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SEC FORM 3 SEC Form 3

FORM 3

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

INITIAL STATEMENT OF BENEFICIAL OWNERSHIP OF SECURITIES

Filed pursuant to Section 16(a) of the Securities Exchange Act of 1934
or Section 30(h) of the Investment Company Act of 1940

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1. Name and Address of Reporting Person^*

ORBIMED ADVISORS LLC

(Last)

(First)

(Middle)

601 LEXINGTON AVENUE

54TH FLOOR

(Street)

NEW YORK

10022

(City)

(State)

(Zip)

2. Date of Event Requiring Statement (Month/Day/Year)
10/10/2024

3. Issuer Name and Ticker or Trading Symbol
Upstream Bio, Inc. [ UPB ]

4. Relationship of Reporting Person(s) to Issuer
(Check all applicable)

	Director		10% Owner
	Officer (give title below)		Other (specify below)

5. If Amendment, Date of Original Filed (Month/Day/Year)

6. Individual or Joint/Group Filing (Check Applicable Line)

	Form filed by One Reporting Person
	Form filed by More than One Reporting Person

Table I - Non-Derivative Securities Beneficially Owned
1. Title of Security (Instr. 4)	2. Amount of Securities Beneficially Owned (Instr. 4)	3. Ownership Form: Direct (D) or Indirect (I) (Instr. 5)	4. Nature of Indirect Beneficial Ownership (Instr. 5)
Common Stock	251,760	I	By OrbiMed Israel Partners II, L.P.⁽¹⁾⁽²⁾
Common Stock	1,007,040	I	By OrbiMed Private Investments VIII, LP⁽²⁾⁽³⁾

Table II - Derivative Securities Beneficially Owned (e.g., puts, calls, warrants, options, convertible securities)
1. Title of Derivative Security (Instr. 4)	2. Date Exercisable and Expiration Date (Month/Day/Year)		3. Title and Amount of Securities Underlying Derivative Security (Instr. 4)		4. Conversion or Exercise Price of Derivative Security	5. Ownership Form: Direct (D) or Indirect (I) (Instr. 5)	6. Nature of Indirect Beneficial Ownership (Instr. 5)
1. Title of Derivative Security (Instr. 4)	Date Exercisable	Expiration Date	Title	Amount or Number of Shares	4. Conversion or Exercise Price of Derivative Security	5. Ownership Form: Direct (D) or Indirect (I) (Instr. 5)	6. Nature of Indirect Beneficial Ownership (Instr. 5)
Series A redeemable convertible preferred stock	⁽⁴⁾	⁽⁴⁾	Common Stock	524,500	⁽⁴⁾	I	By OrbiMed Israel Partners II, L.P.⁽¹⁾⁽²⁾
Series A redeemable convertible preferred stock	⁽⁴⁾	⁽⁴⁾	Common Stock	2,098,000	⁽⁴⁾	I	By OrbiMed Private Investments VIII, LP⁽²⁾⁽³⁾
Series B redeemable convertible preferred stock	⁽⁴⁾	⁽⁴⁾	Common Stock	197,456	⁽⁴⁾	I	By OrbiMed Israel Partners II, L.P.⁽¹⁾⁽²⁾
Series B redeemable convertible preferred stock	⁽⁴⁾	⁽⁴⁾	Common Stock	789,833	⁽⁴⁾	I	By OrbiMed Private Investments VIII, LP⁽²⁾⁽³⁾

1. Name and Address of Reporting Person^*

ORBIMED ADVISORS LLC

(Last)

(First)

(Middle)

601 LEXINGTON AVENUE

54TH FLOOR

(Street)

NEW YORK

10022

(City)

(State)

(Zip)

1. Name and Address of Reporting Person^*

OrbiMed Capital GP VIII LLC

(Last)

(First)

(Middle)

601 LEXINGTON AVENUE

54TH FLOOR

(Street)

NEW YORK

10022

(City)

(State)

(Zip)

1. Name and Address of Reporting Person^*

OrbiMed Advisors Israel II Ltd

(Last)

(First)

(Middle)

601 LEXINGTON AVENUE

54TH FLOOR

(Street)

NEW YORK

10022

(City)

(State)

(Zip)

1. Name and Address of Reporting Person^*

OrbiMed Israel GP II, L.P.

(Last)

(First)

(Middle)

601 LEXINGTON AVENUE

54TH FLOOR

(Street)

NEW YORK

10022

(City)

(State)

(Zip)

Explanation of Responses:

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

2. Each of the OrbiMed Israel GP II, OrbiMed Israel II, OrbiMed Capital GP VIII LLC ("GP VIII"), and OrbiMed Advisors LLC ("OrbiMed Advisors") 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. The Reporting Persons have designated a representative, Erez Chimovits, to serve on the Issuer's board of directors. This report shall not be deemed an admission that any such entity or person is a beneficial owner of such securities for purposes of Section 16 of the Exchange Act, or for any other purpose.

3. Shares held by OrbiMed Private Investments VIII, LP ("OPI VIII"). GP VIII is the general partner of OPI VIII, and 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 shares held by OPI VIII.

4. Each share of Series A redeemable convertible preferred stock and Series B redeemable convertible preferred stock (collectively, the "Preferred Stock") is convertible into Common Stock on a 1.049-for-one basis at the option of the holder, and will convert automatically upon closing of the Issuer's initial public offering into the number of shares shown in column 3 without payment of consideration. The Preferred Stock has no expiration date.

	/s/ Carl L. Gordon, Member of OrbiMed Advisors LLC	10/10/2024
	/s/ Carl L. Gordon, Member of OrbiMed Capital GP VIII LLC	10/10/2024
	/s/ Carl L. Gordon, Director of OrbiMed Advisors Israel II Ltd.	10/10/2024
	/s/ Carl L. Gordon, Director of OrbiMed Israel GP II, L.P.	10/10/2024
	** Signature of Reporting Person	Date
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 5 (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).
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