EX-10.1



 Exhibit 10.1 

Amendment No. 4 to Collaboration and License Agreement 

This Amendment No. 4 to Collaboration and License Agreement (this “Amendment No. 4”) is made and effective
as of January 31, 2016, by and between Proteostasis Therapeutics, Inc., a corporation existing under the laws of the State of Delaware, having a place of business at 200 Technology Square,
4th Floor, Cambridge, MA 02139 (“PTI”) and Astellas Pharma Inc., a Japanese corporation having its principal place of business at 5-1 Nihonbashi-Honcho 2-Chome,
Chuo-ku, Tokyo 103-8411, Japan (“Astellas”). Each of Astellas and PTI is sometimes referred to individually herein as a “Party” and collectively as the “Parties”. 

Reference is hereby made to that certain Collaboration and License Agreement dated November 4, 2014 and amended on May 1,
2015, August 5, 2015, and December 1, 2015 by and between the Parties (the “Agreement”). Capitalized terms used, but not defined herein shall have the meanings ascribed to such terms in the Agreement. 

WHEREAS, the Parties now wish to further amend the Agreement pursuant to the terms and conditions set forth herein; 

NOW, THEREFORE, in consideration of the premises, the mutual covenants contained herein and other valuable consideration, the receipt and
sufficiency of which are hereby acknowledged, the Parties hereby agree as follows: 
 1. Section 2.3(b) is deleted in its entirety and
replaced with the following language: 
  

	 	“(b)	Hit Series. Following the HTS Phase for each Project, PTI will present the results of the HTS Phase to the JRC and the JRC will assess the results of the HTS Phase in accordance with the guideline set forth in
the Research Plan (Hit Series Criteria Guideline) and the potential development path for various screened Active Compounds. Following the presentation of the results of the HTS Phase to the JRC, Astellas may designate one or more Hit Series to be
taken forward into the Optimization Phase by providing written notice to PTI no later than July 31, 2016. Following the conclusion of the HTS Phase, if an Active Compound is not included in a Hit Series designated by Astellas to be taken
forward into the Optimization Phase, it will thereafter be a Discontinued Compound and may not thereafter be designated as part of a Hit Series.” 


2. The Parties agree to amend the Research Plan to conduct additional experiments (the “Additional Experiments”) as approved by the
Joint Research Committee under Section 5.2(b)(iv). Astellas shall bear one million dollars ($1,000,000) of the costs and expenses, and PTI shall bear remaining costs and expenses necessary to conduct the Additional Experiments. The Parties
agree that Section 6.2 (a), (b), and (c) of the Agreement shall not apply during the period from February 1, 2016 to July 31, 2016. 

3. Except as amended hereby, all other terms of the Agreement shall remain unchanged and in full force and effect. 

4. This Amendment No. 4 will be governed by, and construed in accordance with, the laws of the state of New York, without taking into
consideration any choice of law principles that would lead to the application of the laws of another jurisdiction. 







 IN WITNESS WHEREOF, the Parties have caused this Amendment No. 4 to be executed by their duly authorized
representatives. 
  

									
	ASTELLAS PHARMA INC.	 		 	PROTEOSTASIS THERAPEUTICS, INC.
					
	By:	 	/s/ Shunichiro Matsumoto	 		 	By:	 	/s/ Meenu Chhabra
	 Name: Shunichiro Matsumoto
 Title:
Vice President, Innovation Management
	 		 	 Name: Meenu Chhabra
 Title:
President and Chief Executive Officer



  
 2