Document:

EX-4.3

 Exhibit 4.3 

THIS WARRANT AND THE SHARES OF CAPITAL STOCK ISSUED UPON ANY EXERCISE HEREOF HAVE NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933, AS AMENDED (THE
“SECURITIES ACT”), OR ANY APPLICABLE STATE SECURITIES LAWS AND MAY NOT BE SOLD OR OTHERWISE TRANSFERRED TO ANY PERSON, INCLUDING A PLEDGEE, UNLESS (1) EITHER (A) A REGISTRATION STATEMENT WITH RESPECT THERETO SHALL BE EFFECTIVE
UNDER THE SECURITIES ACT, OR (B) THAT AN EXEMPTION FROM REGISTRATION UNDER THE SECURITIES ACT IS AVAILABLE, AND (2) THERE SHALL HAVE BEEN COMPLIANCE WITH ALL APPLICABLE STATE SECURITIES OR “BLUE SKY” LAWS. 

Void after 5:00p.m. New York Time on the Expiration Date (as defined below) 

 

			
	 Warrant No. A-1
		[DATE]

 WARRANT TO PURCHASE SERIES A CONVERTIBLE PREFERRED 

STOCK OF 
 PROTEOSTASIS
THERAPEUTICS, INC. 
 This is to Certify that, FOR VALUE RECEIVED, [PURCHASER NAME], or its permitted assigns (“Holder”), is
entitled to purchase, subject to the provisions of this Warrant, from Proteostasis Therapeutics, Inc., a Delaware corporation (the “Company”), [NUMBER OF SHARES] fully paid, validly issued and nonassessable shares of Series A Convertible
Preferred Stock of the Company (“Preferred Stock”) at a price per share equal to [PRICE], at any time or from time to time during the period from [DATE] to [DATE] (the “Expiration Date”), but not later than 5:00 p.m. New York
City Time on the Expiration Date. The number of shares of Preferred Stock to be received upon the exercise of this Warrant and the price to be paid for each share of Preferred Stock may be adjusted from time to time as hereinafter set forth. The
shares of Preferred Stock deliverable upon such exercise, and as adjusted from time to time, are hereinafter referred to as “Warrant Shares” and the exercise price for each Warrant Share, as in effect at any time and as adjusted from time
to time is hereinafter referred to as the “Exercise Price.” 
 (a) EXERCISE OF WARRANT 

(1) This Warrant may be exercised in whole or in part at any time or from time to time on or after [DATE] until the Expiration Date (the
“Exercise Period”), provided, however, that if either such day is a day on which banking institutions in the Commonwealth of Massachusetts are authorized by law to close, then on the next succeeding day which shall not be such a day. 

 

 (2) This Warrant may be exercised by presentation and surrender hereof to the Company at its
principal office, or at the office of its stock transfer agent, if any, with the Purchase Form annexed hereto as Exhibit A, duly executed and accompanied by payment of the Exercise Price for the number of Warrant Shares specified in such form. As
soon as practicable after each such exercise of this Warrant, but not later than ten (10) business days from the date of such exercise, the Company shall issue and deliver to the Holder a certificate or certificate for the Warrant Shares
issuable upon such exercise, registered in the name of the Holder or its designee. If this Warrant should be exercised in part only, the Company shall, upon surrender of this Warrant for cancellation, execute and deliver a new Warrant evidencing the
rights of the Holder hereof to purchase the balance of the Warrant Shares purchasable hereunder. Upon receipt by the Company of this Warrant at its office, or by the stock transfer agent of the Company at its office, in proper form for exercise, the
Holder shall be deemed to be the holder of record of the shares of Preferred Stock issuable upon such exercise, notwithstanding that the stock transfer books of the Company shall then be closed or that certificates representing such shares of
Preferred Stock shall not then be physically delivered to the Holder. 
 (3) At any time during the Exercise Period, the Holder may, at its
option, elect to exercise this Warrant, in whole or in part (a “Net Issue Exercise”), by surrendering this Warrant at the principal office of the Company or at the office of its stock transfer agent, accompanied by a notice stating such
Holder’s intent to effect such Net Issue Exercise, the number of Warrant Shares in respect of which this Warrant is being exercised and the date on which the Holder requests that such exercise occur (the “Notice of Net Issue
Exercise”). The Net Issue Exercise shall take place on the date specified in the Notice of Net Issue Exercise or, if later, the date the Notice of Net Issue Exercise is received by the Company (the “Net Issue Exercise Date”).
Certificates for the shares issuable upon such Net Issue Exercise and, if applicable, a new warrant of like tenor evidencing the balance of the shares remaining subject to this Warrant, shall be issued as of the Net Issue Exercise Date and delivered
to the Holder within ten (10) business days following the Net Issue Exercise Date. In connection with any Net Issue Exercise, the number of Warrant Shares that the Company shall be required to issue shall be equal to (i) the number of
Warrant Shares in respect of which this Warrant is being exercised as specified by the applicable Notice of Net Issue Exercise (the “Total Number”) less (ii) the number of Warrant Shares equal to the quotient obtained by dividing
(A) the product of the Total Number and the existing Exercise Price by (B) the current market value of a Warrant Share. Current market value shall have the meaning set forth in Section (c) below, except that for purposes hereof, the
date of exercise, as used in such Section (c), shall mean the Net Issue Exercise Date and that any reference to Common Stock, as used in paragraph (4) of such Section (c), shall mean the series or class of capital stock of the Company for which
this Warrant is exercisable on the Net Issue Exercise Date. 
 (b) RESERVATION OF SHARES. The Company shall at all times reserve for
issuance and/or delivery upon exercise of this Warrant such number of shares of its Preferred Stock as shall be required for issuance and delivery upon exercise of the Warrants. 

  
 2 

 (c) FRACTIONAL SHARES. No fractional shares or script representing fractional shares shall be
issued upon the exercise of this Warrant. With respect to any fraction of a share called for upon any exercise hereof, the Company shall pay to the Holder an amount in cash equal to such fraction multiplied by the current market value of a share,
determined as follows: 
 (1) If the date for such determination is the date on which the Company’s common stock is
first sold to the public by the Company in a firm commitment public offering under the Securities Act of 1933, as amended, then the initial public offering price (before deducting commissions, discounts or expenses) at which the common stock is sold
in such offering; or 
 (2) If the Common Stock is listed on a national securities exchange or admitted to unlisted trading
privileges on such exchange or listed for trading on the Nasdaq National Market System (NMS), the current market value shall be the last reported sale price of the Common Stock on such exchange or market on the last business day prior to the date of
exercise of this Warrant or if no such sale is made on such day, the average closing bid and asked prices for such day on such exchange or market; or 

(3) If the Common Stock is not so listed or admitted to unlisted trading privileges, but is traded on the Nasdaq Global Market
or the OTC Bulletin Board, the current Market Value shall be the last reported sale price for such day on such market and if the Common Stock is not so traded, the current market value shall be the mean of the last reported bid and asked prices
reported on the last business day prior to the date of the exercise of this Warrant; or 
 (4) If the Common Stock is not so
listed or admitted to unlisted trading privileges or if the bid and asked prices are not so reported, the current market value shall be an amount (not less than book value thereof, as of the end of the most recent fiscal year of the Company ending
prior to the date of the exercise of the Warrant) as is determined in such reasonable manner as may be prescribed by the Board of Directors of the Company. 

(d) EXCHANGE, TRANSFER, ASSIGNMENT OR LOSS OF WARRANT. This Warrant is exchangeable, without expense, at the option of the Holder, upon
presentation and surrender hereof to the Company or at the office of its stock transfer agent, if any, for other warrants of different denominations entitling the holder thereof to purchase in the aggregate the same number of shares of Preferred
Stock purchasable hereunder. Upon surrender of this Warrant to the Company at its principal office or at the office of its stock transfer agent, if any, with the Assignment Form annexed hereto as Exhibit B, duly executed and funds sufficient to pay
any transfer tax, and, if requested by the Company, an opinion of counsel reasonably acceptable to the Company that any such assignment may be made without registration under the Securities Act of 1933, as amended, the Company shall, without charge,
execute and deliver a new Warrant in the name of the assignee or assignees named in such instrument of assignment and this Warrant shall promptly be canceled. This Warrant may be divided or combined with other warrants which carry the same rights
upon presentation hereof at the principal office of the Company or at the office of its stock transfer agent, if any, together with a written notice specifying the names and denominations in which new Warrants are to be issued and signed by the
Holder hereof. The term “Warrant” as used herein includes any Warrants into which this Warrant may be divided or exchanged. Upon receipt by the Company of evidence satisfactory to it of the loss, theft, destruction or mutilation of this
Warrant, and (in the case of loss, theft or destruction) of reasonably satisfactory indemnification, and upon surrender and cancellation of this Warrant, if mutilated, the Company will execute and deliver a new Warrant of like tenor and date. 

  
 3 

 (e) RIGHTS OF THE HOLDER. The Holder shall not, by virtue hereof, be entitled to any rights of a
shareholder in the Company, either at law or equity, and the rights of the Holder are limited to those expressed in the Warrant and are not enforceable against the Company except to the extent set forth herein. 

(f) ANTI-DILUTION PROVISIONS. The Exercise Price in effect at any time and the number and kind of securities purchasable upon the exercise of
the this Warrant shall be subject to adjustment from time to time upon the happening of certain events as follows: 
 (1) In
case the Company shall (i) declare a dividend or make a distribution on its outstanding shares of Preferred Stock in shares of Preferred Stock, (ii) subdivide or reclassify its outstanding shares of Preferred Stock into a greater number of
shares, or (iii) combine or reclassify its outstanding shares of Preferred Stock into a smaller number of shares, and there is not a simultaneous adjustment to the conversion price thereof, then there shall be an equitable adjustment of the
Exercise Price in effect at the time of the record date for such dividend or distribution or of the effective date of such subdivision, combination or reclassification so that it shall equal the price determined by multiplying the Exercise Price at
that time by a fraction, the denominator of which shall be the number of shares of Preferred Stock outstanding after giving effect to such action, and the numerator of which shall be the number of shares of Preferred Stock outstanding immediately
prior to such action. Such adjustment shall be made successively whenever any event listed above shall occur and shall be in addition to any subsequent adjustments to the conversion price of the Preferred Stock. 

(2) Whenever the Exercise Price payable upon exercise of this Warrant is adjusted pursuant to Section (f)(l) above, the number
of Warrant Shares purchasable upon exercise of this Warrant at that time shall simultaneously be adjusted by multiplying the number of Warrant Shares initially issuable upon exercise of this Warrant by the Exercise Price in effect on the date hereof
and dividing the product so obtained by the Exercise Price, as adjusted. 

  
 4 

 (3) Whenever the Exercise Price is adjusted, as herein provided, the Company
shall promptly but no later than 10 days after any request for such an adjustment by the Holder, cause a notice setting forth the adjusted Exercise Price and adjusted number of Warrant Shares issuable upon exercise of this Warrant, and, if
requested, information describing the transactions giving rise to such adjustments, to be mailed to the Holder at its last address appearing in the Company’s books and records, and shall notify its transfer agent, if any, of such adjustment.
The Company may retain a firm of independent certified public accountants selected by the Board of Directors (who may be the regular accountants employed by the Company) to make any computation required by this Section (f)(3), and a certificate
signed by such firm shall be conclusive evidence of the correctness of such adjustment. 
 (4) In the event that at any
time, as a result of an adjustment made pursuant to Section (f)(1) above, the Holder of this Warrant thereafter shall become entitled to receive any shares of the Company, other than Preferred Stock, thereafter the number of such shares so
receivable upon exercise of this Warrant shall be subject to adjustment from time to time in a manner and on terms as nearly equivalent as practicable to the provisions with respect to the Preferred Stock contained in Sections (f)(1) to (f)(3),
inclusive above. 
 (5) Irrespective of any adjustments in the Exercise Price or the number or kind of shares purchasable
upon exercise of this Warrant, this Warrant and/or any replacement warrant or warrants theretofore or thereafter issued may continue to express the same price and number and kind of shares as are stated in this Warrant. 

(g) OFFICER’S CERTIFICATE. Whenever the Exercise Price shall be adjusted as required by the provisions of the foregoing Section, the
Company shall forthwith file in the custody of its Secretary or an Assistant Secretary at its principal office and with its stock transfer agent, if any, an officer’s certificate showing the adjusted Exercise Price determined as herein
provided, setting forth in reasonable detail the facts requiring such adjustment, including a statement of the number of additional shares of Common Stock, if any, and such other facts as shall be necessary to show the reason for and the manner of
computing such adjustment. Each such officer’s certificate shall be made available at all reasonable times for inspection by the Holder and the Company shall, forthwith after each such adjustment, mail a copy by certified mail of such
certificate to the Holder. 
 (h) NOTICES TO WARRANT HOLDERS. So long as this Warrant shall be outstanding, (i) if the Company shall
pay any dividend or make any distribution upon the Preferred Stock or Common Stock, or (ii) if the Company shall offer to the holders of Preferred Stock or Common Stock for subscription or purchase by them any share of any class or any other
rights, or (iii) if any capital reorganization of the Company, reclassification of the capital stock of the Company, consolidation or merger of the Company with or into another corporation, sale, lease or transfer of all or substantially all of
the property and assets of the Company to another corporation, or voluntary or involuntary dissolution, liquidation or winding up of the Company shall be effected, then in any such case, the Company shall cause to be mailed by certified mail to the
Holder, at least five business days prior the date specified in (x) or (y) below, as the case may be, a notice containing a brief description of the proposed action and stating the date on which (x) a record is to be taken for the
purpose of such dividend, distribution or rights, or (y) such reclassification, reorganization, consolidation, merger, conveyance, lease, dissolution, liquidation or winding up is to take place and the date, if any is to be fixed, as of which
the holders of Preferred Stock or Common Stock or other securities shall receive cash or other property deliverable upon such reclassification, reorganization, consolidation, merger, conveyance, dissolution, liquidation or winding up. 

  
 5 

 (i) RECLASSIFICATION, REORGANIZATION OR MERGER. In case of any reclassification, capital
reorganization or other change of outstanding shares of Preferred Stock of the Company, or in the case of any consolidation or merger of the Company with or into another corporation (other than a merger with a subsidiary in which merger the Company
is the continuing corporation and which does not result in any reclassification, capital reorganization or other change of outstanding shares of Preferred Stock) or in the case of any sale, lease or conveyance to another corporation of all or
substantially all of the assets of the Company, the Company shall, as a condition precedent to such transaction, cause effective provisions to be made so that the Holder shall have the right thereafter by exercising this Warrant at any time prior to
the Expiration Date to purchase the kind and amount of shares of stock and other securities and property receivable upon such reclassification, capital reorganization and other change, consolidation, merger, sale or conveyance by a holder of the
number of shares of Preferred Stock which might have been purchased upon exercise of this Warrant immediately prior to such reclassification, change, consolidation, merger, sale or conveyance. Any such provision shall include provision for
adjustments which shall be as nearly equivalent as may be practicable to the adjustments provided for in this Warrant. The foregoing provisions of this Section (i) shall similarly apply to successive reclassifications, capital reorganizations
and changes of shares of Preferred Stock and to successive consolidations, mergers, sales or conveyances. Without limiting the generality of the foregoing provisions of this Section (i), this Section (i) shall be applicable to any mandatory
conversion of the Preferred Stock into any series or class of capital stock of the Company and/or any other securities of the Company, provided that, as a result of such mandatory conversion and immediately thereafter, there shall be no outstanding
shares of Preferred Stock. 
 (j) COMPLIANCE WITH SECURITIES ACT. 

(1) Unregistered Securities. The Holder acknowledges that neither this Warrant, nor the Warrant Shares, have been registered
under the Securities Act and agrees not to sell, pledge, distribute, offer for sale, transfer or otherwise dispose of this Warrant or any Warrant Shares in the absence of (i) an effective registration statement under the Securities Act covering
this Warrant or such Warrant Shares and registration or qualification of this Warrant or such Warrant Shares under any applicable “blue sky” or state securities law then in effect, or (ii) the availability of an exemption from any
such registration and qualification. 
 (2) Legend. Any certificates delivered to the Holder representing Warrant Shares
shall bear the following legend or a legend in substantially similar form: 
 “THE SHARES REPRESENTED BY THIS CERTIFICATE HAVE BEEN
TAKEN FOR INVESTMENT AND THEY MAY NOT BE SOLD OR OTHERWISE TRANSFERRED BY ANY PERSON, INCLUDING A PLEDGEE, IN THE ABSENCE OF AN EFFECTIVE REGISTRATION STATEMENT FOR THE SHARES UNDER THE SECURITIES ACT OF 1933, AS AMENDED, OR IF AN EXEMPTION FROM
REGISTRATION IS THEN AVAILABLE.” 

  
 6 

 (k) GOVERNING LAW. This Warrant will be governed by and construed in accordance with and governed
by the laws of the Commonwealth of Massachusetts, without giving effect to the conflict of law principles thereof. 
 (1) NOTICES. All
notices, requests and other communications hereunder shall be in writing, shall be either (i) delivered by hand, (ii) made by facsimile transmission, (iii) sent by overnight courier, or (iv) sent by registered mail, postage
prepaid, return receipt requested. In the case of notices from the Company to the Holder, they shall be sent to the address last furnished to the Company in writing by the Holder. All notices from the Holder to the Company shall be delivered to the
Company at its offices at Proteostasis Therapeutics, Inc., c/o HealthCare Ventures, 55 Cambridge Parkway, Suite 301, Cambridge, MA 02142-1234, facsimile number (617) 252-4342, or such other address and facsimile number as the Company shall so
notify the Holder. All notices, requests and other communications hereunder shall be deemed to have been given (i) by hand, at the time of the delivery thereof to the receiving party at the address of such party described above, (ii) if
made by facsimile transmission, at the time that receipt thereof has been acknowledged by electronic confirmation or otherwise, (iii) if sent by overnight courier, on the next business day following the day such notice is delivered to the
courier service, or (iv) if sent by registered mail, on the fifth (5th) business day following the day such mailing is made. 

(m) Amendments and Waivers. Any term of this Warrant may be amended and the observance of any other term of this Warrant may be waived (either
generally or in a particular instance and either retroactively or prospectively), pursuant to any written instrument signed by the Company and the Holder. Any amendment or waiver effected in accordance with this Section 2(m) shall be binding on
the Holder of this Warrant (and of any securities into which this Warrant is exercisable), each future holder of all such securities and the Company. 

  
 7 

 
			
	PROTEOSTASIS THERAPEUTICS, INC.
		
	By:		 
			Title:
			Printed Name:

  

			
	ACKNOWLEDGED AND AGREED:
	
	[NAME OF PURCHASER]
		
	By:		 
			Title:
			Printed Name:

  
 8 

 Exhibit A 

PURCHASE FORM 
  

	To:	Proteostasis Therapeutics, Inc. 

 The undersigned pursuant to the provisions set forth in the attached Warrant
(No. _____), (the “Warrant”) hereby irrevocably elects to (check one): 
 (A) purchase ______ shares of the Series A Convertible
Preferred Stock, par value $0.001 per share, of Proteostasis Therapeutics, Inc. (the “Preferred Stock”), covered by such Warrant and herewith makes payment of $__________ representing the full purchase price for such shares at the price
per share provided for in such Warrant; or 
 (B) effect a Net Issue Exercise of this Warrant with respect to a total of [_____] shares of
Preferred Stock pursuant to, and in accordance with, the provisions of Section (a)(3) of the Warrant (the undersigned hereby acknowledges and agrees that the number of shares of Preferred Stock actually issued to the undersigned as a result of such
Net Issue Exercise will be less than such [_____] shares of Preferred Stock, in accordance with the provisions of Section (a)(3) of the Warrant). 

The Preferred Stock for which the Warrant may be exercised shall be known herein as the “Warrant Shares.” All capitalized terms used
but not defined herein shall have the meanings ascribed to such terms in the Warrant. 
 The undersigned is aware that the Warrant Shares
have not been and, subject to certain registration rights which the undersigned may otherwise possess, will not be registered under the Securities Act of 1933, as amended (the “Securities Act”) or any state securities laws. The undersigned
understands that reliance by the Company on exemptions under the Securities Act is predicated in part upon the truth and accuracy of the statements of the undersigned in this Purchase Form. 

The undersigned agrees that it will in no event sell or distribute or otherwise dispose of all or any part of the Warrant Shares unless
(1) there is an effective registration statement under the Securities Act and applicable state securities laws covering any such transaction involving the Warrant Shares, or (2) such transaction is exempt from registration. The undersigned
consents to the placing of a legend on its certificate for the Warrant Shares stating that the sale of the Warrant Shares has not been registered and setting forth the restriction on transfer contemplated hereby and to the placing of a stop transfer
order on the books of the Company and with any transfer agents against the Warrant Shares until the Warrant Shares may be legally resold or distributed without restriction. 

The undersigned has considered the federal and state income tax implications of the exercise of the Warrant and the purchase and subsequent
sale of the Warrant Shares. 

 
			
	
	 
		
	Dated:		 

  
 2 

 Exhibit B 

ASSIGNMENT FORM 

ASSIGNMENT SEPARATE FROM WARRANT 

FOR VALUE RECEIVED, ______________________ hereby sells, assigns, and transfers unto _______________________
(i) _________________________ (__________) the right to purchase __________ shares of Series A Convertible Preferred Stock, par value $0.001 per share, of Proteostasis Therapeutics, Inc. (the “Company”) pursuant to the warrant No. A-_
(the “Warrant”) delivered herewith and standing in the name of the undersigned on the books of the Company, and does hereby irrevocably constitute and appoint the Company its attorney to transfer the said Warrant on the books of the
Company with full power of substitution in the premises. 
 Dated: ____________________, __________  

 

			
		
	By:	 	 
	Print Name:
	Title:EX-10.1

 Exhibit 10.1 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH “[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY
WITH THE SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION REQUESTING CONFIDENTIAL TREATMENT PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED. 

RESEARCH, DEVELOPMENT AND COMMERCIALIZATION AGREEMENT 

by and between 

Proteostasis Therapeutics, Inc. 

and 
 Cystic Fibrosis
Foundation Therapeutics, Inc. 
 Dated March 20, 2012 

 CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH “[***]”. A COMPLETE
VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION REQUESTING CONFIDENTIAL TREATMENT PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS
AMENDED. 
  

 TABLE OF CONTENTS 

 

							
	 Article 1 Definitions
		 	1	  
	 Article 2 Research Plan
		 	7	  
	 2.1
		 Commencement; Objective.
		 	7	  
	 2.2
		 Duration of the Research Plan.
		 	7	  
	 2.3
		 Research Diligence.
		 	8	  
	 2.4
		 Research Plan.
		 	8	  
	 2.5
		 Project Advisory Group.
		 	8	  
	 2.6
		 Joint Steering Committee.
		 	9	  
	 2.7
		 Development Committee.
		 	10	  
	 Article 3 Award Payments; Records
		 	10	  
	 3.1
		 Research Funding.
		 	10	  
	 3.2
		 Records; Reporting Obligations; Audits.
		 	12	  
	 Article 4 Commercialization; Royalties
		 	13	  
	 4.1
		 Development and Commercialization of a Product.
		 	13	  
	 4.2
		 Royalties.
		 	13	  
	 4.3
		 Change of Control.
		 	14	  
	 4.4
		 Royalty Disposition.
		 	14	  
	 4.5
		 Tax.
		 	15	  
	 4.6
		 Royalties to PTI.
		 	15	  
	 4.7
		 Sales Reports.
		 	16	  
	 Article 5 Confidentiality
		 	16	  
	 5.1
		 Confidentiality.
		 	16	  
	 5.2
		 Publicity; Use of Name.
		 	17	  
	 Article 6 Publication
		 	18	  
	 6.1
		 Publication of Results.
		 	18	  
	 Article 7 Indemnification
		 	19	  
	 7.1
		 Indemnification by PTI.
		 	19	  
	 7.2
		 Indemnification by CFFT.
		 	20	  
	 7.3
		 Claims Procedures.
		 	20	  
	 7.4
		 Participation; Assuming Control of the Defense.
		 	20	  
	 7.5
		 Limitation of Liability.
		 	20	  
	 Article 8 Intellectual Property
		 	21	  
	 8.1
		 Ownership.
		 	21	  
	 8.2
		 Exclusive License Grant to PTI.
		 	21	  
	 8.3
		 Preparation.
		 	21	  
	 8.4
		 Costs.
		 	21	  
	 8.5
		 Abandonment.
		 	21	  
	 8.6
		 Compounds for Research.
		 	22	  
	 8.7
		 No License.
		 	22	  
	 Article 9 Term and Termination
		 	22	  
	 9.1
		 Term.
		 	22	  
	 9.2
		 Termination by CFFT With Cause.
		 	22	  
	 9.3
		 Termination for CFFT Breach.
		 	23	  
	 9.4
		 General Effect of Termination; Survival.
		 	23	  
	 9.5
		 Interruption License.
		 	23	  
	 Article 10 Representations and Warranties
		 	24	  
	 10.1
		 Representations and Warranties of PTI.
		 	24	  
	 10.2
		 Representations and Warranties of CFFT.
		 	24	  
	 Article 11 Miscellaneous Provisions
		 	25	  
	 11.1
		 Governing Law.
		 	25	  
	 11.2
		 Dispute Resolution.
		 	25	  
	 11.3
		 Interpretation.
		 	26	  
	 11.4
		 Waiver.
		 	26	  
	 11.5
		 Force Majeure.
		 	27	  
	 11.6
		 Severability.
		 	27	  
	 11.7
		 Assignment.
		 	27	  
	 11.8
		 Counterparts.
		 	27	  
	 11.9
		 No Agency.
		 	27	  
	 11.10
		 Notice.
		 	28	  
	 11.11
		 Headings.
		 	29	  
	 11.12
		 Entire Agreement.
		 	29	  
	 11.13
		 No Impairment.
		 	30	  
	 11.14
		 Anti-Terrorism.
		 	30	  

  
 - ii - 

 CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH “[***]”. A COMPLETE
VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION REQUESTING CONFIDENTIAL TREATMENT PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS
AMENDED. 
  

 EXHIBITS 
  

			
	Exhibit A – Research Plan and Budget
	
	Exhibit B – Pre-Approved Trademark Uses

  
 - iii - 

 CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH “[***]”. A COMPLETE
VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION REQUESTING CONFIDENTIAL TREATMENT PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS
AMENDED. 
  

 RESEARCH, DEVELOPMENT AND COMMERCIALIZATION AGREEMENT 

This Agreement is made on this 20th day of March, 2012 (the “Effective
Date”) by and between Proteostasis Therapeutics, Inc. (“PTI”), a Delaware corporation with its principal office at 200 Technology Square, Fourth Floor, Cambridge, MA 02139, and Cystic Fibrosis Foundation Therapeutics, Inc.
(“CFFT”), a nonprofit corporation with its principal offices at 6931 Arlington Road, Bethesda, Maryland, 20814, and shall become effective on the Effective Date (as defined herein). PTI and CFFT are each a “Party,”
and, collectively, the “Parties.” 
 WHEREAS, CFFT’s principal charitable mission is the discovery and development of
drugs to cure or mitigate Cystic Fibrosis, to which CFFT brings significant scientific and human resources and financial support; 

WHEREAS, PTI desires to conduct the Research Plan with the support of CFFT with the aim of potentially developing and commercializing a
Product; and 
 WHEREAS, CFFT wishes to support the Research Plan; 

NOW, THEREFORE, in consideration of the mutual covenants set forth in this Agreement, and for other good and valuable consideration, the
receipt and sufficiency of which are hereby acknowledged, the Parties agree as follows: 
 Article 1 

Definitions 
 For purposes
of this Agreement, the terms defined in this Article 1 shall have the following meanings: 
 1.1. “Affiliate” shall mean,
with respect to any Person, any other Person who directly or indirectly, by itself or through one or more intermediaries, controls, or is controlled by, or is under direct or indirect common control with, such Person. The term “control” as
used in this Section 1.1 means the possession, direct or indirect, of the power to direct or cause the direction of the management and policies of a Person, whether through the ownership of voting securities, by contract or otherwise. Control
will be presumed if one Person owns, either of record or beneficially, more than fifty percent (50%) of the voting stock of any other Person. 

1.2. “Agreement” means this agreement, together with all appendices, exhibits and schedules hereto, and as the same may be
amended or supplemented from time to time hereafter by a written agreement duly executed by authorized representatives of each Party hereto. 

1.3. “Applicable Law” shall mean all applicable foreign, federal, state or local laws, statutes, rules, regulations, orders,
judgments and ordinances, and the applicable policies of any and all locations at which the Research Program is conducted. 

  
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AMENDED. 
  

 1.4. “Approval” shall mean, with respect to any country, all technical,
medical and scientific licenses, registrations, authorizations and approvals of any Regulatory Authority necessary for commercial sale of a Product in that country including and where applicable, approval of NDAs, supplements and amendments,
approval of labeling, packaging, price, reimbursement and manufacturing. 
 1.5. “Award” means an amount equal to [***], up
to a maximum of [***], which Award shall be funded by CFFT to PTI for the Research Plan in accordance with the terms, and subject to the conditions, set forth in this Agreement. 

1.6. “Budget” shall mean the total amount of monies estimated and agreed to by the Parties for the costs and expenses of the
Research Plan, as set forth in the Research Plan, which (a) may be amended from time to time solely upon the mutual written agreement of the Parties, and (b) shall detail the projected allocation and use of: (i) the funds to be paid
by CFFT to PTI with respect of the Award; and (ii) the Matched Funds. 
 1.7. “CFFT” shall have the meaning set forth
in the preamble of this Agreement. 
 1.8. “CFFT Designees” shall have the meaning set forth in Section 2.5.1. 

1.9. “CFFT Patents” shall mean a Patent that claims or discloses a CFFT Sole Invention. 

1.10. “CFFT Sole Invention” shall have the meaning set forth in Section 8.1. 

1.11. “CFTR” shall mean the human Cystic Fibrosis Transmembrane conductance Regulator protein. 

1.12. “Change of Control” shall mean (a) the merger or consolidation of PTI into or with another corporation,
partnership, joint venture, trust or other entity, or the merger or consolidation of any corporation, partnership, joint venture, trust or other entity into or with PTI (in which consolidation or merger the stockholders of PTI receive distributions
of cash or securities as a result of such consolidation or merger in complete exchange for their shares of capital stock of PTI), unless, upon consummation of such merger or consolidation, the holders of voting securities of PTI immediately prior to
such transaction or series of related transactions continue to own, directly or indirectly, not less than a majority of the voting power of the surviving corporation, partnership, joint venture, trust or other entity, (b) the sale or other
disposition in one transaction or a series of related transactions of all or substantially all the assets of PTI, or (c) an exclusive license, in a single transaction or series of related transactions by PTI or any subsidiary of PTI, of all or
substantially all of the assets of PTI and its subsidiaries taken as a whole, and results in a cessation of all or substantially all of the research, development and commercialization activities of PTI and its subsidiaries. 

1.13. “Combination Product” shall have the meaning set forth in Section 1.37.4. 

  
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AMENDED. 
  

 1.14. “Commercially Reasonable Efforts” shall mean, with respect to a Party,
those efforts reasonably used by other companies of similar size as such Party for products of similar commercial potential at a similar stage in their lifecycle. 

1.15. “Confidential Information” shall have the meaning set forth in Section 5.1.1. 

1.16. “Controlled” (except in the context of Section 1.1) shall mean the legal authority or right of a Party hereto
(whether by sole, joint or other ownership interest, license or otherwise, other than pursuant to this Agreement) to grant a license or sublicense of intellectual property rights to another party, without breaching the terms of any agreement with a
Third Party. 
 1.17. “CPR” shall have the meaning set forth in Section 11.2.3. 

1.18. “Cystic Fibrosis” shall mean any one or all of the human diseases commonly known as cystic fibrosis. 

1.19. “Default” shall have the meaning set forth in Section 9.2. 

1.20. “Disposition Royalty” shall have the meaning set forth in Section 4.2.4. 

1.21. “Dispute” shall have the meaning set forth in Section 11.2.1. 

1.22. “Dollars” shall have the meaning set forth in Section 3.1.1. 

1.23. “Effective Date” shall have the meaning set forth in the preamble of this Agreement. 

1.24. “Equipment” means any equipment purchased with the Award. 

1.25. “Field” shall mean Cystic Fibrosis, Non-Classical Cystic Fibrosis, and other pulmonary diseases. 

1.26. “First Commercial Sale” shall mean the first sale of a Product in the Field by PTI or an Affiliate, licensee,
sublicensee, transferee or successor of PTI in a country in the Territory following Approval of the Product in that country or, if no such Approval or similar marketing approval is required, the date upon which a Product is first commercially sold
in that country in an arms-length transaction. For clarity, the supply of a Product in the Field as part of a compassionate use program shall not constitute a First Commercial Sale. 

1.27. “GAAP” shall mean then-current U.S. generally accepted accounting principles consistently applied or, if applicable,
the International Financial Reporting Standards. 
 1.28. “Interruption” shall occur if at any time during the period
between the Effective Date and the date of First Commercial Sale of a Product, PTI, its Affiliates, licensees, sublicensees, 

  
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AMENDED. 
  

 
transferees or successors are not exercising Commercially Reasonable Efforts to develop or commercialize any Product in the Field for a continuous period of one hundred eighty
(180) consecutive days. 
 1.29. “Interruption License” shall have the meaning set forth in Section 9.5. 

1.30. “Joint Invention” shall have the meaning set forth in Section 8.1. 

1.31. “Joint Patents” shall mean a Patent that claims or discloses a Joint Invention. 

1.32. “JSC” shall have the meaning set forth in Section 2.6.1. 

1.33. “Know-How” means any invention, discovery, development, data, information, process, method, technique, materials or
other know-how, whether or not patentable, and any physical embodiments of any of the foregoing (such as laboratory notebooks). 
 1.34.
“Losses” shall have the meaning set forth in Section 7.1. 
 1.35. “Matched Funds” shall have the
meaning set forth in Section 3.1.4. 
 1.36. “NDA” means a new drug application, biological license application,
marketing authorization application, or similar application or submission for Approval of a pharmaceutical product filed with a Regulatory Authority. 

1.37. “Net Sales” with respect to any Product shall mean the gross amount invoiced by or on behalf of the selling party and
its Affiliates, licensees, sublicensees, transferees and/or successors (the “Selling Entities”) for Products sold in bona fide, arms-length transactions to Third Parties other than Selling Entities, less (a) normal and
customary trade, quantity and/or cash discounts from the gross invoice price which are actually allowed or taken; (b) transportation, freight, postage, importation, shipping insurance and other handling expenses; (c) amounts repaid or
credited by reasons of defects, recalls, returns, rebates or allowances of goods or because of retroactive price reductions specifically identifiable to the Product; (d) rebates (or the equivalent thereof) and administrative fees paid to
medical healthcare organizations, to group purchasing organizations or to trade customers in line with approved contract terms or other normal and customary understandings and arrangements; (e) Third Party rebates (or equivalent thereof) or
charge-backs to the extent actually allowed, including such payments mandated by programs of relevant governmental entities; (f) duties, tariffs, excise, sales, value-added and other taxes (excluding income and similar taxes based on net
income), if any, actually paid and directly related to the sale that are not reimbursed by the buyer; (g) reasonable reserves made for uncollectible amounts on previously sold products; (h) discounts pursuant to indigent patient programs
and patient discount programs and coupon discounts; and (i) any other specifically identifiable amounts included in the Product’s gross invoice price that should be credited for reasons substantially equivalent to those listed above; all
as determined in accordance with the Selling Entity’s usual and customary accounting methods and GAAP. 

  
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AMENDED. 
  

 1.37.1. In the case of any sale or other disposal of a Product between or among two Selling
Entities for resale, Net Sales shall be calculated as above only on the value charged or invoiced on the first arm’s-length sale thereafter to a Third Party that is not a Selling Entity. 

1.37.2. In the case of any sale which is not invoiced or is delivered before invoice, Net Sales shall be calculated at the time of shipment or
when the Product is paid for, if paid for before shipment or invoice. 
 1.37.3. In the case of any sale or other disposal for value, such
as barter or counter-trade, of any Product, or part thereof, other than in an arm’s length transaction exclusively for money, Net Sales shall be calculated as above on the value of the consideration received. 

1.37.4. In the event the Product is sold (whether in a finished dosage form, in a form suitable for cellular based therapy, or otherwise)
containing the Product in combination with one or more other active ingredients (a “Combination Product”), the Net Sales of the Product, for the purposes of determining royalty payments, shall be determined by multiplying the Net
Sales (as defined above in this Section) of the Combination Product by the fraction, A/(A+B) where A is average sale price of the Product when sold separately in finished form and B is the average sale price of the other product(s) sold separately
in finished form, provided that the formula set forth above shall not apply if the Product is only sold in combination form and if each of the active ingredients in a Combination Product results from the Research Plan and in each such event the
following sentence shall apply: In the event that such average sale price cannot be determined for both the Product and the other product(s) in combination, Net Sales for purposes of determining royalty payments shall be mutually agreed upon in good
faith by the Parties based on relative value contributed by each component, which such agreement shall not be unreasonably withheld, conditioned or delayed. 

1.38. “Non-Classical Cystic Fibrosis” means a disease or syndrome reasonably linked to malfunction of the CFTR protein by
medical literature. 
 1.39. “Non-Publishing Party” shall have the meaning set forth in Section 6.1. 

1.40. “Owner” shall have the meaning set forth in Section 5.1.2. 

1.41. “PAG” shall have the meaning set forth in Section 2.5.1. 

1.42. “Party(ies)” shall have the meaning set forth in the preamble of this Agreement. 

1.43. “Patents” means all issued patents and existing patent applications and all patent applications hereafter filed,
including any continuation, continuation-in-part, division, provisional, priority, or any substitute applications, any patent issued with respect to any such patent applications, any reissue, reexamination, renewal or extension (including any
supplementary protection certificate) of any such patent, and any confirmation patent or registration patent or patent of addition based on any such patent, and all foreign counterparts of any of the foregoing. 

  
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AMENDED. 
  

 1.44. “Person” means an individual, sole proprietorship, partnership,
limited partnership, limited liability partnership, corporation, limited liability company, business trust, joint stock company, trust, incorporated association, joint venture or similar entity or organization, including a government or political
subdivision or department or agency of a government. 
 1.45. “Prime Rate” shall mean the average prime rate published in
the Wall Street Journal during the relevant period (calculated by dividing (a) the sum of the prime rates for each of the days during the relevant period, by (b) the number of days in the relevant period). 

1.46. “Product” means a pharmaceutical product containing or comprised of (i) a compound identified or developed during
the Term of this Agreement that is a corrector or potentiator of the mutant DF508 CFTR and that is selected by PTI for clinical development to obtain Approval for use in the Field; or (ii) a
diagnostic developed during the Term of this Agreement that is related to a compound described in the preceding clause (i) and that is selected by PTI to obtain Approval for use in the Field. 

1.47. “Program Coordinator” shall have the meaning set forth in Section 2.5.1. 

1.48. “Proposals” shall have the meaning set forth in Section 11.2.3. 

1.49. “PTI” shall have the meaning set forth in the preamble of this Agreement. 

1.50. “PTI Designees” shall have the meaning set forth in Section 2.5.1. 

1.51. “PTI Patents” shall mean a Patent that claims or discloses a PTI Sole Invention. 

1.52. “PTI Sole Invention” shall have the meaning set forth in Section 8.1. 

1.53. “Publishing Party” shall have the meaning set forth in Section 6.1. 

1.54. “Recipient” shall have the meaning set forth in Section 5.1.2. 

1.55. “Recipient Notice Requirement” shall have the meaning set forth in Section 5.1.3. 

1.56. “Regulatory Authority” means any applicable government regulatory authority involved in granting approvals for the
manufacturing, marketing, reimbursement and/or pricing of a Product in the Territory, including, in the United States, the United States Food and Drug Administration and any successor governmental authority having substantially the same function.

 1.57. “Research Plan” shall mean the research plan attached hereto in Exhibit A, which shall cover the
work performed under the Agreement until the Research Termination Date. 
 1.58. “Research Plan Technology” shall have the
meaning set forth in Section 8.1. 

  
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AMENDED. 
  

 1.59. “Research Program” shall mean the research program conducted pursuant
to the Research Plan. 
 1.60. “Research Termination Date” shall mean the date that is the first anniversary of the
Effective Date, unless extended or earlier terminated pursuant to Section 2.2. 
 1.61. “Results” shall have the
meaning set forth in Section 6.1. 
 1.62. “Royalty Cap” shall have the meaning set forth in Section 4.2.1. 

1.63. “Securities Regulatory Authority” shall have the meaning set forth in Section 5.1.3. 

1.64. “Selling Entity” is defined in Section 1.37. 

1.65. “Term” shall have the meaning set forth in Section 9.1. 

1.66. “Territory” shall mean worldwide. 

1.67. “Third Party” shall mean any Person which is not a Party or an Affiliate of any Party to this Agreement. 

1.68. “Transfer Notice” shall have the meaning set forth in Section 4.4. 

Article 2 
 Research Plan

 2.1. Commencement; Objective. PTI shall be solely responsible for the conduct of the Research Plan as set forth herein. CFFT
shall provide the financial support hereinafter specified, and consultation, advice as provided herein through its participation on the PAG and JSC as provided below, and certain research material and know-how that CFFT determines in its sole
discretion can be made available for use in the conduct of the Research Plan and PTI determines is necessary or useful for the conduct of the Research Plan, including human primary epithelial cells, to be used to validate assays, serve as positive
controls, or test the efficacy/potency of discovered compounds. 
 2.2. Duration of the Research Plan. Conduct of the research
performed pursuant to the Research Plan shall commence promptly after the Effective Date and shall conclude on the Research Termination Date, unless earlier terminated in accordance with the provisions of Article 9 hereof. The Parties may mutually
agree in writing to extend the Research Program and the Research Termination Date. 

  
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AMENDED. 
  

 2.3. Research Diligence. 

2.3.1. Generally. PTI shall use Commercially Reasonable Efforts to conduct the Research Program in accordance with, and to effect, the
Research Plan. In furtherance of the foregoing, and in accordance with the terms and conditions of this Agreement (including Section 2.3.2 below), PTI shall commit to the Research Program (i) the level of staffing required by the Research
Plan, with such staff that possess the necessary experience, training and scientific expertise in order for PTI to fulfill its obligations hereunder, and (ii) the infrastructure (e.g., laboratories, offices, equipment and facilities) required
by the Research Plan. 
 2.3.2. Obligations of PTI. Subject to the terms and conditions of this Agreement, and without limiting the
generality of Section 2.3.1 above, PTI shall be solely responsible for the sponsorship, conduct and oversight of the Research Program, which responsibilities shall include, without limitation, (a) utilizing Commercially Reasonable Efforts
to develop and commercialize a Product in the Field; (b) responding to all reasonable requests and inquiries of CFFT for information regarding any of the subject matter hereof during the term of the Research Program; and (c) at PTI’s
election, promptly following the end of the Term (i) returning to CFFT or its designees the Equipment, or (ii) purchasing CFFT’s interest in all or any such Equipment by paying to CFFT an amount equal to [***] of the fair market value
of such Equipment, as evidenced by PTI seeking quotes from [***] dealers of such Equipment. 
 2.4. Research Plan. At each meeting,
the PAG shall consider, review, reevaluate and discuss the Research Plan, taking into consideration ongoing research outcomes and other scientific and commercial developments. Modifications to the Research Plan may be proposed by any Party and shall
be discussed by the PAG and recommendations made in accordance with Section 2.5. 
 2.5. Project Advisory Group. 

2.5.1. Composition and Purposes. During the term of the Research Plan, a Program Advisory Group (“PAG”) shall
facilitate communication between the Parties, and make recommendations, with respect to the Research Plan. The PAG shall consist of four (4) members, two (2) of whom shall be designated by PTI (the “PTI Designees”), and
two (2) of whom shall be designated by CFFT (the “CFFT Designees”). Each Party (a) shall select a coordinator for the Research Program (the “Program Coordinator”) from among its designees to the PAG (who
may be changed at any time or from time to time by such Party with written notice to the other Party), and (b) may change any of its designees to the PAG at any time or from time to time with written notice to the other Party. The Program
Coordinator of PTI shall serve as the Chairperson of the PAG. 
 2.5.2. Responsibilities. Without limiting the generality of the
foregoing, the PAG shall: 
 (a) consider, review, reevaluate and discuss the Research Plan, evaluate any proposed revisions to the
Research Plan, and give its recommendations to the JSC regarding any proposed amendments to the Research Plan; 

  
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AMENDED. 
  

 (b) monitor the progress of the Research Program, and make recommendations to PTI’s
research team as needed on next steps to implement the Research Plan; and 
 (c) make such other recommendations to the JSC as are relevant
to the Research Plan. 
 2.5.3. Termination. The PAG shall be dissolved upon the Research Termination Date, unless the Parties
otherwise agree in writing. 
 2.5.4. Meetings. The PAG shall meet no less frequently than once in each three (3) month period
during the term of the Research Program; provided, however, that the PAG may meet more or less frequently upon mutual agreement of the Program Coordinators. The first meeting of the PAG shall be held within ninety (90) days of the
Effective Date. Meetings of the PAG shall be held at such times and locations as may be mutually agreed by the Program Coordinators, which times and locations shall be communicated in writing (including by email) to the other members of the PAG with
reasonable advance notice of the meeting. At least one (1) PTI Designee and one (1) CFFT Designee shall be required to participate in a meeting for such meeting to be deemed a quorum. So long as a quorum is present at a meeting, the PAG
may make, or decide to make, recommendations to PTI, or take, or decide to take, such actions as are within the scope of the PAG’s authority hereunder. Members of the PAG may attend each meeting either in person or by means of telephone or
other telecommunications device that allows all participants to hear and speak at such meeting simultaneously. At least five (5) business days prior to each meeting, PTI shall deliver (including by email) to the CFFT Designees written material
detailing the progress made on the Research Plan since the last meeting of the PAG. Within twenty (20) days after the date of each meeting, the PTI Designees shall prepare and deliver (including by email) to the CFFT Designees written minutes
of such meeting setting forth in reasonable detail all discussions or recommendations of the PAG made at such meeting, which such minutes shall be subject to the approval of CFFT’s Program Coordinator. 

2.5.5. Discussions/Recommendations. As a general matter, and except as otherwise provided for herein, the PAG shall discuss the items
set forth in Sections 2.5.1 and 2.5.2, make unanimous, non-binding recommendations to the JSC as a result of such discussions, and facilitate communication between the Parties with respect to the Research Plan. 

2.5.6. Expenses. Each Party shall pay its own expenses (including travel and lodging expenses) incurred in connection with its
participation on the PAG. 
 2.6. Joint Steering Committee. 

2.6.1. Composition and Purposes. PTI and CFFT shall establish a Joint Steering Committee (“JSC”) which shall consist of
an equal number of senior management personnel from each Party with the requisite experience and seniority to enable them to make decisions on behalf of the Parties with respect to the initiation, planning and performance of the activities of the
Research 

  
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AMENDED. 
  

 
Plan, as may be agreed by the Parties from time to time. The JSC shall initially have a total of four (4) members, two (2) of whom shall be designated by PTI and two (2) of whom
shall be designated by CFFT. No member shall concomitantly serve on the PAG and the JSC. The Chair of the JSC will be appointed from among the members of the JSC designated by CFFT. The JSC shall be dissolved on the Research Termination Date, unless
the Parties otherwise agree in writing. The JSC shall meet, in person or by means of telephone or other telecommunications device that allows all participants to hear and speak at such meeting simultaneously, semi-annually, or with such other
frequency, and at such time and location or by such means, as may be established by the JSC, for the following purposes: 
 (a) to provide
general oversight of the Research Program; 
 (b) to periodically review the Budget, overall goals and strategy of the Research Program;

 (c) to determine that the Award funds were applied solely for the Research Plan in accordance with the Budget; and 

(d) to discuss and attempt to resolve any deadlocked issues submitted to it by the PAG. 

2.6.2. Voting and Deadlocks. PTI members shall, collectively, have one (1) vote on the JSC, and the CFFT members shall,
collectively, have one (1) vote on the JSC. Decisions of the JSC shall be made by unanimous vote. In the event a deadlock occurs, the JSC shall attempt to resolve such deadlock for a period of twenty (20) days by engaging in good faith
discussions. If such deadlock is not resolved after such twenty (20) day period, then, such deadlock shall be resolved in accordance with the dispute resolution process set forth in Section 11.2, except that (i) any dispute requiring
the amendment of this Agreement, including the exhibits hereto, shall require the agreement of both Parties without regard to Section 11.2 and (ii) any dispute relating to amendments to the Research Plan will be resolved by PTI in its sole
discretion. 
 2.7. Development Committee. Once a compound has been selected by PTI for clinical development, PTI shall maintain a
development committee appropriate to the stage of development of the Product. Such committee shall meet at least semi-annually. CFFT will have the right, but not the obligation, to designate one (1) non-voting member to such committee. 

Article 3 
 Award
Payments; Records 
 3.1. Research Funding. 

3.1.1. Payments. PTI shall submit an invoice in United States Dollars (“Dollars”) to CFFT on a quarterly basis for
payment with respect to the work conducted under the Research Plan, including work delegated to and carried out by contractors under the general direction of PTI 

  
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AMENDED. 
  

 
scientists, during the previous calendar quarter, which invoice shall include a report describing the use of the Award funds and the Matched Funds (including a detailed breakdown of the actual
costs of the Research Plan and how such Award funds and Matched Funds have been allocated and in fact used in respect of the Research Plan). Invoices shall be accompanied by documentation evidencing actual expenditures from the previous quarter,
including the identity of FTEs. For all non-USD expenditures, documentation of the currency conversion rate must be provided. Invoices shall be paid quarterly by CFFT within [***] following receipt by CFFT. All payments to be made hereunder
(including pursuant to Article 4) shall be made in Dollars and, at the option and direction of the receiving party, shall be made by cashier’s or certified check or by wire transfer of immediately available funds. 

3.1.2. Limitations. Notwithstanding Section 3.1.1 above or any contrary provision contained herein, CFFT shall not be required to
make any payment or additional payment in respect of the Award: 
 (a) in excess of [***]; 

(b) upon the occurrence or during the continuance of any uncured default or any material breach by PTI of any of its covenants or obligations
under this Agreement (including PTI’s obligations under Sections 3.1.3 and 3.1.4 below); 
 (c) if a case or proceeding (i) under
the bankruptcy laws of the United States, or relevant non-U.S. law, now or hereafter in effect is filed against PTI or all or substantially all of its assets and such petition or application is not dismissed within sixty (60) days after the
date of its filing or PTI shall file any answer admitting and not contesting such petition, or (ii) under the bankruptcy laws of the United States, or relevant non-U.S. law, now or hereafter in effect or under any insolvency, reorganization,
receivership, dissolution or liquidation law or statute of any jurisdiction now or hereafter in effect (whether at law or equity) is filed by PTI for all or substantially all of its assets; or 

(d) if this Agreement is terminated by any Party in accordance with Article 9. 

3.1.3. Budget. PTI hereby covenants and agrees to use the Award funds provided by CFFT to PTI hereunder solely to fund the Research
Plan in accordance with the Budget (including making applicable payments to subcontractors and vendors). In addition, if, upon conclusion of the Research Program or the termination of this Agreement in accordance herewith, PTI is in possession of
unspent or uncommitted Award funds, then, PTI shall, within sixty (60) days following conclusion of the Research Plan or termination of this Agreement, as applicable, refund such unspent Award funds to CFFT in such manner as CFFT shall
reasonably instruct PTI. 
 3.1.4. Matched Funds. The Parties agree, acknowledge and recognize that the Award represents only partial
financial support for the Research Plan, and PTI agrees to fund [***] (the “Matched Funds”). 

  
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AMENDED. 
  

 3.1.5. Competition. PTI hereby agrees and acknowledges that nothing contained herein
shall restrict or prevent CFFT’s ability to provide funding to, or take any other action with respect to, any Person that competes with a Product, the business, operations, or research of PTI; and PTI hereby waives any claim against CFFT with
respect to any such competing activities; provided, however, that CFFT shall use PTI Confidential Information only in accordance with the provisions of this Agreement, and PTI does not waive any claims relating to use or misuse of PTI
Confidential Information not in accordance with this Agreement. 
 3.2. Records; Reporting Obligations; Audits. 

3.2.1. Records. PTI shall prepare and maintain complete and accurate books and records in connection with the Research Program
(including financial records of expenditures under the Award and the Matched Funds) and the development and commercialization of any Product, and shall keep all such books and records in a manner that is consistent with its document retention
policy. Not more than twice per year during the term of the Research Program, CFFT shall have the right, upon reasonable advanced written notice, to inspect such books and records relating to the Research Program at the offices of PTI during normal
business hours. 
 3.2.2. Response to Inquiries. PTI shall use Commercially Reasonable Efforts to make its personnel (including
licensees, sublicensees, transferees, successors, and subcontractors) involved in conducting the Research Program available to discuss (whether in person or via telephone) with CFFT the books and records delivered by PTI to CFFT at such time or
times as CFFT may reasonably request. 
 3.2.3. Audit. Not more than once per year prior to the Research Termination Date and during
the first year following the Research Termination Date, upon thirty (30) days prior written notice from CFFT, PTI shall permit agents of an independent, certified public accounting firm of nationally recognized standing appointed by CFFT and
reasonably acceptable to PTI, to audit and examine such books and records of PTI as may be necessary for verifying PTI’s compliance with Section 3 and Section 4. Any and all records audited and examined by agents of such accounting
firm shall be deemed PTI’s Confidential Information. PTI may require the accounting firm to sign a reasonably acceptable non-disclosure agreement before providing the accounting firm with access to PTI’s facilities, books or records. Upon
completion of the audit, the accounting firm shall provide both PTI and CFFT a written report disclosing any discrepancies in the reports submitted by PTI or the royalties paid by PTI, and, in each case, the specific details concerning any
discrepancies. No other information shall be provided to CFFT. CFFT shall pay the costs of such audit and examination of the books and records of PTI, provided, however, that, if such audit and examination reveals a
material breach of this Agreement or a discrepancy of more than five percent (5%) with respect to other information previously provided by PTI to CFFT, then, in addition to PTI rectifying such discrepancy, the costs of such audit and
examination shall be borne by PTI and PTI shall reimburse CFFT for such costs. 

  
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AMENDED. 
  

 3.2.4. Reports; Notices. PTI shall furnish to CFFT the following reports or notices:

 (a) Concurrent with the invoice described in Section 3.1.1, a report on the progress made toward achieving the purposes of the
Research Plan, and the development of any Product. 
 (b) As soon as practicable after the Research Termination Date, a closing report
customary for a Research Program at such stage of development which shall (i) be prepared by PTI or a PTI-approved Third Party reasonably satisfactory to CFFT, and (ii) shall set forth PTI’s final analysis, summary tables, data
listings, results and conclusions from the Research Plan. 
 (c) As soon as practicable, and in any event within sixty (60) days after
January 1 of each fiscal year following the Research Termination Date, progress reports and status updates on PTI’s activities with respect to the Research Plan Technology and any Products including the development and commercialization of
any Products. PTI shall include the requirements of this Section 3.2.4(c) in any agreements with sublicensees relating to the development or commercialization of any Products. 

Article 4 

Commercialization; Royalties 

4.1. Development and Commercialization of a Product. 

4.1.1. Development and Commercialization of a Product. Following the Research Termination Date, PTI shall use Commercially Reasonable
Efforts to develop and commercialize a Product in the Field in the United States or in one or more countries of the European Union. 

4.1.2. Commercialization of Product. Except as provided in Section 9.5, PTI and its Affiliates, licensees, sublicensees,
transferees and successors shall have the exclusive rights to develop, commercialize, market, sell and distribute any or all Products throughout the Territory. 

4.2. Royalties. In consideration of CFFT’s payments and licenses to PTI hereunder, PTI shall pay to CFFT the following royalties,
which shall be payable as set forth hereinafter in this Section 4.2: 
 4.2.1. a royalty equal to four (4) times the amount of the
Award (the “Royalty Cap”), such royalty to be paid by PTI to CFFT in as follows: 
 (a) within [***] of First Commercial
Sale, an amount equal to [***]; and 
 (b) an amount equal to the Royalty Cap minus [***] in two (2) equal installments paid within
[***] of the first and second anniversaries of First Commercial Sale. 
 provided that, the royalty payments pursuant to
Section 4.2.1(b) above shall not exceed [***] of Net Sales in the year preceding any year in which a payment is due; any excess of [***] of Net Sales shall be carried over to the following year(s) and added to the payments otherwise due subject
to the aforementioned [***] limitation until the Royalty Cap is fully offset; 

  
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AMENDED. 
  

 4.2.2. an additional royalty payment payable within [***] after [***] of First Commercial
Sale equal to [***] if aggregate Net Sales of the Product in the Field exceed [***] in the first [***] after First Commercial Sale; 

4.2.3. an additional royalty payment payable within [***] after the [***] of First Commercial Sale equal to [***] if aggregate Net Sales of
the Product in the Field exceed [***] by the [***] of First Commercial Sale; and 
 4.2.4. [***] of any amount PTI receives in connection
with the license, sale, or other transfer to a Third Party of rights in the Research Plan Technology other than a Change of Control (a “Disposition Royalty”), provided, however, that the Disposition Royalty shall not
exceed and shall be credited against the Royalty Cap. PTI shall notify CFFT promptly of any transaction that would cause the payment of a Disposition Royalty. 

4.3. Change of Control. 

4.3.1. Alternative Payment. In the event of proposed Change of Control, PTI shall notify CFFT within (30) days following the
execution of a definitive agreement providing for a Change of Control transaction and CFFT may elect to accept in lieu of the royalties specified in Section 4.2 the following: 

(a) if the Change of Control occurs prior to the selection by PTI of a compound intended for Approval as a Product in the Field, a one-time
payment to CFFT; equal to the consideration CFFT would have received if it had 1.5 million shares of PTI common stock; or; 
 (b) if
the Change of Control occurs after the selection by PTI of a compound intended for Approval as a Product in the Field, an amount equal to the consideration CFFT would have received if it had owned 2.5 million shares of PTI common stock. 

4.3.2. Payment Mechanism. If CFFT elects the option in 4.3.1 of this Section, such payment shall be made at the same time as payments
are made to the PTI preferred shareholders in the event of a Change of Control transaction and such preferred shareholders exercise their conversion rights. 

4.4. Royalty Disposition. If CFFT should wish to assign, sell or otherwise transfer rights in or to any of the Royalties due or to
become due from PTI, its Affiliates, successors, assignees, licensees or sublicensees under any of the provisions of this Agreement, or to undertake any transaction which would have the same or a similar effect as any such assignment, sale or
transfer, it will provide PTI with [***] prior written notice (a “Transfer Notice”), and during that [***] period will at PTI’s request negotiate with PTI in good faith, with the objective of reaching an agreement under which
those CFFT rights which were the subject of the Transfer Notice would be assigned, 

  
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AMENDED. 
  

 
sold or transferred to PTI, its successors or assigns in lieu of an assignment, sale, transfer or other transaction to or with a Third Party. If at the end of the [***] period referenced above
PTI and CFFT have been unsuccessful in negotiating mutually agreeable terms of assignment, sale or transfer, then CFFT shall be under no further obligation to PTI under this Section 4.4, unless it shall not conclude a transaction with a Third
Party covering the rights which were the subject of the initial Transfer Notice within [***] after the date of delivery of that Transfer Notice, in which event any subsequent effort to assign, sell or transfer any of those rights shall be once again
subject to the terms of this Section 4.4. 
 4.5. Tax. Any income tax or other tax which PTI is required by applicable legal
requirements to withhold or pay to a governmental authority with respect to monies payable under this section will be deducted from the amount of such payments and paid to the relevant governmental authority. Any amounts actually deducted, withheld
or paid pursuant to the foregoing sentence will be treated for all purposes of this Agreement as paid to the Person in respect of which such withholding, deduction or payment was made. If PTI or any of its Affiliates is required to make any such
payment, deduction or withholding, PTI will notify CFFT of such requirement thirty (30) days prior to the first time any particular type of payment requires such payment, deduction or withholding, and thereafter with respect to each subsequent
payment of that type, indicate the details of the payment, deduction or withholding. Upon written request from CFFT, PTI will promptly provide (or cause to be provided) to CFFT a certificate or other documentary evidence establishing the payment to
the relevant governmental authority of any amount withheld or deducted by PTI or its Affiliates. No deduction shall be made or a reduced amount shall be deducted if PTI or its paying Affiliate is timely furnished with the necessary documents
prescribed by applicable legal requirement in a form reasonably satisfactory to PTI identifying that the payment is exempt from tax or subject to a reduced tax rate. PTI (and its Affiliates) and CFFT will reasonably cooperate in completing and
filing documents required under the provisions of any applicable tax treaty or under any other applicable legal requirement, in order to enable PTI to make such payments to CFFT without any deduction or withholding, or any reduced deduction or
withholding, if feasible without significant expense. 
 4.6. Royalties to PTI. In the event that, pursuant to Section 9.5, the
Interruption License becomes effective and thereafter is maintained by CFFT, in lieu of any other royalties pursuant to this Agreement (other than royalties or payments under Section 4.2 previously paid by PTI to CFFT in accordance with this
Agreement), CFFT shall pay PTI [***] of any amount CFFT receives with respect to the Product (including amounts received in connection with sublicenses of the Interruption License), provided, however, that CFFT’s share shall
increase and PTI’s share shall decrease by [***] for [***], but in no event shall the royalty payable to PTI under this Section 4.6 be decreased below [***] of any amount CFFT receives with respect to the Product (including amounts
received in connection with sublicenses of the Interruption License). 

  
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AMENDED. 
  

 4.7. Sales Reports. 

4.7.1. Within sixty (60) days after the end of each quarter, PTI shall furnish or cause to be furnished to CFFT a written sales report or
reports covering the relevant period setting forth in detail the Net Sales during such period. With respect to sales of Products invoiced in Dollars, the Net Sales amounts and the amounts due to CFFT hereunder shall be expressed in Dollars. With
respect to sales of Products invoiced in a currency other than Dollars, the Net Sales and amounts due to CFFT hereunder shall be expressed in the domestic currency of the party making the sale, together with the Dollar equivalent of the amount
payable to CFFT, calculated by translating foreign currency sales into Dollars in accordance with PTI’s accounting policies. If any licensee or sublicensee makes any sales invoiced in a currency other than its domestic currency, the Net Sales
shall be converted to its domestic currency in accordance with the licensee’s or sublicensee’s normal accounting principles. PTI shall keep accurate records in sufficient detail to enable the amounts due hereunder to be determined and to
be verified by CFFT. 
 4.7.2. In case of any delay in payment by PTI to CFFT not occasioned by force majeure in accordance with
Section 11.5, interest shall be calculated at [***] (or, if lower, the highest percentage permitted by Applicable Law) from the tenth (10th) day after the date upon which the applicable
payment first becomes due from PTI. 
 Article 5 

Confidentiality 
 5.1
Confidentiality. 
 5.1.1. Definition of Confidential Information. For purposes of this Agreement, “Confidential
Information” shall mean all information Recipient (as defined below) received from the Owner (as defined below) in connection with this Agreement, including (a) with respect to both Parties, the financial terms of this Agreement and
any other terms of this Agreement that a Party believes disclosure of which would be harmful to it, and (b) any other Know-How, confidential or proprietary information, or any other knowledge, information, data, reports, documents or materials,
owned, developed or possessed by Owner, whether in tangible or intangible form, the confidentiality of which Owner takes reasonable measures to protect. “Confidential Information” shall not, however, include any information of Owner that:
(a) is already known to Recipient at the time of its disclosure; (b) becomes publicly known through no wrongful act of Recipient; (c) is received from a Third Party free to disclose it to Recipient and without any obligations to Owner
to keep confidential; (d) is independently developed by Recipient without use of the Confidential Information; or (e) is communicated to a Third Party without confidentiality requirements with express written consent of Owner. 

5.1.2. Non-Disclosure. During the term of this Agreement and for a period of five (5) years thereafter, each Party
(“Recipient”) shall hold all Confidential Information it receives or received from or on behalf of the other Party (“Owner”) in strict confidence, and, other than as provided herein or without first obtaining the
prior written consent of Owner, Recipient shall not disclose any Confidential Information of Owner to any Person, except to directors, officers, employees, consultants, committee members, volunteers, contractors, subcontractors, licensees,

  
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AMENDED. 
  

 
sublicensees, accountants or counsel of Recipient who have a need to know and who are subject to terms of confidentiality that are no less stringent than such confidentiality terms under this
Agreement. Recipient shall use not less than a reasonable degree of care to protect such Confidential Information of Owner. 
 5.1.3.
Required Disclosure. Notwithstanding Section 5.1.2 above, Recipient’s disclosure of Confidential Information shall not be prohibited if such disclosure is required by a legally binding requirement; provided, however,
that, Recipient shall have first given prompt notice to Owner of any possible requirement and Owner shall have been afforded a reasonable opportunity to prevent or limit such disclosure (the “Recipient Notice Requirement”);
provided, further, that the Recipient Notice Requirement shall not apply to proceedings which, by applicable law, are of a nature that the existence of such proceedings may not be disclosed or made public in which case Recipient shall
take all legally available measures to minimize or avoid the public disclosure of Owner Confidential Information. In the event that Recipient discloses any Owner Confidential Information pursuant to the immediately preceding sentence, Recipient
shall cooperate with Owner, at Owner’s sole cost and expense, in the prosecution of any appeal that Owner decides to pursue. For any disclosures of this Agreement required by the Securities and Exchange Commission or other body regulating
PTI’s or its Affiliates’ securities (“Securities Regulatory Authority”), PTI shall exercise good faith efforts to give confidential treatment of the information described in Section 5.1.1(a), and PTI shall provide
CFFT with contemporaneous copies of the requests for confidential treatment filed with such Securities Regulatory Authority. 
 5.1.4. No
Use of Confidential Information. Recipient hereby agrees and acknowledges that, other than as provided herein or without first obtaining Owner’s prior written consent, Recipient shall not use any of Owner’s Confidential Information.

 5.2. Publicity; Use of Name. 

5.2.1. Initial Press Release. The Parties shall mutually agree upon the timing and content of any initial press release or other public
announcement relating to this Agreement and the transactions contemplated herein. 
 5.2.2. Future Press Releases. Except to the
extent already disclosed in the initial press release or other public announcement referenced in Section 5.2.1 above, and except as may be otherwise provided herein, neither Party shall issue any press release or make any public announcement
concerning the terms of this Agreement or the transactions described herein without the prior written consent of the other Party, which such consent shall not be unreasonably withheld, conditioned or delayed; provided, however, that it
shall not be unreasonable for any Party to withhold consent with respect to any press release or public announcement containing any of such Party’s Confidential Information; and, provided, further, that this Section 5.2.2
shall not preclude any Party from issuing any such press release or making any such public announcement if such Party reasonably believes that any such release or announcement is (a) legally required by Applicable Laws, or (b) required by
the rules of any stock exchange on which such Party’s (or such Party’s Affiliates’) securities are listed. 

  
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AMENDED. 
  

 5.2.3. Review. In each instance, the Party desiring to issue any press release or to
make any public announcement shall provide the other Party with a written copy of the proposed release or announcement in sufficient time prior to public release to allow such other Party to comment upon such release or announcement prior to its
public release. In addition, each press release or public announcement issued or made pursuant to this Section 5.2 shall include CFFT-approved language acknowledging CFFT’s funding of the Research Plan. 

5.2.4. No Trademark License. Except as may be otherwise provided herein, no Party shall have any right, express or implied, to use in
any manner the name or other designation of the other Party or any other trade name, trademark or logos of the other Party for any purpose. 

5.2.5. Approved Uses. Notwithstanding the foregoing or any contrary provision contained herein, in connection with: (a) any
description by CFFT of its research portfolio and of its industry discovery and development program, or (b) CFFT’s fundraising activities, marketing materials or reporting requirements, CFFT shall be entitled to use or disclose, and PTI
hereby pre-approves CFFT’s use or disclosure of: (i) the mark “PTI” and PTI’s logo, provided that PTI provides prior written approval of such use, (ii) a general description of PTI, (iii) the existence and a
general description of the nature of this Agreement (excluding financial terms), and (iv) a general description of the nature of the Research Program consistent with the confidentiality terms herein; provided, however, CFFT shall
properly use any and all PTI trademarks in a manner so as to not diminish its goodwill. Notwithstanding the foregoing or any contrary provision contained herein, in connection with any description by PTI or its Affiliates of its research portfolio
and of its industry discovery and development program, PTI shall be entitled to use or disclose, and CFFT hereby pre-approves PTI’s use or disclosure of: (i) the mark “CFFT” and CFFT’s logo, provided that CFFT provides prior
written approval of such use, (ii) a general description of CFFT, (iii) the existence and a general description of the nature of this Agreement (excluding financial terms), and (iv) a general description of the nature of the Research
Program consistent with the confidentiality terms herein. The Parties agree that the uses of the mark “PTI” and PTI’s logo by CFFT and the uses of the mark “CFFT” and CFFTs logo, in each case, that are set forth on
Exhibit B, are hereby approved pursuant to this Section 5.2.5 shall not be subject to the foregoing prior written approval requirements. 

Article 6 
 Publication

 6.1. Publication of Results. PTI reserves the first right to publish or publicly present the data generated during the
performance of, or as a result of, the Research Program (the “Results”), subject to the following terms and conditions. To the extent PTI decides not to publish or publicly present the Results, PTI shall in its sole discretion allow
CFFT to publish or publicly present such Results in accordance with this Article 6, such consent will be binding, if and only if, provided in writing in accordance with the notice provisions contained herein. The Party proposing to publish or

  
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AMENDED. 
  

 
publicly present the Results (the “Publishing Party”) will submit a draft of any proposed manuscript, speech, poster or other disclosure to the other Party (the
“Non-Publishing Party”) for comments at least sixty (60) days prior to submission for publication or oral presentation. The Non-Publishing Party shall notify the Publishing Party in writing within thirty (30) days of
receipt of such draft with its comments, which shall be reasonably incorporated by the Publishing Party. The comments of the Non-Publishing Party shall include but not be limited to whether such draft contains (a) information of the
Non-Publishing Party which it considers to be Confidential Information under the provisions of Article 5 hereof, (b) information, including chemical structures of a Product, that if published would have an adverse effect on a Patent which the
Non-Publishing Party intends to file or has filed, or (c) information, which the Non-Publishing Party reasonably believes would be likely to have a material adverse impact on the development or commercialization of a Product. In any such
notification, the Non-Publishing Party shall indicate with specificity its suggestions regarding the manner and degree to which the Publishing Party may disclose such information. In the case of item (a) above, no Party shall publish the
Confidential Information of the other Party without the prior written consent of such other Party in violation of Article 5 of this Agreement. In the case of item (b) above, the Non-Publishing Party may request a delay and the Publishing Party
shall delay such publication, for a period not exceeding an additional one hundred and twenty (120) days, to permit the timely preparation and filing of a patent application or an application for a certificate of invention on the information
involved. In the case of item (c) above, if the Publishing Party shall disagree with the Non-Publishing Party’s assessment of the impact of the publication, then the issue shall be referred to the Program Coordinator of each Party who
shall attempt in good faith to reach a fair and equitable resolution of this disagreement. If the disagreement is not resolved in this manner within fourteen (14) days of referral to the respective Program Coordinators, then the decision of
publication shall be subject to the Dispute Resolution provisions at Section 11.2, subject always to the confidentiality provisions of Article 5 hereof. The Parties agree that authorship of any publication will be determined based on the
customary standards then being applied in the relevant scientific journal. PTI shall acknowledge the financial support of CFFT in all Research Program publications. 

Article 7 

Indemnification 
 7.1.
Indemnification by PTI. PTI shall indemnify, defend and hold harmless CFFT, its Affiliates, and their respective directors, officers, employees and agents (including the CFFT Designees), from and against any and all claims, suits and demands of
Third Parties and losses, liabilities, damages for personal injury, property damage or otherwise, costs, penalties, fines and expenses (including reasonable fees of attorneys) (collectively, “Losses”) arising out of or resulting
from: 
 7.1.1. the conduct of Research Program by PTI and any breach of, or inaccuracy in, any of representations or warranty made by PTI
in this Agreement, or any breach or violation of any covenant or agreement of PTI in or pursuant to this Agreement; 

  
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AMENDED. 
  

 7.1.2. any Product developed in whole or in part as a result of the Research Program; and

 7.1.3. any claim of infringement or misappropriation of intellectual property with respect to the Research Program or any Product
developed in whole or in part as a result of the Research Program. 
 7.2. Indemnification by CFFT. CFFT shall indemnify, defend and
hold harmless PTI, its Affiliates, and their respective directors, officers, employees and agents (including the PTI Designees), from and against any and all Losses arising out of or resulting from: 

7.2.1. any breach of, or inaccuracy in, any of representations or warranty made by CFFT in this Agreement, or any breach or violation of any
covenant or agreement of CFFT in or pursuant to this Agreement; and 
 7.2.2. following any exercise by CFFT of its rights under the
Interruption License, the development, manufacture, use, sale, storage or handling of a Product or a compound described in the definition of Product by CFFT or its Affiliates or their representatives, agents, authorized licensees, sublicensees or
subcontractors under this Agreement. 
 7.3. Claims Procedures. The indemnified party under Section 7.1 or 7.2 shall give notice
to the indemnifying party promptly after receipt by the indemnified party of notice of the commencement of any action, suit or proceeding. Subject to Section 7.5, the indemnifying party shall have the right to assume and manage the defense
thereof (with counsel reasonably satisfactory to the indemnified party), including the right to settle, compromise or litigate with respect to any such claim (but only after obtaining the indemnified party’s prior written consent with respect
to any proposed settlement, compromise or litigation; provided, however, that the indemnifying party shall not be required to obtain the indemnified party’s prior written consent in connection with any proposed settlement,
compromise or litigation if, in connection with and following any such settlement, compromise or litigation, the indemnified party (a) has no liability (monetary or otherwise), (b) has not waived any of its rights and has not admitted to
any wrongdoing or guilt, (c) is not subject to any injunction or other equitable or non-monetary relief, and (d) receives a full and unconditional release of all applicable claims and liability). 

7.4. Participation; Assuming Control of the Defense. Notwithstanding Section 7.3 above, the indemnified party may participate in
the defense of any claim at the indemnified party’s sole expense, with counsel reasonably acceptable to the indemnifying party. 

7.5. Limitation of Liability. NEITHER PARTY SHALL BE LIABLE TO THE OTHER PARTY FOR ANY SPECIAL, INDIRECT, INCIDENTAL, CONSEQUENTIAL,
PUNITIVE OR EXEMPLARY DAMAGES, INCLUDING, BUT NOT LIMITED TO, LOST PROFITS, IN CONNECTION WITH SUCH PARTY’S BREACH OF THIS AGREEMENT. 

  
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AMENDED. 
  

 Article 8 

Intellectual Property 

8.1. Ownership. All Know-How and Patents arising out of the Research Program that are invented, conceived, generated or made
exclusively by PTI or its Affiliates (in the case of each of PTI and its Affiliates, directly or through others acting on its behalf) during the term of this Agreement (a “PTI Sole Invention”) and all Know-How and Patents arising
out of the Research Program that are invented, conceived, generated or made exclusively by CFFT or its Affiliates (directly or through others acting on its behalf) during the term of this Agreement (a “CFFT Sole Invention”) shall be
solely owned by the Party inventing, conceiving, generating or making the Know-How. All Know-How and Patents arising out of the Research Program that are invented, conceived, generated or made by both Parties or their respective Affiliates (directly
or through others acting on its behalf) during the term of this Agreement (a “Joint Invention,” and together with the PTI Sole Inventions and the CFFT Sole Inventions, the “Research Plan Technology”) shall be
jointly owned by the CFFT and PTI. Inventorship shall be determined in accordance with United States patent laws. 
 8.2. Exclusive
License Grant to PTI. Subject to Section 9.5, CFFT hereby grants and agrees to grant to PTI, the consideration of which is acknowledged, an exclusive (even as to CFFT), fully paid up, worldwide, perpetual license with the right to grant
sublicenses to all its rights under the CFFT Sole Inventions and CFFT Patents, and under CFFT’s interest in the Joint Inventions and the Joint Patents for all purposes, including to make, have made, use, sell, have sold, offer to sell, and
import Products. CFFT acknowledges and agrees that it does not retain any rights to any Sole Invention or any Joint Invention or any Patents claiming such Inventions for any purpose whatsoever. 

8.3. Preparation. PTI will control in its sole discretion the preparation, filing, prosecution, maintenance and enforcement of all PTI
Patents, CFFT Patents and Joint Patents. During the Term, CFFT will have the right to review, and PTI will deliver to CFFT, all patent applications directed to CFFT Sole Inventions and Joint Inventions prior to their filing. CFFT agrees to execute
any documents of assignment, declaration, or otherwise reasonably necessary for PTI to file, prosecute, maintain and enforce the PTI Patents, CFFT Patents and Joint Patents. 

8.4. Costs. PTI shall be responsible for all costs incurred in the preparation, prosecution, maintenance and enforcement of PTI
Patents, CFFT Patents, and Joint Patents. 
 8.5. Abandonment. Notwithstanding any contrary provision contained herein and to the
extent possible under pre-existing intellectual property obligations of PTI, prior to PTI (or any Affiliate, licensee, sublicensee, transferee or successor of PTI) abandoning any PTI Patents or Joint Patents (including abandonment for failure to pay
any required fees) for any reason other than an insurmountable prosecution obstacle as solely determined by PTI, PTI shall promptly notify CFFT, or cause CFFT to be notified, of such pending abandonment, whereupon CFFT shall have the right and
opportunity to prosecute or maintain the applicable Patent at CFFT’s own expense. PTI hereby agrees to exercise its good faith efforts to obtain such consents, on CFFT’s behalf, as may be necessary, advisable or appropriate for CFFT to
exercise its rights under this Section 8.5. 

  
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AMENDED. 
  

 8.6. Compounds for Research. During the term of the Agreement, PTI will upon request
provide CFFT with a non-exclusive right for it or a Third Party to use one or more compounds discovered by PTI as a result of it performing the Research Plan that is not incorporated in any Product and that PTI selects in its sole discretion for it
to provide to a limited number of researchers designated by CFFT to be used solely for non-commercial research purposes in the Field. 

8.7. No License. Except as provided in Section 9.5, nothing in this Agreement shall be construed as a grant or obligation of grant
of any license of any kind or a change of title from PTI to CFFT or any Third Party under any Patent or Know-how owned or controlled by PTI unless explicitly stated herein. 

Article 9 
 Term and
Termination 
 9.1. Term. This Agreement shall become effective as of the Effective Date and, unless earlier terminated pursuant
to the other provisions of this Article 9, shall terminate at such time as when there are no longer any payment obligations under Article 4 hereto (the “Term”). 

9.2. Termination by CFFT With Cause. Notwithstanding any provision contained herein to the contrary, CFFT may, without prejudice to any
other remedies available to it at law or in equity, terminate this Agreement upon the occurrence of any of the following events (each, a “Default”) (provided, however, that, in each instance (other than pursuant to
Section 9.2.3), PTI shall have thirty (30) days following the earlier of PTI’s receipt of written notice from CFFT to PTI of the occurrence of a Default or PTI becoming aware of such Default to cure such Default): 

9.2.1. Any material breach or default by PTI in the performance of any of its material covenants or obligations hereunder; 

9.2.2. Any representation or warranty made by PTI in this Agreement is not true in any material respects as of the date made; or 

9.2.3. A case or proceeding (i) under the bankruptcy laws of the United States now or hereafter in effect is filed against PTI or all or
substantially all of its assets and such petition or application is not dismissed within sixty (60) days after the date of its filing or PTI shall file any answer admitting and not contesting such petition, or (ii) under the bankruptcy
laws of the United States now or hereafter in effect or under any insolvency, reorganization, receivership, dissolution or liquidation law or statute of any jurisdiction now or hereafter in effect (whether at law or equity) is filed by PTI for all
or substantially all of its assets. 

  
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AMENDED. 
  

 9.3. Termination for CFFT Breach. Notwithstanding any provision contained herein to
the contrary, PTI may, without prejudice to any other remedies available to it at law or in equity, terminate this Agreement in the event CFFT shall have (a) materially breached or defaulted in the performance of any of its material covenants
or obligations hereunder or (b) any representation or warranty made by CFFT in this Agreement is not true in any material respects as of the date made, in each of clause (a) and (b), where such breach or default shall have continued for
thirty (30) days after written notice thereof was provided to CFFT by PTI. 
 9.4. General Effect of Termination; Survival. 

9.4.1. Termination or expiration of this Agreement for any reason shall be without prejudice to any rights that shall have accrued to the
benefit of any Party prior to such termination or expiration. Such termination or expiration shall not relieve any Party from obligations which are expressly indicated to survive termination of this Agreement. 

9.4.2. If this Agreement is terminated for any reason, all of the Parties’ rights and obligations under, or the provisions contained in,
Sections 3.2, 8.1, 8.2, 8.7, and 9.4, and Article 1, Article 4, Article 5, Article 6, and Article 11. 
 9.4.3. Subject to Section 8.5
and to the license that may be granted under Section 9.5.1, upon termination or expiration of this Agreement, PTI will retain ownership or exclusive rights, as the case may be, to the Research Plan Technology, including the rights licensed to
PTI by CFFT pursuant to Article 8 of this Agreement (including intellectual property rights). 
 9.5. Interruption License. Effective
as of the Effective Date, PTI hereby grants to CFFT with respect to the Research Plan the license described in Section 9.5.1 below (the “Interruption License”), which shall become exercisable by CFFT upon: (i) CFFT
providing PTI with written notice of an Interruption that identifies the Product forming the basis for the alleged Interruption and provides reasonable details to substantiate the claim of the Interruption; and (ii) either (a) PTI fails to
refute in writing the existence of the Interruption within sixty (60) days of the date of CFFT’s written notice of the Interruption, or (b) within such sixty (60) day period, PTI fails to present to CFFT a plan reasonably
acceptable to CFFT for PTI to resume Commercially Reasonable Efforts with respect to the Product that formed the basis for the Interruption: 

9.5.1. An irrevocable, exclusive (even as to PTI) worldwide license, with the right to sublicense, under the all of PTI’s interest in the
Research Plan Technology to develop, manufacture, have manufactured, use, sell, offer to sell and import the Product that created the basis for the Interruption, as applicable, solely for use in continuing development or commercialization of that
same Product in the Field. 
 9.5.2. In the event that PTI transfers all of or certain of its rights and obligations to develop and
commercialize a Product in the Field at any time, the Third Party to which PTI transfers all or certain rights and obligations to develop and commercialize the Product in the Field shall be subject to the obligations of the Interruption License. The
Interruption License shall be deemed to constitute intellectual property as defined in Section 365(n) of the U.S. Bankruptcy 

  
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AMENDED. 
  

 
Code. PTI agrees that CFFT, as a licensee of such rights, shall retain and may exercise all of its rights and elections under the U.S. Bankruptcy Code; provided, however, that
nothing in this Agreement shall be deemed to constitute a present exercise of such rights and elections. 
 9.5.3. In connection with this
Section 9.5, PTI will deliver to CFFT at CFFT’s expense, within sixty (60) days following the date when the Interruption License becomes effective, copies of all materials and data relating to the Product that formed the basis for the
Interruption, and all other materials and data that PTI may own and/or Control that are required by CFFT to develop and commercialize such Product. 

9.5.4. In connection with this Section 9.5, CFFT will assume all costs and expenses relating to the filing, prosecution, maintenance and
enforcement of all Joint Patents and Patents covering the Product that formed the basis for the Interruption arising after the effective date of the Interruption License, including any and all costs and expenses associated with registering the
Interruption License at patent offices throughout the Territory. 
 Article 10 

Representations and Warranties 

10.1. Representations and Warranties of PTI. PTI represents and warrants to CFFT that: (a) this Agreement has been duly executed
and delivered by PTI and constitutes the valid and binding obligation of PTI, enforceable against PTI in accordance with its terms, except as enforceability may be limited by bankruptcy, fraudulent conveyance, insolvency, reorganization, moratorium
and other laws relating to or affecting creditors’ rights generally and by general equitable principles; (b) the execution, delivery and performance of this Agreement have been duly authorized by all necessary action on the part of PTI and
its directors and stockholders; (c) the individual executing this Agreement on behalf of PTI is duly authorized to do so; and (d) no provision contained in this Agreement violates any other agreement to which PTI is bound or otherwise
subject. 
 10.2. Representations and Warranties of CFFT. CFFT represents and warrants to PTI that: (a) this Agreement has been
duly executed and delivered by CFFT and constitutes the valid and binding obligation of CFFT, enforceable against CFFT in accordance with its terms, except as enforceability may be limited by bankruptcy, fraudulent conveyance, insolvency,
reorganization, moratorium and other laws relating to or affecting creditors’ rights generally and by general equitable principles; (b) the execution, delivery and performance of this Agreement have been duly authorized by all necessary
action on the part of CFFT and its directors; (c) the individual executing this Agreement on behalf of CFFT is duly authorized to do so; (d) no provision contained in this Agreement violates any other agreement to which CFFT is bound or
otherwise subject; and (e) CFFT has all necessary right and authority to grant the licenses in this Agreement and to provide the materials set forth in this Agreement or the Research Plan. 

  
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AMENDED. 
  

 Article 11 

Miscellaneous Provisions 

11.1. Governing Law. This Agreement shall be governed by and construed in accordance with the internal laws of the Commonwealth of
Massachusetts. 
 11.2. Dispute Resolution. 

11.2.1. In the event of any dispute, claim or controversy arising out of, relating to or in any way connected to the interpretation of any
provision of this Agreement, the performance of either Party under this Agreement or any other matter under this Agreement, including any action in tort, contract or otherwise, at equity or law (a “Dispute”), either Party may at any
time provide the other Party written notice specifying the terms of such Dispute in reasonable detail. As soon as practicable after receipt of such notice, the JSC shall meet at a mutually agreed upon time and location for the purpose of resolving
such Dispute. Members of the JSC shall engage in good faith discussions and negotiations for a period of up to thirty (30) days to resolve the Dispute or negotiate an interpretation or revision of the applicable portion of this Agreement which
is mutually agreeable to both Parties without the necessity of formal dispute resolution procedures relating thereto. 
 11.2.2. In the
event that a Dispute arises with respect to scientific or technical aspects of the Research Plan or the conduct of the Research Program, and such Dispute is not resolved by the JSC pursuant to Section 11.2.1, then the Dispute shall be referred
to a panel of three independent scientific experts in the Field. Each Party will appoint one such expert, and the two experts so chosen will select a third who will serve as chairperson of the panel. The independent expert panel’s decision
shall be final and binding and its costs shall be borne as directed by the independent panel. Each Party shall cooperate in good faith with the panel. In the event that the Parties are unable to agree as to whether a particular dispute is governed
by this Section 11.2.2, then this Section 11.2.2 shall be utilized to resolve such dispute. 
 11.2.3. In the event a Dispute
arises, other than those Disputes described in Section 11.2.2, and such Dispute is not resolved by the JSC pursuant to Section 11.2.1, then the Parties shall resolve such Dispute by final and binding arbitration. Whenever a Party decides
to institute arbitration proceedings, it shall give written notice to that effect to the other party. Arbitration shall be held in Washington, D.C., according to the then-current commercial arbitration rules of the Center for Public Resources
(“CPR”), except to the extent such rules are inconsistent with this Section 11.2. The arbitration will be conducted by a panel of three (3) arbitrators. Each Party will appoint one such arbitrator, and the two arbitrators
so chosen will select a third who will serve as chairperson of the panel. Any arbitrator chosen or selected hereunder shall have educational training and industry experience sufficient to demonstrate a reasonable level of relevant scientific,
financial, medical and industry knowledge. Within twenty (20) days of the selection of the arbitrators, each Party shall submit to the arbitrators a proposed resolution of the Dispute that is the subject of the arbitration (the
“Proposals”). The arbitrators shall thereafter select one of the Proposals so submitted as the resolution of the Dispute, but may not alter the terms of either Proposal and may 

  
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AMENDED. 
  

 
not resolve the Dispute in a manner other than by selection of one of the submitted Proposals. If a Party fails to submit a Proposal in accordance with the terms of this Section 11.2.3, the
arbitrators shall select the Proposal of the other Party as the resolution of the Dispute. The arbitrators shall agree to render their opinion within thirty (30) days of the final arbitration hearing. No arbitrator shall have the power to award
punitive damages under this Agreement regardless of whether any such damages are contained in a Proposal, and such award is expressly prohibited. The proceedings and decisions of the arbitrators shall be confidential, final and binding on all of the
Parties. Judgment on the award so rendered may be entered in a court having jurisdiction thereof. The Parties shall share the costs of arbitration according to the decision of the arbitrators. 

11.2.4. Nothing in this Section 11.2 will preclude either Party from seeking equitable relief or interim or provisional relief from a
court of competent jurisdiction, including a temporary restraining order, preliminary injunction or other interim equitable relief, concerning a dispute either prior to or during any arbitration if necessary to protect the interests of such Party or
to preserve the status quo pending the arbitration proceeding. 
 11.3. Interpretation. Except where the context expressly requires
otherwise, (a) the use of any gender herein shall be deemed to encompass references to either or both genders, and the use of the singular shall be deemed to include the plural (and vice versa), (b) the words “include”,
“includes” and “including” shall be deemed to be followed by the phrase “without limitation”, (c) the word “will” shall be construed to have the same meaning and effect as the word “shall”,
(d) any definition of or reference to any agreement, instrument or other document herein shall be construed as referring to such agreement, instrument or other document as from time to time amended, supplemented or otherwise modified (subject
to any restrictions on such amendments, supplements or modifications set forth herein), (e) any reference herein to any Person shall be construed to include the Person’s successors and assigns, (f) the words “herein”,
“hereof” and “hereunder”, and words of similar import, shall be construed to refer to this Agreement in its entirety and not to any particular provision hereof, (g) all references herein to sections, exhibits or schedules
shall be construed to refer to sections, exhibits or schedules of this Agreement, and references to this Agreement include all exhibits and schedules hereto, (h) the word “notice” means notice in writing (whether or not specifically
stated) and shall include notices, consents, approvals and other written communications contemplated under this Agreement, (i) provisions that require that a Party, the Parties or any committee hereunder “agree,” “consent”
or “approve” or the like shall require that such agreement, consent or approval be specific and in writing, whether by written agreement, letter, approved minutes or otherwise (but excluding e-mail and instant messaging, unless expressly
indicated otherwise), (j) references to any specific law, rule or regulation, or article, section or other division thereof, shall be deemed to include the then-current amendments thereto or any replacement or successor law, rule or regulation
thereof, and (k) the term “or” shall be interpreted in the inclusive sense commonly associated with the term “and/or.” 

11.4. Waiver. No provision of this Agreement may be waived except in writing by both Parties hereto. No failure or delay by either
Party hereto in exercising any right or remedy hereunder or under applicable law will operate as a waiver thereof, or a waiver of any right or remedy on any subsequent occasion. 

  
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AMENDED. 
  

 11.5. Force Majeure. Neither Party will be in breach hereof by reason of its delay in
the performance of or failure to perform any of its obligations hereunder, if that delay or failure is caused by strikes, acts of God or the public enemy, riots, incendiaries, interference by civil or military authorities, compliance with
governmental priorities for materials, or any fault beyond its reasonable control. In such event PTI or CFFT, as the case may be, shall immediately notify the other Party of such inability and of the period for which such inability is expected to
continue. The Party giving such notice shall thereupon be excused from such of its obligations under this Agreement as it is thereby disabled from performing for so long as it is so disabled. To the extent possible, each Party shall use reasonable
efforts to minimize the duration of any force majeure. 
 11.6. Severability. Should one or more provisions of this Agreement be or
become invalid, then the Parties hereto shall attempt to agree upon valid provisions in substitution for the invalid provisions, which in their economic effect come so close to the invalid provisions that it can be reasonably assumed that the
Parties would have accepted this Agreement with those new provisions. If the Parties are unable to agree on such valid provisions, the invalidity of such one or more provisions of this Agreement shall nevertheless not affect the validity of the
Agreement as a whole, unless the invalid provisions are of such essential importance for this Agreement that it may be reasonably presumed that the Parties would not have entered into this Agreement without the invalid provisions. 

11.7. Assignment. This Agreement may not be assigned or otherwise transferred by either Party without the prior written consent of the
other Party; provided, however, that either Party may assign this Agreement, without the consent of the other Party, (i) to any of its Affiliates, if the assigning Party unconditionally guarantees the full performance of its
Affiliate’s obligations hereunder, or (ii) in connection with such Party’s merger, consolidation or transfer or sale of all or substantially all of the assets of such Party, provided that in the case of an asset sale, the
acquiring party expressly assumes in full in writing such Party’s obligations under this Agreement. Any purported assignment in contravention of this Section 11.7 shall, at the option of the non-assigning Party, be null and void and of no
effect. No assignment shall release either Party from responsibility for the performance of any accrued obligation of such Party hereunder. This Agreement shall be binding upon and enforceable against the successor to or any permitted assignees from
either of the Parties hereto. 
 11.8. Counterparts. This Agreement may be executed in duplicate via facsimile or PDF file, each of
which shall be deemed to be original and both of which shall constitute one and the same Agreement. 
 11.9. No Agency. Nothing
herein contained shall be deemed to create an agency, joint venture, partnership or similar relationship between CFFT and PTI. Notwithstanding any of the provisions of this Agreement, neither Party to this Agreement shall at any time enter into,
incur, or hold itself out to Third Parties as having authority to enter into or incur, on behalf of the other Party, 

  
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AMENDED. 
  

 
any commitment, expense, or liability whatsoever, and all contracts, expenses and liabilities in connection with or relating to the obligations of each Party under this Agreement shall be made,
paid, and undertaken exclusively by such Party on its own behalf and not as an agent or representative of the other. 
 11.10.
Notice. All communications between the Parties with respect to any of the provisions of this Agreement will be sent to the addresses set out below, or to such other addresses as may be designated by one party to the other by notice pursuant
hereto, by prepaid, certified air mail (which shall be deemed received by the other Party on the seventh (7th) business day following deposit in the mails), or by facsimile transmission, or
other electronic means of communication (which shall be deemed received when transmitted), with confirmation by first class letter, postage pre-paid, given by the close of business on or before the next following business day: 

if to CFFT, at: 
 Robert J.
Beall, Ph.D. 
 President and CEO 

6931 Arlington Rd.; Suite 200 

Bethesda, Maryland 20814 

Phone:    301-907-2541 

Fax:        301-907-2699 

Email:     [***] 

with a copy to: 
 Kenneth I.
Schaner, Esq. 
 Schaner & Lubitz, PLLC 

6931 Arlington Rd.; Suite 200 

Bethesda, Maryland 20814 

Phone:    240-482-2848 

Fax:        202-470-2241 

Email:     [***] 

  
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AMENDED. 
  

 if to PTI, at: 

Mark J. Enyedy, CEO 

Proteostasis Therapeutics, Inc. 

200 Technology Square, Suite 402 

Cambridge, Massachusetts 02139 

Phone:    617-225-0096 

Fax:        617-225-7801 

Email:     [***] 

with a copy to: 
 Paul M.
Kinsella 
 Ropes & Gray 

Prudential Tower 
 800 Boylston
Street 
 Boston, MA 02199-3600 

Phone:    617-951-7921 

Fax:        617-235-0822 

11.11. Headings. The paragraph headings are for convenience only and will not be deemed to affect in any way the language of the
provisions to which they refer. 
 11.12. Entire Agreement. This Agreement contains the entire understanding of the Parties relating
to the matters referred to herein, and may only be amended by a written document, duly executed on behalf of the respective Parties. 

  
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AMENDED. 
  

 11.13. No Impairment. Neither Party will, by amendment of its organizational or
governing documents, or through reorganization, recapitalization, consolidation, merger, dissolution, sale, transfer or assignment of assets, issuance of securities, or any other voluntary action, avoid or seek to avoid the observance or performance
of any of the terms, provisions, covenants or agreements of this Agreement, but rather will at all times in good faith assist in the carrying out of all such terms, provisions, covenants and agreements and in the taking of all such actions as may be
necessary, advisable or appropriate in order to protect the rights of the other Party against impairment. 
 11.14.
Anti-Terrorism. In accordance with the U.S. Department of the Treasury Anti-Terrorist Financing Guidelines, PTI shall take reasonable steps to ensure that the payments received from CFFT are not distributed to terrorists or their support
networks or used for activities that support terrorism or terrorist organizations. PTI certifies that it is in compliance with all laws, statutes and regulations restricting U.S. persons from dealing with any individuals, entities, or groups subject
to Office of Foreign Assets Control (OFAC) sanctions. 
 (Remainder of page intentionally left blank) 

  
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AMENDED. 
  

 IN WITNESS WHEREOF, the undersigned have executed this Research, Development and
Commercialization Agreement as of the date first written above. 
  

									
	CYSTIC FIBROSIS FOUNDATION THERAPEUTICS, INC.				PROTEOSTASIS THERAPEUTICS, INC.
					
	By:		 /s/ Robert J. Beall
				By:		 /s/ Mark J. Enyedy

	Name:		Robert J. Beall, Ph.D.				Name:		Mark J. Enyedy
	Title:		President and CEO				Title:		Chief Executive Officer

  
 Signature Page to
Research, Development and Collaboration Agreement 

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AMENDED. 
  

 Exhibit A 

Research Plan and Budget 

(see attached) 
 [***]

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AMENDED. 
  

 Exhibit B 

Pre-Approved Trademark Uses 

Pre-Approved Uses by CFFT: 
  

	 	•	 	Use of PTI name and logo in CFFT corporate presentations 

 Pre-Approved Uses by PTI: 

 

	 	•	 	Use of CFFT name and logo in PTI corporate presentations 

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AMENDED. 
  

 Amendment No. 1 to the Research, Development and Commercialization Agreement 

This Amendment No. 1 (“Amendment”) is made as of May 6, 2013 (“Effective Date”) by and between Cystic Fibrosis
Foundation Therapeutics, Inc. (“CFFT”) and Proteostasis Therapeutics, Inc. (“PTI”) to that certain Research, Development and Commercialization Agreement dated as of March 20, 2012 (the “Agreement”). Capitalized
terms used in this Amendment and not defined shall have the meaning ascribed to them in the Agreement. 
 WHEREAS CFFT and PTI desire to
modify certain terms and conditions of the Agreement; 
 NOW THEREFORE, in consideration of the mutual covenants contained in this
Agreement, the parties hereby agree as follows: 
  

	 	1.	Section 1.5 of the Agreement is hereby deleted in its entirety and replaced with the following: 

“1.5. “Award” means an amount equal to [***], up to a maximum of [***], which Award shall be funded by CFFT to PTI for
the Research Plan in accordance with the terms, and subject to the conditions, set forth in this Agreement.” 
  

	 	2.	Section 3.1.2 (a) of the Agreement is hereby deleted in its entirety and replaced with the following: 

“(a) in excess of [***];”. 

Except as herein modified, all other terms and conditions of the Agreement shall remain the same and in full force and effect. 

IN WITNESS WHEREOF, the parties have caused this Amendment to be executed by their respective duly authorized representatives as of the
Effective Date. 
  

									
	CYSTIC FIBROSIS FOUNDATION THERAPEUTICS, INC.				PROTEOSTASIS THERAPEUTICS, INC.
					
	By:		 /s/ Robery J. Beall
				By:		 /s/ David M. Weiner

	Name:		Robert J. Beall, Ph.D.				Name:		David M. Weiner, MD
	Title:		President and CEO				Title:		Interim CEO and CMO
	Date:		February 8, 2014				Date:		February 14, 2014

 CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH “[***]”. A COMPLETE
VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION REQUESTING CONFIDENTIAL TREATMENT PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS
AMENDED. 
  

 Amendment No. 2 to the 

Research, Development and Commercialization Agreement of March 20, 2012 and as
first amended by Amendment No. 1 as of May 6, 2013 (collectively, the “Agreement”) by and between 

Proteostasis Therapeutics, Inc. 

and 
 Cystic Fibrosis Foundation
Therapeutics, Inc. 
 This Amendment No. 2 is entered into by and between Proteostasis Therapeutics, Inc. (“PTI”) and the
Cystic Fibrosis Foundation Therapeutics, Inc. (“CFFT”) as of the 1st day of January, 2014. 

WHEREAS, PTI has requested supplemental funding of [***] for conducting additional research according to the research plan (the
“Supplemental Research Plan”) attached to this Amendment No. 2 as Exhibit A, and CFFT is willing to provide such funding (the “Supplemental Award”) in accordance with this Amendment; 

NOW THEREFORE, the Parties agree as follows: 

1. Agreement. Except as specified in this Amendment No. 2, the terms and conditions of the Agreement shall remain in full force and effect; and
the capitalized terms in this Amendment shall have the same meaning as in the Agreement. 
 2. Amendments. The Agreement is hereby amended as
follows: 
 (a) The following sections of the Agreement are hereby amended: 

(i) The amount specified in Section 1.5, of “[***]”, shall be increased by the Supplemental Awards provided
pursuant to Amendments No. 1 and 2 to “[***]” , which shall be inserted in lieu thereof; 
 (ii) The term
Matched Funds shall also include PTI funding equal to [***] provided pursuant to Amendments No. 1 and 2; 
 (iii) The
amount specified in Section 3.1.2(a) shall be increased by deleting “[***]” and inserting in lieu thereof “[***]; 

 CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH “[***]”. A COMPLETE
VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION REQUESTING CONFIDENTIAL TREATMENT PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS
AMENDED. 
  

 (iv) The percentage “[***]” specified in Sections 4.2.1 and 4.2.4
shall be deleted and “[***]” shall be inserted in lieu thereof; 
 (v) The number of shares “1.5 million”
specified in Section 4.3.1(a) shall be deleted and “2.852 million” shall be inserted in lieu thereof; 
 (vi)
The number of shares “2.5 million” specified in Section 4.3.1(b) shall be deleted and “4.753 million” shall be inserted in lieu thereof; 

(b) The Exhibits attached to this Amendment No. 2 shall be as follows: Exhibit A shall be the Supplemental Research Plan and shall
specify the work to be performed by PTI in connection with this Supplemental Award; Exhibit B shall specify the Supplemental Budget for the Supplemental Research Plan and shall cover this Supplemental Award and PTI Matched Funds. 

(c) The Supplemental Award provided by this Amendment 2 shall be paid by CFFT quarterly in accordance with this Supplemental Budget after
receipt of invoices from PTI. 
 In WITNESS WHEREOF, the undersigned have executed this Amendment No. 2 as of the date first written above. 

 

									
	CYSTIC FIBROSIS FOUNDATION THERAPEUTICS, INC.				PROTEOSTASIS THERAPEUTICS, INC.
					
	By:		 /s/ Robert J. Beall
				By:		 /s/ David M. Weiner

	Name:		Robert J. Beall, Ph.D.				Name:		David M. Weiner, MD
	Title:		President and CEO				Title:		Interim CEO and CMO
	Date:		February 14, 2014				Date:		February 14, 2014

 CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH “[***]”. A COMPLETE
VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION REQUESTING CONFIDENTIAL TREATMENT PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS
AMENDED. 
  

 EXHIBIT A 

SUPPLEMENTAL RESEARCH PLAN 
 [***]

 CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH “[***]”. A COMPLETE
VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION REQUESTING CONFIDENTIAL TREATMENT PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS
AMENDED. 
  

 EXHIBIT B 

SUPPLMENTAL BUDGET FOR THE SUPPLEMENTAL RESEARCH PLAN 

[***]

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