Document:

EX-4.2

 Exhibit 4.2 

THIRD AMENDED AND RESTATED INVESTOR RIGHTS AGREEMENT 

This Agreement, dated as of June 9, 2010, is entered into by and among (i) Inotek Pharmaceuticals Corporation, a Delaware
corporation (the “Company”), and (ii) the entities listed on Exhibit A hereto (the “Investors” and each individually, an “Investor”). 

BACKGROUND 
 WHEREAS, the
Company and certain of the Investors entered into a Second Amended and Restated Investor Rights Agreement dated as of August 21, 2007, as amended (the “Prior Investor Rights Agreement”), in connection with the purchase by such
Investors (the “Series C Purchasers”) of the Company’s Series C Convertible Preferred Stock; 
 WHEREAS, pursuant to
the Series AA Convertible Preferred Stock Purchase Agreement of even date herewith, as amended from time to time (the “Purchase Agreement”) certain purchasers of the Series AA Convertible Preferred Stock of the Company (the
“Series AA Purchasers”) have agreed that the execution of this Agreement is a condition to the sale of the Series AA Convertible Preferred Stock; 

WHEREAS, pursuant to Section 13(d) of the Prior Investor Rights Agreement, the Prior Investor Rights Agreement may be amended by the
Company and the holders of at least sixty-six and two-thirds percent (66 and 2/3%) of the Common Stock issued or issuable upon conversion of the Restricted Stock (as that term is defined in the Prior Investor Rights Agreement) (the
“Requisite Holders”); and 
 WHEREAS, in order to induce the Series AA Purchasers to enter into the Purchase Agreement and
in order to provide the Series AA Purchasers with certain rights contained in the Prior Investor Rights Agreement, the Company and the Requisite Holders desire to amend and restate the Prior Investor Rights Agreement in its entirety to read as
set forth in this Agreement. 
 NOW, THEREFORE, in consideration of the mutual covenants herein contained and other good and valuable
consideration, the receipt and sufficiency of which are hereby acknowledged, the Company, the Requisite Holders and the Investors agree as follows: 

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

“Board of Directors” shall mean the board of directors of the Company as constituted from time to time. 

“Code” shall mean the Internal Revenue Code of 1986, as amended from time to time. 

“Commission” shall mean the Securities and Exchange Commission, or any other federal agency at the time administering the
Securities Act. 

 “Common Stock” shall mean the Common Stock, $0.01 par value, of the Company, as
constituted as of the date of this Agreement. 
 “Conversion Shares” shall mean shares of Common Stock issued or issuable
upon conversion of the Preferred Stock. 
 “ERISA” shall mean the Employee Retirement Income Security Act of 1974, as
amended. 
 “Exchange Act” shall mean the Securities Exchange Act of 1934, as amended, or any similar federal statute, and
the rules and regulations of the Commission thereunder, all as the same shall be in effect at the time. 
 “Indebtedness”
shall mean all obligations, contingent and otherwise, which should, in accordance with generally accepted accounting principles, be classified upon the obligor’s balance sheet (or notes thereto) as liabilities (other than trade credit or
accounts payable incurred in the ordinary course of business), including (i) liabilities secured by any mortgage on property owned or acquired subject to such mortgage, whether or not the liability secured thereby shall have been assumed,
(ii) all guaranties, endorsements and other contingent obligations, in respect of Indebtedness of others, whether or not the same are or should be so reflected in said balance sheet (or the notes thereto), except guaranties by endorsement of
negotiable instruments for deposit or collection or similar transactions in the ordinary course of business and (iii) the present value of any lease payments due under leases required to be capitalized in accordance with applicable Statements
of Financial Accounting Standards, determined by discounting all such payments at the interest rate determined in accordance with applicable Statements of Financial Accounting Standards. 

“Key Employee” or “Key Employees” shall mean and include the President, chief executive officer, chief financial
officer, chief medical officer, chief scientific officer, vice presidents of operations, research, development, sales or marketing, or any other individual who performs a significant role in the operations of the Company or a Subsidiary as may be
reasonably designated by the Board of Directors of the Company. 
 “Person or Persons” shall mean an individual,
corporation, limited liability company, partnership, joint venture, trust, or unincorporated organization, or a government or any agency or political subdivision thereof. 

“Preferred Stock” shall mean the Company’s Series AA Convertible Preferred Stock, $0.001 par value (the “Series
AA Preferred Stock”). 
 “Qualified Public Offering” shall mean a fully underwritten, firm commitment public
offering of shares of Common Stock pursuant to an effective registration under the Securities Act at a price per share of at least $7.65 (subject to appropriate adjustment in the event of any stock dividend, stock split, combination or other similar
recapitalization with respect to the Common Stock) and with aggregate gross proceeds to the Company in excess of $40,000,000 before deduction of underwriting discounts and commissions. 

  
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 “Registration Expenses” shall mean the expenses so described in Section 8.

 “Restricted Stock” shall mean (i) the Conversion Shares, (ii) all shares of Common Stock issued by the Company
in respect of such shares and all shares of Common Stock that the Investors may hereafter purchase pursuant to their rights of first offer, rights of first refusal or otherwise, or shares of Common Stock issued on conversion or exercise of such
securities, excluding Conversion Shares that have been (a) registered under the Securities Act pursuant to an effective registration statement filed thereunder and disposed of in accordance with the registration statement covering them or
(b) publicly sold pursuant to Rule 144 under the Securities Act, and (iii) the MedImmune Director Equity Compensation (as defined in the Third Amended and Restated Stockholders Agreement dated as of the date hereof, by and among the
Company and the stockholders party thereto, as amended from time to time). 
 “Securities Act” shall mean the Securities
Act of 1933, as amended, or any similar federal statute, and the rules and regulations of the Commission thereunder, all as the same shall be in effect at the time. 

“Selling Expenses” shall mean the expenses so described in Section 8. 

“Subsidiary” or “Subsidiaries” shall mean any corporation, limited liability company, partnership, or other
business entity of which the Company and/or any of its other Subsidiaries (as herein defined) directly or indirectly owns at the time outstanding shares of every class of such corporation, membership or partnership interests of such limited
liability company or partnership, or other equity securities of such other business entity, other than directors’ qualifying shares comprising at least fifty percent (50%) of the voting power of such corporation, limited liability company,
partnership, or other business entity. 
 2. Restrictive Legend. Each certificate representing Preferred Stock and Conversion Shares
shall, except as otherwise provided in this Section 2 or in Section 3, be stamped or otherwise imprinted with a legend substantially in the following form: 

“THIS SECURITIES REPRESENTED BY THIS CERTIFICATE HAVE NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933 OR APPLICABLE STATE SECURITIES
LAWS. THESE SECURITIES HAVE BEEN ACQUIRED FOR INVESTMENT AND NOT WITH A VIEW TO DISTRIBUTION OR RESALE, AND MAY NOT BE SOLD, MORTGAGED, PLEDGED, HYPOTHECATED OR OTHERWISE TRANSFERRED WITHOUT AN EFFECTIVE REGISTRATION STATEMENT FOR SUCH SECURITIES
UNDER THE SECURITIES ACT OF 1933 AND APPLICABLE STATE SECURITIES LAWS, OR THE AVAILABILITY OF AN EXEMPTION FROM THE REGISTRATION PROVISIONS OF THE SECURITIES ACT OF 1933 AND APPLICABLE STATE SECURITIES LAWS.” 

A certificate shall not bear such legend if in the opinion of counsel satisfactory to the Company (it being agreed that Goodwin Procter LLP shall be
satisfactory) the securities represented thereby may be publicly sold without registration under the Securities Act and any applicable state securities laws. 

  
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 3. Notice of Proposed Transfer. Prior to any proposed transfer of any Preferred Stock or
Conversion Shares (other than under the circumstances described in Sections 4, 5 or 6), the holder thereof shall give written notice to the Company of its intention to effect such transfer. Each such notice shall describe the manner of the
proposed transfer and, if requested by the Company, shall be accompanied by an opinion of counsel satisfactory to the Company (it being agreed that Goodwin Procter LLP shall be satisfactory) to the effect that the proposed transfer may be effected
without registration under the Securities Act and any applicable state securities laws, whereupon the holder of such stock shall be entitled to transfer such stock in accordance with the terms of its notice; provided, however, that no
such opinion of counsel shall be required for a transfer to one or more partners or members of the transferor (in the case of a transferor that is a partnership or a limited liability company, respectively, or to a liquidating trust for the benefit
of such partners or members) or to an affiliated corporation (in the case of a transferor that is a corporation) or from a grantor trust to its grantors; provided, further, however, that any transferee other than a transferee
receiving such shares for no consideration shall execute and deliver to the Company a representation letter in form reasonably satisfactory to the Company’s counsel to the effect that the transferee is acquiring such shares for its own account,
for investment purposes and without any view to distribution thereof. Each certificate for Preferred Stock or Conversion Shares transferred as above provided shall bear the legend set forth in Section 2, except that such certificate shall not
bear such legend if (i) such transfer is made in accordance with the provisions of Rule 144 (or any other rule permitting public sale without registration under the Securities Act) or (ii) the opinion of counsel referred to above is
to the further effect that the transferee and any subsequent transferee (other than an affiliate of the Company) would be entitled to transfer such securities in a public sale without registration under the Securities Act. The restrictions provided
for in this Section 3 shall not apply to securities which are not required to bear the legend prescribed by Section 2 in accordance with the provisions of that Section. 

4. Required Registration. 

(a) At any time on or after one hundred eighty (180) days after the earlier of (i) the closing of the Company’s first firm
commitment underwritten public offering of its Common Stock registered under the Securities Act (the “IPO”), or (ii) the third anniversary of the initial closing of the purchase of Preferred Stock under the Purchase Agreement,
the holders of Restricted Stock constituting at least 50% in interest of the total shares of Restricted Stock then outstanding may request the Company to register under the Securities Act the shares of Restricted Stock held by such requesting holder
or holders for sale in the manner specified in such notice, provided that such request shall be for at least twenty five percent (25%) of the total shares of Restricted Stock then outstanding and having an anticipated aggregate offering price
of at least $5,000,000. 
 (b) Following receipt of any notice under this Section 4, the Company shall immediately notify all holders
of Restricted Stock from whom notice has not been received and such holders shall then be entitled within thirty (30) days thereafter to request the Company to include in the requested registration all or any portion of their shares of
Restricted Stock. The 

  
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Company shall use its reasonable best efforts to register under the Securities Act, for public sale in accordance with the method of disposition described in paragraph (a) above, the number
of shares of Restricted Stock specified in such notice (and in all notices received by the Company from other holders within thirty (30) days after the giving of such notice by the Company). The Company shall be obligated to register Restricted
Stock pursuant to this Section 4 on two (2) occasions only; provided, however, that such obligation shall be deemed satisfied only when a registration statement covering all shares of Restricted Stock specified in notices
received as aforesaid for sale in accordance with the method of disposition specified by the requesting holders shall have become effective or if such registration statement has been withdrawn prior to the consummation of the offering at the request
of the holders of not less than a majority of the shares of Restricted Stock to be included in such registration (other than as a result of a material adverse change in the business or condition, financial or otherwise, of the Company). 

(c) The Company shall be entitled to include in any registration statement referred to in this Section 4 shares of Common Stock to be
sold by the Company for its own account, except as and to the extent that, in the opinion of the managing underwriter, such inclusion would adversely affect the marketing of the Restricted Stock to be sold. Except for registration statements on Form S-4, S-8 or any successor thereto, the Company will not file with the Commission any other registration statement with respect to its Common Stock, whether for its own account or that of other
stockholders, from the date of receipt of a notice from requesting holders requesting sale pursuant to an underwritten offering pursuant to this Section 4 until the completion of the period of distribution of the registration contemplated
thereby. 
 (d) If in the opinion of the managing underwriter the inclusion of all of the Restricted Stock requested to be registered under
this Section 4 would adversely affect the marketing of such shares, shares to be sold by the holders of Restricted Stock, if any, shall be excluded only after any shares to be sold by the Company have been excluded, in such manner that the
shares to be sold shall be allocated among the selling holders pro rata based on their ownership of Restricted Stock relative to the other selling holders. 

(e) Notwithstanding anything to the contrary in this Section 4, the Company shall not be required to effect more than two
(2) registrations pursuant to this Section 4 provided such registrations have been declared or ordered effective. 
 5.
Incidental Registration. If the Company at any time (other than pursuant to Section 4 or Section 6) proposes to register any of its securities under the Securities Act for sale to the public, whether for its own account or for the
account of other security holders or both (except with respect to registration statements on Forms S-4, S-8 or another form not available for registering the Restricted Stock for sale to the public), each such time it will give written notice
to all holders of outstanding Restricted Stock of its intention so to do. Upon the written request of any such holder, received by the Company within thirty (30) days after the giving of any such notice by the Company, to register any of its
Restricted Stock, the Company will use its reasonable best efforts to cause the Restricted Stock as to which registration shall have been so requested to be included in the securities to be covered by the registration statement proposed to be filed
by the Company, all to the extent requisite to permit the sale or other disposition by the holder of such Restricted Stock so registered. In the event that any registration pursuant to this Section 5 shall be, in whole or in part, an
underwritten public offering of Common Stock, the 

  
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number of shares of Restricted Stock to be included in such an underwriting may be reduced (pro rata among the requesting holders based upon the number of shares of Restricted Stock owned
by such holders) if and to the extent that the managing underwriter shall be of the opinion that such inclusion would adversely affect the marketing of the securities to be sold by the Company therein; provided that with respect to any registration
of the Company’s securities other than a registration for the Company’s initial public offering, (a) all other securities are first entirely excluded from the registration; and (b) the holders’ Restricted Stock shall not be
reduced to a number such that the holders’ Restricted Stock being registered represents less than twenty five percent (25%) of the total amount of securities being registered by the Company. 

6. Registration on Form S-3. If at any time (i) a holder or holders of Restricted Stock request that the Company file a
registration statement on Form S-3 or any successor thereto for a public offering of all or any portion of the shares of Restricted Stock held by such requesting holder or holders, and (ii) the Company is a registrant entitled to use
Form S-3 or any successor thereto to register such shares, then the Company shall use its reasonable best efforts to register under the Securities Act on Form S-3 or any successor thereto, for public sale in accordance with the method of
disposition specified in such notice, the number of shares of Restricted Stock specified in such notice; provided that the anticipated aggregate offering price in each registration on Form S-3 shall exceed $1,000,000. Whenever the Company is
required by this Section 6 to use its reasonable best efforts to effect the registration of Restricted Stock, each of the procedures and requirements of Section 4 (including but not limited to the requirement that the Company notify all
holders of Restricted Stock from whom notice has not been received and provide them with the opportunity to participate in the offering) shall apply to such registration, provided, however, that there shall be no limitation on the
number of registrations on Form S-3 which may be requested and obtained under this Section 6, and provided, further, however, that the requirements contained in the first sentence of Section 4(a) shall not apply
to any registration on Form S-3 which may be requested and obtained under this Section 6. 
 7. Registration Procedures. If
and whenever the Company is required by the provisions of Sections 4, 5 or 6 to use its reasonable best efforts to effect the registration of any shares of Restricted Stock under the Securities Act, the Company will, as expeditiously as
possible: 
 (a) prepare and file with the Commission a registration statement (which, in the case of an underwritten public offering
pursuant to Section 4, shall be on Form S-1 or other form of general applicability satisfactory to the managing underwriter selected as therein provided) with respect to such securities and use its reasonable best efforts to cause such
registration statement to become and remain effective for the period of the distribution contemplated thereby (determined as hereinafter provided); provided, that the Company’s obligation to file a registration statement, or cause such
registration statement to become and remain effective, shall be suspended for a period not to exceed ninety (90) days in any 12-month period if there exists at the time material non-public information relating to the Company which, in the
reasonable opinion of the Company, should not be disclosed. 
 (b) prepare and file with the Commission such amendments and supplements to
such registration statement and the prospectus used in connection therewith as may be 

  
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necessary to keep such registration statement effective for the period specified in paragraph (a) above and comply with the provisions of the Securities Act with respect to the disposition
of all Restricted Stock covered by such registration statement in accordance with the sellers’ intended method of disposition set forth in such registration statement for such period; 

(c) furnish to each seller of Restricted Stock and to each underwriter such number of copies of the registration statement and the prospectus
included therein (including each preliminary prospectus), and any amendments or supplements thereto, as such persons reasonably may request in order to facilitate the public sale or other disposition of the Restricted Stock covered by such
registration statement; 
 (d) use its reasonable best efforts to register or qualify the Restricted Stock covered by such registration
statement under the securities or “blue sky” laws of such jurisdictions as the sellers of Restricted Stock or, in the case of an underwritten public offering, the managing underwriter reasonably shall request, provided,
however, that the Company shall not for any such purpose be required to qualify generally to transact business as a foreign corporation in any jurisdiction where it is not so qualified or to consent to general service of process in any such
jurisdiction; 
 (e) use its reasonable best efforts to list the Restricted Stock covered by such registration statement with any securities
exchange or nationally recognized quotation service on which the Common Stock of the Company is then listed; 
 (f) provide a transfer agent
and registrar and CUSIP number for all such Restricted Stock, not later than the effective date of such registration statement; 
 (g)
immediately notify each seller of Restricted Stock and each underwriter under 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 of which
the Company has knowledge as a result of which the prospectus contained in such registration statement, as then in effect, includes an untrue statement of a material fact or omits to state a material fact required to be stated therein or necessary
to make the statements therein not misleading in light of the circumstances then existing, and amend or supplement such prospectus in order to cause such prospectus not to include any untrue statement of a material fact or omit to state a material
fact required to be stated therein or necessary to make the statements therein not misleading in the light of the circumstances then existing; 

(h) if the offering is underwritten and at the request of any seller of Restricted Stock, use its reasonable best efforts to furnish on the
date that Restricted Stock is delivered to the underwriters for sale pursuant to such registration: (i) an opinion dated such date of counsel representing the Company for the purposes of such registration, addressed to the underwriters and to
such seller, stating that such registration statement has become effective under the Securities Act and that (A) to the best knowledge of such counsel, no stop order suspending the effectiveness thereof has been issued and no proceedings for
that purpose have been instituted or are pending or contemplated under the Securities Act, (B) the registration statement, the related prospectus and each amendment or supplement thereof comply as to form in all material respects with the
requirements of the Securities Act (except that such counsel need not express any 

  
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opinion as to financial statements contained therein) and (C) to such other effects as reasonably may be requested by counsel for the underwriters or by such seller or its counsel and
(ii) a letter dated such date from the independent public accountants retained by the Company, addressed to the underwriters and to such seller, stating that they are independent public accountants within the meaning of the Securities Act and
that, in the opinion of such accountants, the financial statements of the Company included in the registration statement or the prospectus, or any amendment or supplement thereof, comply as to form in all material respects with the applicable
accounting requirements of the Securities Act, and such letter shall additionally cover such other financial matters (including information as to the period ending no more than five business days prior to the date of such letter) with respect to
such registration as such underwriters reasonably may request; 
 (i) make available for inspection by each seller of Restricted Stock, any
underwriter participating in any distribution pursuant to such registration statement, and any attorney, accountant or other agent retained by such seller or underwriter, all financial and other records, pertinent corporate documents and properties
of the Company, and cause the Company’s officers, directors and employees to supply all information reasonably requested by any such seller, underwriter, attorney, accountant or agent in connection with such registration statement. The rights
granted pursuant to this subsection (i) may not be assigned or otherwise conveyed by such person or by any subsequent transferee of any such rights without the written consent of the Company, which consent shall not be unreasonably withheld;
provided that the Company may refuse such written consent if the proposed transferee is a competitor of the Company as determined by the Company’s Board of Directors; and provided further, that no such written consent shall be required if the
transfer is made to a party who is not a competitor of the Company and who is a parent, subsidiary, affiliate, partner or group member of such person; 

(j) advise each selling holder of Restricted Stock, promptly after it shall receive notice or obtain knowledge thereof, of the issuance of any
stop order by the Commission suspending the effectiveness of such registration statement or the initiation or threatening of any proceeding for such purpose and promptly use all reasonable efforts to prevent the issuance of any stop order or to
obtain its withdrawal if such stop order should be issued; 
 (k) cooperate with the selling holders of Restricted Stock and the managing
underwriters, if any, to facilitate the timely preparation and delivery of certificates representing Restricted Stock to be sold, such certificates to be in such denominations and registered in such names as such holders or the managing underwriters
may request at least two business days prior to any sale of Restricted Stock; and 
 (l) permit any holder of Restricted Stock which holder,
in the sole and exclusive judgment, exercised in good faith, of such holder, might be deemed to be a controlling person of the Company, to participate in good faith in the preparation of such registration or comparable statement and to require the
insertion therein of material, furnished to the Company in writing, which in the reasonable judgment of such holder and its counsel should be included, subject to review by the Company and its counsel after consultation with such holder. 

For purposes of Section 7(a) and 7(b) and of Section 4(c), the period of distribution of Restricted Stock in a firm commitment
underwritten public offering shall be 

  
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deemed to extend until each underwriter has completed the distribution of all securities purchased by it, and the period of distribution of Restricted Stock in any other registration shall be
deemed to extend until the earlier of the sale of all Restricted Stock covered thereby and ninety (90) days after the effective date thereof. 

In connection with each registration hereunder, the sellers of Restricted Stock will furnish to the Company in writing such information with
respect to themselves and the proposed distribution by them as reasonably shall be necessary in order to assure compliance with federal and applicable state securities laws. 

In connection with each registration pursuant to Sections 4, 5 or 6 covering an underwritten public offering, the Company and each
seller agree to enter into a written agreement with the managing underwriter selected in the manner provided in Section 7(m) below in such form and containing such provisions as are customary in the securities business for such an arrangement
between such underwriter and companies of the Company’s size and investment stature. 
 (m) In the case of any registration effected
pursuant to Section 4, the Investors holding at least a majority of the Restricted Stock then outstanding shall have the right to designate the managing underwriter, provided such managing underwriter is reasonably acceptable to the Company. In
the case of any other registration effected pursuant to this Agreement, the Company shall have the exclusive right to designate the managing underwriter. 

8. Expenses. All expenses incurred by the Company in complying with Sections 4, 5, 6 and 7, including, without limitation, all
registration and filing fees, printing expenses, fees and disbursements of counsel and independent public accountants for the Company, fees and expenses (including counsel fees) incurred in connection with complying with state securities or
“blue sky” laws, fees of the Financial Industry Regulatory Authority, fees of transfer agents and registrars, costs of insurance, and fees of up to $15,000 and disbursements of one counsel for the sellers of Restricted Stock, but excluding
any Selling Expenses, are called “Registration Expenses”. All underwriting discounts, selling commissions and transfer taxes, and the fees of more than one counsel to the sellers of Restricted Stock, applicable to the sale of Restricted
Stock are called “Selling Expenses”. 
 The Company will pay all Registration Expenses in connection with each registration
statement under Sections 4, 5 and 6. All Selling Expenses in connection with each registration statement under Sections 4, 5 or 6 shall be borne by the participating sellers in proportion to the number of shares sold by each, or by such
participating sellers other than the Company (except to the extent the Company shall be a seller) as they may agree. 
 9.
Indemnification and Contribution. 
 (a) In the event of a registration of any of the Restricted Stock under the Securities Act
pursuant to Sections 4, 5 or 6, the Company will indemnify and hold harmless each seller of such Restricted Stock thereunder, each partner, member, officer, and director of such seller, each underwriter of such Restricted Stock thereunder and
each other person, if any, who controls such seller or underwriter within the meaning of the Securities Act, against any 

  
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losses, claims, damages or liabilities, joint or several, to which such seller, underwriter or controlling person may become subject under the Securities Act or otherwise, insofar as such losses,
claims, damages or liabilities (or actions in respect thereof) arise out of or are based upon (i) any untrue statement or alleged untrue statement of any material fact contained in any registration statement under which such Restricted Stock
was registered under the Securities Act pursuant to Sections 4, 5 or 6, any preliminary prospectus or final prospectus contained therein, or any amendment or supplement thereof, or arise out of or are based upon 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, or (ii) any violation or alleged violation by the Company of the Securities Act, the Exchange Act, any state securities
law, or any rule or regulation promulgated under the Securities Act, the Exchange Act, or any state securities law in connection with the offering covered by such registration statement; and will reimburse each such seller, each such underwriter and
each such controlling person for any legal or other expenses reasonably incurred by them in connection with investigating or defending any such loss, claim, damage, liability or action, provided, however, that the Company will not be
liable in any such case to a particular seller, underwriter or controlling person if and to the extent that any such loss, claim, damage or liability arises out of or is based upon an untrue statement or alleged untrue statement or omission or
alleged omission so made in conformity with information furnished by such seller, underwriter or controlling person in writing specifically for use in such registration statement or prospectus; and provided, further, that no
seller shall be liable for amounts paid in settlement of any such loss, claim, damage, liability or action by the Company which is effected without the consent of such seller, which shall not be unreasonably withheld. 

(b) In the event of a registration of any of the Restricted Stock under the Securities Act pursuant to Sections 4, 5 or 6, each seller of
such Restricted Stock thereunder, severally and not jointly, will indemnify and hold harmless the Company, each person, if any, who controls the Company within the meaning of the Securities Act, each officer of the Company who signs the registration
statement, each director of the Company, each underwriter and each person who controls any underwriter within the meaning of the Securities Act, against all losses, claims, damages or liabilities, joint or several, to which the Company or such
officer, director, underwriter or controlling person may become subject under the Securities Act or otherwise, insofar as such losses, claims, damages or liabilities (or actions in respect thereof) arise out of or are based upon any untrue statement
or alleged untrue statement of any material fact contained in the registration statement under which such Restricted Stock was registered under the Securities Act pursuant to Sections 4, 5 or 6, any preliminary prospectus or final prospectus
contained therein, or any amendment or supplement thereof, or arise out of or are based upon 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,
and will reimburse the Company and each such officer, director, underwriter and controlling person for any legal or other expenses reasonably incurred by them in connection with investigating or defending any such loss, claim, damage, liability or
action, provided, however, that such seller will be liable hereunder in any such case if and only to the extent that any such loss, claim, damage or liability arises out of or is based upon an untrue statement or alleged untrue
statement or omission or alleged omission made in reliance upon and in conformity with information pertaining to such seller, as such, furnished in writing to the Company by such seller specifically for use in such registration statement or
prospectus, and provided, further, however, that the liability of each seller hereunder shall be limited to the proportion of any such loss, claim, damage, liability or 

  
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expense which is equal to the proportion that the public offering price of the shares sold by such seller under such registration statement bears to the total public offering price of all
securities sold thereunder, but not in any event to exceed the net proceeds received by such seller from the sale of Restricted Stock covered by such registration statement. 

(c) Promptly after receipt by an indemnified party hereunder of notice of the commencement of any action, such indemnified party shall, if a
claim in respect thereof is to be made against the indemnifying party hereunder, notify the indemnifying party in writing thereof, but the omission so to notify the indemnifying party shall not relieve it from any liability which it may have to such
indemnified party other than under this Section 9 and shall only relieve it from any liability which it may have to such indemnified party under this Section 9 if and to the extent the indemnifying party is prejudiced by such omission. In
case any such action shall be brought against any indemnified party and it shall notify the indemnifying party of the commencement thereof, the indemnifying party shall be entitled to participate in and, to the extent it shall wish, to assume and
undertake the defense thereof with counsel reasonably satisfactory to such indemnified party, and, after notice from the indemnifying party to such indemnified party of its election so to assume and undertake the defense thereof, the indemnifying
party shall not be liable to such indemnified party under this Section 9 for any legal expenses subsequently incurred by such indemnified party in connection with the defense thereof other than reasonable costs of investigation and of liaison
with counsel so selected, provided, however, that, if the defendants in any such action include both the indemnified party and the indemnifying party and the indemnified party shall have reasonably concluded that there may be
reasonable defenses available to it which are different from or additional to those available to the indemnifying party or if the interests of the indemnified party reasonably may be deemed to conflict with the interests of the indemnifying party,
the indemnified party shall have the right to select a separate counsel and to assume such legal defenses and otherwise to participate in the defense of such action, with the expenses and fees of such separate counsel and other expenses related to
such participation to be reimbursed by the indemnifying party as incurred. 
 (d) In order to provide for just and equitable contribution to
joint liability under the Securities Act in any case in which either (i) any holder of Restricted Stock exercising rights under this Agreement, or any controlling person of any such holder, makes a claim for indemnification pursuant to this
Section 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 9 provides for indemnification in such case, or (ii) contribution under the Securities Act may be required on the part of any such selling holder or any such controlling
person in circumstances for which indemnification is provided under this Section 9; then, and in each such case, the Company and such holder will contribute to the aggregate losses, claims, damages or liabilities to which they may be subject
(after contribution from others) in such proportion so that such holder is responsible for the portion represented by the percentage that the public offering price of its Restricted Stock offered by the registration statement bears to the public
offering price of all securities offered by such registration statement, and the Company is responsible for the remaining portion; provided, however, that, in any such case, (A) no such holder will be required to contribute any
amount in excess of the public offering price (but not in any event to exceed the net proceeds received by such holder 

  
 11 

 
from such sale of Restricted Stock) of all such Restricted Stock received by such holder; and (B) no person or entity guilty of fraudulent misrepresentation (within the meaning of
Section 11(f) of the Securities Act) will be entitled to contribution from any person or entity who was not guilty of such fraudulent misrepresentation. 

10. Changes in Common Stock or Preferred Stock. If, and as often as, there is any change in the Common Stock or the Preferred Stock by
way of a stock split, stock dividend, combination or reclassification, or through a merger, consolidation, reorganization or recapitalization, or by any other means, appropriate adjustment shall be made in the provisions hereof so that the rights
and privileges granted hereby shall continue with respect to the Common Stock and the Preferred Stock as so changed. 
 11. Rule 144
Reporting. With a view to making available the benefits of certain rules and regulations of the Commission which may at any time permit the sale of the Restricted Stock to the public without registration, at all times after ninety (90) days
after any registration statement covering a public offering of securities of the Company under the Securities Act shall have become effective, the Company agrees to: 

(a) make and keep public information available, as those terms are understood and defined in Rule 144 under the Securities Act; 

(b) use its reasonable best efforts to file with the Commission in a timely manner all reports and other documents required of the Company
under the Securities Act and the Exchange Act; and 
 (c) furnish to each holder of Restricted Stock forthwith upon request a written
statement by the Company as to its compliance with the reporting requirements of such Rule 144 and of the Securities Act and the Exchange Act, a copy of the most recent annual or quarterly report of the Company, and such other reports and
documents so filed by the Company as such holder may reasonably request in availing itself of any rule or regulation of the Commission allowing such holder to sell any Restricted Stock without registration. 

12. Covenants of the Company. 

(a) Affirmative Covenants of the Company Other Than Reporting Requirements. Without limiting any other covenants and provisions hereof
or in the Company’s Charter, and except to the extent the following covenants and provisions of this Section 12(a) are waived in any instance by the holders of at least sixty-six and two-thirds percent (66 and 2/3%) of the Restricted
Stock, or by vote or written consent of the Board of Directors (which such vote or consent shall include the affirmative vote or consent of at least a majority of the directors designated by the holders of Preferred Stock), the Company covenants and
agrees that until the consummation of a Qualified Public Offering it will perform and observe the following covenants and provisions, and will cause each Subsidiary, if and when such Subsidiary exists, to perform and observe such of the following
covenants and provisions as are applicable to such Subsidiary: 
 (i) Payment of Taxes and Trade Debt. Pay and discharge, and cause
each Subsidiary to pay and discharge, all taxes, assessments and governmental charges or levies 

  
 12 

 
imposed upon it or upon its income, profits or business, or upon any properties belonging to it, prior to the date on which penalties attach thereto, and all lawful claims which, if unpaid, might
become a lien or charge upon any properties of the Company or any Subsidiary; provided, however, that neither the Company nor any Subsidiary shall be required to pay any such tax, assessment, charge, levy or claim which is being
contested in good faith and by appropriate proceedings if the Company or any Subsidiary shall have set aside on its books sufficient reserves, if any, with respect thereto. Pay and cause each Subsidiary to pay, when due, or in conformity with
customary trade terms, all lease obligations, all trade debt, and all other Indebtedness incident to the operations of the Company or its Subsidiaries, except such as are being contested in good faith and by proper proceedings if the Company or
Subsidiary concerned shall have set aside on its books sufficient reserves, if any, with respect thereto. 
 (ii) Maintenance of
Insurance. Maintain, and cause each Subsidiary to maintain, insurance with responsible and reputable insurance companies or associations in such amounts and covering such risks as is customarily carried by companies engaged in similar businesses
and owning similar properties in the same general areas in which the Company or such Subsidiary operates. 
 (iii) Preservation of
Corporate Existence. Preserve and maintain, and, unless the Company deems it not to be in its best interests, cause each Subsidiary to preserve and maintain, its corporate existence, rights, franchises and privileges in the jurisdiction of its
incorporation, and qualify and remain qualified, and cause each Subsidiary to qualify and remain qualified, as a foreign corporation in each jurisdiction in which such qualification is necessary or desirable in view of its business and operations or
the ownership or lease of its properties. Secure, preserve and maintain, and cause each Subsidiary to secure, preserve and maintain, all material licenses and other material rights to use intellectual property owned or possessed by it and deemed by
the Company to be necessary to the conduct of the business and the businesses of its Subsidiaries, taken as a whole. 
 (iv) Compliance
with Laws. Comply, and cause each Subsidiary to comply, with the requirements of all applicable laws, rules, regulations and orders of any governmental authority, where noncompliance would have a material adverse effect on the business,
operations, affairs or condition (financial or otherwise) of the Company. 
 (v) Inspection. Upon reasonable request and notice (but
in no event more than twice annually), permit each of the Investors who owns at least three hundred thousand (300,000) shares of Common Stock (including Common Stock then issuable upon conversion of such Investor’s Restricted Stock, the
number of shares subject to appropriate adjustment to reflect any stock split, stock dividend, reverse stock split or similar corporate event affecting the Restricted Stock and the Common Stock) or any agents or representatives thereof, to examine
and make copies of and extracts from the books of account of, and visit and inspect the properties of the Company and any Subsidiary, to discuss the affairs, finances and accounts of the Company and any Subsidiary with any of its officers, directors
or Key Employees and independent accountants, and consult with and advise the management of the Company and any Subsidiary as to their affairs, finances and accounts, all at reasonable times during normal business hours. Except for the disclosure of
information of a non-technical nature, including financial information, which such Investor discloses to its partners, members 

  
 13 

 
and/or shareholders generally, each Investor agrees that it will keep confidential and will not disclose or divulge (other than to its professional advisors) any confidential and proprietary
information that such Investor may obtain from the Company pursuant to financial statements, reports and other materials submitted by the Company as required hereunder, or pursuant to visitation or inspection rights granted hereunder (the
“Confidential Information”) unless such information is required by law to be disclosed or is or becomes known to the Investor from a source other than the Company or is or becomes publicly known other than through the actions or
inaction’s of the Investors, or unless the Company gives its written consent to such Investor’s release of such information; provided, however that nothing in this Section 12(a)(v) shall be construed or deemed to restrict or
prohibit MedImmune Ventures, Inc. (“MVI”) from disclosing Confidential Information which is non-technical in nature to employees and agents of AstraZeneca plc or any of its affiliates (as such term is defined under the Securities
Act) for use solely relating to making investment decisions relating to the Company or undertaking financial or similar appraisals relating to MVI’s investment in the Company. 

(vi) Keeping of Records and Books of Account. Keep, and cause each Subsidiary to keep, adequate records and books of account in which
complete entries will be made in accordance with generally accepted accounting principles consistently applied, reflecting all financial transactions of the Company and any Subsidiary, and in which, for each fiscal year, all proper reserves for
depreciation, depletion, returns of merchandise, obsolescence, amortization, taxes, bad debts and other purposes in connection with its business shall be made. 

(vii) Maintenance of Properties. Maintain and preserve, and cause each Subsidiary to maintain and preserve, all of its properties and
assets, necessary for the proper conduct of its business, in good repair, working order and condition, ordinary wear and tear excepted. 

(viii) By-laws. At all times, cause the bylaws of the Company to provide that, unless otherwise required by the laws of the State of
Delaware, (i) any two directors or any holder or holders of at least twenty percent (20%) of the outstanding Series AA Preferred Stock shall have the right to call a meeting of the Board of Directors or stockholders; and (ii) a
majority of the total number of members of the Board of Directors then in office, including at least three directors designated by the holders of Series AA Preferred Stock, shall constitute a quorum for all purposes. 

(ix) Indemnification. At all times maintain provisions in the Company’s Fourth Amended and Restated Certificate of Incorporation
(as in effect from time to time) (the “Charter”) and Bylaws of the Company, as amended, indemnifying all directors against liability to the maximum extent permitted under the laws of State of Delaware. 

(x) Non-Competition, Non-Solicitation and Non-Disclosure Agreements. The Company will obtain
from each Key Employee of the Company a duly executed Non-Competition and Non-Solicitation Agreement and a duly executed Confidentiality Agreement (each of which will endure for a minimum of one year from the termination of such Key Employee’s
termination of employment with the Company) in a form agreed upon by the Board of Directors (including at least a majority of the directors designated by the holders of Preferred Stock). 

  
 14 

 (xi) Meetings of Directors. Hold meetings of the Company’s Board of Directors not
less than four (4) times a year unless otherwise agreed by the Board of Directors, with at least one meeting per quarter or such other schedule as the Board of Directors shall prescribe. 

(xii) Option Plan and Vesting of Options. Maintain an equity compensation or stock option plan in a form satisfactory to the Board of
Directors reserving 8,298,879 shares of Common Stock for issuance pursuant to such plan. Except as otherwise approved by the Board of Directors or any compensation committee thereof, all shares of Common Stock, and all options and other securities
exercisable for or convertible into the capital stock of the Company, issued or granted after the date hereof to employees, directors, consultants and other service providers under any compensatory plan or arrangement of the Company shall be subject
to vesting at a rate of twenty-five percent (25%) on each of the first four anniversaries of such issuance or grant, and there shall be no acceleration of such vesting provisions. 

(xiii) D&O Insurance. The Company shall maintain insurance for the acts and omissions of its directors and officers, with coverage
to be approved by the Board of Directors; provided, however, that to the extent commercially practicable, aggregate coverage shall be in amount of at least $3 million. 

(xiv) Scientific Advisory Board Representation. Subject to the approval of the Board of Directors, not to be unreasonably withheld,
the Company will cause a representative of Care Capital LLC to sit on any scientific advisory board or similar board of advisors when, as and if constituted from time to time by the Company. 

(xv) New Developments. Where reasonably practicable, cause all technological developments, patentable or unpatentable inventions,
discoveries or improvements by the Company’s or any Subsidiary’s officers or employees to be documented in accordance with the appropriate professional standards, cause all officers and Key Employees and, to the best of the Company’s
or any Subsidiary’s ability, consultants of the Company or any Subsidiary, to execute non-disclosure and assignment of inventions agreements in a form agreed upon by all members of the Board of Directors in favor of the Company or any
Subsidiary and, where possible and deemed by management to be commercially appropriate based on the advice of legal counsel and other considerations, to file and prosecute United States and foreign patent or copyright applications relating to and
protecting such developments on behalf of the Company or any Subsidiary. 
 (xvi) Notice of Adverse Changes. Promptly after the
occurrence thereof and in any event within 10 days after each occurrence, notify the Company’s Board of Directors of any Material Adverse Change in the operations or financial condition of the Company or any material default in any other
material agreement to which the Company is a party. 
 (xvii) Notice of Proceedings. Promptly after the commencement thereof, notify
the Company’s Board of Directors of all actions, suits, litigations and proceedings pending or, to the knowledge of the Company, threatened against the Company affecting any of its respective properties or assets, or against any officer,
director, Key Employee or holder of more than 5% of the capital stock of the Company relating to such person’s performance of duties for 

  
 15 

 
the Company or relating to his stock ownership in the Company or otherwise relating to the business of the Company, including, without limiting their generality, actions pending or, to the
knowledge of the Company, threatened involving the prior employment of any of the Company’s officers or employees in their use in connection with the Company’s business of any information or techniques allegedly proprietary to any of their
former employees, or any event or condition on the basis of which such litigation, proceeding or investigation might properly be instituted before any court or governmental department, commission, board, bureau, agency or instrumentality, domestic
or foreign, affecting the Company or any Subsidiary. 
 (xviii) Board Committees. Any audit or compensation committee of the Board
of Directors shall have at least one member who is a Series AA Director (as defined in the Third Amended and Restated Stockholders Agreement dated as of the date hereof by among the Company and the other parties thereto). The Series AA Director
designated by Devon Park Bioventures, L.P. shall have a right to be a member of the Compensation Committee. The Series AA Director designated by Rho Ventures IV (QP), L.P. shall have a right to be a member of each committee of the Board of
Directors. 
 (b) Negative Covenants of the Company. Without limiting any other covenants and provisions hereof or in the
Company’s Charter, the Company covenants and agrees that, until the consummation of a Qualified Public Offering or, while this Agreement remains outstanding, it will not take any of the following actions, and will cause each Subsidiary, if and
when such Subsidiary exists, to not take any of the following actions, to the extent applicable to such Subsidiary, in each case without (i) the written consent or waiver of holders of not less than sixty-six and two-thirds percent (66 and
2/3%) of the Restricted Stock, or (ii) to the extent permitted by the Company’s Charter, the vote or written consent of the Board of Directors that includes the affirmative vote or consent of at least a majority of the directors designated
by the holders of Preferred Stock: 
 (i) Restrictions on Indebtedness. Create, incur, assume or suffer to exist, or permit any
Subsidiary to create, incur, assume or suffer to exist, any liability with respect to Indebtedness for money borrowed which exceeds, in the aggregate, $3,000,000, or which is secured by or creates any lien on Intellectual Property of the
Company. 
 (ii) Assumptions or Guaranties of Indebtedness of Other Persons. Assume, guarantee, endorse or otherwise become directly
or contingently liable on, or permit any Subsidiary to assume, guarantee, endorse or otherwise become directly or contingently liable on (including, without limitation, liability by way of agreement, contingent or otherwise, to purchase, to provide
funds for payment, to supply funds to or otherwise invest in the debtor or otherwise to assure the creditor against loss) any Indebtedness of any other Person, except for guaranties by endorsement of negotiable instruments for deposit or collection
in the ordinary course of business, and except for the guaranties of the permitted obligations of any wholly-owned Subsidiary. 
 (iii)
Ownership of Subsidiaries. Purchase or hold beneficially any stock, other securities or evidences of Indebtedness in, or make any investment in any other Person, excluding a wholly-owned Subsidiary of the Company. 

  
 16 

 (iv) Dealings with Affiliates and Others. Other than as contemplated by this Agreement,
and other than transactions in the ordinary course of business involving less than $25,000 (when combined with all other related transactions described in this paragraph with regard to the foregoing exceptions), enter into, after the date of this
Agreement, any transaction, including, without limitation, any loans or extensions of credit or royalty agreements, with any officer, director or affiliate of the Company or any Subsidiary or any member of their respective immediate families or any
corporation or other entity directly or indirectly affiliated with one or more of such officers, directors or members of their immediate families unless such transaction is approved in advance by a majority of the disinterested members of the Board
of Directors 
 (v) Prohibited Agreements. The Company shall not permit any material Subsidiary to: 

(1) liquidate, dissolve or wind-up; 

(2) consolidate or merge into or with any other entity or entities (except a consolidation or merger into the Company in which the Company is
the surviving corporation); 
 (3) sell, transfer or exclusively license all or substantially all of such Subsidiary’s assets (except
a sale, transfer or exclusive license of all or substantially all of such Subsidiary’s assets to the Company); or 
 (4) affect any
transaction that would cause such Subsidiary to no longer constitute a “Subsidiary” under this Agreement.” 
 (vi)
Declaration or Payment of Dividends. Declare or pay a dividend on any shares of capital stock of the Company. 
 (c) Reporting
Requirements. Until the consummation of a Qualified Public Offering or a Change of Control Transaction (as that term is defined in the Company’s Charter), the Company will furnish to each Investor who, together with its Affiliates, owns at
least two percent (2%) of the Common Stock determined on a fully diluted, as converted basis: 
 (i) Monthly and Quarterly
Reports: (A) as soon as available and in any event within thirty (30) days after the end of each calendar month, a report in a form to be agreed upon by the Board of Directors, which report shall include a business update and overview
and unaudited statements of income and cash flow for the Company and its Subsidiaries as of the end of such month; and (B) as soon as available and in any event within forty-five (45) days after the end of each calendar quarter, an
unaudited balance sheet of the Company and its Subsidiaries as of the end of such quarter and unaudited statements of income and retained earnings of the Company and its Subsidiaries for such quarter and for the period commencing at the end of the
previous fiscal year and ending with the end of such quarter, setting forth in each case in comparative form the corresponding figures for the corresponding period of the preceding fiscal year, and including comparisons to quarterly budgets, a cash
flow analysis for such quarter, a schedule showing each expenditure of a capital nature during such quarter, and a summary discussion of the Company’s principal functional areas, all in reasonable detail, which shall all be reviewed by the CPA
(as defined below) if so requested by the majority of the Board of Directors, including at least a majority of the directors designated by the holders of Preferred Stock; 

  
 17 

 (ii) Annual Reports: as soon as available and in any event within one hundred fifty
(150) days after the end of each fiscal year of the Company (unless otherwise determined by the Board of Directors), a copy of the annual audit report for such year for the Company and its Subsidiaries, including therein an audited consolidated
balance sheet of the Company and its Subsidiaries as of the end of such fiscal year and audited consolidated statements of income and retained earnings of the Company and its Subsidiaries for such fiscal year, setting forth in each case in
comparative form the corresponding figures for the preceding fiscal year, all such consolidated statements to be prepared in accordance with generally accepted accounting principles (“GAAP”) and duly certified by such major
independent public accountants of recognized national standing approved by a majority of the Board of Directors (the “CPA”, which must be one of the “Big 4” accounting firms unless otherwise agreed by the Board of
Directors (and agree to furnish unaudited copies of the aforementioned annual financial statements as soon as reasonably possible but not later than ninety (90) days of the end of the fiscal year). The financial statements delivered pursuant to
subsection (i) and this subsection (ii) shall be provided with a certificate executed by the chief financial officer of the Company certifying that such financial statements were prepared in accordance with GAAP (with the exception of
footnotes that may be required by GAAP) applied on a consistent basis with prior periods and fairly represent the financial condition of the Company as of the date they were prepared and the results of operations of the Company for the period
indicated, subject to, in the case of interim financial statements, year-end audit adjustments. 
 (iii) Business Plan; Budgets: as
soon as available after approval by the Board of Directors and in any event no less than thirty (30) days prior to the end of each fiscal year of the Company, a business plan and monthly operating budgets for the forthcoming fiscal year; 

(iv) Written Reports: promptly upon receipt or publication thereof, any written reports submitted to the Company by independent public
accountants in connection with an annual or interim audit of the books of the Company and its Subsidiaries made by such accountants or by consultants or other experts in connection with such consultant’s or other expert’s review of the
Company’s operations or industry, and written reports prepared by the Company to comply with other investment or loan agreements; and 

(v) Other Information: such other information respecting the business, properties or the condition or operations, financial or other,
of the Company or any of its Subsidiaries as any such Investor may from time to time reasonably request. 
 The holders of Restricted Stock hereby covenant
and agree that all of the information disclosed to such holders pursuant to the provisions of this Section 12(c) shall be treated in accordance with the last sentence of Section 12(a)(v) of this Agreement. 

(d) Legends and Opinions. Notwithstanding anything herein to the contrary, the Company shall not require an opinion of counsel before
authorizing the transfer of Preferred Stock or Conversion Shares or the removal of the legend set forth in Section 2: (i) for routine sales under Rule 144; (ii) after the Preferred Stock or Conversion Shares become eligible for resale
under Rule 144 and (iii) for distributions for partnerships and limited liability companies. 

  
 18 

 13. Miscellaneous. 

(a) All covenants and agreements contained in this Agreement by or on behalf of any of the parties hereto shall bind and inure to the benefit
of the respective successors and permitted assigns of the parties hereto, whether so expressed or not. 
 The rights to cause the Company
to register Restricted Stock pursuant to Sections 4, 5 or 6 of this Agreement may be assigned by a holder of Restricted Stock to a transferee or assignee of Restricted Stock which (a) is a subsidiary, parent, general partner, limited partner,
retired partner, member or retired member of such holder, (b) is such holder’s family member or trust for the benefit of an individual holder or a family member of such holder, or (c) acquires at least three hundred thousand
(300,000) shares of Restricted Stock (as adjusted for stock splits, stock dividends, reverse stock splits, stock combinations or other similar capitalization changes) or all of the transferor’s shares of Restricted Stock; provided,
however, the transferor shall furnish to the Company written notice of the name and address of such transferee or assignee and the securities with respect to which such registration rights are being assigned and such transferee or assignee
shall furnish to the Company its agreement in writing to be subject to all obligations of a holder of Restricted Stock set forth in this Agreement. 

(b) All notices, requests, consents and other communications hereunder shall be in writing and shall be delivered in person, mailed by
certified or registered mail, return receipt requested, or sent by telecopier or telex, addressed as follows: 
 if to the Company or any
other party hereto, at the address of such party set forth in the Purchase Agreement; 
 if to any subsequent holder of Preferred Stock or
Conversion Shares, to it at such address as may have been furnished to the Company in writing by such holder; 
 or, in any case, at such other address or
addresses as shall have been furnished in writing to the Company (in the case of a holder of Preferred Stock or Conversion Shares or to the holders of Preferred Stock or Conversion Shares (in the case of the Company) in accordance with the
provisions of this paragraph. 
 (c) This Agreement shall be governed by and construed in accordance with the internal laws of the State of
Delaware, without regard to its principles of conflicts of laws. The parties hereto agree to submit to the jurisdiction of the United States federal and state courts of the State of Delaware with respect to the breach or interpretation of this
Agreement or the enforcement of any and all rights, duties, liabilities, obligations, powers, and other relations between the parties arising under this Agreement. 

(d) This Agreement may not be amended or modified, and no provision hereof may be waived, without the written consent of the Company and the
holders of at least sixty-six 

  
 19 

 
and two-thirds percent (66 and 2/3%) of the Common Stock issued or issuable upon conversion of the Restricted Stock; provided, that any amendment to this Agreement that imposes additional
obligations upon a holder of Restricted Stock not proportionately imposed upon all other holders of Restricted Stock shall require the separate consent of the affected holder(s). 

(e) This Agreement may be executed in two or more counterparts, each of which shall be deemed an original, but all of which together shall
constitute one and the same instrument. 
 (f) The obligations of the Company to register shares of Restricted Stock under Sections 4,
5 or 6 shall terminate as to any holder (i) the fifth anniversary of the date of a Qualified Public Offering or (ii) on such date as all shares of Restricted Stock held by such holder may immediately be sold under Rule 144 during any
ninety (90) day period. 
 (g) The Company shall not grant to any third party any registration rights more favorable than or
inconsistent with any of those contained herein, so long as any of the registration rights under this Agreement remains in effect. 
 (h) If
any provision of this Agreement shall be held to be illegal, invalid or unenforceable, such illegality, invalidity or unenforceability shall attach only to such provision and shall not in any manner affect or render illegal, invalid or unenforceable
any other provision of this Agreement, and this Agreement shall be carried out as if any such illegal, invalid or unenforceable provision were not contained herein. 

(i) For purposes of this Agreement, any calculation of the number of shares of capital stock of the Company owned by a party hereto shall take
into account and aggregate all shares of capital stock of the Company owned by all of such party’s affiliates (as such term is defined under the Securities Act). 

(j) Any person or entity which, after the date hereof, purchases shares of Series AA Preferred Stock pursuant to the terms of the Purchase
Agreement and thereby becomes a “Purchaser” thereunder shall become a party to this Agreement by executing and delivering to the Company an Instrument of Accession in the form attached hereto as Schedule I, whereupon such person
shall be deemed an “Investor” for all purposes hereof. 
 (k) This Agreement (including the Schedules and any exhibits hereto),
the Charter and the other Financing Documents (as defined in the Purchase Agreement) constitute the full and entire understanding and agreement between the parties with respect to the subject matter hereof, and any other written or oral agreement
relating to the subject matter hereof existing between the parties are expressly canceled. The Prior Investor Rights Agreement is hereby amended and restated and superseded and replaced in its entirety by this Agreement, and shall be of no further
force or effect. 
 [REMAINDER OF PAGE INTENTIONALLY LEFT BLANK] 

  
 20 

 IN WITNESS WHEREOF, the parties hereto have executed this Second Amended and Restated Investor
Rights Agreement as of the day and year first written above. 
 COMPANY 
  

			
	INOTEK PHARMACEUTICALS CORPORATION
		
	By:	 	 /s/ Paul G. Howes

	Name:	 	Paul G. Howes
	Title:	 	President and Chief Executive Officer

  
 Signature Page for
the Third Amended and Restated Investor Rights Agreement 

 INVESTORS 
  

			
	DEVON PARK BIOVENTURES L.P.
		
	BY:	 	DEVON PARK ASSOCIATES, L.P.
		 	ITS GENERAL PARTNER
		
	BY:	 	 /s/ Devang V. Kantesaria

	NAME:	 	Devang V. Kantesaria
	TITLE:	 	General Partner
	
	CARE CAPITAL INVESTMENTS II, LP
		
	By:	 	Care Capital II, LLC,
		 	as general partner of Care Capital Investments II, LP
		
	By:	 	 /s/ David R. Ramsay

	Name:	 	David R. Ramsay
	Title:	 	Partner
	
	CARE CAPITAL OFFSHORE INVESTMENTS II, LP
		
	By:	 	Care Capital II, LLC,
		 	as general partner of Care Capital Offshore Investments II, LP
		
	By:	 	 /s/ David R. Ramsay

	Name:	 	David R. Ramsay
	Title:	 	Partner

  
 Signature Page for
the Third Amended and Restated Investor Rights Agreement 

			
	MEDIMMUNE VENTURES, INC.
		
	By:	 	 /s/ Eva Jack

	Name:	 	Eva Jack
	Title	 	Managing Director

  
 Signature Page for
the Third Amended and Restated Investor Rights Agreement 

 PITANGO VENTURE CAPITAL FUND IV L.P. 
  

			
	By:	 	Pitango V.C. Fund IV, L.P.,
		 	its general partner
		
	By:	 	Pitango G.P. Capital Holdings Ltd,
		 	its general partner

  

									
	By:	 	  
	 		 	By:	 	 /s/ Bruce E. Crocker

					
	Name:	 	  
	 		 	Name:	 	  

					
	Title:	 	  
	 		 	Title:	 	  

 PITANGO VENTURE CAPITAL FUND PRINCIPALS IV L.P. 
  

			
	By:	 	Pitango V.C. Fund IV, L.P.,
		 	its general partner
		
	By:	 	Pitango G.P. Capital Holdings Ltd,
		 	its general partner

  

									
	By:	 	  
	 		  	By:	  	 /s/ Bruce E. Crocker

					
	Name:	 	  
	 		  	Name:	  	  

					
	Title:	 	  
	 		  	Title:	  	  

  
 Signature Page for
the Third Amended and Restated Investor Rights Agreement 

			
	RHO VENTURES IV, L.P.
		
	By:	 	Rho Management Ventures IV, L.L.C., General Partner
		
	By:	 	 /s/ Jeffrey I. Martin

	Name:	 	Jeffrey I. Martin
	Title:	 	Attorney-In-Fact
	
	RHO VENTURES IV GmbH & CO. BETEILIGUNGS KG
		
	By:	 	Rho Capital Partners Verwaltungs GmbH, General Partner
		
	By:	 	 /s/ Jeffrey I. Martin

	Name:	 	Jeffrey I. Martin
	Title:	 	Attorney-In-Fact
	
	RHO VENTURES IV (QP), L.P.
		
	By:	 	Rho Management Ventures IV, L.L.C., General Partner
		
	By:	 	 /s/ Jeffrey I. Martin

	Name:	 	Jeffrey I. Martin
	Title:	 	Attorney-In-Fact
	
	RHO MANAGEMENT TRUST I
		
	By:	 	Rho Capital Partners, Inc., as Investment Adviser
		
	By:	 	 /s/ Jeffrey I. Martin

	Name:	 	Jeffrey I. Martin
	Title:	 	Attorney-In-Fact

  
 Signature Page for
the Third Amended and Restated Investor Rights Agreement 

			
	BIOMEDICAL SCIENCES INVESTMENT FUND PTE LTD
		
	By:	 	 /s/ Chu Swee Yeok

	Name:	 	Chu Swee Yeok
	Title:	 	Director

  
 Signature Page for
the Third Amended and Restated Investor Rights Agreement 

 Exhibit A 

Investors 
 As of the
Initial Closing on June 9, 2010 
 DEVON PARK BIOVENTURES, L.P. 

Pitango Venture Capital Fund IV L.P. 
 Pitango Venture Capital
Fund Principals IV L.P. 
 Care Capital Investments II, LP 

Care Capital Offshore Investments II, LP 
 Rho Management Trust I

 Rho Ventures IV, L.P. 
 Rho Ventures IV (QP), L.P. 

Rho Ventures IV GmbH & Co. BETEILIGUNGS KG 
 MedImmune
Ventures, Inc. 
 Biomedical Sciences Investment Fund Pte Ltd 

 SCHEDULE I 

INOTEK PHARMACEUTICALS CORPORATION 

INSTRUMENT OF ACCESSION 

The undersigned,                     , as
a condition precedent to becoming the owner or holder of record of                     
(            ) shares of the Series AA Convertible Preferred Stock, par value $0.001 per share, of Inotek Pharmaceuticals Corporation, a Delaware corporation (the
“Company”), hereby agrees to become an “Investor” under that certain Third Amended and Restated Investor Rights Agreement dated as of June 9, 2010 by and among the Company and certain other stockholders of the
Company. This Instrument of Accession shall take effect and shall become an integral part of, and the undersigned shall become a party to and bound by, said Investor Rights Agreement immediately upon execution and delivery to the Company of this
Instrument. 
 IN WITNESS WHEREOF, this INSTRUMENT OF ACCESSION has been duly executed by or on behalf of the undersigned, as a sealed
instrument under the laws of the State of Delaware, as of the date below written. 
  

			
	Signature:
	
	  

	(Print Name)	 	  

 

					
	Address:	 	
	  

	  

		
	Date:	 	  

	
	Accepted:
	
	INOTEK PHARMACEUTICALS CORPORATION
		
	By:	 	  

		 	Name:	 	Paul G. Howes
		 	Title:	 	President and Chief Executive Officer
		
	Date:EX-4.3.1

 Exhibit 4.3.1 

THIRD AMENDED AND RESTATED STOCKHOLDERS AGREEMENT 

STOCKHOLDERS AGREEMENT made this 9th day of June, 2010 by and among (i) Inotek
Pharmaceuticals Corporation, a Delaware corporation (the “Company”), (ii) holders of Common Stock or options to acquire Common Stock or of Series X Convertible Preferred Stock (as defined below) whose names are set forth under
the heading “Holders” on Schedule I hereto and each person who shall, after the date hereof, acquire shares of Common Stock or Series X Convertible Preferred Stock and join in and become a party to this Agreement by executing and
delivering to the Company an Instrument of Accession in the form of Schedule II hereto (the persons described in this clause (ii) are referred to herein collectively as the “Holders” and singularly as a
“Holder”) and (iii) those persons whose names are set forth under the heading “Investors” on Schedule I hereto and each person who shall, after the date hereof, acquire shares of Series AA Convertible
Preferred Stock (as defined below) and join in and become a party to this Agreement by executing and delivering to the Company an Instrument of Accession in the form of Schedule III hereto (the persons described in this clause (iii) are
referred to herein collectively as the “Investors”). The Holders and the Investors are sometimes collectively referred to herein as the “Stockholders.” 

WITNESSETH: 
 WHEREAS, the
Investors are acquiring simultaneously herewith shares of the Company’s Series AA Convertible Preferred Stock, par value $0.001 per share (the “Series AA Convertible Preferred Stock”), of the Company pursuant to a certain
Series AA Convertible Preferred Stock Purchase Agreement dated as of the date hereof, by and among the Investors and the Company, as amended from time to time (the “Purchase Agreement”); 

WHEREAS, simultaneously with the execution and consummation of the Purchase Agreement: (i) the Company is issuing Series X Convertible
Preferred Stock, par value $0.001 per share (the “Series X Convertible Preferred Stock” and together with the Series AA Convertible Preferred Stock, the “Preferred Stock”) to certain Holders as set forth on Schedule
I; and (ii) all of the issued and outstanding shares of the Company’s Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, and Series C Convertible Preferred Stock are being converted to Common Stock, par value $.01
per share (the “Common Stock”) pursuant to the Company’s certificate of incorporation, as in effect on the date hereof; 

WHEREAS, the Company and certain Holders entered into an Amended and Restated Stockholders Agreement dated as of August 21, 2007, as
amended (the “Prior Stockholders Agreement”); and 
 WHEREAS, in order to induce the Investors to enter into the Purchase
Agreement and in order to provide the Investors with certain rights, the Company and the Requisite Holders (as such terms are defined in the Prior Stockholders Agreement) desire to amend and restate the Prior Stockholders Agreement in its entirety
to read as set forth in this Agreement. 
  

 Third Amended and Restated Stockholders Agreement – Page 2 

NOW, THEREFORE, in consideration of the mutual covenants herein contained and other good and valuable consideration, the receipt and
sufficiency of which are hereby acknowledged, the Company, the Holders and the Investors agree as follows: 
 1. Prohibited
Transfers. Each Holder and Investor agrees that it shall not Transfer, all or any part of the Shares (as hereinafter defined) owned by such Holder or Investor except in compliance with the terms of this Agreement. For purposes of this Agreement,
(i) the term “Shares” shall mean and include all shares of Common Stock and Preferred Stock of the Company and all other securities of the Company that may be exchangeable for, convertible into or issued in exchange for or in
respect of shares of Common Stock or Preferred Stock (whether by way of stock split, stock dividends, combination, reclassification, reorganization or any other means), in each case whether now owned or hereafter acquired; and (ii) the term
“Transfer” shall mean any sale, assignment, encumbrance, hypothecation, pledge, conveyance in trust, gift, transfer pursuant to the laws of descent and distribution, or any other transfer or disposition of any kind, including, but
not limited to, transfers to receivers, levying creditors, trustees or receivers in bankruptcy proceedings or general assignees for the benefit of creditors, whether voluntary or by operation of law. The Company shall not transfer on its books any
Shares owned by a Holder or Investor unless the provisions hereof have been complied with in full. Any purported Transfer by a Holder or Investor of Shares without full compliance with the provisions of this Agreement shall be null and void. 

2. Right of First Refusal on Dispositions by the Stockholders. 

(a) (i) If at any time any Stockholder (the “Transferring Stockholder”) wishes to Transfer all or any portion of the Shares
owned by such Stockholder (the “Offered Shares”), such Transferring Stockholder shall submit a written offer (the “Offer”) to sell such Offered Shares to the Investors (with a copy to the Company), on terms and
conditions, including price, not less favorable to the Investors than those on which such Stockholder proposes to sell such Shares to the proposed transferee or purchaser (the “Purchaser”). The Offer shall disclose the identity of
the Purchaser and the number of Offered Shares, and shall describe in reasonable detail the material terms and conditions of the Transfer, including without limitation, the price per share to be paid for the Offered Shares (the “Price Per
Share”), and shall include a copy of any written offer, letter of intent or other written document signed by the Purchaser setting forth the proposed terms and conditions of the Transfer (the “Terms”). 

(ii) Each Investor shall have the right to purchase from the Transferring Stockholder that number of the Offered Shares as shall be equal to
the aggregate Offered Shares multiplied by a fraction, the numerator of which is the number of Shares (on an as-converted to Common Stock basis) then owned by such Investor on the date the Transferring Stockholder delivers the Offer to the
Investors, and the denominator of which is the aggregate number of Shares (on an as-converted to Common Stock basis) then owned by all the Investors (other than the Transferring Stockholders, if such Transferring Stockholder is an Investor) on the
date the Transferring Holder delivers the Offer to the Investors. For purposes of Section 2 of this Agreement only, the number of Shares owned by an Investor shall include the Series AA Convertible Preferred Stock, any Common Stock into which
the Series AA Convertible Preferred 

  Third Amended and Restated Stockholders Agreement – Page
 3
 
  

 
Stock converts and any shares of Common Stock acquired by an Investor pursuant to the Purchase Agreement or this Agreement, but shall not include any Common Stock issued upon the conversion of
Series A Convertible Preferred Stock, Series B Convertible Preferred Stock, or Series C Convertible Preferred Stock. The amount of Offered Shares each Investor is entitled to purchase under this Section 2 shall be referred to as such
Investor’s “Pro Rata Fraction.” Any Investor that desires to purchase all or any portion of its Pro Rata Fraction of the Offered Shares shall deliver notice (an “Investor Notice”) to the Transferring
Stockholder of its intent to purchase all or any portion of its Pro Rata Fraction of the Offered Shares on the Terms, including the Price Per Share, as set forth in the Offer, within 15 days of such Investor’s receipt of the Offer. Each
Investor shall include in the Investor Notice the number of additional Offered Shares, if any, in addition to such Investor’s Pro Rata Fraction, that such Investor desires to purchase if the other Investors have not collectively agreed to
purchase all of the Offered Shares (an “Under-subscription Election”). Such Investor Notice shall be delivered in accordance with the provisions of Section 9 below and shall, when taken in conjunction with the Offer be deemed
to constitute a valid, legally binding and enforceable agreement for the sale and purchase of the Investor’s Pro Rata Fraction of the Offered Shares covered thereby. In the event an Investor does not elect to purchase or transfer such
Investor’s right to purchase such Investor’s Pro Rata Fraction of the Offered Shares, then the Offered Shares not purchased by such Investor shall be offered to the Investors making Under-subscription Elections on a pro rata basis
with any other Investors making Under-subscription Elections, and such procedure shall be repeated until all available Offered Shares not purchased by other Investors shall be offered to all Investors desiring to purchase more than their Pro Rata
Fraction of the Offered Shares. Any Investor shall be entitled to assign its right to purchase all or any portion of its rights to purchase Offered Shares pursuant to this Section 2 to (a) any other Investor, or (b) any Investor
Permitted Transferee (as defined below) of such Investor. 
 (iii) The closing of the purchase and sale of the Offered Shares to the
Investors delivering Investor Notices shall take place on the date which is fifteen (15) days from the completion of the procedures set forth in Section 2(a)(i) – (ii) above. The Transferring Stockholder shall promptly give each
such Investor notice of the date and time of closing. At the closing, each Investor shall pay the total purchase price of the Offered Shares which each Investor has elected to purchase, if any (which shall be equal to the product of (a) the
number of Offered Shares to be purchased by such Investor and (b) the Price Per Share) by wire transfer of immediately available funds to an account designated by the Transferring Stockholder (unless the Offer provided for payment over time or
by promissory note) against delivery of a certificate or certificates representing the Offered Shares to be purchased by each Investor, each certificate to be properly endorsed for transfer or accompanied by duly executed stock powers. Any Investor
purchasing Offered Shares may request waivers of any liens, evidence of good title to the Offered Shares and such other documents and agreements as it may reasonably deem necessary in connection with the Transfer. 

(b) In the event that the Investors, taken together, do not purchase all of the Offered Shares offered by the Transferring Stockholder
pursuant to and within the time periods set forth above, then the Transferring Stockholder shall comply with the provisions of Section 3 below. 

  Third Amended and Restated Stockholders Agreement – Page
 4
 
  

 3. Right of Participation in Sales. 

(a) In the event that the Investors do not elect to purchase from a Transferring Stockholder all of the Offered Shares contemplated by, and
pursuant to, Section 2 and the Transferring Stockholder wishes to Transfer to a Purchaser all or a portion of such remaining Offered Shares (the “Offered Co-Sale Shares”), such Transferring Stockholder shall give notice (the
“Co-Sale Notice”) to each Investor that did not elect to purchase Offered Shares (the “Co-Sale Investors”), which notice shall state that such Co-Sale Investors shall have the right to require, as a condition to the
Transfer of Offered Co-Sale Shares, that the Purchaser purchase from the Co-Sale Investors each such Co-Sale Investor’s Co-Sale Shares (as defined below) at the same Per Share Price and on the same Terms as involved in such Transfer. Each
Co-Sale Investor’s number of “Co-Sale Shares” shall be equal to the product of (a) the number of Offered Co-Sale Shares, and (b) a fraction, the numerator of which is the number of Shares (on an as-converted to Common
Stock basis) owned by the Co-Sale Investor on the date the Co-Sale Notice is given (excluding any shares of Common Stock received by the Investor upon the conversion of any Series A Convertible Preferred Stock, Series B Convertible Preferred Stock,
or Series C Convertible Preferred Stock) and the denominator of which is the number of Shares (on an as-converted to Common Stock basis) issued and outstanding on the date the Co-Sale Notice is given. Each Co-Sale Investor wishing to participate in
any such sale or disposition shall notify the Transferring Stockholder of such intention as soon as practicable after receipt of the Co-Sale Notice, and in all events within fifteen (15) days after receipt thereof, and such notification shall
set forth the number of Shares, not to exceed the Co-Sale Shares, that such Co-Sale Investor desires to Transfer to the Purchaser; and upon such election the number of Offered Co-Sale Shares to be Transferred by the Transferring Stockholder to the
Purchaser shall be correspondingly reduced. Any Investor delivering the aforementioned notification to the Transferring Stockholder shall be referred to herein as a “Co-Sale Participant.” For purposes of this Section 3, the
term “Purchaser” shall mean any proposed transferee or purchaser of Shares from any Holder and/or Investor, as applicable. 

(b) The closing of the sale of Offered Co-Sale Shares from the Transferring Stockholder and, if applicable, Co-Sale Shares from Co-Sale
Participants, to the Purchaser shall take place on a date not earlier than 10 days and not later than 60 days following the expiration of the time periods referenced in (a) above. At such closing, each Co-Sale Participant shall deliver to the
Purchaser one or more certificates, properly endorsed for Transfer, which represent the number of Co-Sale Shares which such Co-Sale Participant has elected to sell; provided, however, that if the Purchaser objects to the delivery of
Preferred Stock in lieu of Common Stock, each Co-Sale Participant may convert such Co-Sale Shares into Common Stock and deliver such shares of Common Stock, and the Company agrees to make any such conversion concurrent with the actual transfer of
such Co-Sale Shares to the Purchaser. Upon receipt of the certificate or certificates representing such Co-Sale Shares and concurrently with the purchase of Offered Co-Sale Shares from the Transferring Stockholder, the Purchaser shall remit to each
Co-Sale Participant, by wire transfer of immediately available funds, the purchase price of the Co-Sale Shares (which purchase price, with respect to each Co-Sale Participant, shall be equal to the product of the number of Co-Sale Shares that such
Co-Sale Participant has elected to sell and the Price Per Share). To the extent that the Purchaser refuses to purchase Co-Sale Shares from a Co-Sale Participant, the Transferring Stockholder shall not sell to such Purchaser any Offered Co-Sale
Shares unless and until, simultaneously with such sale, such Transferring Stockholder 

  Third Amended and Restated Stockholders Agreement – Page
 5
 
  

 
purchases the Co-Sale Shares from the Co-Sale Participant on the Terms, including the Per Share Price. The Transferring Stockholder shall use his, her or its reasonable best efforts to obtain the
agreement of the Purchaser to the participation of the Co-Sale Participants in the contemplated Transfer. The provisions of this Section 3 shall not apply to the sale of any Shares by a Holder to an Investor pursuant to an Offer under
Section 2. No Transfer of Shares shall be effective unless, contemporaneously with such Transfer, the Purchaser executes and delivers to the Company an Instrument of Accession in the form of Schedule II agreeing to be bound by the
provisions of this Agreement. 
 (c) In the event that the Transferring Stockholder does not Transfer the Offered Co-Sale Shares to the
Purchaser within the required time periods, then any subsequent Transfer of all or any portion of the Offered Co-Sale Shares, shall again be subject to the rights granted in Section 2 and this Section 3, as applicable, and shall require
compliance by a Transferring Stockholder with the procedures described in such Sections. 
 (d) Any exercise or non-exercise of any
Investor’s rights under Section 2 or 3, as applicable, with respect to a particular Transfer of Shares by a Founder shall not adversely affect the Investors’ rights with respect to other Transfers of Shares by any Founder. 

4. Permitted Transfers. 

(a) Anything herein to the contrary notwithstanding, the provisions of Sections 1, 2 and 3 shall not apply to a Transfer to: (i) the
spouse, children, parents or siblings of such Holder (collectively, “Family Members”), (ii) the estate of such Holder, (iii) any trust solely for the benefit of such Holder or any Family Member(s) (a “Family
Trust”), (iv) any partnership, corporation or limited liability company which is controlled by such Holder or any such Family Member(s) (“Family Wealth Planning Entity”); provided that, any change in the beneficiaries
of a Family Trust or the equity holders of a Family Wealth Planning Entity which results in such Family Trust not being solely for the benefit of a Holder or the Family Members of such Holder or the Family Wealth Planning Entity not being controlled
by such Holder or the Family Members of such Holder shall be a Transfer of Shares which is subject to the provisions of Sections 1, 2 and 3, and (v) the Company pursuant to the repurchase of Shares of Common Stock from officers, employees,
directors or consultants of the Company which are subject to restrictive stock purchase agreements under which the Company has the option to repurchase such shares upon the occurrence of certain events, including termination of employment. In
addition, anything herein to the contrary notwithstanding, the provisions of Sections 1, 2 and 3 shall not apply to a Transfer by an Investor to (w) any entities controlled by, controlling or under common control with such Investor, (x) if
the Investor is a partnership, any partners, former partners or affiliated partnerships managed by the same manager or managing partner or management company, or managed by an entity controlling, controlled by, or under common control with, such
manager or managing partner or management company, (y) stockholders, members or equity holder of such Investor transferor (or to a liquidating trust for the benefit of such partners or members) or (z) from a grantor trust to its grantors
or to an affiliated entity (each an “Investor Permitted Transferee”). 
 (b) In the event of any such Transfer, other than
pursuant to subsection (a)(v) of this Section 4, the transferee of the Shares shall hold the Shares so acquired with all the rights 

  Third Amended and Restated Stockholders Agreement – Page
 6
 
  

 
conferred by, and subject to all the restrictions imposed by this Agreement, and as a condition to such Transfer, other than pursuant to subsection (a)(v) of this Section 4, each such
transferee shall execute and deliver an Instrument of Accession in the form of Schedule II agreeing to be bound by the provisions of this Agreement. 

(c) The provisions of Sections 1, 2 and 3 shall not apply to the sale of Shares by a Holder or Investor in a firm commitment underwritten
public offering pursuant to a registration statement filed with, and declared effective by, the Securities and Exchange Commission under the Securities Act of 1933, as amended (the “Securities Act”) (“IPO”). 

5. Drag-Along Rights of Investors. 

(a) If, at any time, the holders of at least sixty-six and two-thirds percent (66 and 2/3%) of the outstanding shares of the Series AA
Convertible Preferred Stock vote in favor of (i) the consolidation or merger of the Company into or with any other entity or entities, (ii) the sale, transfer or exclusive license of all or substantially all the assets of the Company, or
(iii) the sale or other exchange of all of the outstanding shares of the Company’s capital stock (each, an “Acquisition”), then each of the Stockholders shall be obligated to use their best efforts to effect the closing of
such Acquisition, including without limitation, to (i) vote all of their voting Shares in favor of such Acquisition, should such vote be required for the consummation of such Acquisition, (ii) sell, transfer, or exchange all of their
voting Shares in connection with such Acquisition, with the consideration to be paid in respect of such sale, transfer, or exchange to be allocated or distributed among the Stockholders in accordance with the terms of the Company’s Certificate
of Incorporation then in effect (the “Company Charter”), including without limitation the priority and preferences of the Preferred Stock, and (iii) execute and deliver such instruments of conveyance and transfer and take such
other action, including executing any purchase agreement, merger agreement, indemnity agreement, escrow agreement or related documents, as necessary to consummate the Acquisition. If any Stockholder fails or refuses to vote or sell their Shares as
required by (and execute and deliver any required documents), or vote their Shares in contravention of, this section, then such Stockholder hereby grants the Chief Executive Officer of the Company an irrevocable proxy and power of attorney, coupled
with an interest, to vote such Shares or give written consent in accordance with the terms of this Section 5 and to execute any instruments necessary or advisable to effect such grant, and hereby appoints the Chief Executive Officer as its
attorney in fact, to sell such Shares in accordance with the terms of this Section 5, and the Chief Executive Officer shall so vote or sell such Shares and execute and deliver such documents. This proxy shall terminate upon the closing of an
IPO. At the closing of an Acquisition, each of the Stockholders shall deliver, against receipt of the consideration payable in such transaction, certificates representing that number of voting Shares which such Stockholder is bound to transfer
pursuant to any agreement effected in connection with the Acquisition, with all endorsements or other instruments necessary for transfer. In the event that any Stockholder fails or refuses to comply with the provisions of this section, the Company,
the Stockholders and the purchaser in such Acquisition, at their option, may elect to proceed with such Acquisition notwithstanding such failure or refusal and, in such event and upon tender of the specified consideration to any such Stockholder,
the rights of any such Stockholder with respect to such Shares of such Stockholder shall cease. 

  Third Amended and Restated Stockholders Agreement – Page
 7
 
  

 (b) The obligations of each Stockholder with respect to an Acquisition are imposed and
undertaken in reliance upon the premise that, and subject to the subsequent condition that, distribution of the net proceeds of the Acquisition, including without limitation, if structured as a sale of stock, will be made to the Stockholders in
accordance with the procedures (including, without limitation, the priority and preferences granted to the holders of Preferred Stock) set forth in the Company Charter. 

(c) In connection with an Acquisition, the Stockholders who are not accredited investors (as that term is defined in Rule 501 of the
Securities Act) will, at the request of the Company, appoint a purchaser representative (as such term is defined in Rule 501 of the Securities Act) reasonably acceptable to the Company. 

6. Right of Participation. 

(a) Participation in Company Equity Issuances. The Company shall not issue, sell or exchange, agree or obligate itself to issue, sell
or exchange, or reserve or set aside for issuance, sale or exchange, any (i) shares of Common Stock, (ii) any other equity security of the Company, including without limitation, the Preferred Stock, (iii) any debt security of the
Company (other than debt with no equity feature) including without limitation, any debt security which by its terms is convertible into or exchangeable for any equity security of the Company, (iv) any security of the Company that is a
combination of debt and equity, or (v) any option, warrant or other right to subscribe for, purchase or otherwise acquire any such equity security or any such debt security of the Company (the securities referenced in (i) through
(v) are referred to herein as “Offered Securities”), unless in each case the Company shall have first offered to sell such Offered Securities to the Investors as follows: 

(i) The Company shall give each Investor a written notice (the “Offer Notice”). The date on which the Company gives the
Offer Notice is hereinafter referred to as the “Notice Date.” The Offer Notice shall describe (A) the number of Offered Securities for which the Company has received a bona fide, arms’ length written offer of purchase and
the name(s) of the prospective purchaser(s), (B) the price and a summary of the terms and conditions upon which the prospective purchaser(s) have offered to purchase such Offered Securities, and (C) with respect to each Investor, such
Investor’s Basic Amount (as defined below) of the Offered Securities. The Offer Notice shall be accompanied by a copy of any written offer, letter of intent or other written document signed by the prospective purchaser(s) setting forth the
proposed terms and conditions of the sale. 
 (ii) Each Investor shall have the right to purchase (x) that portion of the Offered
Securities as the number of Shares (on an as-converted to Common Stock basis) then held by such Investor (excluding any shares of Common Stock received by the Investor upon the conversion of any Series A Convertible Preferred Stock, Series B
Convertible Preferred Stock, or Series C Convertible Preferred Stock) bears to the total number of outstanding shares of Common Stock of the Company (assuming for this purpose the issuance of all shares of Common Stock upon conversion or exercise of
any securities convertible into Common Stock or securities convertible or exchangeable into Common Stock) (the “Basic Amount”), and (y) with respect to each Investor who elects to purchase its full Basic Amount, such additional
portion of the Offered Securities as such Investor shall indicate it will purchase should the other Investors 

  Third Amended and Restated Stockholders Agreement – Page
 8
 
  

 
subscribe for less than their Basic Amounts (the “Undersubscription Amount”), at a price and on such other terms as shall have been set forth in the Offer Notice. Notwithstanding
any provision in this Section 6 to the contrary, any Investor which chooses to exercise the right of participation set forth in this Section 6 may designate as purchasers under such right itself or its Investor Permitted Transferees in
such proportions as it deems appropriate. 
 (b) Notice of Acceptance. Any Investor may elect to purchase all or any portion of such
Investor’s Basic Amount by delivery of an acceptance notice to the Company not later than fifteen (15) days after delivery of the Offer Notice made pursuant to Section 6(a)(i), which shall be evidenced by a writing signed by such
Investor and shall set forth such of the Investor’s Basic Amount as such Investor elects to purchase and, in the case of any Investor who elects to purchase all of its Basic Amount, such Undersubscription Amount as such Investor shall elect to
purchase (the “Notice of Acceptance”). If the Basic Amounts subscribed for by all Investors are less than the total Offered Securities, then each Investor who has set forth Undersubscription Amounts in its Notice of Acceptance shall
be entitled to purchase, in addition to the Basic Amounts subscribed for, all Undersubscription Amounts it has subscribed for; provided, however, that should the Undersubscription Amounts subscribed for exceed the difference between
the Offered Securities and the Basic Amounts subscribed for (the “Available Undersubscription Amount”), each Investor who has subscribed for any Undersubscription Amount shall be entitled to purchase only that portion of the
Available Undersubscription Amount as the Undersubscription Amount subscribed for by such Investor bears to the total Undersubscription Amounts subscribed for by all Investors, subject to rounding by the Board of Directors to the extent it
reasonably deems necessary. 
 (c) Conditions to Acceptances and Purchase. 

(i) Permitted Sales of Refused Securities. In the event that Notices of Acceptance are not given by the Investors in respect of all
the Offered Securities, the Company shall have ninety (90) days from the expiration of the 15 day period set forth in Section 6(b) to close the sale of all or any part of such Offered Securities as to which Notices of Acceptance have not
been given by the Investors (the “Refused Securities”) to the Person or Persons specified in the Offer Notice, but only for cash and otherwise in all respects upon terms and conditions, including, without limitation, unit price and
interest rates, which are no more favorable to such other Person or Persons or less favorable to the Company than those set forth in the Offer Notice. 

(ii) Reduction in Amount of Offered Securities. In the event the Company shall propose to sell less than all the Refused Securities
(any such sale to be in the manner and on the terms specified in Section 6(c)(i) above), then each Investor may, at its sole option, but shall not be required to, reduce the number of, or other units of the Offered Securities specified in its
respective Notices of Acceptance to an amount which shall be not less than the amount of the Offered Securities which the Investor elected to purchase pursuant to Section 6(b) multiplied by a fraction, (i) the numerator of which shall be
the amount of Offered Securities which the Company actually proposes to sell, and (ii) the denominator of which shall be the amount of all Offered Securities. In the event that any Investor so elects to reduce the number or amount of Offered
Securities specified in its respective Notices of Acceptance, the Company may not sell or otherwise dispose of more than the reduced amount of the Offered Securities until such securities have again been offered to the Investors in accordance with
Section 6(a). 

  Third Amended and Restated Stockholders Agreement – Page
 9
 
  

 (iii) Closing. At the closing, which shall include full payment to the Company, of
the sale to such other Person or Persons of all or less than all the Refused Securities, the Investors shall purchase from the Company, and the Company shall sell to the Investors, the number of Offered Securities specified in the Notices of
Acceptance, as may be reduced pursuant to Section 6(c)(ii) if the Investors have so elected, upon the terms and conditions specified in the Offer Notice. The purchase by the Investors of any Offered Securities is subject in all cases to the
preparation, execution and delivery by the Company and the Investors of a purchase agreement relating to such Offered Securities reasonably satisfactory in form and substance to the Investors and their respective counsel. 

(d) Further Sale. In each case, any Offered Securities not purchased by the Investors or other Person or Persons in accordance with
Section 6(c) may not be sold or otherwise disposed of until they are again offered to the Investors under the procedures specified in Sections 6(a), 6(b) and 6(c). 

(e) Termination of Right of First Refusal. The rights of the Investors under this Section 6 shall terminate immediately prior to,
but subject to, the earlier to occur of the consummation of a Qualified Public Offering or a Change of Control Transaction, as each such term is defined in the Company Charter. 

(f) Exception. The rights of the Investors under this Section 6 shall not apply to, and Offered Securities shall not include: 

(i) Common Stock issued as a stock dividend to holders of Common Stock or Preferred Stock or upon any subdivision or combination of shares of
Common Stock, 
 (ii) Preferred Stock issued as a dividend to holders of Preferred Stock or upon any subdivision or combination of shares
of Preferred Stock, 
 (iii) Series AA Convertible Preferred Stock issued pursuant to the Purchase Agreement and any shares of Series X
Convertible Preferred Stock issued by the Company now or in the future, 
 (iv) shares of Common Stock issued upon conversion of the
Company’s Series A Preferred Stock, Series B Preferred Stock, Series C Preferred Stock, Series AA Convertible Preferred Stock or Series X Convertible Preferred Stock, in each case provided such issuance is pursuant to the terms of such
security, 
 (v) any shares of Common Stock issued by the Company pursuant to stock purchase, stock grant or stock option arrangements for
employees, directors or consultants of the Company, all under arrangements approved by the Board of Directors in accordance with the Company Charter, 

(vi) any securities issued pursuant to the acquisition of another entity by the Company by merger (whereby the Company owns no less than 51%
of the voting power of such corporation) or purchase of substantially all of such entity’s stock or assets, if such acquisition is approved by a majority of the Board of Directors, 

  Third Amended and Restated Stockholders Agreement – Page
 10
 
  

 (vii) any securities issued in connection with a commercial loan or lease with a financial
institution, or other similar agreement that is primarily of a non-equity financing nature, provided that such transaction or agreement is approved by the Board of Directors, 

(viii) securities issued pursuant to the conversion or exercise of convertible or exercisable securities outstanding as of the date hereof,

 (ix) any securities, or part thereof, with respect to which the holders of at least sixty-six and two-thirds percent (66 and 2/3%) of
the issued and outstanding shares of Preferred Stock agree in writing shall not constitute Offered Securities, 
 (x) Common Stock issued
pursuant to a bona fide, firm commitment public offering, and 
 (xi) Any issuances by the Company set forth in Article IV, Part A,
Section 5E of the Company’s certificate of incorporation as in effect on the date hereof. 
 7. Election of Directors;
Vacancies and Removal; Committees. 
 (a) Each of the Stockholders agrees to vote, whether in person at a meeting or by written consent
in lieu thereof, all of the Shares now owned or hereafter acquired by such party (and attend, in person or by proxy, all meetings of stockholders called for the purpose of electing directors), and the Company agrees to take all actions (including,
but not limited to the nomination of specified persons) to cause and maintain the election to the Board of Directors of the Company, to the extent permitted pursuant to the Company Charter, in accordance with the following: 

(i) one (1) person who shall be the then current Chief Executive Officer, who shall initially be Paul Howes; 

(ii) five (5) persons who shall be designated by the following holders of the Series AA Convertible Preferred Stock for so long as they
hold Series AA Convertible Preferred Stock and if any such holder no longer holds Series AA Convertible Preferred Stock, then a person designated by the holders of at least sixty-six and two-thirds percent (66 and 2/3%) of the Series AA Convertible
Preferred Stock (the “Series AA Directors”): one person designated by Devon Park Bioventures, L.P., (“DPB”) who shall initially be Devang Kantesaria; one person designated by Care Capital LLC
(“Care”), who shall initially be Dr. Jerry Karabelas; one person designated by Rho Ventures IV (QP), L.P. (“Rho”), who shall initially be Martin Vogelbaum; one person designated by Pitango Venture Capital Fund
IV, L.P. and Pitango Venture Capital Fund Principals IV L.P. (collectively, “Pitango”), who shall initially be Ittai Harel; and one person designated by MedImmune Ventures, Inc. (“MedImmune” and collectively with
DPB, Care, Rho and Pitango, the “Principal Investors”), who shall initially be William Bertrand; 
 (iii) one
(1) person who shall be an independent director with relevant experience designated by the holders of a majority of the outstanding shares of Common Stock, 

  Third Amended and Restated Stockholders Agreement – Page
 11
 
  

 
Series X Convertible Preferred Stock and Series AA Convertible Preferred Stock, acting together as a single class on an as converted to Common Stock basis (the “Independent
Director”), who shall initially be Michael Loberg; and 
 (iv) one (1) person designated by the majority of the other
directors then in office, who shall initially be David King. 
 (b) Each of the parties further covenants and agrees to vote or given
written consent, to the extent possible, all Shares now owned or hereafter acquired by such party so that the Company’s Board of Directors shall consist of no more than eight (8) members. 

(c) In the absence of any designation from the persons or groups so designating directors as specified above, the director previously
designated by them and then serving shall be reelected if still eligible to serve as provided herein. 
 (d) No party hereto shall vote to
remove any member of the Company’s Board of Directors designated in accordance with the aforesaid procedure unless the persons or groups so designating directors as specified above so vote, and, if such persons or groups so vote then the
non-designating party or parties shall likewise so vote. The removal of the Independent Director shall require the approval of holders of a majority of the outstanding shares of Series AA Convertible Preferred Stock, Series X Convertible Preferred
Stock and Common Stock, voting together as a single class on an as converted to Common Stock basis. The removal of the director referred to in Section 7(a)(i) shall require the approval of holders of a majority of the outstanding shares of
Series AA Convertible Preferred Stock and Common Stock, voting together as a single class on an as converted to Common Stock basis. The removal of the director referred to in Section 7(a)(iv) shall require the approval of a majority of the
other directors then in office. 
 (e) Any vacancy on the Board of Directors created by the resignation, removal, incapacity or death of any
person designated under this Section 7 shall be filled by another person designated in a manner so as to preserve the constituency of the Board as provided in Section 7(a) above. 

(f) Each of the parties and the Company further agrees that: (i) at least one of the Series AA Directors shall have a right to be a
member of every committee of the Company’s Board of Directors, including without limitation, the Executive, Compensation, and Audit Committees, if, as and when such committees shall be constituted by the Board of Directors from time to time;
(ii) the Series AA Director designated by DPB shall have a right to be a member of the Compensation Committee; and (iii) the Series AA Director designated by Rho shall have a right to be a member of each committee of the Company’s
Board of Directors. 
 (g) The Board of Directors of the Company shall meet at least four times per year, unless otherwise agreed by a vote
of a majority of the members of the Board of Directors. 
 (h) The Company shall pay the reasonable out-of-pocket expenses incurred by any
non-employee director in connection with attending meetings of the Board or any committee thereof or other meetings or events attended on behalf of the Company. At the discretion of the Board of Directors, the Company may pay the reasonable
out-of-pocket expenses incurred by any Observers (as defined below) in connection with attending meetings of the Board or any committee thereof or other meetings or events attended on behalf of the Company. 

  Third Amended and Restated Stockholders Agreement – Page
 12
 
  

 (i) In the event that the Company pays any compensation to any member of the Board of
Directors of the Company that is designated by MedImmune Ventures, Inc. (each a “MedImmune Designee”) in recognition of his or her service on the Board of Directors of the Company, such compensation (including any equity
compensation, the “MedImmune Director Equity Compensation”) otherwise payable to the MedImmune Designee shall, upon the direction of such MedImmune Designee, be paid directly to MedImmune. Nothing in this Section 7(i) shall
create an obligation on the part of the Company to pay any compensation to the MedImmune Designee. 
 (j) The Company shall seek and obtain
the approval of a majority of the members of the Board of Directors before entering into any agreement, transaction or business arrangement that exceeds a value of $500,000. 

(k) The Company shall seek and obtain the unanimous approval of the members of the Board of Directors before making any offer of employment
to, or hiring any family member of an employee of the Company. 
 (l) The Company shall invite the Principal Investors and Biomedical
Sciences Investment Fund Pte Ltd (collectively, the “Observer Investors”) to send a representative (collectively, the “Observers”) to attend all meetings of the Company’s Board of Directors (whether in person,
telephonic or other) in a non-voting, observer capacity and shall provide to each such Observer, concurrently with the members of the Board of Directors, and in the same manner, notice of such meeting and a copy of all materials provided to such
members. The rights of the Observer Investors shall terminate and be of no further force or effect in the event that such Observer Investor does not hold any shares of Preferred Stock or Common Stock (including any Common Stock issuable upon
conversion of any Preferred Stock held by such Observer Investor). Except for the disclosure of financial and other information of a non-technical nature, which each Observer discloses to employees of the Observer Investor for which such Observer is
acting as representative and partners, members and/or shareholders of such Observer Investor (provided such parties are subject to similar confidentiality obligations as set forth herein), each Observer shall, as a condition to attendance at any
meeting of the Company’s Board of Directors or receipt of any materials provided to members of the Company’s Board of Directors in connection therewith, agree that it will keep confidential and will not disclose or divulge any confidential
and proprietary information that such Observer may obtain from the Company as a result of being an Observer (the “Confidential Information”) unless such information is required by law to be disclosed or is or becomes known to the
Observer from a source other than the Company or the Board of Directors that is not bound by obligations of confidentiality to the Company or is or becomes publicly known other than through the actions or inaction’s of the Observers, or unless
the Company gives its written consent to such Observer’s release of such information. Without the prior written consent of the Company, the rights granted to the Observer Investors under this Section 7(l) may not be transferred by the
Observer Investors to any party. Notwithstanding the foregoing, the Board of Directors may request the Observers to be excluded from a meeting or portion thereof if the Company believes upon advice of counsel that such exclusion is reasonably
necessary to preserve the attorney-client privilege or to protect highly confidential information pertaining to a strategic transaction competitive to any Observer Investor or its affiliates. 

  Third Amended and Restated Stockholders Agreement – Page
 13
 
  

 8. Termination. This Agreement, and the respective rights and obligations of the
parties hereto, shall terminate upon the earlier to occur of a Qualified Public Offering or a Change of Control Transaction, as each such term is defined in the Company Charter, except that the provisions of Section 18 shall survive a Qualified
Public Offering. 
 9. Notices. All notices and other communications hereunder shall be in writing and shall be deemed to have been
given when delivered or mailed by first class, registered or certified mail (air mail if to or from outside the United States), return receipt requested, postage prepaid, if to each Holder at his respective address set forth on
Schedule I hereto or on the Instrument of Accession pursuant to which he became a party to this Agreement, and if to the Investors, at their respective addresses set forth on Schedule I hereto or to such other address as the
addressee shall have furnished to the other parties hereto in the manner prescribed by this Section 9. 
 10. Failure to Deliver
Shares. If a Stockholder becomes obligated to sell any Shares owned by, or held for the benefit of, such Stockholder to another party hereto and fails to deliver such shares in accordance with the terms of this Agreement, such other party hereto
may, at its option, in addition to all other remedies it may have, send to the Company for the benefit of such Stockholder the purchase price for such Shares as is herein specified. Thereupon, the Company upon written notice to said Stockholder,
(a) shall cancel on its books the certificate(s) representing the Shares to be sold and (b) shall issue, in lieu thereof, in the name of such other party, a new certificate(s) representing such Shares, and thereupon all of said
Stockholder’s rights in and to such Shares shall terminate. The Company may exercise a similar remedy in enforcing its rights under Section 2. 

11. Right to Conduct Activities. The Company and each Investor acknowledge that some or all of the Investors are professional
investment funds and, as such, invest in numerous portfolio companies, some of which may be competitive with the Company’s business. No Investor shall be liable to the Company or to any Holder or other Investor for any claim arising from,
related to, or in connection with: (a) any investment by such Investor in any entity that is competitive with the Company; or (b) any actions or omissions by any partner, officer, manager, employee, representative or agent of any Investor
in assisting any such entity that is competitive with the Company, whether or not such action or omission was taken as a board member of such entity or otherwise, and whether or not such action or omission has a detrimental effect on the Company.

 12. Specific Performance. The rights of the parties under this Agreement are unique and, accordingly, the parties shall, in
addition to such other remedies as may be available to any of them at law or in equity, have the right to enforce their rights hereunder by actions for specific performance to the extent permitted by law. 

13. Legend. The certificates representing the Shares shall bear on their face a legend indicating the existence of the restrictions
imposed hereby. 

  Third Amended and Restated Stockholders Agreement – Page
 14
 
  

 14. Entire Agreement. This Agreement (including the Schedules and any exhibits
hereto), the Company Charter and the other Financing Documents (as defined in the Purchase Agreement) constitute the full and entire understanding and agreement between the parties with respect to the subject matter hereof, and any other written or
oral agreement relating to the subject matter hereof existing between the parties are expressly canceled. The Prior Stockholders Agreement is hereby amended and restated and superseded and replaced in its entirety by this Agreement, and shall be of
no further force or effect. 
 15. Waivers, Amendments and Further Agreements. Except as otherwise expressly provided herein, this
Agreement may not be amended, and the provisions hereof may not be waived, except by an instrument in writing executed by (i) the Company and (ii) Investors holding at least sixty-six and two-thirds percent (66 and 2/3%) of the shares of
the Series AA Convertible Preferred Stock; provided, however, that no amendment shall be made to the rights of the Principal Investors to designate directors pursuant to Section 7 without the written consent of the respective Principal Investor
entitled to designate such director(s). Any waiver by any party of a breach of any provision of this Agreement shall not operate or be construed as a waiver of any subsequent breach of that provision or of any other provision hereof. Each of the
parties hereto agrees to execute all such further instruments and documents and to take all such further action as any other party may reasonably require in order to effectuate the terms and purposes of this Agreement. Notwithstanding the foregoing,
this Agreement may not be amended or terminated and the observance of any term of this Agreement may not be waived with respect to any Investor or Holder without the written consent of such Investor or Holder unless such amendment, termination or
waiver applies to all Investors or Holders, as the case may be, in the same fashion. 
 16. Assignment; Successors and Assigns. This
Agreement shall be binding upon and shall inure to the benefit of the parties hereto and their respective heirs, executors, legal representatives, successors and permitted transferees, except as may be expressly provided otherwise herein. 

17. Subsequent Closing Purchasers. Any person or entity which, after the date hereof, purchases shares of Series AA Convertible
Preferred Stock pursuant to the terms of the Purchase Agreement and thereby becomes a “Purchaser” thereunder shall become a party to this Agreement by executing and delivering to the Company an Instrument of Accession in the form attached
hereto as Schedule III, whereupon such person shall be deemed an “Investor” for all purposes hereof. 
 18. Lock-up
Agreement. If requested in writing by the underwriters for the initial underwritten public offering of securities of the Company, each Holder and Investor who is a party to this Agreement shall agree not to sell publicly any Shares (other than
Shares being registered in such offering), without the consent of such underwriters, for a period not to exceed one hundred eighty (180) days following the effective date of the registration statement relating to such offering; provided,
however, that all persons entitled to registration rights with respect to shares of Common Stock who are not parties to this Agreement, all other persons selling shares of Common Stock in such offering, all persons holding at least one percent
(1%) of the capital stock of the Company on a fully diluted basis and all officers and directors of the Company shall also have agreed not to sell publicly their Common Stock under the circumstances and pursuant

  Third Amended and Restated Stockholders Agreement – Page
 15
 
  

 
to the terms set forth in this Section 18; and provided further that if the underwriters release any of the foregoing directors, officers or 1% stockholders from the obligation to not
publicly sell securities for such period of time, then each holder of Shares subject to this Section 18 shall also be released from such obligation in the same proportion as the shares of Shares held by such holder bears to the total number of
shares included in any such registration. 
 19. Severability. In case any one or more of the provisions contained in this Agreement
shall for any reason be held to be invalid, illegal or unenforceable in any respect, such invalidity, illegality or unenforceability shall not affect any other provision of this Agreement and such invalid, illegal and unenforceable provision shall
be reformed and construed so that it will be valid, legal, and enforceable to the maximum extent permitted by law. 
 20.
Counterparts. This Agreement may be executed in two or more counterparts, each of which shall be deemed an original, but all of which together shall constitute one and the same instrument. 

21. Section Headings. The headings contained in this Agreement are for reference purposes only and shall not in any way affect the
meaning or interpretation of this Agreement. 
 22. Governing Law. This Agreement shall be construed and enforced in accordance with
and governed by the internal laws of the State of Delaware, without regard to its principles of conflicts of laws. The parties hereto agree to submit to the jurisdiction of the United States federal and state courts of the State of Delaware with
respect to the breach or interpretation of this Agreement or the enforcement of any and all rights, duties, liabilities, obligations, powers, and other relations between the parties arising under this Agreement. 

23. Future Holders. The Company shall use its commercially reasonable efforts to require that any person or entity acquiring shares of
the Company’s capital stock that, after such acquisition, would hold at least 1% of the Company’s capital stock, on an as-converted to Common Stock basis, shall be subject to the provisions of this Agreement as a Holder. 

[REMAINDER OF PAGE INTENTIONALLY LEFT BLANK] 

 Signature Page for the Third Amended and Restated Stockholders Agreement 

 

 IN WITNESS WHEREOF, the undersigned have executed this Third Amended and Restated
Stockholders Agreement as a sealed instrument as of the day and year first above written. 
  

			
	INOTEK PHARMACEUTICALS CORPORATION
		
	By:	 	 /s/ Paul G. Howes

	Name:	 	Paul G. Howes
	Title:	 	President Chief Executive Officer

 Signature Page for the Third Amended and Restated Stockholders Agreement 

 

			
	HOLDERS:
		
	By:	 	 /s/ Paul G. Howes

		 	Paul G. Howes
		
	By:	 	 /s/ James G. Ham, III

		 	James G. Ham, III
		
	By:	 	 /s/ Rudolf Baumgartner

		 	Rudolf Baumgartner
		
	By:	 	 /s/ William McVicar

		 	William McVicar

 Signature Page for the Third Amended and Restated Stockholders Agreement 

 

			
	Csaba Szabo 2006 Grantor Retained Annuity Trust
		
	By:	 	 /s/ Mark M. Christopher

		 	Mark M. Christopher, Trustee

 Signature Page for the Third Amended and Restated Stockholders Agreement 

 

			
	INVESTORS:
	
	CARE CAPITAL INVESTMENTS II, LP
		
	By:	 	Care Capital II, LLC,
		 	as general partner of Care Capital Investments II, LP
		
	By:	 	 /s/ David R. Ramsay

	Name:	 	David R. Ramsay
	Title:	 	Partner
	
	CARE CAPITAL OFFSHORE INVESTMENTS II, LP
		
	By:	 	Care Capital II, LLC,
		 	as general partner of Care Capital Offshore Investments II, LP
		
	By:	 	 /s/ David R. Ramsay

	Name:	 	David R. Ramsay
	Title:	 	Partner

 Signature Page for the Third Amended and Restated Stockholders Agreement 

 

									
	MEDIMMUNE VENTURES, INC.	 		 		 	
					
	By:	 	 /s/ Eva Jack
	 		 		 	
	Name:	 	Eva Jack	 		 		 	
	Title:	 	Managing Director	 		 		 	

 Signature Page for the Third Amended and Restated Stockholders Agreement 

 

			
	RHO VENTURES IV, L.P.
		
	By:	 	Rho Management Ventures IV, L.L.C., General Partner
		
	By:	 	 /s/ Jeffrey I. Martin

	Name:	 	Jeffrey I. Martin
	Title:	 	Attorney-In-Fact
	
	RHO VENTURES IV GmbH & CO. BETEILIGUNGS KG
		
	By:	 	Rho Capital Partners Verwaltungs GmbH, General Partner
		
	By:	 	 /s/ Jeffrey I. Martin

	Name:	 	Jeffrey I. Martin
	Title:	 	Attorney-In-Fact
	
	RHO VENTURES IV (QP), L.P.
		
	By:	 	Rho Management Ventures IV, L.L.C., General Partner
		
	By:	 	 /s/ Jeffrey I. Martin

	Name:	 	Jeffrey I. Martin
	Title:	 	Attorney-In-Fact
	
	RHO MANAGEMENT TRUST I
		
	By:	 	Rho Capital Partners, Inc., as Investment Adviser
		
	By:	 	 /s/ Jeffrey I. Martin

	Name:	 	Jeffrey I. Martin
	Title:	 	Attorney-In-Fact

 Signature Page for the Third Amended and Restated Stockholders Agreement 

 

									
	PITANGO VENTURE CAPITAL FUND IV L.P.	 		 		 	
					
	By:	 	Pitango V.C. Fund IV, L.P.,	 		 		 	
		 	its general partner	 		 		 	
					
	By:	 	Pitango G.P. Capital Holdings Ltd,	 		 		 	
		 	its general partner	 		 		 	
					
	By:	 	  
	 		 	By:	 	 /s/ Bruce E. Cocker

	Name:	 	  
	 		 	Name:	 	  

	Title:	 	  
	 		 	Title:	 	  

			
	PITANGO VENTURE CAPITAL FUND PRINCIPALS IV L.P.	 		 	
					
	By:	 	Pitango V.C. Fund IV, L.P.,	 		 		 	
		 	its general partner	 		 		 	
					
	By:	 	Pitango G.P. Capital Holdings Ltd,	 		 		 	
		 	its general partner	 		 		 	
					
	By:	 	  
	 		 	By:	 	 /s/ Bruce E. Cocker

	Name:	 	  
	 		 	Name:	 	  

	Title:	 	  
	 		 	Title:	 	  

 Signature Page for the Third Amended and Restated Stockholders Agreement 

 

									
	BIOMEDICAL SCIENCES INVESTMENT FUND PTE LTD	 		 	
					
	By:	 	 /s/ Chu Swee Yeok
	 		 		 	
	Name:	 	Chu Swee Yeok	 		 		 	
	Title:	 	Director	 		 		 	
				
	DEVON PARK BIOVENTURES, L.P.	 		 		 	
					
	By:	 	Devon Park Associates, its general partner	 		 		 	
					
	By:	 	 /s/ Devang V. Kantesaria
	 		 		 	
	Name:	 	Devang V. Kantesaria	 		 		 	
	Title:	 	General Partner	 		 		 	

 SCHEDULE I 

INOTEK PHARMACEUTICALS CORPORATION 

SCHEDULE OF HOLDERS AND INVESTORS 
  

					
	 Names and Addresses
	  	No. of Shares	 
		  			
		
	HOLDERS	  			
		
	 	  	Shares of Common Stock	 
		
	 *Andrew L. Salzman, M.D.
	  	 	77,076	  
	 *The Andrew L. Salzman GRAT-2004, James Salzman Trustee
	  	 	0	  
	 *The Salzman Family Irrevocable Trust 2004, James Salzman Trustee
	  	 	501	  
	 *Csaba Szabo, M.D., Ph.D.
	  	 	53,699	  
	 *Csaba Szabo 2006 Grantor Retained Annuity Trust, Mark M. Christopher, Trustee
	  	 	0	  
	 *The Szabo Family Irrevocable Trust 2004, Mark M. Christopher, Trustee
	  	 	928	  
	 *Garry J. Southan, Ph.D.
	  	 	29,389	  
		
	 	  	Shares of Series X
Convertible Preferred
Stock	 
		
	 See Attached
	  			
		
	INVESTORS	  			
		
	 	  	Shares of Series AA
Convertible Preferred
Stock	 
		
	 Devon Park Bioventures, L.P.
	  	 	See Attached	  
	 Care Capital Investments II, LP
	  			
	 Care Capital Offshore Investments II, LP
	  			
	 Rho Management Trust I
	  			
	 Rho Ventures IV, L.P.
	  			
	 Rho Ventures IV (QP), L.P.
	  			
	 Rho Ventures IV GmbH & Co. BETEILIGUNGS KG
	  			
	 MedImmune Ventures, Inc.
	  			
	 Pitango Venture Capital Fund IV L.P.
	  			
	 Pitango Venture Capital Fund Principals IV L.P.
	  			
	 Biomedical Sciences Investment Fund Pte Ltd
	  			

 SCHEDULE II 

INOTEK PHARMACEUTICALS CORPORATION 

INSTRUMENT OF ACCESSION 

The undersigned,                     , as
a condition precedent to becoming the owner or holder of record of                     
(            ) shares of the          stock, par value [$0.01/$0.001] per share, of Inotek Pharmaceuticals Corporation, a Delaware
corporation (the “Company”), hereby agrees to become a “Holder” under that certain Third Amended and Restated Stockholders Agreement dated as of June 9, 2010, by and among the Company and certain other
stockholders of the Company. This Instrument of Accession shall take effect and shall become an integral part of, and the undersigned shall become a party to and bound by, said Stockholders Agreement immediately upon execution and delivery to the
Company of this Instrument. 
 IN WITNESS WHEREOF, this INSTRUMENT OF ACCESSION has been duly executed by or on behalf of the undersigned,
as a sealed instrument under the laws of the State of Delaware, as of the date below written. 
  

					
	Signature:
	
	  

	(Print Name)	 	  

					
	
	Address:
	  

	  

		
	Date:	 	  

	
	Accepted:
	
	INOTEK PHARMACEUTICALS CORPORATION

 
					
		
	By:	 	  

		 	Name:	 	Paul G. Howes
		 	Title:	 	President and Chief Executive Officer
		
	Date:	 	  

 SCHEDULE III 

INOTEK PHARMACEUTICALS CORPORATION 

INSTRUMENT OF ACCESSION 

The undersigned,                     , as
a condition precedent to becoming the owner or holder of record of                     
(            ) shares of the Series AA Convertible Preferred Stock, par value $0.001 per share, of Inotek Pharmaceuticals Corporation, a Delaware corporation (the
“Company”), hereby agrees to become an “Investor” under that certain Third Amended and Restated Stockholders Agreement dated as of [            ], 2010, by
and among the Company and certain other stockholders of the Company. This Instrument of Accession shall take effect and shall become an integral part of, and the undersigned shall become a party to and bound by, said Stockholders Agreement
immediately upon execution and delivery to the Company of this Instrument. 
 IN WITNESS WHEREOF, this INSTRUMENT OF ACCESSION has been duly
executed by or on behalf of the undersigned, as a sealed instrument under the laws of the State of Delaware, as of the date below written. 
  

			
	Signature:
	
	  

	(Print Name)	 	  

 
					
	
	Address:
	  

	  

		
	Date:	 	
		 	  

	
	Accepted:
	
	INOTEK PHARMACEUTICALS CORPORATION
		
	By:	 	
		 	  

		 	Name:	 	Paul G. Howes
		 	Title:	 	President and Chief Executive Officer
		
	Date:

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