UPB · Upstream Bio, Inc.

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.

Includes 1,405 shares of Common Stock previously acquired under the Issuer's 2024 Employee Stock Purchase Plan.

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.

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.

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.

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.

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.

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.

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.

Pursuant to an agreement with OrbiMed Advisors LLC, OrbiMed Capital GP VIII LLC, OrbiMed Israel GP II, L.P., and OrbiMed Advisors Israel II Limited, the Reporting Person is obligated to transfer any securities issued under any such stock options or other awards, or the economic benefit thereof, to OrbiMed Advisors LLC, OrbiMed Capital GP VIII LLC, OrbiMed Israel GP II, L.P., and OrbiMed Advisors Israel II Limited, which will in turn ensure that such securities or economic benefits are provided to OrbiMed Private Investments VIII, LP and OrbiMed Israel Partners II, L.P.

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.

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.

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.

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.

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.

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.

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.

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.

The shares underlying this option shall vest in forty-eight equal monthly installments following January 1, 2026, subject to the Reporting Person's continued service on each such vesting date.

The shares underlying this option shall vest in forty-eight equal monthly installments following January 1, 2026, subject to the Reporting Person's continued service on each such vesting date.

Represents restricted stock units ("RSUs") granted pursuant to the Issuer's 2024 Stock Option and Incentive Plan. Each RSU represents the contingent right to receive one share of the Issuer's Common Stock upon vesting. The RSUs shall vest in sixteen equal quarterly installments following January 1, 2026, subject to the Reporting Person's continued service on each such vesting date.

Represents restricted stock units ("RSUs") granted pursuant to the Issuer's 2024 Stock Option and Incentive Plan. Each RSU represents the contingent right to receive one share of the Issuer's Common Stock upon vesting. The RSUs shall vest in sixteen equal quarterly installments following January 1, 2026, subject to the Reporting Person's continued service on each such vesting date.

The shares underlying this option shall vest in forty-eight equal monthly installments following January 1, 2026, subject to the Reporting Person's continued service on each such vesting date.

Represents restricted stock units ("RSUs") granted pursuant to the Issuer's 2024 Stock Option and Incentive Plan. Each RSU represents the contingent right to receive one share of the Issuer's Common Stock upon vesting. The RSUs shall vest in sixteen equal quarterly installments following January 1, 2026, subject to the Reporting Person's continued service on each such vesting date.

The shares underlying this option shall vest in forty-eight equal monthly installments following January 1, 2026, subject to the Reporting Person's continued service on each such vesting date.

Represents restricted stock units ("RSUs") granted pursuant to the Issuer's 2024 Stock Option and Incentive Plan. Each RSU represents the contingent right to receive one share of the Issuer's Common Stock upon vesting. The RSUs shall vest in sixteen equal quarterly installments following January 1, 2026, subject to the Reporting Person's continued service on each such vesting date.

Represents restricted stock units ("RSUs") granted pursuant to the Issuer's 2024 Stock Option and Incentive Plan. Each RSU represents the contingent right to receive one share of the Issuer's Common Stock upon vesting. The RSUs shall vest in sixteen equal quarterly installments following January 1, 2026, subject to the Reporting Person's continued service on each such vesting date.

Includes 1,581 shares of Common Stock previously acquired under the Issuer's 2024 Employee Stock Purchase Plan.

The shares underlying this option shall vest in forty-eight equal monthly installments following January 1, 2026, subject to the Reporting Person's continued service on each such vesting date.

The shares underlying this option shall vest upon the earlier of (i) June 10, 2026 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.

Pursuant to an agreement with OrbiMed Advisors LLC, OrbiMed Capital GP VIII LLC, OrbiMed Israel GP II, L.P., and OrbiMed Advisors Israel II Limited, the Reporting Person is obligated to transfer any securities issued under any such stock options or other awards, or the economic benefit thereof, to OrbiMed Advisors LLC, OrbiMed Capital GP VIII LLC, OrbiMed Israel GP II, L.P., and OrbiMed Advisors Israel II Limited, which will in turn ensure that such securities or economic benefits are provided to OrbiMed Private Investments VIII, LP and OrbiMed Israel Partners II, L.P.

The shares underlying this option shall vest upon the earlier of (i) June 10, 2026 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.

The shares underlying this option shall vest upon the earlier of (i) June 10, 2026 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.

The shares underlying this option shall vest upon the earlier of (i) June 10, 2026 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.

The shares underlying this option shall vest upon the earlier of (i) June 10, 2026 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.

The shares underlying this option shall vest upon the earlier of (i) June 10, 2026 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.

The shares underlying this option shall vest in forty-eight equal monthly installments following February 6, 2025, subject to the Reporting Person's continued service on each such vesting date.

The shares underlying this option shall vest in forty-eight equal monthly installments following February 6, 2025, subject to the Reporting Person's continued service on each such vesting date.

The shares underlying this option shall vest in forty-eight equal monthly installments following February 6, 2025, subject to the Reporting Person's continued service on each such vesting date.

The shares underlying this option shall vest in forty-eight equal monthly installments following February 6, 2025, subject to the Reporting Person's continued service on each such vesting date.

The shares underlying this option shall vest in forty-eight equal monthly installments following February 6, 2025, subject to the Reporting Person's continued service on each such vesting date.

25% of the shares underlying this option shall vest on December 16, 2025, with the remainder vesting in thirty-six equal monthly installments thereafter, subject to the Reporting Person's continued service on such vesting date.

Each share of the Issuer's Series A preferred stock and Series B preferred stock (collectively, the "Preferred Stock") converted into Common Stock on a 1.049-for-one basis upon closing of the Issuer's initial public offering without payment of consideration. The Preferred Stock had no expiration date.

The securities reported are held directly by AI Upstream LLC ("AI Upstream") and may be deemed to be beneficially owned by AI Biotechnology LLC ("AI Biotechnology"), Access Industries Holdings LLC ("AIH"), Access Industries Management, LLC ("AIM") and Len Blavatnik because (i) Mr. Blavatnik controls AIM and AIH, (ii) AIM controls AIH, (iii) AIH owns all of the voting units of AI Biotechnology and (iv) AI Biotechnology owns all of the voting units of AI Upstream. Each of the reporting persons (other than AI Upstream) disclaims beneficial ownership of these securities, except to the extent of its or his pecuniary interest therein, and this form shall not be construed as an admission that any such reporting person is the beneficial owner of any of the securities reported on this form.

Each share of the Issuer's Series A preferred stock and Series B preferred stock (collectively, the "Preferred Stock") converted into Common Stock on a 1.049-for-one basis upon closing of the Issuer's initial public offering without payment of consideration. The Preferred Stock had no expiration date.

The securities reported are held directly by AI Upstream LLC ("AI Upstream") and may be deemed to be beneficially owned by AI Biotechnology LLC ("AI Biotechnology"), Access Industries Holdings LLC ("AIH"), Access Industries Management, LLC ("AIM") and Len Blavatnik because (i) Mr. Blavatnik controls AIM and AIH, (ii) AIM controls AIH, (iii) AIH owns all of the voting units of AI Biotechnology and (iv) AI Biotechnology owns all of the voting units of AI Upstream. Each of the reporting persons (other than AI Upstream) disclaims beneficial ownership of these securities, except to the extent of its or his pecuniary interest therein, and this form shall not be construed as an admission that any such reporting person is the beneficial owner of any of the securities reported on this form.

These securities are held of record by OrbiMed Private Investments VIII, LP ("OPI VIII"). OrbiMed Capital GP VIII LLC ("GP VIII") is the general partner of OPI VIII, and OrbiMed Advisors LLC ("OrbiMed Advisors") is the managing member of GP VIII. By virtue of such relationships, GP VIII and OrbiMed Advisors may be deemed to have voting power and investment power over the securities held by OPI VIII and, as a result, may be deemed to have beneficial ownership over such securities. OrbiMed Advisors exercises voting and investment power through a management committee comprised of Carl L. Gordon, Sven H. Borho, and W. Carter Neild, each of whom disclaims beneficial ownership of the securities held by OPI VIII.

Each of Advisors II, Israel GP, OrbiMed Advisors, and GP VIII disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its pecuniary interest therein, if any. OrbiMed Advisors, GP VIII. Advisors II, and Israel GP have designated a representative, Chimovits, an employee of OrbiMed Advisors and a director of Advisors II, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any such person or entity is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Each share of the Issuer's Series A preferred stock and Series B preferred stock (collectively, the "Preferred Stock") converted into Common Stock on a 1.049-for-one basis upon closing of the Issuer's initial public offering without payment of consideration. The Preferred Stock had no expiration date.

The securities reported are held directly by AI Upstream LLC ("AI Upstream") and may be deemed to be beneficially owned by AI Biotechnology LLC ("AI Biotechnology"), Access Industries Holdings LLC ("AIH"), Access Industries Management, LLC ("AIM") and Len Blavatnik because (i) Mr. Blavatnik controls AIM and AIH, (ii) AIM controls AIH, (iii) AIH owns all of the voting units of AI Biotechnology and (iv) AI Biotechnology owns all of the voting units of AI Upstream. Each of the reporting persons (other than AI Upstream) disclaims beneficial ownership of these securities, except to the extent of its or his pecuniary interest therein, and this form shall not be construed as an admission that any such reporting person is the beneficial owner of any of the securities reported on this form.

These securities are held of record by OrbiMed Israel Partners II, L.P. ("OIP II"). OrbiMed Israel GP II, L.P. ("Israel GP") is the general partner of OIP II, and OrbiMed Advisors Israel II Limited ("Advisors II") is the general partner of Israel GP. By virtue of such relationships, Israel GP and Advisors II may be deemed to have voting and investment power over the securities held by OIP II and, as a result, may be deemed to have beneficial ownership over such securities. Advisors II exercises voting and investment power through an investment committee comprised of Carl L. Gordon, David P. Bonita, and the Reporting Person, each of whom disclaims beneficial ownership of the securities held by OIP II.

Each of the Reporting Person, Advisors II, Israel GP, OrbiMed Advisors, and GP VIII disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of his or its pecuniary interest therein, if any. This report shall not be deemed an admission that any of the Reporting Person, Advisors II, Israel GP, OrbiMed Advisors, or GP VIII is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Each share of Series B redeemable convertible preferred stock automatically converted into Common Stock on a 1.049-for-one basis upon closing of the Issuer's initial public offering without payment of consideration. The Series B redeemable convertible preferred stock had no expiration date.

Each share of Series A redeemable convertible preferred stock and Series B redeemable convertible preferred stock automatically converted into shares of the Issuer's common stock on a one-for-1.049 basis immediately prior to the closing of the Issuer's initial public offering and have no expiration date.

These securities are held of record by OrbiMed Israel Partners II, L.P. ("OIP II"). OrbiMed Israel GP II, L.P. ("Israel GP") is the general partner of OIP II, and OrbiMed Advisors Israel II Limited ("Advisors II") is the general partner of Israel GP. By virtue of such relationships, Israel GP and Advisors II may be deemed to have voting and investment power over the securities held by OIP II and, as a result, may be deemed to have beneficial ownership over such securities. Advisors II exercises voting and investment power through an investment committee comprised of Carl L. Gordon, David P. Bonita, and the Reporting Person, each of whom disclaims beneficial ownership of the securities held by OIP II.

Each of the Reporting Person, Advisors II, Israel GP, OrbiMed Advisors, and GP VIII disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of his or its pecuniary interest therein, if any. This report shall not be deemed an admission that any of the Reporting Person, Advisors II, Israel GP, OrbiMed Advisors, or GP VIII is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Each share of Series A redeemable convertible preferred stock and Series B redeemable convertible preferred stock automatically converted into shares of the Issuer's common stock on a one-for-1.049 basis immediately prior to the closing of the Issuer's initial public offering and have no expiration date.

These securities are held of record by OrbiMed Private Investments VIII, LP ("OPI VIII"). OrbiMed Capital GP VIII LLC ("GP VIII") is the general partner of OPI VIII, and OrbiMed Advisors LLC ("OrbiMed Advisors") is the managing member of GP VIII. By virtue of such relationships, GP VIII and OrbiMed Advisors may be deemed to have voting power and investment power over the securities held by OPI VIII and, as a result, may be deemed to have beneficial ownership over such securities. OrbiMed Advisors exercises voting and investment power through a management committee comprised of Carl L. Gordon, Sven H. Borho, and W. Carter Neild, each of whom disclaims beneficial ownership of the securities held by OPI VIII.

Each of the Reporting Person, Advisors II, Israel GP, OrbiMed Advisors, and GP VIII disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of his or its pecuniary interest therein, if any. This report shall not be deemed an admission that any of the Reporting Person, Advisors II, Israel GP, OrbiMed Advisors, or GP VIII is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Each share of Series A redeemable convertible preferred stock and Series B redeemable convertible preferred stock automatically converted into shares of the Issuer's common stock on a one-for-1.049 basis immediately prior to the closing of the Issuer's initial public offering and have no expiration date.

These securities are held of record by OrbiMed Israel Partners II, L.P. ("OIP II"). OrbiMed Israel GP II, L.P. ("Israel GP") is the general partner of OIP II, and OrbiMed Advisors Israel II Limited ("Advisors II") is the general partner of Israel GP. By virtue of such relationships, Israel GP and Advisors II may be deemed to have voting and investment power over the securities held by OIP II and, as a result, may be deemed to have beneficial ownership over such securities. Advisors II exercises voting and investment power through an investment committee comprised of Carl L. Gordon, David P. Bonita, and the Reporting Person, each of whom disclaims beneficial ownership of the securities held by OIP II.

Each of the Reporting Person, Advisors II, Israel GP, OrbiMed Advisors, and GP VIII disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of his or its pecuniary interest therein, if any. This report shall not be deemed an admission that any of the Reporting Person, Advisors II, Israel GP, OrbiMed Advisors, or GP VIII is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Each share of Series A redeemable convertible preferred stock and Series B redeemable convertible preferred stock automatically converted into shares of the Issuer's common stock on a one-for-1.049 basis immediately prior to the closing of the Issuer's initial public offering and have no expiration date.

These securities are held of record by OrbiMed Israel Partners II, L.P. ("OIP II"). OrbiMed Israel GP II, L.P. ("Israel GP") is the general partner of OIP II, and OrbiMed Advisors Israel II Limited ("Advisors II") is the general partner of Israel GP. By virtue of such relationships, Israel GP and Advisors II may be deemed to have voting and investment power over the securities held by OIP II and, as a result, may be deemed to have beneficial ownership over such securities. Advisors II exercises voting and investment power through an investment committee comprised of Carl L. Gordon, David P. Bonita, and Erez Chimovits ("Chimovits"), each of whom disclaims beneficial ownership of the securities held by OIP II.

Each of Advisors II, Israel GP, OrbiMed Advisors, and GP VIII disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of its pecuniary interest therein, if any. OrbiMed Advisors, GP VIII. Advisors II, and Israel GP have designated a representative, Chimovits, an employee of OrbiMed Advisors and a director of Advisors II, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any such person or entity is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.

Each share of Series A redeemable convertible preferred stock and Series B redeemable convertible preferred stock automatically converted into shares of the Issuer's common stock on a one-for-1.049 basis immediately prior to the closing of the Issuer's initial public offering and have no expiration date.

These securities are held of record by OrbiMed Private Investments VIII, LP ("OPI VIII"). OrbiMed Capital GP VIII LLC ("GP VIII") is the general partner of OPI VIII, and OrbiMed Advisors LLC ("OrbiMed Advisors") is the managing member of GP VIII. By virtue of such relationships, GP VIII and OrbiMed Advisors may be deemed to have voting power and investment power over the securities held by OPI VIII and, as a result, may be deemed to have beneficial ownership over such securities. OrbiMed Advisors exercises voting and investment power through a management committee comprised of Carl L. Gordon, Sven H. Borho, and W. Carter Neild, each of whom disclaims beneficial ownership of the securities held by OPI VIII.

Each of the Reporting Person, Advisors II, Israel GP, OrbiMed Advisors, and GP VIII disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), except to the extent of his or its pecuniary interest therein, if any. This report shall not be deemed an admission that any of the Reporting Person, Advisors II, Israel GP, OrbiMed Advisors, or GP VIII is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.