Part I Business Boundless Bio develops ecDNA-targeted oncology therapies, with lead candidate BBI-355 in Phase 1/2 trials, leveraging its Spyglass platform and ECHO diagnostic Overview Boundless Bio develops ecDNA-directed oncology therapies, with lead candidate BBI-355 in Phase 1/2 trials and a Kinesin program advancing - The company's mission is to develop transformative therapies for patients with intractable oncogene amplified cancers by interrogating ecDNA biology22 - Lead candidate BBI-355, a CHK1 inhibitor, is in a Phase 1/2 trial (POTENTIATE) for oncogene amplified cancers, with preliminary data expected in H2 202524 - The Kinesin program is advancing, with a development candidate nomination expected by mid-2025 and an IND submission planned for H1 202624 - The company strategically discontinued the BBI-825 program in December 2024 after assessing preliminary pharmacokinetic data from its Phase 1/2 STARMAP trial25 - The proprietary ECHO diagnostic is being used as a clinical trial assay to detect ecDNA and select patients for the BBI-355 POTENTIATE trial26 Unmet Need and Role of ecDNA in Cancer Oncogene amplification, driven by ecDNA in 14-17% of cancers, leads to poor survival and rapid therapeutic resistance, highlighting a critical unmet need - Patients with oncogene amplified tumors have significantly worse survival rates compared to those with mutations or fusions of the same oncogenes5051 - Standard targeted therapies, such as CDK4/6 and FGFR inhibitors, have demonstrated poor overall response rates in patients with corresponding gene amplifications57 - ecDNA is a primary driver of oncogenesis, found in 14-17% of cancer patients, and is associated with even worse survival outcomes than other forms of oncogene amplification697680 - ecDNA facilitates rapid therapeutic resistance by enabling genomic plasticity, such as oncogene switching or amplifying resistance genes like KRAS G12C788389 Our Approach and Spyglass Platform Boundless Bio targets ecDNA function using its Spyglass platform, identifying synthetic lethal vulnerabilities in oncogene amplified tumors - The company's strategy is to inhibit cellular machinery essential for ecDNA function (e.g., replication, segregation), creating a synthetic lethal effect in cancer cells reliant on ecDNA9293 - The Spyglass platform is a proprietary system for identifying and validating ecDNA-related drug targets9597 - Spyglass utilizes a library of ~2,000 cancer models (~300 in-house), specialized analytical tools (including CRISPR and imaging), and extensive bioinformatics data to identify vulnerabilities98102 - The platform has identified multiple potential targets across the ecDNA life cycle, including those involved in segregation, replication, transcription, and repair105 Our Pipeline of ecDNA-Directed Therapeutic Candidates The pipeline features BBI-355 (CHK1 inhibitor) in Phase 1/2, a Kinesin program, and the ECHO diagnostic for patient selection - The pipeline includes BBI-355 (CHK1 inhibitor), a Kinesin program, and BBI-098 (CNS-penetrant CHK1 inhibitor), all discovered internally via the Spyglass platform110112116 - BBI-355 is an oral, selective CHK1 inhibitor designed to exploit elevated replication stress in ecDNA-enabled cancer cells. Preliminary clinical data from the POTENTIATE trial is expected in H2 2025113127 - Preliminary Phase 1 data for BBI-355 showed good oral bioavailability, target engagement (pCHK1 reduction), and stable disease in 5 of 18 evaluable subjects, with one patient showing ~20% tumor regression160163166 - The Kinesin program targets a novel kinesin essential for ecDNA segregation. The company has developed oral nanomolar degraders and expects to nominate a development candidate by mid-2025 and submit an IND in H1 2026183 - BBI-098 is a second, CNS-penetrant CHK1 inhibitor nominated as a development candidate, potentially for CNS indications like glioblastoma176 Competition The company faces competition from major biopharma and biotech firms, including clinical-stage CHK1 inhibitors and other ecDNA researchers - The company faces broad competition from entities developing precision oncology therapies and treatments based on synthetic lethality188 - Direct competitors for the BBI-355 CHK1 inhibitor program include Acrivon Therapeutics, Esperas Pharma, Sumitomo Pharma, and PharmaEngine, all of whom have CHK1 inhibitors in clinical development190 - While Boundless Bio is a leader in ecDNA-directed therapeutics, it notes Econic Biosciences as another early-stage company focused on ecDNA research191 Intellectual Property The IP portfolio includes 25 patent families covering CHK1 inhibitors and the ECHO diagnostic, with expirations between 2041-2045 - As of March 27, 2025, the company's IP portfolio includes 25 solely owned patent families, with 4 issued U.S. patents and 14 pending U.S. non-provisional applications194 - The CHK1 program (BBI-355, BBI-098) is protected by 10 patent families, with expected patent expirations in 2041-2045197 - The precision medicine program, including the ECHO diagnostic, is covered by patent families with expected expirations in 2041-2044198 - The company also protects its technology through trade secrets and has registered trademarks for "Boundless Bio" and "ECHO" in the U.S. and other jurisdictions203204 Manufacturing, Commercialization, and Regulation The company outsources manufacturing, plans internal commercialization, and navigates extensive FDA regulations for therapeutics and companion diagnostics - The company does not own or operate manufacturing facilities and relies entirely on third-party contract manufacturers for its ecDTx supply205 - Boundless Bio plans to build its own sales and marketing infrastructure to commercialize approved products in the U.S. and other key markets207 - The company's operations are subject to extensive regulation by the FDA, including requirements for preclinical studies (GLP), clinical trials (IND, GCP), and manufacturing (cGMP) before an NDA can be submitted for approval208211 - The company may pursue expedited FDA programs like Fast Track, Breakthrough Therapy, or Accelerated Approval to speed up development and review227228230 - Development of a companion diagnostic, like ECHO, is also regulated by the FDA as a medical device, likely requiring a Premarket Approval (PMA) to be approved contemporaneously with the therapeutic product240241 Human Capital and Corporate Information As of March 21, 2025, Boundless Bio had 64 employees, with 47 in R&D, and was founded in 2018 as Pretzel Therapeutics - As of March 21, 2025, the company had 64 full-time employees, with 47 dedicated to R&D262 - The company was founded on April 10, 2018, as Pretzel Therapeutics, Inc. and changed its name to Boundless Bio, Inc. on July 8, 2019265 Risk Factors The company faces significant financial losses, unproven novel science, clinical trial uncertainties, reliance on third parties, and intense competition - Financial Risks: The company has a history of significant losses ($65.4M in 2024) and expects them to continue. It will require substantial additional capital to fund operations, and failure to secure it could force delays or termination of programs273275 - Development & Regulatory Risks: The company's ecDNA-targeting approach is novel and unproven. Clinical trials are long and expensive with uncertain outcomes. The lead candidate, BBI-355, could fail, and development of a necessary companion diagnostic (ECHO) faces its own regulatory and technical hurdles287292316 - Reliance on Third Parties: Boundless Bio depends on third parties for manufacturing its ecDTx and conducting clinical trials. Poor performance by these partners could significantly delay development and commercialization344347 - Commercialization Risks: The company faces significant competition from well-funded pharmaceutical companies. Success depends on market acceptance, securing adequate reimbursement from payors, and building a commercial organization, none of which is guaranteed363368375 - Intellectual Property Risks: The ability to obtain, maintain, and enforce patents is critical and uncertain. Patents may be challenged, invalidated, or circumvented by competitors432 Unresolved Staff Comments The company reports no unresolved staff comments from the SEC - None520 Cybersecurity The company's cybersecurity program, guided by NIST, is overseen by the Audit Committee, with no material risks identified to date - The company's cybersecurity risk management program is based on the NIST Cybersecurity Framework principles (Identify, Protect, Detect, Respond, Recover)521 - Oversight is provided by the Audit Committee of the Board of Directors, which receives periodic reports from management524 - As of the filing date, no known cybersecurity threats or incidents have had a material impact on the company523 Properties The company leases 80,168 square feet of headquarters space in San Diego, California, under a lease expiring in October 2034 - The company leases approximately 80,168 square feet of laboratory and office space in San Diego, California527 - The current lease expires in October 2034527 Legal Proceedings There are no material pending legal proceedings involving the company or its property - There is no material pending legal proceeding to which the company is a party528 Mine Safety Disclosures This item is not applicable to the company - Not applicable529 Part II Market for Registrant's Common Equity, Related Stockholder Matters, and Issuer Purchases of Equity Securities Common stock began trading on Nasdaq in March 2024; the company has never paid dividends and reallocated IPO proceeds to advance its pipeline - Common stock began trading on Nasdaq under the symbol "BOLD" on March 28, 2024532 - The company has never paid dividends and does not intend to in the foreseeable future534 - The IPO on April 2, 2024, generated net proceeds of approximately $87.7 million538 - Use of IPO proceeds has been updated: funds from the discontinued BBI-825 program will be reallocated to advance BBI-355, the Kinesin program, and for general corporate purposes539540 Reserved This item is reserved Management's Discussion and Analysis of Financial Condition and Results of Operations The company reported a $65.4 million net loss in 2024, with $152.1 million cash expected to fund operations into 2027, requiring future capital Results of Operations Net loss increased to $65.4 million in 2024 due to higher R&D and G&A expenses, partially offset by increased interest income Results of Operations (in thousands) | | Year Ended December 31, | | Change | | :--- | :--- | :--- | :--- | | | 2024 | 2023 | Amount | | Research and development | $55,267 | $42,637 | $12,630 | | General and administrative | $18,000 | $12,159 | $5,841 | | Total operating expenses | $73,267 | $54,796 | $18,471 | | Loss from operations | ($73,267) | ($54,796) | ($18,471) | | Total other income, net | $7,904 | $5,362 | $2,542 | | Net loss | ($65,363) | ($49,434) | ($15,929) | - R&D expenses increased by $12.6 million, primarily due to a $9.2 million rise in direct program costs for the BBI-355 and BBI-825 clinical trials, alongside higher personnel and stock compensation costs571 - G&A expenses increased by $5.8 million, driven by a $2.6 million increase in stock-based compensation, a $1.2 million rise in personnel costs, and a $0.8 million increase in costs related to operating as a public company572573 Liquidity and Capital Resources As of December 31, 2024, the company had $152.1 million in cash, expected to fund operations into 2027, but requires substantial future funding - As of December 31, 2024, the company held $152.1 million in cash, cash equivalents, and short-term investments576 - Current cash position is expected to fund operations into 2027576 Cash Flow Summary (in thousands) | | Year Ended December 31, | Change | | :--- | :--- | :--- | :--- | | | 2024 | 2023 | Amount | | Net cash used in operating activities | ($60,841) | ($46,855) | ($13,986) | | Net cash used in investing activities | ($26,101) | ($38,260) | $12,159 | | Net cash provided by financing activities | $89,823 | $97,897 | ($8,074) | - The company has future aggregate operating lease commitments of $72.5 million, expiring in October 2034586 Critical Accounting Policies and Estimates Critical accounting policies include estimating accrued R&D expenses and valuing stock-based compensation, both requiring significant judgment - Accrued R&D Expenses: The company is required to estimate expenses for services performed by third-party vendors (e.g., CROs) before invoices are received. This involves estimating the level of service completed based on contracts and communication with personnel591592 - Stock-Based Compensation: The company uses the Black-Scholes model to determine the fair value of equity awards. This requires subjective assumptions for expected term, volatility, and risk-free rate. Prior to the IPO, determining the fair value of the company's common stock was also a critical estimate595596 Quantitative and Qualitative Disclosures About Market Risk The company faces minimal interest rate or foreign currency risk due to short-term investments and limited international contracts - Interest rate risk on the company's cash and short-term investments is not considered significant due to the short-term nature of the portfolio603 - Foreign currency exchange risk from contracts with overseas vendors is considered negligible, and the company does not engage in hedging604 - Inflation is not believed to have had a material effect on the company's results of operations606 Financial Statements and Supplementary Data Financial statements and the independent auditor's report are included starting on page F-1 of the Form 10-K - The company's financial statements and the auditor's report are located at the end of the report, beginning on page F-1607 Changes in and Disagreements with Accountants on Accounting and Financial Disclosure The company reports no changes in or disagreements with its accountants on accounting and financial disclosure - None608 Controls and Procedures Disclosure controls were effective as of December 31, 2024, with no material changes to internal controls during the quarter - Management concluded that disclosure controls and procedures were effective as of December 31, 2024610 - A management report on internal control over financial reporting is not included due to the transition period for newly public companies611 - No material changes were made to internal control over financial reporting during the quarter ended December 31, 2024612 Other Information SVP of Finance adopted a 10b5-1 plan, while the former CFO terminated her plan in Q4 2024 - On December 27, 2024, David Hinkle (SVP, Finance) adopted a Rule 10b5-1 trading plan covering 12,000 shares, expiring December 31, 2025614 - On October 18, 2024, former CFO Jami Rubin terminated her trading plan following her departure from the company614617 Disclosure Regarding Foreign Jurisdictions that Prevent Inspections This item is not applicable - None615 Part III Directors, Executive Officers, and Corporate Governance Information on directors, executive officers, and corporate governance is incorporated by reference from the 2025 proxy statement - Information is incorporated by reference from the definitive proxy statement for the 2025 Annual Meeting of Stockholders619 Executive Compensation Executive compensation information is incorporated by reference from the 2025 proxy statement - Information is incorporated by reference from the definitive proxy statement for the 2025 Annual Meeting of Stockholders620 Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters Security ownership and equity compensation plan details are incorporated by reference from the 2025 proxy statement - Information is incorporated by reference from the definitive proxy statement for the 2025 Annual Meeting of Stockholders621 Certain Relationships and Related Transactions, and Director Independence Related person transactions and director independence information is incorporated by reference from the 2025 proxy statement - Information is incorporated by reference from the definitive proxy statement for the 2025 Annual Meeting of Stockholders622 Principal Accountant Fees and Services Principal accountant fees and services information is incorporated by reference from the 2025 proxy statement; KPMG LLP is the auditor - Information is incorporated by reference from the definitive proxy statement for the 2025 Annual Meeting of Stockholders623 - The company's independent public accounting firm is KPMG LLP623 Part IV Exhibits and Financial Statement Schedules This section provides an index of all exhibits filed with or incorporated by reference into the Form 10-K - This section contains the Exhibit Index, listing all documents filed as part of the report626627 Form 10-K Summary The company indicates that no Form 10-K summary is provided - None631 Financial Statements Report of Independent Registered Public Accounting Firm KPMG LLP issued an unqualified opinion on the 2024 and 2023 financial statements, without an opinion on internal controls - KPMG LLP provided an unqualified audit opinion on the financial statements for the years ended December 31, 2024 and 2023644 - The audit was conducted in accordance with PCAOB standards. An audit of internal control over financial reporting was not performed as it was not required646 Financial Statements Data Financial statements show a $65.4 million net loss in 2024, increased assets from IPO proceeds, and a shift to positive equity Balance Sheet Data (in thousands) | | Dec 31, 2024 | Dec 31, 2023 | | :--- | :--- | :--- | | Total Assets | $206,409 | $129,894 | | Cash, cash equivalents, & short-term investments | $152,114 | $120,752 | | Total Liabilities | $55,767 | $9,359 | | Total stockholders' equity / (deficit) | $150,642 | ($127,082) | Statement of Operations Data (in thousands) | | Year Ended Dec 31, 2024 | Year Ended Dec 31, 2023 | | :--- | :--- | :--- | | Research and development | $55,267 | $42,637 | | General and administrative | $18,000 | $12,159 | | Loss from operations | ($73,267) | ($54,796) | | Net loss | ($65,363) | ($49,434) | | Net loss per share | ($3.85) | ($40.65) | Notes to Financial Statements Notes detail the April 2024 IPO, a March 2024 reverse stock split, lease commitments, stock-based compensation, and NOL carryforwards - The company completed its IPO on April 2, 2024, raising net proceeds of approximately $87.7 million. All convertible preferred stock was converted to common stock662 - A 1-for-19.5 reverse stock split was effected on March 19, 2024, and all share data has been retroactively adjusted664 - The company entered into a new 120-month lease (the 2024 Lease) for its headquarters, which commenced in November 2024 and has total minimum lease payments of $72.5 million728729 - In August 2024, the company repriced outstanding stock options, reducing the exercise price to $3.56 per share, resulting in $857,000 of incremental stock-based compensation expense to be recognized over time742745 - As of Dec 31, 2024, the company had federal NOL carryforwards of $91.9 million and state NOLs of $183.3 million, but a full valuation allowance is recorded against these deferred tax assets759
Boundless Bio, Inc.(BOLD) - 2024 Q4 - Annual Report