Document:

EX-10.3

 Exhibit 10.3 

SECURITIES ISSUANCE AGREEMENT 

THIS SECURITIES ISSUANCE AGREEMENT (the “Agreement”), dated as of January 13, 2015, by and among ZIOPHARM
Oncology, Inc., a Delaware corporation (the “Issuer”), the University of Texas System Board of Regents on behalf of The University of Texas M.D. Anderson Cancer Center, an agency of the State of Texas (“MD
Anderson”). Capitalized terms used herein but not otherwise defined shall have the meanings given to them in Section 1.4. 

RECITALS 
 A. Effective as
of January 9, 2015, the Issuer and Intrexon Corporation, a Virginia corporation (“Intrexon” and together with the Issuer, the “Issuer Group”), executed a side letter agreement (the “Side Letter
Agreement”), in connection with that certain License Agreement of even date herewith between the Board of Regents (the “Board”) of the University of Texas System, on behalf of MD Anderson (the “License
Agreement”), pursuant to which the Board, on behalf of MD Anderson, is licensing the rights to certain technology to the Issuer Group, as licensees. 

B. As recited by the Side Letter Agreement, in consideration of, among other things, MD Anderson’s agreement to undertake any and all
extraordinary efforts to expedite and/or shorten its contracting, review and approval processes and to conclude and execute the License Agreement on or before the Accelerated Closing Deadline (as defined in the Side Letter Agreement), each member of
the Issuer Group has agreed to issue and sell to MD Anderson certain shares of common stock of such member of the Issuer Group. 
 C. The
Issuer and MD Anderson are executing and delivering this Agreement in reliance upon the exemption from registration afforded by Section 4(a)(2) of the Securities Act of 1933, as amended (the “Securities Act”), and Rule 506(b)
of Regulation D (“Regulation D”) as promulgated by the United States Securities and Exchange Commission (the “Commission”) under the Securities Act. 

AGREEMENT 
 NOW,
THEREFORE, IN CONSIDERATION of the mutual covenants contained in this Agreement, and for other good and valuable consideration the receipt and adequacy of which are hereby acknowledged, the Issuer and MD Anderson agree as follows: 

ARTICLE I 
 PURCHASE AND
SALE 
 1.1 Authorization of Sale of Shares. 

(a) Issuer Shares. Subject to the terms and conditions of this Agreement, the Issuer shall issue to MD Anderson One Million, Five
Hundred Ninety-Seven Thousand, Six Hundred Two (1,597,602) shares of Issuer Common Stock (the “Issuer Shares”). 

  
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 (b) Capital Adjustments. If after the date hereof, but prior to the date the Issuer Shares
have been issued to MD Anderson in accordance with Section 1.3(a): (i) the outstanding shares of Issuer Common Stock shall be subdivided or split into a greater number of shares or a dividend in Issuer Common Stock shall be paid in respect
of Issuer Common Stock or (ii) the outstanding shares of Issuer Common Stock are combined, then all share quantities in this Agreement not yet issued shall be appropriately adjusted to reflect such stock split, stock dividend or conjunction. If
after the date hereof, but prior to the date the Issuer Shares have been issued to MD Anderson in accordance with Section 1.3(a): (i) the Issuer shall pay a dividend in securities of the Issuer (other than in Issuer Common Stock) or of
other property (including cash) on Issuer Common Stock, or (ii) there shall occur any merger, consolidation, capital reorganization or reclassification in which Issuer Common Stock is converted or exchanged for securities, cash or other
property, the class or series of stock constituting Issuer Common Stock for purposes of this Agreement, shall be appropriately adjusted to reflect such other dividend, merger, consolidation, capital reorganization or reclassification. After any
event referenced in clauses (i) through (ii) of the immediately preceding sentence is consummated, if applicable, all references herein to Issuer Common Stock shall be deemed to refer to the capital stock or property (including cash) into
or for which the Issuer Common Stock was converted or exchanged, with the necessary changes in detail. 
 1.2 Closing. Subject to the
terms and conditions set forth in this Agreement, at the Closing, the Issuer shall issue and sell to MD Anderson, and MD Anderson shall purchase from the Issuer, the Issuer Shares. The closing of the issuance of the Issuer Shares to MD Anderson by
the Issuer (the “Closing”) will occur, subject to the conditions set forth in Article V, within the time period specified in the License Agreement or on such other date as the Issuer and MD Anderson may agree upon (the
“Closing Date”). The Closing shall take place at the offices of Cooley LLP, 500 Boylston Street, Boston, Massachusetts, 02116 or at such other place as the Issuer and MD Anderson may agree upon. 

1.3 Closing Deliverables. 

(a) Promptly following the Closing, the Issuer shall deliver to MD Anderson certificates representing the Issuer Shares purchased at the
Closing, registered in the names of MD Anderson. 
 (b) At the Closing, the Issuer and MD Anderson shall execute and deliver the
Registration Rights Agreement. 
 1.4 Defined Terms Used in This Agreement. In addition to the terms defined elsewhere in this
Agreement, the following terms have the meanings indicated: 
 “Affiliate” means, with respect to any Person, any other
Person that directly or indirectly controls or is controlled by or under common control with such Person. For the purposes of this definition, “control,” when used with respect to any Person, means the possession, directly or
indirectly, of the power to direct or cause the direction of the management and policies of such Person, whether through the ownership of voting securities, by contract or otherwise; and the terms of “affiliated,”
“controlling” and “controlled” have meanings correlative to the foregoing. 

  
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 “Issuer Common Stock” means the Issuer’s common stock, par value $0.001 per
share. 
 “Issuer Covered Person” means, with respect to the Issuer as an “issuer” for purposes of Rule 506
promulgated under the Securities Act, any Person listed in the first paragraph of Rule 506(d)(1). 
 “NASDAQ” means the
NASDAQ Stock Market, LLC. 
 “Person” means an individual or a corporation, partnership, trust, incorporated or
unincorporated association, joint venture, limited liability company, joint stock company, government (or an agency or political subdivision thereof) or other entity of any kind. 

“Registration Rights Agreement” means that certain Registration Rights Agreement of even date herewith, among the Issuer and
MD Anderson, in the form of Exhibit A attached to this Agreement. 
 “Trading Day” means a NASDAQ trading day.

 “Transaction Documents” means this Agreement, the Registration Rights Agreement, the License Agreement, and the
schedules and exhibits attached hereto and thereto. 
 ARTICLE II 

REPRESENTATIONS AND WARRANTIES OF THE ISSUER 

Subject to and except as set forth in the SEC Documents (as defined below) or on the Disclosure Schedule which is arranged in sections
corresponding to the sub-section numbered provisions contained below in this Section, the Issuer hereby represents and warrants to MD Anderson as of the date hereof as follows: 

2.1 Organization, Good Standing and Power. The Issuer is a corporation duly incorporated, validly existing and in good standing under
the laws of the State of Delaware and has the requisite corporate power to own, lease and operate its properties and assets and to conduct its business as it is now being conducted and as described in the reports filed by the Issuer with the
Commission pursuant to the reporting requirements of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), since the end of the Issuer’s 2013 fiscal year through the date hereof, including, without limitation,
the Issuer’s most recent quarterly report on Form 10-Q. The Issuer does not have any subsidiaries. The Issuer is qualified to do business as a foreign corporation and is in good standing in every jurisdiction in which the nature of the business
conducted or property owned by it makes such qualification necessary, except for any jurisdiction(s) (alone or in the aggregate) in which the failure to be so qualified will not have a Material Adverse Effect. For the purposes of this Agreement,
“Material Adverse Effect” means any effect on the business, operations, properties or financial condition of the Issuer that is material and adverse to the Issuer, taken as a whole, and any condition, circumstance or situation that
would prohibit the Issuer from entering into and performing any of its obligations hereunder. 
 2.2 Authorization; Enforcement. The
Issuer has the requisite corporate power and authority to enter into and perform the Transaction Documents and to issue and sell the Issuer 

  
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Shares to be issued by the Issuer in accordance with the terms hereof. The execution, delivery and performance of this Agreement by the Issuer and the consummation by it of the transactions
contemplated hereby have been duly and validly authorized by all necessary corporate action, and no further consent or authorization of the Issuer, its board of directors or stockholders is required. When executed and delivered by the Issuer, this
Agreement shall constitute a valid and binding obligation of the Issuer enforceable against the Issuer in accordance with its terms, except as such enforceability may be limited by applicable bankruptcy, reorganization, moratorium, liquidation,
conservatorship, receivership or similar laws relating to, or affecting generally the enforcement of, creditor’s rights and remedies or by other equitable principles of general application. The Issuer’s board of directors, at a meeting
duly called and held, adopted resolutions approving the transactions contemplated hereby, including the issuance of the Issuer Shares to be issued by the Issuer pursuant to this Agreement. 

2.3 Issuance of Issuer Shares. The Issuer Shares to be issued and sold by the Issuer hereunder have been duly authorized by all
necessary corporate action and, when paid for and issued in accordance with the terms hereof, will be validly issued, fully paid and nonassessable. In addition, the Issuer Shares will be free and clear of all liens, claims, charges, security
interests or agreements, pledges, assignments, covenants, restrictions or other encumbrances created by, or imposed by, the Issuer (collectively, “Encumbrances”) and rights of refusal of any kind imposed by the Issuer (other than
restrictions on transfer under applicable securities laws) and the holder of the Issuer Shares shall be entitled to all rights accorded to a holder of Issuer Common Stock. 

2.4 No Conflicts; Governmental Approvals. The execution, delivery and performance of the Transaction Documents by the Issuer and the
consummation by the Issuer of the transactions contemplated hereby do not and will not (i) violate any provision of the Issuer’s certificate of incorporation or bylaws as currently in effect, (ii) conflict with, or constitute a default (or an
event which, with notice or lapse of time or both, would become a default) under, or give to others any rights of termination, amendment, acceleration or cancellation of, any agreement, mortgage, deed of trust, indenture, note, bond, license, lease
agreement, instrument or obligation to which the Issuer is a party or by which the Issuer’s properties or assets are bound, or (iii) result in a violation of any federal, state, local or foreign statute, rule, regulation, order, judgment or
decree (including federal and state securities laws and regulations) applicable to the Issuer or by which any property or asset of the Issuer is bound or affected. The Issuer is not required under federal, state, foreign or local law, rule or
regulation to obtain any consent, authorization or order of, or make any filing or registration with, any court or governmental agency in order for it to execute, deliver or perform any of its obligations under this Agreement or issue and sell the
Issuer Shares to be issued by the Issuer in accordance with the terms hereof (other than any filings, consents and approvals which may be required to be made by the Issuer under applicable state and federal securities laws, rules or regulations
prior to or subsequent to the Closing). 
 2.5 Capitalization. The issued and outstanding shares of capital stock of the Issuer have
been validly issued, are fully paid and nonassessable and are not subject to any preemptive rights, rights of first refusal or similar rights. The Issuer has an authorized, issued and outstanding capitalization as set forth in the Issuer’s most
recent annual report on Form 10-K or quarterly report on Form 10-Q (other than the grant of additional awards under the Issuer’s 

  
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equity incentive plans or changes in the number of outstanding shares of Issuer Common Stock due to the issuance of shares upon the exercise or conversion of securities exercisable for, or
convertible or exchangeable into, shares of Issuer Common Stock outstanding). Except as disclosed in the Issuer’s most recent annual report on Form 10-K or quarterly report on Form 10-Q, the Issuer does not have outstanding any options to
purchase, or any rights or warrants to subscribe for, or any securities or obligations convertible into, or exchangeable for, or any contracts or commitments to issue or sell, any shares of capital stock or other securities (other than the grant of
additional awards under the Issuer’s equity incentive plans). 
 2.6 SEC Documents, Financial Statements. The Issuer represents
and warrants that as of the date hereof, the Issuer Common Stock is registered pursuant to Section 12(b) of the Exchange Act. Since January 1, 2013, the Issuer has timely filed all reports, schedules, forms, statements and other documents
required to be filed by it with the Commission pursuant to the reporting requirements of the Exchange Act (the “SEC Documents”). At the times of their respective filing, all such reports, schedules, forms, statements and other
documents of the Issuer complied in all material respects with the requirements of the Exchange Act and the rules and regulations of the Commission promulgated thereunder. At the times of their respective filings, such reports, schedules, forms,
statements and other documents of the Issuer did not contain any untrue statement of a material fact or omit to state a material fact required to be stated therein or necessary in order to make the statements therein, in light of the circumstances
under which they were made, not misleading. As of the date hereof, the Issuer meets the “Registrant Requirements” for eligibility to use Form S-3 set forth in General Instruction I.A to Form S-3. As of their respective dates, the financial
statements of the Issuer included in the SEC Documents complied in all material respects with applicable accounting requirements and the published rules and regulations of the Commission or other applicable rules and regulations with respect
thereto. Such financial statements have been prepared in accordance with generally accepted accounting principles applied on a consistent basis during the periods involved (except (i) as may be otherwise indicated in such financial statements or the
notes thereto or (ii) in the case of unaudited interim statements, to the extent they may not include footnotes or may be condensed or summary statements), and fairly present in all material respects the consolidated financial position of the Issuer
as of the dates thereof and the results of operations and cash flows for the periods then ended (subject, in the case of unaudited statements, to normal year-end audit adjustments). 

2.7 Accountants. The Issuer represents and warrants that McGladrey LLP, whose report on the financial statements of the Issuer is filed
with the Commission in the Issuer’s Annual Report on Form 10-K for the year ended December 31, 2013, was, at the time such report was issued, an independent registered public accounting firm as required by the Securities Act. Except as
described in the SEC Documents and as preapproved in accordance with the requirements set forth in Section 10A of the Exchange Act, to the Issuer’s knowledge, McGladrey LLP has not engaged in any non-audit services prohibited by subsection
(g) of Section 10A of the Exchange Act on behalf of the Issuer. 
 2.8 Internal Controls. The Issuer has established and
maintains a system of internal accounting controls sufficient to provide reasonable assurances that: (i) transactions are executed in accordance with management’s general or specific authorization; (ii) transactions are recorded as necessary to
permit preparation of financial statements in conformity with generally accepted 

  
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accounting principles in the United States and to maintain accountability for assets; (iii) access to assets is permitted only in accordance with management’s general or specific
authorization; and (iv) the recorded accountability for assets is compared with existing assets at reasonable intervals and appropriate action is taken with respect to any differences. 

2.9 Disclosure Controls. The Issuer has established and maintains disclosure controls and procedures (as such term is defined in
Rules 13a-15 and 15d-15 under the Exchange Act). Since the date of the most recent evaluation of such disclosure controls and procedures, there have been no significant changes in internal controls or in other factors with respect to the Issuer
that could significantly affect the Issuer’s internal controls, including any corrective actions with regard to significant deficiencies and material weaknesses. The Issuer is in compliance in all material respects with all provisions currently
in effect and applicable to the Issuer of the Sarbanes-Oxley Act of 2002, and all rules and regulations promulgated thereunder or implementing the provisions thereof. 

2.10 No Material Adverse Change. Except as disclosed in the SEC Documents, since December 31, 2013, the Issuer has not
(i) experienced or suffered any Material Adverse Effect, (ii) incurred any material liabilities, obligations, claims or losses (whether liquidated or unliquidated, secured or unsecured, absolute, accrued, contingent or otherwise) other than
those incurred in the ordinary course of the Issuer’s business or (iii) declared, made or paid any dividend or distribution of any kind on its capital stock. 

2.11 No Undisclosed Events or Circumstances. Except as disclosed in the SEC Documents, since December 31, 2013, except for the
consummation of the transactions contemplated herein, to the Issuer’s knowledge, no event or circumstance has occurred or exists with respect to the Issuer or its businesses, properties, prospects, operations or financial condition, which,
under applicable law, rule or regulation, requires public disclosure or announcement by the Issuer but which has not been so publicly announced or disclosed. 

2.12 Litigation. Except as disclosed in the SEC Documents, no action, suit, proceeding or investigation is currently pending or, to the
knowledge of the Issuer, has been threatened in writing against the Issuer that: (i) concerns or questions the validity of this Agreement; (ii) concerns or questions the right or authority of the Issuer to enter into the Transaction Documents and to
perform its obligations thereunder; or (iii) is reasonably likely to have a Material Adverse Effect. The Issuer is neither a party to nor subject to the provisions of any material order, writ, injunction, judgment or decree of any court or
government agency or instrumentality. There is no action, suit, proceeding or investigation by the Issuer currently pending or that the Issuer intends to initiate that would have a Material Adverse Effect. 

2.13 Compliance. The Issuer (i) is not in violation of any provision of the Issuer’s certificate of incorporation or bylaws
as currently in effect, (ii) is not in default under or in violation of (and no event has occurred that has not been waived that, with notice or lapse of time or both, would result in a default by the Issuer under), nor has the Issuer received
notice of a claim that it is in default under or that it is in violation of, any indenture, loan or credit agreement or any other agreement or instrument to which it is a party or by which it or any of its properties is bound (whether or not such
default or violation has been waived), (iii) is not in violation of any order of any court, arbitrator or governmental body, or (iii) is not or has not been in violation 

  
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of any statute, rule or regulation of any governmental authority, including without limitation all foreign, federal, state and local laws applicable to its business, except in each case (other
than with respect to clause (i) above) for such defaults or violations as would not have a Material Adverse Effect. 
 2.14 Listing
and Maintenance Requirements. The Issuer is in compliance with the requirements of the NASDAQ for continued listing of the Issuer Common Stock thereon and the Issuer has not received any notification that, and has no knowledge that the NASDAQ is
contemplating terminating such listing. The issuance and sale of the Issuer Shares hereunder does not contravene the rules and regulations of the NASDAQ in any material respect. 

2.15 Investment Company Act. The Issuer is not and, after giving effect to the offering and sale of the Issuer Shares, will not be an
“investment company” or an entity “controlled” by an “investment company,” as such terms are defined in the Investment Company Act of 1940. 

2.16 Private Placement. Neither the Issuer nor its Affiliates, nor any Person acting on its or their behalf, (i) has engaged in any
form of general solicitation or general advertising (within the meaning of Regulation D under the Securities Act) in connection with the offer or sale of the Issuer Shares hereunder, (ii) has, directly or indirectly, made any offers or sales of any
security or solicited any offers to buy any security, under any circumstances that would require registration of the sale and issuance by the Issuer of the Issuer Shares under the Securities Act or (iii) has issued any shares of Issuer Common Stock
or shares of any series of preferred stock or other securities or instruments convertible into, exchangeable for or otherwise entitling the holder thereof to acquire shares of Issuer Common Stock which would be integrated with the sale of the Issuer
Shares to MD Anderson for purposes of the Securities Act or of any applicable stockholder approval provisions, including, without limitation, under the rules and regulations of any exchange or automated quotation system on which any of the
securities of the Issuer are listed or designated, nor will the Issuer or any of its Affiliates take any action or steps that would require registration of any of the Issuer Shares under the Securities Act or cause the offering of the Issuer Shares
to be integrated with other offerings. Assuming the accuracy of the representations and warranties of MD Anderson, the offer and sale of the Issuer Shares to be issued by the Issuer to MD Anderson pursuant to this Agreement will be exempt from the
registration requirements of the Securities Act. 
 2.17 No Manipulation of Stock. The Issuer has not taken and will not, in
violation of applicable law, take, any action outside the ordinary course of business designed to or that might reasonably be expected to cause or result in unlawful manipulation of the price of the Issuer Common Stock. 

2.18 Brokers. Neither the Issuer nor any of the officers, directors or employees of the Issuer has employed any broker or finder in
connection with the transaction contemplated by this Agreement. 
 2.19 OFAC. Neither the Issuer nor, to the Issuer’s knowledge,
any director, officer, agent, employee, Affiliate or person acting on behalf of the Issuer, is currently subject to any U.S. sanctions administered by the Office of Foreign Assets Control of the U.S. Treasury Department. 

2.20 Reliance. The Issuer understands that the foregoing representations and warranties shall be deemed material and to have been
relied upon by MD Anderson. 

  
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 ARTICLE III 

REPRESENTATIONS, WARRANTIES AND COVENANTS OF MD ANDERSON 

MD Anderson hereby represents, warrants and covenants to the Issuer as follows: 

3.1 Authorization and Power. MD Anderson has the requisite power and authority to enter into and perform the Transaction Documents and
to purchase the Issuer Shares being sold to it hereunder. The execution, delivery and performance of this Agreement by MD Anderson and the consummation by it of the transactions contemplated hereby have been duly authorized by all necessary
corporate action, and no further consent or authorization of MD Anderson or its board of regents, board of directors, stockholders or other governing body is required. When executed and delivered by MD Anderson, this Agreement shall constitute a
valid and binding obligation of MD Anderson, enforceable against MD Anderson in accordance with its terms, except as such enforceability may be limited by applicable bankruptcy, insolvency, reorganization, moratorium, liquidation, conservatorship,
receivership or similar laws relating to, or affecting generally the enforcement of, creditor’s rights and remedies or by other equitable principles of general application. 

3.2 No Conflict. The execution, delivery and performance of the Transaction Documents by MD Anderson and the consummation by MD
Anderson of the transactions contemplated hereby do not and will not (i) violate any provision of MD Anderson’s charter or organizational documents, (ii) conflict with, or constitute a default (or an event which with notice or lapse of time or
both would become a default) under, or give to others any rights of termination, amendment, acceleration or cancellation of, any agreement, mortgage, deed of trust, indenture, note, bond, license, lease agreement, instrument or obligation to which
MD Anderson is a party or by which MD Anderson’s properties or assets are bound, or (iii) result in a violation of any federal, state, local or foreign statute, rule, regulation, order, judgment or decree (including federal and state securities
laws and regulations) applicable to MD Anderson or by which any property or asset of MD Anderson are bound or affected, except, in all cases, other than violations (with respect to federal and state securities laws) above, for such conflicts,
defaults, terminations, amendments, acceleration, cancellations and violations as would not, individually or in the aggregate, materially and adversely affect MD Anderson’s ability to perform its obligations under this Agreement. 

3.3 Purchaser Sophistication; Accredited Investor. MD Anderson (a) is knowledgeable, sophisticated and experienced in making, and is
qualified to make decisions with respect to, investments in shares presenting an investment decision like that involved in the purchase of the Issuer Shares, including investments in securities issued by the Issuer and investments in comparable
companies, and has requested, received, reviewed and considered all information it deemed relevant in making an informed decision to purchase the Issuer Shares; (b) in connection with its decision to purchase the Issuer Shares, relied only upon the
SEC Documents, other publicly available information, and the representations and warranties of the Issuer contained herein; (c) is an “accredited investor” pursuant to Rule 501 of Regulation D under the Securities Act; (d) is
acquiring the Issuer Shares for its own account for investment 

  
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only and with no present intention of distributing any of the Issuer Shares or any arrangement or understanding with any other persons regarding the distribution of the Issuer Shares; (e) has not
been organized, reorganized or recapitalized specifically for the purpose of investing in the Issuer Shares; (f) will not, directly or indirectly, offer, sell, pledge, transfer or otherwise dispose of (or solicit any offers to buy, purchase or
otherwise acquire to take a pledge of) any of the Issuer Shares except in compliance with the Securities Act and applicable state securities laws; (g) understands that the Issuer Shares are being offered and sold to it in reliance upon specific
exemptions from the registration requirements of the Securities Act and state securities laws, and that the Issuer is relying upon the truth and accuracy of, and MD Anderson’s compliance with, the representations, warranties, agreements,
acknowledgments and understandings of MD Anderson set forth herein in order to determine the availability of such exemptions and the eligibility of MD Anderson to acquire the Issuer Shares; (h) understands that its investment in the Issuer Shares
involves a significant degree of risk, including a risk of total loss of MD Anderson’s investment (provided that such acknowledgment in no way diminishes the representations, warranties and covenants made by the Issuer hereunder); and (i)
understands that no United States federal or state agency or any other government or governmental agency has passed upon or made any recommendation or endorsement of the Issuer Shares. 

3.4 Principal Office. MD Anderson maintains its principal executive office in Houston, Texas. 

3.5 Restricted Shares. MD Anderson acknowledges that the Issuer Shares are restricted securities and must be held indefinitely unless
subsequently registered under the Securities Act or (if the Issuer is not selling the Issuer Shares pursuant to Rule 144 promulgated under the Securities Act) the Issuer receives an opinion of counsel reasonably satisfactory to the Issuer that
such registration is not required. MD Anderson is aware of the provisions of Rule 144 promulgated under the Securities Act which provide a safe harbor for the limited resale of stock purchased in a private placement subject to the satisfaction of
certain conditions (if applicable), including, among other things, the existence of a public market for the stock, the availability of certain current public information about the Issuer, the resale occurring after certain holding periods have been
met, the sale being conducted through a “broker’s transaction” or a transaction directly with a “market maker” and the number of shares of the stock being sold during any three-month period not exceeding specified
limitations. MD Anderson further acknowledges and understands that the Issuer may not be satisfying the current public information requirement of Rule 144 at the time MD Anderson wishes to sell the Issuer Shares and, if so, MD Anderson may be
precluded from selling the Issuer Shares under Rule 144 even if the required holding period has been satisfied. 
 3.6 Ownership of
Capital Stock. As of the date hereof, excluding the Issuer Shares, MD Anderson and its Affiliates beneficially own no shares of capital stock of the Issuer. 

3.7 Stock Legends. MD Anderson acknowledges that certificates evidencing the Issuer Shares shall bear a restrictive legend in
substantially the following form (and including related stock transfer instructions and record notations): 
 THESE SECURITIES HAVE NOT BEEN
REGISTERED WITH THE SECURITIES AND EXCHANGE COMMISSION OR THE SECURITIES 

  
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COMMISSION OF ANY STATE IN RELIANCE UPON AN EXEMPTION FROM REGISTRATION UNDER THE SECURITIES ACT OF 1933, AS AMENDED (THE “SECURITIES ACT”), AND, ACCORDINGLY, MAY NOT BE OFFERED OR SOLD
EXCEPT PURSUANT TO AN EFFECTIVE REGISTRATION STATEMENT UNDER THE SECURITIES ACT OR PURSUANT TO AN AVAILABLE EXEMPTION FROM, OR IN A TRANSACTION NOT SUBJECT TO, THE REGISTRATION REQUIREMENTS OF THE SECURITIES ACT AND IN ACCORDANCE WITH APPLICABLE
STATE SECURITIES LAWS OR BLUE SKY LAWS AS EVIDENCED BY A LEGAL OPINION OF COUNSEL REASONABLY SATISFACTORY TO THE COMPANY. 
 3.8 No
Legal, Tax or Investment Advice. MD Anderson understands that nothing in this Agreement or any other materials presented by or on behalf of the Issuer to MD Anderson in connection with the purchase of the Issuer Shares constitutes legal, tax or
investment advice. MD Anderson has consulted such legal, tax and investment advisors as it, in its sole discretion, has deemed necessary or appropriate in connection with its purchase of the Issuer Shares. 

3.9 Brokers and Finders. No Person will have, as a result of the transactions contemplated by this Agreement, any valid right, interest
or claim against or upon the Issuer or MD Anderson for any commission, fee or other compensation pursuant to any agreement, arrangement or understanding entered into by or on behalf of MD Anderson. 

3.10 Regulation M. MD Anderson is aware that the anti-manipulation rules of Regulation M under the Exchange Act may apply to sales of
Issuer Common Stock and other activities with respect to Issuer Common Stock. 
 ARTICLE IV 

COVENANTS OF THE PARTIES 

4.1 Lockup. 
 (a)
Agreement to Lock-Up. MD Anderson hereby agrees that it will not, without the prior written consent of the Issuer during the period commencing on the Closing Date and ending on the date that is one hundred twenty (120) days after the
Closing Date (i) lend, offer, pledge, sell, contract to sell, sell any option or contract to purchase, purchase any option or contract to sell, grant any option, right or warrant to purchase, or otherwise transfer or dispose of, directly or
indirectly, any shares of Issuer Common Stock; or (ii) enter into any swap or other arrangement that transfers to another, in whole or in part, any of the economic consequences of ownership of any shares of Issuer Common Stock, whether any such
transaction described in clause (a) or (b) above is to be settled by delivery of Issuer Common Stock or other securities, in cash or otherwise; provided, that this Section 4.1 shall not apply to any transfer of Issuer Shares by MD Anderson to
its Affiliates, provided that as a condition of such transfer, such Affiliate agrees in writing to be bound by the provisions of this Section 4.1 to the same extent as MD Anderson. 

(b) Stop Transfer Instructions. In order to enforce the foregoing covenant, the Issuer may impose stop-transfer instructions with
respect to the shares of Issuer Common Stock of MD Anderson (and transferees and assignees thereof) until the end of such restricted period. 

  
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 4.2 Further Transfers. Without in any way limiting the provisions of Section 4.1, MD
Anderson covenants that the Issuer Shares will only be sold, offered for sale, pledged, loaned, or otherwise disposed of pursuant to an effective registration statement under, and in compliance with the requirements of, the Securities Act or
pursuant to an available exemption from the registration requirements of the Securities Act, and in compliance with any applicable state securities laws. In connection with any transfer of Issuer Shares other than pursuant to an effective
registration statement or Rule 144, the Issuer may require MD Anderson to provide to the Issuer an opinion of counsel selected by MD Anderson, the form and substance of which opinion shall be reasonably satisfactory to the Issuer, to the effect that
such transfer does not require registration under the Securities Act. 
 4.3 Furnishing of Information. In order to enable MD
Anderson to sell the Issuer Shares under Rule 144, until the date that the Issuer Shares cease to be Registrable Securities (as defined in the Registration Rights Agreement) (and for no less than 12 months from the Closing), the Issuer shall use its
commercially reasonable efforts to timely file (or obtain extensions in respect thereof and file within the applicable grace period) all reports required to be filed by the Issuer after the date hereof pursuant to the Exchange Act. If, during such
period, the Issuer is not required to file reports pursuant to the Exchange Act, it shall use its commercially reasonable efforts to prepare and furnish to MD Anderson and make publicly available in accordance with Rule 144(c) such information as is
required for MD Anderson to sell the Issuer Shares under Rule 144. 
 4.4 No Integration. The Issuer shall not, and shall use its
commercially reasonable efforts to ensure that no Affiliate of the Issuer shall, sell, offer for sale or solicit offers to buy or otherwise negotiate in respect of any security (as defined in Section 2 of the Securities Act) that will be
integrated with the offer or sale of the Issuer Shares pursuant to this Agreement in a manner that would require the registration under the Securities Act of the sale of the Issuer Shares to MD Anderson, or that will be integrated with the offer or
sale of the Issuer Shares pursuant to this Agreement for purposes of the rules and regulations of the NASDAQ such that it would require stockholder approval prior to the closing of such other transaction unless stockholder approval is obtained
before the closing of such subsequent transaction. 
 ARTICLE V 

CONDITIONS TO CLOSING 
 5.1
Conditions Precedent to the Obligations of MD Anderson. The obligation of MD Anderson to acquire the Issuer Shares at the Closing is subject to the satisfaction or waiver by MD Anderson, at or before the Closing, of each of the following
conditions: 
 (a) Representations and Warranties. The representations and warranties of the Issuer contained in Article II
shall be true and correct in all respects as of the date of this Agreement and as of the Closing Date. 

  
 11 

 (b) Performance. The Issuer shall have performed and complied with all covenants,
agreements, obligations and conditions contained in this Agreement that are required to be performed or complied with by the Issuer on or before the Closing. 

(c) No Injunction. No statute, rule, regulation, executive order, decree, ruling or injunction shall have been enacted, entered,
promulgated or endorsed by any court or governmental authority of competent jurisdiction that prohibits the consummation of any of the transactions contemplated by the Transaction Documents. 

(d) Listing of Additional Shares. The Issuer shall have submitted a Listing of Additional Shares Notification with the NASDAQ covering
all of the Issuer Shares. 
 (e) License Agreement. Each Licensee shall have executed and delivered the License Agreement, and the
License Agreement shall be in full force and effect. 
 (f) Registration Rights Agreement. The Issuer shall have executed and
delivered the Registration Rights Agreement, and the Registration Rights Agreement shall be in full force and effect. 
 5.2 Conditions
Precedent to the Obligations of the Issuer. The obligation of the Issuer to issue the Issuer Shares at the Closing is subject to the satisfaction or waiver by the Issuer, at or before the Closing, of each of the following conditions: 

(a) Representations and Warranties. The representations and warranties of MD Anderson contained in Article III shall be true and
correct in all respects as of the Closing. 
 (b) Performance. MD Anderson shall have performed, satisfied and complied in all
material respects with all covenants, agreements and conditions required by the Transaction Documents to be performed, satisfied or complied with by MD Anderson at or prior to the Closing. 

(c) No Injunction. No statute, rule, regulation, executive order, decree, ruling or injunction shall have been enacted, entered,
promulgated or endorsed by any court or governmental authority of competent jurisdiction that prohibits the consummation of any of the transactions contemplated by the Transaction Documents 

(d) “Bad Actor” Certifications. The Issuer and each Issuer Covered Person shall have provided to the Issuer a properly
completed and executed questionnaire in the form of Exhibit B hereto prior to the date hereof and on or prior to the Closing Date no “bad actor” disqualifying event described in Rule 506(d)(1)(i)-(viii) of the Securities Act (a
“Disqualification Event”) is applicable to the Issuer or, to the Issuer’s knowledge, the Issuer Covered Person, except for a Disqualification Event as to which Rule 506(d)(2)(ii–iv) or (d)(3), is applicable. 

(e) License Agreement. MD Anderson shall have executed and delivered the License Agreement, and the License Agreement shall be in full
force and effect. 

  
 12 

 (f) Registration Rights Agreement. MD Anderson shall have executed and delivered the
Registration Rights Agreement, and the Registration Rights Agreement shall be in full force and effect. 
 (g) Intrexon
Documentation. MD Anderson shall deliver evidence satisfactory to the Issuer that Intrexon has executed and delivered a securities issuance agreement and registration rights agreement in form and substance reasonably satisfactory to the Issuer.

 ARTICLE VI 

MISCELLANEOUS 
 6.1
Survival of Warranties. Unless otherwise set forth in this Agreement, the representations and warranties of the Issuer and MD Anderson contained in or made pursuant to this Agreement (a) shall survive the execution and delivery of this
Agreement and the Closing for a period of three (3) years after the Closing; provided, however, notwithstanding the foregoing, the representations and warranties of the Issuer set forth in Sections 2.1, 2.2 and 2.3 shall survive the execution
and delivery of this Agreement and the Closing indefinitely; and (b) shall in no way be affected by any investigation or knowledge of the subject matter thereof made by or on behalf of MD Anderson or the Issuer. 

6.2 No Finder’s Fees. Each party represents that it neither is nor will be obligated for any finder’s fee or commission in
connection with this transaction. The Issuer agrees to indemnify and to hold harmless MD Anderson from any liability for any commission or compensation in the nature of a finder’s or broker’s fee arising out of this transaction (and the
costs and expenses of defending against such liability or asserted liability) for which the Issuer or any of its officers, employees or representatives is responsible. MD Anderson, severally, agrees to indemnify and hold harmless the Issuer from any
liability for any commission or compensation in the nature of a finder’s or broker’s fee arising out of this transaction (and the costs and expenses of defending against such liability or asserted liability) for which MD Anderson or any of
its officers, employees or representatives is responsible. 
 6.3 Fees and Expenses. Each party shall pay the fees and expenses of
its advisors, counsel, accountants and other experts, if any, and all other expenses, incurred by such party incident to the negotiation, preparation, execution, delivery and performance of this Agreement. 

6.4 Entire Agreement. The Transaction Documents, together with the Exhibits and Schedules thereto, contain the entire understanding of
the parties with respect to the subject matter hereof and supersede all prior agreements and understandings, oral or written, with respect to such matters, which the parties acknowledge have been merged into such documents, exhibits and schedules.

 6.5 Notices. Any and all notices or other communications or deliveries required or permitted to be provided hereunder shall be in
writing and shall be deemed given and effective on the earliest of (a) the date of transmission, if such notice or communication is delivered via facsimile or email at the facsimile number or email address specified in this Section prior to 4:00
p.m. (New York City time) on a Trading Day, (b) the next Trading Day after the date of transmission, if such notice or communication is delivered via facsimile or email at the facsimile 

  
 13 

 
number or email address specified in this Section on a day that is not a Trading Day or later than 4:00 p.m. (New York City time) on any Trading Day, (c) the Trading Day following the date of
deposit with a nationally recognized overnight courier service, or (d) upon actual receipt by the party to whom such notice is required to be given. The addresses, facsimile numbers and email addresses for such notices and communications are those
set forth below, or such other address or facsimile number as may be designated in writing hereafter, in the same manner, by any such Person: 
  

			
	If to the Issuer:	  	ZIOPHARM Oncology, Inc.
		  	1 First Avenue
		  	Parris Building, #34
		  	Boston, MA 02129
		  	Attention: Chief Executive Officer
		  	Email: cbelbel@ziopharm.com
		  	Fax No.: 617.778.0420
		
	with copies (which copies	  	Cooley LLP
	shall not constitute notice	  	500 Boylston Street
	to the Issuer) to:	  	Boston, MA 02116
		  	Attention: Marc Recht
		  	Email: mrecht@cooley.com
		  	Fax No.: 617.937.2400
		
	If to MD Anderson	  	 University of Texas System Board of Regents on behalf of The University of Texas M.D. Anderson Cancer Center

Legal Services-Unit 1674
 P.O. Box 301407

Houston, Texas 77230-1407
 Attention: Legal Services

 
 And
  

Legal Services-1MC11.3433
 The University of Texas M. D. Anderson
Cancer Center
 7007 Bertner Avenue
 Houston, Texas
77030-3907
 Attention: Legal Services

 6.6 Amendments; Waivers. This Agreement and any term hereof may be amended, terminated or waived only
with the written consent of the Issuer and MD Anderson. No waiver of any default with respect to any provision, condition or requirement of this Agreement shall be deemed to be a continuing waiver in the future or a waiver of any subsequent default
or a waiver of any other provision, condition or requirement hereof, nor shall any delay or omission of either party to exercise any right hereunder in any manner impair the exercise of any such right. 

  
 14 

 6.7 Construction. The headings herein are for convenience only, do not constitute a part
of this Agreement and shall not be deemed to limit or affect any of the provisions hereof. The language used in this Agreement will be deemed to be the language chosen by the parties to express their mutual intent, and no rules of strict
construction will be applied against any party. 
 6.8 Successors and Assigns. This Agreement shall be binding upon and inure to the
benefit of the parties and their successors and permitted assigns. The Issuer may not assign this Agreement or any rights or obligations hereunder without the prior written consent of MD Anderson; provided, however, that no such
consent shall be required in connection with any assignment (i) occurring by operation of law in connection with any merger or consolidation to which the Issuer is a party, (ii) in connection with the acquisition of all or substantially all of the
assets of the Issuer or (iii) any other similar business combination transaction involving the Issuer. MD Anderson may assign its rights under this Agreement only to a Person to whom MD Anderson assigns or transfers all Issuer Shares held by MD
Anderson; provided, that (i) following such transfer or assignment, the further disposition of the Issuer Shares by the transferee or assignee is restricted under the Securities Act and applicable state securities laws, (ii) as a
condition of such transfer, such transferee agrees in writing to be bound by all of the terms and conditions of this Agreement as a party hereto and (iii) such transfer shall have been made in accordance with the applicable requirements of this
Agreement and with all laws applicable thereto. 
 6.9 Persons Entitled to Benefit of Agreement. This Agreement is intended for the
benefit of the parties hereto and their respective permitted successors and assigns and is not for the benefit of, nor may any provision hereof be enforced by, any other person. 

6.10 State Agency Limitations. MD Anderson is an agency of the State of Texas and under the Constitution and laws of the State of Texas
possesses certain rights and privileges, is subject to certain limitations and restrictions, and only has such authority as is granted to it under the Constitution and laws of the State of Texas. Notwithstanding any provision hereof, nothing in this
Agreement is intended to be, nor will it be construed to be, a waiver of the sovereign immunity of the State of Texas or a prospective waiver or restriction of any of the rights, remedies, claims, and privileges of the State of Texas. Moreover,
notwithstanding the generality or specificity of any provision hereof, the provisions of this agreement as they pertain to MD Anderson are enforceable only to the extent authorized by the Constitution and laws of the State of Texas. 

6.11 Governing Law; Dispute Resolution. This Agreement will be governed by the laws of the State of Texas without regard to conflict of
law principles. In the event of any dispute between the Issuer on the one hand, and MD Anderson on the other (a “Dispute”), the parties agree that such Dispute shall be first submitted for resolution for a period of ten
(10) calendar days to designated senior officers of each of the parties who hold legal authority to resolve and settle such dispute. If any Dispute cannot be resolved and settled within such period, then to the extent authorized by the law
governing the power and authority of each party, the parties agree to submit such Dispute to full and binding arbitration that will be undertaken and conducted under the auspices of the American Arbitration Association by a panel of three
(3) arbitrators pursuant to that organization’s Commercial Arbitration Rules then in effect, as modified by and subject to the following terms: 

(a) MD Anderson, on the one hand, and the Issuer, on the other, will each choose one arbitrator and those two arbitrators will select the
third arbitrator. 

  
 15 

 (b) The fees and expenses of the arbitrators shall be borne in equal shares by the parties. 

(c) Each party shall bear the fees and expenses of its legal representation in the arbitration. 

(d) The arbitral tribunal shall not reallocate either the fees and expenses of the arbitrators or of the parties’ legal representation.

 (e) The arbitration shall be held in Nashville, Tennessee, USA which shall be the seat of the arbitration. 

(f) The arbitrators may not award, and no party may seek, indirect, incidental, consequential, punitive, exemplary, special, or enhanced
damages, or prejudgment interest, or attorneys’ fees or costs, nor may the arbitrators apply any multiplier to any award of actual damages, except as may be required by statute. 

(g) The arbitrators must issue a reasoned award, setting forth the arbitrators’ findings of fact and conclusions of law. 

(h) The award of the arbitrators may be entered in any court of competent jurisdiction. The award rendered by the arbitrators shall be final
and binding on the parties, except that the award is subject to limited judicial review and vacatur for the following reasons only: (i) the award was procured by corruption, fraud, or undue means, (ii) the award was tainted by evidence of
partiality or corruption by any of the arbitrators, (iii) the award was tainted by misconduct by any of the arbitrators, (iv) the arbitrators exceeded their powers, and/or (v) the award evidences a manifest disregard of the law or is
contrary to public policy. If the parties are unable to resolve a Dispute through binding arbitration, then any lawsuit pertaining to such Dispute that is brought by one party against another must be presented to and decided by a state or federal
court in the home locale of the defendant party (that being Houston, Texas for MD Anderson, and Boston, Massachusetts for the Issuer). 

6.12 Counterparts; Execution. This Agreement may be executed in three (3) or more counterparts, each of which shall be deemed an
original, but all of which together shall constitute one and the same instrument. Counterparts may be delivered via facsimile, electronic mail (including pdf or any electronic signature complying with the U.S. federal ESIGN Act of 2000, e.g.,
www.docusign.com) or other transmission method and any counterpart so delivered shall be deemed to have been duly and validly delivered and be valid and effective for all purposes. 

6.13 Severability. If any provision hereof should be held invalid, illegal or unenforceable in any respect, then, to the fullest extent
permitted by law, (a) all other provisions hereof shall remain in full force and effect and shall be liberally construed in order to carry out the intentions of the parties as nearly as may be possible and (b) the parties shall use their best
efforts to replace the invalid, illegal or unenforceable provision(s) with valid, legal and enforceable provision(s) which, insofar as practical, implement the purposes of such provision(s) in this Agreement. 

[SIGNATURE PAGES TO FOLLOW] 

  
 16 

 IN WITNESS WHEREOF, the parties hereto have caused this Securities Issuance Agreement to
be duly executed by their respective authorized signatories as of the date first indicated above. 
  

			
	THE ISSUER:
	
	ZIOPHARM ONCOLOGY, INC.
		
	By:	 	 /s/ Jonathan Lewis

		 	Jonathan Lewis, M.D., Ph.D.
		 	Chief Executive Officer

 SIGNATURE PAGE TO SECURITIES
ISSUANCE AGREEMENT 

 IN WITNESS WHEREOF, the parties hereto have caused this Securities Issuance Agreement to
be duly executed by their respective authorized signatories as of the date first indicated above. 
  

			
	MD ANDERSON:
	
	BOARD OF REGENTS OF THE UNIVERSITY OF TEXAS SYSTEM
	On behalf of The University of Texas M.D. Anderson Cancer Center
		
	By:	 	 /s/ Ronald A. DePinho, MD

	Name:	 	 Ronald A. DePinho, MD

	Title:	 	 President

 SIGNATURE PAGE TO SECURITIES
ISSUANCE AGREEMENT 

 Exhibit A 

REGISTRATION RIGHTS AGREEMENT 

[See Attached] 

 Exhibit B 

“BAD ACTOR” QUESTIONNAIRE FORMS 

 ZIOPHARM ONCOLOGY, INC. 

CONFIDENTIAL Rule 506 Disqualification Event Questionnaire (“Individual”) 

COMPLETED ON BEHALF
OF:                      

This questionnaire is being furnished to you to obtain information in connection with a potential offering (the
“Offering”) of securities under Rule 506 of the Securities Act of 1933 (the “Securities Act”). As used in this questionnaire, “you” also refers to any entity on whose behalf you
are responding. 
 Please review Exhibit A and confirm that you can make all of the statements on behalf of yourself, as well as any entity
that you control, directly or indirectly. If you cannot make one or more of the statements, please contact us to provide details. If you have doubts regarding whether you can make all of the statements, please contact us. 

By completing and signing this questionnaire, you also indicate: (i) your consent for Cooley LLP and its clients to rely upon the
information provided; (ii) your agreement to promptly notify Cooley LLP and the Issuer of securities of any changes in information provided that occurs after the date you sign the questionnaire and prior to the applicable offering of
securities; and (iii) your confirmation that the statements on Exhibit A are true and correct, to the best of your knowledge and belief after a reasonable investigation, as of the date you sign the questionnaire, as they pertain to you and to
any entity that you control.1 
 Please return this Questionnaire to Cooley LLP, Attn:
Christopher Gerry, by e-mail to cgerry@cooley.com. If you have any questions with respect to these matters, please contact Chris at cgerry@cooley.com or 617-937-2323. 

The statements on Exhibit A are true and correct to the best of my knowledge, information and belief after a reasonable investigation as of the date below.

  

							
	  
	 		 	  

	Date	 		 	(Signature)
				
		 		 		 	  

		 		 		 	(Printed Name)
				
		 		 		 	  

		 		 		 	Title (if applicable)
				
	Address:	 	  
	 		 	
			
	  
	 		 	

  

	1 	While the SEC has not provided specific guidance as to what they mean by “control” in this context, in other contexts the SEC has determined that control means the possession, direct or indirect, of the
power to direct or cause the direction of the management and policies of a person, whether through the ownership of voting securities, by contract, or otherwise. 

 Exhibit A 
  

	1.	Criminal Convictions. 

 You have not been convicted, within ten years before the sale of
the securities (or five years, in the case of issuers, their predecessors and affiliated issuers), of any felony or misdemeanor: 
  

	 	•	 	in connection with the purchase or sale of any security; 

  

	 	•	 	involving the making of any false filing with the SEC; or 

  

	 	•	 	arising out of the conduct of the business of an underwriter, broker, dealer, municipal securities dealer, investment advisor or paid solicitor of purchasers of securities. 

 

	2.	Court Orders, Injunctions and Decrees. 

 Your are not subject to any order, judgment or
decree of any court of competent jurisdiction, entered within five years before the sale of the securities, that, at the time of such sale, restrains or enjoins you from engaging or continuing to engage in any conduct or practice: 

 

	 	•	 	in connection with the purchase or sale of any security; 

  

	 	•	 	involving the making of any false filing with the SEC; or 

  

	 	•	 	arising out of the conduct of the business of an underwriter, broker, dealer, municipal securities dealer, investment adviser or paid solicitor of purchasers of securities. 

 

	3.	Final Orders from Specified State or Federal Regulators. 

 You are not subject to a final
order of a state securities commission (or an agency of officer of a state performing similar functions); a state authority that supervises or examines banks, savings associations, or credit unions; a state insurance commission (or an agency or
officer of a state performing similar functions); an appropriate federal banking agency; the Commodity Futures Trading Commission; or the National Credit Union Administration that: 

 

	 	•	 	at the time of the sale of the securities, bars you from: 

  

	 	•	 	association with an entity regulated by such commission, authority, agency or officer; 

  

	 	•	 	engaging in the business of securities, insurance or banking; or 

  

	 	•	 	engaging in savings association or credit union activities; or 

  

	 	•	 	constitutes a final order based on a violation of any law or regulation that prohibits fraudulent, manipulative, or deceptive conduct entered within ten years before the sale of the securities. 

 

	4.	SEC Disciplinary Orders. 

 You are not subject to an order of the SEC entered pursuant to
section 15(b) or 15B(c) of the Securities Exchange Act of 1934 (the “Exchange Act”) or section 203(e) or 203(f) of the Investment Advisers Act of 1940 (the “Advisers Act”) that, at the time of the sale of the securities: 

 

	 	•	 	suspends or revokes your registration as a broker, dealer, municipal securities dealer or investment adviser; 

  

	 	•	 	places limitations on the activities, functions or operations of, or imposes civil money penalties on, such person; or 

  

	 	•	 	bars you from being associated with any entity or from participating in the offering of any penny stock. 

	5.	SEC Cease and Desist Orders. 

 You are not subject to any order of the SEC, entered
within five years before the sale of the securities, that, at the time of such sale, orders you to cease and desist from committing or causing a future violation of: 
  

	 	•	 	any scienter-based anti-fraud provision of the federal securities laws, including, but not limited to, Section 17(a)(1) of the Securities Act, Section 10(b) of the Exchange Act and Rule 10b-5 thereunder, and
Section 206(1) of the Advisers Act or any other rule or regulation thereunder; or 

  

	 	•	 	Section 5 of the Securities Act. 

  

	6.	Suspension or Expulsion from SRO Membership or Association with an SRO Member. 

 You have
not been suspended or expelled from membership in, or suspended or barred from association with a member of, a securities self-regulatory organization (e.g., a registered national securities exchange or a registered national or affiliated securities
association) for any act or omission to act constituting conduct inconsistent with just and equitable principles of trade. 
  

	7.	SEC Refusal or Stop Order. 

 You have not filed (as a registrant or issuer), nor were you
named as an underwriter in any registration statement or Regulation A offering statement filed with the SEC that, within five years before the sale of the securities, was the subject of a refusal order, stop order, or order suspending the Regulation
A exemption, or is, at the time of the sale of the securities, the subject of an investigation or proceeding to determine whether a stop order or suspension order should be issued. 

 

	8.	U.S. Postal Service False Representation Orders. 

 You are not subject to a United States
Postal Service false representation order entered within five years before the sale of the securities, nor are you, at the time of the sale of the securities, subject to a temporary restraining order or preliminary injunction with respect to conduct
alleged by the United States Postal Service to constitute a scheme or device for obtaining money or property through the mail by means of false representations. 
  

	9.	Commission-based Solicitors. 

 You are not aware of any person or entity, other than any
person or entity engaged directly by the issuer, entitled (directly or indirectly) to receive any remuneration in connection with this offering other than as identified by you in writing to the issuer’s outside corporate counsel within the 20
days prior to the consummation of the offering. 

 ZIOPHARM ONCOLOGY, INC. 

CONFIDENTIAL Rule 506 Disqualification Event Questionnaire (“Entity”) 

COMPLETED ON BEHALF OF: BOARD OF REGENTS OF THE UNIVERSITY OF TEXAS
SYSTEM, On behalf of The University of Texas M.D. Anderson Cancer Center 
  

 
 This
questionnaire is being furnished to you to obtain information in connection with a potential offering (the “Offering”) of securities under Rule 506 of the Securities Act of 1933 (the “Securities Act”).
As used in this questionnaire, “you” refers to any entity on whose behalf you are responding. 
 Please review
Exhibit A and confirm that you can make all of the statements on behalf of Entity. If you cannot make one or more of the statements, please contact us to provide details. If you have doubts regarding whether you can make all of the statements,
please contact us. 
 By completing and signing this questionnaire, you also indicate that: (i) Cooley LLP and its clients may rely
upon the information provided; (ii) you will notify Cooley LLP and the Issuer of securities of any changes in information provided that occurs after the date you sign the questionnaire and prior to the applicable offering of securities; and
(iii) the statements on Exhibit A are true and correct, to the best of your knowledge and belief after a reasonable investigation, as of the date you sign the questionnaire. 

Please return this Questionnaire to Cooley LLP, Attn: Christopher Gerry, by e-mail to cgerry@cooley.com. If you have any questions with
respect to these matters, please contact Chris at cgerry@cooley.com or 617-937-2323. 
 The statements on Exhibit A are true and correct to the best of
my knowledge, information and belief after a reasonable investigation as of the date below. 
  

			
	BOARD OF REGENTS OF THE UNIVERSITY OF TEXAS SYSTEM
	On behalf of The University of Texas M.D. Anderson Cancer Center
		
	By:	 	  

	Name:	 	  

	Title:	 	  

	
	  

	Date	 	

 Exhibit A 
  

	1.	Criminal Convictions. 

 You have not been convicted, within ten years before the sale of
the securities (or five years, in the case of issuers, their predecessors and Affiliated Issuers), of any felony or misdemeanor: 
  

	 	•	 	in connection with the purchase or sale of any security; 

  

	 	•	 	involving the making of any false filing with the SEC; or 

  

	 	•	 	arising out of the conduct of the business of an underwriter, broker, dealer, municipal securities dealer, investment advisor or paid solicitor of purchasers of securities. 

 

	2.	Court Orders, Injunctions and Decrees. 

 You are not subject to any order, judgment or
decree of any court of competent jurisdiction, entered within five years before the sale of the securities, that, at the time of such sale, restrains or enjoins Entity from engaging or continuing to engage in any conduct or practice: 

 

	 	•	 	in connection with the purchase or sale of any security; 

  

	 	•	 	involving the making of any false filing with the SEC; or 

  

	 	•	 	arising out of the conduct of the business of an underwriter, broker, dealer, municipal securities dealer, investment adviser or paid solicitor of purchasers of securities. 

 

	3.	Final Orders from Specified State or Federal Regulators. 

 You are not subject to a final
order of a state securities commission (or an agency of officer of a state performing similar functions); a state authority that supervises or examines banks, savings associations, or credit unions; a state insurance commission (or an agency or
officer of a state performing similar functions); an appropriate federal banking agency; the Commodity Futures Trading Commission; or the National Credit Union Administration that: 

 

	 	•	 	at the time of the sale of the securities, bars Entity from: 

  

	 	•	 	association with an entity regulated by such commission, authority, agency or officer; 

  

	 	•	 	engaging in the business of securities, insurance or banking; or 

  

	 	•	 	engaging in savings association or credit union activities; or 

  

	 	•	 	constitutes a final order based on a violation of any law or regulation that prohibits fraudulent, manipulative, or deceptive conduct entered within ten years before the sale of the securities. 

 

	4.	SEC Disciplinary Orders. 

 You are not subject to an order of the SEC entered pursuant to
section 15(b) or 15B(c) of the Securities Exchange Act of 1934 (the “Exchange Act”) or section 203(e) or 203(f) of the Investment Advisers Act of 1940 (the “Advisers Act”) that, at the time of the sale of the securities: 

 

	 	•	 	suspends or revokes Entity’s registration as a broker, dealer, municipal securities dealer or investment adviser; 

  

	 	•	 	places limitations on the activities, functions or operations of, or imposes civil money penalties on, such person; or 

  

	 	•	 	bars Entity from being associated with any entity or from participating in the offering of any penny stock. 

	5.	SEC Cease and Desist Orders. 

 You are not subject to any order of the SEC, entered
within five years before the sale of the securities, that, at the time of such sale, orders Entity to cease and desist from committing or causing a future violation of: 
  

	 	•	 	any scienter-based anti-fraud provision of the federal securities laws, including, but not limited to, Section 17(a)(1) of the Securities Act, Section 10(b) of the Exchange Act and Rule 10b-5 thereunder, and
Section 206(1) of the Advisers Act or any other rule or regulation thereunder; or 

  

	 	•	 	Section 5 of the Securities Act. 

  

	6.	Suspension or Expulsion from SRO Membership or Association with an SRO Member. 

 You have
not been suspended or expelled from membership in, or suspended or barred from association with a member of, a securities self-regulatory organization (e.g., a registered national securities exchange or a registered national or affiliated securities
association) for any act or omission to act constituting conduct inconsistent with just and equitable principles of trade. 
  

	7.	SEC Refusal or Stop Order. 

 You have not filed (as a registrant or issuer), nor was
Entity named as an underwriter in any registration statement or Regulation A offering statement filed with the SEC that, within five years before the sale of the securities, was the subject of a refusal order, stop order, or order suspending the
Regulation A exemption, or is, at the time of the sale of the securities, the subject of an investigation or proceeding to determine whether a stop order or suspension order should be issued. 

 

	8.	U.S. Postal Service False Representation Orders 

 You are not subject to a United States
Postal Service false representation order entered within five years before the sale of the securities, nor is Entity, at the time of the sale of the securities, subject to a temporary restraining order or preliminary injunction with respect to
conduct alleged by the United States Postal Service to constitute a scheme or device for obtaining money or property through the mail by means of false representations. 
  

	9.	Affiliated Issuers 

 If you are controlled by any other entity or if any other entity is
an affiliated issuer of the issuer conducting the Offering as a result of your voting power or beneficial ownership of the issuer conducting the Offering, then you can confirm that each such entity can also make the statements set forth in
paragraphs 1 through 8 above. 
 [If You are the issuer in the offering, include the item below:] 

 

	10.	Other Issuer Covered Persons 

 Entity, the issuer in the offering, has distributed,
collected, and thoroughly reviewed a “Rule 506 Disqualification Questionnaire” from each Other Issuer Covered Person (defined herein). With respect to securities of the issuer to be offered and sold in the offering, each of issuer’s
predecessors (if any), affiliated issuers, directors, executive officers, other officers of the issuer participating in the offering, beneficial owner of 20% or more of the issuer’s outstanding voting equity securities, calculated on the basis
of voting power, promoters (as that term is defined in Rule 405 under the Securities Act) (each, an “Other Issuer Covered Person” and, together, “Other Issuer Covered 

 
Persons”) completed such questionnaire and confirmed that the statements on Exhibit A of such Other Issuer Covered Person’s questionnaire is true and correct as of the
date such Other Issuer Covered Person signed the questionnaire. You have no reason to believe, nor has any fact or circumstance come to the attention of the Entity, that (i) any of the Other Issuer Covered Persons incorrectly completed their
questionnaire or (ii) any of the Other Issuer Covered Persons will be unable to make the statements set forth in Exhibit A to their questionnaire prior to the offering of the securities.EX-10.4

 Exhibit 10.4 

EXECUTION VERSION 

REGISTRATION RIGHTS AGREEMENT 

THIS REGISTRATION RIGHTS AGREEMENT (this “Agreement”) is made and entered into as of January 13, 2015, by and
among ZIOPHARM Oncology, Inc., a Delaware corporation (the “Issuer”), and the University of Texas System Board of Regents on behalf of The University of Texas M.D. Anderson Cancer Center, an agency of the State of Texas (“MD
Anderson”), and shall become effective as of the Closing (as defined in the Issuance Agreement, defined below). 
 RECITALS

 A. This Agreement is being entered into pursuant to the Securities Issuance Agreement between the Issuer and MD Anderson dated as of
January 13, 2015 (the “Issuance Agreement”). 
 AGREEMENT 

NOW, THEREFORE, IN CONSIDERATION of the mutual covenants contained in this Agreement, and for other good and valuable consideration the
receipt and adequacy of which are hereby acknowledged, the Issuer and MD Anderson agree as follows: 
 ARTICLE I 

DEFINITIONS 
 Capitalized terms used and
not otherwise defined herein shall have the meanings given such terms in the Issuance Agreement. As used in this Agreement, the following terms shall have the following meanings: 

“Affiliate” means, with respect to any Person, any other Person that directly or indirectly controls or is controlled by or
under common control with such Person. For the purposes of this definition, “control,” when used with respect to any Person, means the possession, directly or indirectly, of the power to direct or cause the direction of the
management and policies of such Person, whether through the ownership of voting securities, by contract or otherwise; and the terms “affiliated,” “controlling” and “controlled” have meanings
correlative to the foregoing. 
 “Board” means the Board of Directors of the Issuer. 

“Business Day” means any day except Saturday, Sunday and any day which shall be a legal holiday or a day on which banking
institutions in the state of New York generally are authorized or required by law or other government actions to close. 
 “Closing
Date” means the date of the closing of the acquisition and issuance of the Issuer Shares pursuant to the Issuance Agreement. 

“Commission” means the Securities and Exchange Commission. 

  
 1. 

 “Effectiveness Date” the 120th calendar day following the Closing Date;
provided, however, that if the Effectiveness Date falls on a day that is not a Business Day, then the Effectiveness Date shall be extended to the next Business Day. 

“Effectiveness Period” shall have the meaning set forth in Article II. 

“Exchange Act” means the Securities Exchange Act of 1934, as amended. 

“Filing Date” means the fifteenth (15th) Business Day following the
Closing Date; provided, however, that if the Filing Date falls on a day that is not a Business Day, then the Filing Date shall be extended to the next Business Day. 

“Holder” or “Holders” means the holder or holders, as the case may be, from time to time of Registrable
Securities. 
 “Indemnified Party” shall have the meaning set forth in Section 5.3(a). 

“Indemnifying Party” shall have the meaning set forth in Section 5.3(a). 

“Issuer Common Stock” means, the Issuer’s Common Stock, par value $0.001 per share. 

“Issuer Shares” means the shares of Issuer Common Stock. 

“Losses” shall have the meaning set forth in Section 5.1. 

“Person” means an individual or a corporation, partnership, trust, incorporated or unincorporated association, joint venture,
limited liability company, joint stock company, government (or an agency or political subdivision thereof) or other entity of any kind. 

“Proceeding” means an action, claim, suit, investigation or proceeding (including, without limitation, an investigation or
partial proceeding, such as a deposition), whether commenced or threatened. 
 “Prospectus” means any prospectus included
in a Registration Statement (including, without limitation, a prospectus that includes any information previously omitted from a prospectus filed as part of an effective registration statement in reliance upon Rule 430A promulgated under the
Securities Act), as amended or supplemented by any prospectus supplement, with respect to the terms of the offering of any portion of the Registrable Securities covered by a Registration Statement, and all other amendments and supplements to any
such Prospectus, including post-effective amendments, and all material incorporated by reference in such Prospectus. 
 “Registrable
Securities” means all of the Issuer Shares issued to MD Anderson pursuant to the Issuance Agreement or otherwise held by MD Anderson on the date that the Registration Statement contemplated by Section 2.1 is filed by the Issuer, and
any securities issued with respect to, or in exchange for or in replacement of such shares of Issuer Common Stock upon any stock split, stock dividend, recapitalization, subdivision, merger or similar event; provided,

  
 2. 

 
however, that the applicable Holder has completed and delivered to the Issuer a Selling Stockholder Questionnaire; and provided further that such securities shall no longer be deemed
Registrable Securities if (i) such securities have been sold pursuant to a Registration Statement, (ii) such securities have been sold in compliance with Rule 144, or (ii) all such securities may be sold without limitation or
restriction pursuant to Rule 144. 
 “Registration Statement” means the registration statements and any additional
registration statements contemplated by Article II, including (in each case) the related Prospectus, amendments and supplements to such registration statement or Prospectus, including pre- and post-effective amendments, all exhibits thereto, and all
material incorporated by reference in such registration statement. 
 “Rule 144” means Rule 144 promulgated by the
Commission pursuant to the Securities Act, as such Rule may be amended from time to time, or any similar rule or regulation hereafter adopted by the Commission having substantially the same effect as such Rule. 

“Rule 415” means Rule 415 promulgated by the Commission pursuant to the Securities Act, as such Rule may be amended from time
to time, or any similar rule or regulation hereafter adopted by the Commission having substantially the same effect as such Rule. 

“Securities Act” means the Securities Act of 1933, as amended. 

“Selling Stockholder Questionnaire” means a questionnaire in the form attached as Annex B hereto, or such other form
of questionnaire as may reasonably be requested by the Issuer from time to time. 
 “Transaction Documents” means this
Agreement, the Issuance Agreement, the License Agreement (as defined in the Issuance Agreement), and the schedules and exhibits attached hereto and thereto. 

ARTICLE II 
 REGISTRATION

 2.1 Registration Obligations; Filing Date Registration. On or prior to the Filing Date, the Issuer shall prepare and file with
the Commission a Registration Statement covering the resale of the Registrable Securities as would permit the sale and distribution of all the Registrable Securities from time to time pursuant to Rule 415 in the manner reasonably requested by the
Holder. The Registration Statement shall be on Form S-3 (except if the Issuer is not then eligible to register for resale the Registrable Securities on Form S-3, in which case such registration shall be on another appropriate form in accordance with
the Securities Act and the rules promulgated thereunder and the Issuer shall undertake to register the Registrable Securities on Form S-3 as soon as practicable following the availability of such form, provided that the Issuer shall use reasonable
best efforts to maintain the effectiveness of the Registration Statement then in effect until such time as a Registration Statement on Form S-3 covering the Registrable Securities has been declared effective by the Commission). The Registration
Statement shall contain the “Plan of Distribution” section in substantially the form attached hereto as Annex A. The Issuer shall use reasonable best efforts to cause the Registration Statement filed by it to be declared effective
under the Securities Act as promptly as practicable 

  
 3. 

 
after the filing thereof but in any event on or prior to the Effectiveness Date, and, subject to Section 3.1(m) hereof, to keep such Registration Statement continuously effective under the
Securities Act until such date as all Registrable Securities covered by such Registration Statement have ceased to be Registrable Securities (the “Effectiveness Period”). By 5:30 pm Eastern Time on the Business Day following the
Effective Date, the Issuer shall file with the Commission in accordance with Rule 424 under the Securities Act the final prospectus to be used in connection with sales pursuant to such Registration Statement. 

ARTICLE III 

REGISTRATION PROCEDURES 

3.1 Registration Procedures. In connection with the Issuer’s registration obligations hereunder, the Issuer shall: 

(a) Prepare and file with the Commission on or prior to the Filing Date, a Registration Statement on Form S-3 (or if the Issuer is not then
eligible to register for resale the Registrable Securities on Form S-3 such Registration Statement shall be on another appropriate form in accordance with the Securities Act and the rules and regulations promulgated thereunder) in accordance with
the method or methods of distribution thereof as described on Annex A hereto (except if otherwise directed by all of the Holders), and use reasonable best efforts to cause the Registration Statement to become effective and remain effective as
provided herein. 
 (b) Prepare and file with the Commission such amendments, including post-effective amendments, to the Registration
Statement as may be necessary to keep the Registration Statement continuously effective (subject to Section 3.1(l)) as to the applicable Registrable Securities for the Effectiveness Period and prepare and file with the Commission such additional
Registration Statements, if necessary, in order to register for resale under the Securities Act all of the Registrable Securities; cause the related Prospectus to be amended or supplemented by any required Prospectus supplement, and as so
supplemented or amended to be filed pursuant to Rule 424 (or any similar provisions then in force) promulgated under the Securities Act; respond promptly to any comments received from the Commission with respect to the Registration Statement or any
amendment thereto and promptly provide the Holders true and complete copies of all correspondence from and to the Commission relating to such Registration Statement; and comply in all material respects with the provisions of the Securities Act and
the Exchange Act with respect to the disposition of all Registrable Securities covered by the Registration Statement during the applicable period in accordance with the intended methods of disposition by the Holders thereof set forth in the
Registration Statement as so amended or in such Prospectus as so supplemented. 
 (c) At the time the Commission declares the Registration
Statement effective, each Holder shall be named as a selling stockholder in the Registration Statement and the related Prospectus in such a manner as to permit such Holder to deliver such Prospectus to purchasers of Registrable Securities included
in the Registration Statement in accordance with applicable law, subject to the terms and conditions hereof. From and after the date the Registration Statement is declared effective, any Holder not named as a selling stockholder in the Registration
Statement at the time of effectiveness may request that the Issuer amend or supplement the Registration 

  
 4. 

 
Statement to include such Holder as a selling stockholder, and the Issuer shall, as promptly as practicable and in any event upon the later of (x) ten (10) Business Days after such date
or (y) ten (10) Business Days after the expiration of any Deferral Period (as defined in Section 3.1(l)) that is either in effect or put into effect within ten (10) Business Days of such date: 

(i) if required by applicable law, prepare and file with the Commission a post-effective amendment to the Registration
Statement or prepare and, if required by applicable law, file a supplement to the related Prospectus or a supplement or amendment to any document incorporated therein by reference or file with the Commission any other required document so that the
Holder is named as a selling stockholder in the Registration Statement and the related Prospectus in such a manner as to permit such Holder to deliver such Prospectus to purchasers of such Holder’s Registrable Securities included in the Shelf
Registration Statement in accordance with applicable law and, if the Issuer shall file a post-effective amendment to the Registration Statement, use its reasonable best efforts to cause such post-effective amendment to be declared effective under
the Securities Act as promptly as is practicable, but in any event by the date that is sixty (60) days after the date such post-effective amendment is required by this clause to be filed; 

(ii) provide such Holder copies of any documents filed pursuant to Section 3.1(c)(i); and 

(iii) notify such Holder as promptly as practicable after the effectiveness under the Securities Act of any post-effective
amendment filed pursuant to Section 3.1(c)(i); 
 (d) Promptly notify the Holders of Registrable Securities (i)(A) when a Registration
Statement, a Prospectus or any Prospectus supplement or pre- or post-effective amendment to the Registration Statement is filed; (B) when the Commission notifies the Issuer whether there will be a “review” of such Registration
Statement and whenever the Commission comments in writing on such Registration Statement, and if requested by such Holders, furnish to them a copy of such comments and the Issuer’s responses thereto and (C) with respect to the Registration
Statement or any post-effective amendment filed by the Issuer, when the same has become effective; (ii) of any request by the Commission or any other Federal or state governmental authority for amendments or supplements to the Registration Statement
or Prospectus or for additional information of the Issuer; (iii) of the issuance by the Commission of any stop order suspending the effectiveness of the Registration Statement covering any or all of the Registrable Securities or the initiation of
any Proceedings for that purpose; (iv) of the receipt by the Issuer of any notification with respect to the suspension of the qualification or exemption from qualification of any of the Registrable Securities of the Issuer for sale in any
jurisdiction, or the initiation or threatening of any Proceeding for such purpose; and (v) of the occurrence of any event that makes any statement made in the Registration Statement or Prospectus or any document incorporated or deemed to be
incorporated therein by reference untrue in any material respect or that requires any revisions to such Registration Statement, Prospectus or other documents so that, in the case of such Registration Statement or the Prospectus, as the case may be,
it 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, in the light of the circumstances under which they were made, not misleading.

  
 5. 

 (e) Use reasonable best efforts to avoid the issuance of, and, if issued, to obtain the
withdrawal of, (i) any order suspending the effectiveness of the Registration Statement or (ii) any suspension of the qualification (or exemption from qualification) of any of the Registrable Securities for sale in any U.S. jurisdiction.

 (f) If requested by the Holders of a majority of the Registrable Securities, (i) promptly incorporate in a Prospectus supplement or
post-effective amendment to the Registration Statement such information as such Holders reasonably request to be included therein and (ii) make all required filings of such Prospectus supplement or such post-effective amendment as soon as
practicable after the Issuer has received notification of the matters to be incorporated in such Prospectus supplement or post-effective amendment. 

(g) Furnish to each Holder, without charge and upon request, at least one conformed copy of each Registration Statement and each amendment
thereto, including financial statements and schedules, and, to the extent requested by such Person, all documents incorporated or deemed to be incorporated therein by reference, and all exhibits (including those previously furnished or incorporated
by reference) promptly after the filing of such documents with the Commission. 
 (h) Promptly deliver to each Holder, without charge, as
many copies of the Prospectus or Prospectuses (including each form of prospectus) and each amendment or supplement thereto as such Persons may reasonably request; and the Issuer hereby consents to the use of such Prospectus and each amendment or
supplement thereto by each of the selling Holders in connection with the offering and sale of the Registrable Securities covered by such Prospectus and any amendment or supplement thereto. 

(i) Cooperate with the Holders to facilitate the timely preparation and delivery of certificates representing Registrable Securities of the
Issuer to be sold pursuant to a Registration Statement. 
 (j) Upon the occurrence of any event contemplated by Section 3.1(d)(v), as
promptly as practicable prepare a supplement or amendment, including a post-effective amendment, to the Registration Statement or a supplement to the related Prospectus or any document incorporated or deemed to be incorporated therein by reference,
and file any other required document so that, as thereafter delivered, neither the Registration Statement nor such Prospectus will contain an untrue statement of a material fact or omit to state a material fact required to be stated therein or
necessary to make the statements therein, in the light of the circumstances under which they were made, not misleading. 
 (k) Use
reasonable best efforts to cause all Registrable Securities relating to the Registration Statement to be listed on the NASDAQ Stock Market, LLC or any subsequent securities exchange, quotation system or market, if any, on which similar securities
issued by the Issuer are then listed or traded. 
 (l) The Issuer may require each selling Holder to furnish to the Issuer information
regarding such Holder and the distribution of such Registrable Securities as is required by law to be disclosed in the Registration Statement, and the Issuer may exclude from such registration the Registrable Securities of any such Holder who fails
to furnish such information within fifteen (15) days after receiving such request. 

  
 6. 

 (m) If (i) there is material non-public information regarding the Issuer which the Board
reasonably determines not to be in the Issuer’s best interest to disclose and which the Issuer is not otherwise required to disclose, or (ii) there is a significant business opportunity (including, but not limited to, the acquisition or
disposition of assets (other than in the ordinary course of business) or any merger, consolidation, tender offer or other similar transaction) available to the Issuer which the Board reasonably determines not to be in the Issuer’s best interest
to disclose, then the Issuer may postpone or suspend filing or effectiveness of a Registration Statement for a period (a “Deferral Period”) not to exceed forty-five (45) consecutive days, provided that the Issuer may not
postpone or suspend its obligation under this Section 3.1(m) for more than ninety (90) days in the aggregate during any 12-month period; provided, however, that no such postponement or suspension by the Issuer shall be permitted for more than
one forty-five (45) day period, arising out of the same set of facts, circumstances or transactions. 
 (n) The Issuer shall use
reasonable best efforts to register or qualify, or cooperate with the Holders of the Registrable Securities included in the Registration Statement in connection with the registration or qualification of, the resale of the Registrable Securities
under applicable securities or “blue sky” laws of such states of the United States as any such Holder requests in writing and to do any and all other acts or things necessary or advisable to enable the offer and sale in such jurisdictions
of the Registrable Securities covered by the Registration Statement; provided, however, that the Issuer shall not be required to (i) qualify generally to do business in any jurisdiction where it is not then so qualified or (ii) take any
action that would subject it to general service of process or to taxation in any jurisdiction to which it is not then so subject. 
 (o) The
Issuer will comply with all rules and regulations of the Commission to the extent and so long as they are applicable to the Registration and will make generally available to its security holders (or otherwise provide in accordance with
Section 11(a) of the Securities Act) an earnings statement (which need not be audited) satisfying the provisions of Section 11(a) of the Securities Act and Rule 158 thereunder, no later than 45 days after the end of a 12-month period (or
90 days, if such period is a fiscal year) beginning with the Issuer’s first fiscal quarter commencing after the effective date of the Registration Statement. 

3.2 Holder Covenants. Each Holder covenants and agrees by its acquisition of such Registrable Securities that: 

(a) (i) it will not sell any Registrable Securities under the Registration Statement until it has received copies of the Prospectus as then
amended or supplemented as contemplated in Section 3.1(h) and notice from the Issuer that such Registration Statement and any post-effective amendments thereto have become effective as contemplated by Section 3.1(d) and (ii) it and its
officers, directors or Affiliates, if any, will comply with the prospectus delivery requirements of the Securities Act as applicable to them in connection with sales of Registrable Securities pursuant to the Registration Statement. 

  
 7. 

 (b) Upon receipt of a notice from the Issuer of the occurrence of any event of the kind described
in Section 3.1(d) (ii), 3.1(d)(iii), 3.1(d)(iv), 3.1(d)(v) or 3.1(m), such Holder will forthwith discontinue disposition of such Registrable Securities under the Registration Statement until such Holder’s receipt of the copies of the
supplemented Prospectus and/or amended Registration Statement contemplated by Section 3.1(j), or until it is advised in writing by the Issuer that the use of the applicable Prospectus may be resumed, and, in either case, has received copies of any
additional or supplemental filings that are incorporated or deemed to be incorporated by reference in such Prospectus or Registration Statement. 

(c) Such Holder is bound by the “Lock Up” provisions of Section 4.1 of the Issuance Agreement and notwithstanding any provision
of this Agreement, such Holder will not sell, transfer, pledge, lend, offer or otherwise dispose of any Registrable Securities except in compliance with Section 4.1 of the Issuance Agreement. 

ARTICLE IV 
 REGISTRATION
EXPENSES 
 4.1 Registration Expenses. All reasonable fees and expenses incident to the performance of or compliance with this
Agreement by the Issuer (excluding underwriters’ discounts and commissions and all fees and expenses of legal counsel, accountants and other advisors for any Holder except as specifically provided below), except as and to the extent specified
in this Section 4.1, shall be borne by the Issuer whether or not a Registration Statement is filed by the Issuer or becomes effective and whether or not any Registrable Securities are sold pursuant to a Registration Statement. The fees and expenses
referred to in the foregoing sentence shall include, without limitation, (i) all registration and filing fees (including, without limitation, fees and expenses (A) with respect to filings required to be made with the NASDAQ Stock Market, LLC
and each other securities exchange or market on which Registrable Securities are required hereunder to be listed, (B) with respect to filings required to be made by the Issuer with the Financial Industry Regulatory Authority and (C) in
compliance with state securities or Blue Sky laws by the Issuer or with respect to Registrable Securities, (ii) messenger, telephone and delivery expenses, (iii) fees and disbursements of counsel for the Issuer, (iv) Securities Act liability
insurance, if the Issuer so desires such insurance, and (v) fees and expenses of all other Persons retained by the Issuer in connection with the consummation of the transactions contemplated by this Agreement, including, without limitation, the
Issuer’s independent public accountants). In addition, the Issuer shall be responsible for all of its internal expenses incurred in connection with the consummation of the transactions contemplated by this Agreement (including, without
limitation, all salaries and expenses of its officers and employees performing legal or accounting duties), the expense of any annual audit, the fees and expenses incurred in connection with the listing of the Registrable Securities on any
securities exchange as required hereunder. 
 ARTICLE V 

INDEMNIFICATION 
 5.1
Indemnification by the Issuer. The Issuer shall, notwithstanding any termination of this Agreement, indemnify and hold harmless each Holder, its permitted assignees, officers, directors, agents, brokers (including brokers who offer and sell
Registrable Securities as 

  
 8. 

 
principal as a result of a pledge or any failure to perform under a margin call of Issuer Common Stock), underwriters, investment advisors and employees, each Person who controls any such Holder
or permitted assignee (within the meaning of Section 15 of the Securities Act or Section 20 of the Exchange Act) and the officers, directors, agents and employees of each such controlling Person, and the respective successors, assigns,
estate and personal representatives of each of the foregoing, to the fullest extent permitted by applicable law, from and against any and all claims, losses, damages, liabilities, penalties, judgments, costs (including, without limitation, costs of
investigation) and expenses (including, without limitation, reasonable attorneys’ fees and expenses) (collectively, “Losses”), arising out of or relating to any untrue or alleged untrue statement of a material fact contained in
the Registration Statement, any Prospectus, as supplemented or amended, if applicable, or arising out of or relating to any omission or alleged omission of a material fact required to be stated therein or necessary to make the statements therein (in
the case of any Prospectus or form of prospectus or supplement thereto, in the light of the circumstances under which they were made) not misleading, except (i) to the extent, but only to the extent, that such untrue statements or omissions or
alleged untrue statements or omissions are based upon information regarding such Holder furnished in writing to the Issuer by such Holder expressly for use in such Registration Statement, such Prospectus or in any amendment or supplement thereto (it
being understood that each Holder has approved Annex A hereto for this purpose); or (ii) in the case of an occurrence of an event of the type specified in Section 3.1(d)(ii)-(v), the use by a Holder of an outdated or defective Prospectus, but
only if and to the extent that following such receipt the misstatement or omission giving rise to such Loss would have been corrected; provided, however, that the indemnity agreement contained in this Section 5.1 shall not apply to amounts paid in
settlement of any Losses if such settlement is effected without the prior written consent of the Issuer, which consent shall not be unreasonably withheld. The Issuer shall notify such Holder promptly of the institution, threat or assertion of any
Proceeding of which the Issuer is aware in connection with the transactions contemplated by this Agreement. Such indemnity shall remain in full force and effect regardless of any investigation made by or on behalf of an Indemnified Party (as defined
in Section 5.3(a) hereof) and shall survive the transfer of the Registrable Securities by the Holder. 
 5.2 Indemnification by
Holders. Each Holder and its permitted assignees shall, severally and not jointly, indemnify and hold harmless the Issuer, its directors, officers, agents and employees, each Person who controls the Issuer (within the meaning of Section 15
of the Securities Act and Section 20 of the Exchange Act), and the directors, officers, agents or employees of such controlling Persons, and the respective successors, assigns, estate and personal representatives of each of the foregoing, to
the fullest extent permitted by applicable law, from and against all Losses, as incurred, arising out of or relating to any untrue or alleged untrue statement of a material fact contained in any Registration Statement, any Prospectus, as
supplemented or amended, if applicable, or arising out of or relating to any omission or alleged omission of a material fact required to be stated therein or necessary to make the statements therein (in the case of any Prospectus or supplement
thereto, in the light of the circumstances under which they were made) not misleading, to the extent, but only to the extent, that such untrue statement or omission or alleged untrue statement or omission is contained in or omitted from any
information regarding such Holder furnished in writing to the Issuer by such Holder expressly for use in therein, and that such information was reasonably relied upon by the Issuer for use therein, or to the extent that such information relates to
such Holder or such Holder’s proposed method of distribution of Registrable Securities and was furnished in writing by such Holder expressly for use therein (it being understood that each Holder has approved Annex A hereto for this
purpose). 

  
 9. 

 5.3 Conduct of Indemnification Proceedings. 

(a) If any Proceeding shall be brought or asserted against any Person entitled to indemnity hereunder (an “Indemnified
Party”), such Indemnified Party promptly shall notify the Person from whom indemnity is sought (the “Indemnifying Party”) in writing, and the Indemnifying Party shall assume the defense thereof, including the employment of
counsel reasonably satisfactory to the Indemnified Party and the payment of all fees and expenses incurred in connection with defense thereof; provided, that the failure of any Indemnified Party to give such notice shall not relieve the Indemnifying
Party of its obligations or liabilities pursuant to this Agreement, except (and only) to the extent that it shall be finally determined by a court of competent jurisdiction (which determination is not subject to appeal or further review) that such
failure shall have proximately and materially adversely prejudiced the Indemnifying Party. 
 (b) An Indemnified Party shall have the right
to employ separate counsel in any such Proceeding and to participate in the defense thereof, but the fees and expenses of such counsel shall be at the expense of such Indemnified Party or Parties unless: (1) the Indemnifying Party has agreed in
writing to pay such fees and expenses; or (2) the Indemnifying Party shall have failed promptly to assume the defense of such Proceeding and to employ counsel reasonably satisfactory to such Indemnified Party in any such Proceeding; or
(3) the named parties to any such Proceeding (including any impleaded parties) include both such Indemnified Party and the Indemnifying Party, and such Indemnified Party shall have been advised by counsel (which shall be reasonably acceptable
to the Indemnifying Party) that a conflict of interest is likely to exist if the same counsel were to represent such Indemnified Party and the Indemnifying Party (in which case, the Indemnifying Party shall be responsible for reasonable fees and
expenses of no more than one counsel (together with appropriate local counsel) for the Indemnified Parties). The Indemnifying Party shall not be liable for any settlement of any such Proceeding effected without its written consent, which consent
shall not be unreasonably withheld or delayed. No Indemnifying Party shall, without the prior written consent of the Indemnified Party, effect any settlement of any pending Proceeding in respect of which any Indemnified Party is or could have been a
party, unless such settlement (i) includes an unconditional release of such Indemnified Party from all liability on claims that are the subject matter of such Proceeding and (ii) does not include a statement as to or an admission of fault,
culpability or a failure to act by or on behalf of any Indemnified Party. 
 (c) All fees and expenses of the Indemnified Party (including
reasonable fees and expenses to the extent incurred in connection with investigating or preparing to defend such Proceeding in a manner not inconsistent with this Section) shall be paid to the Indemnified Party, as incurred, within twenty (20)
Business Days of written notice thereof to the Indemnifying Party (regardless of whether it is ultimately determined that an Indemnified Party is not entitled to indemnification hereunder; provided, that the Indemnifying Party may require such
Indemnified Party to undertake to reimburse all such fees and expenses to the extent it is finally judicially determined that such Indemnified Party is not entitled to indemnification hereunder). 

  
 10. 

 5.4 Contribution. 

(a) If a claim for indemnification under Section 5.1 or 5.2 is unavailable to an Indemnified Party because of a failure or refusal
of a governmental authority to enforce such indemnification in accordance with its terms (by reason of public policy or otherwise), then each Indemnifying Party, in lieu of indemnifying such Indemnified Party, shall contribute to the amount paid or
payable by such Indemnified Party as a result of such Losses, in such proportion as is appropriate to reflect the relative fault of the Indemnifying Party and Indemnified Party in connection with the actions, statements or omissions that resulted in
such Losses as well as any other relevant equitable considerations. The relative fault of such Indemnifying Party and Indemnified Party shall be determined by reference to, among other things, whether any action in question, including any untrue or
alleged untrue statement of a material fact or omission or alleged omission of a material fact, has been taken or made by, or relates to information supplied by, such Indemnifying, Party or Indemnified Party, and the parties’ relative intent,
knowledge, access to information and opportunity to correct or prevent such action, statement or omission. The amount paid or payable by a party as a result of any Losses shall be deemed to include, subject to the limitations set forth in
Section 5.3, any reasonable attorneys’ or other reasonable fees or expenses incurred by such party in connection with any Proceeding to the extent such party would have been indemnified for such fees or expenses if the indemnification
provided for in this Section was available to such party in accordance with its terms. 
 (b) The parties hereto agree that it would not be
just and equitable if contribution pursuant to this Section 5.4 were determined by pro rata allocation or by any other method of allocation that does not take into account the equitable considerations referred to in the immediately preceding
paragraph. No Person guilty of fraudulent misrepresentation (within the meaning of Section 11(f) of the Securities Act) shall be entitled to contribution from any Person who was not guilty of such fraudulent misrepresentation. 

(c) The indemnity and contribution agreements contained in this Article V are in addition to any liability that the Indemnifying Parties may
have to the Indemnified Parties. 
 ARTICLE VI 

RULE 144 
 6.1 Rule
144. As long as any Holder owns any Registrable Securities, the Issuer covenants to use its commercially reasonable efforts to timely file (or obtain extensions in respect thereof and file within the applicable grace period) all reports required
to be filed by the Issuer after the date hereof pursuant to Section 13(a) or 15(d) of the Exchange Act. The Issuer further covenants that it will take such further action as any Holder may reasonably request, all to the extent required from
time to time to enable such Person to sell the Registrable Securities without registration under the Securities Act within the limitation of the exemptions provided by Rule 144 promulgated under the Securities Act, including providing any legal
opinions relating to such sale pursuant to Rule 144. Upon the request of any Holder, the Issuer shall deliver to such Holder a written certification of a duly authorized officer as to whether it has complied with such requirements. 

  
 11. 

 ARTICLE VII 

MISCELLANEOUS 
 7.1
Effectiveness. The Issuer’s obligations hereunder shall be conditioned upon the occurrence of the Closing under the Issuance Agreement, and this Agreement shall not be effective until such Closing. If the Issuance Agreement shall be
terminated prior to the Closing, then this Agreement shall be void and of no further force or effect (and no party hereto shall have any rights or obligations with respect to this Agreement). 

7.2 Limitations Under Texas State Law. MD Anderson is an agency of the State of Texas and under the Constitution and laws of the State
of Texas possesses certain rights and privileges, is subject to certain limitations and restrictions, and only has such authority as is granted to it under the Constitution and laws of the State of Texas. Notwithstanding any provision contained in
this Agreement, nothing in this Agreement is intended to be, nor will it be construed to be, a waiver of the sovereign immunity of the State of Texas or a prospective waiver or restriction of any of the rights, remedies, claims, and privileges of
the State of Texas. Moreover, notwithstanding the generality or specificity of any provision hereof, the provisions of this agreement as they pertain to MD Anderson are enforceable only to the extent authorized by the Constitution and laws of the
State of Texas. 
 7.3 Remedies. In the event of a breach by the Issuer or by a Holder, of any of their obligations under this
Agreement, each non-breaching Holder and Issuer, as the case may be, in addition to being entitled to exercise all rights granted by law and under this Agreement, including recovery of damages, will be entitled to specific performance of its rights
under this Agreement. The Issuer and each Holder agree that monetary damages would not provide adequate compensation for any losses incurred by reason of a breach by it of any of the provisions of this Agreement and hereby further agrees that, in
the event of any action for specific performance in respect of such breach, it shall waive the defense that a remedy at law would be adequate. 

7.4 Entire Agreement; Amendment. This Agreement and the other Transaction Documents contain the entire understanding and agreement of
the parties with respect to the matters covered hereby and, except as specifically set forth herein or therein, neither the Issuer nor any Holder make any representation, warranty, covenant or undertaking with respect to such matters, and they
supersede all prior understandings and agreements with respect to said subject matter, all of which are merged herein. This Agreement and any term hereof may be amended, terminated or waived only with the written consent of the Issuer and the
Holders of at least a majority of all Registrable Securities then outstanding. Any amendment or waiver effected in accordance with this Section 7.4 shall be binding upon each Holder (and their permitted assigns). 

7.5 No Inconsistent Agreements. The Issuer will not on or after the date of this Agreement enter into any agreement with respect to its
securities that is inconsistent with the rights granted to the Holders in this Agreement or otherwise conflicts with the provisions hereof. The rights granted to the Holders hereunder do not in any way conflict with and are not inconsistent with the
rights granted to the holders of the Issuer’s securities under any agreement in effect on the date hereof. 

  
 12. 

 7.6 No Piggyback on Registration. Without the prior written consent of the Holders of a
majority of the Registrable Securities, no Registration Statement relating to the offer and sale of Registrable Securities shall register any transaction in any securities of the Issuer, other than the offer and sale of Registrable Securities by the
Holders thereof. 
 7.7 Notices. Any and all notices or other communications or deliveries required or permitted to be provided
hereunder shall be in writing and shall be deemed given and effective on the earliest of (a) the date of transmission, if such notice or communication is delivered via facsimile or email at the facsimile number or email address specified in
this Section prior to 4:00 p.m. (New York City time) on a Trading Day, (b) the next Trading Day after the date of transmission, if such notice or communication is delivered via facsimile or email at the facsimile number or email address
specified in this Section on a day that is not a Trading Day or later than 4:00 p.m. (New York City time) on any Trading Day, (c) the Trading Day following the date of deposit with a nationally recognized overnight courier service, or
(d) upon actual receipt by the party to whom such notice is required to be given. The addresses, facsimile numbers and email addresses for such notices and communications are those set forth below, or such other address or facsimile number as
may be designated in writing hereafter, in the same manner, by any such Person: 
  

			
	If to the Issuer:	  	ZIOPHARM Oncology, Inc.
		  	1 First Avenue
		  	Parris Building, #34
		  	Boston, MA 02129
		  	Attention: Chief Executive Officer
		  	Email: cbelbel@ziopharm.com
		  	Fax No.: 617.778.0420
		
	with copies (which copies	  	Cooley LLP
	shall not constitute notice	  	500 Boylston Street
	to the Issuer) to:	  	Boston, MA 02116
		  	Attention: Marc Recht
		  	Email: mrecht@cooley.com
		  	Fax No.: 617.937.2400

  
 13. 

			
	If to MD Anderson	  	 University of Texas System Board of Regents on

behalf of The University of Texas M.D. Anderson

		  	Cancer Center
		  	Legal Services-Unit 1674
		  	P.O. Box 301407
		  	Houston, Texas 77230-1407
		
		  	And
		
		  	Legal Services-1MC11.3433
		  	The University of Texas M. D. Anderson Cancer Center
		  	7007 Bertner Avenue
		  	Houston, Texas 77030-3907
		
		  	Attention: Legal Services
		  	
		  	

 7.8 Waivers. No waiver by either party of any default with respect to any provision, condition or
requirement of this Agreement shall be deemed to be a continuing waiver in the future or a waiver of any other provision, condition or requirement hereof, nor shall any delay or omission of any party to exercise any right hereunder in any manner
impair the exercise of any such right accruing to it thereafter. 
 7.9 Successors and Assigns. This Agreement shall be binding upon
and inure to the benefit of the parties and their successors and permitted assigns and shall inure to the benefit of each Holder and its successors and assigns. The Issuer may not assign this Agreement or any of its rights or obligations hereunder
without the prior written consent of the Holders of at least a majority of all Registrable Securities then outstanding. 
 7.10
Assignment of Registration Rights. The rights of each Holder hereunder, including the right to have the Issuer register for resale Registrable Securities in accordance with the terms of this Agreement, shall be assignable by each Holder of
all or a portion of the Registrable Securities if: (i) the Holder agrees in writing with the transferee or assignee to assign such rights, and a copy of such agreement is furnished to the Issuer within a reasonable time after such assignment, (ii)
the Issuer is, within a reasonable time after such transfer or assignment, furnished with written notice of (a) the name and address of such transferee or assignee, and (b) the securities with respect to which such registration rights are being
transferred or assigned, (iii) following such transfer or assignment the further disposition of such securities by the transferee or assignees is restricted under the Securities Act and applicable state securities laws, and (iv) at or before the
time the Issuer receives the written notice contemplated by clause (ii) of this Section, the transferee or assignee agrees in writing with the Issuer to be bound by all of the provisions of this Agreement. The rights to assignment shall apply
to the Holders (and to subsequent) successors and assigns. 
 7.11 Counterparts. This Agreement may be executed in two (2) or more
counterparts, each of which shall be deemed an original, but all of which together shall constitute one and the same instrument. Counterparts may be delivered via facsimile, electronic mail (including pdf or

  
 14. 

 
any electronic signature complying with the U.S. federal ESIGN Act of 2000, e.g., www.docusign.com) or other transmission method and any counterpart so delivered shall be deemed to have been duly
and validly delivered and be valid and effective for all purposes. 
 7.12 Termination. This Agreement shall terminate at the end of
the Effectiveness Period, except that Articles IV and V and this Article VII shall remain in effect in accordance with their terms. 
 7.13
Governing Law; Dispute Resolution. This Agreement will be governed by the laws of the State of Texas without regard to conflict of law principles. In the event of any dispute between the Issuer on the one hand, and MD Anderson on the other (a
“Dispute”), the Parties agree that such Dispute shall be first submitted for resolution for a period of ten (10) calendar days to designated senior officers of each of the Parties who hold legal authority to resolve and settle
such dispute. If any Dispute cannot be resolved and settled within such period, then to the extent authorized by the law governing the power and authority of each Party, the Parties agree to submit such Dispute to full and binding arbitration that
will be undertaken and conducted under the auspices of the American Arbitration Association by a panel of three (3) arbitrators pursuant to that organization’s Commercial Arbitration Rules then in effect, as modified by and subject to the
following terms: 
 (a) MD Anderson and the Issuer will each choose one arbitrator and those two arbitrators will select the third
arbitrator. 
 (b) The fees and expenses of the arbitrators shall be borne in equal shares by the Parties. 

(c) Each Party shall bear the fees and expenses of its legal representation in the arbitration. 

(d) The arbitral tribunal shall not reallocate either the fees and expenses of the arbitrators or of the Parties’ legal representation.

 (e) The arbitration shall be held in Nashville, Tennessee, USA which shall be the seat of the arbitration. 

(f) The arbitrators may not award, and no Party may seek, indirect, incidental, consequential, punitive, exemplary, special, or enhanced
damages, or prejudgment interest, or attorneys’ fees or costs, nor may the arbitrators apply any multiplier to any award of actual damages, except as may be required by statute. 

(g) The arbitrators must issue a reasoned award, setting forth the arbitrators’ findings of fact and conclusions of law. 

(h) The award of the arbitrators may be entered in any court of competent jurisdiction. The award rendered by the arbitrators shall be final
and binding on the Parties, except that the award is subject to limited judicial review and vacatur for the following reasons only: (i) the award was procured by corruption, fraud, or undue means, (ii) the award was tainted by evidence of
partiality or corruption by any of the arbitrators, (iii) the award was tainted by 

  
 15. 

 
misconduct by any of the arbitrators, (iv) the arbitrators exceeded their powers, and/or (v) the award evidences a manifest disregard of the law or is contrary to public policy. If the
Parties are unable to resolve a Dispute through binding arbitration, then any lawsuit pertaining to such Dispute that is brought by one Party against another must be presented to and decided by a state or federal court in the home locale of the
defendant party (that being Houston, Texas for MD Anderson and Boston, Massachusetts for the Issuer). 
 7.14 Cumulative Remedies.
The remedies provided herein are cumulative and not exclusive of any remedies provided by law. 
 7.15 Severability. The provisions
of this Agreement are severable and, in the event that any court of competent jurisdiction shall determine that any one or more of the provisions or part of the provisions contained in this Agreement shall, for any reason, be held to be invalid,
illegal or unenforceable in any respect, such invalidity, illegality or unenforceability shall not affect any other provision or part of a provision of this Agreement and this Agreement shall be reformed and construed as if such invalid or illegal
or unenforceable provision, or part of such provision, had never been contained herein, so that such provisions would be valid, legal and enforceable to the maximum extent possible. 

7.16 Headings. The headings herein are for convenience only, do not constitute a part of this Agreement and shall not be deemed to
limit or affect any of the provisions hereof. 
 [SIGNATURE PAGES TO FOLLOW] 

  
 16. 

 IN WITNESS WHEREOF, the parties hereto have caused this Registration Rights Agreement to
be duly executed by their respective authorized officers as of the date first above written. 
  

			
	THE ISSUER:
	
	ZIOPHARM ONCOLOGY, INC.
		
	By:	 	 /s/ Jonathan Lewis

		 	Jonathan Lewis, M.D., Ph.D.
		 	Chief Executive Officer

 SIGNATURE PAGE TO REGISTRATION
RIGHTS AGREEMENT 

 IN WITNESS WHEREOF, the parties hereto have caused this Registration Rights Agreement to
be duly executed by their respective authorized officers as of the date first above written. 
  

			
	MD ANDERSON:
	
	BOARD OF REGENTS OF THE UNIVERSITY OF TEXAS SYSTEM
	On behalf of The University of Texas M.D. Anderson Cancer Center
		
	By:	 	 /s/ Ronald A. DePinho, MD

	Name:	 	 Ronald A. DePinho, MD

	Title:	 	 President

 SIGNATURE PAGE TO REGISTRATION
RIGHTS AGREEMENT 

 ANNEX A 

PLAN OF DISTRIBUTION 
 The
selling stockholders, which as used herein includes donees, pledgees, transferees or other successors-in-interest selling shares of common stock or interests in shares of common stock received after the date of this prospectus from a selling
stockholder as a gift, pledge, partnership distribution or other transfer, may, from time to time, sell, transfer or otherwise dispose of any or all of their shares of common stock or interests in shares of common stock on any stock exchange, market
or trading facility on which the shares are traded or in private transactions. The selling stockholders may sell their shares of our common stock pursuant to this prospectus at fixed prices, at prevailing market prices at the time of sale, at prices
related to the prevailing market price, at varying prices determined at the time of sale, or at negotiated prices. 
 The selling
stockholders may use any one or more of the following methods when disposing of shares or interests therein: 
  

	 	•	 	ordinary brokerage transactions and transactions in which the broker-dealer solicits purchasers; 

  

	 	•	 	block trades in which the broker-dealer will attempt to sell the shares as agent, but may position and resell a portion of the block as principal to facilitate the transaction; 

 

	 	•	 	purchases by a broker-dealer as principal and resale by the broker-dealer for its account; 

  

	 	•	 	an exchange distribution in accordance with the rules of the applicable exchange; 

  

	 	•	 	privately negotiated transactions; 

  

	 	•	 	short sales; 

  

	 	•	 	through the writing or settlement of options or other hedging transactions, whether through an options exchange or otherwise; 

  

	 	•	 	broker-dealers may agree with the selling stockholders to sell a specified number of such shares at a stipulated price per share; 

  

	 	•	 	a combination of any such methods of sale; and 

  

	 	•	 	any other method permitted pursuant to applicable law. 

 The selling stockholders may, from
time to time, pledge or grant a security interest in some or all of the shares of common stock owned by them and, if they default in the performance of their secured obligations, the pledgees or secured parties may offer and sell the shares of
common stock, from time to time, under this prospectus, or under an amendment to this prospectus under Rule 424(b)(3) or other applicable provision of the Securities Act amending the list of selling stockholders to include the pledgee, transferee or
other successors in interest as selling stockholders under this prospectus. The selling stockholders also may transfer the shares of common stock in other circumstances, in which case the transferees, pledgees or other successors in interest will be
the selling beneficial owners for purposes of this prospectus. 

 In connection with the sale of our common stock or interests therein, the selling stockholders
may enter into hedging transactions with broker-dealers or other financial institutions, which may in turn engage in short sales of the common stock in the course of hedging the positions they assume. The selling stockholders may also sell shares of
our common stock short and deliver these securities to close out their short positions, or loan or pledge the common stock to broker-dealers that in turn may sell these securities. The selling stockholders may also enter into option or other
transactions with broker-dealers or other financial institutions or the creation of one or more derivative securities which require the delivery to such broker-dealer or other financial institution of shares offered by this prospectus, which shares
such broker-dealer or other financial institution may resell pursuant to this prospectus (as supplemented or amended to reflect such transaction). 

The aggregate proceeds to the selling stockholders from the sale of the common stock offered by them will be the purchase price of the common
stock less discounts or commissions, if any. Each of the selling stockholders reserves the right to accept and, together with their agents from time to time, to reject, in whole or in part, any proposed purchase of common stock to be made directly
or through agents. We will not receive any of the proceeds from this offering. 
 The selling stockholders and any underwriters,
broker-dealers or agents that participate in the sale of the common stock or interests therein may be “underwriters” within the meaning of Section 2(11) of the Securities Act. Any discounts, commissions, concessions or profit they
earn on any resale of the shares may be underwriting discounts and commissions under the Securities Act. Selling stockholders who are “underwriters” within the meaning of Section 2(11) of the Securities Act will be subject to the
prospectus delivery requirements of the Securities Act. 
 To the extent required, the shares of our common stock to be sold, the names of
the selling stockholders, the respective purchase prices and public offering prices, the names of any agents, dealer or underwriter, any applicable commissions or discounts with respect to a particular offer will be set forth in an accompanying
prospectus supplement or, if appropriate, a post-effective amendment to the registration statement that includes this prospectus. 
 In
order to comply with the securities laws of some states, if applicable, the common stock may be sold in these jurisdictions only through registered or licensed brokers or dealers. In addition, in some states the common stock may not be sold unless
it has been registered or qualified for sale or an exemption from registration or qualification requirements is available and is complied with. 

We have advised the selling stockholders that the anti-manipulation rules of Regulation M under the Exchange Act may apply to sales of shares
in the market and to the activities of the selling stockholders and their affiliates. In addition, we will make copies of this prospectus (as it may be supplemented or amended from time to time) available to the selling stockholders for the purpose
of satisfying the prospectus delivery requirements of the Securities Act. The selling stockholders may indemnify any broker-dealer that participates in transactions involving the sale of the shares against certain liabilities, including liabilities
arising under the Securities Act. 
 We have agreed to indemnify the selling stockholders against liabilities, including liabilities under
the Securities Act and state securities laws, relating to the registration of the shares offered by this prospectus. 

 We have agreed with the selling stockholders to keep the registration statement of which this
prospectus constitutes a part effective until such time as the shares offered by the selling stockholders have been effectively registered under the Securities Act and disposed of in accordance with such registration statement, the shares offered by
the selling stockholders have been disposed of pursuant to Rule 144 under the Securities Act or the shares offered by the selling stockholders may be resold pursuant to Rule 144 without restriction or limitation (including without the requirement to
be in compliance with Rule 144(c)(1)) or another similar exemption under the Securities Act. 

 ANNEX B 

SELLING STOCKHOLDER NOTICE AND QUESTIONNAIRE 

ZIOPHARM Oncology, Inc. 

Selling Stockholder Notice and Questionnaire 

The undersigned beneficial owner of common stock, $0.001 par value per share (the “Common Stock”), of ZIOPHARM Oncology, Inc.
(the “Company”), (the “Registrable Securities”) understands that the Company has filed or intends to file with the Securities and Exchange Commission (the “Commission”) a registration statement (the
“Registration Statement”) for the registration and resale under Rule 415 of the Securities Act of 1933, as amended (the “Securities Act”), of the Registrable Securities, in accordance with the terms of the
Registration Rights Agreement, dated as of January 13, 2015 (the “Registration Rights Agreement”), among the Company and the Purchasers named therein. The purpose of this Questionnaire is to facilitate the filing of the
Registration Statement under the Act that will permit you to resell the Registrable Securities in the future. The information supplied by you will be used in preparing the Registration Statement. All capitalized terms not otherwise defined herein
shall have the meanings ascribed thereto in the Registration Rights Agreement. 
 Certain legal consequences arise from being named as a
selling stockholder in the Registration Statement and the related Prospectus. Accordingly, holders and beneficial owners of Registrable Securities are advised to consult their own securities law counsel regarding the consequences of being named or
not being named as a selling stockholder in the Registration Statement and the related Prospectus. 
 NOTICE 

The undersigned beneficial owner (the “Selling Stockholder”) of Registrable Securities hereby elects to include the
Registrable Securities owned by it and listed below in Item 3 (unless otherwise specified under such Item 3) in the Registration Statement. 

QUESTIONNAIRE 
  

	1.	Name. 

  

	 	(a)	Full Legal Name of Selling Stockholder 

  

	
	  

  

	 	(b)	Full Legal Name of Registered Holder (if not the same as (a) above) through which Registrable Securities Listed in Item 3 below are held: 

 

	
	  

  

	 	(c)	Full Legal Name of Natural Control Person (which means a natural person who directly or indirectly alone or with others has power to vote or dispose of the securities covered by the questionnaire): 

 

	
	  

	2.	Address for Notices to Selling Stockholder: 

  

			
	  

	
	  

	
	  

			
		
	Telephone:	 	  

			
		
	Fax:	 	  

			
		
	Contact Person:	 	  

			
		
	E-mail address of Contact Person:	 	  

  

	3.	Beneficial Ownership of Registrable Securities: 

  

	 	(a)	Type and Number of Registrable Securities beneficially owned: 

  

	
	  

	
	  

	
	  

  

	4.	Broker-Dealer Status: 

  

	 	(a)	Are you a broker-dealer? 

Yes   ̈    No  
 ̈ 
  

	 	Note:	If yes, the Commission’s staff has indicated that you should be identified as an underwriter in the Registration Statement. 

  

	 	(b)	Are you an affiliate of a broker-dealer? 

Yes   ̈    No  
 ̈ 
  

	 	Note:	If yes, provide a narrative explanation below: 

  

	
	  

	
	  

  

	 	(c)	If you are an affiliate of a broker-dealer, do you certify that you bought the Registrable Securities in the ordinary course of business, and at the time of the purchase of the Registrable Securities to be resold, you
had no agreements or understandings, directly or indirectly, with any person to distribute the Registrable Securities? 

Yes   ̈    No  
 ̈ 
  

	 	Note:	If no, the Commission’s staff has indicated that you should be identified as an underwriter in the Registration Statement. 

	5.	Beneficial Ownership of Other Securities of the Company Owned by the Selling Stockholder. 

Except as set forth below in this Item 5, the undersigned is not the beneficial or registered owner of any securities of the Company
other than the Registrable Securities listed above in Item 3. 
  

	 	(a)	As of             , 201    , the Selling Stockholder owned outright (including shares registered in Selling Stockholder’s name
individually or jointly with others, shares held in the name of a bank, broker, nominee, depository or in “street name” for its account),              shares of the Company’s
capital stock (excluding the Registrable Securities). If “zero,” please so state. 

  

	 	(b)	In addition to the number of shares Selling Stockholder owned outright as indicated in Item 5(a) above, as of             , 201    ,
the Selling Stockholder had or shared voting power or investment power, directly or indirectly, through a contract, arrangement, understanding, relationship or otherwise, with respect to
             shares of the Company’s capital stock (excluding the Registrable Securities). If “zero,” please so state. 

If the answer to Item 5(b) is not “zero,” please complete the following tables: 

Sole Voting Power: 
  

			
	Number of
Shares	  	
Nature of Relationship Resulting in Sole Voting Power

		  	
		  	
		  	

 Shared Voting Power: 
  

					
	 Number of
Shares
	  	 With Whom Shared
	  	 Nature of Relationship

		  		  	
		  		  	
		  		  	

 Sole Investment power: 
  

			
	 Number of
Shares
	  	
Nature of Relationship Resulting in Sole Investment Power

		  	
		  	
		  	

 Shared Investment power: 

 

					
	 Number of

Shares
	  	 With Whom Shared
	  	 Nature of Relationship

		  		  	
		  		  	
		  		  	

  

	 	(c)	As of             , 201    , the Selling Stockholder had the right to acquire the following shares of the Company’s common stock
pursuant to the exercise of outstanding stock options, warrants or other rights (excluding the Registrable Securities). Please describe the number, type and terms of the securities, the method of ownership, and whether the undersigned holds sole or
shared voting and investment power. If “none”, please so state. 

  

			
	  

	
	  

  

	6.	Relationships with the Company: 

 Except as set forth below, neither the undersigned
nor any of its affiliates, officers, directors or principal equity holders (owners of 5% of more of the equity securities of the undersigned) has held any position or office or has had any other material relationship with the Company (or its
predecessors or affiliates) during the past three years. 
 State any exceptions here: 

 

			
	  

	
	  

  

	7.	Plan of Distribution: 

 The undersigned has reviewed the form of Plan of Distribution
attached as Annex A to the Registration Rights Agreement, and hereby confirms that, except as set forth below, the information contained therein regarding the undersigned and its plan of distribution is correct and complete. 

State any exceptions here: 
  

			
	  

	
	  

 *********** 

The undersigned agrees to promptly notify the Company of any inaccuracies or changes in the information provided herein that may occur
subsequent to the date hereof and prior to the effective date of any applicable Registration Statement filed pursuant to the Registration Rights Agreement. 

 By signing below, the undersigned consents to the disclosure of the information contained herein
in its answers to Items 1 through 7 and the inclusion of such information in each Registration Statement filed pursuant to the Registration Rights Agreement and each related Prospectus. The undersigned understands that such information will be
relied upon by the Company in connection with the preparation or amendment of any such Registration Statement and the related Prospectus. 

By signing below, the undersigned acknowledges that it understands its obligation to comply, and agrees that it will comply, with the
provisions of the Exchange Act and the rules and regulations thereunder, particularly Regulation M. The undersigned also acknowledges that it understands that the answers to this Questionnaire are furnished for use in connection with Registration
Statements filed pursuant to the Registration Rights Agreement and any amendments or supplements thereto filed with the Commission pursuant to the Securities Act. 

The undersigned hereby acknowledges and is advised of the following Interpretation A.65 of the July 1997 SEC Manual of Publicly Available
Telephone Interpretations regarding short selling: 
 “An Issuer filed a Form S-3 registration statement for a secondary offering of
common stock which is not yet effective. One of the selling shareholders wanted to do a short sale of common stock “against the box” and cover the short sale with registered shares after the effective date. The issuer was advised that the
short sale could not be made before the registration statement become effective, because the shares underlying the short sale are deemed to be sold at the time such sale is made. There would, therefore, be a violation of Section 5 if the shares
were effectively sold prior to the effective date.” 
 By returning this Questionnaire, the undersigned will be deemed to be aware
of the foregoing interpretation. 
 I confirm that, to the best of my knowledge and belief, the foregoing statements (including without
limitation the answers to this Questionnaire) are correct. 
 IN WITNESS WHEREOF the undersigned, by authority duly given, has caused this
Questionnaire to be executed and delivered either in person or by its duly authorized agent. 
  

											
	Dated:	 	  
	 		 	Beneficial Owner:	 	  

 

									
		 		 	By:	 	  

					
		 		 		 	Name:	 	
					
		 		 		 	Title:

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