Upstream Bio Inc 2025年度报告

UPSTREAM BIO, INC. 2025 ANNUAL REPORT UNITED STATESSECURITIES AND EXCHANGE COMMISSION (Mark One) ցANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934For the fiscal year ended December 31, 2025ORտTRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934For the transition period from _________________ to _________________Commission File Number: 001-42366 Upstream Bio, Inc.(Exact name of Registrant as specified in its charter) Registrant’s telephone number, including area code: (781) 208-2466 Securities registered pursuant to Section 12(b) of the Act: Title of each classTradingsymbol(s)Name of each exchange on which registeredCommon Stock, par value $0.001 per shareUPBThe Nasdaq Global Select Market Securities registered pursuant to Section 12(g) of the Act: None Indicate by check mark if the Registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. YESցNOտ Indicate by check mark whether the Registrant: (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during thepreceding 12 months (or for such shorter period that the Registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90days. YESցNOտ Indicate by check mark whether the Registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T(§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the Registrant was required to submit such files). YESցNOտ Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerginggrowth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company” and “emerging growth company” in Rule 12b-2 of theExchange Act. Large accelerated filerտNon-accelerated filerց Accelerated filerտSmaller reporting companyցEmerging growth companyց If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revisedfinancial accounting standards provided pursuant to Section 13(a) of the Exchange Act.տ Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness of its internal control overfinancial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its auditreport.տ If securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the filing reflect thecorrection of an error to previously issued financial statements.տ Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation received by any of theregistrant’s executive officers during the relevant recovery period pursuant to §240.10D-1(b).տ Indicate by check mark whether the Registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). YESտNOց As of June 30, 2025, the last business day of the Registrant’s most recently completed second fiscal quarter, the aggregate market value of the voting and non-votingcommon equity held by non-affiliates of the Registrant, based on the closing price of the shares of common stock on The Nasdaq Global Select Market on June 30,2025, was approximately $467,859,469. The number of shares of Registrant’s common stock outstanding as of March 20, 2026 was 54,419,986. Portions of the Registrant’s definitive proxy statement for its 2026 Annual Meeting of Stockholders to be filed pursuant to Regulation 14A within 120 days of the endof the Registrant’s fiscal year ended December 31, 2025 are incorporated by reference in Part III of this Annual Report on Form 10-K to the extent stated herein. Table of Contents PART I Item 1.Business3Item 1A.Risk Factors50Item 1B.Unresolved Staff Comments105Item 1C.Cybersecurity106Item 2.Properties106Item 3.Legal Proceedings106Item 4.Mine Safety Disclosures107 PART II Item 5.Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of EquitySecurities108Item 6.[Reserved]108Item 7.Management’s Discussion and Analysis of Financial Condition and Results of Operations109Item 7A.Quantitative and Qualitative Disclosures About Market Risk121Item 8.Financial Statements and Supplementary Data121Item 9.Changes in and Disagreements With Accountants on Accounting and Financial Disclosure121Item 9A.Controls and Procedures121Item 9B.Other Information122Item 9C.Disclosure Regarding Foreign Jurisdictions that Prevent Inspections122 PART III Item 10.Directors, Executive Officers and Corporate Governance123Item