Center for Technology Licensing 1155 York Avenue New York, NY 10065 P: 646.962.7045 innovation.weill.cornell.edu

Exhibit 10.21

Center for Technology Licensing 0000 Xxxx Xxxxxx Xxx Xxxx, XX 00000 P: 646.962.7045 xxxxxxxxxx.xxxxx.xxxxxxx.xxx

February 11, 2024

Xxxxx Xxxxxxxxx

Chief Business and Legal Officer

Lexeo Therapeutics, Inc.

000 Xxxx Xxxxxx Xxxxx, 0xx Floor

New York, NY 10010

Via email: xxxxxxxxxxx@xxxxxxx.xxx

RE: THIRD AMENDMENT

to the FIRST LICENSE AGREEMENT by and between Lexeo Therapeutics, Inc. (hereinafter “Licensee”) and Cornell University (“Cornell”) (each a “Party”) effective May 28, 2020 and amended a first time effective July 4, 2022 and a second time effective September 28, 2022 (Cornell Contract C2020-11-13204) (the “First License Agreement”)

Effective the date of the last signature hereto (“Amendment Date”), the Parties agree to hereby modify the First License Agreement as follows:

1) Appendix A: Inventions is hereby amended to include:

CORNELL DOCKET		TITLE		INVENTORS		SPONSOR FUNDING DISCLOSED BY INVENTOR		ADDITIONAL INFO
10699 (LEXE-014)		Gene Therapy for APOE4-associated Alzheimer’s Disease		Xxxxxx X. Xxxxxxx Xxxxx Günaydin Xxxxxxx X. Xxxxxxxx Xxxxx Xxxxxx Xxxxx Xxxxxx		Lexeo RCA		Portfolio APOE

2) Appendix B1: Patent Rights is hereby amended to include:

CORNELL DOCKET		TITLE		FILING DATE		COUNTRY		APPLICATION NO.		STATUS
10699-01-US		Methods and Pharmaceutical Compositions for the Treatment and the Prevention of Alzheimer’s Disease		April 18, 2023		United States		63/496,910		Filed
10699-02-US		Methods and Pharmaceutical Compositions for the Treatment and the Prevention of Alzheimer’s Disease		October 23, 2023		United States		63/592,469		Filed
10699-03-US		Methods and Pharmaceutical Compositions for the Treatment and the Prevention of Alzheimer’s Disease		October 20, 2023		United States		63/592,123		Filed

3) The lists of dockets on the cover page and in the Notices section of the First License Agreement shall include “D-10699”.

4) The lead paragraph in Paragraph 3.3(a)(iii) is hereby amended to read:

(iii) develop a Licensed Product based on Cornell Dockets D-9134, or D-10405, D-10699, or IND 018406 (“Portfolio APOE”) as follows, wherein each row in the following table is an obligation under this Paragraph 3.3(a)(iii):

MILESTONE TO BE ACHIEVED		TIME FROM EFFECTIVE DATE BY WHICH MILESTONE MUST BE ACHIEVED
Commence a Phase II Clinical Trial of a Licensed Product		Five (5) years
File a BLA for a Licensed Product		Ten (10) years

; and

5) As consideration for this Amendment, Licensee will pay Cornell an amendment fee of Thirty Thousand Dollars ($30,000.00) within thirty (30) days of the Amendment Date.

6) These changes do not otherwise change the terms and conditions of the First License Agreement.

7) This Amendment may be executed by electronic signatures or by facsimile and in two (2) or more counterparts, each of which shall be deemed an original and all of which together shall constitute but one and the same instrument.

IN WITNESS WHEREOF, both Cornell and Licensee have executed this Amendment by their respective and duly authorized officers on the day and year written.

CORNELL UNIVERSITY						LEXEO THERAPEUTICS, INC.
By:		/s/ Xxxx Xxxxxxxxx				By:		/s/ R. Xxxxx Xxxxxxxx
		[Signature of Authorized Officer]						[Signature of Authorized Officer]
Name:		Xxxx Xxxxxxxxx				Name:		X. Xxxxx Xxxxxxxx
Title:		Senior Managing Director				Title:		Chief Executive Officer
Date:		Feb 16, 2024				Date:		Feb 16, 2024

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