[To be separately provided to the Investors]

Exhibit 10.1

Apricus Biosciences, Inc.

11975 El Camino Real, Suite 300

San Diego, California 92130

Gentlemen:

The undersigned (collectively, the “Investors”) hereby severally confirm their respective agreements with Apricus Biosciences, Inc., a Nevada corporation (the “Company”), as follows:

1. This Subscription Agreement, including the Terms and Conditions For Purchase of Securities attached hereto as Annex I (collectively, (this “Agreement”), is made as of the date set forth below between the Company and the Investors.

2. The Company has authorized the sale and issuance to the Investors, at the First Closing (as defined in Section 4.1 of Annex I), of an aggregate of (i) 1,306,819 shares (the “First Closing Shares”) of its common stock, par value $0.001 per share (the “Common Stock”) and (ii) warrants (each, a “First Closing Warrant” and, collectively, the “First Closing Warrants”) to purchase an aggregate of 653,409 shares of Common Stock at an exercise price per share equal to $0.88 (the “First Closing Warrant Shares”), in substantially the form attached hereto as Exhibit B. The Company has authorized the sale and issuance to the Investors, at the Subsequent Closing (as defined in Section 4.1 of Annex I), of an aggregate of (i) 6,647,728 shares (the “Subsequent Closing Shares,” and together with the First Closing Shares, the “Shares”) of Common Stock and (ii) warrants (each, a “Subsequent Closing Warrant” and, collectively, the “Subsequent Closing Warrants,” and together with the First Closing Warrants, the “Warrants”) to purchase an aggregate of 3,323,864 shares of Common Stock at an exercise price per share equal to $0.88 (the “Subsequent Closing Warrant Shares,” and together with the First Closing Warrant Shares, the “Warrant Shares”), in substantially the form attached hereto as Exhibit B. At each Closing, the Company will issue to each Investor, and each Investor will purchase from the Company, the number of Shares and receive a Warrant exercisable for a number of Warrant Shares, in each case in the amounts set forth on the Signature Page (as defined below) of such Investor, and in exchange therefor, each Investor shall pay the aggregate price set forth on the Signature Page of such Investor (the “Purchase Price”). The Shares, the Warrants and the Warrant Shares are collectively referred to herein as the “Securities”.

3. The offering and sale of the Securities (the “Offering”) are being made pursuant to (1) an effective Registration Statement on Form S-3, File No. 333-198066 (the “Registration Statement”) filed by the Company with the Securities and Exchange Commission (the “Commission”) (including the prospectus contained therein (the “Base Prospectus”), (2) if applicable, certain “free writing prospectuses” (as that term is defined in Rule 405 under the Securities Act of 1933, as amended (the “Securities Act”)), that have been or will be filed with the Commission and delivered to the Investors on or prior to the date hereof (the “Issuer

Free Writing Prospectus”), containing certain supplemental information regarding the Securities, the terms of the Offering and the Company and (3) a Prospectus Supplement (the “Prospectus Supplement” and together with the Base Prospectus, the “Prospectus”) containing certain supplemental information regarding the Securities and terms of the Offering that has been or will be filed with the Commission and delivered to the Investors on or prior to the date hereof. Notwithstanding anything contained herein to the contrary, the information and disclosure contained in any Free Writing Prospectus and the Prospectus Supplement shall be consistent with the terms set forth herein and in the Warrant, and nothing contained therein shall modify the terms of this Agreement or the Warrant.

4. The Company and each Investor agree that at each Closing such Investor will purchase from the Company and the Company will issue and sell to such Investor the Shares and the Warrants set forth below for the aggregate Purchase Price set forth below. The Shares and the Warrants shall be purchased pursuant to this Agreement, the Warrant and the Terms and Conditions for Purchase of Securities attached hereto as Annex I and incorporated herein by this reference as if fully set forth herein.

5. The manner of settlement of the Shares purchased by each Investor at each Closing hereunder shall be as follows (and the Company shall take such actions as may be required to effect the following):

Delivery by crediting the account of such Investor’s prime broker (as specified by such Investor on Exhibit A annexed hereto) with the Depository Trust Company (“DTC”) through its Deposit/Withdrawal At Custodian (“DWAC”) system, whereby such Investor’s prime broker shall initiate a DWAC transaction on the applicable Closing Date using its DTC participant identification number, and released by Wells Fargo Shareowner Services, the Company’s transfer agent (the “Transfer Agent”), at the Company’s direction. NO LATER THAN (A) IN THE CASE OF THE FIRST CLOSING, THE FIRST CLOSING DATE, AND (B) IN THE CASE OF THE SUBSEQUENT CLOSING, THE SUBSEQUENT CLOSING DATE, SUCH INVESTOR AND THE COMPANY, AS APPLICABLE, SHALL:

[To be separately provided to the Investors]

6. The executed Warrants shall be delivered to the Investors by the Company at each Closing.

7. Each Investor severally represents as to itself (and not the other Investor) that (a) other than the transactions contemplated by the Prior Subscription Agreement (as defined in Annex I), including the issuance of shares of Common Stock and warrants pursuant to the terms thereof, it has had no position, office or other material relationship within the past three years with the Company (which, for the avoidance of doubt, excludes ownership of Shares), and (b) it is not a member of the Financial Industry Regulatory Authority, Inc. (“FINRA”) or an Associated Person (as such term is defined under the FINRA’s NASD Membership and Registration Rules Section 1011) as of each Closing.

8. Each Investor represents that it has received (or otherwise had made available to it by the filing by the Company of an electronic version thereof with the Commission on or prior to the date hereof) the Base Prospectus, dated August 25, 2014, which is a part of the Company’s Registration Statement, the documents incorporated by reference therein and any free writing prospectus (collectively, the “Disclosure Package”), prior to or in connection with the receipt of this Agreement. Each Investor acknowledges that, prior to the delivery of this Agreement to the Company, the Investors will receive certain additional information regarding the Offering, including pricing information which shall be consistent with the terms set forth herein (the “Offering Information”). Such information may be provided to the Investors by any means permitted under the Securities Act, including the Prospectus Supplement, a free writing prospectus and oral communications, but all such information shall be provided prior to the execution of this Agreement by the Investors and shall be consistent with the terms set forth herein.

9. No offer by the Investors to buy Shares and Warrants will be accepted and no part of the Purchase Price will be delivered to the Company until the Investors have received or have public access to the Offering Information and the Company has accepted such offer by countersigning a copy of this Agreement, and the Company hereby covenants to deliver or otherwise provide access to the Offering Information concurrently with or prior to its execution of this Agreement.

10. The Company acknowledges that the only material, non-public information relating to the Company or its subsidiaries that the Company, its employees or agents has provided to the Investors in connection with the Offering prior to the date hereof is the existence of the Offering.

[REMAINDER OF PAGE INTENTIONALLY LEFT BLANK]

Number of First Closing Shares: 821,336

Purchase Price per Share: $ 0.88

First Closing Aggregate Purchase Price: $722,775.68

Number of First Closing Warrant Shares subject to Warrants (Equal to Number of First Closing Shares multiplied by 0.5 and rounded down to the nearest whole number): 410,668

Number of Subsequent Closing Shares: 4,178,097

Purchase Price per Share: $ 0.88

Subsequent Closing Aggregate Purchase Price: $3,676,725.36

Number of Subsequent Closing Warrant Shares subject to Warrants (Equal to Number of Subsequent Closing Shares multiplied by 0.5 and rounded down to the nearest whole number): 2,089,048

Please confirm that the foregoing correctly sets forth the agreement between us by signing in the space provided below for that purpose.

Agreed and Accepted

this 12th of January, 2016:

Number of First Closing Shares: 485,483

Purchase Price per Share: $ 0.88

First Closing Aggregate Purchase Price: $ 427,225.04

Number of First Closing Warrant Shares subject to Warrants (Equal to Number of First Closing Shares multiplied by 0.5 and rounded down to the nearest whole number): 242,741

Number of Subsequent Closing Shares: 2,469,631

Purchase Price per Share: $ 0.88

Subsequent Closing Aggregate Purchase Price: $2,173,275.28

Number of Subsequent Closing Warrant Shares subject to Warrants (Equal to Number of Subsequent Closing Shares multiplied by 0.5 and rounded down to the nearest whole number): 1,234,815

Please confirm that the foregoing correctly sets forth the agreement between us by signing in the space provided below for that purpose.

Agreed and Accepted

this 12th day of January, 2016:

ANNEX I

TERMS AND CONDITIONS FOR PURCHASE OF SECURITIES

1. Authorization and Sale of the Securities. Subject to the terms and conditions of this Agreement, the Company has authorized the sale of the Securities.

2. Agreement to Sell and Purchase the Securities.

2.1 At each Closing (as defined in Section 4.1), the Company will sell to each Investor, and each Investor will severally purchase from the Company, upon the terms and conditions set forth herein, the number of Shares and Warrants set forth on the last page of the Agreement to which these Terms and Conditions for Purchase of Securities are attached as Annex I (the “Signature Page”) for the aggregate purchase price therefor set forth on the Signature Page on which such Investor’s name appears.

2.2 The Company proposes to enter into substantially this same form of Subscription Agreement with certain other investors listed on Schedule 2.2 (the “Other Investors”) and expects to complete sales of Shares and Warrants to them in the amount, price and such times as set forth on Schedule 2.2, provided that (a) the aggregate purchase price payable in respect of all Shares and Warrants issued to the Investors and the Other Investors at all Closings and the closings of the transactions contemplated by such other Subscription Agreements shall not exceed $10,000,000, (b) such other Subscription Agreement shall contain a voting agreement of all Other Investors or any affiliates thereof that hold any shares of Common Stock substantially on the terms set forth in Section 22 of this Annex I, and the Investors hereunder shall be made express third party beneficiaries of such voting agreement such that the Investors hereunder have the direct right to enforce the same, including to obtain specific performance in respect thereof on the terms set forth in such other Subscription Agreements, and (c) such Other Investors will not receive the registration rights, preemptive rights, board designation rights or expense reimbursement set forth herein. Copies of each such Subscription Agreement have been provided to the Investors and such agreements shall not hereafter be amended or modified without the prior written consent of the Investors.

2.3 The Company confirms that neither it nor any other Person acting on its behalf has provided the Investors or their agents or counsel with any information that constitutes or could reasonably be expected to constitute material, nonpublic information, except as will be disclosed in the Prospectus and/or in the Company’s Form 8-K to be filed with the Commission in connection with the Offering.

3. Representations and Warranties of the Company. The Company represents and warrants as of the date hereof and as of the date of each Closing as follows:

3.1 The Company and each Subsidiary (as defined below) has been duly organized and is validly existing as a corporation in good standing (or the foreign equivalent thereof) under the laws of each of their respective jurisdictions of organization. The Company and each Subsidiary is duly qualified to do business and is in good standing as a foreign corporation in each jurisdiction in which its ownership or lease of property or the conduct of its business requires such qualification and has all power and authority necessary to own or hold its

properties and to conduct the business in which it is engaged, except where the failure to so qualify, be in good standing or have such power or authority (i) would not have, singularly or in the aggregate, a material adverse effect on the condition (financial or otherwise), results of operations, assets, properties or business or prospects of the Company or any Subsidiary, taken as a whole, or (ii) impair in any material respect the ability of the Company to perform its obligations under this Agreement or to consummate any transactions contemplated by the Agreement, the Registration Statement, the Disclosure Package or the Prospectus (any such effect as described in clauses (i) or (ii), a “Material Adverse Effect”). The Company owns, directly or indirectly, only the following corporations, partnerships, limited liability partnerships, limited liability companies, associations or other entities: not applicable (each, a “Subsidiary” and, collectively, the “Subsidiaries”).

3.2 The Company has the full right, power and authority to enter into this Agreement, the Warrant Amendment (as hereinafter defined) and the Warrants and to perform and to discharge its obligations hereunder and thereunder; and each of this Agreement, the Warrant Amendment and the Warrants has been duly authorized, executed and delivered by the Company, and constitute valid and binding obligations of the Company enforceable in accordance with its terms, except as may be limited by bankruptcy, insolvency, reorganization or other similar laws relating to enforcement of creditors’ rights generally and by general principles of equity.

3.3 The Company has an authorized capitalization as set forth in the Registration Statement, the Disclosure Package and the Prospectus, and all of the issued shares of capital stock of the Company have been duly authorized and validly issued, are fully paid and non-assessable, have been issued in all material respects in compliance with United States federal and state securities laws, and conform to the description thereof contained in the Registration Statement, the Disclosure Package and the Prospectus. As of January 7, 2016, there were 50,414,481 shares of Common Stock issued and outstanding, no shares of Preferred Stock, par value $0.001 of the Company, issued and outstanding and 13,065,956 shares of Common Stock were issuable upon the exercise of all options, warrants and convertible securities outstanding as of such date. All of the Company’s options, warrants and other rights to purchase or exchange any securities for shares of the Company’s capital stock have been duly authorized and validly issued and were issued in all material respects in compliance with United States federal and state securities laws. None of the outstanding shares of Common Stock was issued in violation of any preemptive rights, rights of first refusal or other similar rights to subscribe for or purchase securities of the Company. There are no authorized or outstanding shares of capital stock, options, warrants, preemptive rights, rights of first refusal or other rights to purchase, or equity or debt securities convertible into or exchangeable or exercisable for, any capital stock of the Company or any Subsidiary other than those described above or accurately described in the Registration Statement, the Disclosure Package and the Prospectus. The description of the Company’s stock option, stock bonus and other stock plans or arrangements, and the options or other rights granted thereunder, as described in the Registration Statement, the Disclosure Package and the Prospectus, accurately and fairly present in all material respects the information required to be shown with respect to such plans, arrangements, options and rights.

3.4 The shares of Common Stock and Warrants to be issued and sold by the Company to the Investors under the Agreement and the Warrant Shares have been duly authorized and the Common Stock, when issued and delivered against payment therefor as provided in the Agreement and the Warrant Shares, when issued and delivered against payment therefore as provided in the Warrants, will be validly issued, fully paid and non-assessable and free of any preemptive or similar rights and will conform to the description thereof contained in the Disclosure Package and the Prospectus.

3.5 The execution, delivery and performance of the Agreement, the Warrant Amendment and the Warrants by the Company, the issue and sale of the shares of Common Stock and Warrants by the Company and the consummation of the transactions contemplated hereby, by the Warrant Amendment and by the Warrants will not (with or without notice or lapse of time or both): (i) result in any violation of the provisions of the articles or by-laws (or analogous governing instruments, as applicable) of the Company or any Subsidiary; (ii) result in the violation of any law, statute, rule, regulation, judgment, order or decree of any court or governmental agency or body, domestic or foreign, having jurisdiction over the Company or any Subsidiary or any of their properties or assets, or (iii) violate or result in a breach of or constitute (with due notice or lapse of time or both) a default under, permit the termination of any provision of, or result in the termination of, the acceleration of the maturity of, or the acceleration of the performance of any right or obligation of the Company or any Subsidiary under, or require any consent under, any material contract, agreement, lease, license, indenture or other understanding or arrangement to which the Company or any Subsidiary is a party or otherwise bound, other than the requirement to obtain Stockholder Approval of the Subsequent Closing.

3.6 At the time the Registration Statement became or becomes effective, at the date of this Agreement and at each Closing Date (as defined in Section 4.1), the Registration Statement conformed and will conform in all material respects to the requirements of the Securities Act and the published rules and regulations thereunder and did not and will not contain any untrue statement of a material fact or omit to state any material fact required to be stated therein or necessary to make the statements therein not misleading; the Prospectus, at the time the Prospectus was issued and at each Closing Date (as defined in Section 4.1), conformed and will conform in all material respects to the requirements of the Securities Act and the published rules and regulations thereunder and did not and will not contain an untrue statement of a material fact or omit to state a material fact necessary in order to make the statements therein, in light of the circumstances under which they were made, not misleading

3.7 The financial statements, together with the related notes and schedules, included or incorporated by reference in the Registration Statement, the Disclosure Package and the Prospectus fairly present in all material respects the financial position and the results of operations and changes in financial position of the Company and its Subsidiaries and other consolidated entities at the respective dates or for the respective periods therein specified. Such financial statements and related notes and schedules have been prepared in accordance with the generally accepted accounting principles in the United States (“GAAP”) applied on a consistent basis throughout the periods involved except as may be set forth in the related notes included or incorporated by reference in the Disclosure Package. The financial

statements, together with the related notes and schedules, included or incorporated by reference in the Registration Statement, the Disclosure Package and the Prospectus comply in all material respects with the Securities Act, the Securities Exchange Act of 1934, as amended (the “Exchange Act”), and the Rules and Regulations and the rules and regulations under the Exchange Act. No other financial statements or supporting schedules or exhibits are required by the Securities Act or the Rules and Regulations to be described, or included or incorporated by reference in the Registration Statement, the Disclosure Package or the Prospectus. There is no pro forma or as adjusted financial information which is required to be included in the Registration Statement, the Disclosure Package or the Prospectus or a document incorporated by reference therein in accordance with the Securities Act and the Rules and Regulations which has not been included or incorporated as so required. The pro forma and pro forma as adjusted financial information and the related notes included or incorporated by reference in the Registration Statement, the Disclosure Package and the Prospectus have been properly compiled and prepared in accordance with the applicable requirements of the Securities Act and the Rules and Regulations and present fairly the information shown therein, and the assumptions used in the preparation thereof are reasonable and the adjustments used therein are appropriate to give effect to the transactions and circumstances referred to therein.

3.8 Except as set forth in the Registration Statement, the Disclosure Package and the Prospectus, there is no action, suit, claim or proceeding pending to which the Company or any Subsidiary is a party or of which any property or assets of the Company or any Subsidiary is the subject which is required to be described in the Registration Statement, the Disclosure Package or the Prospectus or a document incorporated by reference therein and is not described therein, or which, singularly or in the aggregate, if determined adversely to the Company or any Subsidiary could be material to the Company or any Subsidiary or prevent or delay the consummation of the transactions contemplated hereby; and to the best of the Company’s knowledge, no such action, suit, claim or proceedings is threatened. For purposes of this Agreement, “knowledge of the Company” or similar phrases means the knowledge of the officers of the Company and its Subsidiaries, after due inquiry.

3.9 To the Company’s knowledge, the Company and each of its Subsidiaries own or possess adequate rights or licenses to use all trademarks, trade names, service marks, service mark registrations, service names, patents, patent rights, copyrights, inventions, licenses, approvals, governmental authorizations, trade secrets and other intellectual property rights (collectively, “Intellectual Property”) necessary to conduct their respective businesses as now conducted. None of the Company’s active and registered Intellectual Property have expired or terminated, or, by the terms and conditions thereof, will expire or terminate within two years from the date of the Agreement. The Company and its Subsidiaries do not have any knowledge of any infringement by the Company or its Subsidiaries of, and, to the Company’s knowledge, neither the Company, any Subsidiary nor their respective business or operations (including products sold thereby) are, or have been in the past three years, infringing, any Intellectual Property of others, or of any such development of similar or identical trade secrets or technical information by others with respect to the Company’s or its Subsidiaries’ Intellectual Property, and there is no claim, action or proceeding being made or brought against, or to the Company’s knowledge, being threatened against, the Company or its Subsidiaries regarding Intellectual Property.

3.10 The Company and each of its Subsidiaries (i) are, and have been in the last three years, in material compliance with any and all applicable foreign, federal, state and local laws and regulations, including those administered by the U.S. Food and Drug Administration (“FDA”) or similar governmental body and those relating to the protection of human health and safety or the environment and with respect to hazardous or toxic substances or wastes, pollutants or contaminants (“Environmental Laws”), (ii) have received and hold all material permits, licenses or other approvals required of them under applicable laws (including Environmental Laws) to conduct their respective businesses and (iii) are, and have been in the last three years in material compliance with all terms and conditions of any such permit, license or approval. Neither the Company nor any Subsidiary has received any written information or notice from the FDA or other domestic or foreign governmental or regulatory authority that would reasonably be expected to lead to cessation of sales of any product of the Company or any Subsidiary or the denial of any application for marketing or other approval currently pending before, or proposed to be filed by the Company or any Subsidiary thereof with, the FDA or other domestic or foreign governmental or regulatory authority.

3.11 The Company and each Subsidiary has good and marketable title in fee simple to, or have valid rights to lease or otherwise use, all items of real or personal property which are material to the business of the Company and any Subsidiary, free and clear of all liens, encumbrances, security interests, claims and defects that do not, singularly or in the aggregate, materially affect the value of such property and do not interfere with the use made and proposed to be made of such property by the Company or any Subsidiary; and all of the leases and subleases material to the business of the Company or any Subsidiary, and under which the Company or any Subsidiary holds properties described in the Registration Statement, the Disclosure Package and the Prospectus, are in full force and effect, and neither the Company nor any Subsidiary has received any notice of any material claim of any sort that has been asserted by anyone adverse to the rights of the Company or any Subsidiary under any of the leases or subleases mentioned above, or affecting or questioning the rights of the Company or any Subsidiary to the continued possession of the leased or subleased premises under any such lease or sublease.

3.12 The Company and each Subsidiary carries, or is covered by, insurance (including directors’ and officers’ liability insurance) provided by recognized, financially sound and reputable institutions with policies in such amounts and covering such risks as is adequate for the conduct of their respective businesses and the value of its properties and as is customary for companies engaged in similar businesses in similar industries. The Company has no reason to believe that it or any Subsidiary will not be able (i) to renew its existing insurance coverage as and when such policies expire or (ii) to obtain comparable coverage from similar institutions as may be necessary or appropriate to conduct their respective businesses as now conducted and at a cost that would not result in a Material Adverse Effect. Neither the Company nor any Subsidiary has been denied any insurance coverage that it has sought or for which it has applied.

3.13 The Company and each Subsidiary possesses all material licenses, certificates, authorizations and permits issued by, and have made all declarations and filings with, the

appropriate local, state, federal or foreign regulatory agencies or bodies which are necessary or desirable for the ownership of its properties or the conduct of their respective businesses as described in the Registration Statement, the Disclosure Package and the Prospectus (collectively, the “Governmental Permits”). The Company and each Subsidiary is in, and has been for the last three years in, compliance in all material respects with all such Governmental Permits, and all such Governmental Permits are valid and in full force and effect.

3.14 The Company and each of its Subsidiaries (i) have timely filed (or filed an extension to file) all necessary federal, state, local and foreign tax returns, and all such filed returns were true, complete and correct, (ii) have paid all federal, state, local and foreign taxes, assessments, governmental or other charges due and payable for which it is liable, including, without limitation, all sales and use taxes and all taxes which the Company or any Subsidiary is obligated to withhold from amounts owing to employees, creditors and third parties (including independent contractors), and (iii) do not have any tax deficiency or claims outstanding or assessed or, to the best of its knowledge, proposed against any of them, except those, in each of the cases described in clauses (i), (ii) and (iii) of this Section 3.14, that would not, singularly or in the aggregate, be material to the Company.

3.15 The Registration Statement has been declared effective by the Commission, and no stop order has been issued or is pending or, to the knowledge of the Company, threatened by the Commission with respect thereto.

3.16 The Company and its Subsidiaries have no liability or obligation of any nature (whether accrued, absolute, contingent or otherwise), other than (i) liabilities and obligations disclosed in the Registration Statement, the Disclosure Package and the Prospectus, (ii) liabilities and obligations incurred in the ordinary course of business since the date of the last financial statements included in the Registration Statement, the Disclosure Package and the Prospectus that would not reasonably be expected to be material to Company, (iii) liabilities under contracts (other than any such liability resulting from a breach or default thereunder) and (iv) liabilities and obligations incurred in connection with this Agreement and the transactions contemplated by this Agreement.

3.17 Neither the Company nor any Subsidiary or, to the knowledge of the Company, any of the other parties thereto is in breach or violation of or in default under, or committed or failed to perform any act which would result in a default under (in each case, with or without notice or lapse of time or both), any document, contract or other agreement required to be described in the Registration Statement, the General Disclosure Package or the Prospectus or to be filed as an exhibit to the Registration Statement in any material respect.

3.18 Neither the Company nor any Subsidiary thereof has either voluntarily or involuntarily initiated, conducted or issued, or caused to be initiated, conducted or issued, any recall, field notification, field correction, market withdrawal or replacement, warning, “dear doctor” letter, investigator notice, safety alert or other notice or action relating to an alleged lack of safety, lack of efficacy, adulteration, misbranding or lack of regulatory compliance of any product sold, marketed or distributed by the Company or any Subsidiary thereof. Neither the Company nor any Subsidiary thereof are aware of any facts which are reasonably likely to cause, and neither the Company nor any Subsidiary thereof has received

any written notice that the FDA or other domestic or foreign governmental or regulatory authority has commenced, or threatened to initiate, any action to cause (A) the seizure, recall, market withdrawal or replacement of any product sold, marketed or distributed by the Company or any Subsidiary thereof, (B) a change in the marketing classification or a material change in the labeling or advertising of any product sold, marketed or distributed by the Company or any Subsidiary thereof, or (C) a termination, suspension or injunction of the manufacture, marketing, storage or distribution of any product sold, marketed or distributed by the Company or any Subsidiary thereof.

3.19 Since the date of the latest audited financial statements included in the Registration Statement, no event, development, set of facts or circumstance has occurred that has had or is reasonably likely to have a Material Adverse Effect.

3.20 The Board of Directors of the Company has unanimously approved the execution of this Agreement, the Warrant Amendment and the Warrants and the consummation of the transactions contemplated hereby and thereby and no approval of the stockholders of the Company is required in connection with the execution and delivery of this Agreement, the Warrant Amendment or the Warrants or the consummation of the transactions contemplated hereby or thereby, other than the requirement to obtain Stockholder Approval of the Subsequent Closing. Each director and executive officer of the Company intends, to the knowledge of the Company, to vote all of the shares of capital stock of the Company owned thereby in favor of all matters to be presented to the stockholders of the Company in connection with seeking the Stockholder Approval. Without limiting the foregoing, the approval of the Board of Directors of the Company constitutes approval for purposes of any anti-takeover statute or similar statute or regulation that is or may become applicable to the transactions contemplated by this Agreement.

4. Closings and Delivery of the Securities and Funds.

4.1 Closing.

(a) First Closing. Subject to the satisfaction or waiver of the conditions set forth in Section 4.2(a) and Section 4.2(b) below, the completion of the purchase and sale of the First Closing Shares and the First Closing Warrants (the “First Closing”) shall occur no later than the second business day after the execution of this Agreement by the Investors and the Company (the “First Closing Date”), in accordance with Rule 15c6-l promulgated under the Securities Exchange Act of 1934, as amended (the “Exchange Act”). At the First Closing, (a) the Company shall cause Wells Fargo Shareowner Services, the Company’s “Transfer Agent”, to deliver to each Investor the number of First Closing Shares set forth on the Signature Page of such Investor registered in the name of such Investor or, if so indicated on the Investor Questionnaire of such Investor attached hereto as Exhibit A, in the name of a nominee designated by such Investor, (b) the Company shall cause to be delivered to such Investor a First Closing Warrant for the number of First Closing Warrant Shares set forth on the Signature Page of such Investor and (c) the aggregate purchase price for the First Closing Shares and the First Closing Warrants being purchased by such Investor at such First Closing as set forth on the Signature Page of such Investor will be delivered by or on behalf of such Investor to the Company. Notwithstanding anything contained herein to the contrary, if the First Closing shall not have occurred on or prior to the date that is two (2) business days after the execution of this Agreement by the Investors and the Company (unless the First

Closing shall not have occurred due to a breach by an Investor of the terms hereof), then the Investors may terminate this Agreement without further liability of any kind to the Company or the Investors, provided that (i) any such termination of this Agreement shall not relieve any party hereto of any liability in respect of any breach hereof arising prior to the termination of this Agreement (or following such termination with respect to any provisions that survive the termination of this Agreement), and (ii) this last sentence of Section 4.1(a) and Sections 2.3, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 18, 19, 23 and 24 shall survive any such termination.

(b) Subsequent Closing. Subject to the satisfaction or waiver of the conditions set forth in Section 4.2(c) and Section 4.2(d) below, the completion of the purchase and sale of the Subsequent Closing Shares and the Subsequent Closing Warrants (the “Subsequent Closing”) shall occur no later than three (3) business days after the Stockholder Approval Date (the “Subsequent Closing Date”), in accordance with Rule 15c6-l promulgated under the Exchange Act. At the Subsequent Closing, (a) the Company shall cause the Transfer Agent to deliver to each Investor the number of Subsequent Closing Shares set forth on the Signature Page of such Investor registered in the name of such Investor or, if so indicated on the Investor Questionnaire of such Investor attached hereto as Exhibit A, in the name of a nominee designated by such Investor, (b) the Company shall cause to be delivered to such Investor a Subsequent Closing Warrant for the number of Subsequent Closing Warrant Shares set forth on the Signature Page of such Investor and (c) the aggregate purchase price for the Subsequent Closing Shares and the Subsequent Closing Warrants being purchased by such Investor at such Subsequent Closing as set forth on the Signature Page of such Investor will be delivered by or on behalf of such Investor to the Company. For the avoidance of doubt, a Subsequent Closing shall not occur if the Stockholder Approval has not occurred or if the other conditions to the Subsequent Closing set forth in Section 4.2(c) and Section 4.2(d) have not been satisfied or waived. If the Subsequent Closing has not occurred on or prior to April 29, 2016 (which date may be extended in the sole discretion of the Company or the Investors to no later May 31, 2016 but only if the conditions to the Subsequent Closing set forth in Section 4.2(c) and Section 4.2(d) shall not have been satisfied or waived on or prior to April 29, 2016, provided that if the Closing shall not have occurred on or prior to April 29, 2016 and the reason therefor is the breach by any party of its representations, warranties, covenants or agreements hereunder, the breaching party shall not have the right to exercise the extension right described in this sentence), no Subsequent Closing shall occur hereunder and the Company and the Investors shall be relieved of all obligations in respect thereof, without limitation of any liability of any such party for any breach of any terms hereof that relate thereto. Notwithstanding anything else in this Agreement to the contrary, in the event the Company and the Investors determine that no Stockholder Approval is required in connection with the Subsequent Closing, the closing of the Subsequent Closing Shares and Subsequent Closing Warrants shall occur at the First Closing, or if the First Closing has already been consummated, then within (3) business days following such determination by the Company and the Investors, but subject to the satisfaction or waiver of the conditions set forth in Section 4.2(c) and Section 4.2(d).

4.2 Conditions to the Obligations of the Parties.

(a) Conditions to the Company’s Obligations for the First Closing. The Company’s obligation to issue and sell the First Closing Shares and the First Closing Warrants to each Investor at the First Closing shall be subject to: (i) the receipt by the Company from such Investor of the purchase price for the First Closing Shares and the First Closing Warrants being purchased hereunder at the First Closing by such Investor as set forth on the Signature Page thereof and (ii) the accuracy on the First Closing Date of the representations and warranties made by such Investor in this Agreement and the fulfillment of and compliance with those undertakings and covenants of such Investor to be fulfilled or complied with prior to the First Closing Date pursuant to this Agreement. Each Investor shall deliver a certificate to the Company on the First Closing Date to the foregoing effect.

(b) Conditions to Each Investor’s Obligations for the First Closing. Each Investor’s obligation to purchase the First Closing Shares and the First Closing Warrants at the First Closing will be subject to (i) the accuracy on the First Closing Date of the representations and warranties made by the Company in this Agreement and the fulfillment of and compliance with those undertakings and covenants of the Company to be fulfilled or complied with prior to the First Closing Date pursuant to this Agreement, (ii) the Company having executed and delivered to the Investors a counterpart signature page to that certain Amendment to Warrants, dated as of the date hereof by and between the Company and the Investors (the “Amendment Agreement”), and such Amendment Agreement being effective and in full force and effect on the First Closing Date, and (iii) the amendment to the Bylaws of the Company, the form of which is attached as Exhibit C hereto, shall be effective prior to or as of the First Closing Date and written evidence thereof shall have been provided to the Investors prior to the First Closing Date. The Company shall deliver a certificate to the Investors on the First Closing Date to the foregoing effect.

(c) Conditions to the Company’s Obligations for the Subsequent Closing. The Company’s obligation to issue and sell the Subsequent Closing Shares and the Subsequent Closing Warrants to each Investor at the Subsequent Closing shall be subject to: (i) the First Closing shall have been consummated, (ii) the Stockholder Approval shall have been obtained and be in full force and effect as of the Subsequent Closing Date, (iii) the receipt by the Company from such Investor of the purchase price for the Subsequent Closing Shares and the Subsequent Closing Warrants being purchased hereunder at the Subsequent Closing by such Investor as set forth on the Signature Page thereof, (iv) the accuracy on the Subsequent Closing Date of the representations and warranties made by such Investor in this Agreement and the fulfillment of and compliance with those undertakings and covenants of such Investor to be fulfilled or complied with prior to the Subsequent Closing Date pursuant to this Agreement, and (v) no temporary restraining order, preliminary or permanent injunction or other order issued by any court of competent jurisdiction or other governmental authority preventing the consummation of the transactions contemplated hereby shall be in effect and no action, suit or proceeding shall be pending that seeks to enjoin or otherwise prohibit the consummation of the transactions contemplated by this Agreement. Each Investor shall deliver a certificate to the Company on the Subsequent Closing Date to the foregoing effect.

(d) Conditions to each Investor’s Obligations for the Subsequent Closing. Each Investor’s obligation to purchase the Subsequent Closing Shares and the Subsequent

Closing Warrants at the Subsequent Closing will be subject to (i) the First Closing shall have been consummated, (ii) the Stockholder Approval shall have been obtained and be in full force and effect as of the Subsequent Closing Date, (iii) the accuracy on the Subsequent Closing Date of the representations and warranties made by the Company in this Agreement and the fulfillment of and compliance with those undertakings and covenants of the Company to be fulfilled or complied with prior to the Subsequent Closing Date pursuant to this Agreement, (iv) the Amendment Agreement shall be in full force and effect on the Subsequent Closing Date, (v) the Weighted Average Price (as defined in the Warrants) of a share of Common Stock as of the date that would otherwise be the Subsequent Closing Date (assuming, solely for these purposes the satisfaction of this condition and the occurrence of the Subsequent Closing on the first (1^st) business day following the receipt of the Stockholder Approval) shall be at least equal to $0.704, (vi) since the Execution Date, there shall have not occurred any event, circumstance, occurrence or state of facts that, individually or in the aggregate, has had or is reasonably likely to have a Material Adverse Effect, and (vii) no temporary restraining order, preliminary or permanent injunction or other order issued by any court of competent jurisdiction or other governmental authority preventing the consummation of the transactions contemplated hereby shall be in effect and no action, suit or proceeding shall be pending that seeks to enjoin or otherwise prohibit the consummation of the transactions contemplated by this Agreement. The Company shall deliver a certificate to the Investors on the Subsequent Closing Date to the foregoing effect. If the condition to the Subsequent Closing set forth in clause (v) or clause (vi) of the immediately preceding sentence is not satisfied or waived as of the date that would otherwise be the Subsequent Closing Date (assuming, solely for these purposes the satisfaction of all conditions to the Subsequent Closing (including the condition set forth in such clause (v) or (vi)) and the occurrence of the Subsequent Closing on the first (1^st) business day following the receipt of the Stockholder Approval), then, at the election of the Investors, no Subsequent Closing shall occur hereunder and the Company and the Investors shall be relieved of all obligations in respect thereof, without limitation of any liability of any such party for any breach of any terms hereof that relate thereto.

4.3 Delivery of Funds. To settle the Shares purchased by each Investor through DTC’s Deposit/Withdrawal at Custodian (“DWAC”) delivery system, (a) on the First Closing Date, each Investor shall remit by wire transfer the amount of funds equal to the aggregate purchase price for the First Closing Shares and the First Closing Warrants being purchased by such Investor at the First Closing, and (b) on the Subsequent Closing Date, each Investor shall remit by wire transfer the amount of funds equal to the aggregate purchase price for the Subsequent Closing Shares and the Subsequent Closing Warrants being purchased by such Investor at the Subsequent Closing, in each case to the following account designated by the Company:

[To be separately provided to the Investors]

4.4 Delivery of Shares. To settle the Shares purchased by each Investor through DTC’s DWAC delivery system, (i) with respect to the First Closing, no later than the First Closing Date, and (ii) with respect to the Subsequent Closing Date, no later than the Subsequent Closing Date, such Investor shall direct the broker-dealer at which the account or accounts to be credited with the Shares being purchased by such Investor at such Closing are maintained,

which broker/dealer shall be a DTC participant, to set up a DWAC instructing the Transfer Agent to credit such account or accounts with the Shares being acquired at such Closing. Such DWAC instruction shall indicate the settlement date for the deposit of the Shares, which date shall be the applicable Closing Date. At each Closing, the Company shall direct the Transfer Agent to credit each Investor’s account or accounts with the Shares being purchased by it hereunder at such Closing pursuant to the information contained in the DWAC.

5. Representations, Warranties and Covenants of the Investors.

Each Investor severally (as to itself and not the other Investor) acknowledges, represents and warrants to, and agrees with, the Company that:

5.1 Such Investor (a) is knowledgeable, sophisticated and experienced in making, and is qualified to make decisions with respect to, investments in securities representing an investment decision like that involved in the purchase of the Securities, including investments in securities issued by the Company and investments in comparable companies, (b) has answered all questions on the Signature Page and the Investor Questionnaire and the answers thereto are true and correct as of the date hereof and will be true and correct as of the Closing Date and (c) in connection with its decision to purchase the Shares and the Warrants set forth on the Signature Page, has received (or had full access to) and is relying only upon the Disclosure Package and the documents incorporated by reference therein and the Offering Information and the representations and warranties set forth herein and in the Warrant.

5.2 (a) Such Investor has full right, power, authority and capacity to enter into this Agreement and to consummate the transactions contemplated hereby and has taken all necessary action to authorize the execution, delivery and performance of this Agreement, and (b) this Agreement constitutes a valid and binding obligation of such Investor enforceable against such Investor in accordance with its terms, except as enforceability may be limited by applicable bankruptcy, insolvency, reorganization, moratorium or similar laws affecting creditors’ and contracting parties’ rights generally and except as enforceability may be subject to general principles of equity (regardless of whether such enforceability is considered in a proceeding in equity or at law) and except as to the enforceability of any rights to indemnification or contribution that may be violative of the public policy underlying any law, rule or regulation (including any federal or state securities law, rule or regulation).

5.3 Such Investor understands that nothing in this Agreement, the Prospectus, the Disclosure Package, the Offering Information or any other materials presented to the Investor in connection with the purchase and sale of the Shares and the Warrants constitutes legal, tax or investment advice. Such Investor has consulted such legal, tax and investment advisors and made such investigation as it, in its sole discretion, has deemed necessary or appropriate in connection with its purchase of Shares and Warrants. Such Investor also understands that there is no established public trading market for the Warrants being offered in the Offering, and that the Company does not expect such a market to develop. In addition, the Company does not intend to apply for listing of the Warrants on any securities exchange or other trading market. Such Investor understands that without an active market, the liquidity of the Warrants will be limited.

5.4 Since December 1, 2015, representing the date at which the Company first contacted such Investor about the Offering, such Investor has not disclosed any information regarding the Offering to any third parties (other than its employees or the employees of its affiliates or their respective legal, accounting and other advisors) and has not engaged in any purchases or sales of the securities of the Company (including, without limitation, any Short Sales (as defined herein) involving the Company’s securities). Such Investor covenants that it will not engage in any purchases or sales of the securities of the Company (including Short Sales), other than the purchases of the Shares and the Warrants as contemplated hereby, prior to the time that the transactions contemplated by this Agreement are publicly disclosed (it being understood and agreed that such transactions shall be publicly disclosed no later than one business day following the execution of this Agreement by all parties hereto). Such Investor agrees that it will not use any of the Securities acquired pursuant to this Agreement to cover any short position in the Common Stock if doing so would be in violation of applicable securities laws. For purposes hereof, “Short Sales” include, without limitation, all “short sales” as defined in Rule 200 promulgated under Regulation SHO under the Exchange Act, whether or not against the box, and all types of direct and indirect stock pledges, forward sales contracts, options, puts, calls, short sales, swaps, “put equivalent positions” (as defined in Rule 16a-1(h) under the Exchange Act) and similar arrangements (including on a total return basis), and sales and other transactions through non-U.S. broker dealers or foreign regulated brokers.

6. Survival of Representations, Warranties and Agreements. Notwithstanding any investigation made by any party to this Agreement, all covenants, agreements, representations and warranties made by the Company and the Investors herein will survive the execution of this Agreement, the delivery to the Investors of the Shares and Warrants being purchased and the payment therefor at each Closing.

7. Notices. All notices, requests, consents and other communications hereunder will be in writing, will be mailed or sent by facsimile or e-mail and, if mailed (a) if within the domestic United States by first-class registered or certified airmail, or nationally recognized overnight express courier, postage prepaid, or (b) if delivered from outside the United States, by International Federal Express and will be deemed given (i) if delivered by first-class registered or certified mail domestic, three business days after so mailed, (ii) if delivered by nationally recognized overnight carrier, one business day after so mailed, (iii) if delivered by International Federal Express, two business days after so mailed and (iv) if delivered by facsimile or e-mail, upon the sending thereof so long as a copy of the same is also sent by one of the other means set forth in clauses (i)-(iii) and will be delivered and addressed as follows:

(a) if to the Company, to:

Apricus Biosciences, Inc.

11975 El Camino Real, Suite 300

San Diego, California 92130

Attention: Chief Executive Officer

Email: ***@***

with a copy (which shall not constitute notice) to:

Latham & Watkins LLP

12670 High Bluff Drive

San Diego, California 92130

Attention: Cheston J. Larson

Email: ***@***

(b) if to any Investor, at its address on the Signature Page hereto, or at such other address or addresses as may have been furnished to the Company in writing.

8. Changes. This Agreement may not be modified or amended except pursuant to an instrument in writing signed by the Company and the Investors.

9. Headings. The headings of the various sections of this Agreement have been inserted for convenience of reference only and will not be deemed to be part of this Agreement.

10. Severability. In case any provision contained in this Agreement should be invalid, illegal or unenforceable in any respect, the validity, legality and enforceability of the remaining provisions contained herein will not in any way be affected or impaired thereby.

11. Governing Law. This Agreement will be governed by, and construed in accordance with, the internal laws of the State of New York, without giving effect to the principles of conflicts of law that would require the application of the laws of any other jurisdiction.

12. Counterparts. This Agreement may be executed in two or more counterparts, each of which will constitute an original, but all of which, when taken together, will constitute but one instrument, and will become effective when one or more counterparts have been signed by each party hereto and delivered to the other parties. The Company and the Investors acknowledge and agree that the Company shall deliver its counterpart to the Investors along with the Prospectus Supplement (or the filing by the Company of an electronic version thereof with the Commission).

13. Press Release. The Company and the Investors agree that the Company shall (a) prior to the opening of the financial markets in New York City on January 13, 2016 issue a press release announcing the Offering and disclosing all material information regarding the Offering, and (b) as promptly as practicable on January 13, 2016 file a current report on Form 8-K with the Securities and Exchange Commission including, but not limited to, a form of this Agreement and the form of Warrant as exhibits thereto, provided that the Company shall not issue any such press release or file or otherwise publicize such current report on Form 8-K without the prior consent of the Investors, it being agreed that the Company shall provide drafts of such press release and current report to the Investors for their review and comment and will include therein any reasonable comments of the Investors thereon. Without limiting the foregoing, the Company shall not make any public statements or disclosures regarding the Investors or the transactions contemplated hereby without the prior consent of the Investors.

14. Termination. In the event that any of the conditions to closing in Section 4.2(b) shall not have been satisfied in full and shall not have been expressly waived in writing by the

Investors on or prior to the second business day following the date of the execution of this Agreement by all parties, this Agreement shall terminate upon the delivery of written notice thereof by the Investors to the Company provided that (i) any such termination of this Agreement shall not relieve any party hereto of any liability in respect of any breach hereof arising prior to the termination of this Agreement (or following such termination with respect to any provisions that survive the termination of this Agreement), and (ii) this Section 14, the last sentence of Section 4.1(a) and Sections 2.3, 6, 7, 8, 9, 10, 11, 12, 13, 15, 18, 19, 23 and 24 shall survive any such termination.

15. Registration Rights.

15.1 Upon request of the Investors (which the Investors may deliver from time to time on one or more occasions), the Company shall file a registration statement covering any or all of the shares of capital stock of the Company held by the Investors or any affiliate thereof and any shares of capital stock issuable to the Investors upon the exercise of any convertible security (including Warrants and the warrants that were issued pursuant to the Prior Subscription Agreement (the “Prior Warrants”)) from time to time, which registration statement shall provide for the resale of such shares and, following the filing thereof, the Company shall use commercially reasonable efforts to have such registration statement declared effective as promptly as practicable; provided that (i) a Form S-3 registration will be utilized unless the Company is prohibited from using a Form S-3 registration, (ii) assuming use of a Form S-3 registration, the Company shall file such registration statement within sixty (60) days after the request of the Investors and, if Form S-3 is not available, the Company shall file such other registration statement within ninety (90) days after the request of the Investors, and (iii) the Company will bear all costs associated with preparation and filing the registration statement and maintaining the effectiveness of such registration statement and all other costs and expenses incurred in connection with any offering made pursuant to the terms thereof (including the costs and expenses of one counsel for the Investors), but excluding underwriting discounts and commissions. The Company shall use commercially reasonable efforts to cause such registration statement to remain effective until all shares subject thereto have been sold or otherwise disposed of by the Investors. If the Investors shall elect for any such registration to be an underwritten offering, the Company shall provide such assistance in connection therewith as the Investors may reasonably request, including allowing the underwriters to conduct due diligence and causing the accountants and counsel to the Company to cooperate in connection therewith, including by providing customary comfort letters and legal opinions The requirements under this Section 15.1 will terminate when upon the Investors and their affiliates owning less than five percent (5%) of the outstanding shares of common stock of the Company (assuming conversion of all convertible securities, including the Warrants and the Prior Warrants, held by the Investors and their affiliates).

15.2 The Company shall indemnify each Investor and, as applicable, each of its officers, affiliates, directors, partners, beneficiaries, members, and each person controlling each such Investor within the meaning of either Section 15 of the Securities Act or Section 20 of the Exchange Act, with respect to each registration effected pursuant to the terms hereof, and each underwriter, if any, and each person who controls any such underwriter within the meaning of either Section 15 of the Securities Act or Section 20 of the Exchange Act, against

all claims, losses, damages and liabilities (or actions in respect thereof) arising out of or based on any untrue statement (or alleged untrue statement) of a material fact contained in any registration statement, prospectus, offering circular or other document utilized in connection with any such registration, or based on any omission (or alleged omission) to state therein a material fact required to be stated therein or necessary to make the statements therein not misleading, or any violation by the Company of the Securities Act or the Exchange Act or any rule or regulation thereunder applicable to the Company and relating to action or inaction required of the Company in connection with any such registration, and will reimburse each such Investor and, as applicable, each of its affiliates, officers, directors, partners, beneficiaries, and members, and each person controlling each such Investor within the meaning of either Section 15 of the Securities Act or Section 20 of the Exchange Act, each such underwriter and each person who controls any such underwriter within the meaning of either Section 15 of the Securities Act or Section 20 of the Exchange Act, for any legal and any other expenses reasonably incurred in connection with investigating and defending any such claim, loss, damage, liability or action; provided, however, that the Company will not be liable in any such case to the extent that any such claim, loss, damage, liability or expense arises out of or is based on any untrue statement or omission (or alleged untrue statement or omission) based upon written information furnished to the Company by the Investors or the underwriters in connection with any such Registration and stated to be specifically for use in any registration statement, prospectus, offering circular or other document utilized in connection with any such registration.

15.3 If the indemnification provided for in this Section 15 is held by a court of competent jurisdiction to be unavailable to an indemnified party with respect to any loss, liability, claim, damage or expense referred to herein, then the Company, in lieu of indemnifying such indemnified party hereunder, shall contribute to the amount paid or payable by such indemnified party as a result of such loss, liability, claim, damage or expense in such proportion as is appropriate to reflect the relative fault of the Company, on the one hand, and of the indemnified party, on the other hand, in connection with the statements or omissions which resulted in such loss, liability, claim, damage or expense, as well as any other relevant equitable considerations; provided, however, that the contribution obligations of any Investor shall be limited to an amount equal to the net proceeds that such Investor receives in respect of the shares sold by such Investor in the registration to which such contribution is being made. The relative fault of the Company and of the indemnified party shall be determined by reference to, among other things, whether the untrue (or alleged untrue) statement of a material fact or the omission (or alleged omission) to state a material fact relates to information supplied by the Company or by the indemnified party and the parties’ relative intent, knowledge, access to information and opportunity to correct or prevent such statement or omission.

16. Resale of Securities. Each Investor agrees that it shall not resell any Securities acquired pursuant to the terms hereof for a period of six (6) months following the First Closing Date, provided that the foregoing shall not preclude the Investors from selling any such Securities in connection with any change of control of the Company or any announcement by any person (including the Company) that it is seeking to effect a change of control of the Company.

17. Interim Covenants; Other Matters

17.1 During the period from the date of this Agreement and continuing until the earlier of the (i) termination of this Agreement, and (ii) the Subsequent Closing, the Company will not, and will not permit any of its Subsidiaries to, without the prior written consent of the Investors, (1) issue, grant, deliver or sell, or authorize the issuance, grant, delivery or sale of, or purchase, repurchase, redeem or otherwise acquire, or propose the purchase, repurchase, redemption or other acquisition of, any equity or equity-linked securities of the Company or any of its Subsidiaries (including any securities or rights convertible into or exercisable or exchangeable for equity securities of the Company or any of its Subsidiaries), except that nothing contained in this Section 17.1 shall prohibit the issuance of any of the foregoing to, or the repurchase of any of the foregoing from, employees, consultants or directors of the Company or any Subsidiary thereof (solely in the case of repurchases, in connection with the cessation of service to the Company or its Subsidiaries) pursuant to the Company’s equity plans in existence as of the date hereof and described in the Registration Statement, the Disclosure Package and the Prospectus, (2) adopt or propose any change in its Articles of Incorporation, By-laws or comparable organizational documents, (3) make any declaration, set aside or payment of any dividend or other distribution with respect to any capital stock thereof, (4) incur, assume or guarantee any indebtedness for borrowed money or otherwise if the principal amount of all such indebtedness so incurred, assumed or guaranteed would exceed $1,000,000 in the aggregate, or (5) otherwise take any action that would have, or be reasonably likely to have, an adverse effect on the ability of the Company to consummate the transactions contemplated hereby.

17.2 On the date hereof, the Company has adopted the amendment to the Bylaws thereof in the form attached as Exhibit C hereto.

17.3 If there is any stock split, combination or similar action taken by the Company on or prior to the occurrence of the First Closing or the Subsequent Closing, then share numbers and purchase prices referred to herein shall be subject to proportional adjustment, subject to the approval of the Investors.

18. Additional Director.

18.1 So long as the Investors and their controlled affiliates beneficially own (as set forth in Rule 13d-3 of the rules and regulations promulgated under the Exchange Act but assuming that any convertible securities (including the Warrants and the Prior Warrants) owned by the Investors or any controlled affiliate thereof are immediately exercisable) shares of Common Stock that satisfies the Ownership Threshold, the Investors will have the right, at any time on or after the First Closing Date, to direct the Company to appoint one person (the “Sarissa Designee”) to the Board of Directors (the “Board”) of the Company reasonably acceptable to the Board, it being understood and agreed that upon the exercise by the Investors of the right to appoint the Sarissa Designee, such Sarissa Designee shall be placed in the class of directors chosen by the Investors (so long as the Company maintains a staggered Board). Upon the exercise by the Investors of their rights set forth in this Section 18, the Company shall promptly thereafter expand the size of the Board by one seat and appoint the Sarissa Designee to fill the resulting vacancy. If, at any time following the appointment of any Sarissa Designee to the Board, such Sarissa Designee shall resign therefrom or be unable to serve on the Board, then the Investors, so long as they and their controlled affiliates

beneficially own (as set forth in Rule 13d-3 of the rules and regulations promulgated under the Exchange Act but assuming that any convertible securities (including the Warrants and the Prior Warrants) owned by the Investors or any controlled affiliate thereof are immediately exercisable) shares of Common Stock that satisfies the Ownership Threshold shall have the right to designate a replacement therefor and promptly following such designation, the Company shall cause such person to become a member of the Board as the Sarissa Designee. For purposes hereof, the “Ownership Threshold” will be deemed satisfied so long as the Investors and their controlled affiliates beneficially own (as set forth in Rule 13d-3 of the rules and regulations promulgated under the Exchange Act but assuming that any convertible securities (including the Warrants and the Prior Warrants) have been converted into Common Stock) at least 4,635,878 shares of Common Stock (which amount shall be subject to adjustment for stock splits, combinations or similar actions).

18.2 The Sarissa Designee agrees to submit (to the extent not already submitted) to the Company a fully completed copy of the Company’s standard directors’ and officers’ questionnaire, conflict of interest questionnaire, and other reasonable and customary director onboarding documentation required by the Company in connection with the appointment or election of a new director as soon as practicable on or after the exercise by Sarissa of its rights set forth in this Section 18 and to be governed by the same obligations regarding conflicts of interest, fiduciary duties, trading and disclosure policies and other governance guidelines as are applicable to all other directors of the Company. As a condition to the Sarissa Designee’s appointment to the Board and nomination at any annual meeting, the Investors agree to provide to the Company, and request that the Sarissa Designee provide to the Company, such information as is required to be disclosed in proxy statements under applicable law or would otherwise be necessary for inclusion of the Sarissa Designee in connection with the appointment or election of a member of the Board.

18.3 The Company shall use reasonable best efforts to cause the election of the Sarissa Designee so nominated by the Investors at each meeting of the stockholders at which such election is considered (including listing the Sarissa Designee in the proxy statement and proxy card prepared, filed and delivered in connection with such meeting and recommending that the Company’s stockholders vote in favor of the election of the Sarissa Designee (along with all other Company nominees) and otherwise supporting the Sarissa Designee for election in a manner no less rigorous and favorable than the manner in which the Company supports its other nominees).

18.4 Notwithstanding anything to the contrary in this Agreement, if at any time after the date hereof, the Investors (together with its controlled affiliates) cease to beneficially own (as set forth in Rule 13d-3 of the rules and regulations promulgated under the Exchange Act but assuming that any convertible securities (including the Warrants) owned by the Investors or any controlled affiliate thereof are immediately exercisable) shares of Common Stock that satisfies the Ownership Threshold, then the Sarissa Designee shall promptly tender his resignation from the Board and any committee of the Board on which he is a member and the Company shall have no further obligations under this Section 18.

19. Preemptive Rights.

19.1 In the event that the Company determines to issue shares of Common Stock or other securities or instruments convertible into shares of Common Stock (“Equity Securities”), other than Excluded Securities (as defined below) (such Equity Securities excluding Excluded Securities, the “Proposed Securities”), the Company shall provide written notice (a “Preemptive Rights Notice”) thereof to the Investors so long as the Investors (together with its controlled affiliates) beneficially own (as set forth in Rule 13d-3 of the rules and regulations promulgated under the Exchange Act but assuming that any convertible securities (including the Warrants and the Prior Warrants) owned by the Investors or any controlled affiliate thereof are immediately exercisable) shares of Common Stock that satisfies the Ownership Threshold. The Preemptive Rights Notice must be delivered to the Investors at least five (5) business days prior to the date of such issuance and shall set forth a summary of the material terms of such Proposed Securities, including the amount of Proposed Securities to be issued, the purchase price therefor and the date of issuance of such Proposed Securities. Each Investor shall have the right (a “Preemptive Right”) to purchase a portion (the “Pro Rata Portion”) of the Proposed Securities equal to up to the number of Proposed Securities proposed to be issued multiplied by a fraction, the numerator of which the number of shares of Common Stock owned by such Investor at the time of the Preemptive Rights Notice (assuming, for these purposes, the conversion or exercise of any securities of the Company that are convertible into or exercisable for shares of Common Stock, including the Warrants and the Prior Warrants), and the denominator of which is the number of shares of Common Stock that are issued and outstanding as of the date of the Preemptive Rights Notice. Each Investor that desires to exercise its Preemptive Rights hereunder must exercise such Preemptive Right within five (5) business days after receipt of the Preemptive Rights Notice from the Company, and any failure to exercise such Preemptive Right within such time period shall be deemed a waiver of the Preemptive Right in respect of the Proposed Securities referred to in the related Preemptive Rights Notice.

19.2 Upon the expiration of the offering periods described above, the Company will be free to sell such Proposed Securities that the Investors have not elected to purchase during the ninety (90) days following such expiration on terms and conditions not materially more favorable to the purchasers thereof than those offered to such Investors. Any Proposed Securities that the Investors do not elect to purchase and that are offered or sold by the Company after such ninety (90)-day period must be reoffered to the Investors pursuant to the terms hereof.

19.3 Notwithstanding anything to the contrary set forth in this Section 19, the Company may offer and sell Proposed Securities without prior notice to the Investors if the Company has been advised by an investment bank, underwriter, placement agent or other financial advisor that compliance with the terms of Section 19.1 could reasonably be expected to jeopardize the ability of the Company to consummate such offering; provided, however, that, subject to the rules and regulations of the Commission and the Nasdaq Stock Market LLC, immediately following the consummation of the applicable offering, each Investor shall have the right thereafter to purchase up to a number of Proposed Securities such that the Investors own the same percentage of the outstanding Common Stock of the Company that they (and their affiliates) owned immediately prior to such offering giving rise to the Preemptive Rights described herein (assuming any convertible securities held by the Investors and their affiliates (including the Warrants and the Prior Warrants) have been exercised) on the same

terms, conditions and price provided for in the applicable offering and under the same conditions and within the timeframe set forth in Section 19.1.

19.4 For purposes hereof, “Excluded Securities” means (a) any shares of capital stock of the Company issued as a dividend or distribution on any outstanding shares of capital stock thereof, (b) any shares of Common Stock or options or other rights to acquire shares of Common Stock issued or granted to employees, service providers, officers, directors, managers of, or contractors, consultants or advisors to, the Company or any of its Subsidiaries pursuant to incentive, service or employment agreements, equity purchase or equity option plans, equity bonuses or awards, warrants, contracts or other arrangements that are approved by the Board, (c) any shares of capital stock issued by the Company upon the exercise or conversion of warrants to purchase capital stock of the Company or other convertible securities (i) outstanding immediately prior to the First Closing or (ii) issued after the First Closing pursuant to an exemption from this Section 19 or otherwise in compliance with this Section 19, (d) any shares of Common Stock or securities convertible into or exercisable for shares of Common Stock that are issued in connection with any bona fide third party debt financing of the Company that is approved by the Board, and (e) any shares of Common Stock or securities convertible into or exercisable for shares of Common Stock that are issued as consideration (and not financing) pursuant to the acquisition of another person that is not an affiliated of the Company or any of its Subsidiaries by the Company or any of its Subsidiaries or a license, collaboration, distribution or similar commercial arrangement entered into by the Company or any of its Subsidiaries with a person that is not an affiliate of the Company or any of its Subsidiaries and that is approved by the Board (other than any such arrangement primarily for capital-raising purposes).

19.5 Each Investor acknowledges and agrees that such Investor’s execution of this Agreement shall serve as a waiver, in respect of the shares of Common Stock to be issued to the Investors pursuant to this Agreement and the Other Investors in accordance with the terms hereof, of the Preemptive Rights Notice requirement for the Preemptive Rights set forth and defined in the Subscription Agreement between the Company and the Investors dated February 10, 2015 (the “Prior Subscription Agreement”), and consents to the calculation of such Investor’s Pro Rata Portion (as defined in, and pursuant to the rights under, the Prior Subscription Agreement) of the Shares and Warrants being sold pursuant to this Agreement and the Subscription Agreements with the Other Investors, notwithstanding any requirements to the contrary in the Prior Subscription Agreement; provided that the foregoing waiver shall be void and of no further force or effect if the First Closing and the First Closing with the Other Investors shall not have been consummated on or before the second business day following the date hereof.

20. Termination of Covenants under Prior Subscription Agreement. Upon execution of this Agreement by the Company and the Investors, Sections 17, 18, and 19 of the Prior Subscription Agreement shall thereafter be of no further force or effect.

21. Stockholder Approval.

21.1 The Company shall provide each stockholder entitled to vote at a special meeting of stockholders of the Company (the “Stockholder Meeting”), which shall be held as soon as

reasonably possible following the mailing of the proxy statement to the stockholders of the Company in respect thereof (the “Proxy Statement”), but not later than three business days prior to April 29, 2016, unless such date is extended in the sole discretion of the Company or the Investors pursuant to Section 4.1(b), in which case the Stockholder Meeting shall be held not later than three business days prior to May 31, 2016 (three business days prior to April 29, 2016 or May 31, 2016, as applicable, being referred to herein as the “Stockholder Meeting Outside Date”), a copy of the Proxy Statement, at the expense of the Company, soliciting each such stockholder’s affirmative vote at the Stockholder Meeting for approval of a proposal providing for issuance of the Subsequent Closing Shares and Subsequent Closing Warrants and such other matters relating thereto as the Investors may reasonably request, in each case in compliance with the rules and regulations of the Nasdaq Stock Market LLC, the Articles of Incorporation of the Company, the Bylaws of the Company and applicable law (collectively, the “Stockholder Approval”, and the date the Stockholder Approval is obtained, the “Stockholder Approval Date”). As reasonably promptly as practicable after execution of this Agreement, but in no event later than January 25, 2016, the Company shall, in consultation with the Investors, prepare and file with the Securities Exchange Commission (the “Commission”), the preliminary Proxy Statement and related proxy materials in compliance with Section 14 of the Exchange Act. As reasonably promptly as practicable after comments, if any, are received from the Commission thereon and after the furnishing by the Company and the Investors of all information required to be contained therein, the Company shall, in consultation with the Investors, prepare and the Company shall file any required amendments to the Proxy Statement with the Commission. The Company shall notify the Investors reasonably promptly of the receipt of any comments from the Commission or its staff and of any request by the Commission or its staff for amendments or supplements to the Proxy Statement or for additional information and shall consult with the Investors regarding, and supply the Investors with copies of, all correspondence between the Company or any of its representatives, on the one hand, and the Commission or its staff, on the other hand, with respect to the Proxy Statement. Prior to filing or mailing the initial Proxy Statement or any proposed amendment of or supplement to the Proxy Statement, the Company shall provide the Investors a reasonable opportunity to review and comment on such document and shall incorporate therein any reasonable comments of the Investors thereto. The Company shall use its best efforts to have the Proxy Statement cleared by the Commission and shall thereafter mail to the stockholders of the Company as reasonably promptly as possible the Proxy Statement and all other proxy materials for the Stockholder Meeting.

21.2 The Company hereby covenants and agrees that (a) the Proxy Statement will, when filed, comply as to form in all material respects with the applicable requirements of the Exchange Act and (b) none of the information included or incorporated by reference in the Proxy Statement will, at the date it is first mailed to the stockholders of the Company or at the time of the Stockholder Meeting or at the time of any amendment or supplement thereof, contain any untrue statement of a material fact or omit to state any material fact required to be stated therein or necessary in order to make the statements therein, in light of the circumstances under which they are made, not misleading.

21.3 The Company shall take, in accordance with applicable law and its Articles of Incorporation and Bylaws, all action necessary to convene the Stockholder Meeting as

promptly as reasonably practicable but no later than April 1, 2016 and to submit at the Stockholder Meeting for approval by the requisite vote of the stockholders of the Company the matters subject to Stockholder Approval. In connection with the Stockholder Meeting and any adjournment or postponement thereof, (i) the Board of Directors shall recommend that its stockholders vote in favor of all matters submitted thereto as such meeting and (ii) neither the Board of Directors nor any committee thereof shall withdraw or modify, or propose or resolve to withdraw or modify in a manner adverse to the Investors, such recommendation. The Company shall take all lawful action to solicit from the stockholders of the Company proxies in favor of the Stockholder Approval and take all other action reasonably necessary or advisable to secure the vote or consent of the stockholders that are required by the rules of Nasdaq Stock Market LLC and applicable law, including, if necessary or appropriate or if requested by the Investors, adjourning the Stockholder Meeting to solicit additional proxies. For the avoidance of doubt, if requested by the Investors and subject to compliance with applicable law, the Company shall adjourn or postpone the Stockholder Meeting, but no later than three business days prior to Stockholder Meeting Outside Date, if necessary to solicit additional proxies to allow for the matters subject to the Stockholder Meeting to be duly adopted and approved by the stockholders of the Company. The Company will enforce any and all voting agreements entered into by the Other Investors in respect of the matters subject to the Stockholder Meeting.

22. Voting Agreement. Each of the Investors agrees to vote all shares of voting capital stock of the Company (including but not limited to all shares of Common Stock) registered in its name or beneficially owned by it as of the date hereof and any and all other securities of the Company legally or beneficially acquired by it after the date hereof (other than the First Closing Shares) at the Stockholder Meeting in favor of the Stockholder Approval (i.e., the proposal providing for issuance of the Subsequent Closing Shares and Subsequent Closing Warrants in compliance with the rules and regulations of the Nasdaq Stock Market LLC). In the event that such Investor fails to vote the shares it is entitled to vote in the manner set forth above, such Investor shall be deemed immediately upon the existence of such breach to have appointed the Chief Executive Officer of the Company, with full power of substitution, as the proxy of such Investor with respect to the matters set forth herein, and hereby authorizes and directs such proxy to represent and vote such Investor’s shares to ensure that such shares will be voted as set forth herein. Each of the Investors acknowledges that each proxy granted hereby, including any successive proxy if need be, is given to secure the performance of a duty, is coupled with an interest, and shall be irrevocable until the duty is performed. Each Investor hereby revokes any and all previous proxies with respect to the shares of the Company’s voting capital stock as it relates to the Stockholder Meeting. Each Investor agrees not to grant any proxy with respect to such shares of voting capital stock of the Company or enter into or agree to be bound by any voting trust agreement or other arrangement of any kind that is inconsistent with the provisions of this Agreement. Notwithstanding the foregoing and for clarity, the First Closing Shares shall not be not counted for purposes of the Stockholder Approval pursuant to the rules of the Nasdaq Stock Market LLC.

23. Expenses; Indemnity. Except as otherwise expressly set forth herein, each party shall pay any fees or expenses incurred thereby in connection with the execution of this Agreement and the consummation of the transactions contemplated hereby. Notwithstanding the foregoing, at the First Closing, the Company shall pay or reimburse the Investors in respect of all fees and

expenses of outside legal counsel to the Investors, such payment or reimbursement in respect of the fees and expenses of outside legal counsel not to exceed $40,000 in the aggregate. In addition, should any litigation, action or proceeding be commenced or threatened in connection with the transactions contemplated by this Agreement or other documents and agreements being executed in connection therewith, the Company will indemnify and hold the Investors harmless with respect thereto, including in respect of reasonable fees and expenses of outside legal counsel to the Investors, provided that the foregoing shall not apply in the case of (a) any litigation, action or proceeding commenced by the Company in connection with any breach by the Investors of the representations, warranties or covenants of the Investors set forth in this Agreement, or (b) the gross negligence or willful misconduct of the Investors, in each case as determined in a final and non-appealable judgment of a court of competent jurisdiction.

24. Specific Performance. Each party hereby acknowledges and agrees that the failure of the other parties to perform their respective agreements and covenants hereunder will cause irreparable injury to the other parties, for which damages, even if available, will not be an adequate remedy. Accordingly, each party hereby agrees that any other party shall be entitled to the issuance of injunctive relief by any court of competent jurisdiction to compel performance of such party’s obligations, and the parties waive the requirement to post a bond or other collateral in connection therewith or any defense that money damages is a sufficient remedy.

25. Further Assurances. The Company agrees to execute and deliver, and cause each of its Subsidiaries to execute and deliver, and each Investor agrees to execute and deliver, such other documents, certificates, agreements and other writings and to take such other actions as may be reasonably necessary or desirable in order to consummate or implement expeditiously the transactions contemplated by this Agreement and the other documents referred to herein.

EXHIBIT A

APRICUS BIOSCIENCES, INC.

INVESTOR QUESTIONNAIRE

Pursuant to Section 4 of Annex I to the Agreement, please provide us with the following information: