X0609 4 2026-09-16 0002022626 Upstream Bio, Inc. UPB 0002031691 Houghton Adam false UPSTREAM BIO, INC. 890 WINTER STREET, SUITE 200 WALTHAM MA 02451 false true false false Chief Business Officer false Common Stock 2026-09-16 4 S false 700 5.49 D 22901 D The Issuer has adopted a "sell-to-cover" policy to satisfy the tax withholding obligations of the Reporting Person. The sales reported on this Form 4 represent the number of shares required to be sold by the Reporting Person to cover tax withholding obligations in connection with the vesting of restricted stock units. Such sales were automatic and not at the discretion of the Reporting Person. /s/ Allison Ambrose, Attorney-in-Fact 2026-09-17