Document:

Warrant issued by the Registrant to Cowen Healthcare Royalty Partners II, L.P.

 Exhibit 4.12 
 WARRANT 
 ZOGENIX, INC. 

WARRANTS FOR THE PURCHASE OF SHARES OF COMMON STOCK 

 

			
	 No. W-2011-1
	 	225,000 Shares

THIS CERTIFIES that, for value received, Zogenix, Inc., a Delaware corporation (the “Company”), upon the surrender of
this Warrant to the Company at the address specified herein, at any time during the Exercise Period (as defined below) will upon receipt of the Exercise Price (as defined below), sell and deliver to Cowen Healthcare Royalty Partners II, L.P. (the
“Holder”) up to the number of duly authorized, validly issued and fully paid and nonassessable shares of common stock of the Company, par value $0.001 per share, set forth above. The term “Common Stock” shall mean the
aforementioned common stock of the Company. The “Exercise Period” shall begin on July 18, 2011 (the “Issue Date”) and shall end on July 18, 2021, unless earlier terminated or exercised pursuant to the terms
hereof. During the Exercise Period, the Holder may purchase such number of shares of Common Stock at a purchase price per share equal to $9.00 as appropriately adjusted pursuant to Section G hereof (the “Exercise Price”).

 The number of shares of Common Stock to be received upon the exercise of this Warrant and the price to be paid for a share of
Common Stock are subject to adjustment from time to time as hereinafter set forth. The shares of Common Stock deliverable upon such exercise, as adjusted from time to time, are hereinafter sometimes referred to as “Warrant Shares.”

 Section A. Exercise of Warrant 

1. Method of Exercise. This Warrant may be exercised in whole or in part, at any time or from time to time, during
the Exercise Period by presentation and surrender hereof to the Company at 12671 High Bluff Drive, Suite 200, San Diego, California 92130 (or at such other address as the Company or its agent may hereafter designate in writing to the Holder), with
the Notice of Exercise Form contained herein duly executed and accompanied by a wire transfer of immediately available funds, cash or a certified or official bank check drawn to the order of “Zogenix, Inc.” in the amount of the Exercise
Price multiplied by the number of Warrant Shares specified in such form. If this Warrant should be exercised in part only, the Company shall, upon surrender of this Warrant, promptly execute and deliver a new Warrant evidencing the rights of the
Holder thereof to purchase the balance of the Warrant Shares purchasable hereunder. Upon receipt by the Company during the Exercise Period of this Warrant and such Notice of Exercise Form, in proper form for exercise, together with proper payment of
the Exercise Price, at such office, the Holder shall be deemed to be the holder of record of the number of Warrant Shares specified in such form; provided, however, that if the date of such receipt by the Company or its agent is a date
on which the stock transfer books of the Company are closed, such person shall be deemed to have become the record holder of such shares on, and such certificate shall be dated, the next succeeding business day on which the stock transfer books of
the Company are open. The Company shall pay any and all documentary, stamp or similar issue or transfer taxes payable in respect of the issue or delivery of such Warrant Shares. Any new or substitute Warrant issued under this Section A or any other
provision of this Warrant shall be dated the date of this Warrant. Upon exercise of this Warrant, the Company or its warrant agent shall, within three (3) business days, cause to be issued and shall promptly deliver upon written order of the
Holder of this Warrant, and in such name or names as such Holder may designate, a certificate or certificates for the Warrant Shares, which Warrant Shares shall be issued unlegended and free of

 
any resale restrictions, except as otherwise provided herein or in the Stock and Warrant Purchase Agreement dated July 18, 2011, as amended from time to time (the “Purchase
Agreement”). If in any case the Company shall fail to issue and deliver the shares of Common Stock to Holder upon Holder’s exercise of this Warrant within three (3) business days after exercise, in addition to any other
liabilities the Company may have hereunder and under applicable law, the Company shall pay or reimburse Holder on demand for all out-of-pocket expenses, including, without limitation, reasonable fees and expenses of legal counsel, incurred by Holder
as a result of such failure. 
 2. Cashless Exercise. In lieu of exercising this Warrant as specified in
Section A.1., the Holder may from time to time convert this Warrant, in whole or in part, by surrender of this Warrant (with a duly executed Notice of Exercise in the form attached hereto) at the principal office of Company, in which event Company
shall issue to Holder the number of Warrant Shares computed using the following formula: 
 X
        =         Y (A-B) 

                    
          A 
 Where: 

X = the number of Warrant Shares to be issued to Holder. 

Y = the number of Warrant Shares purchasable under this Warrant (at the date of such calculation). 

A = the fair market value of one share of Common Stock. 

B = Exercise Price (as adjusted to the date of such calculation). 

The fair market value of the Warrant Shares shall be determined pursuant to Section A.3. 

3. Fair Market Value. If the Company’s Common Stock is traded in a public market, the fair market value of a
Warrant Share shall be the average of the closing prices for a share of Common Stock reported for the ten (10) business days immediately before Holder delivers this Warrant together with its Notice of Exercise Form to the Company. If the
Company’s Common Stock is not traded in a public market, the Board of Directors of the Company shall determine fair market value in its reasonable good faith judgment. 

4. Treatment of Warrant Upon Acquisition of Company. 

4.1 “Acquisition”. For the purpose of this Warrant, “Acquisition” means any sale,
exclusive license, or any other transfer or disposition of all or substantially all of the assets of the Company, or any reorganization, consolidation, merger or sale of outstanding capital stock of the Company where the holders of the
Company’s securities before the transaction beneficially own less than a majority of the outstanding voting securities of the surviving entity after the transaction. 

4.2 Treatment of Warrant at Acquisition. 

(A) The Company shall provide Holder with at least ten (10) days’ prior written notice of an Acquisition in
which the sole consideration is cash, and either (a) Holder shall exercise its conversion or purchase right under this Warrant and such exercise will be deemed effective immediately prior to the consummation of such Acquisition or (b) if
Holder elects not to 

  
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exercise the Warrant, this Warrant will expire upon the consummation of such Acquisition. The Company shall provide, at the time of delivery of notice of such Acquisition, such reasonable
information as the Holder may request in connection with such contemplated Acquisition giving rise to such notice. 
 (B) Upon the closing of any Acquisition other than as particularly described in subsection (A) above, as a condition to the closing of such Acquisition, the surviving or successor entity shall assume
the obligations of this Warrant, and this Warrant shall be exercisable for the same securities, cash, and property as would be payable for the Warrant Shares issuable upon exercise of the unexercised portion of this Warrant as if such Warrant Shares
were outstanding on the record date for the Acquisition and subsequent closing. The Exercise Price and/or number of Warrant Shares shall be adjusted accordingly. 

(C) Notwithstanding the foregoing provisions of Section A.4.2(B), in the event of an Acquisition in which all of the
following requirements are met, this Warrant, to the extent not exercised or converted on or prior to the closing of such Acquisition, shall terminate and be of no further force or effect as of immediately following such closing: (i) the
acquirer is subject to the reporting requirements of Section 13 or Section 15(d) of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), (ii) the class and series of shares or other security of the
acquirer that would be received by Holder in connection with such Acquisition were Holder to exercise or convert this Warrant on or prior to the closing thereof is listed for trading on a national securities exchange or approved for quotation on an
automated inter-dealer quotation system, and (iii) Holder would not be contractually restricted from publicly re-selling within three (3) months following the closing of such Acquisition, nor restricted under applicable securities laws
from publicly re-selling within six (6) months following the closing of such Acquisition (assuming for such determination that Holder would convert this Warrant pursuant to Section A.2 above), all of the acquirer shares and/or other securities
that would be received by Holder in such Acquisition were Holder to exercise or convert this Warrant in full on or prior to the closing thereof. Notwithstanding anything herein to the contrary, the Holder shall not have the right to exercise any
portion of this Warrant, pursuant to Section A or otherwise, to the extent that after giving effect to such issuance after exercise, the Holder (together with the Holder’s affiliates), as set forth on the applicable Notice of Exercise, would
beneficially own in excess of 9.99% of the number of shares of the Common Stock outstanding immediately after giving effect to such issuance. The Holder may void the 9.99% limitation upon seventy five (75) days prior notice to the Company. For
purposes of the foregoing sentence, the number of shares of Common Stock beneficially owned by the Holder and its affiliates shall include the number of shares of Common Stock issuable upon exercise of this Warrant with respect to which the
determination of such sentence is being made, but shall exclude the number of shares of Common Stock which would be issuable upon (A) exercise of the remaining, nonexercised portion of this Warrant beneficially owned by the Holder or any of its
affiliates and (B) exercise or conversion of the unexercised or nonconverted portion of any other securities of the Company (including, without limitation, any other Warrants) subject to a limitation on conversion or exercise analogous to the
limitation contained herein beneficially owned by the Holder or any of its affiliates. Except as set forth in the preceding sentence, for purposes of this provision, beneficial ownership shall be calculated in accordance with Section 13(d) of
the Exchange Act. To the extent that the limitation contained in this provision applies, the determination of whether this Warrant is exercisable (in relation to other securities owned by the Holder) and of which a portion of this Warrant is
exercisable shall be in the sole discretion of such Holder, and the submission of a Notice of Exercise shall be deemed to be such Holder’s determination of whether this Warrant is exercisable (in relation to other securities owned by such
Holder) and of which portion of this Warrant is exercisable, in each case subject to such aggregate percentage limitation, and the Company shall have no 

  
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obligation to verify or confirm the accuracy of such determination. For purposes of this provision, in determining the number of outstanding shares of Common Stock, the Holder may rely on the
number of outstanding shares of Common Stock as reflected in (x) the Company’s most recent Form 10-Q or Form 10-K, as the case may be, (y) a more recent public announcement by the Company or (z) any other notice by the
Company or the Company’s Transfer Agent setting forth the number of shares of Common Stock outstanding. In any case, the number of outstanding shares of Common Stock shall be determined after giving effect to the conversion or exercise of
securities of the Company, including this Warrant, by the Holder or its affiliates since the date as of which such number of outstanding shares of Common Stock was reported. 
 Section B. Warrant Register. This Warrant will be registered in a register (the “Warrant Register”) to be maintained by the Company or its agent at its principal
office in the name of the record holder to whom it has been distributed. The Company may deem and treat the registered holder of this Warrant as the absolute owner thereof (notwithstanding any notation of ownership or other writing hereon made by
anyone), for the purpose of any exercise thereof or any distribution to the holder thereof and for all other purposes, and the Company shall not be affected by any notice to the contrary. 

Section C. Reservation of Shares. The Company hereby agrees that at all times there shall be reserved
for issuance and delivery upon exercise of this Warrant all shares of its Common Stock or other shares of capital stock of the Company from time to time issuable upon exercise of this Warrant. All such shares shall be duly authorized and, when
issued upon such exercise in accordance with the terms of this Warrant, shall be validly issued, fully paid and nonassessable, free and clear of all liens, security interests, charges and other encumbrances or restrictions on sale and free and clear
of all preemptive rights. 
 Section D. Transfer of Warrant. Subject to compliance with applicable federal and
state securities laws and the applicable restrictions on transfer and/or assignment of the Purchase Agreement, this Warrant and all rights hereunder are transferable, in whole or in part, without charge to the Holder hereof (except for transfer
taxes), upon surrender of this Warrant properly endorsed. 
 Section E. Lost, Mutilated or Missing Warrant. Upon
receipt by the Company of evidence reasonably satisfactory to it of the loss, theft, destruction or mutilation of this Warrant, and (in the case of loss, theft or destruction) of reasonably satisfactory indemnification, and upon surrender and
cancellation of this Warrant, if mutilated, the Company, at its expense, shall execute and deliver a new Warrant of like tenor and date. 
 Section F. Rights of the Holder. Subject to applicable law, the Holder shall not, by virtue hereof, be entitled to any rights or subject to any obligation or liability of a
shareholder in the Company, either at law or equity, and the rights of the Holder are limited to those expressed in this Warrant. 
 Section G. Adjustments. The Exercise Price and the number of shares purchasable hereunder are subject to adjustment from time to time as follows: 

1. Stock Dividend, Split or Subdivision of Shares. If the number of shares of Common Stock outstanding at any time
after the date hereof is increased by a stock dividend payable to all holders of Common Stock in shares of Common Stock or by a subdivision or split-up of shares of Common Stock, then, following the record date fixed for the determination of holders
of Common Stock entitled to receive such stock dividend, subdivision or split-up, the Exercise Price shall be appropriately decreased and the number of shares of Common Stock issuable on exercise of each Warrant shall be increased in proportion to
such increase in outstanding shares. 

  
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 2. Combination of Shares. If, at any time after the date hereof, the
number of shares of Common Stock outstanding is decreased by a combination or consolidation of the outstanding shares of Common Stock, by reclassification, reverse stock split or otherwise, then, following the record date for such combination, the
Exercise Price shall be appropriately increased and the number of shares of Common Stock issuable on exercise of each Warrant shall be decreased in proportion to such decrease in outstanding shares. 

3. Calculations. All calculations under this Section G shall be made to the nearest one-tenth of a cent ($.001), or
to the nearest one-tenth of a share, as the case may be. 
 4. Certificate as to Adjustments. Upon the
occurrence of each adjustment or readjustment of the Exercise Price and/or Warrant Shares, the Company, at its own expense, shall promptly notify Holder and compute such adjustment or readjustment in accordance with the terms hereof and furnish to
each Holder a certificate setting forth such adjustment or readjustment and showing in detail the facts upon which such adjustment or readjustment is based. The Company shall, upon the written request, at any time, of any such Holder, furnish or
cause to be furnished to such Holder a like certificate setting forth: (a) such adjustments and readjustments; (b) the Exercise Price at the time in effect; and (c) the number of shares and the amount, if any of other property that at
the time would be received upon the exercise of the Warrant. 
 Section H. Fractional Shares. No fractional
shares of the Company’s Common Stock will be issued in connection with any exercise hereunder but in lieu of such fractional shares the Company shall make a cash refund therefor equal in amount to the product of the applicable fraction
multiplied by the Exercise Price paid by the Holder for one Warrant Share upon such exercise. 
 Section I. Notices of
Certain Events. In addition to any other notices required to be given by the Company hereby, in the event: 
 1. the Company authorizes the issuance to all holders of its Common Stock of rights or warrants to subscribe for or purchase shares of its Common Stock or of any other subscription rights or warrants; or

 2. the Company authorizes the distribution to all holders of its Common Stock of evidences of its indebtedness
or assets (other than cash dividends or distributions except extraordinary cash dividends or distributions); or 

3. of any capital reorganization or reclassification or recapitalization of the Common Stock (other than a subdivision or
combination of the outstanding Common Stock and other than a change in par value of the Common Stock) or of any consolidation or merger to which the Company is a party or of the conveyance or transfer of all or substantially all of the properties
and assets of the Company, or any other Acquisition; or 
 4. of the voluntary or involuntary dissolution,
liquidation or winding-up of the Company; or 
 5. any other actions would require an adjustment or early
termination under Sections A or G hereof; 

  
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then the Company will cause to be mailed to the Holder, at least ten (10) days before the applicable record or effective date hereinafter specified (unless some other period of notice is
expressly set forth herein), a notice stating (A) the date as of which the holders of Common Stock of record entitled to receive any such rights, warrants or distributions are to be determined, or (B) the date on which any such
consolidation, merger, conveyance, transfer, dissolution, liquidation or winding-up or other event is expected to become effective. 
 Section J. Listing on Securities Exchanges. The Company will list on the Nasdaq Capital Market and each national securities exchange on which any Common Stock may at any time be listed all
shares of Common Stock from time to time issuable upon the exercise of this Warrant, subject to official notice of issuance upon the exercise of this Warrant, and will maintain such listing so long as any other shares of its Common Stock are so
listed. Any such listing will be at the Company’s expense. 
 Section K. Successors. All the provisions of
this Warrant by or for the benefit of the Company shall bind and inure to the benefit of its respective successors and assigns. 

Section L. Headings. The headings of sections of this Warrant have been inserted for convenience of reference only, are not
to be considered a part hereof and shall in no way modify or restrict any of the terms or provisions hereof. 
 Section M.
Amendments. The terms and provisions of this Warrant may not be modified or amended, or any provisions hereof waived, temporarily or permanently, except by written consent of the Company and the Holder hereof. 

Section N. Notices. Unless otherwise provided in this Warrant, all notices, requests, consents and other communications
hereunder shall be in writing, shall be sent by a nationally recognized overnight express courier postage prepaid, and shall be deemed given one day after being so sent, or if delivered by hand shall be deemed given on the date of such delivery to
such party, or if sent to such party (in the case of a Holder) at its address in the Warrant Register that will be maintained by the Company or its agent in accordance with Section B hereof or (in the case of the Company) at its address set forth
above, Attention: General Counsel, or to such other address as is designated by written notice, similarly given to each other party hereto. 
 Section O. Governing Law. This Agreement shall be governed by and construed in accordance with the laws of the State of New York, without giving effect to its principles regarding
conflicts of law. 
 Section P. 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 of all the provisions hereof and in taking all such action as may be necessary or appropriate to protect Holder’s rights under this Warrant
against impairment; provided, however, that notwithstanding the foregoing, nothing in this Section P shall restrict or impair the Company’s right to effect changes to the rights and privileges associated with the Warrant
Shares with the requisite consent of the stockholders as may be required to amend the Certificate of Incorporation from time to time so long as such amendment affects the rights and privileges granted to Holder associated with the Warrant Shares in
the same manner as the other holders of outstanding shares of the same series and class as the Warrant Shares. 

  
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 Section Q. Registration Under Securities Act of 1933, As Amended. The
Company agrees that the Warrant Shares shall have certain incidental, or “Piggyback,” and S-3 registration rights pursuant to and as set forth in the Third Amended and Restated Investors’ Rights Agreement dated December 2, 2009
(as amended and in effect from time to time, the “IRA”). For the avoidance of doubt, such registration rights shall not include demand registration rights (except to the extent that S-3 rights may be deemed demand rights or the Holder may
have been granted demand registration rights under a separate agreement). The provisions set forth in the IRA 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 Warrant 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
Warrant Shares granted to the Holder. 
 Section R. Automatic Conversion Upon Expiration. In the event that, on
July 18, 2021, the fair market value of one Warrant Share as determined in accordance with Section A.3 above is greater than the Exercise Price in effect on such date, then this Warrant shall automatically be deemed on and as of such date to be
converted pursuant to Section A.2 above as to all Warrant Shares for which it shall not previously have been exercised or converted, and the Company shall promptly deliver a certificate representing the Warrant Shares issued upon such conversion to
Holder. 
 Section S. Waiver of Jury Trial. TO THE FULLEST EXTENT PERMITTED BY APPLICABLE
LAW, THE COMPANY AND HOLDER EACH WAIVE THEIR RIGHT TO A JURY TRIAL OF ANY CLAIM OR CAUSE OF ACTION ARISING OUT OF OR BASE UPON THIS WARRANT, INCLUDING CONTRACT, TORT, BREACH OF DUTY AND ALL OTHER CLAIMS. THIS WAIVER IS A MATERIAL INDUCEMENT FOR BOTH
PARTIES TO ENTER INTO THIS WARRANT. EACH PARTY HAS REVIEWED THIS WAIVER WITH ITS COUNSEL. 
 Section T.
Counterparts. This Warrant may be executed in counterparts, all of which together shall constitute one and the same instrument. 

 

  
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 IN WITNESS WHEREOF, the Company has duly caused this Warrant to be signed and attested by its duly
authorized officer and to be dated as of July 18, 2011. 
  

			
	ZOGENIX, INC.
		
	By:	 	/s/    Ann D. Rhoads        
	Name:	 	Ann D. Rhoads
	Title:	 	Chief Financial Officer
	
	COWEN HEALTHCARE ROYALTY PARTNERS II, L.P.
	
	By Cowen Healthcare Royalty GP, LLC, its General Partner
		
	By:	 	/s/    Todd C. Davis         
	Name:	 	Todd C. Davis
	Title:	 	Managing Director

  
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 NOTICE OF EXERCISE 

Date:             , 20     

The undersigned hereby elects to exercise this Warrant to purchase
            shares of Common Stock and hereby makes payment of $            in payment of the exercise price thereof. 

or 
 The
undersigned hereby elects to convert the attached Warrant into Share in the manner specified in the Warrant. This conversion is exercised for             shares of Common Stock covered by
the Warrant. 
 [Strike paragraph that does not apply.] 

Certificate(s) representing the Warrant Shares shall be delivered to the following address: 

 

			
	  

	 [Holder’s Name]

 

	By:	 	 
	Name:	 	
	Title:	 	

  
 9Second Amendment to Third Amended and Restated Invetors'

 Exhibit 4.13 
 ZOGENIX, INC. 
 SECOND
AMENDMENT TO 
 THIRD AMENDED AND
RESTATED INVESTORS’ RIGHTS AGREEMENT 
 This Second
Amendment (this “Amendment”) to that certain Third Amended and Restated Investors’ Rights Agreement, dated as of December 2, 2009, as amended pursuant to that certain Amendment to Third Amended and Restated Investors’
Rights Agreement dated July 1, 2010 (as amended through the date hereof, the “Rights Agreement”), by and among Zogenix, Inc., a Delaware corporation (the “Company”), and the persons and entities (each an
“Investor” and collectively, the “Investors”) listed on Exhibit A thereto, is entered into by and among the Company, the Investors (including Cowen Healthcare Royalty Partners II, L.P.
(“CHRP”), effective as of the closing of the transactions contemplated by that certain Financing Agreement (defined below). 
 RECITALS 
 WHEREAS: In connection with that certain Financing
Agreement by and between the Company and CHRP, dated June 30, 2011 (the “Financing Agreement”), that certain warrant to purchase 225,000 shares of the Company’s Common Stock issued to CHRP in connection with the closing of
the transactions contemplated by the Financing Agreement (the “CHRP Warrant”), and certain shares to be purchased by CHRP as contemplated under the Financing Agreement, CHRP desires to become, and the Company and the Investors
desire CHRP to become, a party to the Rights Agreement in order to obtain certain “piggyback” and Form S-3 registration rights granted to the Investors in the Rights Agreement. 

WHEREAS: Under Section 5.1 of the Rights Agreement, the Holders of at least 67% of the outstanding shares of the Registrable
Securities may amend, on behalf of all other Holders of Registrable Securities, the Rights Agreement. 
 WHEREAS: The
undersigned Holders of at least 67% of the outstanding shares of Registrable Securities and the Company desire to amend the Rights Agreement to effect the intent of the foregoing recitals. 

NOW, THEREFORE: In consideration of the above recitals and for other good and valuable consideration, the receipt and adequacy of
which is hereby acknowledged, the parties hereto hereby agree as follows: 
  

	1.	Definitions. 

Unless otherwise defined herein, the capitalized terms used herein shall have the same meaning ascribed to such terms in the Rights
Agreement. 
  

	2.	Amendments to the Rights Agreement. 

 a. The following definitions are hereby added to Section 1.1: 

“CHRP” shall mean Cowen Healthcare Royalty Partners II, L.P.” 

 “CHRP Warrant” shall mean that certain warrant issued to
CHRP on the Closing Date as defined in the Financing Agreement.” 
 b. The definition of “Holder” is hereby
amended and restated as set forth below: 
 “Holder” shall mean (i) any Investor holding
Registrable Securities, (ii) solely for purposes of Sections 2.1(e), 2.2, 2.3(d), 2.4, 2.5, 2.6, 2.7, 2.9, 2.10, 2.11, 2.12 and 5 of this Agreement, GECC to the extent that it holds Registrable Securities (iii) solely for purposes of
Sections 2.1(e), 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.9, 2.10, 2.11, 2.12 and 5 of this Agreement, each of CIT and SVB to the extent it holds Registrable Securities, (iv) solely for purposes of Sections 2.1(e), 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.9,
2.10, 2.11, 2.12, 2.13, 2.14 and 5 of this Agreement, CHRP to the extent it holds Registrable Securities, and (v) any holder of Registrable Securities to whom the registration rights conferred by this Agreement have been duly and validly
transferred in accordance with Section 2.12 of this Agreement.” 
 c. The definitions of Oxford Warrants and SVB
Warrants are hereby amended and restated as set forth below: 
 “Oxford Warrants” shall mean those certain
warrants dated June 30, 2008, July 1, 2010 and June 30, 2011, issued to Oxford.” 
 “SVB
Warrants” shall mean those certain warrants dated July 1, 2010 and June 30, 2011, used to SVB.” 
 d. The
definition of “Registrable Securities” is hereby amended and restated as set forth below: 

“Registrable Securities” shall mean (i) shares of Common Stock issued or issuable pursuant to the
conversion of the Shares or the Investor Notes or exercise of the Investor Warrants or the Oxford Warrants, and solely for purposes of Sections 2.1(e), 2.2, 2.3(d), 2.4, 2.5, 2.6, 2.7, 2.9, 2.10, 2.11, 2.12 and 5 of this Agreement, shares of Common
Stock issuable pursuant to the conversion of the GE Shares or exercise of the GECC Warrant, and solely for purposes of Sections 2.1(e), 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.9, 2.10, 2.11, 2.12 and 5 of this Agreement, shares of Common Stock issuable
pursuant to the conversion of the CIT Shares, SVB Shares or exercise of the CIT Warrant or SVB Warrant; and solely for purposes of Sections 2.1(e), 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.9, 2.10, 2.11, 2.12, 2.13, 2.14 and 5 of this Agreement, shares of
Common Stock (a) issued to CHRP pursuant to the Stock and Warrant Purchase Agreement dated June 30, 2011, between the Company and CHRP (such shares, the “CHRP Closing Shares”) and (b) issuable pursuant to the exercise
of the CHRP Warrant, and (ii) any Common Stock of the Company issued as a dividend or other distribution with respect to or in exchange for or in replacement of the Shares referenced in clause (i) above (or the shares of Common Stock
referenced in clause (i) above); provided, however, that Registrable Securities shall not include any shares of Common Stock described in clause (i) or (ii) above which have previously been registered or which have been
sold to the public either pursuant to a registration statement or 

 
Rule 144, or which have been sold in a private transaction in which the transferor’s rights under this Agreement are not validly assigned in accordance with this Agreement; provided
further, that for the avoidance of doubt the shares of Common Stock issuable pursuant to the conversion of the GE Shares, CIT Shares, Oxford Shares or SVB Shares, or exercise of the GECC Warrant, CIT Warrant, Oxford Warrants, SVB Warrants or
CHRP Warrant, and the CHRP Closing Shares, shall not be Registrable Securities for purposes of Section 2.8 of this Agreement.” 
 e. The second paragraph of Section 2.1(e) is hereby amended and restated as set forth below: 
 Notwithstanding any other provision of this Section 2.1, if the underwriters advise the Initiating Holders in writing that market factors require a limitation on the number of shares to be
underwritten, the number of Registrable Securities and Other Shares that may be so included shall be allocated as follows: (i) first, among all the Holders (excluding GECC, CIT, SVB and CHRP) requesting to include Registrable Securities held by
such Holders, assuming conversion; (ii) second, to GECC, CIT and SVB; (iii) third, to CHRP; (iv) fourth, to the Other Selling Shareholders; and (v) fifth, to the Company, which the Company may allocate, at its discretion, for its
own account, or for the account of other holders or employees of the Company. 
 f. The following Investor is hereby added to
Exhibit A of the Rights Agreement: 
 Solely for purposes of Sections 2.1(e), 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.9,
2.10, 2.11, 2.12, 2.13, 2.14 and 5 of the Agreement, CHRP. 
  

	3.	Limitation of Rights of CHRP. 

 It is expressly understood by the parties to this Amendment that CHRP shall be a party to the Rights Agreement with respect to the CHRP Closing Shares and the Registrable Securities issuable upon exercise
of the CHRP Warrant only for the purpose of those certain rights and obligations set forth in Sections 2.1(e), 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.9, 2.10, 2.11, 2.12, 2.13, 2.14 and 5 of the Rights Agreement. For clarification and to avoid confusion,
CHRP shall have no rights, and the Company and the Investors shall have no obligations to CHRP, with respect to the sections of the Rights Agreement entitled (i) “Request for Registration,” as set forth in Section 2.1(a) to the
Rights Agreement (except as provided in Section 2.1(e) thereof), (ii) “Covenants of the Company,” as set forth in Section 3 to the Rights Agreement, and (iii) “Right of First Refusal,” as set forth in
Section 4 to the Rights Agreement. 
  

	4.	Addition of CHRP to the Rights Agreement. 

 Concurrently with the execution and delivery of this Amendment, CHRP shall execute and deliver a counterpart signature page to the Rights Agreement and CHRP will, upon delivery to the Company of such
counterpart signature page, become a party to, and will be bound by, the Rights Agreement as a Holder of Registrable Securities to the extent set forth in this Amendment and the Rights Agreement, as amended by this Amendment. 

	5.	Full Force and Effect. 

 Except as amended above, the Rights Agreement shall remain in full force and effect. 
  

	6.	Governing Law. 

 This
Amendment shall be governed in all respects by the internal laws of the State of California as applied to agreements entered into among California residents to be performed entirely within California, without regard to principles of conflicts of
law. 
  

	7.	Titles and Subtitles. 

The titles and subtitles used in this Amendment are used for convenience only and are not to be considered in construing or interpreting
this Amendment. 
  

	8.	Counterparts. 

 This
Amendment may be executed in any number of counterparts, each of which shall be enforceable against the parties that execute such counterparts, and all of which together shall constitute one instrument. 

 

	9.	Telecopy Execution and Delivery. 

 A facsimile, telecopy or other reproduction of this Amendment may be executed by one or more parties hereto and delivered by such party by facsimile or any similar electronic transmission device pursuant
to which the signature of or on behalf of such party can be seen. Such execution and delivery shall be considered valid, binding and effective for all purposes. At the request of any party hereto, all parties hereto agree to execute and deliver an
original of this Amendment as well as any facsimile, telecopy or other reproduction thereof. 
 (Remainder of Page
Intentionally Left Blank) 

 IN WITNESS WHEREOF, this Amendment is executed as of the date first written above.

  

			
	 COMPANY:
  

ZOGENIX, INC.

		
	By:	 	/s/    Ann D. Rhoads         
		 	 Name: Ann D. Rhoads

		 	 Title: Chief Financial Officer

 SIGNATURE PAGE TO SECOND
AMENDMENT TO 
 THIRD AMENDED AND
RESTATED INVESTORS’ RIGHTS AGREEMENT 

			
	 INVESTORS:
  

OXFORD FINANCE LLC
 (successor in
interest to Oxford Finance
 Corporation)

  

			
	By:	 	 /s/    T.A. Lex
        

  

			
	Print Name:	 	 T.A. Lex

  

			
	Title:	 	 COD

 SIGNATURE PAGE TO SECOND
AMENDMENT TO 
 THIRD AMENDED AND
RESTATED INVESTORS’ RIGHTS AGREEMENT 

 
			
	 Solely for the purposes of Sections 2.1(e), 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.10, 2.11, 2.12 and 5 of the Rights
Agreement:
  
 INVESTORS:

 
 SVB FINANCIAL GROUP

 

	By:	 	/s/    Michael Kruse         

  

			
	Print Name:	 	Michael Kruse

  

			
	Title:	 	Treasurer

 SIGNATURE PAGE TO SECOND
AMENDMENT TO 
 THIRD AMENDED AND
RESTATED INVESTORS’ RIGHTS AGREEMENT 

 
			
	 Solely for the purposes of Sections 2.1(e), 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.9, 2.10, 2.11, 2.12, 2.13, 2.14 and 5 of the
Rights Agreement:
  
 INVESTORS:

 
 COWEN HEALTHCARE ROYALTY PARTNERS II, L.P.

 
 By:     Cowen Healthcare Royalty GP, LLC

                Its General Partner

 

	By:	 	/s/    Todd C. Davis         

  

			
	Print Name:	 	Todd C. Davis

  

			
	Title:	 	Managing Director

 SIGNATURE PAGE TO SECOND
AMENDMENT TO 
 THIRD AMENDED AND
RESTATED INVESTORS’ RIGHTS AGREEMENT 

 
			
	 INVESTORS:
  

CLARUS LIFESCIENCES I, L.P.

By:     Clarus Ventures I Management, L.P.
              its general partner
  

By:     Clarus Ventures I, LLC

            its general partner

 

	By:	 	/s/    Kurt C. Wheeler         

  

			
	Print Name:	 	Kurt C. Wheeler

  

			
	Title:	 	Managing Director

 SIGNATURE PAGE TO SECOND
AMENDMENT TO 
 THIRD AMENDED AND
RESTATED INVESTORS’ RIGHTS AGREEMENT 

			
	 INVESTORS:
  

DOMAIN PARTNERS VI, L.P.

By:     One Palmer Square Associate VI, L.L.C.
             its General Partner
  

	By:	 	/s/    Lisa A. Kraeutler         

  

			
	Print Name:	 	Lisa A. Kraeutler

  

			
	Title:	 	Attorney-in-Fact

  

			
	 DP VI ASSOCIATES, L.P.
 By:     One Palmer Square Associates VI, L.L.C.,

            its General Partner

 

	By:	 	/s/    Lisa A. Kraeutler         

  

			
	Print Name:	 	Lisa A. Kraeutler

  

			
	Title:	 	Attorney-in-Fact

  

			
	 DOMAIN PARTNERS VII, L.P.
 By:     One Palmer Square Associate VII, L.L.C.

            its General Partner

 

	By:	 	/s/    Lisa A. Kraeutler         

  

			
	Print Name:	 	Lisa A. Kraeutler

  

			
	Title:	 	Attorney-in-Fact

 SIGNATURE PAGE TO SECOND
AMENDMENT TO 
 THIRD AMENDED AND
RESTATED INVESTORS’ RIGHTS AGREEMENT 

			
	 INVESTORS
  

DP VII ASSOCIATES, L.P.

By:     One Palmer Square Associates VII, L.L.C.,
             its General Partner
  

	By:	 	/s/    Lisa A. Kraeutler         

  

			
	Print Name:	 	Lisa A. Kraeutler

  

			
	Title:	 	Attorney-in-Fact

 SIGNATURE PAGE TO SECOND
AMENDMENT TO 
 THIRD AMENDED AND
RESTATED INVESTORS’ RIGHTS AGREEMENT 

 
			
	 INVESTORS:
  

SCALE VENTURE PARTNERS II, LP

By:     Scale Venture Management II, LLC
             its General Partner
  

	By:	 	/s/    Louis C. Bock         

  

			
	Print Name:	 	Louis C. Bock

  

			
	Title:	 	Managing Director

 SIGNATURE PAGE TO SECOND
AMENDMENT TO 
 THIRD AMENDED AND
RESTATED INVESTORS’ RIGHTS AGREEMENT 

 
			
	 INVESTORS:
  

THOMAS, MCNERNEY & PARTNERS, L.P.

 

	By:	 	/s/    Alex Zisson         

  

			
	Print Name:	 	Alex Zisson

  

			
	Title:	 	Manager

  

			
	 TMP NOMINEE, LLC

 

	By:	 	/s/    James E. Thomas         

  

			
	Print Name:	 	James E. Thomas

  

			
	Title:	 	Manager

  

			
	 TMP ASSOCIATES, L.P.

 

	By:	 	/s/    Alex Zisson         

  

			
	Print Name:	 	Alex Zisson

  

			
	Title:	 	Manager

 SIGNATURE PAGE TO SECOND
AMENDMENT TO 
 THIRD AMENDED AND
RESTATED INVESTORS’ RIGHTS AGREEMENT 

 
			
	 INVESTORS:
  

THOMAS, MCNERNEY & PARTNERS II, L.P.

 

	By:	 	/s/    Alex Zisson         

  

			
	Print Name:	 	Alex Zisson

  

			
	Title:	 	Manager

  

			
	 TMP NOMINEE II, LLC

 

	By:	 	/s/    James E. Thomas         

  

			
	Print Name:	 	James E. Thomas

  

			
	Title:	 	Manager

  

			
	 TMP ASSOCIATES II, L.P.

 

	By:	 	/s/    Alex Zisson         

  

			
	Print Name:	 	Alex Zisson

  

			
	Title:	 	Manager

 SIGNATURE PAGE TO SECOND
AMENDMENT TO 
 THIRD AMENDED AND
RESTATED INVESTORS’ RIGHTS AGREEMENT 

			
	 INVESTORS:
  

ABINGWORTH BIOVENTURES IV
 EXECUTIVES
LP
 acting by:
  
 Its manager Abingworth Management Ltd
  

	By:	 	/s/    James Abell         

  

			
	Print Name:	 	James Abell

  

			
	Title:	 	Director

  

			
	 ABINGWORTH BIOVENTURES IV LP
 acting by:
  
 Its manager
Abingworth Management Ltd
  

	By:	 	/s/    James Abell         

  

			
	Print Name:	 	James Abell

  

			
	Title:	 	Director

 SIGNATURE PAGE TO SECOND
AMENDMENT TO 
 THIRD AMENDED AND
RESTATED INVESTORS’ RIGHTS AGREEMENT 

 
			
	 INVESTORS:
  

CHICAGO GROWTH PARTNERS II, L.P.
  

By:     Chicago Growth Management II, LP
 Its:      General Partner
  
 By:     Chicago Growth Management II, LLC
 Its:     
General Partner
  

	By:	 	/s/    A. M. Minocherhomjee         

  

			
	Print Name:	 	A. M. Minocherhomjee

  

			
	Title:	 	Managing Partner

 SIGNATURE PAGE TO SECOND
AMENDMENT TO 
 THIRD AMENDED AND
RESTATED INVESTORS’ RIGHTS AGREEMENT

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