UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): June 11, 2015

Mast Therapeutics, Inc.

(Exact name of Registrant as Specified in Its Charter)

Registrant’s Telephone Number, Including Area Code: (858) 552-0866

Not Applicable

(Former Name or Former Address, if Changed Since Last Report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instructions A.2. below):

Item 5.02 Departure of Directors or Certain Officers; Election of Directors; Appointment of Certain Officers; Compensatory Arrangements of Certain Officers.

2015 Omnibus Incentive Plan

On June 11, 2015, at the Mast Therapeutics, Inc. (the “Company”) 2015 Annual Meeting of Stockholders (the “Annual Meeting”), the Company’s stockholders approved the Mast Therapeutics, Inc. 2015 Omnibus Incentive Plan (the “2015 Plan”) and it became effective as of that date. The Company’s board of directors (the “Board”) approved the 2015 Plan on April 17, 2015, subject to stockholder approval at the Annual Meeting. The Company’s directors and employees, including the Company’s named executive officers who currently are employed by the Company, Brian M. Culley, the Company’s Chief Executive Officer, and R. Martin Emanuele, the Company’s Senior Vice President, Development (the “NEOs”), and Brandi L. Roberts, the Company’s Chief Financial Officer, are eligible to participate in the 2015 Plan.

The 2015 Plan amends, restates and renames the Company’s 2014 Omnibus Incentive Plan (the “2014 Plan”), and, accordingly, no new awards may be granted under the 2014 Plan, which was the Company’s sole active plan under which equity compensation awards could be granted before the Annual Meeting. All outstanding awards under the 2014 Plan and the Company’s 2013 Omnibus Incentive Plan, Amended and Restated 2008 Omnibus Incentive Plan, 2008 Omnibus Incentive Plan and 2005 Equity Incentive Plan (collectively, the “Prior Plans”) will continue to be governed by the terms of the plan under which they were awarded.

Below is a summary of the principal differences between the 2015 Plan and the 2014 Plan:

A more detailed summary of the 2015 Plan is set forth in “Proposal 3—Approval of the Mast Therapeutics, Inc. 2015 Omnibus Incentive Plan” in the Company’s definitive proxy statement on Schedule 14A for the Annual Meeting, which was filed with the Securities and Exchange Commission on April 29, 2015, and is incorporated herein by reference. That summary and the summary in this report of the principal differences between the 2015 Plan and the 2014 Plan are qualified in their entirety by reference to the 2015

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Plan, a copy of which is filed as Exhibit 10.1 to this report.

On June 11, 2015, the members of the Board who are “independent directors” under the rules of the NYSE MKT LLC (the stock exchange on which the Company’s common stock is currently listed) (the “Board’s Independent Directors”) approved the following forms of stock option grant agreements for use under the 2015 Plan for options awarded to the Company’s non-employee directors and employees, including its executive officers: (a) form of Non-Statutory Stock Option Grant Agreement—Director (for grants to the Company’s non-employee directors); (b) form of Incentive Stock Option Grant Agreement – Exempt Employees; (c) form of Incentive Stock Option Grant Agreement – Non-Exempt Employees; (d) form of CEO Incentive Stock Option Grant Agreement (for grants to the Company’s Chief Executive Officer); and (e) form of CMO Incentive Stock Option Grant Agreement (for grants to the Company’s Chief Medical Officer). Copies of the forms described in (a) through (e) in the preceding sentence are attached as Exhibits 10.2, 10.3, 10.4, 10.5 and 10.6, respectively. There are no material differences in the terms of these new forms of stock option grant agreements compared to the forms used for option grants under the 2014 Plan, which were filed with the Securities and Exchange Commission as exhibits to the Company’s current report on Form 8-K on June 20, 2014, except that the form of Incentive Stock Option Grant Agreement – Non-Exempt Employees is a new form.

2015 Executive Incentive Plan

On June 11, 2015, the Board adopted the 2015 Executive Incentive Plan (the “Incentive Plan”) and approved corporate performance objectives thereunder, as further discussed below. However, only the Board’s Independent Directors deliberated and voted on the Incentive Plan; Mr. Culley abstained. The Incentive Plan will be governed and administered by the Board, but Mr. Culley will not be present during the deliberation or voting regarding his compensation.  The Incentive Plan is for the period beginning January 1, 2015 and ending December 31, 2015 (the “Plan Period”) and all of the Company’s officers are eligible to participate, including the NEOs and the Company’s Chief Financial Officer.

The Incentive Plan assigns each participant an incentive target expressed as a percentage of the participant’s annual base salary.  The actual amount of the participant’s award, if any, will be based on achievement of performance objectives approved by the Board.  A participant’s award will be based entirely (100%) on the Company’s achievement of corporate performance objectives, unless the Board approves individual performance objectives for a participant, in which case that participant’s award will be based 25% on the participant’s achievement of individual objectives and 75% on the Company’s achievement of corporate objectives. However, the award for the Company’s Chief Executive Officer is based entirely (100%) on the Company’s achievement of corporate objectives.

The following table lists the incentive targets (expressed as a percentage of the officer’s annual base salary) assigned to the officers of the Company eligible to participate in the Incentive Plan:

The Board may grant an award that is less than the incentive target if it determines performance partially met objectives or was less than acceptable, or it may grant an award that exceeds the incentive target if it determines performance exceeded objectives or was excellent in view of prevailing conditions; provided, however, that no award may be granted to a participant in excess of three (3) times such participant’s base salary. In evaluating performance, the Board will consider the achievement of objectives, the degree to which performance exceeded an objective, the partial achievement of an objective, the quality of achievement, the difficulty in achieving the objective, conditions that affected the ability to achieve objectives and such other factors as the Board determines are appropriate to consider. In determining the actual payout amount of an award, the Board will take into account the recommendations of the Company’s Chief Executive Officer. The awards generally will be paid in cash; however, the Board has discretion to determine the composition of each award.

Payment of any award will be made in a single sum on or before March 14, 2016. Subject to any contractual obligations the Company may owe a participant, (a) a participant has not earned and does not have any right or entitlement to any award until the time it is actually paid to such participant, and (b) the Board has absolute discretion to abolish the Incentive Plan at any time or to alter the terms and conditions under which awards will be paid, with or without any reason and with or without prior notice. In order to have earned an award, the applicable participant must have been continuously employed with the Company through and including the date of payment of his or her award, and if the employment of a participant is terminated (whether voluntarily or involuntarily) during the Plan Period or prior to payment of his or her award, whether or not any award payment is made to that participant will be at the absolute discretion of the Board.

The corporate performance objectives under the Incentive Plan were approved by the Board’s Independent Directors, after considering recommendations from the Company’s Chief Executive Officer, and reflect the Independent Directors’ assessment of near-term goals that are expected to enhance stockholder value if achieved. The corporate objectives involve: (a) patient enrollment in the EPIC study,

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the Company’s ongoing Phase 3 study of vepoloxamer (MST-188) in sickle cell disease, patient enrollment in the EPIC extension study (referred to as EPIC-E), and progress with regulatory affairs and other aspects of development of vepoloxamer for sickle cell disease; (b) patient enrollment in the planned Phase 2 study of vepoloxamer in heart failure and progress with other aspects of research and development of vepoloxamer for heart failure, (c) patient enrollment in the ongoing Phase 2 study of vepoloxamer in acute limb ischemia and progress with other aspects of research and development of vepoloxamer for arterial disease, including stroke; (d) progress with clinical development of AIR001 in heart failure with preserved ejection fraction; (e) progress with intellectual property-related initiatives, and (f) cash management.

As of the date of this report, the Board had not approved individual performance objectives for any participant. If the Board approves individual performance objectives for a participant, they will be tailored to that participant’s role in the Company and relate to one or more of the following categories: (i) progress and plans relating to research and development of the Company’s product candidates in one or more indications, including nonclinical, clinical, manufacturing and/or regulatory activities, (ii) budget, finance and financial controls and reporting, (iii) corporate management and planning, (iv) collaborative development and/or commercialization arrangements, including partnering and licensing arrangements, government funding, and/or other strategic opportunities (v) compliance and risk management, and (vi) investor relations and communication.

Pursuant to the Incentive Plan, if a corporate or individual performance objective becomes irrelevant or undesirable during the Plan Period or if a strategic change affects one or more objectives, then, for each such affected objective, the Board, after considering the recommendations of the Company’s Chief Executive Officer, may (A) if objectives are weighted, adjust the weightings of one or more existing objectives, (B) substitute one or more new objectives, if objectives are weighted, with appropriate weightings for new and existing objectives, (C) eliminate one or more existing objectives and, if objectives are weighted, re-weight objectives or (D) take no action.

The foregoing description of the terms of the Incentive Plan is subject to, and qualified in its entirety by, the Incentive Plan, which is attached hereto as Exhibit 10.7 and incorporated herein by reference.

Mr. Lief’s Resignation from the Board

Jack Lief previously notified the Company of his intent to resign from the Board to avoid any potential conflict of interest given his position as President and Chief Executive Officer of Arena Pharmaceuticals, Inc. and Arena’s development of a product candidate for the treatment of vascular diseases, including pulmonary arterial hypertension (“PAH”).  Mast Therapeutics’ product candidate, AIR001, has been tested in Phase 1 and Phase 2 clinical studies for the treatment of PAH and the Company currently is developing AIR001 for heart failure with preserved ejection fraction.  On June 11, 2015, Mr. Lief delivered notice to the Board of his resignation from the Board and from all committees of the Board, effective as of August 7, 2015.  Mr. Lief’s decision to resign was not due to any disagreement with the Company known to any of its executive officers on any matter relating to the Company’s operations, policies or practices.

Item 5.07 Submission of Matters to a Vote of Security Holders.

On June 11, 2015, the Company held the Annual Meeting. The following is a brief description of each matter voted upon at the Annual Meeting and final voting results showing the number of votes cast for and against, as well as the number of abstentions and broker non-votes as to each such matter, as applicable.

Proposal 1—To elect five directors to hold office until the next annual meeting of stockholders and until their respective successors are elected and qualified or until their earlier resignation or removal:

In accordance with the above results, each nominee was elected to serve as director.

Proposal 2—To ratify the appointment of PricewaterhouseCoopers LLP as the Company’s independent registered public accounting firm for the fiscal year ending December 31, 2015:

In accordance with the above results, the appointment of PricewaterhouseCoopers LLP was ratified.

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Proposal 3—To approve the Mast Therapeutics, Inc. 2015 Omnibus Incentive Plan:

In accordance with the above results, the Mast Therapeutics, Inc. 2015 Omnibus Incentive Plan was approved.

Item 9.01 Financial Statements and Exhibits.

(d) Exhibits.

The list of exhibits called for by this Item is incorporated by reference to the Exhibit Index immediately following the signature page of this report.

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SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

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Exhibit Index

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