplifications on ecDNA are a frequent mechanism of clinical resistance to multiple therapeutic modalities INITIAL ONCOGENE CANCER DRIVER CLINICAL THERAPY ONCOGENE AMPLIFICATION DRIVING RECURRENCE NSCLC • ALKfusion • Wang 2019 J Hem Onc Takezawa 2012 Canc Disc EGFRmut KRAS • ALK, EGFR, ROS1
Slide 16: ecDNA enable cancer cells to become resistant by rapidly adapting oncogene dependency
ecDNA enable cancer cells to become resistant to therapies by rapidly adapting oncogene dependency Cell viability over time FGFR inhibitor resistant gastric cancer cells Gastric cancer cells pre-treatment FGFR inhibitor Days of FGFR2 inhibition (infigratinib) EGFR MYC Oncogene copy number over time
Slide 17: Tumors employ ecDNA to rapidly enable new oncogenic drivers
Tumors employ ecDNA to rapidly enable new oncogenic drivers, even under combination target inhibition Oncogene copy on ecDNA changes dynamically New oncogene populations can arise on ecDNA in response to sequential targeted therapeutic pressure in response to combination targeted therapeutic pressur
Slide 18: Driving a new treatment paradigm by targeting ecDNA pathways
Driving a new treatment paradigm by targeting ecDNA pathways that enable tumor evolution and resistance Traditional Targeted Therapy: Next Generation Precision Oncology: Develop targeted inhibitors against activated oncodriver Exploit underlying vulnerabilities in ecDNA-driven cells targets, but cel
Slide 19: Spyglass: platform that interrogates ecDNA biology to identify synthetic lethal targets
Spyglass: unique platform that interrogates ecDNA biology to identify synthetic lethal targets in cancer Proprietary target and drug discovery engine 18
Slide 20: Spyglass reveals cancer targets intersecting distinct nodes of ecDNA lifecycle
Spyglass reveals cancer targets, both novel and validated, that intersect distinct nodes of ecDNA lifecycle CHK1 BBI-355 Novel, oral, selective inhibitor of CHK1 Kinesin CHK1 is master regulator of replication stress, including that induced by ecDNA BBI-940 (Phase 1 clinical) Novel, oral, selective
Slide 21: BBI-940: novel Kinesin oral degrader
BBI-940: novel Kinesin oral degrader Targets DNA segregation in cancer
Slide 22: Spyglass screening identified Kinesin as an ecDNA-associated target
Spyglass screening identified Kinesin as an ecDNA-associated target BBI ecDNA target ranking DepMap ecDNA selective dependency classification Heuristic scoring method combining internal ecDNA classifier status data sets with large public resources identifying genes and pathways critical for ecDNA-hi
Slide 23: Kinesin regulates DNA segregation and viability of ecDNA dependent cells
Kinesin regulates DNA segregation and the viability of ecDNA dependent cells ecDNA (no centromere) • Chromosome segregation is primarily dependent on interactions between the mitotic spindle microtubules and the centromere chromosome • ecDNA lack centromeres and likely rely on distinct mitotic centr
Slide 24: Kinesin knockdown caused ecDNA mis-segregation and reduced ecDNA levels
Genetic knockdown of Kinesin resulted in mis-segregation of ecDNA during mitosis and reduced cellular ecDNA levels over time ecDNA displayed a “lagging” phenotype Knock down of kinesin led to reduced Model for during mitosis in the absence of Kinesin levels of ecDNA in cancer cells Kinesin inhibitio
Slide 25: Genetic inactivation of Kinesin caused anti-proliferation of amplified tumor cell lines
Genetic inactivation of Kinesin resulted in significant anti-proliferation of oncogene amplified tumor cell lines ecDNA- FGFR2 ecDNA+ Therapy: No drug No drug +FGFRi Anti-tumor activity in MYCN amplified cancer cell line shControl ishNT ishKinesin shKinesin Days Kinesin KD resulted in significant re
Slide 26: Kinesin inhibitor scaffold identified and optimized into potent degraders
Boundless identified a Kinesin inhibitor scaffold via high-throughput screens of >1M compounds Extensive medicinal chemistry effort optimized potent, cell-active, heterobifunctional degraders HTS/HTL Inhibitor/ligand SAR Degrader optimization • nM inhibitors • nM heterobifunctional degraders uM bioc
Slide 27: BBI-940 is a novel Kinesin oral degrader
BBI-940 is a novel Kinesin oral degrader Product Preclinical Property TPP BBI-940 Oral Druggable Space beyond Lipinski’s Rule of Five* Route of administration Oral PO bioavailability (mouse/rat/dog) >20% In vitro potency (HiBit DC50/DC90, Dmax%) <10nM/<100nM, >90% CYPi >1uM hERG >1000x over target K
Slide 28: BBI-940 showed strong binding, potent inhibition and degradation of Kinesin
BBI-940 demonstrated strong binding, potent inhibition, and remarkable degradation of Kinesin target, with favorable kinetics Binding affinity over time Max Kinesin degradation achieved by 2 hr Nearcomplete Near complete resynthesis Kinesin byby6 6hrhr resynthesis BBI-940 100 BBI-769 24h 7769 Only B
Slide 29: BBI-940 degraded Kinesin with selectivity over other kinesins and targets
BBI-940 degraded cellular Kinesin with exquisite selectivity over other kinesins and cellular targets ▪ BBI-940 elicited rapid and selective degradation of only Kinesin in human breast cancer cell line Differentially expressed proteins after treatment with BBI-940 ▪ BBI-940 demonstrated selectivity
Slide 30: Cell line screen identified tumor types sensitive to Kinesin degradation
Cancer cell line screen identified multiple tumor types with high sensitivity to Kinesin degradation, including breast cancer Sensitivity correlation (by AUC) across key indications (N ~ 800) Kinesin degrader sensitivity (AUC) Breast OncoTree Lineage of Tumor types cancer ~15% of cell lines sensitiv
Slide 31: Sensitivity to Kinesin degradation in breast cancer lines correlates with ecDNA status
In vitro sensitivity to Kinesin degradation in breast cancer cell lines is correlated with ecDNA status Cancer cell line sensitivity to Kinesin degradation Cancer cell line sensitivity to Kinesin degradation segmented by ecDNA status segmented by FGFR1 and ecDNA status • Breast cancer cell lines wer
Slide 32: BBI-940 induced tumor regressions as single agent in breast cancer CDX model
BBI-940 induced tumor regressions as a single agent in breast cancer CDX in vivo model HCC 1187 HCC 1187 HCC 1187 HCC 1187 DNA staining of metaphase spread HCC 1187 Tumor volume over time in TNBC-LAR CDX HCC 1187 Body weight over time HCC 1187 1500 1500 1500 Body Weight Change (%) Body Weight Change
Slide 33: Steady state PK/PD of BBI-940 tracked with anti-tumor activity in mice
Steady state PK/PD of BBI-940 tracked with anti-tumor activity in tumor bearing mice Kinesin degradation at BBI-940 doses vs. time Kinesin % Degradation to Vehicle Control Vinculin * Kinesin Vinculin Kinesin Vinculin *Approximate level of degradation required for maximal TGI • Orally administered BB
Slide 34: BBI-940 well tolerated in 28-day GLP-toxicity studies in rat and dog
BBI-940 was well tolerated in 28-day GLP-toxicity and toxicokinetic studies in rat and dog • No deaths • No dose-related findings in: Plasma concentration of BBI-940 in Dog GLP Study, Day 28 - Body weight or food consumption - Cage-side observations or clinical exams Low dose (mg/kg/day) BBI-940 pla
Slide 35: First-in-human Phase 1 study of BBI-940 in metastatic breast cancer
First-in-human, phase 1 study of BBI-940 in metastatic breast cancer Kinesin Oral Molecular Degrader for Oncology (KOMODO-1) Phase 1 Dose Escalation (Part 1A,B) Phase 1 Expansion (Part 2A,B,C) (n=16-40) (n=44-56) 1A 1B 2A 2B 2C Dose Escalation Backfill 2B or 2C : Expand to biomarker cohorts after MT
Slide 36: BBI-940 summary: first-in-class Kinesin degrader advancing in the clinic
BBI-940 summary: first-in-class Kinesin degrader advancing in the clinic Novel Kinesin BBI-940 (Phase 1 clinical) • Potentially first-in-class, oral, selective Kinesin degrader • Kinesin is a novel cancer target essential for ecDNA segregation but non-essential for normal chromosome segregation • In
Slide 37: Boundless Bio: leading a new area of cancer biology and targeting a large unmet need
Boundless Bio: leading a new area of cancer biology and targeting a large unmet need
Slide 38: Boundless has identified additional novel ecDNA targets for ecDTx discovery
Boundless has identified additional novel ecDNA targets for ecDTx discovery efforts Target D: epigenetic regulator Stage: Hit to Lead Selective molecular glue degrader New discovery targets: Target A: ubiquitin enzyme Stage: Hit Identification Target B: Kinesin interactor Stage: Assay Development Ta
Slide 39: Boundless Bio is leading a differentiated approach to oncogene amplified cancers
Boundless Bio is leading a compelling and differentiated approach to address oncogene amplified cancers Dedicated to • Oncogene amplifications: one of cancer’s highest unmet medical needs; expansive addressable market Oncogene Amplified • ecDNA: a root cause of amplification; Boundless Bio’s unique
Slide 40: Boundless Bio: a breakthrough biotech company leading the next wave of innovation in cancer treatment
Boundless Bio: a breakthrough biotech company leading the next wave of innovation in cancer treatment 39
Slide 41: Unbound by convention, bound to save lives
Unbound by convention, bound to save lives www.boundlessbio.com @BoundlessBio
Slide 42: Bibliography of recent reviews and publications covering ecDNA
Bibliography of recent reviews and publications covering ecDNA—active hyperlinks 2025 Paul Mischel, Howard Chang Nature: Genetic elements promote retention of extrachromosomal DNA in cancer cells 2025 Lillian Siu NEJM: Extrachromosomal DNA – Amping Up Cancer 2024 Paul Mischel, Howard Chang Nature: E