SCHEDULE 13G/A 0001104659-25-012954 0001232258 XXXXXXXX LIVE 1 Common Stock, par value $0.001 per share 09/30/2025 0002022626 Upstream Bio, Inc. 91678A107 890 Winter Street Suite 200 Waltham MA 02451 Rule 13d-1(d) HBM Healthcare Investments (Cayman) Ltd. E9 2195111.00 0.00 2195111.00 0.00 2195111.00 N 4.1 CO Voting and investment power over the shares held by HBM Healthcare Investments (Cayman) Ltd. is exercised by the board of directors of HBM Healthcare Investments (Cayman) Ltd. (the "Board"). The Board consists of Jean-Marc LeSieur, Richard H. Coles, Sophia Harris, Dr. Andreas Wicki, Mark Kronenfeld, M.D., and Richard Paul Woodhouse, none of whom has individual voting or investment power with respect to the shares. Upstream Bio, Inc. 890 Winter Street, Suite 200, Waltham, MA, 02451 HBM Healthcare Investments (Cayman) Ltd. (the "Reporting Person") Governors Square, 23 Lime Tree Bay Avenue, PO Box 30852, Grand Cayman, KY1-1204, Cayman Islands Cayman Islands, British West Indies Y As of September 30, 2025, the Reporting Person may be deemed the beneficial owner of 2,195,111 shares of Common Stock, which represent approximately 4.1% of the shares of Common Stock outstanding. The percentage set forth herein is calculated based on 53,909,427 shares of Common Stock outstanding as of August 4, 2025, as reported in the Issuer's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on August 6, 2025. 4.1% 2,195,111 0 2,195,111 0 N Y Y Y Y Y Y HBM Healthcare Investments (Cayman) Ltd. /s/ Jean-Marc LeSieur 11/14/2025