X0609 4 2026-06-09 0002022626 Upstream Bio, Inc. UPB 0001857250 Fleming Harold Edward false UPSTREAM BIO, INC. 890 WINTER STREET, SUITE 200 WALTHAM MA 02451 true false false false false Stock Option (Right to Buy) 6.69 2026-06-09 4 A false 17096 0 A 2036-06-08 Common Stock 17096 17096 D The shares underlying this option shall vest in full upon the earlier of (i) June 9, 2027 and (ii) the date of the next Annual Meeting of Stockholders of the Issuer, subject to the Reporting Person's continued service on such vesting date. Mr. Fleming has agreed to receive and hold for the benefit of Enavate Sciences, LP, any securities granted to him for his service as a director on the Issuer's board of directors. As such, Mr. Fleming disclaims beneficial ownership of, and all right, title and interest in, the option and the shares issuable upon exercise thereof. /s/ Allison Ambrose, Attorney-in-Fact 2026-06-11