8-K

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): August 14, 2014

Mast Therapeutics, Inc.

(Exact name of registrant as specified in its charter)

Delaware	001-32157	84-1318182
(State or other jurisdiction of incorporation)	(Commission File Number)	(IRS Employer Identification No.)

12390 El Camino Real, Suite 150, San Diego, California	92130
(Address of principal executive offices)	(Zip Code)

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:

¨ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

¨ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

¨ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

¨ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Item 8.01. Other Events.

Beginning on August 14, 2014, the information attached as Exhibit 99.1 to this report relating to Mast Therapeutics, Inc. (the “Company”) and its development programs may be presented from time to time by the Company at various investor and analyst meetings, including at the Canaccord Genuity 34^th Annual Growth Conference.

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.

By filing this report, including the information contained in Exhibit 99.1 attached hereto, the Company makes no admission as to the materiality of any information in this report. The information contained in Exhibit 99.1 hereto is summary information that is intended to be considered in the context of the Company’s filings with the U.S. Securities and Exchange Commission (the “SEC”), including its Annual Report on Form 10-K filed on March 26, 2014, Quarterly Report on Form 10-Q filed on August 11, 2014, and other public announcements that the Company makes, by press release or otherwise, from time to time. The Company undertakes no duty or obligation to publicly update or revise the information contained in this report, although it may do so from time to time as it believes is appropriate. Any such updating may be made through the filing of other reports or documents with the SEC, through press releases, or through other public disclosure.

Forward-Looking Statements

Mast Therapeutics cautions you that statements included in this report, including in Exhibit 99.1 attached hereto, that are not a description of historical facts are forward-looking statements that are based on the Company’s current expectations and assumptions. Such forward-looking statements include, but are not limited to, statements regarding the Company’s development, regulatory and commercialization strategies and plans for its product candidates, including MST-188 in sickle cell disease, arterial disease, heart failure, and AIR001, as well as the timing of activities related to those plans, including commencement and completion of clinical and nonclinical studies. Among the factors that could cause or contribute to material differences between the Company’s actual results and the expectations indicated by the forward-looking statements are risks and uncertainties that include, but are not limited to: the uncertainty of outcomes in ongoing and future studies of its product candidates and the risk that its product candidates may not demonstrate adequate safety, efficacy or tolerability in one or more such studies, including MST-188 in the ongoing EPIC study and phase 2 study in acute lower limb ischemia; delays in the commencement or completion of clinical studies, including as a result of difficulties in obtaining regulatory agency agreement on clinical development plans or clinical study design, opening trial sites, enrolling study subjects, manufacturing sufficient quantities of clinical trial material, completing manufacturing process development activities, being subject to a “clinical hold,” and/or suspension or termination of a clinical study, including due to patient safety concerns or lack of funding; the potential for institutional review boards or the FDA or other regulatory agencies to require additional nonclinical or clinical studies prior to initiation of planned clinical study of a product candidate; the risk that, even if clinical studies are successful, the FDA or another regulatory agency may determine they are not sufficient to support a new drug application; the potential that even if clinical studies of a product candidate in one indication are successful, clinical studies in another indication may not be successful; the Company’s reliance on contract research organizations (CROs), contract manufacturing organizations (CMOs), and other third parties to assist in the conduct of important aspects of development of its product candidates, including clinical studies, manufacturing, and regulatory activities for its product candidates and that such third parties may fail to perform as expected; the Company’s ability to obtain additional funding on a timely basis or on acceptable terms, or at all; the potential for the Company to delay, reduce or discontinue current and/or planned development activities, including clinical studies, partner its product candidates at inopportune times or pursue less expensive but higher-risk and/or lower return development paths if it is unable to raise sufficient additional capital as needed; the risk that the FDA and regulatory agencies outside of the U.S. do not grant marketing approval of a product candidate, on a timely basis, or at all; the risk that, even if the Company successfully develops a product candidate in one or more indications, it may not realize commercial success with its products and may never generate revenue sufficient to achieve profitability; the risk that the Company is not able to adequately protect its intellectual property rights and prevent competitors from duplicating or developing equivalent versions of its product candidates; and other risks and uncertainties more fully described in the Company’s periodic filings with the SEC and press releases.

You are cautioned not to place undue reliance on forward-looking statements, which speak only as of the date they are made. Mast Therapeutics does not intend to revise or update any forward-looking statement set forth in this report to reflect events or circumstances arising after the date hereof, except as may be required by law. This caution is made under the safe harbor provisions of Section 21E of the Securities Exchange Act of 1934, as amended, and Section 27A of the Securities Act of 1933, as amended.

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.

	Mast Therapeutics, Inc.
August 14, 2014	By:	/s/ Patrick L. Keran
		Name: Patrick L. Keran
		Title: President and Chief Operating Officer

Exhibit Index

Exhibit No.	Description
99.1	Mast Therapeutics, Inc. corporate presentation, August 14, 2014

EX-99.1

Exhibit 99.1

NYSE MKT: MSTX Canaccord Genuity 34th Annual Growth Conference Brian M. Culley, CEO August 14, 2014

2 Forward-Looking Statements This presentation includes forward-looking statements about our business prospects, financial position, and development of MST-188 and AIR001 for therapeutic use in humans. Any statement that is not a statement of historical fact should be considered a forward-looking statement. Because forward-looking statements relate to the future, they are subject to inherent risks, uncertainties and changes in circumstances that are difficult to predict. Actual events or performance may differ materially from our expectations indicated by these forward- looking statements due to a number of factors, including, but not limited to, results of our pending and future clinical studies, the timeline for clinical and manufacturing activities and regulatory approval; our dependency on third parties to conduct our clinical studies and manufacture our clinical trial material; our ability to raise additional capital, as needed; our ability to establish and protect proprietary rights related to our product candidates; and other risks and uncertainties more fully described in our press releases and our filings with the SEC, including our annual report on Form 10-K filed with the SEC on March 26, 2014. We caution you not to place undue reliance on any of these forward-looking statements, which speak only as of the date of this presentation. We do not intend to update any forward-looking statement included in this presentation to reflect events or circumstances arising after the date of the presentation, except as may be required by law.

Publicly-traded biopharmaceutical company based in San Diego Developing MST-188 for diseases of membrane dysfunction Near-term focus on rare ("orphan") diseases Sickle Cell Disease (SCD) - phase 3 enrolling Acute Limb Ischemia (ALI) - phase 2 enrolling Longer-term growth into larger markets Heart Failure Stroke Recently acquired Aires Pharmaceuticals (AIR001) Phase 2 asset in Pulmonary Hypertension (PH) Complementary to MST-188 3 Corporate Overview

4 Lead Program MST-188

API Structure: CMC: Large polymer (8,500 Daltons) manufactured by chemical synthesis and proprietary purification process Administration: IV infusion 5 MST-188 Overview HO - (CH2CH2O)79- (CH2CHO)30- (CH2CH2O)79- H CH3 | 5

No Affinity for Healthy Cell Membranes... But Adheres to Damaged Cell Membranes Hydrophobic core adheres to hydrophobic domains in circulation (e.g., damaged cell membranes) 6 MST-188 Mechanism of Action

7 Biophysical mechanism confers multiple pharmacodynamic features MST-188 Pharmacodynamics

MST-188 Clinical Development 8 Preclinical Phase 1 Phase 2 Phase 3 2014 2014 2014 2014 2014 Sickle Cell Disease (orphan) Acute Limb Ischemia* (orphan) Acute Heart Failure Stroke* Enrolling Planned initiation: 1H 2015 Planned initiation: 2H 2014 *In combination with thrombolytics Enrolling

9 Sickle Cell Disease

A chronic, genetic disorder and rare (orphan) disease Affects 90,000 to 100,000 people in the U.S. Characterized by severe deformation (i.e., "sickling") of red blood cells Hallmark of disease is a "vaso-occlusive crisis" Exceedingly painful condition Leading cause of hospitalization Significant unmet need No approved agents to shorten duration or severity of crisis Standard of care (hydration and analgesics) unchanged for >10 years Vaso-occlusion is associated with early death Obstructed blood flow -> hypoxia -> tissue death -> organ failure Average age at death; 42 years (males), 48 years (females) 10 Overview of Sickle Cell Disease

The Complex Pathophysiology of Sickle Cell Disease Requires Multiple Sites of Intervention sRBC Adherence to Endothelium VASO-OCCLUSION ORGAN DAMAGE/FAILURE ANEMIA PAIN INTRAVASCULAR Hemolysis NITRIC OXIDE DEPLETION VASOCONSTRUCTION INFLAMMATION ACTIVATION OF COAGULATION TISSUE ISCHEMIA LOCAL HYPOXIA STRESS LARGE VESSEL DAMAGE Microvascular DAMAGE WBC adherence to RBCs Activated WBCs WBC adherence to endothelium Activated platelets Release of Inflammatory Cytokines Endothelial Cell Activation Free Radical Formation Loss of antithrombotic action Loss of anti- inflammatory action Release of Inflammatory Cytokines Endothelial Cell Retraction/ Exposed Subendothelial Matrix Release of Inflammatory Cytokines Free Radical Formation Stimulation of nociceptors Increased Epinephrine Levels Activated platelets Endothelial Cell Retraction/ Exposed Subendothelial Matrix Increased Platelet Count Activated WBCs Increased WBC Count Release of Inflammatory Cytokines Externalization of phosphatidylserine Polymerization of HbS Membrane Damage Red Cell Dehydration Increased Reticulocyte Counts Plasma Free Hb Irreversibly Sickled Cells Red Cell Arginase Release

12 MST-188: Reduces adhesion of cells to endothelium (anti-inflammatory) Reduces RBC aggregation, improves RBC deformability, lowers viscosity, and restores flow (rheologic) Vaso-Occlusion: Adhesion of poorly-deformable, "sticky" cells to endothelium Physical entrapment of rigid, sickled cells and vessel obstruction Role of MST-188 in Sickle Cell Disease 12 Ischemia: RBCs cannot traverse occlusion to deliver oxygen to tissue, resulting in ischemia, hypoxia and infarction

MST-188 Placebo Before Infusion (Crisis Baseline) Velocity (mm/sec) 0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 2-Hours After Loading Infusion 7-Hours After Loading Infusion Source: J. Investig. Med. 2004;52(6):402-6 (p = 0.00003) 13 MST-188 improved microvascular blood flow in SCD patients in crisis 13 MST-188 Improves Blood Flow Red cell velocity (mm/s) measured by video microscopy in nine sickle cell patients with vaso-occlusive crisis.

Phase 2 Study Source: Blood, September 1, 1997 - Vol 90, No. 5 * 1st generation (non-purified) formulation 14 Subjects Who Received Full Dose+- Subjects Who Received Full Dose+- Subjects Who Received Full Dose+- MST-188* (n=18) Placebo (n=13) p value+-+- Duration of Crisis 44 hours 80 hours 0.025 Duration of Hospitalization 5 days 7 days 0.111 Total Analgesic Use 34mg 145mg 0.045 Parenteral Analgesic Use 27mg 133mg 0.022 +- Excludes patients who had drug administration errors or incomplete pain assessments (16), who withdrew consent (2) and who withdrew because of injection site pain after 15 minutes of infusion. Subjects were excluded equally (n=9) between MST-188 and placebo. +-+- Proportional hazards model adjusted for baseline pain. Randomized, double-blind, placebo-controlled, multi-center study of MST-188* in SCD patients hospitalized for crisis MST-188 significantly improved important efficacy parameters

Source: JAMA, November 17, 2001 - Vol 286, No. 17 15 Randomized, double-blind, placebo- controlled, multi-center study of MST- 188 in 255 patients with SCD Time-to-event analysis demonstrates consistent trend in achievement of crisis resolution Original statistical plan, which required 350 patients, was reduced by almost 30% by prior sponsor (capital constraints), lowering statistical power. Observation period was stopped at 168 hours ("right censoring"), diminishing observable treatment differences Phase 3 Study 15 p = 0.09 All Treated Patients (n=249) Hours After Randomization Distribution Function Children (<16 years) (n=73) p = 0.007

Source: JAMA, November 17, 2001 - Vol 286, No. 17 16 Group MST-188 Placebo p Value All treated patients (n=249) 51.6% 36.6% 0.02 Patients <16 years (n=73) 59.5% 27.8% 0.009 Phase 3 Study Responders analysis is not impacted by "right-censoring" (discontinuation of observation period) MST-188 significantly increased the proportion of patients achieving crisis resolution at 168 hours (end of the observation period)

Randomized, Double-Blind, Placebo-Controlled, Multicenter 388 patients Standard of care +/- MST-188 Primary Efficacy Assessment Duration of crisis Secondary Efficacy Assessments Re-hospitalization for crisis within 14 days Occurrence of acute chest syndrome Power 90% power to detect a 16-hour difference (p=0.05) 85% power to detect a 24-hour difference (p=0.01) 17 Evaluation of Purified 188 In Crisis (EPIC): Pivotal Phase 3 Study Design

Enrollment on-track at 14 months (announced Aug 2014) >45 U.S. sites open Multiple ex-U.S. sites open Most Advanced New Drug in SCD Potential to be first approved drug to treat an on-going vaso-occlusive crisis Substantial head start versus other new drugs in development for SCD Positive Factors for Regulatory Decision-Making Significant unmet need Fast Track designation Orphan Drug designation Healthcare disparity 18 EPIC Success Factors

19 Arterial Disease (MST-188 In Combination with Thrombolytics) Acute Limb Ischemia Stroke

A progressive circulatory problem in which obstructed arteries reduce blood flow to tissues Thrombolytic agents (tPA) are used to treat acute complications Significant morbidity and mortality 20 Acute Ischemic Cerebrovascular Infarction (stroke) Acute Myocardial Infarction (heart attack) Peripheral Arterial Disease Intermittent Claudication Critical Limb Ischemia Acute Limb Ischemia Development Strategy: Develop initially in ALI Expand into other markets Overview of Arterial Disease

‹#›

22 Parameter MST-188* Control Difference p Value N=114 Myocardial Infarct Size (median) 16% 26% 38% reduction 0.031 Myocardial Salvage (median) 13% 4% 125% increase 0.033 Ejection Fraction (median) 52% 46% 13% improvement 0.020 Incidence of Reinfarction 1% 13% 92% reduction 0.016 MST-188 Showed Synergy with Thrombolytics in Heart Attack Source: Circulation 1996; 94: 298-307 *1st generation (non-purified) formulation

23 Clinical Proof-of-Concept Study Biomarkers Clinical outcomes Study Design Randomized, double-blind, and active-controlled Rutherford Class 2A/2B and catheter-directed thrombolysis t-PA +/- low or high dose MST-188 60 subjects (20 per arm) Timing Study initiated Q1 2014 Completion of enrollment anticipated Q4 2015 ALI data can be supportive of clinical development in stroke Phase 2 Study in ALI

24 Heart Failure (Acute Decompensation)

Overview of Heart Failure 25 Chronic condition characterized by decreasing heart function Heart cannot pump enough blood to meet the body's needs Significant Unmet Medical Need Leading healthcare cost in U.S. and Europe Substantial and Growing Market Opportunity > 5 million individuals with heart failure in the U.S. Acute Decompensation Each decompensation event contributes to worsening heart failure and damage to vital organs, decreasing survival probability following the next event MST-188 Membrane-sealant activity may restore weakened cardiac cell membranes, minimizing calcium overload injury Durable effect may indicate a direct improvement in cardiac function

Proof-of-Concept in Heart Failure (nonclinical model of chronic heart failure) 26 Single 2h infusion resulted in improvements in hemodynamic parameters (LVEF, CO) and biomarkers (troponin, NT-proBNP) Troponin associated with 180-day all-cause mortality Elevated NT-proBNP associated with poor prognosis Potentially novel mechanism, compatible with existing treatments Planning to initiate Phase 2 in acute decompensated HF in 1H 2015 Source: data on-file (CHART) * = p<0.05 vs. Control * * * (CHART) * = p<0.05 vs. Control * * * * *

27 AIR001 (sodium nitrite) inhalation solution

Nitrite for intermittent inhalation (via nebulizer) Beneficial effects include dilation of blood vessels and reduced inflammation Positive hemodynamic effects - observed reductions in: pulmonary vascular resistance pulmonary capillary wedge pressure right atrial pressure Safety data in more than 120 subjects (well-tolerated) Additional clinical data expected Q3 2014 from 29 pulmonary arterial hypertension (PAH) patients 28 AIR001

PH is high blood pressure affecting the blood vessels in the lungs Leads to shortness of breath, dizziness, fainting, leg swelling, etc. May result in heart failure Evaluating AIR001 in World Health Organization (WHO) Group 2 Patients (PH associated with left heart disease)* Planned expansion of an ongoing Phase 2a study in PH Evaluate whether AIR001 can reduce PVR, PCWP and RAP Data expected 2H '15 29 AIR001 for Pulmonary Hypertension * Simonneau G, Robbins I, Beghetti M. et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2009; 54: S43-S54.

30 Upcoming News & Events

Cash/investments at 6/30/14: $46.4 million Market capitalization: ~$75 million* Shares outstanding: ~121 million* Average daily volume (3 mo): ~1.2 million* No debt 31 * As of August 11, 2014 MSTX Financial Overview

A Leader in Areas of Significant Unmet Need Sickle Cell Disease: Most advanced (Phase 3) new drug in development Acute Limb Ischemia: Initiated Phase 2 study in Q1 2014 Heart Failure: potential new mechanism with durable effects Recently acquired Aires Pharmaceuticals (AIR001) New Phase 2 opportunities in pulmonary hypertension and heart failure Cash and marketable securities $46.4 million at 6/30/14 No debt 32 Mast Investment Summary