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    Amendment: SEC Form SCHEDULE 13G/A filed by Upstream Bio Inc.

    8/6/25 12:19:41 PM ET
    $UPB
    Biotechnology: Pharmaceutical Preparations
    Health Care
    Get the next $UPB alert in real time by email



    SECURITIES AND EXCHANGE COMMISSION
    Washington, D.C. 20549


    SCHEDULE 13G


    UNDER THE SECURITIES EXCHANGE ACT OF 1934
    (Amendment No. 2)


    UPSTREAM BIO INC

    (Name of Issuer)


    COMMON STOCK

    (Title of Class of Securities)


    91678A107

    (CUSIP Number)


    06/30/2025

    (Date of Event Which Requires Filing of this Statement)


    Check the appropriate box to designate the rule pursuant to which this Schedule is filed:
    Checkbox checked   Rule 13d-1(b)
    Checkbox not checked   Rule 13d-1(c)
    Checkbox not checked   Rule 13d-1(d)






    SCHEDULE 13G

    CUSIP No.
    91678A107


    1Names of Reporting Persons

    FMR LLC
    2Check the appropriate box if a member of a Group (see instructions)

    Checkbox not checked  (a)
    Checkbox not checked  (b)
    3Sec Use Only
    4Citizenship or Place of Organization

    DELAWARE
    Number of Shares Beneficially Owned by Each Reporting Person With:
    5Sole Voting Power

    7,935,525.00
    6Shared Voting Power

    0.00
    7Sole Dispositive Power

    7,936,880.31
    8Shared Dispositive Power

    0.00
    9Aggregate Amount Beneficially Owned by Each Reporting Person

    7,936,880.31
    10Check box if the aggregate amount in row (9) excludes certain shares (See Instructions)

    Checkbox not checked
    11Percent of class represented by amount in row (9)

    14.8 %
    12Type of Reporting Person (See Instructions)

    HC


    SCHEDULE 13G

    CUSIP No.
    91678A107


    1Names of Reporting Persons

    Abigail P. Johnson
    2Check the appropriate box if a member of a Group (see instructions)

    Checkbox not checked  (a)
    Checkbox not checked  (b)
    3Sec Use Only
    4Citizenship or Place of Organization

    UNITED STATES
    Number of Shares Beneficially Owned by Each Reporting Person With:
    5Sole Voting Power

    0.00
    6Shared Voting Power

    0.00
    7Sole Dispositive Power

    7,936,880.31
    8Shared Dispositive Power

    0.00
    9Aggregate Amount Beneficially Owned by Each Reporting Person

    7,936,880.31
    10Check box if the aggregate amount in row (9) excludes certain shares (See Instructions)

    Checkbox not checked
    11Percent of class represented by amount in row (9)

    14.8 %
    12Type of Reporting Person (See Instructions)

    IN


    SCHEDULE 13G

    Item 1. 
    (a)Name of issuer:

    UPSTREAM BIO INC
    (b)Address of issuer's principal executive offices:

    890 WINTER STREET,SUITE 200,WALTHAM,MA,USA,02451
    Item 2. 
    (a)Name of person filing:

    FMR LLC
    (b)Address or principal business office or, if none, residence:

    245 Summer Street, Boston, Massachusetts 02210
    (c)Citizenship:

    Not applicable
    (d)Title of class of securities:

    COMMON STOCK
    (e)CUSIP No.:

    91678A107
    Item 3.If this statement is filed pursuant to §§ 240.13d-1(b) or 240.13d-2(b) or (c), check whether the person filing is a:
    (a)Checkbox not checked   Broker or dealer registered under section 15 of the Act (15 U.S.C. 78o);
    (b)Checkbox not checked   Bank as defined in section 3(a)(6) of the Act (15 U.S.C. 78c);
    (c)Checkbox not checked   Insurance company as defined in section 3(a)(19) of the Act (15 U.S.C. 78c);
    (d)Checkbox not checked   Investment company registered under section 8 of the Investment Company Act of 1940 (15 U.S.C. 80a-8);
    (e)Checkbox not checked   An investment adviser in accordance with § 240.13d-1(b)(1)(ii)(E);
    (f)Checkbox not checked   An employee benefit plan or endowment fund in accordance with § 240.13d-1(b)(1)(ii)(F);
    (g)Checkbox checked   A parent holding company or control person in accordance with § 240.13d-1(b)(1)(ii)(G);
    (h)Checkbox not checked   A savings associations as defined in Section 3(b) of the Federal Deposit Insurance Act (12 U.S.C. 1813);
    (i)Checkbox not checked   A church plan that is excluded from the definition of an investment company under section 3(c)(14) of the Investment Company Act of 1940 (15 U.S.C. 80a-3);
    (j)Checkbox not checked   A non-U.S. institution in accordance with § 240.13d-1(b)(1)(ii)(J). If filing as a non-U.S. institution in accordance with § 240.13d-1(b)(1)(ii)(J),
           please specify the type of institution:
    (k)Checkbox not checked   Group, in accordance with Rule 240.13d-1(b)(1)(ii)(K).
     
    Item 4.Ownership
    (a)Amount beneficially owned:

    7936880.31
    (b)Percent of class:

    14.8  %
    (c)Number of shares as to which the person has:
     (i) Sole power to vote or to direct the vote:

    Please see the responses to Items 5 and 6 on the cover page.

     (ii) Shared power to vote or to direct the vote:

    0.00

     (iii) Sole power to dispose or to direct the disposition of:

    7936880.31

     (iv) Shared power to dispose or to direct the disposition of:

    0.00

    Item 5.Ownership of 5 Percent or Less of a Class.
     
    Item 6.Ownership of more than 5 Percent on Behalf of Another Person.
     
    If any other person is known to have the right to receive or the power to direct the receipt of dividends from, or the proceeds from the sale of, such securities, a statement to that effect should be included in response to this item and, if such interest relates to more than 5 percent of the class, such person should be identified. A listing of the shareholders of an investment company registered under the Investment Company Act of 1940 or the beneficiaries of employee benefit plan, pension fund or endowment fund is not required.


    One or more other persons are known to have the right to receive or the power to direct the receipt of dividends from, or the proceeds from the sale of, the COMMON STOCK of UPSTREAM BIO INC. No one other person's interest in the COMMON STOCK of UPSTREAM BIO INC is more than five percent of the total outstanding COMMON STOCK.
    Item 7.Identification and Classification of the Subsidiary Which Acquired the Security Being Reported on by the Parent Holding Company or Control Person.
     
    If a parent holding company has filed this schedule, pursuant to Rule 13d-1(b)(ii)(G), so indicate under Item 3(g) and attach an exhibit stating the identity and the Item 3 classification of the relevant subsidiary. If a parent holding company has filed this schedule pursuant to Rule 13d-1(c) or Rule 13d-1(d), attach an exhibit stating the identification of the relevant subsidiary.


    See attached Exhibit 99.
    Item 8.Identification and Classification of Members of the Group.
     
    Not Applicable
    Item 9.Notice of Dissolution of Group.
     
    Not Applicable

    Item 10.Certifications:
     
    By signing below I certify that, to the best of my knowledge and belief, the securities referred to above were acquired and are held in the ordinary course of business and were not acquired and are not held for the purpose of or with the effect of changing or influencing the control of the issuer of the securities and were not acquired and are not held in connection with or as a participant in any transaction having that purpose or effect, other than activities solely in connection with a nomination under ?? 240.14a-11.

        SIGNATURE 
     
    After reasonable inquiry and to the best of my knowledge and belief, I certify that the information set forth in this statement is true, complete and correct.

     
    FMR LLC
     
    Signature:Richard Bourgelas
    Name/Title:Duly authorized under Power of Attorney effective as of May 23, 2023, by and on behalf of FMR LLC and its direct and indirect subsidiaries*
    Date:08/05/2025
     
    Abigail P. Johnson
     
    Signature:Richard Bourgelas
    Name/Title:Duly authorized under Power of Attorney effective as of May 23, 2023, by and on behalf of Abigail P. Johnson*
    Date:08/05/2025

    Comments accompanying signature:  *This power of attorney is incorporated herein by reference to Exhibit 24 to the Schedule 13G filed by FMR LLC on August 8, 2023, accession number: 0000315066-23-002397.
    Exhibit Information

    Please see Exhibit 99 for 13d-1(k) (1) agreement.

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