Amendment No. 1 to Collaboration and License Agreement, dated July 1, 2017, with Sanofi-Aventis Deutschland GmbH

This Amendment No. 1 to Collaboration and License Agreement (this “Amendment”), is dated as of July 1st, 2017 (the “Amendment Effective Date”) and is entered into by and between Lexicon Pharmaceuticals, Inc., a Delaware corporation (“Lexicon”), and SANOFI-AVENTIS DEUTSCHLAND GmbH, a German corporation (assignee of SANOFI, a société anonyme under the laws of France), with its principal place of business at 65926 Frankfurt am Main, Germany (“Sanofi”). Lexicon and Sanofi are sometimes referred to herein individually as a “Party” and collectively as the “Parties.” Capitalized terms used but not defined herein shall have the meanings ascribed to such terms in the Agreement.

WHEREAS, Lexicon and SANOFI entered into a Collaboration and License Agreement, dated as of November 5, 2015 (the “Agreement”), and SANOFI subsequently assigned its rights and obligations thereunder to SANOFI-AVENTIS DEUTSCHLAND GmbH as of December 30, 2015.

WHEREAS, Lexicon and Sanofi have agreed to amend (a) the initial Development Plan with respect to T2DM and certain development milestone payments associated therewith, (b) the definition of European Union and (c) such other terms and conditions of the Agreement as contemplated herein.

NOW, THEREFORE, in consideration of the premises and the mutual covenants and agreements of the Parties contained in this Amendment, the Parties hereby agree as follows:

As of the Amendment Effective Date, the initial Development Plan with respect to T2DM contained in Schedule 3.1.2 to the Agreement shall be replaced by the Development Plan for T2DM attached hereto as Exhibit 3.1.2.

For the avoidance of doubt, it is hereby acknowledged that this Amendment is not subject to a Lexicon Consent Right pursuant to Section 1.99(iii).

“Study [**]“ means that certain study described as [**] study in the Development Plan with respect to [**].

“Study [**]” means that certain study described as [**] study in the Development Plan with respect to [**].

“Study [**]” means that certain study described as [**] study in the Development Plan with respect to [**].

“Study [**]” means that certain study described as [**] study in the Development Plan with respect to [**].

“Study [**]” means that certain study described as [**] study in the Development Plan with respect to [**].

“Benefit Data” shall mean the Study Data from Study [**] or from Study [**].

“Initial Data” means [**].

“European Union” or “EU” means the economic, scientific and political organization of member states as it may be constituted from time to time, which as of the Execution Date consists of Austria, Belgium, Bulgaria, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, The Netherlands, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden and the United Kingdom of Great Britain and Northern Ireland and that certain portion of Cyprus included in such organization. For the avoidance of doubt (including for the purpose of Section 12.3.2(iii)), any country which was a member state of the EU as of the Execution Date (including any Major Market), but which subsequently ceases to be a member state of the EU for any reason, including withdrawal, shall not be considered part of the EU as from the date of its effective withdrawal from the EU.

“European Territory” means the European Union and, as applicable, any Major Market which was a member state of the EU as of the Execution Date, but which subsequently ceases to be a member state of the EU for any reason, including withdrawal. For the avoidance of doubt, any country which was a member state of the EU as of the Execution Date (other than a Major Market), but which subsequently ceases to be a member state of the EU for any reason, including withdrawal, shall not be considered part of the European Territory as from the date of its effective withdrawal from the EU.

“Tier 2 Countries” means the European Union (other than Major Markets located in the European Union) (including, notwithstanding the definition of European Union hereunder, any non-Major Market member state of the European Union as of the Effective Date which subsequently ceases to be a member state of the European Union for any reason, including withdrawal), and all current and future members of the European Free Trade Association, or the Commonwealth of Independent States, Brazil, Russia, India, China, South Korea, Australia, New Zealand, Canada, Mexico, Chile, Argentina, Turkey, Taiwan, Singapore, Saudi Arabia, Kuwait, United Arab Emirates, Qatar, and Israel.

Section 3.1.3 of the Agreement shall be deleted and replaced by the following effective as of the Amendment Effective Date:

3.1.3    Decision Points and Positive Results for Development Activities. The Development Plan sets forth certain decision points associated with the completion of certain clinical studies (the “Decision Points”). At each Decision Point, within [**] after the earlier of (i) [**] and (ii) [**], the JSC shall determine whether or not Positive Results have been achieved. With respect to a given Decision Point, “Positive Results” means, based on review of [**] (in the case of clause (i)) or [**] (in the case of clause (ii)) the following, as applicable:

(a)    in the case of [**],[**];

(b)    in the case of [**], [**]; and

(c)    in all other cases, [**].

If Positive Results have not been achieved, then (a) Sanofi may elect to terminate this Agreement as set forth in Section 12.3.2(i)(b) or (b) the JSC may elect to immediately discontinue or cancel all or part of any Development activities under the Development Plan that are conditioned on the achievement of Positive Results with respect to the applicable Decision Point, including any ongoing or planned clinical studies or regulatory filings, or to

modify the Development Plan as it deems appropriate in good faith, in the interest of securing Regulatory Approval for a Licensed Product in the Field in the Major Markets in the Territory.

As a result of the amendment of the initial Development Plan pursuant to Section 1 hereof, Section 7.2.1(a) of the Agreement shall be replaced with the following effective as of the Amendment Effective Date:

(iii)    For the European Territory:

(a)for that portion of aggregate Net Sales of all Licensed Products in the European Territory during a Calendar Year less than or equal to [**], a royalty rate of [**];

(b)for that portion of aggregate Net Sales of all Licensed Products in the European Territory during a Calendar Year greater than [**], but less than or equal to [**], a royalty rate of [**]; and

(c)for that portion of aggregate Net Sales of all Licensed Products in the European Territory during a Calendar Year greater than [**], a royalty rate of [**].

(iv)    For all countries in the Territory, other than the United States and those countries in the European Territory (such countries, “ROW”), the royalty rate shall be [**] of aggregate Net Sales of all Licensed Products in ROW.

THIS AMENDMENT No. 1 TO COLLABORATION AND LICENSE AGREEMENT IS EXECUTED by the authorized representatives of the parties as of the date first written above.

By: _____________________________            By: _________________________________

Name: ___________________________            Name: _______________________________

Title: ____________________________            Title: ________________________________

[**]for T2DM: [**]