# EDGAR Filing Document

**Accession Number:** 0002022626
**File Stem:** 0001193125-26-126342
**Filing Date:** 2026-3
**Character Count:** 15990
**Document Hash:** 79812f2ae352f9fb65a897e0bf6478a3
**Contains OCR:** False
**Source Format:** 

## Filing Content

## Filing Summary
**0001193125-26-126342.hdr.sgml**: 20260326

**ACCESSION NUMBER**: 0001193125-26-126342

**CONFORMED SUBMISSION TYPE**: S-8

**PUBLIC DOCUMENT COUNT**: 13

**FILED AS OF DATE**: 20260326

**DATE AS OF CHANGE**: 20260326

**EFFECTIVENESS DATE**: 20260326

**FILER**: 

**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

**FILING VALUES:**
- **FORM TYPE:** S-8
- **SEC ACT:** 1933 Act
- **SEC FILE NUMBER:** 333-294646
- **FILM NUMBER:** 26798634

**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

**As filed with the Securities and Exchange Commission on March 26, 2026**

**Registration No. 333-**

**UNITED STATES**

**SECURITIES AND EXCHANGE COMMISSION<br>Washington, D.C. 20549**

**FORM S-8<br>REGISTRATION STATEMENT<br>*UNDER***<br>***THE SECURITIES ACT OF 1933***

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**Upstream Bio, Inc.**

**(Exact name of registrant as specified in its charter)**

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---

| | |
|:---|:---|
| **Delaware** | **38-4187694** |
| **(State or other jurisdiction of <br>incorporation or organization)** | **(I.R.S. employer<br>identification no.)** |
| **890 Winter Street, Suite 200**<br>**Waltham, MA**<br>**(Address of principal executive offices)** | **02451**<br>**(Zip Code)** |

---

**Upstream Bio, Inc. 2024 Stock Option and Incentive Plan<br>(Full title of the plan)**

**E. Rand Sutherland, M.D. <br>Chief Executive Officer**

**Upstream Bio, Inc.<br>890 Winter Street, Suite 200**

**Waltham, MA 02451**

**(Name and address of agent for service)** 

**(781) 208-2466**

**(Telephone number, including area code, of agent for service)**

***Copies to:*<br>William D. Collins**

**Karin Yoo<br>Goodwin Procter LLP<br>100 Northern Avenue**

**Boston, Massachusetts 02210<br>(617) 570-1000**

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Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company. See the definitions of "large accelerated filer," "accelerated filer," "smaller reporting company," and "emerging growth company" in Rule 12b-2 of the Exchange Act.

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| | | | |
|:---|:---|:---|:---|
| Large accelerated filer | ☐ | Accelerated filer | ☐ |
| Non-accelerated filer | ☒ | Smaller reporting company | ☒ |
|  |  | Emerging growth company | ☒ |

---

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 7(a)(2)(B) of the Securities Act. ☐

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**EXPLANATORY NOTE**

This Registration Statement on Form S-8 (this "Registration Statement") is being filed by Upstream Bio, Inc. (the "Registrant") with the U.S. Securities and Exchange Commission (the "Commission") to register 2,711,887 additional shares of the Registrant's common stock, par value $0.001 per share ("Common Stock"), available for issuance under the Registrant's 2024 Stock Option and Incentive Plan (the "Plan"), pursuant to the evergreen provisions of the Plan.

These additional shares are of the same class as other securities relating to the Plan for which the Registrant's Registration Statements on Form S-8 filed with the Commission on October 11, 2024 (File No. 333-282614) and March 12, 2025 (File No. 333-285729) (the "Earlier Registration Statements") are effective.

Pursuant to General Instruction E to Form S-8, the contents of the Earlier Registration Statements related to the Plan, except for "Item 8. Exhibits," are incorporated herein by reference, except to the extent supplemented, amended or superseded by the information set forth herein. Only those items of Form S-8 containing new information not contained in the Earlier Registration Statements are presented herein.

**Part II**<br>**INFORMATION REQUIRED IN THE REGISTRATION STATEMENT**

**Item 8. Exhibits.**

The exhibits to this Registration Statement are listed in the Exhibit Index attached hereto and incorporated by reference herein.

**EXHIBIT INDEX**

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| | |
|:---|:---|
| **Exhibit<br>No.** | &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;**Description** |
| 4.1 | [<u>Third Amended and Restated Certificate of Incorporation of Upstream Bio, Inc. (incorporated by reference to Exhibit 3.1 to the Registrant's Current Report on Form 8-K (File No. 001-42366) filed on October 15, 2024).</u>](https://www.sec.gov/Archives/edgar/data/2022626/000119312524237580/d897785dex31.htm) |
| 4.2 | [<u>Second Amended and Restated Bylaws of Upstream Bio, Inc. (incorporated by reference to Exhibit 3.2 to the Registrant's Current Report on Form 8-K (File No. 001-42366) filed on October 15, 2024).</u>](https://www.sec.gov/Archives/edgar/data/2022626/000119312524237580/d897785dex32.htm) |
| 4.3 | [<u>Amended and Restated Investors' Rights Agreement, among the Registrant and certain of its stockholders, dated June 6, 2023 (incorporated by reference to Exhibit 4.2 to the Registrant's Registration Statement on Form S-1 (File No. 333-282197) filed on September 18, 2024).</u>](https://www.sec.gov/Archives/edgar/data/2022626/000119312524221372/d843142dex42.htm) |
| 5.1\* | [<u>Opinion of Goodwin Procter LLP.</u>](upb-ex5_1.htm) |
| 23.1\* | [<u>Consent of PricewaterhouseCoopers LLP, Independent Registered Public Accounting Firm.</u>](upb-ex23_1.htm) |
| 23.2\* | [<u>Consent of Goodwin Procter LLP (included in Exhibit 5.1).</u>](upb-ex5_1.htm) |
| 24.1\* | [<u>Power of Attorney (included on signature page).</u>](#poa) |
| 99.1 | [<u>Upstream Bio, Inc. 2024 Stock Option and Incentive Plan and form of award agreements thereunder (incorporated by reference to Exhibit 10.2 to Amendment No. 1 to the Registrant's Registration Statement on Form S-1 (File No. 333-282197) filed on October 7, 2024).</u>](https://www.sec.gov/Archives/edgar/data/2022626/000119312524233296/d843142dex102.htm) |
| 107\* | [<u>Filing Fee Table.</u>](upb_exfilingfees.htm) |

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\* Filed herewith.

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**SIGNATURES**

Pursuant to the requirements of the Securities Act of 1933, the registrant certifies that it has reasonable grounds to believe that it meets all of the requirements for filing on Form S-8 and has duly caused this registration statement to be signed on its behalf by the undersigned, thereunto duly authorized, in the City of Waltham, Massachusetts, on this 26<sup>th</sup> day of March, 2026.

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| | |
|:---|:---|
| **UPSTREAM BIO, INC.** | **UPSTREAM BIO, INC.** |
| By: | /s/ E. Rand Sutherland |
|  | Name: E. Rand Sutherland, M.D.<br>Title: Chief Executive Officer |

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**POWER OF ATTORNEY AND SIGNATURES**

Each individual whose signature appears below hereby constitutes and appoints each of E. Rand Sutherland, M.D. and Michael Paul Gray, M.B.A. as such person's true and lawful attorney-in-fact and agent with full power of substitution and resubstitution, for such person in such person's name, place and stead, in any and all capacities, to sign any and all amendments (including post-effective amendments) to this Registration Statement on Form S-8, and to file the same, with all exhibits thereto, and all documents in connection therewith, with the Securities and Exchange Commission granting unto each said attorney-in-fact and agent full power and authority to do and perform each and every act and thing requisite and necessary to be done in and about the premises, as fully to all intents and purposes as such person might or could do in person, hereby ratifying and confirming all that any said attorney-in-fact and agent, or any substitute or substitutes of any of them, may lawfully do or cause to be done by virtue hereof.

Pursuant to the requirements of the Securities Act of 1933, as amended, this Registration Statement has been signed by the following persons in the capacities and on the date indicated.

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| | | |
|:---|:---|:---|
| &nbsp;&nbsp;**Name** | &nbsp;&nbsp;**Title** | &nbsp;&nbsp;**Date** |
| &nbsp;&nbsp;/s/ E. Rand Sutherland | &nbsp;&nbsp;Chief Executive Officer and<br>Director<br>(*Principal Executive Officer*) | &nbsp;&nbsp;March 26, 2026 |
| &nbsp;&nbsp;E. Rand Sutherland, M.D. | &nbsp;&nbsp;Chief Executive Officer and<br>Director<br>(*Principal Executive Officer*) | &nbsp;&nbsp;March 26, 2026 |
| &nbsp;&nbsp;/s/ Michael Paul Gray | &nbsp;&nbsp;Chief Financial Officer<br>(*Principal Financial Officer and Principal Accounting Officer*) | &nbsp;&nbsp;March 26, 2026 |
| &nbsp;&nbsp;Michael Paul Gray, M.B.A. | &nbsp;&nbsp;Chief Financial Officer<br>(*Principal Financial Officer and Principal Accounting Officer*) | &nbsp;&nbsp;March 26, 2026 |
| &nbsp;&nbsp;/s/ Ronald C. Renaud, Jr. | &nbsp;&nbsp;Director and Chairman | &nbsp;&nbsp;March 26, 2026 |
| &nbsp;&nbsp;Ronald C. Renaud, Jr., M.B.A. | &nbsp;&nbsp;Director and Chairman | &nbsp;&nbsp;March 26, 2026 |
| &nbsp;&nbsp;/s/ Daniella Beckman | &nbsp;&nbsp;Director | &nbsp;&nbsp;March 26, 2026 |
| &nbsp;&nbsp;Daniella Beckman | &nbsp;&nbsp;Director | &nbsp;&nbsp;March 26, 2026 |
| &nbsp;&nbsp;/s/ Erez Chimovits | &nbsp;&nbsp;Director | &nbsp;&nbsp;March 26, 2026 |
| &nbsp;&nbsp;Erez Chimovits, M.B.A., M.Sc. | &nbsp;&nbsp;Director | &nbsp;&nbsp;March 26, 2026 |
| &nbsp;&nbsp;/s/ H. Edward Fleming, Jr. | &nbsp;&nbsp;Director | &nbsp;&nbsp;March 26, 2026 |
| &nbsp;&nbsp;H. Edward Fleming, Jr., M.D. | &nbsp;&nbsp;Director | &nbsp;&nbsp;March 26, 2026 |
| &nbsp;&nbsp;/s/ Liam Ratcliffe | &nbsp;&nbsp;Director | &nbsp;&nbsp;March 26, 2026 |
| &nbsp;&nbsp;Liam Ratcliffe, M.B.Ch.B., Ph.D., M.B.A. | &nbsp;&nbsp;Director | &nbsp;&nbsp;March 26, 2026 |
| &nbsp;&nbsp;/s/ Marcella Kuhlman Ruddy | &nbsp;&nbsp;Director | &nbsp;&nbsp;March 26, 2026 |
| &nbsp;&nbsp;Marcella Kuhlman Ruddy, M.D., M.S.<br>| &nbsp;&nbsp;Director | &nbsp;&nbsp;March 26, 2026 |

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## Exhibit 5.1

**Exhibit 5.1**

March 26, 2026

Upstream Bio, Inc.

890 Winter Street, Suite 200

Waltham, Massachusetts 02451

Re: <u>Securities Being Registered under Registration Statement on Form S-8</u>

We have acted as your counsel in connection with your filing of a Registration Statement on Form S-8 (the "Registration Statement") pursuant to the Securities Act of 1933, as amended (the "Securities Act"), on or about the date hereof relating to an aggregate of 2,711,887 shares (the "Shares") of Common Stock, par value $0.001 per share ("Common Stock"), of Upstream Bio, Inc., a Delaware corporation (the "Company"), that may be issued pursuant to the Company's 2024 Stock Option and Incentive Plan (the "Plan").

We have reviewed such documents and made such examination of law as we have deemed appropriate to give the opinion set forth below. We have relied, without independent verification, on certificates of public officials and, as to matters of fact material to the opinion set forth below, on certificates of officers of the Company.

For purposes of the opinion set forth below, we have assumed that, at the time Shares are issued, the total number of then unissued Shares, when added to the number of shares of Common Stock issued, subscribed for, or otherwise committed to be issued, does not exceed the number of shares of Common Stock authorized by the Company's certificate of incorporation.

The opinion set forth below is limited to the Delaware General Corporation Law.

Based on the foregoing, we are of the opinion that the Shares have been duly authorized and, when delivered against payment therefor in accordance with the terms of the Plan, will be validly issued, fully paid and nonassessable.

This opinion letter and the opinion it contains shall be interpreted in accordance with the Core Opinion Principles as published in 74 *Business Lawyer* 815 (Summer 2019).

We hereby consent to the inclusion of this opinion as Exhibit 5.1 to the Registration Statement. In giving our consent, we do not admit that we are in the category of persons whose consent is required under Section 7 of the Securities Act or the rules and regulations thereunder.

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| |
|:---|
| Very truly yours, |
| /s/ Goodwin Procter LLP |
| GOODWIN PROCTER LLP |

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## Exhibit 23.1

**Exhibit 23.1**

CONSENT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM

We hereby consent to the incorporation by reference in this Registration Statement on Form S-8 of Upstream Bio, Inc. of our report dated March 26, 2026 relating to the financial statements, which appears in Upstream Bio, Inc.'s Annual Report on Form 10-K for the year ended December 31, 2025.

/s/ PricewaterhouseCoopers LLP

Boston, Massachusetts

March 26, 2026

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## Ex-Filing

?xml version='1.0' encoding='ASCII'? EX-FILING FEES

**Exhibit 107** 

**Calculation of** Filing Fee **Table** 

**Form** S-8

(Form Type)

Upstream Bio, Inc.

(Exact Name of Registrant as Specified in its Charter)

<u>Table 1: Newly Registered Securities</u> 

---

| | | | | | | |
|:---|:---|:---|:---|:---|:---|:---|
| Security Type | **Security Class Title** | **Fee Calculation Rule** | **Proposed Maximum Offering Price Per Unit** <sup>(2)</sup> | **Maximum Aggregate Offering Price** <sup>(2)</sup> | **Fee Rate** | **Amount of Registration Fee** |
| Equity | Common Stock, par value $0.001 per share | 457(c) and 457(h)<br> 2,711,887 shares <sup>(3)</sup> | $8.37 | $22698494.19 | 0.00013810 | $3134.67 |
| **Total Offering Amounts** | **Total Offering Amounts** | **Total Offering Amounts** |  | $22698494.19 |  | $3134.67 |
| **Total Fee Offsets** | **Total Fee Offsets** | **Total Fee Offsets** |  |  |  | ― |
| **Net Fee Due** | **Net Fee Due** | **Net Fee Due** |  |  |  | $3134.67 |

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&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;(1)Pursuant to Rule 416(a) under the Securities Act of 1933, as amended (the "Securities Act"), this Registration Statement shall also cover any additional shares of the Registrant's common stock, par value $0.001 per share ("Common Stock"), that become issuable under the Registrant's 2024 Stock Option and Incentive Plan (the "Plan") by reason of any stock dividend, stock split, recapitalization or any other similar transaction 211effected without the receipt of consideration which results in an increase in the number of our outstanding shares of Common Stock.

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;(2)Estimated solely for the purpose of calculating the registration fee pursuant to Rules 457(c) and 457(h) of the Securities Act, and based on $8.37, the average of the high and low price of the Registrant's Common Stock, as reported on the Nasdaq Global Select Market, on March 24, 2026.

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;(3)Consists of 2,711,887 additional shares issuable under the Plan, which represents an automatic annual increase to the number of shares available for issuance under the Plan effective as of January 1, 2026. Pursuant to such provision, an additional number of shares will automatically be added to the shares authorized for issuance under the Plan on January 1 of each year. Shares available for issuance under the Plan were previously registered on registration statements on Form S-8 filed with the Securities and Exchange Commission on October 11, 2024 (File No. 333-282614) and March 12, 2025 (File No. 333-285729).

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