Document:

EX-4.4

 Exhibit 4.4 

THIS WARRANT AND THE SHARES ISSUABLE HEREUNDER HAVE NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933, AS AMENDED (THE “ACT”), OR ANY APPLICABLE
STATE SECURITIES LAWS, AND, EXCEPT PURSUANT TO THE PROVISIONS OF ARTICLE 5 BELOW, MAY NOT BE OFFERED, SOLD OR OTHERWISE TRANSFERRED WITHOUT AN EFFECTIVE REGISTRATION THEREOF UNDER THE ACT AND ANY APPLICABLE STATE SECURITIES LAWS, OR PURSUANT TO RULE
144 OR AN EXEMPTION FROM THE REGISTRATION REQUIREMENTS OF THE ACT AND ANY APPLICABLE STATE SECURITIES LAWS. 
 WARRANT TO PURCHASE STOCK 

 

			
	Corporation:	  	EVELO THERAPEUTICS, INC., a Delaware corporation
	Number of Shares:	  	25,000 (the “Initial Shares”), plus all Additional Shares (as defined in Section 1.6) which Holder is entitled to purchase pursuant to Section 1.6
	Class of Stock:	  	See Section 1.7
	Warrant Price:	  	See Section 1.7
	Issue Date:	  	November 13, 2015
	Expiration Date:	  	November 13, 2025 (Subject to Section 5.1)

 THIS WARRANT TO PURCHASE STOCK (THIS “WARRANT”) CERTIFIES THAT, for good and valuable consideration,
the receipt of which is hereby acknowledged, COMERICA BANK, a Texas banking association, or its permitted assignee (“Holder”), is entitled to purchase up to the number of fully paid and nonassessable shares of the class of securities (the
“Shares”) of EVELO THERAPEUTICS, INC., a Delaware corporation (the “Company”) at the initial exercise price per Share (the “Warrant Price”), all as set forth above and as adjusted from time to time pursuant to the terms
of this Warrant, subject to the provisions and upon the terms and conditions set forth in this Warrant. This Warrant is issued in connection with that certain Loan and Security Agreement, dated as of November 13, 2015, by and between COMERICA
BANK (“Bank”) and the Company, as amended, modified, supplemented or restated from time to time (the “Loan Agreement”). 

ARTICLE 1 
 EXERCISE

 1.1    Method of Exercise. Holder may exercise this Warrant by a duly executed Notice of Exercise in
substantially the form attached as Appendix I to the principal office of the Company (or such other appropriate location as Holder is so instructed by the Company). Holder shall also deliver to the Company a check, wire transfer (to an account
designated by the Company) or other form of payment acceptable to the Company for the aggregate Warrant Price for the Shares being purchased. 

1.2    [Intentionally Omitted.] 

1.3    Delivery of Certificate and New Warrant. Within 30 days after Holder exercises this Warrant and the Company
receives payment of the aggregate Warrant Price, the Company shall deliver to Holder certificates for the Shares acquired or, if such Shares are not certificated, the Company shall reflect Holder’s ownership of such Shares by book entry in the
Company’s books and records and, if this Warrant has not been fully exercised and has not expired, the Company shall deliver to Holder, a new warrant representing the Shares not so acquired. 

1.4    Replacement of Warrants. In the case of loss, theft or destruction of this Warrant, upon delivery of an
indemnity agreement reasonably satisfactory in form and amount to the Company or, in the case of mutilation, upon surrender and cancellation of this Warrant, the Company at its expense shall execute and deliver, in lieu of this Warrant, a new
warrant of like tenor. 
 1.5    Acquisition of the Company. 

1.5.1    “Acquisition.” For the purpose of this Warrant, “Acquisition” means
(a) any sale, lease, exclusive license, or other disposition of all or substantially all of the assets (including intellectual 

  
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property) of the Company by means of any transaction or series of related transactions, or (b) any reorganization, consolidation, acquisition, merger, sale of the voting securities of the
Company or any other transaction or series of related transactions, in each case where the holders of the Company’s outstanding voting securities before the transaction or series of related transactions beneficially own less than 50% of the
outstanding voting securities of the surviving entity after the transaction or series of related transactions (other than as the result of a bona fide equity financing exclusively for capital raising purposes in which the Company sells and issues
equity securities to venture capital investors (or other investors acceptable to Bank in its sole discretion) and is the surviving and continuing entity in such transaction). 

1.5.2    Treatment of Warrant in the Event of an Acquisition. The Company shall give Holder written
notice at least 20 days prior to the closing of any proposed Acquisition. The Company will use commercially reasonable efforts to cause (i) the acquirer of the Company, (ii) successor or surviving entity or (iii) parent entity in an
Acquisition (the “Acquirer”) to assume this Warrant as a part of the Acquisition. 
 (a)    If
the Acquirer assumes this Warrant, then this Warrant shall be exercisable for the same securities, cash, and property as would be payable for the Shares issuable upon exercise of the unexercised portion of this Warrant as if such Shares were
outstanding on the record date for the Acquisition and subsequent closing of the Acquisition. The Warrant Price shall be adjusted accordingly, and the Warrant Price and number and class of Shares shall continue to be subject to adjustment from time
to time in accordance with the provisions hereof. 
 (b)    If the Acquirer does not assume this Warrant
in connection with the Acquisition, the Company shall give Holder an additional written notice at least ten (10) days prior to the closing of the Acquisition of such fact (the “Non-Assumption
Notice”). In such event, notwithstanding any other provision of this Warrant to the contrary, Holder may immediately exercise this Warrant in the manner specified in this Warrant with such exercise effective immediately prior to closing of the
Acquisition. If the Company has provided a Non-Assumption Notice and Holder elects not to exercise this Warrant, then this Warrant will terminate immediately prior to the later of (i) five (5) business
days after Holder’s receipt of the Non-Assumption Notice, and (ii) the closing of the Acquisition. Notwithstanding any other provision of this Warrant to the contrary if the Acquirer refuses to
assume this Warrant in connection with such Acquisition, other than in connection with an Excluded Acquisition (as defined below), then effective automatically as of the date that is ten (10) days prior to the closing of such Acquisition,
Holder shall have the option to elect to put this Warrant to the Company for cash in an amount, if any, equal to (x) a per Share amount equal to the difference between the Acquisition consideration payable for one Share and the Warrant Price,
times (y) the number of Shares for which this Warrant is then exercisable; provided, that if no cash amount results from the foregoing calculation, then this Warrant will automatically expire immediately prior to the consummation of such
Acquisition. Holder’s exercise of the put right may be conditioned on the closing of the Acquisition. As used herein, an “Excluded Acquisition” means, an Acquisition where the consideration that the holders of the Shares are entitled
to receive on account of the Shares consists entirely of cash and/or shares of common stock that are publicly traded and listed on a national exchange and where the shares, if any, receivable by Holder of this Warrant were Holder to exercise this
Warrant in full immediately prior to the closing of such Acquisition may be publicly re-sold by Holder in their entirety within the three (3) months following such closing pursuant to Rule 144 or an
effective registration statement under the Act. 
 1.6    Number of Shares. This Warrant shall be exercisable for
the Initial Shares, plus, the Additional Shares, as defined below (collectively, the “Shares”), each as may be adjusted from time to time in accordance with the provisions of Section 2 of this Warrant. As used herein, “Additional
Shares” means a number of Shares equal to one and one half percent (1.50%) multiplied by the aggregate principal amount of Growth Capital Advances made by Bank to Borrower in excess of One Million Dollars ($1,000,000) under and as
defined in that certain Loan and Security Agreement between the Company and Bank dated as of the date hereof (the “Loan Agreement”) divided by the Warrant Price (as set forth in Section 1.7 below). 

  
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 1.7    Class of Stock and Warrant Price. The Initial Shares shall be
exercisable for the Company’s Series A Preferred Stock at a price per share equal to Sixty Cents ($0.60) (the “Series A Price”). Any Additional Shares earned prior to the date on which the Company consummates the issuance and sale of
shares of its Series A-2 Preferred Stock (the “A-2 Closing”) shall also be exercisable for the Company’s Series A Preferred Stock at the Series A Price.
From and after the A-2 Closing, any Additional Shares earned shall be exercisable for the Company’s Series A-2 Preferred Stock at a price per share equal to One
Dollar and Twenty Cents ($1.20) (the “Warrant Price”; provided that prior to the A-2 Closing, the “Warrant Price” means the Series A Price. 

ARTICLE 2 
 ADJUSTMENTS
TO THE SHARES 
 2.1    Stock Dividends, Etc. If the Company declares or pays a dividend on the Shares
payable in additional Shares or other securities, then upon exercise of this Warrant, for each Share acquired, Holder shall receive, without cost to Holder, the total number and kind of securities to which Holder would have been entitled had Holder
owned the Shares of record as of the date the dividend occurred; provided, that any such dividend shall only be paid on Additional Shares if the dividend is paid at such time as such Additional Shares have been earned and the Warrant is exercisable
at the time of the dividend for such Additional Shares. 
 2.2    Reclassification, Exchange or Substitution.
Upon any reclassification, exchange, substitution, or other event that results in a change of the number and/or class of the securities issuable upon exercise or conversion of this Warrant, Holder shall be entitled to receive, upon exercise or
conversion of this Warrant, the number and kind of securities and property that Holder would have received for the Shares if this Warrant had been exercised immediately before such reclassification, exchange, substitution, or other event. Such an
event shall include any automatic conversion of the outstanding or issuable securities of the Company of the same class or series as the Shares to common stock pursuant to the terms of the Company’s Certificate of Incorporation upon the closing
of a registered public offering of the Company’s common stock. The Company or its successor shall promptly issue to Holder a new warrant for such new securities or other property. The new warrant shall provide for adjustments which shall be as
nearly equivalent as may be practicable to the adjustments provided for in this Article 2 including, without limitation, adjustments to the Warrant Price, the number of securities or property issuable upon exercise of the new warrant and expiration
date. The provisions of this Section 2.2 shall similarly apply to successive reclassifications, exchanges, substitutions, or other events. 

2.3    Adjustments for Combinations, Etc. If the outstanding Shares are combined or consolidated, by
reclassification, reverse split or otherwise, into a lesser number of Shares, the Warrant Price shall be proportionately increased and the Number of Shares issuable under this Warrant shall be proportionately decreased. If the outstanding Shares are
subdivided, split or multiplied, by reclassification, a stock dividend resulting in the issuance of additional Shares or otherwise, into a greater number of Shares, the Warrant Price shall be proportionately decreased and the Number of Shares
issuable under this Warrant shall be proportionately increased. 
 2.4    Adjustments for Diluting Issuances. In
the event of the issuance by the Company, after the Issue Date of this Warrant, of securities at a price per share less than the Warrant Price that would trigger an anti-dilution adjustment with respect to the Shares in accordance with the
Company’s Certificate of Incorporation and that is not otherwise waived in accordance with the Company’s Certificate of Incorporation (a “Diluting Issuance”), then the number of shares of common stock issuable upon conversion of
the Shares issuable upon exercise of this Warrant shall be adjusted, if applicable, in accordance with those provisions of the Company’s Certificate of Incorporation, a copy of which is attached hereto as Exhibit A, which apply to
Diluting Issuances as if the Shares issuable upon exercise of this Warrant were outstanding on the date of such Diluting Issuance. The provisions set forth for the Shares in the Company’s Certificate of Incorporation relating to the above in
effect as of the Issue Date may not be amended, modified or waived, without the prior written consent of Holder unless such amendment, modification or waiver affects the rights associated with the Shares in the same manner as such amendment,
modification or waiver affects the rights associated with all other shares of the same series and class as the Shares granted to Holder. Under no circumstances shall the aggregate Warrant Price payable by Holder upon exercise of this Warrant
increase as a result of any adjustment arising from a Diluting Issuance. For the avoidance of doubt, there shall be no duplicate antidilution adjustment pursuant to this Section 2.4 and the Company’s Certificate of Incorporation. 

  
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 2.5    No Impairment. The Company shall not, by amendment of its
Certificate of Incorporation or through a reorganization, transfer of assets, consolidation, merger, dissolution, issue, or sale of securities or any other voluntary action, avoid or seek to avoid the observance or performance of any of the terms to
be observed or performed under this Warrant by the Company, but shall at all times in good faith assist in carrying out all the provisions of this Article 2 and in taking all such action as may be necessary or appropriate to protect Holder’s
rights under this Article 2 against impairment. 
 2.6    Certificate as to Adjustments. Upon each adjustment of
the Warrant Price and/or the Number of Shares, the Company at its expense shall promptly compute such adjustment, and furnish Holder with a certificate signed by its Chief Financial Officer setting forth such adjustment and the facts upon which such
adjustment is based. The Company shall, upon written request, furnish Holder a certificate setting forth the Warrant Price and Number of Shares in effect upon the date thereof and the series of adjustments leading to such Warrant Price and Number of
Shares. 
 2.7    Fractional Shares. No fractional Shares shall be issuable upon exercise of this Warrant and the
Number of Shares to be issued shall be rounded down to the nearest whole Share. If a fractional share interest arises upon any exercise of this Warrant, the Company shall eliminate such fractional share interest by paying Holder, at Holder’s
request, an amount computed by multiplying the fractional interest by the fair market value, as determined by the Company’s Board of Directors, of a full Share. 

ARTICLE 3 

REPRESENTATIONS AND COVENANTS OF THE COMPANY 

3.1    Representations and Warranties. The Company hereby represents and warrants to, and agrees with, Holder as
follows as of the Issue Date: 
 3.1.1    The initial Series A Price referenced in Section 1.7 of
this Warrant is not greater than the lowest price per share at which the Company has sold Series A Shares as of the Issue Date. 

3.1.2    All Shares which may be issued upon the exercise of the purchase right represented by this Warrant
in accordance with this Warrant, and all securities, if any, issuable upon conversion of such Shares in accordance with the Company’s Certificate of Incorporation, shall, upon issuance, be duly authorized, validly issued, fully paid and
nonassessable, and free of any liens and encumbrances except for restrictions on transfer provided for herein or under applicable federal and state securities laws. 

3.1.3    The Company’s capitalization table delivered to Holder as of the Issue Date is true and
complete as of the Issue Date. 
 3.2    Notice of Certain Events. If the Company proposes at any time
(a) to declare any dividend or distribution upon its stock, whether in cash, property, stock, or other securities and whether or not a regular cash dividend; (b) to offer for subscription pro rata to the holders of any class or series of
its stock any additional shares of stock of any class or series or other rights (other than pursuant to contractual preemptive or other participation rights held by certain of the Company’s stockholders); (c) to effect any reclassification or
recapitalization of stock; or (d) to merge or consolidate with or into any other corporation (other than mergers or consolidations (i) of a subsidiary of the Company into the Company, or (ii) following which the holders of the
Company’s outstanding voting securities before such merger or consolidation beneficially own at least 50% of the outstanding voting securities of the Company after such merger or consolidation), or sell, lease, exclusively license, or convey
all or substantially all of its assets, or to liquidate, dissolve or wind up, then, in connection with each such event, the Company shall give Holder (1) at least 10 days prior written notice of the date on which a record will be taken for such
dividend, distribution, or subscription rights (and specifying the date on which the holders of stock will be entitled thereto) or for determining rights to vote, if any, in respect of the matters referred to in (a) and (b) above; and
(2) in the case of the matters referred to in (c) and (d) above at least 10 days prior written notice of the date when the same will take place (and specifying the date on which the holders of stock will be entitled to exchange their stock
for securities or other property deliverable upon the occurrence of such event). Upon request, the Company shall provide Holder with such information reasonably necessary for Holder to evaluate its rights as a holder of this Warrant or Shares in the
case of matters referred to (a), (b), (c) and (d) herein above. 

  
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 3.3    Information Rights. So long as Holder holds this Warrant and/or
any of the Shares, the Company shall deliver to Holder, upon Holder’s reasonable request (a) promptly after mailing, copies of all communications, information and/or communiqués to the stockholders of the Company, (b) within
one hundred eighty (180) days after the end of each fiscal year of the Company, the annual audited financial statements of the Company certified by independent public accountants of recognized standing and (c) upon demand by Holder, within
forty-five (45) days after the end of the first three quarters of each fiscal year, the Company’s quarterly, unaudited financial statements; provided, however, the Company shall not be required to provide the foregoing so long as it has
similar reporting obligations under a loan and security agreement with Comerica Bank or following its initial public offering of equity securities pursuant to an effective registration statement under the Act. In addition, and without limiting the
generality of the foregoing, upon demand and prior to an initial public offering of the Company’s common stock and provided Holder holds this warrant and/or any of the Shares, the Company shall deliver to the Holder the financial information
required to be delivered to Major Investors (as defined in that certain Investors Rights Agreement between the Company and its investor(s) dated as of June 29, 2015 (the “Agreement”) a copy of which is attached hereto as Exhibit B),
under Section 3.1(a) to (e) of the Agreement. 
 3.4    Registration Under the Act. The Company agrees
that the Shares or, if the Shares are convertible into common stock of the Company, solely such common stock, shall be deemed “Registrable Securities” or otherwise entitled to “piggy back” registration rights for registrations
initiated by either the Company or a stockholder in accordance with the terms of the Agreement. The Company agrees that no amendments will be made to the Agreement which would have an adverse impact on Holder’s registration rights hereunder,
solely to the extent such adverse impact is disproportionate to the adverse impact of such amendment on all other holders of Registrable Securities (as defined in the Agreement), taken as a whole. By execution of this Warrant, Holder (and any
permitted assignee) shall be deemed to be a party to the Agreement solely for the purpose of the above-mentioned registration rights and, notwithstanding anything to the contrary herein, for the purpose of Section 2.11 (“Market Stand
off” Agreement) of the Agreement. 
 ARTICLE 4 

INVESTMENT REPRESENTATIONS AND COVENANTS 

With respect to the acquisition of this Warrant and any of the Shares issuable upon exercise of this Warrant, Holder hereby represents and
warrants to, and agrees with, the Company as follows: 
 4.1    Purchase Entirely for Own Account. This Warrant
is issued to Holder in reliance upon Holder’s representation to the Company that this Warrant and the Shares issuable upon exercise of this Warrant (and the shares of common stock issuable upon conversion of such Shares) will be acquired for
investment for Holder’s, or its affiliates’, own account, not as a nominee or agent, and not with a view to the resale or distribution of any part thereof other than to an affiliate, and that Holder has no present intention of selling,
granting any participation in, or otherwise distributing the same other than to an affiliate. By executing this Warrant, Holder further represents that Holder does not have any contract, undertaking, agreement or arrangement with any person, other
than an affiliate, to sell, transfer or grant participations to such person or to any third person with respect to this Warrant, the Shares issuable upon exercise of this Warrant or any shares of common stock issuable upon conversion of such Shares.

 4.2    Reliance upon Holder’s Representations. Holder understands that this Warrant and the Shares
issuable upon exercise of this Warrant are not registered under the Act on the ground that the issuance of such securities is exempt from registration under the Act, and that the Company’s reliance on such exemption is predicated on
Holder’s representations set forth herein. 
 4.3    Accredited Investor Status. Holder represents to the
Company that Holder is an Accredited Investor (as defined in the Act). 
 4.4    Restricted Securities. Holder
understands that this Warrant and the Shares issuable upon exercise of this Warrant are “restricted securities” under the federal securities laws inasmuch as they are being acquired from the Company in a transaction not involving a public
offering and that under such federal securities laws and applicable regulations such securities may be resold without registration under the Act only in certain limited circumstances and absent such a circumstance Holder may be required to hold this
Warrant and the Shares to be issued upon any exercise hereof indefinitely. Holder is aware of the provisions of Rule 144 promulgated under the Act. 

  
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 4.5    Disclosure of Information. Holder is aware of the
Company’s business affairs and financial condition and has received or has had full access to all the information it considers necessary or appropriate to make an informed investment decision with respect to the acquisition of this Warrant and
the Shares to be issued upon any exercise hereof. Holder further has had an opportunity to ask questions and receive answers from the Company regarding the terms and conditions of the offering of this Warrant and the Shares to be issued upon any
exercise hereof and to obtain additional information (to the extent the Company possessed such information or could acquire it without unreasonable effort or expense) necessary to verify any information furnished to Holder or to which Holder has
access. 
 4.6    Investment Experience. Holder understands that the purchase of this Warrant and its underlying
securities involves substantial risk. Holder has experience as an investor in securities of companies in the development stage and acknowledges that Holder can bear the economic risk of such Holder’s investment in this Warrant and its
underlying securities and has such knowledge and experience in financial or business matters that Holder is capable of evaluating the merits and risks of its investment in this Warrant and its underlying securities and/or has a preexisting personal
or business relationship with the Company and certain of its officers, directors or controlling persons of a nature and duration that enables Holder to be aware of the character, business acumen and financial circumstances of such persons. 

4.7    No Voting Rights. Holder, as a Holder of this Warrant, will not have any voting rights until the exercise of
this Warrant. 
 ARTICLE 5 

MISCELLANEOUS 

5.1    Term; Exercise Upon Expiration. This Warrant is exercisable in whole or in part, at any time and from time
to time on or before the Expiration Date set forth above; provided, however, that if the Company completes its initial public offering within the one-year period immediately prior to the Expiration
Date, the Expiration Date shall automatically be extended until the earlier of: (a) the first anniversary of the effective date of the Company’s initial public offering, and (b) November 13, 2026. The Company agrees that Holder
may terminate this Warrant, upon notice to the Company, at any time in its sole discretion. 
 5.2    Legends.
This Warrant and the Shares issuable upon exercise of this Warrant (and the securities issuable, directly or indirectly, upon conversion of such Shares, if any) shall be imprinted with a legend in substantially the following form: 

THIS WARRANT AND THE SHARES ISSUABLE HEREUNDER HAVE NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933, AS AMENDED (THE “ACT”), OR
ANY APPLICABLE STATE SECURITIES LAWS, AND, EXCEPT PURSUANT TO THE PROVISIONS OF ARTICLE 5 BELOW, MAY NOT BE OFFERED, SOLD OR OTHERWISE TRANSFERRED WITHOUT AN EFFECTIVE REGISTRATION THEREOF UNDER THE ACT AND ANY APPLICABLE STATE SECURITIES LAWS, OR
PURSUANT TO RULE 144 OR AN EXEMPTION FROM THE REGISTRATION REQUIREMENTS OF THE ACT AND ANY APPLICABLE STATE SECURITIES LAWS. 

5.3    Compliance with Securities Laws on Transfer. This Warrant and the Shares issuable upon exercise of this
Warrant (and the securities issuable, directly or indirectly, upon conversion of such Shares, if any) may not be transferred or assigned in whole or in part without compliance with applicable federal and state securities laws by the transferor and
the transferee. The Company shall not require Bank or a Bank Affiliate (as defined herein) to provide an opinion of counsel or investment representation letter if the transfer is to Bank’s parent company, Comerica Incorporated
(“Comerica”), or any other affiliate of Bank (“Bank Affiliate”). 

  
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 5.4    Transfer Procedure. After receipt of the executed Warrant, Bank
will transfer all of this Warrant to Comerica Ventures Incorporated, a non-banking subsidiary of Comerica and a Bank Affiliate (“Ventures”) and, in connection with such transfer, Ventures shall be
deemed to have restated each of the representations and warranties in Section 4 of this Warrant with respect to itself as of the date thereof. Subject to the provisions of Section 5.3 and Section 2.11 of the Agreement, Holder may
transfer all or part of this Warrant or the Shares issuable upon exercise of this Warrant (or the securities issuable, directly or indirectly, upon conversion of such Shares, if any) by giving the Company notice of the portion of this Warrant being
transferred setting forth the name, address and taxpayer identification number of the transferee and surrendering this Warrant to the Company for reissuance to the transferee(s) (and Holder, if applicable); provided, however, that Holder may
transfer all or part of this Warrant to its affiliates, including, without limitation, Ventures, at any time without notice or the delivery of any other instrument to the Company, and such affiliate shall then be entitled to all the rights and
subject to the obligations of Holder under this Warrant and any related agreements, and the Company shall cooperate fully in ensuring that any stock issued upon exercise of this Warrant is issued in the name of the affiliate that exercises this
Warrant. The terms and conditions of this Warrant shall inure to the benefit of, and be binding upon, the Company and Holders hereof and their respective permitted successors and assigns. 

5.5    Notices. All notices and other communications from the Company to Holder, or vice versa, shall be deemed
delivered and effective when given personally or mailed by first-class registered or certified mail, postage prepaid, or sent via a nationally recognized overnight courier service, fee prepaid, or on the first business day after transmission by
facsimile, at such address or facsimile number as may have been furnished to the Company or Holder, as the case may be, in writing by the Company or such Holder from time to time. Effective upon the receipt of executed Warrant and initial transfer
described in Section 5.4 above, all notices to Holder shall be addressed as follows until the Company receives notice of a change of address in connection with a transfer or otherwise: 

Comerica Ventures Incorporated 

Attn: Warrant Administrator 

1717 Main Street, 5th Floor, MC 6406 

Dallas, Texas 75201 
 Facsimile
No.: XXXXX 
 All notices to the Company shall be addressed as follows, with a copy (which shall not constitute notice) to Latham &
Watkins LLP, John Hancock Tower, 200 Clarendon Street, Boston, MA 02116, Attention: Peter N. Handrinos: 
 EVELO THERAPEUTICS, INC. 

790 Memorial Drive 
 Cambridge,
MA 02139 
 Facsimile No.: (    )
                     

5.6    Amendments; Waiver. This Warrant and any term hereof may be amended, changed, waived, discharged or
terminated only by an instrument in writing signed by the party against which enforcement of such amendment, change, waiver, discharge or termination is sought. 

5.7    Attorneys’ Fees. In the event of any dispute between the parties concerning the terms and provisions of
this Warrant, the party prevailing in such dispute shall be entitled to collect from the other party all costs incurred in such dispute, including reasonable attorneys’ fees. 

5.8    Governing Law. This Warrant shall be governed by and construed in accordance with the laws of the State of
Delaware, without giving effect to its principles regarding conflicts of law that would result in the application of the laws of any other jurisdiction. 

5.9    Confidentiality. The Company hereby agrees to keep the terms and conditions of this Warrant confidential
provided that the Company may provide copies of this Warrant in connection with third party due diligence in equity financing and acquisition transactions provided that the recipient thereof agrees to keep the terms hereof confidential.
Notwithstanding the foregoing confidentiality obligation, the Company may disclose 

  
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information relating to this Warrant in a registration statement filed with the Securities and Exchange Commission or as required by law, rule, regulation, court order or other legal authority,
provided that (i) the Company has given Holder at least ten (10) days’ notice of such required disclosure, and (ii) the Company only discloses information that is required, (as determined in good faith by the Company and its
counsel) to be disclosed. 
 5.10    Counterparts. This Warrant may be executed in counterparts, all of which
taken together shall constitute one and the same instrument. 
 [Balance of Page Intentionally Left Blank] 

  
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 IN WITNESS WHEREOF, each of the parties have caused this Warrant to be duly executed by its duly
authorized officers as of the first date written above. 
  

			
	EVELO THERAPEUTICS, INC.
		
	By:	 	 /s/ Balkrishan Gill

	Name:	 	Balkrishan Gill
	Title:	 	Chief Executive Officer and President
	
	COMERICA BANK
		
	By:	 	 /s/ Jason Pan

	Name:	 	Jason Pan
	Title:	 	Vice President

 [Signature Page to Warrant to Purchase Stock] 

  
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 APPENDIX I 

NOTICE OF EXERCISE 

1.    The undersigned hereby elects to purchase          shares of the [Series A
Preferred Stock/Series A-2 Preferred Stock] stock of EVELO THERAPEUTICS, INC. pursuant to the terms of the attached Warrant, and tenders herewith payment of the purchase price of such shares in full.

 2.    Please issue a certificate or certificates representing said shares in the name of the undersigned or in such
other name as is specified below: 
 Comerica Ventures Incorporated 

Attn: Warrant Administrator 
 1717
Main Street, 5th Floor, MC 6406 
 Dallas, Texas 75201 

Facsimile No. XXXXX 

3.    The undersigned represents it is acquiring the shares solely for its own account and not as a nominee for any other
party and not with a view toward the resale or distribution thereof except in compliance with applicable securities laws, and confirms the representations and warranties set forth in Article 4 of the attached Warrant. 

 

	
	COMERICA VENTURES INCORPORATED or Assignee
	
	  

	(Signature)
	
	  

	(Name and Title)
	
	  

	(Date)

  
 Appendix I 

Page 1 

 Exhibit A 

Anti-Dilution Provisions 
 Second Amended and
Restated Certificate of Incorporation (including all amendments thereto) – ATTACHED HERETO 

  
 Exhibit A 

Page 1 

 Exhibit B 

Investors’ Rights Agreement (including all amendments thereto) – ATTACHED HERETO 

  
 Exhibit B 

Page 1EX-4.5

 Exhibit 4.5 

THIS AMENDED AND RESTATED WARRANT AND THE SHARES ISSUABLE HEREUNDER HAVE NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933, AS AMENDED, AND MAY NOT BE
SOLD, PLEDGED OR OTHERWISE TRANSFERRED EXCEPT IN ACCORDANCE WITH APPLICABLE LAW. 
 AMENDED AND RESTATED WARRANT TO PURCHASE STOCK

  

			
	 Corporation:
	  	EVELO BIOSCIENCES, INC.
	 Number of Shares:
	  	62,497.5
	 Class of Stock:
	  	Series A-1 Preferred
	 Initial Exercise Price:
	  	$0.60024 per share
	 Issue Date:
	  	August 15, 2016
	 Expiration Date:
	  	January 28, 2026

 THIS AMENDED AND RESTATED
WARRANT CERTIFIES THAT, for good and valuable consideration, the receipt of which is hereby acknowledged, PACIFIC WESTERN BANK or its
permitted assignee or transferee (“Holder” ) is entitled to purchase the number of fully paid and nonassessable shares of the class of securities (the “Shares” ) of
EVELO BIOSCIENCES, INC. (the “Company” ) at the initial exercise price per Share (the “Warrant Price” ) all as set forth above and as adjusted
pursuant to Article 2 of this warrant, subject to the provisions and upon the terms and conditions set forth in this warrant. This Warrant amends and restates, and is issued in replacement of, the Warrant to Purchase Stock issued by
EPIVA BIOSCIENCES, INC. (“Epiva” ) to the Holder on January 28, 2016 originally exercisable for 75,000 shares of Series A Preferred Stock of Epiva, which warrant is
cancelled, and of no further force or effect. 
 ARTICLE 1 

EXERCISE 

1.1    Method of Exercise. Holder may exercise this warrant by delivering this warrant and a duly executed Notice
of Exercise in substantially the form attached as Appendix 1 to the principal office of the Company. Unless Holder is exercising the conversion right set forth in Section 1 .2, Holder shall also deliver to the Company a check for the aggregate
Warrant Price for the Shares being purchased. 
 1.2    Conversion Right. In lieu of exercising this warrant as
specified in Section 1.1, Holder may from time to time convert this warrant, in whole or in part, into a number of Shares determined by dividing (a) the aggregate fair market value of the Shares or other securities otherwise issuable upon
exercise of this warrant minus the aggregate Warrant Price of such Shares by (b) the fair market value of one Share. The fair market value of the Shares shall be determined pursuant to Section 1 .3. In connection with each such conversion,
or other exercise of this Warrant pursuant to Section 1.1, Holder shall be deemed to have restated each of the representations and warranties in Section 3.5 of this warrant as of the date thereof. 

1.3     Fair Market Value. If the Shares are traded regularly in a public market, the fair market value of the
Shares shall be the closing price of the Shares (or the closing price of the Company’s stock into which the Shares are convertible) reported for the business day 

 
immediately before Holder delivers its Notice of Exercise to the Company. If the Shares are not regularly traded in a public market, the Board of Directors of the Company shall determine fair
market value in its reasonable good faith judgment. 
 1.4    Delivery of Certificate and New Warrant.
Promptly after Holder exercises or converts this warrant, the Company shall deliver to Holder certificates for the Shares acquired and, if this warrant has not been fully exercised or converted and has not expired, a new warrant representing the
Shares not so acquired. 
 1.5    Replacement of Warrants. On receipt of evidence reasonably
satisfactory to the Company of the loss, theft, destruction or mutilation of this warrant and, in the case of loss, theft or destruction, on delivery of an indemnity agreement reasonably satisfactory in form and amount to the Company or, in the case
of mutilation, on surrender and cancellation of this warrant, the Company at its expense shall execute and deliver, in lieu of this warrant, a new warrant of like tenor. 

1.6    Repurchase on Sale, Merger, or Consolidation of the Company. 

1.6.1 “Acquisition.” For the purpose of this warrant, “Acquisition” means (a) any
sale, exclusive license, or other disposition of all or substantially all of the assets (including intellectual property) of the Company, or (b) any reorganization, consolidation, merger or sale of the voting securities of the Company (other
than a merger or consolidation effective exclusively to change the Company’s domicile) or other transaction, in each case, where the holders of the Company’s securities before the transaction beneficially own less than 50% of the
outstanding voting securities of the surviving entity after the transaction. 
 1.6.2 Exercise Upon Acquisition. Upon the closing of
any Acquisition in which the consideration to be received by the Company’s stockholders consists of cash, marketable securities, or a combination of both cash and marketable securities, this warrant shall be deemed to have been automatically
converted pursuant to Section 1.2 immediately prior to such Acquisition, and thereafter Holder shall participate in the Acquisition on the same terms as other holders of the same class of securities of the Company, provided, however, that if
the fair market value of the Shares, as determined pursuant to Section 1.3, in connection with such Acquisition is less than the aggregate Warrant Price, then this warrant shall terminate without exercise or conversion immediately prior, and
subject, to the closing of such Acquisition. 
 1.6.3 Assumption of Warrant. Upon the closing of any Acquisition not
referred to in Section 1.6.2, the successor entity shall assume the obligations of this warrant, and this warrant shall thereafter be exercisable for the same securities and/or other property as would have been paid for the Shares issuable upon
exercise of the unexercised portion of this warrant as if such Shares were outstanding on and as of the closing of such Acquisition, subject to further adjustment from time to time in accordance with the provisions of this warrant. 

  
 2. 

 ARTICLE 2 

ADJUSTMENTS TO THE SHARES 

2.1    Stock Dividends, Splits, Etc. If the Company declares or pays a dividend
on its common stock payable in common stock, or other securities, or subdivides the outstanding common stock into a greater amount of common stock, then upon exercise of this warrant, for each Share acquired, Holder shall receive, without cost to
Holder, the total number and kind of securities to which Holder would have been entitled had Holder owned the Shares of record as of the date the dividend or subdivision occurred. 

2.2    Reclassification, Exchange or Substitution.
Upon any reclassification, exchange, substitution, or other event that results in a change of the number and/or class of the securities issuable upon exercise or conversion of this warrant, Holder shall be entitled to receive, upon
exercise or conversion of this warrant, the number and kind of securities and property that Holder would have received for the Shares if this warrant had been exercised immediately before such reclassification, exchange, substitution, or other
event. Such an event shall include any automatic conversion of the outstanding or issuable securities of the Company of the same class or series as the Shares to common stock pursuant to the terms of the Company’s Amended and Restated
Certificate of Incorporation upon the closing of a registered public offering of the Company’s common stock. The Company or its successor shall promptly issue to Holder a new warrant for such new securities or other property. The new warrant
shall provide for adjustments which shall be as nearly equivalent as may be practicable to the adjustments provided for in this Article 2 including, without limitation, adjustments to the Warrant Price and to the number of securities or property
issuable upon exercise of the new warrant. The provisions of this Section 2.2 shall similarly apply to successive reclassifications, exchanges, substitutions, or other events. 

2.3    Adjustments for Combinations, Etc. If the outstanding Shares are combined
or consolidated, by reclassification or otherwise, into a lesser number of shares, the Warrant Price shall be proportionately increased. If the outstanding Shares are combined or consolidated, by reclassification or otherwise, into a greater number
of shares, the Warrant Price shall be proportionately decreased. 
 2.4    Adjustments for Diluting
Issuances. Without duplication of any adjustment otherwise provided for in this Section 2, the number of shares of common stock issuable upon conversion of the Shares shall be subject to anti-dilution adjustment from time to time in
accordance with the manner set forth in the Company’s Certificate of Incorporation as if the Shares were issued and outstanding on and as of the date of any such required adjustment. 

2.5    Certificate as to Adjustments. Upon each adjustment of the Warrant Price,
the Company at its expense shall promptly compute such adjustment, and furnish Holder with a certificate of its Chief Financial Officer setting forth such adjustment and the facts upon which such adjustment is based. The Company shall, upon written
request, furnish Holder a certificate setting forth the Warrant Price in effect upon the date thereof and the series of adjustments leading to such Warrant Price. 

2.6    Fractional Shares. No fractional Shares shall be issuable upon exercise or conversion of the
Warrant and the Number of Shares to be issued shall be rounded down to the nearest whole Share. If a fractional share interest arises upon any exercise or conversion of the Warrant, the Company shall eliminate such fractional share interest by
paying Holder an amount computed by multiplying the fractional interest by the fair market value of a full Share. 

  
 3. 

 ARTICLE 3 

REPRESENTATIONS AND COVENANTS OF THE COMPANY AND OF THE HOLDER 

3.1    Representations and Warranties of the Company. The Company hereby represents and warrants to
the Holder as follows: 
 (a)    The initial Warrant Price referenced on the
first page of this warrant is the price per share paid by investors in the Company’s most recent preferred stock financing. 

(b)    All Shares which may be issued upon the exercise of the purchase right
represented by this Warrant in accordance with this Warrant, and all securities, if any, issuable upon conversion of the Shares in accordance with the Company’s Amended and Restated Certificate of Incorporation, shall, upon issuance, be duly
authorized, validly issued, fully paid and nonassessable, and free of any liens and encumbrances except for restrictions on transfer provided for herein or under applicable federal and state securities laws. 

(c)    The Company’s capitalization table attached to this warrant is true and complete as of the Issue Date.

 3.2    Notice of Certain Events. The Company shall provide Holder with not less than 7 days prior
written notice of, including a description of the material facts surrounding, any of the following events: (a) declaration of any dividend or distribution upon its common stock, whether in cash, property, stock, or other securities and whether
or not a regular cash dividend; (b) offering for subscription pro rata to the holders of any class or series of its stock any additional shares of stock of any class or series or other rights; (c) effecting any reclassification or
recapitalization of common stock; or (d) the merger or consolidation with or into any other corporation, or sale, lease, license, or conveyance of all or substantially all of its assets, or liquidation, dissolution or winding up. 

3.3    Information Rights. Prior to an initial public offering of
the Company’s common stock and provided Holder holds this warrant and/or any of the Shares, the Company shall deliver to the Holder the financial information required to be delivered to Major Investors (as defined in the IRA) under
Section 3.l(a) and 3.l(b) pursuant to that certain Investors Rights Agreement dated as of June 16, 2016 by and among the Company and the investors named therein (the “IRA”). 

3.4    Registration Under Securities Act of 1933, as amended. The Company agrees
that the Shares or, if the Shares are convertible into common stock of the Company, such common stock, shall be “Registrable Securities”, and Holder shall be a “Holder” under the IRA. 

3.5    Holder Investment Representations. Holder makes the representations to
the Company set forth in Exhibit A hereof in connection with the issuance of this warrant and the Shares (collectively, the “Securities”). 

  
 4. 

 3.6    Market Stand Off. Holder
agrees that it shall be subject to the Market Standoff provisions in Section 2.11 of the IRA. 

3.7    Company Agreements. If upon exercise
of this warrant (other than in connection with an Acquisition or an initial public offering of the Company’s common stock) Holder continues to hold the Shares, upon the request of the Company, Holder shall execute a counterpart signature page
to the investor and stockholder agreements governing the rights and obligations in respect to the Company’s Series A-1 Preferred Stock. 

ARTICLE 4 

MISCELLANEOUS 

4.1    Term: Exercise Upon Expiration. This warrant is exercisable in whole or
in part, at any time and from time to time on or before the Expiration Date set forth above. If this warrant has not been exercised prior to the Expiration Date, this warrant shall be deemed to have been automatically exercised on the Expiration
Date by “cashless” conversion pursuant to Section 1.2. 

4.2    Legends. This warrant and the Shares (and the securities issuable,
directly or indirectly, upon conversion of the Shares, if any) shall be imprinted with a legend in substantially the following form: 
 THIS SECURITY HAS
NOT BEEN REGISTERED UNDER THE SECURlTIES ACT OF 1933, AS AMENDED, AND MAY NOT BE SOLD, PLEDGED OR OTHERWISE TRANSFERRED EXCEPT IN ACCORDANCE WITH APPLICABLE LAW. 

4.3    Compliance with Securities Laws on Transfer. This warrant and the
Shares issuable upon exercise of this warrant (and the securities issuable, directly or indirectly, upon conversion of the Shares, if any) may not be transferred or assigned in whole or in part without compliance with applicable federal and state
securities laws by the transferor and the transferee. The Company shall not require Holder to provide an opinion of counsel if the transfer is to an affiliate of Holder or if there is no material question as to the availability of current
information as referenced in Rule 144(c), Holder represents that it has complied with Rule 144 (d) and (e) in reasonable detail, the selling broker represents that it has complied with Rule 144(f), and the Company is provided with a copy of
Holder’s notice of proposed sale. 
 4.4    Transfer Procedure.
Subject to the provisions of Section 4.3, Holder may transfer all or part of this warrant or the Shares issuable upon exercise of this warrant (or the securities issuable, directly or indirectly, upon conversion of the Shares, if any) by
giving the Company notice of the portion of the warrant being transferred setting forth the name, address and taxpayer identification number of the transferee and surrendering this warrant to the Company for reissuance to the transferee(s) (and
Holder, if applicable). No surrender or reissuance shall be required for a transfer to an affiliate of Holder. 

4.5    Notices. All notices and other communications from the Company to the
Holder, or vice versa, shall be deemed delivered and effective when given personally or mailed by first -class registered or certified mail, postage prepaid, at such address as may have been furnished to

  
 5. 

 
the Company or the Holder, as the case may be, in writing by the Company or such Holder from time to time. All notices to the Holder shall be addressed as follows: 

Pacific Western Bank 
 Attn:
Warrant Administrator 
 406 Blackwell Street, Suite 240 

Durham, NC 27701 
 All notices to
the Company shall be addressed as follows: 
 EVELO BIOSCIENCES, INC. 

620 Memorial Drive, Suite 208 

Cambridge, MA 02139 
 Attn: Chief
Executive Officer 
 FAX:
                                         

4.6     Amendments. This warrant and any term hereof may be changed, waived, discharged or terminated
only by an instrument in writing signed by the party against which enforcement of such change, waiver, discharge or termination is sought. 

4.7     Attorneys’ Fees. In the event of any dispute between the parties concerning the terms
and provisions of this warrant, the party prevailing in such dispute shall be entitled to collect from the other party all costs incurred in such dispute, including reasonable attorneys’ fees. 

4.8     Governing Law. This warrant shall be governed by and construed in
accordance with the laws of the State of Delaware, without giving effect to its principles regarding conflicts of law that would result in the application of the laws of any other jurisdiction. 

[Signature Page Follows] 

  
 6. 

 IN WITNESS WHEREOF, the undersigned has executed this Amended and Restated Warrant to Purchase Stock as of the
date set forth above. 
  

			
	EVELO BIOSCIENCES, INC.
		
	BY:	 	 /s/ Jennifer Glennon

	Name:	 	Jennifer Glennon
	Name:	 	Assistant Secretary

  

			
	Acknowledged and agreed:
	
	PACIFIC WESTERN BANK

			
		
	By:	 	  

	Name:	 	  

	Title:	 	  

 [Signature Page to Warrant to Purchase Stock] 

 IN WITNESS WHEREOF, the undersigned has executed this Amended and Restated Warrant to Purchase Stock as of the
date set forth above. 
  

			
	EVELO BIOSCIENCES, INC.
		
	By:	 	
                     

	Name:	 	  

	Title:	 	  

  

			
	Acknowledged and agreed:
	
	PACIFIC WESTERN BANK
		
	By:	 	 /s/ John Orlando

	Name:	 	John Orlando
	Title:	 	Vice President

 [Signature Page to Warrant to Purchase Stock] 

 APPENDIX 1 

NOTICE OF EXERCISE 
 1.
The undersigned hereby elects to                      purchase shares of the
                     stock of EVELO BIOSCIENCES, INC. pursuant to the terms of the attached warrant, and tenders herewith payment of the
purchase price of such shares in full. 
 1.     The undersigned hereby elects to convert the attached warrant
into shares in the manner specified in the warrant. This conversion is exercised with respect to                      of the shares covered by the
warrant. 
 [Strike paragraph that does not apply.] 

2.     Please issue a certificate or certificates representing said shares in
the name of the undersigned or in such other name as is specified below: 
  

	
	  

	(Holder’s Name)
	
	  

	  

	(Address)

 3.     The undersigned represents it is
acquiring the shares solely for its own account and not as a nominee for any other party and not with a view toward the resale or distribution thereof except in compliance with applicable securities laws. 

 

	
	PACIFIC WESTERN BANK or Registered Assignee
	
	  

	(Signature)
	
	  

	(Date)

 EXHIBIT A 

INVESTMENT REPRESENTATIONS 

(a)     Holder is aware of the Company’s business affairs and financial condition, and has acquired sufficient information about the
Company to reach an informed and knowledgeable decision to acquire the Securities. Holder is purchasing the Securities for its own account for investment purposes only, not as a nominee or agent, and not with a view towards, or for resale in
connection with, any “distribution” thereof for purposes of the Securities Act of 1933, as amended (the “Securities Act”). Holder has such knowledge and experience in financial business matters and Holder is capable of evaluating
the merits and risks of the purchase of the Securities and of protecting its interests in connection therewith. 
 (b)     Holder
understands that the Securities have not been registered under the Securities Act in reliance upon a specific exemption therefrom, which exemption depends upon, among other things, the bona fide nature of Holder’s in vestment intent as
expressed herein. 
 (c)     Holder further understands that the Securities must be held indefinitely, and Holder must therefore bear
the economic risk therewith, unless the Securities are subsequently registered under the Securities Act or unless an exemption from registration is otherwise available. In addition, Holder understands that the certificate evidencing the Securities
will be imprinted with a legend which prohibits the transfer of the Securities unless they are registered or such registration is not required. 

(d)     Holder is familiar with the provisions of Rule 144, promulgated pursuant to the Securities Act, which, in substance, permits
limited public resale of “restricted securities” acquired, directly or indirectly, from the issuer thereof, in a non-public offering subject to the satisfaction of certain conditions. 

(e)     The Securities may be resold in certain limited circumstances subject to the provisions of Rule 144, which requires, among
other things, the existence of a public market for the Securities, the availability of certain current public information about the Company, the resale occurring not less than one year after a party has purchased and paid for the security to be
sold, the sales being effected through a “broker’s transaction” or in transactions directly with a “market maker” and the number of securities being sold during any three-month period not exceeding specified limitations.

 (f)     Holder further understands that in the event that all of the applicable requirements of Rule 144 are not satisfied,
registration under the Securities Act, compliance with Regulation A, or some other registration exemption will be required. 
 (g)    
Holder is an “accredited investor” as defined in Rule 501(a) of Regulation D promulgated under the Securities Act. 

  
 2.

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