Exhibit 10.1

FIRST AMENDMENT TO THE
EMPLOYMENT AGREEMENT BETWEEN JOHN SHANNON (“EXECUTIVE”) AND XERIS
PHARMACEUTICALS, INC. (“COMPANY”)

THIS FIRST AMENDMENT (this “Amendment”) to the Employment Agreement dated June
6, 2018 between Executive and the Company (the “Employment Agreement”) is made
effective as of August 18, 2020. Capitalized terms used herein, and not
otherwise defined shall have the meanings ascribed thereto in the Employment
Agreement.

RECITALS

WHEREAS, the parties desire to amend the Employment Agreement as set forth
herein.

NOW, THEREFORE, the Agreement is hereby amended and modified as follows:

1.Amendments.
a.Section 1(b) is deleted in its entirety and replaced with the following:

“(b) Position and Duties. During the Term, the Executive shall serve as the
President and Chief Operating Officer of the Company, and shall have supervision
and control over and responsibility for the day-to-day business and affairs of
the Company and shall have such other powers and duties as may from time to time
be prescribed by the Board of Directors of the Company (the “Board”), the Chief
Executive Officer of the Company (the “CEO”) or other authorized executive. The
Executive shall devote his full working time and efforts to the business and
affairs of the Company. Notwithstanding the foregoing, the Executive may serve
on other boards of directors, with the approval of the Board, or engage in
religious, charitable or other community activities as long as such services and
activities are disclosed to the Board and do not materially interfere with the
Executive’s performance of his duties to the Company as provided in this
Agreement.”

b.The first sentence in Section 2(a) is hereby deleted in its entirety and
replaced with the following: “During the Term, the Executive’s annual base
salary shall be $500,000.” The remainder of Section 2(a) shall remain unchanged.

c.The second sentence in Section 2(b) is hereby deleted in its entirety and
replaced with the following: “The Executive’s initial target annual incentive
compensation shall be 50% of his Base Salary (the “Target Annual Incentive
Compensation”).” The remainder of Section 2(b) shall remain unchanged.

2. Miscellaneous.

a.Except for the specific amendments set forth in Section 1 above, the other
terms of the Employment Agreement remain unchanged and in full force and effect.

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b.This Amendment may be executed in two or more counterparts, each of which will
be deemed an original but all of which together will constitute one and the same
instrument.

[Signature Page Follows]

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IN WITNESS WHEREOF, the parties have executed this Amendment as of the date
first set forth above.

XERIS PHARMACEUTICALS, INC.

By: /s/ Paul R. Edick
Paul R. Edick, Chairman and Chief Executive Officer
EXECUTIVE
By: /s/ John Shannon
John Shannon