# EDGAR Filing Document

**Accession Number:** 0001513422
**File Stem:** 0000950170-25-085381
**Filing Date:** 2025-6
**Character Count:** 7479
**Document Hash:** d9574dffb28380b7e0f35f1bfc0756c5
**Contains OCR:** False
**Source Format:** 

## Filing Content

## Filing Summary
**0000950170-25-085381.hdr.sgml**: 20250612

**ACCESSION NUMBER**: 0000950170-25-085381

**CONFORMED SUBMISSION TYPE**: 4

**PUBLIC DOCUMENT COUNT**: 2

**CONFORMED PERIOD OF REPORT**: 20250610

**FILED AS OF DATE**: 20250612

**DATE AS OF CHANGE**: 20250612

**REPORTING-OWNER**: 

**OWNER DATA:**
- **COMPANY CONFORMED NAME:** Beckman Daniella
- **CENTRAL INDEX KEY:** 0001513422

**ORGANIZATION NAME:**

**FILING VALUES:**
- **FORM TYPE:** 4
- **SEC ACT:** 1934 Act
- **SEC FILE NUMBER:** 001-42366
- **FILM NUMBER:** 251042680

**MAIL ADDRESS:**
- **STREET 1:** C/O IDENIX PHARMACEUTICALS, INC.
- **STREET 2:** ONE KENDALL SQUARE, BLDG. 1400
- **CITY:** CAMBRIDGE
- **STATE:** MA
- **ZIP:** 02139
**ISSUER**: 

**COMPANY DATA:**
- **COMPANY CONFORMED NAME:** Upstream Bio, Inc.
- **CENTRAL INDEX KEY:** 0002022626
- **STANDARD INDUSTRIAL CLASSIFICATION:** PHARMACEUTICAL PREPARATIONS [2834]
- **ORGANIZATION NAME:** 03 Life Sciences
- **EIN:** 000000000
- **STATE OF INCORPORATION:** DE
- **FISCAL YEAR END:** 1231

**BUSINESS ADDRESS:**
- **STREET 1:** 890 WINTER STREET, SUITE 200
- **CITY:** WALTHAM
- **STATE:** MA
- **ZIP:** 02451
- **BUSINESS PHONE:** 781-208-2466

**MAIL ADDRESS:**
- **STREET 1:** 890 WINTER STREET, SUITE 200
- **CITY:** WALTHAM
- **STATE:** MA
- **ZIP:** 02451

## Exhibit 24.2

SUBSTITUTE POWER OF ATTORNEY

Under the terms of powers of attorney (each, a "Power of Attorney") previously filed with the U.S. Securities and Exchange Commission, the undersigned was appointed an attorney-in-fact for the below listed individuals, as of October 10, 2024, to, among other things, execute for and on behalf of the following individuals any Forms 3, 4 or 5, Schedule 13D or 13G, or any amendment(s) thereto, in accordance with Section 16(a) of the Securities Exchange Act of 1934, as amended, and the rules thereunder:

Daniella Beckman

Erez Chimovits

Aaron Deykin

H. Edward Fleming, Jr.

Adam Houghton

Liam Ratcliffe

Ronald C. Renaud, Jr.

Marcella Kuhlman Ruddy

E. Rand Sutherland

In accordance with the authority granted under each Power of Attorney, including the full power of substitution, the undersigned hereby appoints Allison Ambrose as substitute attorney-in-fact, on behalf of the individuals listed above, with the power to exercise and execute all of the powers granted or conferred in the original Power of Attorney. For the avoidance of doubt, the foregoing appointment shall not serve as a revocation of the powers granted to the undersigned himself in each Power of Attorney.

This substitute Power of Attorney shall remain in full force and effect with respect to each Power of Attorney until such underlying Power of Attorney is revoked or terminated, unless earlier revoked by the undersigned in a signed writing.

Date: 12/19/24

By: <u>/s/ Michael Gray</u>

Name: Michael Gray

Title: Attorney-in-Fact

------

### UNITED STATES SECURITIES AND EXCHANGE COMMISSION
**Washington, D.C. 20549**

## FORM 4

### STATEMENT OF CHANGES IN BENEFICIAL OWNERSHIP

[ ] Check this box if no longer subject to Section 16. Form 4 or Form 5 obligations may continue. See Instruction 1(b).

[ ] Check this box to indicate that a transaction was made pursuant to a contract, instruction or written plan for the purchase or sale of equity securities of the issuer that is intended to satisfy the affirmative defense conditions of Rule 10b5-1(c). See Instruction 10.

---

| | | |
|:---|:---|:---|
| **1. Name and Address of Reporting Person**<sup>*</sup><br>Beckman Daniella<br><sub>(Last) (First) (Middle)</sub><br>UPSTREAM BIO, INC.<br>890 WINTER STREET, SUITE 200<br><sub>(Street)</sub><br>WALTHAM, MA 02451<br><sub>(City) (State) (Zip)</sub> | **3. Date of Earliest Transaction (Month/Day/Year)**<br>2025-06-10 | **5. Relationship of Reporting Person(s) to Issuer**<br>(Check all applicable)<br>[X] Director [ ] 10% Owner<br>[ ] Officer (give title below) [ ] Other (specify below)<br>_ _ |
| **2. Issuer Name and Ticker or Trading Symbol**<br>Upstream Bio, Inc. [ UPB ] | **4. If Amendment, Date of Original Filed (Month/Day/Year)**<br>  | **6. Individual or Joint/Group Filing (Check Applicable Line)**<br>[X] Form filed by One Reporting Person<br>[ ] Form filed by More than One Reporting Person |

---

## Table I - Non-Derivative Securities

---

|  |  |  |  |  |  |  |  |  |  |  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1. Title of Security | 2. Transaction Date | 2A. Deemed Execution Date | 3. Transaction Code (V) | 3. Transaction Code (V) | 4. Securities Acquired (A) or Disposed of (D) | 4. Securities Acquired (A) or Disposed of (D) | 4. Securities Acquired (A) or Disposed of (D) | 5. Amount of Securities Beneficially Owned | 6. Ownership Form | 7. Nature of Indirect Beneficial Ownership |
| 1. Title of Security | 2. Transaction Date | 2A. Deemed Execution Date | Code | V | Amount | (A) or (D) | Price | 5. Amount of Securities Beneficially Owned | 6. Ownership Form | 7. Nature of Indirect Beneficial Ownership |
|  |  |  |  |  |  |  |  |  |  |  |

---

## Table II - Derivative Securities

---

|  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1. Title of Derivative Security | 2. Conversion or Exercise Price | 3. Transaction Date | 3A. Deemed Execution Date | 4. Transaction Code (V) | 4. Transaction Code (V) | 5. Number of Derivative Securities Acquired (A) or Disposed of (D) | 5. Number of Derivative Securities Acquired (A) or Disposed of (D) | 6. Date Exercisable and Expiration Date | 6. Date Exercisable and Expiration Date | 7. Title and Amount of Underlying Securities | 7. Title and Amount of Underlying Securities | 8. Price of Derivative Security | 9. Number of Derivative Securities Beneficially Owned | 10. Ownership Form | 11. Nature of Indirect Beneficial Ownership |
| 1. Title of Derivative Security | 2. Conversion or Exercise Price | 3. Transaction Date | 3A. Deemed Execution Date | Code | V | (A) | (D) | Date Exercisable | Expiration Date | Title | Amount or Number of Shares | 8. Price of Derivative Security | 9. Number of Derivative Securities Beneficially Owned | 10. Ownership Form | 11. Nature of Indirect Beneficial Ownership |
| Stock Option (Right to Buy) | $11.59 | 2025-06-10 |  | A |  | 17096 |  | <sup>(1)</sup> | 2035-06-09 | Common Stock | 17096 | $0 | 17096 | D |  |

---

### Footnotes:

(1) 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.

**Remarks:**
Exhibit 24.2 - Substitute Power of Attorney

**Signature:** /s/ Allison Ambrose, Attorney-in-Fact  
**Date:** 2025-06-12

### Remarks:

Reminder: Report on a separate line for each class of securities beneficially owned directly or indirectly.

* If the form is filed by more than one reporting person, see Instruction 4 (b)(v).

** Intentional misstatements or omissions of facts constitute Federal Criminal Violations See 18 U.S.C. 1001 and 15 U.S.C. 78ff(a).

Note: File three copies of this Form, one of which must be manually signed. If space is insufficient, see Instruction 6 for procedure.

**Persons who respond to the collection of information contained in this form are not required to respond unless the form displays a currently valid OMB Number.**