Document:

prqr_Ex4_18

		

			Exhibit 4.18

		

		

			Execution Version

		

		
			SHARE PURCHASE AGREEMENT
		

		
			By and Between
		

		
			IONIS PHARMACEUTICALS, INC.
		

		
			AND
		

		
			PROQR THERAPEUTICS N.V.
		

		
			Dated as of October 26, 2018
		

		
			 
		

		
			 
		

		
			

		 

		

			 

		

 

		

			 

		

		

		
			TABLE OF CONTENTS
		

			
					
						 

					
					
						 

					
					
						    

					
					
						Page

				
	
					
						 

					
					
						 

					
					
						 

					
					
						 

				
	
					
						1.

					
					
						Definitions

					
					
						 

					
1
				
	
					
						 

					
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						1.1       Defined Terms

					
					
						 

					
1
				
	
					
						 

					
					
						1.2       Additional Defined Terms

					
					
						 

					
5
				
	
					
						 

					
					
						 

					
					
						 

					
					
						 

				
	
					
						2.

					
					
						Purchase and Sale of Ordinary Shares

					
					
						 

					
5
				
	
					
						 

					
					
						 

					
					
						 

					
					
						 

				
	
					
						3.

					
					
						Closing Date; Deliveries

					
					
						 

					
6
				
	
					
						 

					
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						3.1       Closing Date

					
					
						 

					
6
				
	
					
						 

					
					
						3.2       Deliveries

					
					
						 

					
6
				
	
					
						 

					
					
						 

					
					
						 

					
					
						 

				
	
					
						4.

					
					
						Representations and Warranties of the Company

					
					
						 

					
7
				
	
					
						 

					
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						4.1       Organization, Good Standing and Qualification

					
					
						 

					
7
				
	
					
						 

					
					
						4.2       Capitalization and Voting Rights

					
					
						 

					
7
				
	
					
						 

					
					
						4.3       Subsidiaries

					
					
						 

					
7
				
	
					
						 

					
					
						4.4       Authorization

					
					
						 

					
8
				
	
					
						 

					
					
						4.5       No Defaults

					
					
						 

					
8
				
	
					
						 

					
					
						4.6       No Conflicts

					
					
						 

					
8
				
	
					
						 

					
					
						4.7       No Governmental Authority or Third Party Consents

					
					
						 

					
8
				
	
					
						 

					
					
						4.8       Valid Issuance of Shares

					
					
						 

					
9
				
	
					
						 

					
					
						4.9       Litigation

					
					
						 

					
9
				
	
					
						 

					
					
						4.10     Licenses and Other Rights; Compliance with Laws

					
					
						 

					
9
				
	
					
						 

					
					
						4.11     Company SEC Documents; Financial Statements; Nasdaq Stock Market

					
					
						 

					
9
				
	
					
						 

					
					
						4.12     Absence of Certain Changes

					
					
						 

					
10
				
	
					
						 

					
					
						4.13     Offering

					
					
						 

					
10
				
	
					
						 

					
					
						4.14     No Integration

					
					
						 

					
10
				
	
					
						 

					
					
						4.15     Brokers’ or Finders’ Fees

					
					
						 

					
10
				
	
					
						 

					
					
						 

					
					
						 

					
					
						 

				
	
					
						5.

					
					
						Representations and Warranties of the Investor

					
					
						 

					
10
				
	
					
						 

					
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						5.1       Organization; Good Standing

					
					
						 

					
10
				
	
					
						 

					
					
						5.2       Authorization

					
					
						 

					
11
				
	
					
						 

					
					
						5.3       No Conflicts

					
					
						 

					
11
				
	
					
						 

					
					
						5.4       No Governmental Authority or Third Party Consents

					
					
						 

					
11
				
	
					
						 

					
					
						5.5       Purchase Entirely for Own Account

					
					
						 

					
11
				
	
					
						 

					
					
						5.6       Disclosure of Information

					
					
						 

					
12
				
	
					
						 

					
					
						5.7       Investment Experience and Accredited Investor Status

					
					
						 

					
12
				
	
					
						 

					
					
						5.8       Acquiring Person

					
					
						 

					
12
				
	
					
						 

					
					
						5.9       Restricted Securities

					
					
						 

					
12
				
	
					
						 

					
					
						5.10     Legends

					
					
						 

					
12
				
	
					
						 

					
					
						 

					
					
						 

					
					
						 

				
	
					
						6.

					
					
						Investor’s Conditions to Closing

					
					
						 

					
12
				
	
					
						 

					
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						6.1       Representations and Warranties

					
					
						 

					
12
				
	
					
						 

					
					
						6.2       Covenants

					
					
						 

					
13
				
	
					
						 

					
					
						6.3       Investor Agreement

					
					
						 

					
13
				
	
					
						 

					
					
						6.4       License Agreement

					
					
						 

					
13
				

		 

		

			i

		

 

		

			 

		

	
					
						

					
						 

					
					
						 

					
					
						 

					
					
						 

				
	
					
						7.

					
					
						Company’s Conditions to Closing

					
					
						 

					
13
				
	
					
						 

					
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						7.1       Representations and Warranties

					
					
						 

					
13
				
	
					
						 

					
					
						7.2       Covenants

					
					
						 

					
13
				
	
					
						 

					
					
						7.3       Investor Agreement

					
					
						 

					
13
				
	
					
						 

					
					
						7.4       License Agreement

					
					
						 

					
13
				
	
					
						 

					
					
						 

					
					
						 

					
					
						 

				
	
					
						8.

					
					
						Mutual Conditions to Closing

					
					
						 

					
13
				
	
					
						 

					
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						8.1       HSR Act and Other Qualifications

					
					
						 

					
14
				
	
					
						 

					
					
						8.2       Absence of Litigation

					
					
						 

					
14
				
	
					
						 

					
					
						8.3       No Prohibition

					
					
						 

					
14
				
	
					
						 

					
					
						8.4       Milestones

					
					
						 

					
14
				
	
					
						 

					
					
						 

					
					
						 

					
					
						 

				
	
					
						9.

					
					
						Termination

					
					
						 

					
14
				
	
					
						 

					
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						9.1       Ability to Terminate

					
					
						 

					
14
				
	
					
						 

					
					
						9.2       Effect of Termination

					
					
						 

					
15
				
	
					
						 

					
					
						 

					
					
						 

					
					
						 

				
	
					
						10.

					
					
						Additional Covenants and Agreements

					
					
						 

					
15
				
	
					
						 

					
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						10.1     Market Listing

					
					
						 

					
15
				
	
					
						 

					
					
						 

					
					
						 

					
					
						 

				
	
					
						11.

					
					
						Miscellaneous

					
					
						 

					
16
				
	
					
						 

					
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						11.1     Governing Law

					
					
						 

					
16
				
	
					
						 

					
					
						11.2     Waiver

					
					
						 

					
16
				
	
					
						 

					
					
						11.3     Notices

					
					
						 

					
16
				
	
					
						 

					
					
						11.4     Entire Agreement

					
					
						 

					
16
				
	
					
						 

					
					
						11.5     Amendments

					
					
						 

					
16
				
	
					
						 

					
					
						11.6     Headings; Nouns and Pronouns; Section References

					
					
						 

					
16
				
	
					
						 

					
					
						11.7     Severability

					
					
						 

					
17
				
	
					
						 

					
					
						11.8     Assignment

					
					
						 

					
17
				
	
					
						 

					
					
						11.9     Successors and Assigns

					
					
						 

					
17
				
	
					
						 

					
					
						11.10   Counterparts

					
					
						 

					
17
				
	
					
						 

					
					
						11.11   Third Party Beneficiaries

					
					
						 

					
17
				
	
					
						 

					
					
						11.12   No Strict Construction

					
					
						 

					
17
				
	
					
						 

					
					
						11.13   Survival of Warranties

					
					
						 

					
17
				
	
					
						 

					
					
						11.14   Remedies

					
					
						 

					
18
				
	
					
						 

					
					
						11.15   Expenses

					
					
						 

					
18
				

		
			 
		

		
			Exhibit A – Form of Cross Receipt
		

		
			Exhibit B – Form of Investor Agreement
		

		
			Exhibit C – Notices
		

		
			 
		

		
			 
		

		
			

		 

		

			ii

		

 

		

		
			SHARE PURCHASE AGREEMENT
		

		
			THIS SHARE PURCHASE AGREEMENT (this “Agreement”), dated as of October 26, 2018 (the “Execution Date”), by and between Ionis Pharmaceuticals, Inc. (the “Investor”), a Delaware corporation, and ProQR Therapeutics N.V. (the “Company”), a public company with limited liability incorporated under the laws of the Netherlands.
		

		
			WHEREAS, pursuant to the terms and subject to the conditions set forth in this Agreement, the Company desires to issue and sell to the Investor, and the Investor desires to subscribe for and purchase from the Company, certain ordinary shares, nominal value Euro 0.04 per ordinary share of the Company (the “Ordinary Shares”).
		

		
			NOW, THEREFORE, in consideration of the following mutual promises and obligations, and for good and valuable consideration, the adequacy and sufficiency of which are hereby acknowledged, the Investor and the Company agree as follows:
		

		
			1.         Definitions.
		

		
			1.1       Defined Terms. When used in this Agreement, the following terms shall have the respective meanings specified therefor below:
		

		
			“Affiliate” shall mean, with respect to any Person, another Person which controls, is controlled by or is under common control with such Person. A Person shall be deemed to control another Person if such Person possesses, directly or indirectly, the power to direct or cause the direction of the management and policies of such Person, whether through the ownership of voting securities, by contract or otherwise. Without limiting the generality of the foregoing, a Person shall be deemed to control another Person if any of the following conditions is met: (i) in the case of corporate entities, direct or indirect ownership of more than fifty percent (50%) of the stock or shares having the right to vote for the election of directors, and (ii) in the case of non- corporate entities, direct or indirect ownership of more than fifty percent (50%) of the equity interest with the power to direct the management and policies of such non-corporate entities.
		

		
			“Agreement” shall have the meaning set forth in the preamble, including all Exhibits attached hereto.
		

		
			“Aggregate Purchase Price” shall mean (i) the First Installment with respect to the Initial Closing, (ii) Second Installment with respect to the Second Closing, (iii) the First Development Milestone Payment with respect to the First Development Milestone Closing, and (iv) the Second Development Milestone Payment with respect to the Second Development Milestone Closing.
		

		
			“Business Day” shall mean a day on which commercial banking institutions in New York, New York are open for business.
		

		
			“Closing” shall mean the Initial Closing, the Second Closing, First Development Milestone Closing, and/or the Second Development Milestone Closing, as applicable.
		

		
			
		

		
			

		 

 

		

			 

		

		

		
			“Cross Receipt” shall mean an executed document signed by each of the Company and the Investor, in substantially the form of Exhibit A attached hereto.
		

		
			“Development Milestone Payment” shall have the meaning ascribed to such term in the License Agreement.
		

		
			“Effect” shall have the meaning set forth in the definition of “Material Adverse Effect.” 
		

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

		
			“First Development Milestone” shall mean the first dosing of a Licensed Product in a Pivotal Clinical Study. “Pivotal Clinical Study” shall have the meaning given to such term in the License Agreement.
		

		
			“First Development Milestone Closing” shall mean the closing of the purchase and sale of the First Development Milestone Shares hereunder.
		

		
			“First Development Milestone Payment” shall mean the Development Milestone Payment corresponding to the First Development Milestone, as set forth in Table 1 of Section 5.2.1 of the License Agreement.
		

		
			“First Development Milestone Shares” shall mean a number of Ordinary Shares equal to the quotient of (i) the First Development Milestone Payment divided by (ii) the Share Price.
		

		
			“First Installment” shall have the meaning ascribed to such term in the License Agreement.
		

		
			“First Installment Shares” shall mean 112,473 Ordinary Shares, which is the result of the quotient of (i) the First Installment divided by (ii) an amount equal to (x) 1.2 multiplied by (y) the Share Price.
		

		
			“Governmental Authority” shall mean any court, agency, authority, department or other instrumentality of any government or country or of any national, federal, state, provincial, regional, county, city or other political subdivision of any such government or country or any supranational organization of which any such country is a member.
		

		
			“Initial Closing” shall mean the closing of the purchase and sale of the First Installment Shares hereunder.
		

		
			“Investor Agreement” shall mean that certain Investor Agreement between the Investor and the Company, to be dated as of the Closing Date, in the form of Exhibit B attached hereto, as the same may be amended from time to time.
		

		
			“Law” or “Laws” shall mean all laws, statutes, rules, regulations, orders, judgments, injunctions and/or ordinances of any Governmental Authority.
		

		
			
		

		
			

		 

		

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			“License Agreement” shall mean that certain license agreement between the Company and the Investor dated as of the date hereof, relating to Investor’s point mutation selective targeting approach for autosomal dominant retinitis pigmentosa.
		

		
			“Licensed Product” shall have the meaning ascribed to such term in the License Agreement.
		

		
			“Material Adverse Effect” shall mean any change, event or occurrence (each, an “Effect”) that, individually or when taken together with all other Effects, has (i) a material adverse effect on the business, financial condition, results of operations or prospects of the Company and its subsidiaries, taken as a whole, or (ii) a material adverse effect on the Company’s ability to perform its obligations, or consummate the Transaction, in accordance with the terms of this Agreement, except in the case of (i) or (ii) to the extent that any such Effect results from or arises out of: (A) changes in conditions in the global economy or capital or financial markets generally, including changes in interest or exchange rates, (B) changes in general legal, regulatory, political, economic or business conditions or changes in the International Financial Reporting Standards or interpretations thereof that, in each case, generally affect the biotechnology or biopharmaceutical industries, (C) the announcement, pendency or performance of this Agreement or the License Agreement, or the consummation of the Transaction or the identity of the Investor, (D) any change in the trading prices or trading volume of the Ordinary Shares (it being understood that the facts giving rise to or contributing to any such change may be deemed to constitute, or be taken into account when determining whether there has been or will be, a Material Adverse Effect, except to the extent any of such facts is an Effect referred in clauses (A) through (J) of this definition), (E) acts of war, sabotage or terrorism, or any escalation or worsening of any such acts of war, sabotage or terrorism, (F) earthquakes, hurricanes, floods or other natural disasters, (G) any action taken by the Company contemplated by this Agreement or in accordance with the License Agreement or with the Investor’s written consent, (H) any breach, violation or non-performance by the Investor or any of its Affiliates under the License Agreement, or (I) shareholder litigation arising out of or in connection with the execution, delivery or performance of the Transaction Agreements or the License Agreement; provided, that with respect to clauses (A), (B), (E) and (F) such Effect does not have a materially disproportionate and adverse effect on the Company relative to most other comparable companies and their respective subsidiaries, taken as a whole, in the biotechnology or biopharmaceutical industries.
		

		
			“Organizational Documents” shall mean the Articles of Association of the Company, to be found at (http://ir.proqr.com/corporate-governance) as amended through the date of this Agreement.
		

		
			“Person” shall mean any individual, partnership, limited liability company, firm, corporation, trust, unincorporated organization, government or any department or agency thereof or other entity, as well as any syndicate or group that would be deemed to be a Person under Section 13(d)(3) of the Exchange Act.
		

		
			“Second Closing” shall mean the closing of the purchase and sale of the Second Installment Shares hereunder.
		

		
			
		

		
			

		 

		

			3

		

 

		

			 

		

		

		
			“Second Development Milestone” shall mean the first NDA Approval of a Licensed Product. “NDA Approval” shall have the meaning ascribed to such term in the License Agreement.
		

		
			“Second Development Milestone Closing” shall mean the closing of the purchase and sale of the Second Development Milestone Shares hereunder.
		

		
			“Second Development Milestone Payment” shall mean the Development Milestone Payment corresponding to the Second Development Milestone, as set forth in Table 1 of Section 5.2.1 of the License Agreement.
		

		
			“Second Development Milestone Shares” shall mean a number of Ordinary Shares equal to the quotient of (i) the Second Development Milestone Payment divided by (ii) the Share Price.
		

		
			“Second Installment” shall have the meaning ascribed to such term in the License Agreement.
		

		
			“Second Installment Milestone” shall mean the dosing of the first human subject in a Clinical Study, or, if such Clinical Study is put on hold or terminated due to safety concerns prior to payment of the Second Installment, the date the Clinical Study is removed from such hold or, if the Clinical Study is terminated, the date the next Clinical Study is Initiated. “Clinical Study” and “Initiated” shall have the meanings ascribed to such terms in the License Agreement.
		

		
			“Second Installment Shares” shall mean a number of Ordinary Shares equal to the quotient of (i) the Second Installment divided by (ii) an amount equal to (x) 1.2 multiplied by (y) the Share Price.
		

		
			“Share Price” shall be calculated using the trailing 20-trading day volume weighted average on the Nasdaq Global Market ending on and including the trading day immediately prior to achievement of the applicable Triggering Event.
		

		
			“Shares” shall mean the First Installment Shares, the Second Installment Shares, the First Development Milestone Shares, and/or the Second Development Milestone Shares, as applicable.
		

		
			“Third Party” shall mean any Person (other than a Governmental Authority) other than the Investor, the Company or any Affiliate of the Investor or the Company.
		

		
			“Transaction” means the issuance and sale of the Shares by the Company, and the purchase of the Shares by the Investor, in accordance with the terms hereof.
		

		
			“Transaction Agreements” shall mean this Agreement and the Investor Agreement.
		

		
			“Triggering Event” shall mean the Execution Date, the Second Installment Milestone, the First Development Milestone or the Second Development Milestone, as applicable.
		

		
			
		

		
			

		 

		

			4

		

 

		

			 

		

		

		
			1.2       Additional Defined Terms. In addition to the terms defined in Section 1.1, the following terms shall have the respective meanings assigned thereto in the sections indicated below:
		

			
					
						Defined Term

					
					
						    

					
					
						Section

				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						Closing Date

					
					
						 

					
					
						Section 3.1

				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						Ordinary Shares

					
					
						 

					
					
						Preamble

				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						Company

					
					
						 

					
					
						Preamble

				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						Company SEC Documents

					
					
						 

					
					
						Section 4.11(a)

				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						Equity Limit

					
					
						 

					
					
						Section 2(b)

				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						Exchange Act

					
					
						 

					
					
						Section 4.11(a)

				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						Final Termination Date

					
					
						 

					
					
						Section 9.1(b)

				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						HSR Act

					
					
						 

					
					
						Section 4.7

				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						Investor

					
					
						 

					
					
						Preamble

				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						LAS

					
					
						 

					
					
						Section 4.7

				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						Modified Clause

					
					
						 

					
					
						Section 11.7

				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						Permits

					
					
						 

					
					
						Section 4.10

				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						Original Termination Date

					
					
						 

					
					
						Section 9.1(b)

				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						SEC

					
					
						 

					
					
						Section 4.7

				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						Securities Act

					
					
						 

					
					
						Section 4.11(a)

				

		
			 
		

		
			2.         Purchase and Sale of Ordinary Shares.
		

		
			(a)        Subject to the terms and conditions of this Agreement, the Company shall issue and sell to the Investor, free and clear of all liens, other than any liens arising as a result of any action by the Investor, and the Investor shall purchase from the Company:
		

		
			(i)         At the Initial Closing, the First Installment Shares;
		

		
			(ii)        At the Second Closing, the Second Installment Shares;
		

		
			(iii)      At the First Development Milestone Closing, the First Development Milestone Shares; and
		

		
			
		

		
			

		 

		

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			(iv)      At the Second Development Milestone Closing, the Second Development Milestone Shares.
		

		
			(b)        Notwithstanding the foregoing or anything to the contrary in this Agreement, in no event will the Company issue to the Investor equity in the Company in excess of 18.5% of the issued and outstanding shares of the Company (on an as-issued basis) after giving effect to said issuance and any conversion event that will occur on or before such issuance (the “Equity Limit”). To the extent any portion of the Shares to be issued to the Investor would cause the Investor’s aggregate equity ownership in the Company to exceed the Equity Limit, the Company will issue to the Investor only the amount of Shares that will meet but not exceed such Equity Limit, and the Company will pay to the Investor an amount equal to the remainder of such Shares in cash.
		

		
			(c)        The Company shall not be required to issue any Shares if the issuance of such Shares together with any previous issuances of Shares pursuant to this Agreement would exceed 19.9% of the Company’s outstanding ordinary shares as of the Execution Date (subject to appropriate adjustment for any stock split, stock dividend or other adjustment that occurs after the Execution Date) (the “Exchange Cap”), except that such limitation shall not apply in the event that the Company obtains the approval of its shareholders as required by the applicable rules of The Nasdaq Stock Market for issuances of Shares in excess of such amount; it being acknowledged, for the avoidance of doubt, that the Company has no obligation to seek such approval. If such approval is not obtained, then to the extent any portion of the Shares to be issued to the Investor would cause the Company to issue Shares in excess of the Exchange Cap, the Company will issue to the Investor only the amount of Shares that will meet but not exceed such Exchange Cap, and the Company will pay to the Investor an amount equal to the remainder of such Shares in cash.
		

		
			3.         Closing Date; Deliveries.
		

		
			3.1       Closing Date. Subject to the satisfaction or waiver of all the conditions to the Closing set forth in Sections 6, 7 and 8 hereof, the applicable Closing of the purchase and sale of the Shares hereunder shall be held on the third (3rd) Business Day after the satisfaction of the conditions to such Closing set forth in Sections 6, 7 and 8 (other than those conditions that by their nature are to be satisfied at such Closing), at such other time, date and location as the parties may agree in writing. The date the applicable Closing occurs is hereinafter referred to as the “Closing Date.”
		

		
			3.2       Deliveries.
		

		
			(a)        Deliveries by the Company. At the applicable Closing, the Company shall issue the relevant Shares in book entry format, and the Company shall instruct its transfer agent to register such issuance at the time of such issuance. The Company shall also deliver at such Closing: (i) a duly executed Cross Receipt; (ii) a certificate in form and substance reasonably satisfactory to the Investor and duly executed on behalf of the Company by an authorized executive officer of the Company, certifying that the conditions to such Closing set
		

		
			
		

		
			

		 

		

			6

		

 

		

			 

		

		

		
			forth in Section 7 of this Agreement have been fulfilled; and (iii) with respect to the Initial Closing, an Investor Agreement duly executed by the Company.
		

		
			(b)        Deliveries by the Investor. At the applicable Closing, the Investor shall deliver, or cause to be delivered, to the Company (i) a duly executed Cross Receipt; (ii) a certificate in form and substance reasonably satisfactory to the Company duly executed by an authorized executive officer of the Investor certifying that the conditions to such Closing set forth in Section 8 of this Agreement have been fulfilled; and (iii) with respect to the Initial Closing, an Investor Agreement, duly executed by the Investor.
		

		
			4.         Representations and Warranties of the Company. The Company hereby represents and warrants to the Investor that:
		

		
			4.1       Organization, Good Standing and Qualification.
		

		
			(a)        The Company has been duly incorporated and is validly existing as a public company with limited liability (naamloze vennootschap) under the laws of the Netherlands and has the power and authority to own, lease and operate its properties and to conduct its business as described in the Company SEC Documents, to enter into the Transaction Agreements to issue and sell the Shares and to carry out the other transactions contemplated by the Transaction Agreements.
		

		
			(b)        The Company is qualified to transact business and is in good standing in each jurisdiction in which the character of the properties owned, leased or operated by the Company or the nature of the business conducted by the Company makes such qualification necessary, except where the failure to be so qualified would not have a Material Adverse Effect.
		

		
			4.2       Capitalization and Voting Rights.
		

		
			As of the date hereof, the authorized and issued share capital and outstanding shares in the capital of the Company are as set forth in the Company SEC Documents (except for issuances pursuant to this Agreement, pursuant to reservations, agreements or employee benefit plans referred to in the Company SEC Documents or pursuant to the exercise of convertible securities or options referred to in the Company SEC Documents.
		

		
			All of the ordinary shares in the capital of the Company existing as of the date of this Agreement have been duly authorized and validly issued and are fully paid. None of the outstanding shares in the capital of the Company were issued in violation of the preemptive or other similar rights of any shareholder of the Company.
		

		
			4.3       Subsidiaries. The Company has disclosed all of its subsidiaries required to be disclosed pursuant to Item 601(b)(21) of Regulation S-K in an exhibit to its Annual Report on Form 20-F.
		

		
			
		

		
			

		 

		

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			4.4       Authorization.
		

		
			(a)        All requisite corporate action on the part of the Company, its directors and stockholders required by applicable Law or, assuming the accuracy of the Investor’s representation in Section 5.8, The Nasdaq Stock Market LLC for the authorization, execution and delivery by the Company of the Transaction Agreements and the performance of all obligations of the Company hereunder and thereunder, including the authorization, issuance and delivery of the applicable Shares, has been taken.
		

		
			(b)        This Agreement has been, and upon the execution and delivery of the Investor Agreement by the Company at the Initial Closing, the Investor Agreement will be, duly executed and delivered by the Company, and upon the due execution and delivery of this Agreement by the Investor at the Initial Closing, this Agreement will constitute, and upon the due execution and delivery of the Investor Agreement by the Investor, the Investor Agreement will constitute, valid and legally binding obligations of the Company, enforceable against the Company in accordance with their respective terms (except as such enforceability may be limited by (i) applicable bankruptcy, insolvency, reorganization, moratorium or other Laws of general application relating to or affecting enforcement of creditors’ rights and (ii) rules of Law governing specific performance, injunctive relief or other equitable remedies and limitations of public policy).
		

		
			4.5       No Defaults. The Company is not in default under or in violation of (a) its Organizational Documents, (b) any provision of applicable Law or any ruling, writ, injunction, order, Permit, judgment or decree of any Governmental Authority or (c) any agreement, arrangement or instrument, whether written or oral, by which the Company or any of its assets are bound, except, in the case of subsections (b) and (c), as would not have a Material Adverse Effect. To the knowledge of the Company, there exists no condition, event or act which after notice, lapse of time, or both, would constitute a default or violation by the Company under any of the foregoing, except, in the case of subsections (b) and (c), as would not have a Material Adverse Effect.
		

		
			4.6       No Conflicts. The execution, delivery and performance of the Transaction Agreements and compliance with the provisions thereof by the Company do not and shall not: (a) violate any provision of applicable Law or any ruling, writ, injunction, order, permit, judgment or decree of any Governmental Authority, (b) constitute a breach of, or default under (or an event which, with notice or lapse of time or both, would become a default under) or conflict with, or give rise to any right of termination, cancellation or acceleration of, any agreement, arrangement or instrument, whether written or oral, by which the Company or any of its assets are bound or (c) violate or conflict with any of the provisions of the Company’s Organizational Documents, except, in the case of subsections (a) and (b), as would not have a Material Adverse Effect.
		

		
			4.7       No Governmental Authority or Third Party Consents. No consent, approval, authorization or other order of, or filing with, or notice to, any Governmental Authority or other Third Party is required to be obtained or made by the Company in connection with the authorization, execution and delivery by the Company of any of the Transaction Agreements or with the authorization, issue and sale by the Company of the applicable Shares at the applicable
		

		
			
		

		
			

		 

		

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			Closing, except (i) such filings as may be required to be made with the Securities and Exchange Commission (the “SEC”) and with any state blue sky or securities regulatory authority, which filings shall be made in a timely manner in accordance with all applicable Laws, (ii) as required pursuant to the Hart-Scott-Rodino Antitrust Improvements Act, as amended (the “HSR Act”) and (iii) with respect to the Shares, the filing with The Nasdaq Stock Market LLC of, and the absence of unresolved issues with respect to, a Notification Form: Listing of Additional Shares (the “LAS”).
		

		
			4.8       Valid Issuance of Shares. When issued, sold and delivered at the applicable Closing in accordance with the terms hereof for the Aggregate Purchase Price, the Shares shall be duly authorized, validly issued, fully paid and nonassessable, free from any liens, encumbrances or restrictions on transfer, including preemptive rights, rights of first refusal or other similar rights, other than as arising pursuant to the Transaction Agreements, as a result of any action by the Investor or under federal or state securities Laws.
		

		
			4.9       Litigation. Except as set forth in the Company SEC Documents, there is no action, suit, proceeding or investigation pending (of which the Company has received notice or otherwise has knowledge) or, to the Company’s knowledge, threatened, against the Company or which the Company intends to initiate which has had or is reasonably likely to have a Material Adverse Effect.
		

		
			4.10     Licenses and Other Rights; Compliance with Laws. The Company has all franchises, permits, licenses and other rights and privileges (“Permits”) necessary to permit it to own its properties and to conduct its business as presently conducted and is in compliance thereunder, except where the failure to be in compliance does not and would not have a Material Adverse Effect. To the Company’s knowledge, it has not taken any action that would interfere with the Company’s ability to renew all such Permit(s), except where the failure to renew such Permit(s) would not have a Material Adverse Effect. The Company is and has been in compliance with all Laws applicable to its business, properties and assets, and to the products and services sold by it, except where the failure to be in compliance does not and would not have a Material Adverse Effect.
		

		
			4.11     Company SEC Documents; Financial Statements; Nasdaq Stock Market.
		

		
			(a)        Since December 31, 2017, the Company has timely filed all required reports, schedules, forms, statements and other documents (including exhibits and all other information incorporated therein), and any required amendments to any of the foregoing, with the SEC (the “Company SEC Documents”). As of their respective filing dates, each of the Company SEC Documents complied in all material respects with the requirements of the Securities Act of 1933, as amended (the “Securities Act”), and the Securities Exchange Act of 1934, as amended (the “Exchange Act”), and the rules and regulations of the SEC promulgated thereunder applicable to such Company SEC Documents, and no Company SEC Documents when filed, declared effective or mailed, as applicable, contained any untrue statement of a material fact or omitted to state a material fact required to be stated therein or necessary in order to make the statements therein, in light of the circumstances under which they were made, not misleading.
		

		
			
		

		
			

		 

		

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			(b)        The financial statements of the Company included in its Annual Report on Form 20-F for the fiscal year ended December 31, 2017 and in its quarterly reports on Form 6-K for the quarterly periods ended June 30, 2018, and March 31, 2018 comply as to form in all material respects with applicable accounting requirements and the published rules and regulations of the SEC with respect thereto, have been prepared in accordance with International Financial Reporting Standards as issued by the International Accounting Standards Board applied on a consistent basis throughout the periods involved, except in the case of unaudited, interim financial statements, subject to normal year-end audit adjustments and the exclusion of certain footnotes. Except (i) as set forth in the Company SEC Documents or (ii) for liabilities incurred in the ordinary course of business subsequent to the date of the most recent balance sheet contained in the Company SEC Documents, the Company has no liabilities, whether absolute or accrued, contingent or otherwise, other than those that would not, individually or in the aggregate, have a Material Adverse Effect.
		

		
			(c)        As of the date of this Agreement, the Ordinary Shares are listed on The Nasdaq Global Market, and the Company has taken no action designed to, or which to its knowledge is likely to have the effect of, terminating the registration of the Ordinary Shares under the Exchange Act or delisting the Ordinary Shares from The Nasdaq Global Market. As of the date of this Agreement, the Company has not received any notification that, and has no knowledge that, the SEC or The Nasdaq Stock Market LLC is contemplating terminating such listing or registration.
		

		
			4.12     Absence of Certain Changes. Except as disclosed in the Company SEC Documents, since December 31, 2017, there has not occurred any event that has caused or would reasonably be expected to cause a Material Adverse Effect.
		

		
			4.13     Offering. Subject to the accuracy of the Investor’s representations set forth in in this Agreement, the offer, sale and issuance of the Shares to be issued in conformity with the terms of this Agreement constitute transactions which are exempt from the registration requirements of the Securities Act and from all applicable state registration or qualification requirements. Neither the Company nor any Person acting on its behalf will take any action that would cause the loss of such exemption.
		

		
			4.14     No Integration. The Company has not, directly or through any agent, sold, offered for sale, solicited offers to buy or otherwise negotiated in respect of, any security (as defined in the Securities Act) which is or will be integrated with the Shares sold pursuant to this Agreement in a manner that would require the registration of the Shares under the Securities Act.
		

		
			4.15     Brokers’ or Finders’ Fees. No broker, finder, investment banker or other Person is entitled to any brokerage, finder’s or other fee or commission from the Company in connection with the transactions contemplated by the Transaction Agreements.
		

		
			5.         Representations and Warranties of the Investor. The Investor hereby represents and warrants to the Company as set forth in Sections 5.1 through 5.11, that:
		

		
			5.1       Organization; Good Standing. The Investor is a corporation duly organized, validly existing and in good standing under the laws of Delaware. The Investor has or
		

		
			
		

		
			

		 

		

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			will have all requisite power and authority to enter into the Transaction Agreements to which it is or will be a party, to purchase the applicable Shares and to perform its obligations under and to carry out the other transactions contemplated by the Transaction Agreements to which it is or will be a party.
		

		
			5.2       Authorization. All requisite action on the part of the Investor and its directors and stockholders, required by applicable Law for the authorization, execution and delivery by the Investor of the Transaction Agreements to which it is a party, and the performance of all of its obligations thereunder, including the subscription for and purchase of the Shares, has been taken or will be taken prior to the applicable Closing. This Agreement has been, and upon the execution and delivery of the Investor Agreement at the Initial Closing by the Investor, the Investor Agreement will be, duly executed and delivered by the Investor and upon the due execution and delivery thereof by the Company, will constitute valid and legally binding obligations of the Investor, enforceable against the Investor in accordance with their respective terms (except as such enforceability may be limited by (a) applicable bankruptcy, insolvency, reorganization, moratorium or other Laws of general application relating to or affecting enforcement of creditors’ rights and (b) rules of Law governing specific performance, injunctive relief or other equitable remedies and limitations of public policy).
		

		
			5.3       No Conflicts. The execution, delivery and performance of the Transaction Agreements and compliance with the provisions thereof by the Investor do not and shall not: (a) violate any provision of applicable Law or any ruling, writ, injunction, order, permit, judgment or decree of any Governmental Authority, (b) constitute a breach of, or default under (or an event which, with notice or lapse of time or both, would become a default under) or conflict with, or give rise to any right of termination, cancellation or acceleration of, any agreement, arrangement or instrument, whether written or oral, by which the Investor or any of its assets, are bound, or (c) violate or conflict with any of the provisions of the Investor’s organizational documents (including any articles or memoranda of organization or association, charter, bylaws or similar documents), except as would not impair or adversely affect the ability of the Investor to consummate the Transactions and perform its obligations under the Transaction Agreements and except, in the case of subsections (a) and (b) as would not have a material adverse effect on the Investor.
		

		
			5.4       No Governmental Authority or Third Party Consents. No consent, approval, authorization or other order of any Governmental Authority or other Third Party is required to be obtained by the Investor in connection with the authorization, execution and delivery of any of the Transaction Agreements or with the subscription for and purchase of the Shares, except as required pursuant to the HSR Act.
		

		
			5.5       Purchase Entirely for Own Account. The Shares shall be acquired for investment for the Investor’s own account, not as a nominee or agent, and not with a view to the resale or distribution of any part thereof, and the Investor has no present intention of selling, granting any participation or otherwise distributing the Shares. The Investor does not have and will not have as of the applicable Closing any contract, undertaking, agreement or arrangement with any Person to sell, transfer or grant participation to a Person any of the Shares.
		

		
			
		

		
			

		 

		

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			5.6       Disclosure of Information. The Investor has received all the information from the Company and its management that the Investor considers necessary or appropriate for deciding whether to purchase the Shares hereunder. The Investor further represents that it has had an opportunity to ask questions and receive answers from the Company regarding the Company, its financial condition, results of operations and prospects and the terms and conditions of the offering of the Shares sufficient to enable it to evaluate its investment.
		

		
			5.7       Investment Experience and Accredited Investor Status. The Investor is an “accredited investor” (as defined in Regulation D under the Securities Act). The Investor has such knowledge and experience in financial or business matters that it is capable of evaluating the merits and risks of the investment in the Shares to be purchased hereunder.
		

		
			5.8       Acquiring Person. As of the date of this Agreement and immediately prior to the applicable Closing, neither the Investor nor any of its Affiliates beneficially owns, or will beneficially own (as determined pursuant to Rule 13d-3 under the Exchange Act without regard for the number of days in which a Person has the right to acquire such beneficial ownership), any other securities of the Company.
		

		
			5.9       Restricted Securities. The Investor understands that the Shares, when issued, will be “restricted securities” under the federal securities Laws inasmuch as they are being acquired from the Company in a transaction not involving a public offering and that under such Laws the Shares may be resold without registration under the Securities Act only in certain limited circumstances. The Investor represents that it is familiar with Rule 144 of the Securities Act, as presently in effect.
		

		
			5.10     Legends. The Investor understands that the certificates representing the Shares shall bear the following legends:
		

		
			(a)        “These securities have not been registered under the Securities Act of 1933. They may not be sold, offered for sale, pledged or hypothecated in the absence of a registration statement in effect with respect to the securities under the Securities Act or an opinion of counsel (which counsel shall be reasonably satisfactory to ProQR Therapeutics N.V.) that such registration is not required or unless sold pursuant to Rule 144 of the Securities Act.”;
		

		
			(b)        any legend required by applicable state securities Laws; and
		

		
			(c)        “The securities represented by this certificate are subject to and shall be transferable only upon the terms and conditions of an Investor Agreement dated as of October 26, 2018, by and between ProQR Therapeutics N.V. and the other parties signatory thereto, a copy of which is on file with the Secretary of ProQR Therapeutics N.V.”
		

		
			6.         Investor’s Conditions to Closing. The Investor’s obligation to purchase the Shares at a Closing is subject to the fulfillment as of such Closing of the following conditions (unless waived in writing by the Investor):
		

		
			6.1       Representations and Warranties. (a) The representations and warranties made by the Company in Section 4 hereof shall be true and correct as of the date of this Agreement and as of the Closing Date as though made on and as of such Closing Date, except to
		

		
			
		

		
			

		 

		

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			the extent such representations and warranties are specifically made as of a particular date, in which case such representations and warranties shall be true and correct as of such date; provided,  however, that for purposes of this Section 6.1, all such representations and warranties of the Company shall be deemed to be true and correct for purposes of this Section 6.1 unless the failure or failures of such representations and warranties to be so true and correct, without regard to any “material,” “materiality” or “Material Adverse Effect” qualifiers set forth therein (other than any reference to “material” in Sections 4.11(a) and 4.11(b)), individually or in the aggregate, has had or would reasonably be expected to have a Material Adverse Effect.
		

		
			6.2       Covenants. All covenants and agreements contained in this Agreement to be performed or complied with by the Company on or prior to the Closing Date shall have been performed or complied with in all material respects.
		

		
			6.3       Investor Agreement. The Company shall have duly executed and delivered to the Investor, pursuant to Section 3.2(a) of this Agreement, the Investor Agreement, and such agreement shall be in full force and effect.
		

		
			6.4       License Agreement. The Company shall have duly executed and delivered to the Investor the License Agreement at the Initial Closing, and there shall have been no termination of the License Agreement that, as of the applicable Closing, is effective.
		

		
			7.         Company’s Conditions to Closing. The Company’s obligation to issue and sell the applicable Shares at a Closing is subject to the fulfillment as of such Closing of the following conditions (unless waived in writing by the Company):
		

		
			7.1       Representations and Warranties. The representations and warranties made by the Investor (a) in Section 5 hereof (other than Sections 5.4 and 5.6 hereof) shall be true and correct and (b) in Sections 5.4 and 5.6 hereof shall be true and correct in all material respects, in each case as of the date of this Agreement and as of the Closing Date as though made on and as of such Closing Date (except to the extent such representations and warranties are specifically made as of a particular date, in which case such representations and warranties shall be true and correct as of such date).
		

		
			7.2       Covenants. All covenants and agreements contained in this Agreement to be performed or complied with by the Investor on or prior to the Closing Date shall have been performed or complied with in all material respects.
		

		
			7.3       Investor Agreement. The Investor shall have duly executed and delivered to the Company, pursuant to Section 4.4(b) of this Agreement, the Investor Agreement, and (subject to execution by the Company) such agreement shall be in full force and effect.
		

		
			7.4       License Agreement. The Investor shall have duly executed and delivered to the Company the License Agreement as of the Initial Closing, and there shall have been no termination of the License Agreement that, as of applicable Closing, is effective.
		

		
			8.         Mutual Conditions to Closing. The obligations of the Investor and the Company to consummate a Closing is subject to the fulfillment as of such Closing Date of the following conditions:
		

		
			
		

		
			

		 

		

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			8.1       HSR Act and Other Qualifications. The filings required under the HSR Act in connection with this Agreement shall have been made and the required waiting period shall have expired or been terminated as of such Closing Date, and all other authorizations, consents, waivers, permits, approvals, qualifications and registrations to be obtained or effected with any Governmental Authority, including, without limitation, necessary blue sky permits and qualifications required by any state for the offer and sale to the Investor of the applicable Shares, shall have been duly obtained and shall be in effect as of such Closing Date.
		

		
			8.2       Absence of Litigation. There shall be no action, suit, proceeding or investigation by a Governmental Authority pending or currently threatened in writing against the Company or the Investor that questions the validity of any of the Transaction Agreements, the right of the Company or the Investor to enter into any Transaction Agreement or to consummate the transactions contemplated hereby or thereby or which, if determined adversely, would impose substantial monetary damages on the Company or the Investor as a result of the consummation of the transactions contemplated by any Transaction Agreement.
		

		
			8.3       No Prohibition. (a) No provision of any applicable Law and no judgment, injunction (preliminary or permanent), order or decree that prohibits, makes illegal or enjoins the consummation of the Transaction shall be in effect; and (b) there shall be no unresolved issues with The Nasdaq Stock Market LLC with respect to the LAS.
		

		
			8.4       Milestones. (a) With respect to the Second Closing, the Second Installment Milestone shall have been achieved in accordance with Section 5.1 of the License Agreement; (b) with respect to the First Development Milestone Closing, the First Development Milestone shall have been achieved in accordance with Section 5.2 of the License Agreement, and the Company shall have determined, in its sole discretion, to pay the First Development Milestone Payment in its Ordinary Shares pursuant to the terms and conditions of this Agreement and the License Agreement; and (c) with respect to the Second Development Milestone Closing, the Second Development Milestone shall have been achieved in accordance with Section 5.2 of the License Agreement, and the Company shall have determined, in its sole discretion, to pay the Second Development Milestone Payment in its Ordinary Shares pursuant to the terms and conditions of this Agreement and the License Agreement.
		

		
			9.         Termination.
		

		
			9.1       Ability to Terminate. This Agreement may be terminated at any time prior to a Closing by:
		

		
			(a)        mutual written consent of the Company and the Investor;
		

		
			(b)        upon the termination of the License Agreement pursuant to its terms;
		

		
			(c)        either the Company or the Investor, upon written notice to the other, if any of the mutual conditions to the applicable Closing set forth in Section 8 shall have become incapable of fulfillment by the November 26, 2018 date following the applicable
		

		
			
		

		
			

		 

		

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			Triggering Event, and shall not have been waived in writing by the other party; provided,  however, that the right to terminate this Agreement under this Section 9.1(c) shall not be available to any party whose failure to fulfill any obligation under this Agreement has been the cause of, or resulted in, the failure to consummate the transactions contemplated hereby prior to the November 26, 2018 date following the applicable Triggering Date, as applicable;
		

		
			(d)        the Company, upon written notice to the Investor, so long as the Company is not then in breach of its representations, warranties, covenants or agreements under this Agreement such that any of the conditions set forth in Section 6.1 or 6.2, as applicable, could not be satisfied by the Closing Date, (i) upon a breach of any covenant or agreement on the part of the Investor set forth in this Agreement, or (ii) if any representation or warranty of the Investor shall have been or become untrue, in each case such that any of the conditions set forth in Section 7.1, 7.2, 7.3 or 7.4, as applicable, could not be satisfied by the applicable Closing Date;
		

		
			(e)        the Investor, upon written notice to the Company, so long as the Investor is not then in breach of its representations, warranties, covenants or agreements under this Agreement such that any of the conditions set forth in Section 7.1 or 7.2, as applicable, could not be satisfied by the Closing Date, upon a breach of any covenant or agreement on the part of the Company set forth in this Agreement, or if any representation or warranty of the Company shall have been or become untrue, in each case such that any of the conditions set forth in Section 6.1, 6.2, 6.3 or 6.4, as applicable, could not be satisfied by the applicable Closing Date.
		

		
			9.2       Effect of Termination. In the event of the termination of this Agreement pursuant to Section 9.1 hereof, (a) this Agreement (except for this Section 9.2 and Article XI (other than Section 11.13), and any definitions set forth in this Agreement and used in such sections) shall forthwith become void and have no effect, without any liability on the part of any party hereto or its Affiliates, and (b) all filings, applications and other submissions made pursuant to this Agreement, to the extent practicable, shall be withdrawn from the agency or other Person to which they were made or appropriately amended to reflect the termination of the transactions contemplated hereby; provided,  however, that nothing contained in this Section 9.2 shall relieve any party from liability for fraud or any intentional or willful breach of this Agreement. In the event of a termination of this Agreement pursuant to Section 9.1, the First Installment, Second Installment, First Development Milestone Payment and Second Development Milestone Payment, as applicable, will be paid in cash when due.
		

		
			10.       Additional Covenants and Agreements.
		

		
			10.1     Market Listing. From the date hereof through the applicable Closing Date, Company shall use all reasonable efforts to (a) maintain the listing and trading of the Ordinary Shares on The Nasdaq Global Market and (b) effect the listing of the applicable Shares on The Nasdaq Global Market, including submitting a notice of listing of additional shares with respect to the Shares to The Nasdaq Stock Market LLC no later than fifteen (15) calendar days prior to the Closing Date.
		

		
			
		

		
			

		 

		

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			11.       Miscellaneous.
		

		
			11.1     Governing Law. This Agreement shall be governed by and construed in accordance with the Laws of the State of New York, without regard to the conflict of laws principles thereof that would require the application of the Law of any other jurisdiction.
		

		
			11.2     Waiver. Waiver by a party of a breach hereunder by the other party shall not be construed as a waiver of any subsequent breach of the same or any other provision. No delay or omission by a party in exercising or availing itself of any right, power or privilege hereunder shall preclude the later exercise of any such right, power or privilege by such party. No waiver shall be effective unless made in writing with specific reference to the relevant provision(s) of this Agreement and signed by a duly authorized representative of the party granting the waiver.
		

		
			11.3     Notices. All notices, instructions and other communications hereunder or in connection herewith shall be in writing, shall be sent to the address of the relevant party set forth on Exhibit C attached hereto and shall be (a) delivered personally, (b) sent by registered or certified mail, return receipt requested, postage prepaid, (c) sent via a reputable nationwide overnight courier service or (d) sent by facsimile transmission, with a confirmation copy to be sent by registered or certified mail, return receipt requested, postage prepaid. Any such notice, instruction or communication shall be deemed to have been delivered upon receipt if delivered by hand, three (3) Business Days after it is sent by registered or certified mail, return receipt requested, postage prepaid, one (1) Business Day after it is sent via a reputable nationwide overnight courier service or when transmitted with electronic confirmation of receipt, if transmitted by facsimile (if such transmission is made during regular business hours of the recipient on a Business Day; or otherwise, on the next Business Day following such transmission). Either party may change its address by giving notice to the other party in the manner provided above.
		

		
			11.4     Entire Agreement. This Agreement, the License Agreement and the Investor Agreement (once executed), contain the entire agreement among the parties with respect to the subject matter hereof and thereof and supersede all prior and contemporaneous arrangements or understandings, whether written or oral, with respect hereto and thereto.
		

		
			11.5     Amendments. No provision in this Agreement shall be supplemented, deleted or amended except in a writing executed by an authorized representative of each of the Investor and the Company.
		

		
			11.6     Headings; Nouns and Pronouns; Section References. Headings in this Agreement are for convenience of reference only and shall not be considered in construing this Agreement. Whenever the context may require, any pronouns used herein shall include the corresponding masculine, feminine or neuter forms, and the singular form of names and pronouns shall include the plural and vice-versa. References in this Agreement to a section or subsection shall be deemed to refer to a section or subsection of this Agreement unless otherwise expressly stated.
		

		
			
		

		
			

		 

		

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			11.7     Severability. If, under applicable Laws, any provision hereof is invalid or unenforceable, or otherwise directly or indirectly affects the validity of any other material provision(s) of this Agreement in any jurisdiction (“Modified Clause”), then, it is mutually agreed that this Agreement shall endure and that the Modified Clause shall be enforced in such jurisdiction to the maximum extent permitted under applicable Laws in such jurisdiction; provided that the parties shall consult and use all reasonable efforts to agree upon, and hereby consent to, any valid and enforceable modification of this Agreement as may be necessary to avoid any unjust enrichment of either party and to match the intent of this Agreement as closely as possible, including the economic benefits and rights contemplated herein.
		

		
			11.8     Assignment. Neither this Agreement nor any of the rights or obligations hereunder may be assigned by either the Investor or the Company without (a) the prior written consent of Company in the case of any assignment by the Investor or (b) the prior written consent of the Investor in the case of an assignment by the Company.
		

		
			11.9     Successors and Assigns. This Agreement shall be binding upon and inure to the benefit of the parties hereto and their respective successors and permitted assigns.
		

		
			11.10   Counterparts. This Agreement may be executed in counterparts, each of which shall be deemed an original but which together shall constitute one and the same instrument.
		

		
			11.11   Third Party Beneficiaries. None of the provisions of this Agreement shall be for the benefit of or enforceable by any Third Party, including any creditor of any party hereto. No Third Party shall obtain any right under any provision of this Agreement or shall by reason of any such provision make any claim in respect of any debt, liability or obligation (or otherwise) against any party hereto.
		

		
			11.12   No Strict Construction. This Agreement has been prepared jointly and will not be construed against either party.
		

		
			11.13   Survival of Warranties. The representations and warranties of the Company and the Investor contained in this Agreement shall survive the applicable Closing for eighteen (18) months. The parties hereby acknowledge and agree that the rights of the parties hereunder are special, unique and of extraordinary character, and that if any party refuses or otherwise fails to act, or to cause its Affiliates to act, in accordance with the provisions of this Agreement, such refusal or failure would result in irreparable injury to the Company or the Investor as the case may be, the exact amount of which would be difficult to ascertain or estimate and the remedies at law for which would not be reasonable or adequate compensation. Accordingly, if any party refuses or otherwise fails to act, or to cause its Affiliates to act, in accordance with the provisions of this Agreement, then, in addition to any other remedy which may be available to any damaged party at law or in equity, such damaged party will be entitled to seek specific performance and injunctive relief, without posting bond or other security, and without the necessity of proving actual or threatened damages, which remedy such damaged party will be entitled to seek in any court of competent jurisdiction.
		

		
			
		

		
			

		 

		

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			11.14   Remedies. The rights, powers and remedies of the parties under this Agreement are cumulative and not exclusive of any other right, power or remedy which such parties may have under any other agreement or Law. No single or partial assertion or exercise of any right, power or remedy of a party hereunder shall preclude any other or further assertion or exercise thereof.
		

		
			11.15   Expenses. Each party shall pay its own fees and expenses in connection with the preparation, negotiation, execution and delivery of the Transaction Agreements.
		

		
			(Signature Page Follows)
		

		
			 
		

		
			 
		

		
			

		 

		

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			IN WITNESS WHEREOF, the parties have executed and delivered this Agreement as of the date first above written.
		

			
					
						 

					
					
						IONIS PHARMACEUTICALS, INC.

					
					
						

				
	
					
						 

					
					
						By:

					
					
						 

					
					
						 

				
	
					
						 

					
					
						 

					
					
						Name:   Stanley T. Crooke

					
					
						 

				
	
					
						 

					
					
						 

					
					
						Title:     Chief Executive Officer

					
					
						 

				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						PROQR THERAPEUTICS N.V.

					
					
						 

				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						By:

					
					
						 

					
					
						 

				
	
					
						 

					
					
						 

					
					
						Name:

					
					
						 

				
	
					
						 

					
					
						 

					
					
						Title:

					
					
						 

				

		
			 
		

		
			Signature Page to Stock Purchase Agreementprqr_Ex4_19

		
			Exhibit 4.19
		

		
			 
		

		
			INVESTOR AGREEMENT
		

		
			THIS INVESTOR AGREEMENT (this “Agreement”) is made as of October 26, 2018, by and between Ionis Pharmaceuticals, Inc. (the “Investor”), a Delaware corporation, and ProQR Therapeutics N.V. (the “Company”), a public company with limited liability incorporated under the laws of the Netherlands.
		

		
			WHEREAS, the Share Purchase Agreement, dated as of October 26, 2018, by and between the Investor and the Company (the “Purchase Agreement”) provides for the issuance and sale by the Company to the Investor, and the purchase by the Investor, of a certain number of ordinary shares, nominal value Euro 0.04 per ordinary share of the Company (the “Ordinary Shares”), equal to up to the aggregate number of Shares (as defined in the Purchase Agreement) (the “Purchased Shares”); and
		

		
			WHEREAS, as a condition to consummating the transactions contemplated by the Purchase Agreement, the Investor and the Company have agreed upon certain rights and restrictions as set forth herein with respect to the Purchased Shares and other securities of the Company beneficially owned by the Investor and its Affiliates, and it is a condition to the closing under the Purchase Agreement that this Agreement be executed and delivered by the Investor and the Company.
		

		
			NOW, THEREFORE, in consideration of the premises and mutual agreements hereinafter set forth, and for other valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the parties hereto agree as follows:
		

		
			1.         Definitions. As used in this Agreement, the following terms shall have the following meanings:
		

		
			(a)         “Affiliate” shall mean, with respect to any Person, another Person which controls, is controlled by or is under common control with such Person. A Person shall be deemed to control another Person if such Person possesses, directly or indirectly, the power to direct or cause the direction of the management and policies of such Person, whether through the ownership of voting securities, by contract or otherwise. Without limiting the generality of the foregoing, a Person shall be deemed to control another Person if any of the following conditions is met: (i) in the case of corporate entities, direct or indirect ownership of more than fifty percent (50%) of the stock or shares having the right to vote for the election of directors, and (ii) in the case of non-corporate entities, direct or indirect ownership of more than fifty percent (50%) of the equity interest with the power to direct the management and policies of such non-corporate entities.
		

		
			(b)        “Agreement” shall have the meaning set forth in the preamble to this Agreement, including all Exhibits attached hereto.
		

		
			(c)         “beneficial owner,” “beneficially owns,” “beneficial ownership” and terms of similar import used in this Agreement shall, with respect to a Person, have the meaning set forth in Rule 13d-3 under the Exchange Act (i) assuming the full conversion into, and exercise and exchange for, Ordinary Shares of all Ordinary Share
		

		
			 
		

		
			 
		

		
			

		 

		

			 

		

 

		

		
			Equivalents beneficially owned by such Person and (ii) determined without regard for the number of days in which such Person has the right to acquire such beneficial ownership.
		

		
			(d)        “Business Day” shall mean a day on which commercial banking institutions in New York, New York are open for business.
		

		
			(e)        “Change of Control” shall mean, with respect to the Company, any of the following events: (i) any Person is or becomes the beneficial owner (except that a Person shall be deemed to have beneficial ownership of all shares that any such Person has the right to acquire, whether such right which may be exercised immediately or only after the passage of time), directly or indirectly, of a majority of the total voting power represented by all Ordinary Shares Then Outstanding; (ii) the Company consolidates with or merges into another corporation or entity, or any corporation or entity consolidates with or merges into the Company, other than (A) a merger or consolidation which would result in the voting securities of the Company outstanding immediately prior to such merger or consolidation continuing to represent (either by remaining outstanding or by being converted into voting securities of the surviving entity or any parent thereof) a majority of the combined voting power of the voting securities of the Company or such surviving entity or any parent thereof outstanding immediately after such merger or consolidation, or (B) a merger or consolidation effected to implement a recapitalization of the Company (or similar transaction) in which no Person becomes the beneficial owner, directly or indirectly, of a majority of the total voting power of all Ordinary Shares Then Outstanding or (iii) the Company conveys, transfers or leases all or substantially all of its assets to any Person other than a wholly owned Affiliate of the Company.
		

		
			(f)         “Closing Date” shall have the meaning set forth in the Purchase Agreement.
		

		
			(g)        “Company” shall have the meaning set forth in the preamble to this Agreement.
		

		
			(h)        “Demand Request” shall have the meaning set forth in Section 2.1.
		

		
			(i)         “Disposition” or “Dispose of” shall mean any (i) offer, pledge, sale, contract to sell, sale of any option or contract to purchase, purchase of any option or contract to sell, grant of any option, right or warrant for the sale of, or other disposition of or transfer of any Ordinary Shares, or any Ordinary Share Equivalents, including, without limitation, any “short sale” or similar arrangement, or (ii) swap or any other agreement or any transaction that transfers, in whole or in part, directly or indirectly, the economic consequence of ownership of Ordinary Shares, whether any such swap or transaction is to be settled by delivery of securities, in cash or otherwise.
		

		
			(j)         “Exchange Act” shall mean the Securities Exchange Act of 1934, as amended, and the rules and regulations of the SEC promulgated thereunder.
		

		
			(k)        “Extraordinary Matter” shall have the meaning set forth in Section 4.2.
		

		
			
		

		
			

		 

		

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			(l)         “Filing Date” shall mean (i) with respect to any Registration Statement to be filed on Form F-1 (or any applicable successor form), ninety (90) days after receipt by the Company of a Demand Request for such Registration Statement and (ii) with respect to any Registration Statement to be filed on Form F-3 (or any applicable successor form), sixty (60) days after receipt by the Company of a Demand Request for such Registration Statement.
		

		
			(m)       “Governmental Authority” shall mean any court, agency, authority, department, regulatory body or other instrumentality of any government or country or of any national, federal, state, provincial, regional, county, city or other political subdivision of any such government or country or any supranational organization of which any such country is a member.
		

		
			(n)        “Holders” shall mean (but, in each case, only for so long as such Person remains an Affiliate of the Investor) the Investor and any Permitted Transferee thereof, if any, in accordance with Section 2.12.
		

		
			(o)        “Initiating Holder” shall have the meaning set forth in Section 2.2.
		

		
			(p)        “Interference” shall have the meaning set forth in Section 2.4.
		

		
			(q)        “Investor” shall have the meaning set forth in the preamble to this Agreement.
		

		
			(r)          “Law” or “Laws” shall mean all laws, statutes, rules, regulations, orders, judgments, injunctions and/or ordinances of any Governmental Authority.
		

		
			(s)        “License Agreement” shall mean that certain License Agreement between the Company and the Investor dated as of the date hereof, relating to Investor’s point mutation selective targeting approach for autosomal dominant retinitis pigmentosa.
		

		
			(t)         “Lock-Up Term” shall have the meaning set forth in Section 3.1.
		

		
			(u)        “Modified Clause” shall have the meaning set forth in Section 6.7.
		

		
			(v)         “Ordinary Shares” shall have the meaning set forth in the preamble to this Agreement.
		

		
			(w)       “Ordinary Shares Equivalents” shall mean any options, warrants or other securities or rights convertible into or exercisable or exchangeable for, whether directly or following conversion into or exercise or exchange for other options, warrants or other securities or rights, Ordinary Shares.
		

		
			(x)        “Ordinary Shares Then Outstanding” shall mean, at any time, the issued and outstanding Ordinary Shares at such time, as well as all capital stock issued and outstanding as a result of any stock split, stock dividend, or reclassification of Ordinary Shares distributable, on a pro rata basis, to all holders of Ordinary Shares.
		

		
			
		

		
			

		 

		

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			(y)        “Other Holders” shall mean any Person having rights to participate in a registration of the Company’s securities.
		

		
			(z)        “Permitted Transferee” shall mean a controlled Affiliate of the Investor that is wholly owned, directly or indirectly, by the Investor; it being understood that for purposes of this definition “wholly owned” shall mean an Affiliate in which the Investor owns, directly or indirectly, at least ninety-nine percent (99%) of the outstanding capital stock of such Affiliate, or a Person acquiring all or substantially all of the Investor’s business or assets.
		

		
			(aa)      “Person” shall mean any individual, partnership, firm, corporation, association, trust, unincorporated organization, government or any department or agency thereof or other entity, as well as any syndicate or group that would be deemed to be a Person under Section 13(d)(3) of the Exchange Act.
		

		
			(bb)      “Prospectus” shall mean the prospectus forming a part of any Registration Statement, as supplemented by any and all prospectus supplements and as amended by any and all amendments (including post-effective amendments) and including all material incorporated by reference or explicitly deemed to be incorporated by reference in such prospectus.
		

		
			(cc)      “Purchase Agreement” shall have the meaning set forth in the preamble to this Agreement, and shall include all Exhibits attached thereto.
		

		
			(dd)      “Purchased Shares” shall have the meaning set forth in the preamble to this Agreement, and shall be adjusted for (i) any stock split, stock dividend, share exchange, merger, consolidation or similar recapitalization and (ii) any Common Stock issued as (or issuable upon the exercise of any warrant, right or other security that is issued as) a dividend or other distribution with respect to, or in exchange or in replacement of, the Purchased Shares.
		

		
			(ee)       “registers,” “registered,” and “registration” shall refer to a registration effected by preparing and filing a Registration Statement or similar document in compliance with the Securities Act, and the declaration or ordering of effectiveness of such Registration Statement or document by the SEC.
		

		
			(ff)       “Registrable Securities” shall mean (i) the Purchased Shares, together with any Ordinary Shares issued in respect thereof as a result of any stock split, stock dividend, share exchange, merger, consolidation or similar recapitalization and (ii) any Ordinary Shares issued as (or issuable upon the exercise of any warrant, right or other security that is issued as) a dividend or other distribution with respect to, or in exchange or in replacement of, the Ordinary Shares described in clause (i) of this definition, excluding in all cases, however, (A) any Registrable Securities if and after they have been transferred to a Permitted Transferee in a transaction in connection with which registration rights granted hereunder are not assigned, (B) any Registrable Securities sold to or through a broker or dealer or underwriter in a public distribution or a public securities transaction or (C) Registrable Securities eligible for resale pursuant to Rule 144(b)(1)(i) under the Securities Act.
		

		
			(gg)      “Registration Expenses” shall mean all expenses incurred by the Company in connection with any Required Registration pursuant to Section 2.1 or the
		

		
			
		

		
			

		 

		

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			Company’s compliance with Section 2.6 (excluding clauses (k) and (m) thereof), including, without limitation, all registration and filing fees, fees and expenses of compliance with securities or blue sky Laws (including reasonable fees and disbursements of counsel in connection with blue sky qualifications of any Registrable Securities), expenses of printing (i) certificates for any Registrable Securities in a form eligible for deposit with the Depository Trust Company or (ii) Prospectuses if the printing of Prospectuses is requested by Holders, messenger and delivery expenses, fees and disbursements of counsel for the Company and its independent certified public accountants (including the expenses of any management review, cold comfort letters or any special audits required by or incident to such performance and compliance), Securities Act liability insurance (if the Company elects to obtain such insurance), the reasonable fees and expenses of any special experts retained by the Company in connection with such registration, fees and expenses of other Persons retained by the Company and the reasonable fees and expenses of one (1) counsel for the Holders of Registrable Securities in each Required Registration, selected by the Holders of a majority of the Registrable Securities to be included in such Required Registration.
		

		
			(hh)      “Registration Rights Term” shall have the meaning set forth in Section 2.1.
		

		
			(ii)        “Registration Statement” shall mean any registration statement of the Company under the Securities Act that covers any of the Registrable Securities pursuant to the provisions of this Agreement, including the related Prospectus, all amendments and supplements to such registration statement (including post-effective amendments), and all exhibits and all materials incorporated by reference or explicitly deemed to be incorporated by reference in such Registration Statement.
		

		
			(jj)        “Required Period” with respect to a Required Registration shall mean the earlier of (i) the date on which all Registrable Securities covered by such Required Registration are sold pursuant thereto and (ii) one-hundred twenty (120) days following the first day of effectiveness of the Registration Statement for such Required Registration, in each case subject to extension as set forth herein; provided, however, that in no event will the Required Period expire prior to the expiration of the applicable period referred to in Section 4(3) of the Securities Act and Rule 174 promulgated thereunder.
		

		
			(kk)      “Required Registration” shall have the meaning set forth in Section 2.1.
		

		
			(ll)        “SEC” shall mean the United States Securities and Exchange Commission.
		

		
			(mm)    “Securities Act” shall mean the Securities Act of 1933, as amended, and the rules and regulations of the SEC promulgated thereunder.
		

		
			(nn)      “Selling Expenses” shall mean all underwriting discounts and selling commissions applicable to the sale of Registrable Securities pursuant to this Agreement.
		

		
			(oo)      “Third Party” shall mean any Person other than the Investor, the Company or any of their respective Affiliates.
		

		
			
		

		
			

		 

		

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			(pp)      “Underwritten Registration” or “Underwritten Offering” shall mean a registration in which Registrable Securities are sold to an underwriter for reoffering to the public.
		

		
			(qq)      “Violation” shall have the meaning set forth in Section 2.9(a).
		

		
			2.         Registration Rights.
		

		
			2.1       Required Registration. At such time as (i) the Investor owns at least 10% of the Ordinary Shares Then Outstanding of the Company and (ii) the first Lock-Up Term has expired but no later than the tenth (10th) anniversary of such expiration (the “Registration Rights Term”), the Company receives from any Holder or Holders a written request or requests (each, a “Demand Request”) that the Company file a Registration Statement under the Securities Act to effect the registration (a “Required Registration”) of Registrable Securities, the Company shall use all reasonable efforts to file a Registration Statement covering such Holders’ Registrable Securities as soon as practicable (and by the applicable Filing Date) and shall use all reasonable efforts to, as soon as practicable thereafter, effect the registration of the Registrable Securities of all or such portion of such Holder’s or Holders’ Registrable Securities as are specified in such Demand Request, subject however, to the conditions and limitations set forth herein; provided,  however, that the Company shall not be obligated to effect any registration of Registrable Securities upon receipt of a Demand Request pursuant to this Section 2.1 if:
		

		
			(i)        the Company has already completed one (1) Required Registration;
		

		
			(ii)       the market value of the Registrable Securities proposed to be included in the registration, based on the average closing price during the ten (10) consecutive trading days prior to the making of the Demand Request, is less than $10,000,000;
		

		
			(iii)      the Company shall furnish to the Holders a certificate signed by an authorized officer of the Company stating that (A) within ninety (90) days of receipt of the Demand Request under this Section 2.1, the Company shall file a registration statement for the public offering of securities for the account of the Company (other than a registration of securities (x) issuable pursuant to an employee stock option, stock purchase or similar plan, (y) issuable pursuant to a merger, exchange offer or a transaction of the type specified in Rule 145(a) under the Securities Act or (z) in which the only securities being registered are securities issuable upon conversion of debt securities which are also being registered), or (B) the Company is engaged in a material transaction or has an undisclosed material corporate development, in either case, which would be required to be disclosed in the Registration Statement, and in the good faith judgment of the Company’s Board of Directors, such disclosure would be seriously detrimental to the Company and its stockholders at such time (in which case, the Company shall disclose the matter as promptly as reasonably practicable and thereafter file the Registration Statement, and each Holder agrees not to disclose any information about such material transaction to Third Parties until such disclosure has occurred or such information has entered the public domain other than through breach of this provision by
		

		
			
		

		
			

		 

		

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			such Holder), provided,  however, that the Company shall have the right to only defer the filing of the Registration Statement pursuant to this subsection once in any twelve (12) month period and, such deferral may not exceed a period of more than one-hundred twenty (120) days after receipt of a Demand Request; or
		

		
			(iv)       at any time during the period between the Company’s receipt of the Demand Request and the completion of the Required Registration, any Holder is in breach of or has failed to cause its Affiliates to comply with the obligations and restrictions of Sections 3 or 4 of this Agreement, and such breach or failure is ongoing and has not been remedied.
		

		
			2.2       Underwritten Required Registration Required; Priority in Underwritten Offering. The underwriter for any Underwritten Offering requested pursuant to Section 2.1 shall be selected by a majority in interest of the Holders initiating the Required Registration hereunder (such Holder(s) initiating the registration request, the “Initiating Holders”) and shall be acceptable to the Company. The right of any Holder to include its Registrable Securities in the Underwritten Offering shall be conditioned upon such Holder’s participation in such Underwritten Offering and the inclusion of such Holder’s Registrable Securities to the extent provided herein. All Holders requesting the inclusion of their Registrable Securities in such Underwritten Offering shall (together with the Company as provided in Section 2.6(h)) enter into an underwriting agreement in customary form with the underwriter or underwriters selected for such Underwritten Offering. Notwithstanding any other provision of this Section 2, if the managing underwriter for the Underwritten Offering determines in good faith that marketing factors require a limitation of the number of shares of Registrable Securities to be included in such Underwritten Offering, then the Company shall so advise all Holders which requested inclusion of their Registrable Securities in such Underwritten Offering, and the number of shares of Registrable Securities that may be included in such Underwritten Offering shall be allocated among the Holders in proportion (as nearly as practicable) to the amount of Registrable Securities of the Company owned by each Holder; provided,  however, that the number of shares of Registrable Securities to be included in such Underwritten Offering shall not be reduced unless all other securities are first entirely excluded from such Underwritten Offering. In the event the Company advises the Holders of its intent to decrease the total number of Registrable Securities that may be included by the Holders in such Required Registration such that the number of Registrable Securities included in such Required Registration would be less than seventy-five percent (75%) of all Registrable Securities which the Holders requested be included in such Required Registration, then Holders representing a majority of the Registrable Securities requested to be included in such Required Registration will have the right to withdraw, on behalf of all Holders of all Registrable Securities requested to be so included, such Required Registration, in which case, such Required Registration will not count as a Required Registration for the purposes of Section 2.1(i), and the Company shall bear all Registration Expenses in connection therewith; provided,  that, the right to withdraw a registration and have it not count as a Required Registration may only be exercised once by the Holders (taken collectively).
		

		
			2.3       Priority in Required Registration. With respect to any Required Registration of Registrable Securities requested pursuant to Section 2.1, the Company may also (i) propose to sell Ordinary Shares on its own behalf and (ii) provide written notice of such Required Registration to Other Holders and permit all such Other Holders who request to be
		

		
			
		

		
			

		 

		

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			included in the Required Registration to include any or all Company securities held by such Other Holders in such Required Registration on the same terms and conditions as the Registrable Securities. Notwithstanding the foregoing, if the managing underwriter or underwriters of the Underwritten Offering to which any Required Registration relates advise the Company and the Holders of Registrable Securities that, in its good faith determination, the total amount of securities that such Holders, Other Holders, and the Company intend to include in such Required Registration is in an amount in the aggregate which would adversely affect the success of such Underwritten Offering, then such Required Registration shall include (i) first, all Registrable Securities of the Holders allocated, if the amount is less than all the Registrable Securities requested to be sold, pro rata on the basis of the total number of Registrable Securities held by such Holders; and (ii) second, as many other securities proposed to be included in the Required Registration by the Company and any Other Holders, allocated pro rata among the Company and such Other Holders, on the basis of the amount of securities requested to be included therein by the Company and each such Other Holder so that the total amount of securities to be included in such Underwritten Offering is the full amount that, in the written opinion of such managing underwriter, can be sold without materially and adversely affecting the success of such Underwritten Offering.
		

		
			2.4       Effective Required Registrations. A Required Registration will not be deemed to be effected for purposes of Section 2.1(i) if the Registration Statement for such Required Registration has not been declared effective by the SEC or become effective in accordance with the Securities Act and the rules and regulations thereunder and kept effective for the Required Period. In addition, if after such Registration Statement has been declared or becomes effective, (i) the offering of Registrable Securities pursuant to such Registration Statement is interfered with by any stop order, injunction, or other order or requirement of the SEC or other governmental agency or court such that the continued offer and sale of Registrable Securities being offered pursuant to such Registration Statement would violate applicable Law and such stop order, injunction or other order or requirement of the SEC or other governmental agency or court does not result from any act or omission of any Holder whose Registrable Securities are registered pursuant to such Registration Statement (an “Interference”) and (ii) any such Interference is not cured within sixty (60) days thereof, such Required Registration will be deemed not to have been effected and will not count as a Required Registration. In the event such Interference occurs and is cured, the Required Period relating to such Registration Statement will be extended by the number of days of such Interference, including the date such Interference is cured.
		

		
			2.5       Continuous Effectiveness of Registration Statement. The Company will use all reasonable efforts to cause each Registration Statement filed pursuant to this Section 2 to be declared effective by the SEC or to become effective under the Securities Act as promptly as practicable and to keep each such Registration Statement that has been declared or becomes effective continuously effective for the Required Period.
		

		
			2.6       Obligations of the Company. Whenever required under Section 2.1 to effect the registration of any Registrable Securities, the Company shall, as expeditiously as reasonably possible:
		

		
			
		

		
			

		 

		

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			(a)        prepare and file with the SEC a Registration Statement with respect to such Registrable Securities sought to be included therein; provided that at least five (5) Business Days prior to filing any Registration Statement or Prospectus or any amendments or supplements thereto, the Company shall furnish to the Holders of the Registrable Securities covered by such Registration Statement, their counsel and the managing underwriter copies of all such documents proposed to be filed, and any such Holder shall have the opportunity to comment on any information pertaining solely to such Holder and its plan of distribution that is contained therein and the Company shall make the corrections reasonably requested by such Holder or the managing underwriter with respect to such information prior to filing any such Registration Statement or amendment;
		

		
			(b)        prepare and file with the SEC such amendments and post-effective amendments to any Registration Statement and any Prospectus used in connection therewith as may be necessary to keep such Registration Statement effective for the Required Period, and cause the Prospectus to be supplemented by any required prospectus supplement, and as so supplemented to be filed pursuant to Rule 424 under the Securities Act, to comply with the provisions of the Securities Act with respect to the disposition of all Registrable Securities covered by such registration statement for the Required Period; provided that at least five (5) Business Days prior to filing any such amendments and post effective amendments or supplements thereto, the Company shall furnish to the Holders of the Registrable Securities covered by such Registration Statement, their counsel and the managing underwriter copies of all such documents proposed to be filed, and any such Holder or managing underwriter shall have the opportunity to comment on any information pertaining solely to such Holder and its plan of distribution that is contained therein and the Company shall make the corrections reasonably requested by such Holder and the managing underwriter with respect to such information prior to filing any such Registration Statement or amendment;
		

		
			(c)        furnish to the Holders of Registrable Securities covered by such Registration Statement and the managing underwriter such numbers of copies of such Registration Statement, each amendment and supplement thereto, the Prospectus included in such Registration Statement (including each preliminary prospectus or free writing prospectus) in conformity with the requirements of the Securities Act, and such other documents as they may reasonably request in order to facilitate the disposition of Registrable Securities owned by them;
		

		
			(d)        notify the Holders of Registrable Securities covered by such Registration Statement, promptly after the Company shall receive notice thereof, of the time when such Registration Statement becomes or is declared effective or when any amendment or supplement or any Prospectus forming a part of such Registration Statement has been filed;
		

		
			(e)        notify the Holders of Registrable Securities covered by such Registration Statement promptly of any request by the SEC for the amending or supplementing of such Registration Statement or Prospectus or for additional information and promptly deliver to such Holders copies of any comments received from the SEC;
		

		
			(f)        notify the Holders promptly of any stop order suspending the effectiveness of such Registration Statement or Prospectus or the initiation of any proceedings
		

		
			
		

		
			

		 

		

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			for that purpose, and use all reasonable efforts to obtain the withdrawal of any such order or the termination of such proceedings;
		

		
			(g)        use all reasonable efforts to register and qualify the Registrable Securities covered by such Registration Statement under such other securities or blue sky Laws of such jurisdictions as shall be reasonably requested by the Holders, use all reasonable efforts to keep each such registration or qualification effective, including through new filings, or amendments or renewals, during the Required Period, and notify the Holders of Registrable Securities covered by such Registration Statement of the receipt of any written notification with respect to any suspension of any such qualification; provided,  however, that the Company shall not be required in connection therewith or as a condition thereto to qualify to do business or to file a general consent to service of process in any such states or jurisdictions;
		

		
			(h)        enter into and perform its obligations under an underwriting agreement, in usual and customary form, with the managing underwriter of the Underwritten Offering pursuant to which such Registrable Securities are being offered;
		

		
			(i)         use all reasonable efforts to obtain: (A) at the time of effectiveness of the Registration Statement covering such Registrable Securities, a “cold comfort letter” from the Company’s independent certified public accountants covering such matters of the type customarily covered by “cold comfort letters” as the underwriters may reasonably request; and (B) at the time of any underwritten sale pursuant to such Registration Statement, a “bring-down comfort letter,” dated as of the date of such sale, from the Company’s independent certified public accountants covering such matters of the type customarily covered by “bring-down comfort letters” as the underwriters may reasonably request.
		

		
			(j)         promptly notify each Holder of Registrable Securities covered by such Registration Statement at any time when a Prospectus relating thereto is required to be delivered under the Securities Act of the happening of any event as a result of which the Prospectus included in such Registration Statement or any offering memorandum or other offering document includes an untrue statement of a material fact or omits to state any material fact required to be stated therein or necessary to make the statements therein not misleading in the light of the circumstances then existing, and promptly prepare a supplement or amendment to such Prospectus or file any other required document so that, as thereafter delivered to the purchasers of such Registrable Securities, such Prospectus will not contain an untrue statement of material fact or omit to state any fact necessary to make the statements therein not misleading;
		

		
			(k)        permit any Holder of Registrable Securities covered by such Registration Statement, which Holder in its reasonable judgment could reasonably be deemed to be an underwriter with respect to the Underwritten Offering pursuant to which such Registrable Securities are being offered, or to be a controlling Person of the Company, to reasonably participate in the preparation of such Registration Statement and to require the insertion therein of information to the extent concerning such Holder, furnished to the Company in writing, which in the reasonable judgment of such Holder and its counsel should be included;
		

		
			
		

		
			

		 

		

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			(l)         in connection with any Underwritten Offering, use all reasonable efforts to obtain an opinion or opinions addressed to the underwriter or underwriters in customary form and scope from counsel for the Company;
		

		
			(m)       upon reasonable notice and during normal business hours, subject to the Company receiving customary confidentiality undertakings or agreements from any Holder of Registrable Securities covered by such Registration Statement or other person obtaining access to Company records, documents, properties or other information pursuant to this subsection (m), make available for inspection by a representative of such Holder and any underwriter participating in any disposition of such Registrable Securities and any attorneys or accountants retained by any such Holder or underwriter, relevant financial and other records, pertinent corporate documents and properties of the Company, and use all reasonable efforts to cause the officers, directors and employees of the Company to supply all information reasonably requested by any such representative, underwriter, attorneys or accountants in connection with the Registration Statement;
		

		
			(n)        use all reasonable efforts to comply with all applicable rules and regulations of the SEC relating to such registration and make generally available to its security holders earning statements satisfying the provisions of Section 11(a) of the Securities Act, provided that the Company will be deemed to have complied with this Section 2.6(n) with respect to such earning statements if it has satisfied the provisions of Rule 158;
		

		
			(o)        if requested by the managing underwriter or any selling Holder, promptly incorporate in a prospectus supplement or post-effective amendment such information as the managing underwriter or any selling Holder reasonably requests to be included therein, with respect to the Registrable Securities being sold by such selling Holder, including, without limitation, the purchase price being paid therefor by the underwriters and with respect to any other terms of the Underwritten Offering of Registrable Securities to be sold in such offering, and promptly make all required filings of such prospectus supplement or post-effective amendment;
		

		
			(p)        cause the Registrable Securities covered by such Registration Statement to be listed on each securities exchange, if any, on which equity securities issued by the Company are then listed; and
		

		
			(q)        reasonably cooperate with each selling Holder and each underwriter participating in the disposition of such Registrable Securities and their respective counsel in connection with filings required to be made with the Financial Industry Regulatory Authority, Inc., if any.
		

		
			2.7       Furnish Information. It shall be a condition precedent to the obligations of the Company to take any action pursuant to this Section 2 with respect to the Registrable Securities of any selling Holder that such Holder shall furnish to the Company such information regarding itself and the Registrable Securities held by it as shall be reasonably necessary to effect the registration of such Holder’s Registrable Securities.
		

		
			
		

		
			

		 

		

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			2.8       Expenses. Except as specifically provided herein, all Registration Expenses shall be borne by the Company. All Selling Expenses incurred in connection with any registration hereunder shall be borne by the Holders of Registrable Securities covered by a Registration Statement, pro rata on the basis of the number of Registrable Securities registered on their behalf in such Registration Statement.
		

		
			2.9       Indemnification. In the event any Registrable Securities are included in a Registration Statement under this Agreement:
		

		
			(a)        The Company shall indemnify and hold harmless each Holder including Registrable Securities in any such Registration Statement, any underwriter (as defined in the Securities Act) for such Holder and each Person, if any, who controls such Holder or underwriter within the meaning of Section 15 of the Securities Act or Section 20 of Exchange Act and the officers, directors, owners, agents and employees of such controlling Persons, against any and all losses, claims, damages or liabilities (joint or several) to which they may become subject under any securities Laws including, without limitation, the Securities Act, the Exchange Act, or any other statute or common law of the United States or any other country or political subdivision thereof, or otherwise, including the amount paid in settlement of any litigation commenced or threatened (including any amounts paid pursuant to or in settlement of claims made under the indemnification or contribution provisions of any underwriting or similar agreement entered into by such Holder in connection with any offering or sale of securities covered by this Agreement), and shall promptly reimburse them, as and when incurred, for any legal or other expenses incurred by them in connection with investigating any claims and defending any actions, insofar as any such losses, claims, damages or liabilities (or actions in respect thereof) arise out of or are based upon any of the following statements, omissions or violations (each, a “Violation”): (i) any untrue statement or alleged untrue statement of a material fact contained in or incorporated by reference into such Registration Statement, including any preliminary prospectus or final prospectus contained therein or any free writing prospectus or any amendments or supplements thereto, or in any offering memorandum or other offering document relating to the offering and sale of such securities or (ii) the omission or alleged omission to state therein a material fact required to be stated therein, or necessary to make the statements therein not misleading; provided,  however, the Company shall not be liable in any such case for any such loss, claim, damage, liability or action to the extent that it (A) arises out of or is based upon a Violation which occurs solely in reliance upon and in conformity with written information furnished expressly for use in connection with such registration by such Holder; or (B) is caused by such Holder’s disposition of Registrable Shares during any period during which such Holder is obligated to discontinue any disposition of Registrable Shares as a result of any stop order suspending the effectiveness of any registration statement or prospectus with respect to Registrable Securities.
		

		
			(b)        Each Holder including Registrable Securities in a registration statement shall indemnify and hold harmless the Company, each of its directors, each of its officers who has signed the registration statement, each Person, if any, who controls the Company within the meaning of Section 15 of the Securities Act or Section 20 of the Exchange Act and the officers, directors, owners, agents and employees of such controlling Persons, any underwriter, any other Holder selling securities in such registration statement and any controlling Person of any such underwriter or other Holder, against any losses, claims, damages or liabilities
		

		
			
		

		
			

		 

		

			12

		

 

		

		
			(joint or several) to which any of the foregoing Persons may become subject, under liabilities (or actions in respect thereto) which arise out of or are based upon any Violation, in each case to the extent (and only to the extent) that such Violation: (i) arises out of or is based upon a Violation which occurs solely in reliance upon and in conformity with written information furnished expressly for use in connection with such registration by such Holder; or (ii) is caused by such Holder’s disposition of Registrable Shares during any period during which such Holder is obligated to discontinue any disposition of Registrable Shares as a result of any stop order suspending the effectiveness of any registration statement or prospectus with respect to Registrable Securities. Each such Holder shall pay, as incurred, any legal or other expenses reasonably incurred by any Person intended to be indemnified pursuant to this Section 2.9(b), in connection with investigating or defending any such loss, claim, damage, liability or action; provided,  however, that the indemnity agreement contained in this Section 2.9(b) shall not apply to amounts paid in settlement of any such loss, claim, damage, liability or action if such settlement is effected without consent of the Holder, which consent shall not be unreasonably withheld.
		

		
			(c)        Promptly after receipt by an indemnified party under this Section 2.9 of notice of the commencement of any action (including any action by a Governmental Authority), such indemnified party shall, if a claim in respect thereof is to be made against any indemnifying party under this Section 2.9, deliver to the indemnifying party a written notice of the commencement thereof and the indemnifying party shall have the right to participate in, and, to the extent the indemnifying party so desires, jointly with any other indemnifying party similarly noticed, to assume the defense thereof with counsel mutually satisfactory to the parties; provided,  however, that an indemnified party shall have the right to retain its own counsel, with the reasonable fees and expenses to be paid by the indemnifying party, if representation of such indemnified party by the counsel retained by the indemnifying party would be inappropriate due to actual or potential differing interests between such indemnified party and any other party represented by such counsel in such proceeding. The failure to deliver written notice to the indemnifying party within a reasonable time of the commencement of any such action, if prejudicial to its ability to defend such action, shall relieve such indemnifying party of any liability to the indemnified party under this Section 2.9, but the omission so to deliver written notice to the indemnifying party shall not relieve it of any liability that it may have to any indemnified party otherwise than under this Section 2.9.
		

		
			(d)        In order to provide for just and equitable contribution to joint liability in any case in which a claim for indemnification is made pursuant to this Section 2.9 but it is judicially determined (by the entry of a final judgment or decree by a court of competent jurisdiction and the expiration of time to appeal or the denial of the last right of appeal) that such indemnification may not be enforced in such case notwithstanding the fact that this Section 2.9 provided for indemnification in such case, the Company and each Holder of Registrable Securities shall contribute to the aggregate losses, claims, damages or liabilities to which they may be subject (after contribution from others) in proportion to the relative fault of the Company, on the one hand, and such Holder, severally, on the other hand; provided,  however, that in any such case, no Person guilty of fraudulent misrepresentation (within the meaning of Section 11(f) of the Securities Act) shall be entitled to contribution from any Person who was not guilty of such fraudulent misrepresentation; provided further,  however, that in no event shall any contribution under this Section 2.9(d) on the part of any Holder exceed the net proceeds received
		

		
			
		

		
			

		 

		

			13

		

 

		

		
			by such Holder from the sale of Registrable Securities giving rise to such contribution obligation, except in the case of willful misconduct or fraud by such Holder.
		

		
			(e)        The obligations of the Company and the Holders under this Section 2.9 shall survive the completion of any offering of Registrable Securities in a registration statement under this Agreement and otherwise.
		

		
			2.10     SEC Reports. With a view to making available to the Holders the benefits of Rule 144 under the Securities Act and any other rule or regulation of the SEC that may at any time permit a Holder to sell Registrable Securities of the Company to the public without registration, the Company agrees to at any time that it is a reporting company under Section 13 or 15(d) of the Exchange Act:
		

		
			(a)        file with the SEC in a timely manner all reports and other documents required of the Company under the Exchange Act; and
		

		
			(b)        furnish to any Holder, so long as such Holder owns any Registrable Securities, forthwith upon request (i) a written statement by the Company that it has complied with the reporting requirements of the Exchange Act, (ii) a copy of the most recent annual or quarterly report of the Company and such other reports and documents so filed by the Company, and (iii) such other information as may be reasonably requested in availing any Holder of any rule or regulation of the SEC (exclusive of Rule 144A) which permits the selling of any Registrable Securities without registration.
		

		
			2.11     Assignment of Registration Rights. The rights to cause the Company to register any Registrable Securities pursuant to this Agreement may be assigned in whole or in part (but only with all restrictions and obligations set forth in this Agreement) by a Holder to a Permitted Transferee which acquires Registrable Securities from such Holder; provided,  however, (a) such Holder shall, within five (5) days prior to such transfer, furnish to the Company written notice of the name and address of such Permitted Transferee, details of its status as a Permitted Transferee and details of the Registrable Securities with respect to which such registration rights are being assigned, (b) the Permitted Transferee, prior to or simultaneously with such transfer or assignment, shall agree in writing to be subject to and bound by all restrictions and obligations set forth in this Agreement, (c) the Investor shall continue to be bound by all restrictions and obligations set forth in this Agreement and (d) such transfer or assignment shall be effective only if immediately following such transfer or assignment the further disposition of such Registrable Securities by the Permitted Transferee is restricted under the Securities Act and other applicable securities Law.
		

		
			3.         Restrictions on Dispositions.
		

		
			3.1       Lock-Up. From and after the date of the applicable Closing (as defined in the Purchase Agreement) at which Shares are issued and sold and until the date that is twelve months following such Closing (each a “Lock-Up Term”), without the prior approval of a majority of the Company’s Board of Directors, the Investor shall not, and shall cause its Affiliates not to, Dispose of (x) any of the Purchased Shares issued and sold at such applicable Closing, together with any Ordinary Shares issued in respect thereof as a result of any stock split,
		

		
			
		

		
			

		 

		

			14

		

 

		

		
			stock dividend, share exchange, merger, consolidation or similar recapitalization, and (y) any Common Stock issued as (or issuable upon the exercise of any warrant, right or other security that is issued as) a dividend or other distribution with respect to, or in exchange or in replacement of, the Ordinary Shares described in clause (x) of this sentence; provided,  however, that the foregoing shall not prohibit the Investor from transferring Registrable Securities to a Permitted Transferee in accordance with this Agreement.
		

		
			3.2       Certain Tender Offers. Notwithstanding any other provision of this Section 3, this Section 3 shall not prohibit or restrict any Disposition of Ordinary Shares Then Outstanding and/or Ordinary Share Equivalents by the Investor into (a) a tender offer by a Third Party or (b) an issuer tender offer by the Company.
		

		
			4.         Voting Agreement.
		

		
			4.1       Voting of Securities. From and after the date of this Agreement, other than as permitted by Section 4.2 with respect to Extraordinary Matters, in any vote or action by written consent of the stockholders of the Company (including, without limitation, with respect to the election of directors), the Investor shall, and shall cause its respective Affiliates to, vote or execute a written consent with respect to all voting securities of the Company as to which they are entitled to vote or execute a written consent, in the sole discretion of the Investor, in accordance with the recommendation of the Company’s Board of Directors. In furtherance of this Section 4.1, the Investor shall, and shall cause its Affiliates to, if and when requested by the Company from time to time, promptly execute and deliver to the Company an irrevocable proxy, substantially in the form of Exhibit A attached hereto, and irrevocably appoint the Company or its designees, with full power of substitution, its attorney, agent and proxy to vote (or cause to be voted) or to give consent with respect to, all of the voting securities of the Company as to which the Investor or Affiliate of the Investor is entitled to vote, in the manner and with respect to the matters set forth in this Section 4.1. The Investor acknowledges, and shall cause its Affiliates to acknowledge, that any such proxy executed and delivered shall be coupled with an interest, shall constitute, among other things, an inducement for the Company to enter into this Agreement, shall be irrevocable and binding on any successor in interest of the Investor or Affiliate of the Investor, as applicable, and shall not be terminated by operation of Law upon the occurrence of any event. Such proxy shall operate to revoke and render void any prior proxy as to any voting securities of the Company heretofore granted by the Investor or Affiliate of the Investor, as applicable, to the extent it is inconsistent herewith. Such proxy shall terminate upon the earlier of the expiration or termination of this Section 4.1.
		

		
			4.2       Certain Extraordinary Matters.  The Investor and its Affiliates may vote, or execute a written consent with respect to, any or all of the voting securities of the Company as to which they are entitled to vote or execute a written consent, as they may determine in their sole discretion, with respect to the following matters (each such matter being an “Extraordinary Matter”):
		

		
			(a)        any transaction which would result in a Change of Control; and
		

		
			(b)        any liquidation or dissolution of the Company.
		

		
			
		

		
			

		 

		

			15

		

 

		

		
			4.3       Quorum. In furtherance of Section 4.1, the Investor shall be, and shall cause each of its Affiliates to be, present in person or represented by proxy at all meetings of stockholders to the extent necessary so that all voting securities of the Company as to which they are entitled to vote shall be counted as present for the purpose of determining the presence of a quorum at such meeting.
		

		
			5.         Termination of Certain Rights and Obligations.
		

		
			5.1       Termination of Registration Rights. Except for Section 2.9, which shall survive until the expiration of any applicable statutes of limitation, Section 2 shall terminate automatically and have no further force or effect upon the earliest to occur of:
		

		
			(a)        the expiration of the Registration Rights Term;
		

		
			(b)       the date on which the Common Stock ceases to be registered pursuant to Section 12 of the Exchange Act; and
		

		
			(c)       a liquidation or dissolution of the Company.
		

		
			5.2       Termination of Restrictions on Dispositions.  Section 3 shall terminate and have no further force or effect upon the earliest to occur of:
		

		
			(a)       the consummation by an Offeror of a Change of Control of the Company;
		

		
			(b)       a liquidation or dissolution of the Company; and
		

		
			(c)       the date on which the Common Stock ceases to be registered pursuant to Section 12 of the Exchange Act.
		

		
			5.3       Effect of Termination. No termination pursuant to any of Section 5 shall relieve any of the parties (or the Permitted Transferee, if any) for liability for breach of or default under any of their respective obligations or restrictions under any terminated provision of this Agreement, which breach or default arose out of events or circumstances occurring or existing prior to the date of such termination.
		

		
			6.         Miscellaneous.
		

		
			6.1       Governing Law; Submission to Jurisdiction. This Agreement shall be governed by and construed in accordance with the Laws of the State of New York, without regard to the conflict of laws principles thereof that would require the application of the Law of any other jurisdiction. The parties irrevocably and unconditionally submit to the exclusive jurisdiction of the United States District Court for the Southern District of New York solely and specifically for the purposes of any action or proceeding arising out of or in connection with this Agreement.
		

		
			6.2       Waiver. Waiver by a party of a breach hereunder by another party shall not be construed as a waiver of any subsequent breach of the same or any other provision. No
		

		
			
		

		
			

		 

		

			16

		

 

		

		
			delay or omission by a party in exercising or availing itself of any right, power or privilege hereunder shall preclude the later exercise of any such right, power or privilege by such party. No waiver shall be effective unless made in writing with specific reference to the relevant provision(s) of this Agreement and signed by a duly authorized representative of the party granting the waiver.
		

		
			6.3       Notices. All notices, instructions and other communications hereunder or in connection herewith shall be in writing, shall be sent to the address of the relevant party set forth on Exhibit B attached hereto and shall be (a) delivered personally, (b) sent by registered or certified mail, return receipt requested, postage prepaid, (c) sent via a reputable nationwide overnight courier service or (d) sent by facsimile transmission, with a confirmation copy to be sent by registered or certified mail, return receipt requested, postage prepaid. Any such notice, instruction or communication shall be deemed to have been delivered upon receipt if delivered by hand, three (3) Business Days after it is sent by registered or certified mail, return receipt requested, postage prepaid, one (1) Business Day after it is sent via a reputable nationwide overnight courier service or when transmitted with electronic confirmation of receipt, if transmitted by facsimile (if such transmission is made during regular business hours of the recipient on a Business Day; or otherwise, on the next Business Day following such transmission). Any party may change its address by giving notice to the other parties in the manner provided above.
		

		
			6.4       Entire Agreement. This Agreement and the Purchase Agreement contain the entire agreement among the parties with respect to the subject matter hereof and thereof and supersede all prior and contemporaneous arrangements or understandings, whether written or oral, with respect hereto and thereto.
		

		
			6.5       Amendments. No provision in this Agreement shall be supplemented, deleted or amended except in a writing executed by an authorized representative of each of the parties hereto.
		

		
			6.6       Headings; Nouns and Pronouns; Section References. Headings in this Agreement are for convenience of reference only and shall not be considered in construing this Agreement. Whenever the context may require, any pronouns used herein shall include the corresponding masculine, feminine or neuter forms, and the singular form of names and pronouns shall include the plural and vice-versa. References in this Agreement to a section or subsection shall be deemed to refer to a section or subsection of this Agreement unless otherwise expressly stated.
		

		
			6.7       Severability. If, under applicable Laws, any provision hereof is invalid or unenforceable, or otherwise directly or indirectly affects the validity of any other material provision(s) of this Agreement in any jurisdiction (“Modified Clause”), then, it is mutually agreed that this Agreement shall endure and that the Modified Clause shall be enforced in such jurisdiction to the maximum extent permitted under applicable Laws in such jurisdiction; provided that the parties shall consult and use all reasonable efforts to agree upon, and hereby consent to, any valid and enforceable modification of this Agreement as may be necessary to avoid any unjust enrichment of either party and to match the intent of this Agreement as closely as possible, including the economic benefits and rights contemplated herein.
		

		
			
		

		
			

		 

		

			17

		

 

		

		
			6.8       Assignment. Neither this Agreement nor any rights or duties of a party hereto may be assigned by such party, in whole or in part, without (a) the prior written consent of the Company in the case of any assignment by the Investor, except as provided by Section 2.11 with respect to the Investor’s assignment to a Permitted Transferee; or (b) the prior written consent of the Investor in the case of an assignment by the Company.
		

		
			6.9       Successors and Assigns. This Agreement shall be binding upon and inure to the benefit of the parties hereto and their respective successors and permitted assigns.
		

		
			6.10     Counterparts. This Agreement may be executed in counterparts, each of which shall be deemed an original but which together shall constitute one and the same instrument.
		

		
			6.11     Third Party Beneficiaries. None of the provisions of this Agreement shall be for the benefit of or enforceable by any Third Party. No Third Party shall obtain any right under any provision of this Agreement or shall by reason of any such provision make any claim in respect of any debt, liability or obligation (or otherwise) against any party hereto.
		

		
			6.12     No Strict Construction. This Agreement has been prepared jointly and will not be construed against any party.
		

		
			6.13     Remedies. The rights, powers and remedies of the parties under this Agreement are cumulative and not exclusive of any other right, power or remedy which such parties may have under any other agreement or Law. No single or partial assertion or exercise of any right, power or remedy of a party hereunder shall preclude any other or further assertion or exercise thereof.
		

		
			6.14     Specific Performance. The Investor hereby acknowledges and agrees that the rights of the parties hereunder are special, unique and of extraordinary character, and that if any party refuses or otherwise fails to act, or to cause its Affiliates to act, in accordance with the provisions of this Agreement, such refusal or failure would result in irreparable injury to the Company or the Investor, as the case may be, the exact amount of which would be difficult to ascertain or estimate and the remedies at law for which would not be reasonable or adequate compensation. Accordingly, if any party refuses or otherwise fails to act, or to cause its Affiliates to act, in accordance with the provisions of this Agreement, then, in addition to any other remedy which may be available to any damaged party at law or in equity, such damaged party will be entitled to seek specific performance and injunctive relief, without posting bond or other security, and without the necessity of proving actual or threatened damages, which remedy such damaged party will be entitled to seek in any court of competent jurisdiction.
		

		
			6.15     No Conflicting Agreements. The Investor hereby represents and warrants to the Company that neither it nor any of its Affiliates is, as of the date of this Agreement, a party to, and agrees that neither it nor any of its Affiliates shall, on or after the date of this Agreement, enter into any agreement that conflicts with the rights granted to the Company in this Agreement. The Company hereby represents and warrants to each Holder that it is not, as of the date of this Agreement, a party to, and agrees that it shall not, on or after the date of this Agreement, enter into, any agreement or approve any amendment to its Organizational Documents (as defined in
		

		
			
		

		
			

		 

		

			18

		

 

		

		
			the Purchase Agreement) with respect to its securities that conflicts with the rights granted to the Holders in this Agreement. The Company further represents and warrants that the rights granted to the Holders hereunder do not in any way conflict with the rights granted to any other holder of the Company’s securities under any other agreements.
		

		
			(Signature Page Follows)
		

		
			 
		

		
			 
		

		
			

		 

		

			19

		

 

		

		
			IN WITNESS WHEREOF, the parties have executed and delivered this Agreement as of the date first above written.
		

			
					
						 

					
					
						    

					
					
						IONIS PHARMACEUTICALS, INC.

				
	
					
						 

					
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						 

					
					
						By:

					
					
						 

				
	
					
						 

					
					
						 

					
					
						 

					
					
						Name:

					
					
						 

				
	
					
						 

					
					
						 

					
					
						 

					
					
						Title:

					
					
						 

				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						 

					
					
						PROQR THERAPEUTICS N.V.

				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						 

					
					
						By:

					
					
						 

				
	
					
						 

					
					
						 

					
					
						 

					
					
						Name:

					
					
						 

				
	
					
						 

					
					
						 

					
					
						 

					
					
						Title:

					
					
						 

				

		
			 
		

		
			 
		

		
			 
		

		
			

		 

		

			 

		

 

		

		
			EXHIBIT A
		

		
			FORM OF IRREVOCABLE PROXY
		

		
			In order to secure the performance of the duties of the undersigned pursuant to Section 4.1 of the Investor Agreement, dated as of [__], 2018 (the “Agreement”), by and between [INVESTOR] and [COMPANY] (the “Company”), the undersigned hereby irrevocably appoints [__] and [__], and each of them, the attorneys, agents and proxies, with full power of substitution in each of them, for the undersigned, and in the name, place and stead of the undersigned, to vote (or cause to be voted) or, if applicable, to give consent, in such manners as each such attorney, agent and proxy or his substitute shall in his sole discretion deem proper to record such vote (or consent) in the manners, and with respect to such matters as set forth in Section 4.1 of the Agreement (but in any case, in accordance with any written instruction from the undersigned, properly delivered under Section 4.1 of the Agreement, to vote or give consent as contemplated by Section 4.1 of the Agreement) with respect to all voting securities (whether taking the form of Ordinary Shares or other voting securities of the Company), which the undersigned is or may be entitled to vote at any meeting of the Company held after the date hereof, whether annual or special and whether or not an adjourned meeting or, if applicable, to give written consent with respect thereto. This proxy is coupled with an interest, shall be irrevocable and binding on any successor in interest of the undersigned and shall not be terminated by operation of law upon the occurrence of any event. This proxy shall operate to revoke and render void any prior proxy as to voting securities heretofore granted by the undersigned which is inconsistent herewith. This proxy shall terminate upon the earlier of the expiration or termination of the voting agreement set forth in Section 4.1 of the Agreement.
		

			
					
						 

					
					
						 

					
					
						[_____________________________]

				
	
					
						 

					
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						    

					
					
						By:

					
					
						 

				
	
					
						 

					
					
						 

					
					
						 

					
					
						Name:

					
					
						 

				
	
					
						 

					
					
						 

					
					
						 

					
					
						Title:

					
					
						 

				

		
			 
		

		
			 
		

		
			 
		

		
			

		 

		

			A-1

		

 

		

		
			EXHIBIT B
		

		
			NOTICES
		

		
			(a)        If to the Investor:
		

		
			Ionis Pharmaceuticals, Inc.
		

		
			2855 Gazelle Court
		

		
			Carlsbad, CA 92010
		

		
			U.S.A.
		

		
			Attention: Chief Operating Officer
		

		
			with a copy to:
		

		
			legalnotices@ionisph.com
		

		
			(b)        If to the Company:
		

		
			ProQR Therapeutics N.V.
		

		
			Zernikedreef 9, 2333 CK Leiden
		

		
			The Netherlands
		

		
			31 88 166 7000
		

		
			Attention: Chief Executive Officer
		

		
			with a copy to:
		

		
			Goodwin Procter LLP
		

		
			100 Northern Ave.
		

		
			Boston, MA 02210
		

		
			Attention: Mitch Bloom, Esq. and Danielle Lauzon, Esq.
		

		
			 
		

		
			 
		

		
			

		 

		

			B-1

		

 

		

		
			EXHIBIT C
		

		
			NOTICES
		

		
			(a)        If to the Investor:
		

		
			Ionis Pharmaceuticals, Inc.
		

		
			2855 Gazelle Court
		

		
			Carlsbad, CA 92010 
		

		
			U.S.A.
		

		
			Attention: Chief Operating Officer
		

		
			with a copy to:
		

		
			legalnotices@ionisph.com
		

		
			(b)        If to the Company:
		

		
			ProQR Therapeutics N.V.
		

		
			Zernikedreef 9, 2333 CK Leiden
		

		
			the Netherlands
		

		
			Attention: Chief Executive Officer
		

		
			with a copy to:
		

		
			Goodwin Procter LLP
		

		
			100 Northern Avenue
		

		
			Boston, MA 02210
		

		
			Attention: Mitchell S. Bloom and Danielle M. Lauzon
		

		
			 
		

		
			 
		

		
			

		 

		

			C-1

		

 

		

		
			INVESTOR AGREEMENT
		

		
			By and Between
		

		
			IONIS PHARMACEUTICALS, INC. AND
		

		
			PROQR THERAPEUTICS N.V.
		

		
			Dated as of October 26, 2018
		

		
			 
		

		
			 
		

		

		 

		

			 

		

 

	
					
						

					
						 

					
					
						 

					
					
						 

					
					
						 

				
	
					
						TABLE OF CONTENTS

				
	
					
						 

					
					
						 

					
					
						Page

				
	
					
						1.

					
					
						Definitions

					
1
				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						2.

					
					
						Registration Rights

					
6
				
	
					
						 

					
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						2.1

					
					
						Required Registration

					
6
				
	
					
						 

					
					
						2.2

					
					
						Underwritten Required Registration  Required;  Priority  in  Underwritten Offering

					
7
				
	
					
						 

					
					
						2.3

					
					
						Priority in Required Registration

					
7
				
	
					
						 

					
					
						2.4

					
					
						Effective Required Registrations

					
8
				
	
					
						 

					
					
						2.5

					
					
						Continuous Effectiveness of Registration Statement

					
8
				
	
					
						 

					
					
						2.6

					
					
						Obligations of the Company

					
8
				
	
					
						 

					
					
						2.7

					
					
						Furnish Information

					
11
				
	
					
						 

					
					
						2.8

					
					
						Expenses

					
12
				
	
					
						 

					
					
						2.9

					
					
						Indemnification

					
12
				
	
					
						 

					
					
						2.10

					
					
						SEC Reports

					
14
				
	
					
						 

					
					
						2.11

					
					
						Assignment of Registration Rights

					
14
				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						3.

					
					
						Restrictions on Dispositions

					
14
				
	
					
						 

					
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						3.1

					
					
						Lock-Up

					
14
				
	
					
						 

					
					
						3.2

					
					
						Certain Tender Offers

					
15
				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						4.

					
					
						Voting Agreement

					
15
				
	
					
						 

					
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						4.1

					
					
						Voting of Securities

					
15
				
	
					
						 

					
					
						4.2

					
					
						Certain Extraordinary Matters

					
15
				
	
					
						 

					
					
						4.3

					
					
						Quorum

					
16
				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						5.

					
					
						Termination of Certain Rights and Obligations

					
16
				
	
					
						 

					
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						5.1

					
					
						Termination of Registration Rights

					
16
				
	
					
						 

					
					
						5.2

					
					
						Termination of Restrictions on Dispositions

					
16
				
	
					
						 

					
					
						5.3

					
					
						Effect of Termination

					
16
				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						6.

					
					
						Miscellaneous

					
16
				
	
					
						 

					
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						6.1

					
					
						Governing Law; Submission to Jurisdiction

					
16
				
	
					
						 

					
					
						6.2

					
					
						Waiver

					
16
				
	
					
						 

					
					
						6.3

					
					
						Notices

					
17
				
	
					
						 

					
					
						6.4

					
					
						Entire Agreement

					
17
				
	
					
						 

					
					
						6.5

					
					
						Amendments

					
17
				
	
					
						 

					
					
						6.6

					
					
						Headings; Nouns and Pronouns; Section References

					
17
				
	
					
						 

					
					
						6.7

					
					
						Severability

					
17
				
	
					
						 

					
					
						6.8

					
					
						Assignment

					
18
				
	
					
						 

					
					
						6.9

					
					
						Successors and Assigns

					
18
				
	
					
						 

					
					
						6.10

					
					
						Counterparts

					
18
				
	
					
						 

					
					
						6.11

					
					
						Third Party Beneficiaries

					
18
				
	
					
						 

					
					
						6.12

					
					
						No Strict Construction

					
18
				
	
					
						 

					
					
						6.13

					
					
						Remedies

					
18
				

		
			 
		

		
			
		

		
			

		 

		

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						6.14

					
					
						Specific Performance

					
18
				
	
					
						 

					
					
						6.15

					
					
						No Conflicting Agreements

					
18
				

		
			 
		

		
			Exhibit A – Form of Irrevocable Proxy 
		

		
			Exhibit B – Notices
		

		
			 
		

		
			 
		

		
			

		 

		

			ii

		

 

		

		
			INVESTOR AGREEMENT
		

		
			THIS INVESTOR AGREEMENT (this “Agreement”) is made as of October 26, 2018, by and between Ionis Pharmaceuticals, Inc. (the “Investor”), a Delaware corporation, and ProQR Therapeutics N.V. (the “Company”), a public company with limited liability incorporated under the laws of the Netherlands.
		

		
			WHEREAS, the Share Purchase Agreement, dated as of October 26, 2018, by and between the Investor and the Company (the “Purchase Agreement”) provides for the issuance and sale by the Company to the Investor, and the purchase by the Investor, of a certain number of ordinary shares, nominal value Euro 0.04 per ordinary share of the Company (the “Ordinary Shares”), equal to up to the aggregate number of Shares (as defined in the Purchase Agreement) (the “Purchased Shares”); and
		

		
			WHEREAS, as a condition to consummating the transactions contemplated by the Purchase Agreement, the Investor and the Company have agreed upon certain rights and restrictions as set forth herein with respect to the Purchased Shares and other securities of the Company beneficially owned by the Investor and its Affiliates, and it is a condition to the closing under the Purchase Agreement that this Agreement be executed and delivered by the Investor and the Company.
		

		
			NOW, THEREFORE, in consideration of the premises and mutual agreements hereinafter set forth, and for other valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the parties hereto agree as follows:
		

		
			1.         Definitions. As used in this Agreement, the following terms shall have the following meanings:
		

		
			(a)         “Affiliate” shall mean, with respect to any Person, another Person which controls, is controlled by or is under common control with such Person. A Person shall be deemed to control another Person if such Person possesses, directly or indirectly, the power to direct or cause the direction of the management and policies of such Person, whether through the ownership of voting securities, by contract or otherwise. Without limiting the generality of the foregoing, a Person shall be deemed to control another Person if any of the following conditions is met: (i) in the case of corporate entities, direct or indirect ownership of more than fifty percent (50%) of the stock or shares having the right to vote for the election of directors, and (ii) in the case of non-corporate entities, direct or indirect ownership of more than fifty percent (50%) of the equity interest with the power to direct the management and policies of such non-corporate entities.
		

		
			(b)        “Agreement” shall have the meaning set forth in the preamble to this Agreement, including all Exhibits attached hereto.
		

		
			(c)          “beneficial owner,” “beneficially owns,” “beneficial ownership” and terms of similar import used in this Agreement shall, with respect to a Person, have the meaning set forth in Rule 13d-3 under the Exchange Act (i) assuming the full conversion into, and exercise and exchange for, Ordinary Shares of all Ordinary Share
		

		
			 
		

		
			 
		

		
			

		 

		

			 

		

 

		

		
			Equivalents beneficially owned by such Person and (ii) determined without regard for the number of days in which such Person has the right to acquire such beneficial ownership.
		

		
			(d)        “Business Day” shall mean a day on which commercial banking institutions in New York, New York are open for business.
		

		
			(e)        “Change of Control” shall mean, with respect to the Company, any of the following events: (i) any Person is or becomes the beneficial owner (except that a Person shall be deemed to have beneficial ownership of all shares that any such Person has the right to acquire, whether such right which may be exercised immediately or only after the passage of time), directly or indirectly, of a majority of the total voting power represented by all Ordinary Shares Then Outstanding; (ii) the Company consolidates with or merges into another corporation or entity, or any corporation or entity consolidates with or merges into the Company, other than (A) a merger or consolidation which would result in the voting securities of the Company outstanding immediately prior to such merger or consolidation continuing to represent (either by remaining outstanding or by being converted into voting securities of the surviving entity or any parent thereof) a majority of the combined voting power of the voting securities of the Company or such surviving entity or any parent thereof outstanding immediately after such merger or consolidation, or (B) a merger or consolidation effected to implement a recapitalization of the Company (or similar transaction) in which no Person becomes the beneficial owner, directly or indirectly, of a majority of the total voting power of all Ordinary Shares Then Outstanding or (iii) the Company conveys, transfers or leases all or substantially all of its assets to any Person other than a wholly owned Affiliate of the Company.
		

		
			(f)         “Closing Date” shall have the meaning set forth in the Purchase Agreement.
		

		
			(g)        “Company” shall have the meaning set forth in the preamble to this Agreement.
		

		
			(h)        “Demand Request” shall have the meaning set forth in Section 2.1.
		

		
			(i)         “Disposition” or “Dispose of” shall mean any (i) offer, pledge,
		

		
			sale, contract to sell, sale of any option or contract to purchase, purchase of any option or contract to sell, grant of any option, right or warrant for the sale of, or other disposition of or transfer of any Ordinary Shares, or any Ordinary Share Equivalents, including, without limitation, any “short sale” or similar arrangement, or (ii) swap or any other agreement or any transaction that transfers, in whole or in part, directly or indirectly, the economic consequence of ownership of Ordinary Shares, whether any such swap or transaction is to be settled by delivery of securities, in cash or otherwise.
		

		
			(j)         “Exchange Act” shall mean the Securities Exchange Act of 1934, as amended, and the rules and regulations of the SEC promulgated thereunder.
		

		
			(k)        “Extraordinary Matter” shall have the meaning set forth in Section 4.2.
		

		
			
		

		
			

		 

		

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			(l)         “Filing Date” shall mean (i) with respect to any Registration Statement to be filed on Form F-1 (or any applicable successor form), ninety (90) days after receipt by the Company of a Demand Request for such Registration Statement and (ii) with respect to any Registration Statement to be filed on Form F-3 (or any applicable successor form), sixty (60) days after receipt by the Company of a Demand Request for such Registration Statement.
		

		
			(m)        “Governmental Authority” shall mean any court, agency, authority, department, regulatory body or other instrumentality of any government or country or of any national, federal, state, provincial, regional, county, city or other political subdivision of any such government or country or any supranational organization of which any such country is a member.
		

		
			(n)        “Holders” shall mean (but, in each case, only for so long as such Person remains an Affiliate of the Investor) the Investor and any Permitted Transferee thereof, if any, in accordance with Section 2.12.
		

		
			(o)        “Initiating Holder” shall have the meaning set forth in Section 2.2.
		

		
			(p)        “Interference” shall have the meaning set forth in Section 2.4.
		

		
			(q)        “Investor” shall have the meaning set forth in the preamble to this Agreement.
		

		
			(r)         “Law” or “Laws” shall mean all laws, statutes, rules, regulations, orders, judgments, injunctions and/or ordinances of any Governmental Authority.
		

		
			(s)        “License Agreement” shall mean that certain License Agreement between the Company and the Investor dated as of the date hereof, relating to Investor’s point mutation selective targeting approach for autosomal dominant retinitis pigmentosa.
		

		
			(t)         “Lock-Up Term” shall have the meaning set forth in Section 3.1.
		

		
			(u)        “Modified Clause” shall have the meaning set forth in Section 6.7.
		

		
			(v)         “Ordinary Shares” shall have the meaning set forth in the preamble to this Agreement.
		

		
			(w)       “Ordinary Shares Equivalents” shall mean any options, warrants or other securities or rights convertible into or exercisable or exchangeable for, whether directly or following conversion into or exercise or exchange for other options, warrants or other securities or rights, Ordinary Shares.
		

		
			(x)        “Ordinary Shares Then Outstanding” shall mean, at any time, the issued and outstanding Ordinary Shares at such time, as well as all capital stock issued and outstanding as a result of any stock split, stock dividend, or reclassification of Ordinary Shares distributable, on a pro rata basis, to all holders of Ordinary Shares.
		

		
			
		

		
			

		 

		

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			(y)        “Other Holders” shall mean any Person having rights to participate in a registration of the Company’s securities.
		

		
			(z)        “Permitted Transferee” shall mean a controlled Affiliate of the Investor that is wholly owned, directly or indirectly, by the Investor; it being understood that for purposes of this definition “wholly owned” shall mean an Affiliate in which the Investor owns, directly or indirectly, at least ninety-nine percent (99%) of the outstanding capital stock of such Affiliate, or a Person acquiring all or substantially all of the Investor’s business or assets.
		

		
			(aa)      “Person” shall mean any individual, partnership, firm, corporation, association, trust, unincorporated organization, government or any department or agency thereof or other entity, as well as any syndicate or group that would be deemed to be a Person under Section 13(d)(3) of the Exchange Act.
		

		
			(bb)      “Prospectus” shall mean the prospectus forming a part of any Registration Statement, as supplemented by any and all prospectus supplements and as amended by any and all amendments (including post-effective amendments) and including all material incorporated by reference or explicitly deemed to be incorporated by reference in such prospectus.
		

		
			(cc)      “Purchase Agreement” shall have the meaning set forth in the preamble to this Agreement, and shall include all Exhibits attached thereto.
		

		
			(dd)      “Purchased Shares” shall have the meaning set forth in the preamble to this Agreement, and shall be adjusted for (i) any stock split, stock dividend, share exchange, merger, consolidation or similar recapitalization and (ii) any Common Stock issued as (or issuable upon the exercise of any warrant, right or other security that is issued as) a dividend or other distribution with respect to, or in exchange or in replacement of, the Purchased Shares.
		

		
			(ee)       “registers,” “registered,” and “registration” shall refer to a registration effected by preparing and filing a Registration Statement or similar document in compliance with the Securities Act, and the declaration or ordering of effectiveness of such Registration Statement or document by the SEC.
		

		
			(ff)       “Registrable Securities” shall mean (i) the Purchased Shares, together with any Ordinary Shares issued in respect thereof as a result of any stock split, stock dividend, share exchange, merger, consolidation or similar recapitalization and (ii) any Ordinary Shares issued as (or issuable upon the exercise of any warrant, right or other security that is issued as) a dividend or other distribution with respect to, or in exchange or in replacement of, the Ordinary Shares described in clause (i) of this definition, excluding in all cases, however, (A) any Registrable Securities if and after they have been transferred to a Permitted Transferee in a transaction in connection with which registration rights granted hereunder are not assigned, (B) any Registrable Securities sold to or through a broker or dealer or underwriter in a public distribution or a public securities transaction or (C) Registrable Securities eligible for resale pursuant to Rule 144(b)(1)(i) under the Securities Act.
		

		
			(gg)      “Registration Expenses” shall mean all expenses incurred by the Company in connection with any Required Registration pursuant to Section 2.1 or the
		

		
			
		

		
			

		 

		

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			Company’s compliance with Section 2.6 (excluding clauses (k) and (m) thereof), including, without limitation, all registration and filing fees, fees and expenses of compliance with securities or blue sky Laws (including reasonable fees and disbursements of counsel in connection with blue sky qualifications of any Registrable Securities), expenses of printing (i) certificates for any Registrable Securities in a form eligible for deposit with the Depository Trust Company or (ii) Prospectuses if the printing of Prospectuses is requested by Holders, messenger and delivery expenses, fees and disbursements of counsel for the Company and its independent certified public accountants (including the expenses of any management review, cold comfort letters or any special audits required by or incident to such performance and compliance), Securities Act liability insurance (if the Company elects to obtain such insurance), the reasonable fees and expenses of any special experts retained by the Company in connection with such registration, fees and expenses of other Persons retained by the Company and the reasonable fees and expenses of one (1) counsel for the Holders of Registrable Securities in each Required Registration, selected by the Holders of a majority of the Registrable Securities to be included in such Required Registration.
		

		
			(hh)      “Registration Rights Term” shall have the meaning set forth in Section 2.1.
		

		
			(ii)        “Registration Statement” shall mean any registration statement of the Company under the Securities Act that covers any of the Registrable Securities pursuant to the provisions of this Agreement, including the related Prospectus, all amendments and supplements to such registration statement (including post-effective amendments), and all exhibits and all materials incorporated by reference or explicitly deemed to be incorporated by reference in such Registration Statement.
		

		
			(jj)        “Required Period” with respect to a Required Registration shall mean the earlier of (i) the date on which all Registrable Securities covered by such Required Registration are sold pursuant thereto and (ii) one-hundred twenty (120) days following the first day of effectiveness of the Registration Statement for such Required Registration, in each case subject to extension as set forth herein; provided, however, that in no event will the Required Period expire prior to the expiration of the applicable period referred to in Section 4(3) of the Securities Act and Rule 174 promulgated thereunder.
		

		
			(kk)      “Required Registration” shall have the meaning set forth in Section 2.1.  
		

		
			(ll)        “SEC” shall mean the United States Securities and Exchange Commission.
		

		
			(mm)    “Securities Act” shall mean the Securities Act of 1933, as amended, and the rules and regulations of the SEC promulgated thereunder.
		

		
			(nn)      “Selling Expenses” shall mean all underwriting discounts and selling commissions applicable to the sale of Registrable Securities pursuant to this Agreement.
		

		
			(oo)      “Third Party” shall mean any Person other than the Investor, the Company or any of their respective Affiliates.
		

		
			
		

		
			

		 

		

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			(pp)      “Underwritten Registration” or “Underwritten Offering” shall mean a registration in which Registrable Securities are sold to an underwriter for reoffering to the public.
		

		
			(qq)      “Violation” shall have the meaning set forth in Section 2.9(a).
		

		
			2.         Registration Rights.
		

		
			2.1       Required Registration. At such time as (i) the Investor owns at least 10% of the Ordinary Shares Then Outstanding of the Company and (ii) the first Lock-Up Term has expired but no later than the tenth (10th) anniversary of such expiration (the “Registration Rights Term”), the Company receives from any Holder or Holders a written request or requests (each, a “Demand Request”) that the Company file a Registration Statement under the Securities Act to effect the registration (a “Required Registration”) of Registrable Securities, the Company shall use all reasonable efforts to file a Registration Statement covering such Holders’ Registrable Securities as soon as practicable (and by the applicable Filing Date) and shall use all reasonable efforts to, as soon as practicable thereafter, effect the registration of the Registrable Securities of all or such portion of such Holder’s or Holders’ Registrable Securities as are specified in such Demand Request, subject however, to the conditions and limitations set forth herein; provided,  however, that the Company shall not be obligated to effect any registration of Registrable Securities upon receipt of a Demand Request pursuant to this Section 2.1 if:
		

		
			(i)         the Company has already completed one (1) Required Registration;
		

		
			(ii)       the market value of the Registrable Securities proposed to be included in the registration, based on the average closing price during the ten (10) consecutive trading days prior to the making of the Demand Request, is less than $10,000,000;
		

		
			(iii)      the Company shall furnish to the Holders a certificate signed by an authorized officer of the Company stating that (A) within ninety (90) days of receipt of the Demand Request under this Section 2.1, the Company shall file a registration statement for the public offering of securities for the account of the Company (other than a registration of securities (x) issuable pursuant to an employee stock option, stock purchase or similar plan, (y) issuable pursuant to a merger, exchange offer or a transaction of the type specified in Rule 145(a) under the Securities Act or (z) in which the only securities being registered are securities issuable upon conversion of debt securities which are also being registered), or (B) the Company is engaged in a material transaction or has an undisclosed material corporate development, in either case, which would be required to be disclosed in the Registration Statement, and in the good faith judgment of the Company’s Board of Directors, such disclosure would be seriously detrimental to the Company and its stockholders at such time (in which case, the Company shall disclose the matter as promptly as reasonably practicable and thereafter file the Registration Statement, and each Holder agrees not to disclose any information about such material transaction to Third Parties until such disclosure has occurred or such information has entered the public domain other than through breach of this provision by
		

		
			
		

		
			

		 

		

			6

		

 

		

		
			such Holder), provided,  however, that the Company shall have the right to only defer the filing of the Registration Statement pursuant to this subsection once in any twelve (12) month period and, such deferral may not exceed a period of more than one-hundred twenty (120) days after receipt of a Demand Request; or
		

		
			(iv)       at any time during the period between the Company’s receipt of the Demand Request and the completion of the Required Registration, any Holder is in breach of or has failed to cause its Affiliates to comply with the obligations and restrictions of Sections 3 or 4 of this Agreement, and such breach or failure is ongoing and has not been remedied.
		

		
			2.2       Underwritten Required Registration Required; Priority in Underwritten Offering. The underwriter for any Underwritten Offering requested pursuant to Section 2.1 shall be selected by a majority in interest of the Holders initiating the Required Registration hereunder (such Holder(s) initiating the registration request, the “Initiating Holders”) and shall be acceptable to the Company. The right of any Holder to include its Registrable Securities in the Underwritten Offering shall be conditioned upon such Holder’s participation in such Underwritten Offering and the inclusion of such Holder’s Registrable Securities to the extent provided herein. All Holders requesting the inclusion of their Registrable Securities in such Underwritten Offering shall (together with the Company as provided in Section 2.6(h)) enter into an underwriting agreement in customary form with the underwriter or underwriters selected for such Underwritten Offering. Notwithstanding any other provision of this Section 2, if the managing underwriter for the Underwritten Offering determines in good faith that marketing factors require a limitation of the number of shares of Registrable Securities to be included in such Underwritten Offering, then the Company shall so advise all Holders which requested inclusion of their Registrable Securities in such Underwritten Offering, and the number of shares of Registrable Securities that may be included in such Underwritten Offering shall be allocated among the Holders in proportion (as nearly as practicable) to the amount of Registrable Securities of the Company owned by each Holder; provided,  however, that the number of shares of Registrable Securities to be included in such Underwritten Offering shall not be reduced unless all other securities are first entirely excluded from such Underwritten Offering. In the event the Company advises the Holders of its intent to decrease the total number of Registrable Securities that may be included by the Holders in such Required Registration such that the number of Registrable Securities included in such Required Registration would be less than seventy-five percent (75%) of all Registrable Securities which the Holders requested be included in such Required Registration, then Holders representing a majority of the Registrable Securities requested to be included in such Required Registration will have the right to withdraw, on behalf of all Holders of all Registrable Securities requested to be so included, such Required Registration, in which case, such Required Registration will not count as a Required Registration for the purposes of Section 2.1(i), and the Company shall bear all Registration Expenses in connection therewith; provided,  that, the right to withdraw a registration and have it not count as a Required Registration may only be exercised once by the Holders (taken collectively).
		

		
			2.3       Priority in Required Registration. With respect to any Required Registration of Registrable Securities requested pursuant to Section 2.1, the Company may also (i) propose to sell Ordinary Shares on its own behalf and (ii) provide written notice of such Required Registration to Other Holders and permit all such Other Holders who request to be
		

		
			
		

		
			

		 

		

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			included in the Required Registration to include any or all Company securities held by such Other Holders in such Required Registration on the same terms and conditions as the Registrable Securities. Notwithstanding the foregoing, if the managing underwriter or underwriters of the Underwritten Offering to which any Required Registration relates advise the Company and the Holders of Registrable Securities that, in its good faith determination, the total amount of securities that such Holders, Other Holders, and the Company intend to include in such Required Registration is in an amount in the aggregate which would adversely affect the success of such Underwritten Offering, then such Required Registration shall include (i) first, all Registrable Securities of the Holders allocated, if the amount is less than all the Registrable Securities requested to be sold, pro rata on the basis of the total number of Registrable Securities held by such Holders; and (ii) second, as many other securities proposed to be included in the Required Registration by the Company and any Other Holders, allocated pro rata among the Company and such Other Holders, on the basis of the amount of securities requested to be included therein by the Company and each such Other Holder so that the total amount of securities to be included in such Underwritten Offering is the full amount that, in the written opinion of such managing underwriter, can be sold without materially and adversely affecting the success of such Underwritten Offering.
		

		
			2.4       Effective Required Registrations. A Required Registration will not be deemed to be effected for purposes of Section 2.1(i) if the Registration Statement for such Required Registration has not been declared effective by the SEC or become effective in accordance with the Securities Act and the rules and regulations thereunder and kept effective for the Required Period. In addition, if after such Registration Statement has been declared or becomes effective, (i) the offering of Registrable Securities pursuant to such Registration Statement is interfered with by any stop order, injunction, or other order or requirement of the SEC or other governmental agency or court such that the continued offer and sale of Registrable Securities being offered pursuant to such Registration Statement would violate applicable Law and such stop order, injunction or other order or requirement of the SEC or other governmental agency or court does not result from any act or omission of any Holder whose Registrable Securities are registered pursuant to such Registration Statement (an “Interference”) and (ii) any such Interference is not cured within sixty (60) days thereof, such Required Registration will be deemed not to have been effected and will not count as a Required Registration. In the event such Interference occurs and is cured, the Required Period relating to such Registration Statement will be extended by the number of days of such Interference, including the date such Interference is cured.
		

		
			2.5       Continuous Effectiveness of Registration Statement. The Company will use all reasonable efforts to cause each Registration Statement filed pursuant to this Section 2 to be declared effective by the SEC or to become effective under the Securities Act as promptly as practicable and to keep each such Registration Statement that has been declared or becomes effective continuously effective for the Required Period.
		

		
			2.6       Obligations of the Company. Whenever required under Section 2.1 to effect the registration of any Registrable Securities, the Company shall, as expeditiously as reasonably possible:
		

		
			
		

		
			

		 

		

			8

		

 

		

		
			(a)        prepare and file with the SEC a Registration Statement with respect to such Registrable Securities sought to be included therein; provided that at least five (5) Business Days prior to filing any Registration Statement or Prospectus or any amendments or supplements thereto, the Company shall furnish to the Holders of the Registrable Securities covered by such Registration Statement, their counsel and the managing underwriter copies of all such documents proposed to be filed, and any such Holder shall have the opportunity to comment on any information pertaining solely to such Holder and its plan of distribution that is contained therein and the Company shall make the corrections reasonably requested by such Holder or the managing underwriter with respect to such information prior to filing any such Registration Statement or amendment;
		

		
			(b)        prepare and file with the SEC such amendments and post-effective amendments to any Registration Statement and any Prospectus used in connection therewith as may be necessary to keep such Registration Statement effective for the Required Period, and cause the Prospectus to be supplemented by any required prospectus supplement, and as so supplemented to be filed pursuant to Rule 424 under the Securities Act, to comply with the provisions of the Securities Act with respect to the disposition of all Registrable Securities covered by such registration statement for the Required Period; provided that at least five (5) Business Days prior to filing any such amendments and post effective amendments or supplements thereto, the Company shall furnish to the Holders of the Registrable Securities covered by such Registration Statement, their counsel and the managing underwriter copies of all such documents proposed to be filed, and any such Holder or managing underwriter shall have the opportunity to comment on any information pertaining solely to such Holder and its plan of distribution that is contained therein and the Company shall make the corrections reasonably requested by such Holder and the managing underwriter with respect to such information prior to filing any such Registration Statement or amendment;
		

		
			(c)        furnish to the Holders of Registrable Securities covered by such Registration Statement and the managing underwriter such numbers of copies of such Registration Statement, each amendment and supplement thereto, the Prospectus included in such Registration Statement (including each preliminary prospectus or free writing prospectus) in conformity with the requirements of the Securities Act, and such other documents as they may reasonably request in order to facilitate the disposition of Registrable Securities owned by them;
		

		
			(d)        notify the Holders of Registrable Securities covered by such Registration Statement, promptly after the Company shall receive notice thereof, of the time when such Registration Statement becomes or is declared effective or when any amendment or supplement or any Prospectus forming a part of such Registration Statement has been filed;
		

		
			(e)        notify the Holders of Registrable Securities covered by such Registration Statement promptly of any request by the SEC for the amending or supplementing of such Registration Statement or Prospectus or for additional information and promptly deliver to such Holders copies of any comments received from the SEC;
		

		
			(f)        notify the Holders promptly of any stop order suspending the effectiveness of such Registration Statement or Prospectus or the initiation of any proceedings
		

		
			
		

		
			

		 

		

			9

		

 

		

		
			for that purpose, and use all reasonable efforts to obtain the withdrawal of any such order or the termination of such proceedings;
		

		
			(g)        use all reasonable efforts to register and qualify the Registrable Securities covered by such Registration Statement under such other securities or blue sky Laws of such jurisdictions as shall be reasonably requested by the Holders, use all reasonable efforts to keep each such registration or qualification effective, including through new filings, or amendments or renewals, during the Required Period, and notify the Holders of Registrable Securities covered by such Registration Statement of the receipt of any written notification with respect to any suspension of any such qualification; provided,  however, that the Company shall not be required in connection therewith or as a condition thereto to qualify to do business or to file a general consent to service of process in any such states or jurisdictions;
		

		
			(h)        enter into and perform its obligations under an underwriting agreement, in usual and customary form, with the managing underwriter of the Underwritten Offering pursuant to which such Registrable Securities are being offered;
		

		
			(i)         use all reasonable efforts to obtain: (A) at the time of effectiveness of the Registration Statement covering such Registrable Securities, a “cold comfort letter” from the Company’s independent certified public accountants covering such matters of the type customarily covered by “cold comfort letters” as the underwriters may reasonably request; and (B) at the time of any underwritten sale pursuant to such Registration Statement, a “bring-down comfort letter,” dated as of the date of such sale, from the Company’s independent certified public accountants covering such matters of the type customarily covered by “bring-down comfort letters” as the underwriters may reasonably request.
		

		
			(j)         promptly notify each Holder of Registrable Securities covered by such Registration Statement at any time when a Prospectus relating thereto is required to be delivered under the Securities Act of the happening of any event as a result of which the Prospectus included in such Registration Statement or any offering memorandum or other offering document includes an untrue statement of a material fact or omits to state any material fact required to be stated therein or necessary to make the statements therein not misleading in the light of the circumstances then existing, and promptly prepare a supplement or amendment to such Prospectus or file any other required document so that, as thereafter delivered to the purchasers of such Registrable Securities, such Prospectus will not contain an untrue statement of material fact or omit to state any fact necessary to make the statements therein not misleading;
		

		
			(k)        permit any Holder of Registrable Securities covered by such Registration Statement, which Holder in its reasonable judgment could reasonably be deemed to be an underwriter with respect to the Underwritten Offering pursuant to which such Registrable Securities are being offered, or to be a controlling Person of the Company, to reasonably participate in the preparation of such Registration Statement and to require the insertion therein of information to the extent concerning such Holder, furnished to the Company in writing, which in the reasonable judgment of such Holder and its counsel should be included;
		

		
			
		

		
			

		 

		

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			(l)         in connection with any Underwritten Offering, use all reasonable efforts to obtain an opinion or opinions addressed to the underwriter or underwriters in customary form and scope from counsel for the Company;
		

		
			(m)       upon reasonable notice and during normal business hours, subject to the Company receiving customary confidentiality undertakings or agreements from any Holder of Registrable Securities covered by such Registration Statement or other person obtaining access to Company records, documents, properties or other information pursuant to this subsection (m), make available for inspection by a representative of such Holder and any underwriter participating in any disposition of such Registrable Securities and any attorneys or accountants retained by any such Holder or underwriter, relevant financial and other records, pertinent corporate documents and properties of the Company, and use all reasonable efforts to cause the officers, directors and employees of the Company to supply all information reasonably requested by any such representative, underwriter, attorneys or accountants in connection with the Registration Statement;
		

		
			(n)        use all reasonable efforts to comply with all applicable rules and regulations of the SEC relating to such registration and make generally available to its security holders earning statements satisfying the provisions of Section 11(a) of the Securities Act, provided that the Company will be deemed to have complied with this Section 2.6(n) with respect to such earning statements if it has satisfied the provisions of Rule 158;
		

		
			(o)        if requested by the managing underwriter or any selling Holder, promptly incorporate in a prospectus supplement or post-effective amendment such information as the managing underwriter or any selling Holder reasonably requests to be included therein, with respect to the Registrable Securities being sold by such selling Holder, including, without limitation, the purchase price being paid therefor by the underwriters and with respect to any other terms of the Underwritten Offering of Registrable Securities to be sold in such offering, and promptly make all required filings of such prospectus supplement or post-effective amendment;
		

		
			(p)        cause the Registrable Securities covered by such Registration Statement to be listed on each securities exchange, if any, on which equity securities issued by the Company are then listed; and
		

		
			(q)        reasonably cooperate with each selling Holder and each underwriter participating in the disposition of such Registrable Securities and their respective counsel in connection with filings required to be made with the Financial Industry Regulatory Authority, Inc., if any.
		

		
			2.7       Furnish Information. It shall be a condition precedent to the obligations of the Company to take any action pursuant to this Section 2 with respect to the Registrable Securities of any selling Holder that such Holder shall furnish to the Company such information regarding itself and the Registrable Securities held by it as shall be reasonably necessary to effect the registration of such Holder’s Registrable Securities.
		

		
			
		

		
			

		 

		

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			2.8       Expenses. Except as specifically provided herein, all Registration Expenses shall be borne by the Company. All Selling Expenses incurred in connection with any registration hereunder shall be borne by the Holders of Registrable Securities covered by a Registration Statement, pro rata on the basis of the number of Registrable Securities registered on their behalf in such Registration Statement.
		

		
			2.9       Indemnification. In the event any Registrable Securities are included in a Registration Statement under this Agreement:
		

		
			(a)        The Company shall indemnify and hold harmless each Holder including Registrable Securities in any such Registration Statement, any underwriter (as defined in the Securities Act) for such Holder and each Person, if any, who controls such Holder or underwriter within the meaning of Section 15 of the Securities Act or Section 20 of Exchange Act and the officers, directors, owners, agents and employees of such controlling Persons, against any and all losses, claims, damages or liabilities (joint or several) to which they may become subject under any securities Laws including, without limitation, the Securities Act, the Exchange Act, or any other statute or common law of the United States or any other country or political subdivision thereof, or otherwise, including the amount paid in settlement of any litigation commenced or threatened (including any amounts paid pursuant to or in settlement of claims made under the indemnification or contribution provisions of any underwriting or similar agreement entered into by such Holder in connection with any offering or sale of securities covered by this Agreement), and shall promptly reimburse them, as and when incurred, for any legal or other expenses incurred by them in connection with investigating any claims and defending any actions, insofar as any such losses, claims, damages or liabilities (or actions in respect thereof) arise out of or are based upon any of the following statements, omissions or violations (each, a “Violation”): (i) any untrue statement or alleged untrue statement of a material fact contained in or incorporated by reference into such Registration Statement, including any preliminary prospectus or final prospectus contained therein or any free writing prospectus or any amendments or supplements thereto, or in any offering memorandum or other offering document relating to the offering and sale of such securities or (ii) the omission or alleged omission to state therein a material fact required to be stated therein, or necessary to make the statements therein not misleading; provided, however, the Company shall not be liable in any such case for any such loss, claim, damage, liability or action to the extent that it (A) arises out of or is based upon a Violation which occurs solely in reliance upon and in conformity with written information furnished expressly for use in connection with such registration by such Holder; or (B) is caused by such Holder’s disposition of Registrable Shares during any period during which such Holder is obligated to discontinue any disposition of Registrable Shares as a result of any stop order suspending the effectiveness of any registration statement or prospectus with respect to Registrable Securities.
		

		
			(b)        Each Holder including Registrable Securities in a registration statement shall indemnify and hold harmless the Company, each of its directors, each of its officers who has signed the registration statement, each Person, if any, who controls the Company within the meaning of Section 15 of the Securities Act or Section 20 of the Exchange Act and the officers, directors, owners, agents and employees of such controlling Persons, any underwriter, any other Holder selling securities in such registration statement and any controlling Person of any such underwriter or other Holder, against any losses, claims, damages or liabilities
		

		
			
		

		
			

		 

		

			12

		

 

		

		
			(joint or several) to which any of the foregoing Persons may become subject, under liabilities (or actions in respect thereto) which arise out of or are based upon any Violation, in each case to the extent (and only to the extent) that such Violation: (i) arises out of or is based upon a Violation which occurs solely in reliance upon and in conformity with written information furnished expressly for use in connection with such registration by such Holder; or (ii) is caused by such Holder’s disposition of Registrable Shares during any period during which such Holder is obligated to discontinue any disposition of Registrable Shares as a result of any stop order suspending the effectiveness of any registration statement or prospectus with respect to Registrable Securities. Each such Holder shall pay, as incurred, any legal or other expenses reasonably incurred by any Person intended to be indemnified pursuant to this Section 2.9(b), in connection with investigating or defending any such loss, claim, damage, liability or action; provided,  however, that the indemnity agreement contained in this Section 2.9(b) shall not apply to amounts paid in settlement of any such loss, claim, damage, liability or action if such settlement is effected without consent of the Holder, which consent shall not be unreasonably withheld.
		

		
			(c)        Promptly after receipt by an indemnified party under this Section 2.9 of notice of the commencement of any action (including any action by a Governmental Authority), such indemnified party shall, if a claim in respect thereof is to be made against any indemnifying party under this Section 2.9, deliver to the indemnifying party a written notice of the commencement thereof and the indemnifying party shall have the right to participate in, and, to the extent the indemnifying party so desires, jointly with any other indemnifying party similarly noticed, to assume the defense thereof with counsel mutually satisfactory to the parties; provided,  however, that an indemnified party shall have the right to retain its own counsel, with the reasonable fees and expenses to be paid by the indemnifying party, if representation of such indemnified party by the counsel retained by the indemnifying party would be inappropriate due to actual or potential differing interests between such indemnified party and any other party represented by such counsel in such proceeding. The failure to deliver written notice to the indemnifying party within a reasonable time of the commencement of any such action, if prejudicial to its ability to defend such action, shall relieve such indemnifying party of any liability to the indemnified party under this Section 2.9, but the omission so to deliver written notice to the indemnifying party shall not relieve it of any liability that it may have to any indemnified party otherwise than under this Section 2.9.
		

		
			(d)        In order to provide for just and equitable contribution to joint liability in any case in which a claim for indemnification is made pursuant to this Section 2.9 but it is judicially determined (by the entry of a final judgment or decree by a court of competent jurisdiction and the expiration of time to appeal or the denial of the last right of appeal) that such indemnification may not be enforced in such case notwithstanding the fact that this Section 2.9 provided for indemnification in such case, the Company and each Holder of Registrable Securities shall contribute to the aggregate losses, claims, damages or liabilities to which they may be subject (after contribution from others) in proportion to the relative fault of the Company, on the one hand, and such Holder, severally, on the other hand; provided,  however, that in any such case, no Person guilty of fraudulent misrepresentation (within the meaning of Section 11(f) of the Securities Act) shall be entitled to contribution from any Person who was not guilty of such fraudulent misrepresentation; provided further,  however, that in no event shall any contribution under this Section 2.9(d) on the part of any Holder exceed the net proceeds received
		

		
			
		

		
			

		 

		

			13

		

 

		

		
			by such Holder from the sale of Registrable Securities giving rise to such contribution obligation, except in the case of willful misconduct or fraud by such Holder.
		

		
			(e)        The obligations of the Company and the Holders under this Section 2.9 shall survive the completion of any offering of Registrable Securities in a registration statement under this Agreement and otherwise.
		

		
			2.10     SEC Reports. With a view to making available to the Holders the benefits of Rule 144 under the Securities Act and any other rule or regulation of the SEC that may at any time permit a Holder to sell Registrable Securities of the Company to the public without registration, the Company agrees to at any time that it is a reporting company under Section 13 or 15(d) of the Exchange Act:
		

		
			(a)        file with the SEC in a timely manner all reports and other documents required of the Company under the Exchange Act; and
		

		
			(b)        furnish to any Holder, so long as such Holder owns any Registrable Securities, forthwith upon request (i) a written statement by the Company that it has complied with the reporting requirements of the Exchange Act, (ii) a copy of the most recent annual or quarterly report of the Company and such other reports and documents so filed by the Company, and (iii) such other information as may be reasonably requested in availing any Holder of any rule or regulation of the SEC (exclusive of Rule 144A) which permits the selling of any Registrable Securities without registration.
		

		
			2.11     Assignment of Registration Rights. The rights to cause the Company to register any Registrable Securities pursuant to this Agreement may be assigned in whole or in part (but only with all restrictions and obligations set forth in this Agreement) by a Holder to a Permitted Transferee which acquires Registrable Securities from such Holder; provided,  however, (a) such Holder shall, within five (5) days prior to such transfer, furnish to the Company written notice of the name and address of such Permitted Transferee, details of its status as a Permitted Transferee and details of the Registrable Securities with respect to which such registration rights are being assigned, (b) the Permitted Transferee, prior to or simultaneously with such transfer or assignment, shall agree in writing to be subject to and bound by all restrictions and obligations set forth in this Agreement, (c) the Investor shall continue to be bound by all restrictions and obligations set forth in this Agreement and (d) such transfer or assignment shall be effective only if immediately following such transfer or assignment the further disposition of such Registrable Securities by the Permitted Transferee is restricted under the Securities Act and other applicable securities Law.
		

		
			3.         Restrictions on Dispositions.
		

		
			3.1       Lock-Up. From and after the date of the applicable Closing (as defined in the Purchase Agreement) at which Shares are issued and sold and until the date that is twelve months following such Closing (each a “Lock-Up Term”), without the prior approval of a majority of the Company’s Board of Directors, the Investor shall not, and shall cause its Affiliates not to, Dispose of (x) any of the Purchased Shares issued and sold at such applicable Closing, together with any Ordinary Shares issued in respect thereof as a result of any stock split,
		

		
			
		

		
			

		 

		

			14

		

 

		

		
			stock dividend, share exchange, merger, consolidation or similar recapitalization, and (y) any Common Stock issued as (or issuable upon the exercise of any warrant, right or other security that is issued as) a dividend or other distribution with respect to, or in exchange or in replacement of, the Ordinary Shares described in clause (x) of this sentence; provided,  however, that the foregoing shall not prohibit the Investor from transferring Registrable Securities to a Permitted Transferee in accordance with this Agreement.
		

		
			3.2       Certain Tender Offers. Notwithstanding any other provision of this Section 3, this Section 3 shall not prohibit or restrict any Disposition of Ordinary Shares Then Outstanding and/or Ordinary Share Equivalents by the Investor into (a) a tender offer by a Third Party or (b) an issuer tender offer by the Company.
		

		
			4.         Voting Agreement.
		

		
			4.1       Voting of Securities. From and after the date of this Agreement, other than as permitted by Section 4.2 with respect to Extraordinary Matters, in any vote or action by written consent of the stockholders of the Company (including, without limitation, with respect to the election of directors), the Investor shall, and shall cause its respective Affiliates to, vote or execute a written consent with respect to all voting securities of the Company as to which they are entitled to vote or execute a written consent, in the sole discretion of the Investor, in accordance with the recommendation of the Company’s Board of Directors. In furtherance of this Section 4.1, the Investor shall, and shall cause its Affiliates to, if and when requested by the Company from time to time, promptly execute and deliver to the Company an irrevocable proxy, substantially in the form of Exhibit A attached hereto, and irrevocably appoint the Company or its designees, with full power of substitution, its attorney, agent and proxy to vote (or cause to be voted) or to give consent with respect to, all of the voting securities of the Company as to which the Investor or Affiliate of the Investor is entitled to vote, in the manner and with respect to the matters set forth in this Section 4.1. The Investor acknowledges, and shall cause its Affiliates to acknowledge, that any such proxy executed and delivered shall be coupled with an interest, shall constitute, among other things, an inducement for the Company to enter into this Agreement, shall be irrevocable and binding on any successor in interest of the Investor or Affiliate of the Investor, as applicable, and shall not be terminated by operation of Law upon the occurrence of any event. Such proxy shall operate to revoke and render void any prior proxy as to any voting securities of the Company heretofore granted by the Investor or Affiliate of the Investor, as applicable, to the extent it is inconsistent herewith. Such proxy shall terminate upon the earlier of the expiration or termination of this Section 4.1.
		

		
			4.2       Certain Extraordinary Matters.  The Investor and its Affiliates may vote, or execute a written consent with respect to, any or all of the voting securities of the Company as to which they are entitled to vote or execute a written consent, as they may determine in their sole discretion, with respect to the following matters (each such matter being an “Extraordinary Matter”):
		

		
			(a)        any transaction which would result in a Change of Control; and
		

		
			(b)        any liquidation or dissolution of the Company.
		

		
			
		

		
			

		 

		

			15

		

 

		

		
			4.3       Quorum. In furtherance of Section 4.1, the Investor shall be, and shall cause each of its Affiliates to be, present in person or represented by proxy at all meetings of stockholders to the extent necessary so that all voting securities of the Company as to which they are entitled to vote shall be counted as present for the purpose of determining the presence of a quorum at such meeting.
		

		
			5.         Termination of Certain Rights and Obligations.
		

		
			5.1       Termination of Registration Rights. Except for Section 2.9, which shall survive until the expiration of any applicable statutes of limitation, Section 2 shall terminate automatically and have no further force or effect upon the earliest to occur of:
		

		
			(a)        the expiration of the Registration Rights Term;
		

		
			(b)        the date on which the Common Stock ceases to be registered pursuant to Section 12 of the Exchange Act; and
		

		
			(c)        a liquidation or dissolution of the Company.
		

		
			5.2       Termination of Restrictions on Dispositions.  Section 3 shall terminate and have no further force or effect upon the earliest to occur of:
		

		
			(a)        the consummation by an Offeror of a Change of Control of the Company;
		

		
			(b)        a liquidation or dissolution of the Company; and
		

		
			(c)        the date on which the Common Stock ceases to be registered pursuant to Section 12 of the Exchange Act.
		

		
			5.3       Effect of Termination. No termination pursuant to any of Section 5 shall relieve any of the parties (or the Permitted Transferee, if any) for liability for breach of or default under any of their respective obligations or restrictions under any terminated provision of this Agreement, which breach or default arose out of events or circumstances occurring or existing prior to the date of such termination.
		

		
			6.         Miscellaneous.
		

		
			6.1       Governing Law; Submission to Jurisdiction. This Agreement shall be governed by and construed in accordance with the Laws of the State of New York, without regard to the conflict of laws principles thereof that would require the application of the Law of any other jurisdiction. The parties irrevocably and unconditionally submit to the exclusive jurisdiction of the United States District Court for the Southern District of New York solely and specifically for the purposes of any action or proceeding arising out of or in connection with this Agreement.
		

		
			6.2       Waiver. Waiver by a party of a breach hereunder by another party shall not be construed as a waiver of any subsequent breach of the same or any other provision. No
		

		
			
		

		
			

		 

		

			16

		

 

		

		
			delay or omission by a party in exercising or availing itself of any right, power or privilege hereunder shall preclude the later exercise of any such right, power or privilege by such party. No waiver shall be effective unless made in writing with specific reference to the relevant provision(s) of this Agreement and signed by a duly authorized representative of the party granting the waiver.
		

		
			6.3       Notices. All notices, instructions and other communications hereunder or in connection herewith shall be in writing, shall be sent to the address of the relevant party set forth on Exhibit B attached hereto and shall be (a) delivered personally, (b) sent by registered or certified mail, return receipt requested, postage prepaid, (c) sent via a reputable nationwide overnight courier service or (d) sent by facsimile transmission, with a confirmation copy to be sent by registered or certified mail, return receipt requested, postage prepaid. Any such notice, instruction or communication shall be deemed to have been delivered upon receipt if delivered by hand, three (3) Business Days after it is sent by registered or certified mail, return receipt requested, postage prepaid, one (1) Business Day after it is sent via a reputable nationwide overnight courier service or when transmitted with electronic confirmation of receipt, if transmitted by facsimile (if such transmission is made during regular business hours of the recipient on a Business Day; or otherwise, on the next Business Day following such transmission). Any party may change its address by giving notice to the other parties in the manner provided above.
		

		
			6.4       Entire Agreement. This Agreement and the Purchase Agreement contain the entire agreement among the parties with respect to the subject matter hereof and thereof and supersede all prior and contemporaneous arrangements or understandings, whether written or oral, with respect hereto and thereto.
		

		
			6.5       Amendments. No provision in this Agreement shall be supplemented, deleted or amended except in a writing executed by an authorized representative of each of the parties hereto.
		

		
			6.6       Headings; Nouns and Pronouns; Section References. Headings in this Agreement are for convenience of reference only and shall not be considered in construing this Agreement. Whenever the context may require, any pronouns used herein shall include the corresponding masculine, feminine or neuter forms, and the singular form of names and pronouns shall include the plural and vice-versa. References in this Agreement to a section or subsection shall be deemed to refer to a section or subsection of this Agreement unless otherwise expressly stated.
		

		
			6.7       Severability. If, under applicable Laws, any provision hereof is invalid or unenforceable, or otherwise directly or indirectly affects the validity of any other material provision(s) of this Agreement in any jurisdiction (“Modified Clause”), then, it is mutually agreed that this Agreement shall endure and that the Modified Clause shall be enforced in such jurisdiction to the maximum extent permitted under applicable Laws in such jurisdiction; provided that the parties shall consult and use all reasonable efforts to agree upon, and hereby consent to, any valid and enforceable modification of this Agreement as may be necessary to avoid any unjust enrichment of either party and to match the intent of this Agreement as closely as possible, including the economic benefits and rights contemplated herein.
		

		
			
		

		
			

		 

		

			17

		

 

		

		
			6.8       Assignment. Neither this Agreement nor any rights or duties of a party hereto may be assigned by such party, in whole or in part, without (a) the prior written consent of the Company in the case of any assignment by the Investor, except as provided by Section 2.11 with respect to the Investor’s assignment to a Permitted Transferee; or (b) the prior written consent of the Investor in the case of an assignment by the Company.
		

		
			6.9       Successors and Assigns. This Agreement shall be binding upon and inure to the benefit of the parties hereto and their respective successors and permitted assigns.
		

		
			6.10     Counterparts. This Agreement may be executed in counterparts, each of which shall be deemed an original but which together shall constitute one and the same instrument.
		

		
			6.11     Third Party Beneficiaries. None of the provisions of this Agreement shall be for the benefit of or enforceable by any Third Party. No Third Party shall obtain any right under any provision of this Agreement or shall by reason of any such provision make any claim in respect of any debt, liability or obligation (or otherwise) against any party hereto.
		

		
			6.12     No Strict Construction. This Agreement has been prepared jointly and will not be construed against any party.
		

		
			6.13     Remedies. The rights, powers and remedies of the parties under this Agreement are cumulative and not exclusive of any other right, power or remedy which such parties may have under any other agreement or Law. No single or partial assertion or exercise of any right, power or remedy of a party hereunder shall preclude any other or further assertion or exercise thereof.
		

		
			6.14     Specific Performance. The Investor hereby acknowledges and agrees that the rights of the parties hereunder are special, unique and of extraordinary character, and that if any party refuses or otherwise fails to act, or to cause its Affiliates to act, in accordance with the provisions of this Agreement, such refusal or failure would result in irreparable injury to the Company or the Investor, as the case may be, the exact amount of which would be difficult to ascertain or estimate and the remedies at law for which would not be reasonable or adequate compensation. Accordingly, if any party refuses or otherwise fails to act, or to cause its Affiliates to act, in accordance with the provisions of this Agreement, then, in addition to any other remedy which may be available to any damaged party at law or in equity, such damaged party will be entitled to seek specific performance and injunctive relief, without posting bond or other security, and without the necessity of proving actual or threatened damages, which remedy such damaged party will be entitled to seek in any court of competent jurisdiction.
		

		
			6.15     No Conflicting Agreements. The Investor hereby represents and warrants to the Company that neither it nor any of its Affiliates is, as of the date of this Agreement, a party to, and agrees that neither it nor any of its Affiliates shall, on or after the date of this Agreement, enter into any agreement that conflicts with the rights granted to the Company in this Agreement. The Company hereby represents and warrants to each Holder that it is not, as of the date of this Agreement, a party to, and agrees that it shall not, on or after the date of this Agreement, enter into, any agreement or approve any amendment to its Organizational Documents (as defined in
		

		
			
		

		
			

		 

		

			18

		

 

		

		
			the Purchase Agreement) with respect to its securities that conflicts with the rights granted to the Holders in this Agreement. The Company further represents and warrants that the rights granted to the Holders hereunder do not in any way conflict with the rights granted to any other holder of the Company’s securities under any other agreements.
		

		
			(Signature Page Follows)
		

		
			 
		

		
			 
		

		
			

		 

		

			19

		

 

		

		
			IN WITNESS WHEREOF, the parties have executed and delivered this Agreement as of the date first above written.
		

			
					
						 

					
					
						    

					
					
						IONIS PHARMACEUTICALS, INC.

					
					
						

				
	
					
						 

					
					
						 

					
					
						By:

					
					
						 

				
	
					
						 

					
					
						 

					
					
						 

					
					
						Name:

					
					
						Stanley T. Crooke

				
	
					
						 

					
					
						 

					
					
						 

					
					
						Title:

					
					
						Chief Executive Officer

				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						 

					
					
						PROQR THERAPEUTICS N.V.

				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						 

					
					
						By:

					
					
						 

				
	
					
						 

					
					
						 

					
					
						 

					
					
						Name:

					
					
						 

				
	
					
						 

					
					
						 

					
					
						 

					
					
						Title:

					
					
						 

				
	
					
						 

					
					
						 

					
					
						 

				

		
			 
		

		
			 
		

		
			

		 

		

			 

		

 

		

		
			EXHIBIT A
		

		
			FORM OF IRREVOCABLE PROXY
		

		
			In order to secure the performance of the duties of the undersigned pursuant to Section 4.1 of the Investor Agreement, dated as of [__], 2018 (the “Agreement”), by and between [INVESTOR] and [COMPANY] (the “Company”), the undersigned hereby irrevocably appoints [__] and [__], and each of them, the attorneys, agents and proxies, with full power of substitution in each of them, for the undersigned, and in the name, place and stead of the undersigned, to vote (or cause to be voted) or, if applicable, to give consent, in such manners as each such attorney, agent and proxy or his substitute shall in his sole discretion deem proper to record such vote (or consent) in the manners, and with respect to such matters as set forth in Section 4.1 of the Agreement (but in any case, in accordance with any written instruction from the undersigned, properly delivered under Section 4.1 of the Agreement, to vote or give consent as contemplated by Section 4.1 of the Agreement) with respect to all voting securities (whether taking the form of Ordinary Shares or other voting securities of the Company), which the undersigned is or may be entitled to vote at any meeting of the Company held after the date hereof, whether annual or special and whether or not an adjourned meeting or, if applicable, to give written consent with respect thereto. This proxy is coupled with an interest, shall be irrevocable and binding on any successor in interest of the undersigned and shall not be terminated by operation of law upon the occurrence of any event. This proxy shall operate to revoke and render void any prior proxy as to voting securities heretofore granted by the undersigned which is inconsistent herewith. This proxy shall terminate upon the earlier of the expiration or termination of the voting agreement set forth in Section 4.1 of the Agreement.
		

			
					
						 

					
					
						 

					
					
						[_____________________________]

				
	
					
						 

					
					
						 

					
					
						 

					
					
						 

				
	
					
						 

					
					
						    

					
					
						By:

					
					
						 

				
	
					
						 

					
					
						 

					
					
						 

					
					
						Name:

					
					
						 

				
	
					
						 

					
					
						 

					
					
						 

					
					
						Title:

					
					
						 

				
	
					
						 

					
					
						 

					
					
						 

				

		
			 
		

		
			 
		

		
			

		 

		

			A-1

		

 

		

		
			EXHIBIT B
		

		
			NOTICES
		

		
			(a)        If to the Investor:
		

		
			Ionis Pharmaceuticals, Inc.
		

		
			2855 Gazelle Court
		

		
			Carlsbad, CA 92010 
		

		
			U.S.A.
		

		
			Attention: Chief Operating Officer
		

		
			with a copy to:
		

		
			legalnotices@ionisph.com 
		

		
			(b)        If to the Company:
		

		
			ProQR Therapeutics N.V.
		

		
			Zernikedreef 9, 2333 CK Leiden
		

		
			The Netherlands
		

		
			31 88 166 7000
		

		
			Attention: Chief Executive Officer
		

		
			with a copy to:
		

		
			Goodwin Procter LLP
		

		
			100 Northern Ave.
		

		
			Boston, MA 02210
		

		
			Attention: Mitch Bloom, Esq. and Danielle Lauzon, Esq.
		

		
			 
		

		 

		

			B-1

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