Document:

Warrant to Purchase Shares of Series C2 Preferred Stock

 EXHIBIT 4.5 
 THIS WARRANT HAS NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933, AS AMENDED OR ANY STATE SECURITIES LAWS. NO SALE OR DISPOSITION MAY BE EFFECTED WITHOUT (i) EFFECTIVE REGISTRATION STATEMENTS RELATED THERETO, (ii) AN OPINION
OF COUNSEL OR OTHER EVIDENCE, REASONABLY SATISFACTORY TO THE COMPANY, THAT SUCH REGISTRATIONS ARE NOT REQUIRED, (iii) RECEIPT OF NO-ACTION LETTERS FROM THE APPROPRIATE GOVERNMENTAL AUTHORITIES, OR (iv) OTHERWISE COMPLYING WITH THE
PROVISIONS OF SECTION 7 OF THIS WARRANT. 
 NEUROGESX, INC. 
 WARRANT TO PURCHASE SHARES 
 OF SERIES C-2 PREFERRED STOCK 
 THIS CERTIFIES THAT, for value received, HORIZON TECHNOLOGY FUNDING COMPANY II LLC and its assignees are entitled to subscribe for and purchase that
number of the fully paid and nonassessable shares of Series C-2 Preferred Stock (as adjusted pursuant to Section 4 hereof, the “Shares”) of NEUROGESX, INC., a Delaware corporation (the “Company”), as determined pursuant to
the next paragraph hereof at the price of $0.75 per share (such price and such other price as shall result, from time to time, from the adjustments specified in Section 4 hereof is herein referred to as the “Warrant Price”), subject
to the provisions and upon the terms and conditions hereinafter set forth. As used herein, (a) the term “Series Preferred” shall mean the Company’s Series C-2 Preferred Stock and any stock into or for which such Series C-2
Preferred Stock may hereafter be converted or exchanged, and after the conversion of the Series C-2 Preferred Stock to Common Stock shall mean the Company’s Common Stock, (b) the term “Date of Grant” shall mean July 7, 2006,
and (c) the term “Other Warrants” shall mean any other warrants issued by the Company in connection with the transaction with respect to which this Warrant was issued, and any warrant issued upon transfer or partial exercise of or in
lieu of this Warrant. The term “Warrant” as used herein shall be deemed to include Other Warrants unless the context clearly requires otherwise. 
 The number of shares for which this Warrant is exercisable shall equal the sum of (a) 240,000 plus (b) if and only if, the Company shall have borrowed Loan B (as defined in that certain Venture Loan and
Security Agreement by and among the Company, Horizon Technology Funding Company LLC (“Horizon”) and Oxford Finance Corporation (“Oxford”) dated on or about the Date of Grant (the “Loan Agreement”)), 105,000. 

1. Term. The purchase right represented by this Warrant is exercisable, in whole or in part, at any time and from time to time from the Date of
Grant through seven (7) years after the Date of Grant. The purchase right represented by this Warrant is exercisable, in whole or in part, at any time and from time to time from the Date of Grant through seven (7) years after the Date of
Grant. Notwithstanding the term of this Warrant fixed pursuant to this Section 1, upon the consummation of an Acquisition (as defined below), this Warrant shall automatically be exercised pursuant to Section 10.2 hereof, without any action
by holder. “Acquisition” means: (i) a sale of all or substantially all of 

 
the Company’s assets to an Unaffiliated Entity (as defined below), or (ii) the merger, consolidation or acquisition of the Company with, into or by
an Unaffiliated Entity (other than a merger or consolidation for the principle purpose of changing the domicile of the Company or a bona fide round of preferred stock equity financing), that results in the transfer of more than fifty percent
(50%) of the outstanding voting power of the Company, and where the consideration for the assets of the Company or the Company is cash or securities of a publicly traded company with a market capitalization of not less than Three Hundred Fifty
Million Dollars ($350,000,000). “Unaffiliated Entity” means any entity that is owned or controlled by parties who own less than twenty percent (20%) of the combined voting power of the voting securities of the Company immediately
prior to such merger, consolidation or acquisition. 
 2. Method of Exercise; Payment; Issuance of New Warrant. Subject to
Section 1 hereof, the purchase right represented by this Warrant may be exercised by the holder hereof, in whole or in part and from time to time, at the election of the holder hereof, by (a) the surrender of this Warrant (with the notice
of exercise substantially in the form attached hereto as Exhibit A-1 duly completed and executed) at the principal office of the Company and by the payment to the Company, by certified or bank check, or by wire transfer to an account designated
by the Company (a “Wire Transfer”) of an amount equal to the then applicable Warrant Price multiplied by the number of Shares then being purchased; (b) if in connection with a registered public offering of the Company’s
securities, the surrender of this Warrant (with the notice of exercise form attached hereto as Exhibit A-2 duly completed and executed) at the principal office of the Company together with notice of arrangements reasonably satisfactory to the
Company for payment to the Company either by certified or bank check or by Wire Transfer from the proceeds of the sale of shares to be sold by the holder in such public offering of an amount equal to the then applicable Warrant Price per share
multiplied by the number of Shares then being purchased; or (c) exercise of the “net issuance” right provided for in Section 10.2 hereof. The person or persons in whose name(s) any certificate(s) representing shares of Series
Preferred shall be issuable upon exercise of this Warrant shall be deemed to have become the holder(s) of record of, and shall be treated for all purposes as the record holder(s) of, the shares represented thereby (and such shares shall be deemed to
have been issued) immediately prior to the close of business on the date or dates upon which this Warrant is exercised. In the event of any exercise of the rights represented by this Warrant, certificates for the shares of stock so purchased shall
be delivered to the holder hereof as soon as possible and in any event within thirty (30) days after such exercise and, unless this Warrant has been fully exercised or expired, a new Warrant representing the portion of the Shares, if any, with
respect to which this Warrant shall not then have been exercised shall also be issued to the holder hereof as soon as possible and in any event within such thirty-day period; provided, however, at such time as the Company is subject to the reporting
requirements of the Securities Exchange Act of 1934, as amended, if requested by the holder of this Warrant, the Company shall cause its transfer agent to deliver the certificate representing Shares issued upon exercise of this Warrant to a
broker or other person (as directed by the holder exercising this Warrant) within the time period required to settle any trade made by the holder after exercise of this Warrant. 
 3. Stock Fully Paid; Reservation of Shares. All Shares that may be issued upon the exercise of the rights represented by this Warrant will, upon
issuance pursuant to the terms and conditions herein, be fully paid and nonassessable, and free from all preemptive rights and taxes, 

 
liens and charges with respect to the issue thereof. During the period within which the rights represented by this Warrant may be exercised, the Company will
at all times have authorized, and reserved for the purpose of the issue upon exercise of the purchase rights evidenced by this Warrant, a sufficient number of shares of its Series Preferred to provide for the exercise of the rights represented by
this Warrant and a sufficient number of shares of its Common Stock to provide for the conversion of the Series Preferred into Common Stock. 
 4. Adjustment of Warrant Price and Number of Shares. The number and kind of securities purchasable upon the exercise of this Warrant and the Warrant Price shall be subject to adjustment from time to time upon the occurrence of
certain events, as follows: 
 (a) Reclassification or Merger. Subject to termination pursuant to Section 1, hereof, in case of
any reclassification or change of securities of the class issuable upon exercise of this Warrant (other than a change in par value, or from par value to no par value, or from no par value to par value, or as a result of a subdivision or
combination), or in case of any merger of the Company with or into another corporation (other than a merger with another corporation in which the Company is the acquiring and the surviving corporation and which does not result in any
reclassification or change of outstanding securities issuable upon exercise of this Warrant), the Company, or such successor or purchasing corporation, as the case may be, shall duly execute and deliver to the holder of this Warrant a new Warrant
(in form and substance satisfactory to the holder of this Warrant), so that the holder of this Warrant shall have the right to receive upon exercise of this Warrant, at a total purchase price not to exceed that payable upon the exercise of the
unexercised portion of this Warrant, and in lieu of the shares of Series Preferred theretofore issuable upon exercise of this Warrant the kind and amount of shares of stock, other securities, money and property receivable upon such
reclassification, change, merger or sale by a holder of the number of shares of Series Preferred then purchasable under this Warrant. Any new Warrant shall provide for adjustments that shall be as nearly equivalent as may be practicable to the
adjustments provided for in this Section 4. The provisions of this Section 4(a) shall similarly apply to successive reclassifications, changes, mergers and sales. 
 (b) Subdivision or Combination of Shares. If the Company at any time while this Warrant remains outstanding and unexpired shall subdivide or
combine its outstanding shares of Series Preferred, the Warrant Price shall be proportionately decreased and the number of Shares issuable hereunder shall be proportionately increased in the case of a subdivision and the Warrant Price shall be
proportionately increased and the number of Shares issuable hereunder shall be proportionately decreased in the case of a combination. 
 (c)
Stock Dividends and Other Distributions. If the Company at any time while this Warrant is outstanding and unexpired shall (i) pay a dividend with respect to Series Preferred payable in Series Preferred, then the Warrant Price shall be
adjusted, from and after the date of determination of shareholders entitled to receive such dividend or distribution, to that price determined by multiplying the Warrant Price in effect immediately prior to such date of determination by a fraction
(A) the numerator of which shall be the total number of shares of Series Preferred outstanding immediately prior to such dividend or distribution, and (B) the denominator of which shall be the total number of shares of Series Preferred
outstanding immediately after such 

 
dividend or distribution; or (ii) make any other distribution with respect to Series Preferred (except any distribution specifically provided for in
Sections 4(a) and 4(b)), then, in each such case, provision shall be made by the Company such that the holder of this Warrant shall receive upon exercise of this Warrant a proportionate share of any such dividend or distribution as though it
were the holder of the Series Preferred (or Common Stock issuable upon conversion thereof) as of the record date fixed for the determination of the shareholders of the Company entitled to receive such dividend or distribution. 
 (d) Adjustment of Number of Shares. Upon each adjustment in the Warrant Price, the number of Shares of Series Preferred purchasable hereunder
shall be adjusted, to the nearest whole share, to the product obtained by multiplying the number of Shares purchasable immediately prior to such adjustment in the Warrant Price by a fraction, the numerator of which shall be the Warrant Price
immediately prior to such adjustment and the denominator of which shall be the Warrant Price immediately thereafter. 
 (e) Antidilution
Rights. The other antidilution rights applicable to the Shares of Series Preferred purchasable hereunder are set forth in the Company’s Fourth Amended and Restated Articles of Incorporation, as amended through the Date of Grant (the
“Charter”). The Company shall promptly provide the holder hereof with any restatement, amendment, modification or waiver of the Charter promptly after the same has been made. 
 5. Notice of Adjustments. Whenever the Warrant Price or the number of Shares purchasable hereunder shall be adjusted pursuant to Section 4
hereof, the Company shall make a certificate signed by its chief financial officer setting forth, in reasonable detail, the event requiring the adjustment, the amount of the adjustment, the method by which such adjustment was calculated, and the
Warrant Price and the number of Shares purchasable hereunder after giving effect to such adjustment, and shall cause copies of such certificate to be mailed (without regard to Section 13 hereof, by first class mail, postage prepaid) to the
holder of this Warrant. In addition, whenever the conversion price or conversion ratio of the Series Preferred shall be adjusted, the Company shall make a certificate signed by its chief financial officer setting forth, in reasonable detail, the
event requiring the adjustment, the amount of the adjustment, the method by which such adjustment was calculated, and the conversion price or ratio of the Series Preferred after giving effect to such adjustment, and shall cause copies of such
certificate to be mailed (without regard to Section 13 hereof, by first class mail, postage prepaid) to the holder of this Warrant. 
 6. Fractional Shares. No fractional shares of Series Preferred will be issued in connection with any exercise hereunder, but in lieu of such fractional shares the Company shall make a cash payment therefor based on the fair market
value of the Series Preferred on the date of exercise as reasonably determined in good faith by the Company’s Board of Directors. 
 7.
Compliance with Act; Disposition of Warrant or Shares of Series Preferred. 
 (a) Compliance with Act. The holder of this
Warrant, by acceptance hereof, agrees that this Warrant, and the shares of Series Preferred to be issued upon exercise hereof and any Common Stock issued upon conversion thereof are being acquired for investment and that such 

 
holder will not offer, sell or otherwise dispose of this Warrant, or any shares of Series Preferred to be issued upon exercise hereof or any Common Stock
issued upon conversion thereof except under circumstances which will not result in a violation of the Securities Act of 1933, as amended (the “Act”) or any applicable state securities laws. Upon exercise of this Warrant, unless the
Shares being acquired are registered under the Act and any applicable state securities laws or an exemption from such registration is available, the holder hereof shall confirm in writing that the shares of Series Preferred so purchased (and any
shares of Common Stock issued upon conversion thereof) are being acquired for investment and not with a view toward distribution or resale in violation of the Act and shall confirm such other matters related thereto as may be reasonably requested by
the Company. This Warrant and all shares of Series Preferred issued upon exercise of this Warrant and all shares of Common Stock issued upon conversion thereof (unless registered under the Act and any applicable state securities laws) shall be
stamped or imprinted with a legend in substantially the following form: 
 “THE SECURITIES EVIDENCED HEREBY HAVE NOT BEEN REGISTERED UNDER THE SECURITIES
ACT OF 1933, AS AMENDED, OR ANY STATE SECURITIES LAWS. NO SALE OR DISPOSITION MAY BE EFFECTED WITHOUT (i) EFFECTIVE REGISTRATION STATEMENTS RELATED THERETO, (ii) AN OPINION OF COUNSEL OR OTHER EVIDENCE, REASONABLY SATISFACTORY TO THE
COMPANY, THAT SUCH REGISTRATIONS ARE NOT REQUIRED, (iii) RECEIPT OF NO-ACTION LETTERS FROM THE APPROPRIATE GOVERNMENTAL AUTHORITIES, OR (iv) OTHERWISE COMPLYING WITH THE PROVISIONS OF SECTION 7 OF THE WARRANT UNDER WHICH THESE
SECURITIES WERE ISSUED, DIRECTLY OR INDIRECTLY.” 
 Said legend shall be removed by the Company, upon the request of a holder, at such
time as the restrictions on the transfer of the applicable security shall have terminated. In addition, in connection with the issuance of this Warrant, the holder specifically represents to the Company by acceptance of this Warrant as follows:

 (1) The holder is aware of the Company’s business affairs and financial condition, and has acquired information about the Company
sufficient to reach an informed and knowledgeable decision to acquire this Warrant. The holder is acquiring this Warrant for its own account for investment purposes only and not with a view to, or for the resale in connection with, any
“distribution” thereof in violation of the Act. 
 (2) The holder understands that this Warrant has not been registered under the
Act in reliance upon a specific exemption therefrom, which exemption depends upon, among other things, the bona fide nature of the holder’s investment intent as expressed herein. 
 (3) The holder further understands that this Warrant must be held indefinitely unless subsequently registered under the Act and qualified under any
applicable state securities laws, or unless exemptions from registration and qualification are otherwise available. The holder is aware of the provisions of Rule 144, promulgated under the Act. 
 (4) The holder is an “accredited investor” as such term is defined in Rule 501 of Regulation D promulgated under the Act.

 (b) Disposition of Warrant or Shares. With respect to any offer, sale or other disposition of this
Warrant or any shares of Series Preferred acquired pursuant to the exercise of this Warrant prior to registration of such Warrant or shares, the holder hereof agrees to give written notice to the Company prior thereto, describing briefly the manner
thereof, together with a written opinion of such holder’s counsel, or other evidence, if reasonably satisfactory to the Company, to the effect that such offer, sale or other disposition may be effected without registration or qualification
(under the Act as then in effect or any federal or state securities law then in effect) of this Warrant or such shares of Series Preferred or Common Stock and indicating whether or not under the Act certificates for this Warrant or such shares of
Series Preferred to be sold or otherwise disposed of require any restrictive legend as to applicable restrictions on transferability in order to ensure compliance with such law. Upon receiving such written notice and reasonably satisfactory opinion
or other evidence, the Company, as promptly as practicable but no later than fifteen (15) days after receipt of the written notice, shall notify such holder that such holder may sell or otherwise dispose of this Warrant or such shares of Series
Preferred or Common Stock, all in accordance with the terms of the notice delivered to the Company. If a determination has been made pursuant to this Section 7(b) that the opinion of counsel for the holder or other evidence is not reasonably
satisfactory to the Company, the Company shall so notify the holder promptly with details thereof after such determination has been made. Notwithstanding the foregoing, this Warrant or such shares of Series Preferred or Common Stock may, as to such
federal laws, be offered, sold or otherwise disposed of in accordance with Rule 144 or 144A under the Act, provided that the Company shall have been furnished with such information as the Company may reasonably request to provide a reasonable
assurance that the provisions of Rule 144 or 144A have been satisfied. Each certificate representing this Warrant or the shares of Series Preferred thus transferred (except a transfer pursuant to Rule 144 or 144A) shall bear a legend as to
the applicable restrictions on transferability in order to ensure compliance with such laws, unless in the aforesaid opinion of counsel for the holder, such legend is not required in order to ensure compliance with such laws. The Company may issue
stop transfer instructions to its transfer agent in connection with such restrictions. It shall be a condition to any transfer of this Warrant, that the transferee shall agree in writing to be bound by the terms of this Warrant as if an original
holder hereof. 
 (c) Lock-Up Period; Agreement. In connection with the initial public offering of the Company’s securities and
upon request of the Company or the underwriters managing such offering of the Company’s securities, the holder of this Warrant agrees not to sell, make any short sale of, loan, grant any option for the purchase of, or otherwise dispose of any
securities of the Company, however or whenever acquired (other than those included in the registration) without the prior written consent of the Company or such underwriters, as the case may be, for such period of time (not to exceed 180 days) from
the effective date of such registration as may be requested by the Company or such managing underwriters and to execute an agreement reflecting the foregoing as may be requested by the underwriters at the time of the Company’s initial public
offering. The obligations described in Section 7(c) shall not apply to a registration relating solely to employee benefit plans, or to a registration relating solely to a transaction pursuant to Rule 145 under the Securities Act. In order to
enforce the foregoing covenants, the Company may impose stop-transfer instructions with respect to the securities of the Company held by the holder of this Warrant. The holder of this Warrant agrees that it will not transfer this Warrant or any
shares received directly or 

 
indirectly as a result of the exercise of this Warrant unless the transferee(s) agrees in writing to be bound by all of the provisions of this
Section 7(c). Each certificate representing any securities of the Company held by the holder of this Warrant shall be stamped or otherwise imprinted with a legend substantially similar to the following: 
 “THE SHARES REPRESENTED BY THIS CERTIFICATE ARE SUBJECT TO A LOCK-UP PERIOD OF UP TO 180 DAYS IN THE EVENT OF A PUBLIC OFFERING, AS SET FORTH IN AN
AGREEMENT AMONG THE COMPANY AND THE ORIGINAL HOLDERS OF THESE SHARES, A COPY OF WHICH MAY BE OBTAINED AT THE PRINCIPAL OFFICE OF THE COMPANY.” 
 (d) Applicability of Restrictions. Neither any restrictions of any legend described in this Warrant nor the requirements of Section 7(b) above shall apply to any transfer of, or grant of a security interest in, this Warrant (or
the Series Preferred or Common Stock obtainable upon exercise thereof) or any part hereof (i) to a partner of the holder if the holder is a partnership or to a member of the holder if the holder is a limited liability company, (ii) to a
partnership of which the holder is a partner or to a limited liability company of which the holder is a member, or (iii) to any affiliate of the holder if the holder is a corporation (“affiliate” for purposes herein shall include but
not be limited to a business development company (as such term is defined in Section 2(a)(48) of the Investment Company Act of 1940, as amended) in which, either prior to such transaction or transactions or as a result thereof, any one or more
members of the Warrant holder has an equity ownership interest (individually or together with other such members) of more than 5%); provided, however, in any such transfer, if applicable, the transferee shall agree in writing as a
condition of such transfer to be bound by the terms of this Warrant as if an original holder hereof. 
 8. Rights as Shareholders;
Information. No holder of this Warrant, as such, shall be entitled to vote or receive dividends or be deemed the holder of Series Preferred or any other securities of the Company which may at any time be issuable upon the exercise hereof for any
purpose, nor shall anything contained herein be construed to confer upon the holder of this Warrant, as such, any of the rights of a shareholder of the Company or any right to vote for the election of directors or upon any matter submitted to
shareholders at any meeting thereof, or to receive notice of meetings, or to receive dividends or subscription rights or otherwise until this Warrant shall have been exercised and the Shares purchasable upon the exercise hereof shall have become
deliverable, as provided herein. Notwithstanding the foregoing, the Company will transmit to the holder of this Warrant such information, documents and reports as are generally distributed to the holders of such class or series of the securities of
the Company for which this Warrant is exerciseable concurrently with the distribution thereof to such shareholders. 
 9. Registration
Rights. The holder of this Warrant (including any permitted transferees or assigns) shall be added as a party to the Company’s Third Amended and Restated Investors’ Rights Agreement dated as of November 14, 2005 (the “Rights
Agreement”) so that the holder shall have those rights as set forth in the Joinder Agreement attached hereto as Exhibit A-3. 

 10. Additional Rights. 
 10.1 Acquisition Transactions. The Company shall provide the holder of this Warrant with at least ten (10) days’ written notice prior to
closing thereof of the terms and conditions of an Acquisition transaction. 
 10.2 Right to Convert Warrant into Stock: Net Issuance.

 (a) Right to Convert. In addition to and without limiting the rights of the holder under the terms of this Warrant, the holder shall
have the right to convert this Warrant or any portion thereof (the “Conversion Right”) into shares of Series Preferred as provided in this Section 10.2 at any time or from time to time during the term of this Warrant. Upon exercise of
the Conversion Right with respect to a particular number of shares subject to this Warrant (the “Converted Warrant Shares”), the Company shall deliver to the holder (without payment by the holder of any exercise price or any cash or other
consideration) that number of shares of fully paid and nonassessable Series Preferred as is determined according to the following formula: 
 X = B- A  
                     Y

  

					
	Where:	 	X =	  	the number of shares of Series Preferred that shall be issued to holder
			
		 	Y =	  	the fair market value of one share of Series Preferred
			
		 	A =	  	the aggregate Warrant Price of the specified number of Converted Warrant Shares immediately prior to the exercise of the Conversion Right (i.e., the number of Converted Warrant Shares
multiplied by the Warrant Price)
			
		 	B =	  	the aggregate fair market value of the specified number of Converted Warrant Shares (i.e., the number of Converted Warrant Shares multiplied by the fair market value of one
Converted Warrant Share)

 No fractional shares shall be issuable upon exercise of the Conversion Right, and, if the number
of shares to be issued determined in accordance with the foregoing formula is other than a whole number, the Company shall pay to the holder an amount in cash equal to the fair market value of the resulting fractional share on the Conversion Date
(as hereinafter defined). For purposes of Section 10 of this Warrant, shares issued pursuant to the Conversion Right shall be treated as if they were issued upon the exercise of this Warrant. 
 (b) Method of Exercise. The Conversion Right may be exercised by the holder by the surrender of this Warrant at the principal office of the
Company together with a written statement (which may be in the form of Exhibit A-1 or Exhibit A-2 hereto) specifying that the holder thereby intends to exercise the Conversion Right and indicating the number of shares subject to this
Warrant which are being surrendered (referred to in Section 10.2(a) hereof as the Converted Warrant Shares) in exercise of the Conversion Right. Such conversion shall be effective upon receipt by the 

 
Company of this Warrant together with the aforesaid written statement, or on such later date as is specified therein (the “Conversion Date”), and,
at the election of the holder hereof, may be made contingent upon the closing of the sale of the Company’s Common Stock to the public in a public offering pursuant to a Registration Statement under the Act (a “Public Offering”) or
Acquisition. Certificates for the shares issuable upon exercise of the Conversion Right and, if applicable, a new warrant evidencing the balance of the shares remaining subject to this Warrant, shall be issued as of the Conversion Date and shall be
delivered to the holder within thirty (30) days following the Conversion Date. 
 (c) Determination of Fair Market Value. For
purposes of this Section 10.2, “fair market value” of a share of Series Preferred (or Common Stock if the Series Preferred has been automatically converted into Common Stock) as of a particular date (the “Determination
Date”) shall mean: 
 (i) If the Conversion Right is exercised in connection with and contingent upon a Public Offering, and if the
Company’s Registration Statement relating to such Public Offering (“Registration Statement”) has been declared effective by the Securities and Exchange Commission, then the initial “Price to Public” specified in the final
prospectus with respect to such offering. 
 (ii) If the Conversion Right is not exercised in connection with and contingent upon a Public
Offering, then as follows: 
 (A) If traded on a securities exchange, the fair market value of the Common Stock shall be deemed to be the
average of the closing prices of the Common Stock on such exchange over the five trading days immediately prior to the Determination Date, and the fair market value of the Series Preferred shall be deemed to be such fair market value of the Common
Stock multiplied by the number of shares of Common Stock into which each share of Series Preferred is then convertible; 
 (B) If traded on
the Nasdaq Stock Market or other over-the-counter system, the fair market value of the Common Stock shall be deemed to be the average of the closing bid prices of the Common Stock over the five trading days immediately prior to the Determination
Date, and the fair market value of the Series Preferred shall be deemed to be such fair market value of the Common Stock multiplied by the number of shares of Common Stock into which each share of Series Preferred is then convertible; and

 (C) If there is no public market for the Common Stock, then fair market value shall be determined by the Board of Directors of the Company
in good faith. 
 In making a determination under clauses (A) or (B) above, if on the Determination Date, five trading days had not passed since
the Company’s initial public offering of its Common Stock (“IPO”) effected pursuant to a Registration Statement on Form S-1 (or its successor) filed under the Act, then the fair market value of the Common Stock shall be the
average closing prices or closing bid prices, as applicable, for the shorter period beginning on and including the date of the IPO and ending on the trading day prior to the Determination Date (or if such period includes only one trading day the
closing price or closing bid price, as applicable, for such trading day). 

 10.3 Exercise Prior to Expiration. To the extent this Warrant is not previously exercised as to
all of the Shares subject hereto, and if the fair market value of one share of the Series Preferred is greater than the Warrant Price then in effect, this Warrant shall be deemed automatically exercised pursuant to Section 10.2 above (even if
not surrendered) immediately before its expiration. For purposes of such automatic exercise, the fair market value of one share of the Series Preferred upon such expiration shall be determined pursuant to Section 10.2(c). To the extent this
Warrant or any portion thereof is deemed automatically exercised pursuant to this Section 10.3, the Company agrees to promptly notify the holder hereof of the number of Shares, if any, the holder hereof is to receive by reason of such automatic
exercise. 
 11. Representations and Warranties. The Company represents and warrants to the holder of this Warrant as follows:

 (a) This Warrant has been duly authorized and executed by the Company and is a valid and binding obligation of the Company enforceable in
accordance with its terms, subject to laws of general application relating to bankruptcy, insolvency and the relief of debtors and the rules of law or principles at equity governing specific performance, injunctive relief and other equitable
remedies. 
 (b) The Shares have been duly authorized and reserved for issuance by the Company and, when issued in accordance with the terms
hereof, will be validly issued, fully paid and nonassessable and free from preemptive rights. 
 (c) The rights, preferences, privileges and
restrictions granted to or imposed upon the Series Preferred and the holders thereof are as set forth in the Charter, and on the Date of Grant, each share of the Series Preferred represented by this Warrant is convertible into one share of Common
Stock. 
 (d) The shares of Common Stock issuable upon conversion of the Shares have been duly authorized and reserved for issuance by the
Company and, when issued in accordance with the terms of the Charter will be validly issued, fully paid and nonassessable. 
 (e) The
execution and delivery of this Warrant are not, and the issuance of the Shares upon exercise of this Warrant in accordance with the terms hereof will not be, inconsistent with the Company’s Charter or by-laws, do not and will not contravene any
law, governmental rule or regulation, judgment or order applicable to the Company, and do not and will not conflict with or contravene any provision of, or constitute a default under, any indenture, mortgage, contract or other instrument of which
the Company is a party or by which it is bound (except as would not reasonably be expected to have a material adverse effect on the Company) or require the consent or approval of, the giving of notice to, the registration or filing with or the
taking of any action in respect of or by, any Federal, state or local government authority or agency or other person, except for the filing of notices pursuant to federal and state securities laws, which filings will be effected by the time required
thereby. 

 (f) There are no actions, suits, audits, investigations or proceedings pending or, to the knowledge of
the Company, threatened against the Company in any court or before any governmental commission, board or authority which, if adversely determined, could have a material adverse effect on the ability of the Company to perform its obligations under
this Warrant. 
 (g) The number of shares of Common Stock of the Company outstanding on the date hereof, on a fully diluted basis (assuming
the conversion of all outstanding convertible securities and the exercise of all outstanding options and warrants), does not exceed 144,000,000 shares. 
 12. Modification and Waiver. This Warrant and any provision hereof may be changed, waived, discharged or terminated only by an instrument in writing signed by the party against which enforcement of the same is
sought. 
 13. Notices. Any notice, request, communication or other document required or permitted to be given or delivered to the
holder hereof or the Company shall be delivered, or shall be sent by certified or registered mail, postage prepaid, to each such holder at its address as shown on the books of the Company or to the Company at the address indicated therefor on the
signature page of this Warrant. 
 14. Binding Effect on Successors. This Warrant shall be binding upon any corporation succeeding the
Company by merger, consolidation or acquisition of all or substantially all of the Company’s assets, and all of the covenants and agreements of the Company shall inure to the benefit of the successors and assigns of the holder hereof.

 15. Lost Warrants or Stock Certificates. The Company covenants to the holder hereof that, upon receipt of evidence reasonably
satisfactory to the Company of the loss, theft, destruction or mutilation of this Warrant or any stock certificate and, in the case of any such loss, theft or destruction, upon receipt of an indemnity reasonably satisfactory to the Company, or in
the case of any such mutilation upon surrender and cancellation of such Warrant or stock certificate, the Company will make and deliver a new Warrant or stock certificate, of like tenor, in lieu of the lost, stolen, destroyed or mutilated Warrant or
stock certificate. 
 16. Descriptive Headings. The descriptive headings of the various Sections of this Warrant are inserted for
convenience only and do not constitute a part of this Warrant. The language in this Warrant shall be construed as to its fair meaning without regard to which party drafted this Warrant. 
 17. Governing Law. This Warrant shall be construed and enforced in accordance with, and the rights of the parties shall be governed by, the laws
of the State of Delaware. 
 18. Survival of Representations, Warranties and Agreements. All representations and warranties of the
Company and the holder hereof contained herein shall survive the Date of Grant, the exercise or conversion of this Warrant (or any part hereof) or the termination or expiration of rights hereunder. All agreements of the Company and the holder hereof
contained herein shall survive indefinitely until, by their respective terms, they are no longer operative. 

 19. Remedies. In case any one or more of the covenants and agreements contained in this Warrant
shall have been breached, the holders hereof (in the case of a breach by the Company), or the Company (in the case of a breach by a holder), may proceed to protect and enforce their or its rights either by suit in equity and/or by action at law,
including, but not limited to, an action for damages as a result of any such breach and/or an action for specific performance of any such covenant or agreement contained in this Warrant. 
 20. No Impairment of Rights. The Company will not, by amendment of its Charter or through any other means, avoid or seek to avoid the observance
or performance of any of the terms of this Warrant, but will at all times in good faith assist in the carrying out of all such terms and in the taking of all such action as may be necessary or appropriate in order to protect the rights of the holder
of this Warrant against impairment. 
 21. Severability. The invalidity or unenforceability of any provision of this Warrant in any
jurisdiction shall not affect the validity or enforceability of such provision in any other jurisdiction, or affect any other provision of this Warrant, which shall remain in full force and effect. 
 22. Recovery of Litigation Costs. If any legal action or other proceeding is brought for the enforcement of this Warrant, or because of an alleged
dispute, breach, default, or misrepresentation in connection with any of the provisions of this Warrant, the successful or prevailing party or parties shall be entitled to recover reasonable attorneys’ fees and other costs incurred in that
action or proceeding, in addition to any other relief to which it or they may be entitled. 
 23. Entire Agreement; Modification. This
Warrant constitutes the entire agreement between the parties pertaining to the subject matter contained in it and supersedes all prior and contemporaneous agreements, representations, and undertakings of the parties, whether oral or written, with
respect to such subject matter. 
 The Company has caused this Warrant to be duly executed and delivered as of the Date of Grant specified above. 

 

			
	NEUROGESX, INC.
		
	By:	 	 /s/ Stephen Ghiglieri

	Name:	 	Stephen Ghiglieri
	Title:	 	CFO
		
	Address:	 	981F Industrial Road
		 	San Carlos, CA 94070

 EXHIBIT A-1 
 NOTICE OF EXERCISE 
 To: NEUROGESX, INC. (the “Company”) 
 1. The undersigned hereby: 
  

	 	 ̈	elects to purchase             shares of [Series Preferred Stock] [Common Stock] of the Company pursuant to the
terms of the attached Warrant, and tenders herewith payment of the purchase price of such shares in full, or 

  

	 	 ̈	elects to exercise its net issuance rights pursuant to Section 10.2 of the attached Warrant with respect to
             Shares of [Series Preferred Stock] [Common Stock]. 

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

  

	
	 
                                        
                                       
 

	 (Name)

	
	 
                                        
                                       
 

	
	 
                                        
                                       
 

	 (Address)

 3. The undersigned represents that the aforesaid shares are being acquired for the account of the
undersigned for investment and not with a view to, or for resale in connection with, the distribution thereof and that the undersigned has no present intention of distributing or reselling such shares, all except as in compliance with applicable
securities laws. 
  

	
	  

	 (Signature)

 
                     
     (Date) 

 EXHIBIT A-2 
 NOTICE OF EXERCISE 
 To: NEUROGESX, INC. (the “Company”) 
 1. Contingent upon and effective immediately prior to the closing (the “Closing”) of the Company’s public offering contemplated by the
Registration Statement on Form S        , filed             , 200    , the undersigned hereby:

  ̈ elects to purchase
             shares of [Series Preferred Stock] [Common Stock] of the Company (or such lesser number of shares as may be sold on behalf of the undersigned at the Closing) pursuant to
the terms of the attached Warrant, or 
  ̈ elects to exercise its net issuance rights pursuant to Section 10.2 of the attached Warrant with respect to              Shares of [Series Preferred Stock] [Common
Stock]. 
 2. Please deliver to the custodian for the selling shareholders a stock certificate representing such
             shares. 
 3. The undersigned has instructed the custodian
for the selling shareholders to deliver to the Company $             or, if less, the net proceeds due the undersigned from the sale of shares in the aforesaid public offering. If
such net proceeds are less than the purchase price for such shares, the undersigned agrees to deliver the difference to the Company prior to the Closing. 
  

	
	  

	 (Signature)

 
                     
     (Date) 

 EXHIBIT A-3 
 JOINDER AGREEMENT 
 WHEREAS, the undersigned
             (the “Joining Parties”) and NeurogesX, Inc., a California corporation (the “Company”), have entered into a certain Venture Loan and
Security Agreement (the “LSA”), dated as of                  , 2006, and certain other related agreements contemplated thereby, pursuant
to which, among other things, the Company will issue to the Joining Parties Warrants (the “Warrant”) to purchase an aggregate of up to 840,000 shares of the Company’s Series C-2 Preferred Stock, at an exercise price of $0.75
per share (the “Shares”); 
 WHEREAS, the parties hereto desire the Joining Parties to have certain registration rights with
respect to the shares of Common Stock of the Company issuable upon conversion of the Shares pursuant to Sections 1.1 - 1.14 of that certain Amended and Restated Investors’ Rights Agreement, dated as of November 14, 2005, by and among the
Company and the other parties named therein, as the same may be amended and/or restated from time to time (the “Rights Agreement”), and that the Joining Parties be added to the Rights Agreement as parties thereto for the
purpose of granting such registration rights; 
 WHEREAS, Section 4.3 of the Rights Agreement allows the amendment or waiver of such
Rights Agreement with the written consent of the Company and the holders of at least a majority Registrable Securities, as defined therein, outstanding (the “Majority Holders”); and 
 NOW, THEREFORE, in consideration of the promises contained herein and for other good and valuable consideration, the receipt and sufficiency of which is
hereby mutually acknowledged by the parties hereto, the parties hereby covenant and agree as follows: 
 1. The shares of Common Stock
of the Company issuable upon conversion of the Shares shall constitute “Registrable Securities,” as such term is defined in Section 1.1(g) of the Rights Agreement, for all intents and purposes of the registration rights and related
provisions and obligations set forth in Sections 1.1 through 1.14 inclusive and Section 4 of the Rights Agreement. 
 2. The
Joining Parties shall be treated for all purposes under Section 1.1 through 1.14 inclusive, and Section 4 of the Rights Agreement as “Holders,” as such term is defined in Section 1.01(d) of the Rights Agreement; provided
however, that the Joining Parties shall not be considered “Initiating Holders” as such term is defined in Section 1.1(e). 
 3. The Joining Parties agree to be bound by the terms and conditions of Sections 1.1 through 1.14 inclusive and Section 4 of the Rights Agreement and shall succeed to and assume all of the rights and obligations of Holders of
Registrable Securities for all intents and purposes of such Sections, provided that, the Joining Parties shall not be deemed to possess any rights set forth in Sections 2 or 3 of the Rights Agreement. 

 4. All notices and other communications under the Rights Agreement shall be made to the Joining
Parties at the addresses specified below and thereafter at such other address, notice of which is given in accordance with Section 4.4 of the Rights Agreement: 
  

			
	If to Horizon or Agent:	  	 Horizon Technology Funding Company LLC
 76 Batterson
Park Road
 Farmington, CT 06032
 Attention: Legal
Department
 Fax: (860) 676-8655
 Ph: (860)
676-8654

		
	If to Oxford:	  	 Oxford Finance Corporation
 133 N.Fairfax
Street
 Alexandria, VA 22314
 Attn: Mike Altenburger, Chief
Financial Officer
 Fax: (703) 519-4910
 Ph: (703)
519-6017

 5. The Rights Agreement as modified herein shall remain in full force and effect as
so modified. 
 IN WITNESS WHEREOF, the parties hereto have executed this Agreement as of
the date first written above. 
  

			
	NEUROGESX, INC.
		
	 By:
	 	  

		
	 Name:
	 	  

		
	 Title:
	 	  

 JOINING PARTIES: 
 [TO COME] 
 INVESTORS: 
 See attached pages. 
 Agreed and Accepted:Warrant to Purchase Shares of Series C2 Preferred Stock

 EXHIBIT 4.6 
 THIS WARRANT HAS NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933, AS AMENDED OR ANY STATE SECURITIES LAWS. NO SALE OR DISPOSITION MAY BE EFFECTED WITHOUT (i) EFFECTIVE REGISTRATION STATEMENTS RELATED THERETO, (ii) AN OPINION
OF COUNSEL OR OTHER EVIDENCE, REASONABLY SATISFACTORY TO THE COMPANY, THAT SUCH REGISTRATIONS ARE NOT REQUIRED, (iii) RECEIPT OF NO-ACTION LETTERS FROM THE APPROPRIATE GOVERNMENTAL AUTHORITIES, OR (iv) OTHERWISE COMPLYING WITH THE
PROVISIONS OF SECTION 7 OF THIS WARRANT. 
 NEUROGESX, INC. 
 WARRANT TO PURCHASE SHARES 
 OF SERIES C-2 PREFERRED STOCK 
 THIS CERTIFIES THAT, for value received, HORIZON TECHNOLOGY FUNDING COMPANY III LLC and its assignees are entitled to subscribe for and purchase that
number of the fully paid and nonassessable shares of Series C-2 Preferred Stock (as adjusted pursuant to Section 4 hereof, the “Shares”) of NEUROGESX, INC., a Delaware corporation (the “Company”), as determined pursuant to
the next paragraph hereof at the price of $0.75 per share (such price and such other price as shall result, from time to time, from the adjustments specified in Section 4 hereof is herein referred to as the “Warrant Price”), subject
to the provisions and upon the terms and conditions hereinafter set forth. As used herein, (a) the term “Series Preferred” shall mean the Company’s Series C-2 Preferred Stock and any stock into or for which such Series C-2
Preferred Stock may hereafter be converted or exchanged, and after the conversion of the Series C-2 Preferred Stock to Common Stock shall mean the Company’s Common Stock, (b) the term “Date of Grant” shall mean July 7, 2006,
and (c) the term “Other Warrants” shall mean any other warrants issued by the Company in connection with the transaction with respect to which this Warrant was issued, and any warrant issued upon transfer or partial exercise of or in
lieu of this Warrant. The term “Warrant” as used herein shall be deemed to include Other Warrants unless the context clearly requires otherwise. 
 The number of shares for which this Warrant is exercisable shall equal the sum of (a) 240,000 plus (b) if and only if, the Company shall have borrowed Loan B (as defined in that certain Venture Loan and
Security Agreement by and among the Company, Horizon Technology Funding Company LLC (“Horizon”) and Oxford Finance Corporation (“Oxford”) dated on or about the Date of Grant (the “Loan Agreement”)), 105,000. 

1. Term. The purchase right represented by this Warrant is exercisable, in whole or in part, at any time and from time to time from the Date of
Grant through seven (7) years after the Date of Grant. The purchase right represented by this Warrant is exercisable, in whole or in part, at any time and from time to time from the Date of Grant through seven (7) years after the Date of
Grant. Notwithstanding the term of this Warrant fixed pursuant to this Section 1, upon the consummation of an Acquisition (as defined below), this Warrant shall automatically be exercised pursuant to Section 10.2 hereof, without any action
by holder. “Acquisition” means: (i) a sale of all or substantially all of 

 
the Company’s assets to an Unaffiliated Entity (as defined below), or (ii) the merger, consolidation or acquisition of the Company with, into or by
an Unaffiliated Entity (other than a merger or consolidation for the principle purpose of changing the domicile of the Company or a bona fide round of preferred stock equity financing), that results in the transfer of more than fifty percent
(50%) of the outstanding voting power of the Company, and where the consideration for the assets of the Company or the Company is cash or securities of a publicly traded company with a market capitalization of not less than Three Hundred Fifty
Million Dollars ($350,000,000). “Unaffiliated Entity” means any entity that is owned or controlled by parties who own less than twenty percent (20%) of the combined voting power of the voting securities of the Company immediately
prior to such merger, consolidation or acquisition. 
 2. Method of Exercise; Payment; Issuance of New Warrant. Subject to
Section 1 hereof, the purchase right represented by this Warrant may be exercised by the holder hereof, in whole or in part and from time to time, at the election of the holder hereof, by (a) the surrender of this Warrant (with the notice
of exercise substantially in the form attached hereto as Exhibit A-1 duly completed and executed) at the principal office of the Company and by the payment to the Company, by certified or bank check, or by wire transfer to an account designated
by the Company (a “Wire Transfer”) of an amount equal to the then applicable Warrant Price multiplied by the number of Shares then being purchased; (b) if in connection with a registered public offering of the Company’s
securities, the surrender of this Warrant (with the notice of exercise form attached hereto as Exhibit A-2 duly completed and executed) at the principal office of the Company together with notice of arrangements reasonably satisfactory to the
Company for payment to the Company either by certified or bank check or by Wire Transfer from the proceeds of the sale of shares to be sold by the holder in such public offering of an amount equal to the then applicable Warrant Price per share
multiplied by the number of Shares then being purchased; or (c) exercise of the “net issuance” right provided for in Section 10.2 hereof. The person or persons in whose name(s) any certificate(s) representing shares of Series
Preferred shall be issuable upon exercise of this Warrant shall be deemed to have become the holder(s) of record of, and shall be treated for all purposes as the record holder(s) of, the shares represented thereby (and such shares shall be deemed to
have been issued) immediately prior to the close of business on the date or dates upon which this Warrant is exercised. In the event of any exercise of the rights represented by this Warrant, certificates for the shares of stock so purchased shall
be delivered to the holder hereof as soon as possible and in any event within thirty (30) days after such exercise and, unless this Warrant has been fully exercised or expired, a new Warrant representing the portion of the Shares, if any, with
respect to which this Warrant shall not then have been exercised shall also be issued to the holder hereof as soon as possible and in any event within such thirty-day period; provided, however, at such time as the Company is subject to the reporting
requirements of the Securities Exchange Act of 1934, as amended, if requested by the holder of this Warrant, the Company shall cause its transfer agent to deliver the certificate representing Shares issued upon exercise of this Warrant to a
broker or other person (as directed by the holder exercising this Warrant) within the time period required to settle any trade made by the holder after exercise of this Warrant. 
 3. Stock Fully Paid; Reservation of Shares. All Shares that may be issued upon the exercise of the rights represented by this Warrant will, upon
issuance pursuant to the terms and conditions herein, be fully paid and nonassessable, and free from all preemptive rights and taxes, 

 
liens and charges with respect to the issue thereof. During the period within which the rights represented by this Warrant may be exercised, the Company will
at all times have authorized, and reserved for the purpose of the issue upon exercise of the purchase rights evidenced by this Warrant, a sufficient number of shares of its Series Preferred to provide for the exercise of the rights represented by
this Warrant and a sufficient number of shares of its Common Stock to provide for the conversion of the Series Preferred into Common Stock. 
 4. Adjustment of Warrant Price and Number of Shares. The number and kind of securities purchasable upon the exercise of this Warrant and the Warrant Price shall be subject to adjustment from time to time upon the occurrence of
certain events, as follows: 
 (a) Reclassification or Merger. Subject to termination pursuant to Section 1, hereof, in case of
any reclassification or change of securities of the class issuable upon exercise of this Warrant (other than a change in par value, or from par value to no par value, or from no par value to par value, or as a result of a subdivision or
combination), or in case of any merger of the Company with or into another corporation (other than a merger with another corporation in which the Company is the acquiring and the surviving corporation and which does not result in any
reclassification or change of outstanding securities issuable upon exercise of this Warrant), the Company, or such successor or purchasing corporation, as the case may be, shall duly execute and deliver to the holder of this Warrant a new Warrant
(in form and substance satisfactory to the holder of this Warrant), so that the holder of this Warrant shall have the right to receive upon exercise of this Warrant, at a total purchase price not to exceed that payable upon the exercise of the
unexercised portion of this Warrant, and in lieu of the shares of Series Preferred theretofore issuable upon exercise of this Warrant the kind and amount of shares of stock, other securities, money and property receivable upon such
reclassification, change, merger or sale by a holder of the number of shares of Series Preferred then purchasable under this Warrant. Any new Warrant shall provide for adjustments that shall be as nearly equivalent as may be practicable to the
adjustments provided for in this Section 4. The provisions of this Section 4(a) shall similarly apply to successive reclassifications, changes, mergers and sales. 
 (b) Subdivision or Combination of Shares. If the Company at any time while this Warrant remains outstanding and unexpired shall subdivide or
combine its outstanding shares of Series Preferred, the Warrant Price shall be proportionately decreased and the number of Shares issuable hereunder shall be proportionately increased in the case of a subdivision and the Warrant Price shall be
proportionately increased and the number of Shares issuable hereunder shall be proportionately decreased in the case of a combination. 
 (c)
Stock Dividends and Other Distributions. If the Company at any time while this Warrant is outstanding and unexpired shall (i) pay a dividend with respect to Series Preferred payable in Series Preferred, then the Warrant Price shall be
adjusted, from and after the date of determination of shareholders entitled to receive such dividend or distribution, to that price determined by multiplying the Warrant Price in effect immediately prior to such date of determination by a fraction
(A) the numerator of which shall be the total number of shares of Series Preferred outstanding immediately prior to such dividend or distribution, and (B) the denominator of which shall be the total number of shares of Series Preferred
outstanding immediately after such 

 
dividend or distribution; or (ii) make any other distribution with respect to Series Preferred (except any distribution specifically provided for in
Sections 4(a) and 4(b)), then, in each such case, provision shall be made by the Company such that the holder of this Warrant shall receive upon exercise of this Warrant a proportionate share of any such dividend or distribution as though it
were the holder of the Series Preferred (or Common Stock issuable upon conversion thereof) as of the record date fixed for the determination of the shareholders of the Company entitled to receive such dividend or distribution. 
 (d) Adjustment of Number of Shares. Upon each adjustment in the Warrant Price, the number of Shares of Series Preferred purchasable hereunder
shall be adjusted, to the nearest whole share, to the product obtained by multiplying the number of Shares purchasable immediately prior to such adjustment in the Warrant Price by a fraction, the numerator of which shall be the Warrant Price
immediately prior to such adjustment and the denominator of which shall be the Warrant Price immediately thereafter. 
 (e) Antidilution
Rights. The other antidilution rights applicable to the Shares of Series Preferred purchasable hereunder are set forth in the Company’s Fourth Amended and Restated Articles of Incorporation, as amended through the Date of Grant (the
“Charter”). The Company shall promptly provide the holder hereof with any restatement, amendment, modification or waiver of the Charter promptly after the same has been made. 
 5. Notice of Adjustments. Whenever the Warrant Price or the number of Shares purchasable hereunder shall be adjusted pursuant to Section 4
hereof, the Company shall make a certificate signed by its chief financial officer setting forth, in reasonable detail, the event requiring the adjustment, the amount of the adjustment, the method by which such adjustment was calculated, and the
Warrant Price and the number of Shares purchasable hereunder after giving effect to such adjustment, and shall cause copies of such certificate to be mailed (without regard to Section 13 hereof, by first class mail, postage prepaid) to the
holder of this Warrant. In addition, whenever the conversion price or conversion ratio of the Series Preferred shall be adjusted, the Company shall make a certificate signed by its chief financial officer setting forth, in reasonable detail, the
event requiring the adjustment, the amount of the adjustment, the method by which such adjustment was calculated, and the conversion price or ratio of the Series Preferred after giving effect to such adjustment, and shall cause copies of such
certificate to be mailed (without regard to Section 13 hereof, by first class mail, postage prepaid) to the holder of this Warrant. 
 6. Fractional Shares. No fractional shares of Series Preferred will be issued in connection with any exercise hereunder, but in lieu of such fractional shares the Company shall make a cash payment therefor based on the fair market
value of the Series Preferred on the date of exercise as reasonably determined in good faith by the Company’s Board of Directors. 
 7.
Compliance with Act; Disposition of Warrant or Shares of Series Preferred. 
 (a) Compliance with Act. The holder of this
Warrant, by acceptance hereof, agrees that this Warrant, and the shares of Series Preferred to be issued upon exercise hereof and any Common Stock issued upon conversion thereof are being acquired for investment and that such 

 
holder will not offer, sell or otherwise dispose of this Warrant, or any shares of Series Preferred to be issued upon exercise hereof or any Common Stock
issued upon conversion thereof except under circumstances which will not result in a violation of the Securities Act of 1933, as amended (the “Act”) or any applicable state securities laws. Upon exercise of this Warrant, unless the
Shares being acquired are registered under the Act and any applicable state securities laws or an exemption from such registration is available, the holder hereof shall confirm in writing that the shares of Series Preferred so purchased (and any
shares of Common Stock issued upon conversion thereof) are being acquired for investment and not with a view toward distribution or resale in violation of the Act and shall confirm such other matters related thereto as may be reasonably requested by
the Company. This Warrant and all shares of Series Preferred issued upon exercise of this Warrant and all shares of Common Stock issued upon conversion thereof (unless registered under the Act and any applicable state securities laws) shall be
stamped or imprinted with a legend in substantially the following form: 
 “THE SECURITIES EVIDENCED HEREBY HAVE NOT BEEN REGISTERED UNDER THE SECURITIES
ACT OF 1933, AS AMENDED, OR ANY STATE SECURITIES LAWS. NO SALE OR DISPOSITION MAY BE EFFECTED WITHOUT (i) EFFECTIVE REGISTRATION STATEMENTS RELATED THERETO, (ii) AN OPINION OF COUNSEL OR OTHER EVIDENCE, REASONABLY SATISFACTORY TO THE
COMPANY, THAT SUCH REGISTRATIONS ARE NOT REQUIRED, (iii) RECEIPT OF NO-ACTION LETTERS FROM THE APPROPRIATE GOVERNMENTAL AUTHORITIES, OR (iv) OTHERWISE COMPLYING WITH THE PROVISIONS OF SECTION 7 OF THE WARRANT UNDER WHICH THESE
SECURITIES WERE ISSUED, DIRECTLY OR INDIRECTLY.” 
 Said legend shall be removed by the Company, upon the request of a holder, at such time as the
restrictions on the transfer of the applicable security shall have terminated. In addition, in connection with the issuance of this Warrant, the holder specifically represents to the Company by acceptance of this Warrant as follows: 
 (1) The holder is aware of the Company’s business affairs and financial condition, and has acquired information about the Company sufficient to
reach an informed and knowledgeable decision to acquire this Warrant. The holder is acquiring this Warrant for its own account for investment purposes only and not with a view to, or for the resale in connection with, any “distribution”
thereof in violation of the Act. 
 (2) The holder understands that this Warrant has not been registered under the Act in reliance upon a
specific exemption therefrom, which exemption depends upon, among other things, the bona fide nature of the holder’s investment intent as expressed herein. 
 (3) The holder further understands that this Warrant must be held indefinitely unless subsequently registered under the Act and qualified under any applicable state securities laws, or unless exemptions from
registration and qualification are otherwise available. The holder is aware of the provisions of Rule 144, promulgated under the Act. 
 (4) The holder is an “accredited investor” as such term is defined in Rule 501 of Regulation D promulgated under the Act. 

 (b) Disposition of Warrant or Shares. With respect to any offer, sale or other disposition of this
Warrant or any shares of Series Preferred acquired pursuant to the exercise of this Warrant prior to registration of such Warrant or shares, the holder hereof agrees to give written notice to the Company prior thereto, describing briefly the manner
thereof, together with a written opinion of such holder’s counsel, or other evidence, if reasonably satisfactory to the Company, to the effect that such offer, sale or other disposition may be effected without registration or qualification
(under the Act as then in effect or any federal or state securities law then in effect) of this Warrant or such shares of Series Preferred or Common Stock and indicating whether or not under the Act certificates for this Warrant or such shares of
Series Preferred to be sold or otherwise disposed of require any restrictive legend as to applicable restrictions on transferability in order to ensure compliance with such law. Upon receiving such written notice and reasonably satisfactory opinion
or other evidence, the Company, as promptly as practicable but no later than fifteen (15) days after receipt of the written notice, shall notify such holder that such holder may sell or otherwise dispose of this Warrant or such shares of Series
Preferred or Common Stock, all in accordance with the terms of the notice delivered to the Company. If a determination has been made pursuant to this Section 7(b) that the opinion of counsel for the holder or other evidence is not reasonably
satisfactory to the Company, the Company shall so notify the holder promptly with details thereof after such determination has been made. Notwithstanding the foregoing, this Warrant or such shares of Series Preferred or Common Stock may, as to such
federal laws, be offered, sold or otherwise disposed of in accordance with Rule 144 or 144A under the Act, provided that the Company shall have been furnished with such information as the Company may reasonably request to provide a reasonable
assurance that the provisions of Rule 144 or 144A have been satisfied. Each certificate representing this Warrant or the shares of Series Preferred thus transferred (except a transfer pursuant to Rule 144 or 144A) shall bear a legend as to
the applicable restrictions on transferability in order to ensure compliance with such laws, unless in the aforesaid opinion of counsel for the holder, such legend is not required in order to ensure compliance with such laws. The Company may issue
stop transfer instructions to its transfer agent in connection with such restrictions. It shall be a condition to any transfer of this Warrant, that the transferee shall agree in writing to be bound by the terms of this Warrant as if an original
holder hereof. 
 (c) Lock-Up Period; Agreement. In connection with the initial public offering of the Company’s securities and
upon request of the Company or the underwriters managing such offering of the Company’s securities, the holder of this Warrant agrees not to sell, make any short sale of, loan, grant any option for the purchase of, or otherwise dispose of any
securities of the Company, however or whenever acquired (other than those included in the registration) without the prior written consent of the Company or such underwriters, as the case may be, for such period of time (not to exceed 180 days) from
the effective date of such registration as may be requested by the Company or such managing underwriters and to execute an agreement reflecting the foregoing as may be requested by the underwriters at the time of the Company’s initial public
offering. The obligations described in Section 7(c) shall not apply to a registration relating solely to employee benefit plans, or to a registration relating solely to a transaction pursuant to Rule 145 under the Securities Act. In order to
enforce the foregoing covenants, the Company may impose stop-transfer instructions with respect to the securities of the Company held by the holder of this Warrant. The holder of this Warrant agrees that it will not transfer this Warrant or any
shares received directly or 

 
indirectly as a result of the exercise of this Warrant unless the transferee(s) agrees in writing to be bound by all of the provisions of this
Section 7(c). Each certificate representing any securities of the Company held by the holder of this Warrant shall be stamped or otherwise imprinted with a legend substantially similar to the following: 
 “THE SHARES REPRESENTED BY THIS CERTIFICATE ARE SUBJECT TO A LOCK-UP PERIOD OF UP TO 180 DAYS IN THE EVENT OF A PUBLIC OFFERING, AS SET FORTH IN AN
AGREEMENT AMONG THE COMPANY AND THE ORIGINAL HOLDERS OF THESE SHARES, A COPY OF WHICH MAY BE OBTAINED AT THE PRINCIPAL OFFICE OF THE COMPANY.” 
 (d) Applicability of Restrictions. Neither any restrictions of any legend described in this Warrant nor the requirements of Section 7(b) above shall apply to any transfer of, or grant of a security interest in, this Warrant (or
the Series Preferred or Common Stock obtainable upon exercise thereof) or any part hereof (i) to a partner of the holder if the holder is a partnership or to a member of the holder if the holder is a limited liability company, (ii) to a
partnership of which the holder is a partner or to a limited liability company of which the holder is a member, or (iii) to any affiliate of the holder if the holder is a corporation (“affiliate” for purposes herein shall include but
not be limited to a business development company (as such term is defined in Section 2(a)(48) of the Investment Company Act of 1940, as amended) in which, either prior to such transaction or transactions or as a result thereof, any one or more
members of the Warrant holder has an equity ownership interest (individually or together with other such members) of more than 5%); provided, however, in any such transfer, if applicable, the transferee shall agree in writing as a
condition of such transfer to be bound by the terms of this Warrant as if an original holder hereof. 
 8. Rights as Shareholders;
Information. No holder of this Warrant, as such, shall be entitled to vote or receive dividends or be deemed the holder of Series Preferred or any other securities of the Company which may at any time be issuable upon the exercise hereof for any
purpose, nor shall anything contained herein be construed to confer upon the holder of this Warrant, as such, any of the rights of a shareholder of the Company or any right to vote for the election of directors or upon any matter submitted to
shareholders at any meeting thereof, or to receive notice of meetings, or to receive dividends or subscription rights or otherwise until this Warrant shall have been exercised and the Shares purchasable upon the exercise hereof shall have become
deliverable, as provided herein. Notwithstanding the foregoing, the Company will transmit to the holder of this Warrant such information, documents and reports as are generally distributed to the holders of such class or series of the securities of
the Company for which this Warrant is exerciseable concurrently with the distribution thereof to such shareholders. 
 9. Registration
Rights. The holder of this Warrant (including any permitted transferees or assigns) shall be added as a party to the Company’s Third Amended and Restated Investors’ Rights Agreement dated as of November 14, 2005 (the “Rights
Agreement”) so that the holder shall have those rights as set forth in the Joinder Agreement attached hereto as Exhibit A-3. 

 10. Additional Rights. 
 10.1 Acquisition Transactions. The Company shall provide the holder of this Warrant with at least ten (10) days’ written notice prior to
closing thereof of the terms and conditions of an Acquisition transaction. 
 10.2 Right to Convert Warrant into Stock: Net Issuance.

 (a) Right to Convert. In addition to and without limiting the rights of the holder under the terms of this Warrant, the holder shall
have the right to convert this Warrant or any portion thereof (the “Conversion Right”) into shares of Series Preferred as provided in this Section 10.2 at any time or from time to time during the term of this Warrant. Upon exercise of
the Conversion Right with respect to a particular number of shares subject to this Warrant (the “Converted Warrant Shares”), the Company shall deliver to the holder (without payment by the holder of any exercise price or any cash or other
consideration) that number of shares of fully paid and nonassessable Series Preferred as is determined according to the following formula: 
 X = B- A  
                     Y

  

					
	Where:	 	X =	  	the number of shares of Series Preferred that shall be issued to holder
			
		 	Y =	  	the fair market value of one share of Series Preferred
			
		 	A =	  	the aggregate Warrant Price of the specified number of Converted Warrant Shares immediately prior to the exercise of the Conversion Right (i.e., the number of Converted Warrant Shares
multiplied by the Warrant Price)
			
		 	B =	  	the aggregate fair market value of the specified number of Converted Warrant Shares (i.e., the number of Converted Warrant Shares multiplied by the fair market value of one
Converted Warrant Share)

 No fractional shares shall be issuable upon exercise of the Conversion Right, and, if the number
of shares to be issued determined in accordance with the foregoing formula is other than a whole number, the Company shall pay to the holder an amount in cash equal to the fair market value of the resulting fractional share on the Conversion Date
(as hereinafter defined). For purposes of Section 10 of this Warrant, shares issued pursuant to the Conversion Right shall be treated as if they were issued upon the exercise of this Warrant. 
 (b) Method of Exercise. The Conversion Right may be exercised by the holder by the surrender of this Warrant at the principal office of the
Company together with a written statement (which may be in the form of Exhibit A-1 or Exhibit A-2 hereto) specifying that the holder thereby intends to exercise the Conversion Right and indicating the number of shares subject to this
Warrant which are being surrendered (referred to in Section 10.2(a) hereof as the Converted Warrant Shares) in exercise of the Conversion Right. Such conversion shall be effective upon receipt by the 

 
Company of this Warrant together with the aforesaid written statement, or on such later date as is specified therein (the “Conversion Date”), and,
at the election of the holder hereof, may be made contingent upon the closing of the sale of the Company’s Common Stock to the public in a public offering pursuant to a Registration Statement under the Act (a “Public Offering”) or
Acquisition. Certificates for the shares issuable upon exercise of the Conversion Right and, if applicable, a new warrant evidencing the balance of the shares remaining subject to this Warrant, shall be issued as of the Conversion Date and shall be
delivered to the holder within thirty (30) days following the Conversion Date. 
 (c) Determination of Fair Market Value. For
purposes of this Section 10.2, “fair market value” of a share of Series Preferred (or Common Stock if the Series Preferred has been automatically converted into Common Stock) as of a particular date (the “Determination
Date”) shall mean: 
 (i) If the Conversion Right is exercised in connection with and contingent upon a Public Offering, and if the
Company’s Registration Statement relating to such Public Offering (“Registration Statement”) has been declared effective by the Securities and Exchange Commission, then the initial “Price to Public” specified in the final
prospectus with respect to such offering. 
 (ii) If the Conversion Right is not exercised in connection with and contingent upon a Public
Offering, then as follows: 
 (A) If traded on a securities exchange, the fair market value of the Common Stock shall be deemed to be the
average of the closing prices of the Common Stock on such exchange over the five trading days immediately prior to the Determination Date, and the fair market value of the Series Preferred shall be deemed to be such fair market value of the Common
Stock multiplied by the number of shares of Common Stock into which each share of Series Preferred is then convertible; 
 (B) If traded on
the Nasdaq Stock Market or other over-the-counter system, the fair market value of the Common Stock shall be deemed to be the average of the closing bid prices of the Common Stock over the five trading days immediately prior to the Determination
Date, and the fair market value of the Series Preferred shall be deemed to be such fair market value of the Common Stock multiplied by the number of shares of Common Stock into which each share of Series Preferred is then convertible; and

 (C) If there is no public market for the Common Stock, then fair market value shall be determined by the Board of Directors of the Company
in good faith. 
 In making a determination under clauses (A) or (B) above, if on the Determination Date, five trading days had not passed since
the Company’s initial public offering of its Common Stock (“IPO”) effected pursuant to a Registration Statement on Form S-1 (or its successor) filed under the Act, then the fair market value of the Common Stock shall be the
average closing prices or closing bid prices, as applicable, for the shorter period beginning on and including the date of the IPO and ending on the trading day prior to the Determination Date (or if such period includes only one trading day the
closing price or closing bid price, as applicable, for such trading day). 

 10.3 Exercise Prior to Expiration. To the extent this Warrant is not previously exercised as to
all of the Shares subject hereto, and if the fair market value of one share of the Series Preferred is greater than the Warrant Price then in effect, this Warrant shall be deemed automatically exercised pursuant to Section 10.2 above (even if
not surrendered) immediately before its expiration. For purposes of such automatic exercise, the fair market value of one share of the Series Preferred upon such expiration shall be determined pursuant to Section 10.2(c). To the extent this
Warrant or any portion thereof is deemed automatically exercised pursuant to this Section 10.3, the Company agrees to promptly notify the holder hereof of the number of Shares, if any, the holder hereof is to receive by reason of such automatic
exercise. 
 11. Representations and Warranties. The Company represents and warrants to the holder of this Warrant as follows:

 (a) This Warrant has been duly authorized and executed by the Company and is a valid and binding obligation of the Company enforceable in
accordance with its terms, subject to laws of general application relating to bankruptcy, insolvency and the relief of debtors and the rules of law or principles at equity governing specific performance, injunctive relief and other equitable
remedies. 
 (b) The Shares have been duly authorized and reserved for issuance by the Company and, when issued in accordance with the terms
hereof, will be validly issued, fully paid and nonassessable and free from preemptive rights. 
 (c) The rights, preferences, privileges and
restrictions granted to or imposed upon the Series Preferred and the holders thereof are as set forth in the Charter, and on the Date of Grant, each share of the Series Preferred represented by this Warrant is convertible into one share of Common
Stock. 
 (d) The shares of Common Stock issuable upon conversion of the Shares have been duly authorized and reserved for issuance by the
Company and, when issued in accordance with the terms of the Charter will be validly issued, fully paid and nonassessable. 
 (e) The
execution and delivery of this Warrant are not, and the issuance of the Shares upon exercise of this Warrant in accordance with the terms hereof will not be, inconsistent with the Company’s Charter or by-laws, do not and will not contravene any
law, governmental rule or regulation, judgment or order applicable to the Company, and do not and will not conflict with or contravene any provision of, or constitute a default under, any indenture, mortgage, contract or other instrument of which
the Company is a party or by which it is bound (except as would not reasonably be expected to have a material adverse effect on the Company) or require the consent or approval of, the giving of notice to, the registration or filing with or the
taking of any action in respect of or by, any Federal, state or local government authority or agency or other person, except for the filing of notices pursuant to federal and state securities laws, which filings will be effected by the time required
thereby. 

 (f) There are no actions, suits, audits, investigations or proceedings pending or, to the knowledge of
the Company, threatened against the Company in any court or before any governmental commission, board or authority which, if adversely determined, could have a material adverse effect on the ability of the Company to perform its obligations under
this Warrant. 
 (g) The number of shares of Common Stock of the Company outstanding on the date hereof, on a fully diluted basis (assuming
the conversion of all outstanding convertible securities and the exercise of all outstanding options and warrants), does not exceed 144,000,000 shares. 
 12. Modification and Waiver. This Warrant and any provision hereof may be changed, waived, discharged or terminated only by an instrument in writing signed by the party against which enforcement of the same is
sought. 
 13. Notices. Any notice, request, communication or other document required or permitted to be given or delivered to the
holder hereof or the Company shall be delivered, or shall be sent by certified or registered mail, postage prepaid, to each such holder at its address as shown on the books of the Company or to the Company at the address indicated therefor on the
signature page of this Warrant. 
 14. Binding Effect on Successors. This Warrant shall be binding upon any corporation succeeding the
Company by merger, consolidation or acquisition of all or substantially all of the Company’s assets, and all of the covenants and agreements of the Company shall inure to the benefit of the successors and assigns of the holder hereof.

 15. Lost Warrants or Stock Certificates. The Company covenants to the holder hereof that, upon receipt of evidence reasonably
satisfactory to the Company of the loss, theft, destruction or mutilation of this Warrant or any stock certificate and, in the case of any such loss, theft or destruction, upon receipt of an indemnity reasonably satisfactory to the Company, or in
the case of any such mutilation upon surrender and cancellation of such Warrant or stock certificate, the Company will make and deliver a new Warrant or stock certificate, of like tenor, in lieu of the lost, stolen, destroyed or mutilated Warrant or
stock certificate. 
 16. Descriptive Headings. The descriptive headings of the various Sections of this Warrant are inserted for
convenience only and do not constitute a part of this Warrant. The language in this Warrant shall be construed as to its fair meaning without regard to which party drafted this Warrant. 
 17. Governing Law. This Warrant shall be construed and enforced in accordance with, and the rights of the parties shall be governed by, the laws
of the State of Delaware. 
 18. Survival of Representations, Warranties and Agreements. All representations and warranties of the
Company and the holder hereof contained herein shall survive the Date of Grant, the exercise or conversion of this Warrant (or any part hereof) or the termination or expiration of rights hereunder. All agreements of the Company and the holder hereof
contained herein shall survive indefinitely until, by their respective terms, they are no longer operative. 

 19. Remedies. In case any one or more of the covenants and agreements contained in this Warrant
shall have been breached, the holders hereof (in the case of a breach by the Company), or the Company (in the case of a breach by a holder), may proceed to protect and enforce their or its rights either by suit in equity and/or by action at law,
including, but not limited to, an action for damages as a result of any such breach and/or an action for specific performance of any such covenant or agreement contained in this Warrant. 
 20. No Impairment of Rights. The Company will not, by amendment of its Charter or through any other means, avoid or seek to avoid the observance
or performance of any of the terms of this Warrant, but will at all times in good faith assist in the carrying out of all such terms and in the taking of all such action as may be necessary or appropriate in order to protect the rights of the holder
of this Warrant against impairment. 
 21. Severability. The invalidity or unenforceability of any provision of this Warrant in any
jurisdiction shall not affect the validity or enforceability of such provision in any other jurisdiction, or affect any other provision of this Warrant, which shall remain in full force and effect. 
 22. Recovery of Litigation Costs. If any legal action or other proceeding is brought for the enforcement of this Warrant, or because of an alleged
dispute, breach, default, or misrepresentation in connection with any of the provisions of this Warrant, the successful or prevailing party or parties shall be entitled to recover reasonable attorneys’ fees and other costs incurred in that
action or proceeding, in addition to any other relief to which it or they may be entitled. 
 23. Entire Agreement; Modification. This
Warrant constitutes the entire agreement between the parties pertaining to the subject matter contained in it and supersedes all prior and contemporaneous agreements, representations, and undertakings of the parties, whether oral or written, with
respect to such subject matter. 
 The Company has caused this Warrant to be duly executed and delivered as of the Date of Grant specified
above. 
  

			
	NEUROGESX, INC.
		
	By:	 	 /s/ Stephen Ghiglieri

	Name:	 	Stephen Ghiglieri
	Title:	 	CFO
		
	Address:	 	981F Industrial Road
		 	San Carlos, CA 94070

  

 EXHIBIT A-1 
 NOTICE OF EXERCISE 
 To: NEUROGESX, INC. (the “Company”) 
 1. The undersigned hereby: 
  

	 	 ̈	elects to purchase              shares of [Series Preferred Stock] [Common Stock] of the Company pursuant to the
terms of the attached Warrant, and tenders herewith payment of the purchase price of such shares in full, or 

  

	 	 ̈	elects to exercise its net issuance rights pursuant to Section 10.2 of the attached Warrant with respect to
             Shares of [Series Preferred Stock] [Common Stock]. 

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

  

	
	 
                                        
                                       
 

	 (Name)

	
	
                                        
                                       
 
	
	
                                        
                                       
 
	 (Address)

 3. The undersigned represents that the aforesaid shares are being acquired for the account of the
undersigned for investment and not with a view to, or for resale in connection with, the distribution thereof and that the undersigned has no present intention of distributing or reselling such shares, all except as in compliance with applicable
securities laws. 
  

	
	  

	 (Signature)

 
                     
     (Date) 

 EXHIBIT A-2 
 NOTICE OF EXERCISE 
 To: NEUROGESX, INC. (the “Company”) 
 1. Contingent upon and effective immediately prior to the closing (the “Closing”) of the Company’s public offering contemplated by the Registration
Statement on Form S        , filed                     ,
200    , the undersigned hereby: 
  ̈ elects to purchase              shares of [Series Preferred Stock] [Common Stock] of the Company (or such lesser number of shares as may be sold on
behalf of the undersigned at the Closing) pursuant to the terms of the attached Warrant, or 
  ̈ elects to exercise its net issuance rights pursuant to Section 10.2 of the attached Warrant with respect to
             Shares of [Series Preferred Stock] [Common Stock]. 
 2.
Please deliver to the custodian for the selling shareholders a stock certificate representing such              shares. 
 3. The undersigned has instructed the custodian for the selling shareholders to deliver to the Company
$             or, if less, the net proceeds due the undersigned from the sale of shares in the aforesaid public offering. If such net proceeds are less than the purchase price for
such shares, the undersigned agrees to deliver the difference to the Company prior to the Closing. 
  

	
	
 (Signature)

 
                     
     (Date) 
  

 EXHIBIT A-3 
 JOINDER AGREEMENT 
 WHEREAS, the undersigned
             (the “Joining Parties”) and NeurogesX, Inc., a California corporation (the “Company”), have entered into a certain Venture Loan and
Security Agreement (the “LSA”), dated as of                      , 2006, and certain other related agreements
contemplated thereby, pursuant to which, among other things, the Company will issue to the Joining Parties Warrants (the “Warrant”) to purchase an aggregate of up to 840,000 shares of the Company’s Series C-2 Preferred Stock,
at an exercise price of $0.75 per share (the “Shares”); 
 WHEREAS, the parties hereto desire the Joining Parties to have
certain registration rights with respect to the shares of Common Stock of the Company issuable upon conversion of the Shares pursuant to Sections 1.1 - 1.14 of that certain Amended and Restated Investors’ Rights Agreement, dated as of
November 14, 2005, by and among the Company and the other parties named therein, as the same may be amended and/or restated from time to time (the “Rights Agreement”), and that the Joining Parties be added to the Rights
Agreement as parties thereto for the purpose of granting such registration rights; 
 WHEREAS, Section 4.3 of the Rights Agreement
allows the amendment or waiver of such Rights Agreement with the written consent of the Company and the holders of at least a majority Registrable Securities, as defined therein, outstanding (the “Majority Holders”); and 

NOW, THEREFORE, in consideration of the promises contained herein and for other good and valuable consideration, the receipt and sufficiency of which
is hereby mutually acknowledged by the parties hereto, the parties hereby covenant and agree as follows: 
 1. The shares of Common
Stock of the Company issuable upon conversion of the Shares shall constitute “Registrable Securities,” as such term is defined in Section 1.1(g) of the Rights Agreement, for all intents and purposes of the registration rights and
related provisions and obligations set forth in Sections 1.1 through 1.14 inclusive and Section 4 of the Rights Agreement. 
 2.
The Joining Parties shall be treated for all purposes under Section 1.1 through 1.14 inclusive, and Section 4 of the Rights Agreement as “Holders,” as such term is defined in Section 1.01(d) of the Rights Agreement;
provided however, that the Joining Parties shall not be considered “Initiating Holders” as such term is defined in Section 1.1(e). 
 3. The Joining Parties agree to be bound by the terms and conditions of Sections 1.1 through 1.14 inclusive and Section 4 of the Rights Agreement and shall succeed to and assume all of the rights and
obligations of Holders of Registrable Securities for all intents and purposes of such Sections, provided that, the Joining Parties shall not be deemed to possess any rights set forth in Sections 2 or 3 of the Rights Agreement. 

 4. All notices and other communications under the Rights Agreement shall be made to the Joining
Parties at the addresses specified below and thereafter at such other address, notice of which is given in accordance with Section 4.4 of the Rights Agreement: 
  

			
	If to Horizon or Agent:	  	 Horizon Technology Funding Company LLC
 76 Batterson
Park Road
 Farmington, CT 06032
 Attention: Legal
Department
 Fax: (860) 676-8655
 Ph: (860)
676-8654

		
	If to Oxford:	  	 Oxford Finance Corporation
 133 N.Fairfax
Street
 Alexandria, VA 22314
 Attn: Mike Altenburger, Chief
Financial Officer
 Fax: (703) 519-4910
 Ph: (703)
519-6017

 5. The Rights Agreement as modified herein shall remain in full force and effect as
so modified. 
 IN WITNESS WHEREOF, the parties hereto have executed this Agreement as of
the date first written above. 
  

			
	NEUROGESX, INC.
		
	 By:
	 	  

		
	 Name:
	 	  

		
	 Title:
	 	  

 JOINING PARTIES: 
 [TO COME] 
 INVESTORS: 
 See attached pages. 
 Agreed and Accepted:

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