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): September 7, 2016

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.)
3611 Valley Centre Drive, Suite 500, San Diego, CA		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 (see General Instructions A.2. below):

¨ 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 7.01 Regulation FD Disclosure.

The information furnished in Exhibit 99.1 to this report, which relates 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.  

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.

In accordance with General Instruction B.2. of Form 8-K, the information in Item 7.01 of this report and Exhibit 99.1 hereto shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liability of that section, nor shall it be deemed incorporated by reference in any of the Company’s filings under the Securities Act of 1933, as amended, or the Exchange Act, whether made before or after the date hereof, regardless of any incorporation language in such a filing, except as expressly set forth by specific reference in such a filing.

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 14, 2016, Quarterly Report on Form 10-Q filed on August 9, 2016, 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 in this report, including in Exhibit 99.1 attached hereto, that are not a description of historical facts are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by the use of words referencing future events or circumstances such as “expect,” “intend,” “plan,” “anticipate,” “believe,” and “will,” among others.  Examples of forward-looking statements include, but are not limited to, statements regarding the Company’s development, regulatory and commercialization strategies and plans for its investigational new drugs, vepoloxamer (also known as MST-188) and AIR001, as well as the timing of activities and events related to those plans, including commencement and completion of clinical studies, announcements of study results, submission of applications to regulatory authorities for marketing approval, and product launch, and prospects for clinical, regulatory and commercial success.  Forward-looking statements should not be read as guarantees of future performance or results because they involve the Company’s beliefs and assumptions based on currently available information and are subject to significant known and unknown risks and uncertainties that may cause actual performance and results to differ materially from expectations indicated by the forward-looking statements.  Some of the factors that could cause actual performance or results to differ include, without limitation: the potential for additional delays in EPIC study closeout procedures, including blinded data validation and quality assurance/quality control procedures; the inherent uncertainty of outcomes in clinical studies and the risk that the Company’s product candidates may not demonstrate adequate safety, efficacy or tolerability in one or more such studies, including vepoloxamer in the EPIC study; the risk that, even if EPIC results are positive, the FDA or other regulatory agencies may determine they are not sufficient to support a new drug application; uncertainties related to future feedback from the FDA regarding the development of vepoloxamer, including the risks that the FDA may determine another Phase 3 study or other clinical or nonclinical studies are necessary to demonstrate vepoloxamer’s development and/or safety for the treatment of patients with sickle cell disease or may require changes to manufacturing controls or processes, any of which could delay filing of a new drug application, significantly increase the cost of vepoloxamer’s development and/or ultimately lead to denial of regulatory approval of vepoloxamer; the Company’s need for additional funding to continue to operate as a going concern; risks associated with the Company’s ability to manage operating expenses and obtain additional capital as needed; uncertainty related to the Company’s ability to comply with the terms and conditions under its debt facility and risk that it may be required to repay its outstanding debt obligations on an accelerated basis and/or at a time that could be detrimental to the Company’s financial condition, operations and/or business strategy, including prepayment of $10 million of the principal balance of its debt facility if results from EPIC are not positive and/or are not available on or before October 14, 2016; delays in the commencement or completion of clinical studies, including the EPIC study, the Phase 2 study of vepoloxamer in heart failure, and the Phase 2 studies of AIR001 in HFpEF, 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 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 the risk that such third parties may fail to perform as expected, leading to delays in product candidate development, regulatory approval, commercial launch and/or inability to meet future market demand for any approved products; the potential for the Company to significantly delay, reduce or discontinue current and/or planned development, regulatory and commercial-readiness activities or sell or license its assets at inopportune times 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 and may never achieve profitability; the risk that the Company is not able to obtain and maintain effective patent coverage or other market exclusivity protections for its products, if approved, or that the use or manufacture of the Company’s products may infringe the proprietary rights of others; and other risks and uncertainties more fully described in the Company’s press releases and periodic filings with the SEC.

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 Exchange Act 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.
Date:  September 7, 2016	By:	/s/ Brandi L. Roberts
		Brandi L. Roberts
		Chief Financial Officer and Senior Vice President

Exhibit Index

Exhibit Number	Description
99.1	Mast Therapeutics, Inc. corporate presentation, September 7, 2016

EX-99.1

Corporate Overview September 7, 2016 Exhibit 99.1

Safe Harbor Statement This presentation includes forward-looking statements about our business prospects, financial position, and development of vepoloxamer 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, manufacturing and regulatory activities; failure to obtain regulatory approval of our product candidates; our dependency on third parties to conduct clinical studies and supply or manufacture clinical trial material and/or product for commercial sale, if approved; our ability to raise additional capital as needed; our ability to repay outstanding debt as payments come due; 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 quarterly report on Form 10-Q filed with the SEC on August 9, 2016. 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.

Preclinical Phase 1 Phase 2 Phase 3 Heart Failure (HFpEF) Preclinical Phase 1 Phase 2 Phase 3 Sickle Cell Disease Heart Failure (HFrEF) Ischemic Stroke Vepoloxamer* AIR001* Product Candidate Pipeline Enrolling Top-line results expected Sep. 2016 Phase 2-ready Enrolling *Investigational new drug

Vepoloxamer: A Novel Biophysical Agent Mechanism hypothesis: Vepoloxamer adheres to damaged cell membranes, correcting defects in membrane surface tension, an underlying feature of multiple diseases Potential benefits of “biophysical” mechanism of action: Targets damaged tissue; little or no activity in healthy tissue Not metabolized; no active metabolites to track, no difference in fast vs slow metabolizers, less susceptible to drug-drug interactions Less susceptible to genetic variation; independent of receptors, etc. Damaged Cell Membrane? Vepoloxamer Adheres Normal Cell Membrane? Vepoloxamer Inactive

Pathologies and Conditions Related to Defects in Membrane Surface Tension Sickle Cell Disease Chronic & Acute Heart Failure Ischemic Stroke Surface Tension Pathologies Elevated blood viscosity Cellular aggregation Cellular adhesion Loss of membrane barrier function / repair capacity Dysfunctional coagulation Examples

Vepoloxamer in Sickle Cell Disease Objective: Improve blood flow to prevent ischemic injury and shorten duration of crisis Phase 3 Study – Enrollment Complete

Overview of Sickle Cell Disease A chronic genetic disorder and rare (orphan) disease Affects ~100,000 people in the U.S. and is characterized by severe deformation of red blood cells Hallmark of disease is a “vaso-occlusive crisis” (VOC) Reduces blood flow and causes ischemic injury to tissues and organs Exceedingly painful condition and a leading cause of hospitalization 80-100k hospitalizations annually in the U.S. with average hospital stay of 4-5 days Current treatment is palliative Consisting of hydration and IV opioids Does not treat underlying pathophysiology of the disease No VOC interventional therapy available Significant unmet need No approved agents to shorten duration or severity of crisis Shorter life expectancy due to ischemic injury (~45y) Sources: Life-expectancy: Hassell, K. Am J Prev Med 2010; 38(4S): S512-521; Utilization data calculated from data in Brousseau, D., et al., Acute Care Utilization and Rehospitalizations for Sickle Cell Disease JAMA Apr 7 2010 and HCUP 2010-2012; SCD prevalent pop: Brousseau DC, Panepinto JA, Nimmer M, Hoffmann RG. The number of people with sickle-cell disease in the United States: national and state estimates. Am J Hematol 2010;85:77-8; Steinberg, M.H., Management of Sickle Cell Disease, New Eng J Med; 1999; Vol 340, No 13; Platt, et al., Mortality in Sickle Cell Disease (N Engl J Med 1994;330:1639-44)

Vepoloxamer in Sickle Cell Disease (SCD) The underlying pathology of vaso-occlusive crisis is reduced blood flow Studies suggest vepoloxamer improves blood flow by addressing multiple pathological mechanisms: Adhesion Hemolysis Aggregation Viscosity Objective of treatment with vepoloxamer: Improve blood flow to prevent ischemic injury and shorten the duration of crisis

Vepoloxamer Improved Blood Flow in Sickle Cell Patients Source: J. Investig. Med. 2004;52(6):402-6 Vepoloxamer 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 7-Hours After Loading Double-blind assessment of red cell velocity in nine sickle cell patients experiencing vaso-occlusive crisis (p = .00003) Vepoloxamer significantly improved microvascular blood flow in sickle cell patients experiencing crisis (randomized sub-study)

Vepoloxamer Development History Over 100 nonclinical studies completed Phase 2 SCD – statistically significant shorter crisis and less opioid use Phase 2 ACS* – ~50% shorter hospitalization stay vs. historical control Phase 3 SCD – shorter duration of crisis (p-value = 0.07) Lessons learned from prior sponsors and applied to Mast’s Phase 3 study: Vepoloxamer has activity in SCD Study design is key to success (prior endpoint poorly designed) Key FDA feedback: Utilize a clinically meaningful endpoint Use as objective an endpoint as possible Avoid use of pain scores due to variability Provide a plan to minimize data loss (*Acute chest syndrome, a serious complication of sickle cell crisis)

The Phase 3 “EPIC” Study Evaluation of Purified Poloxamer 188 In Vaso-Occlusive Crisis Largest placebo-controlled study in sickle cell disease ever concluded Double-Blind, Placebo-Controlled, International (~75 sites) 388 patients, randomized 1:1 to standard of care +/- vepoloxamer 1hr loading dose followed by 48h continuous infusion Primary Endpoint Duration of crisis (time of randomization to last dose of parenteral opioid) Secondary Endpoints Re-hospitalization for VOC within 14 days Occurrence of acute chest syndrome within 120 hours of randomization Other Assessments Safety Duration of hospitalization Biomarkers Opioid utilization Sub-study outcomes

EPIC Study: Primary Endpoint Assessment: Duration of vaso-occlusive crisis Definition: Time from randomization to last dose of parenteral opioid (LPO) Advantages: Aligns with FDA recommendations Sensitive and specific data collection Objective Minimal data loss Medical expert support Clinically meaningful to experts in the field Powering: 90% power to detect a 17% difference in treatment arms with a statistical significance level of p=0.05

EPIC Study: Safety DSMB Evaluations Independent, unblinded DSMB (4 clinicians and 1 statistician) Meetings at 25, 58, 145 and 250 patients DSMB meeting held at 250 patients No unexpected safety signals identified DSMB members deemed no additional meetings were necessary

EPIC Study: Key Characteristics U.S. patients = ~60% Average patient age = 15 years (range 4-46, ~30% adults) Hydroxyurea use = >60% Blinded analysis at 250 patients: Average duration of crisis (pooled) & coefficient of variation consistent with statistical assumptions in study design (79h and ~50%) Minimal regional variability (U.S. vs ex-U.S.) Top-line data anticipated September 2016

Vepoloxamer in SCD: Regulatory Considerations Significant unmet need – no disease-modifying therapies for an ongoing crisis Support among medical / advocacy / patient communities Orphan Drug Designation Fast Track Designation SCD is part of FDA “Patient-Focused Drug Development Initiative” Healthcare disparity concerns NDA-supportive clinical studies: Thorough QT study - complete Special population study - enrolling Repeat-administration study – enrolling One patient who completed the EPIC Study has subsequently received three doses of vepoloxamer in the elective repeat-dose study

Vepoloxamer: Commercial Opportunity in Sickle Cell Disease

SCD: A Lifetime of Complications Source: Martin H. Steinberg, M.D., Management of Sickle Cell Disease, New Eng J Med; 1999; Vol 340, No 13 Infant Adolescent Transition Childhood Young Adult Mature Adult Adult Senior Diagnosis (at birth) Daily penicillin prophylaxis (through age 5) Transfusions may begin for cerebral infarction (stroke) Acute Chest Syndrome (common complication of VOC) Splenectomy (usually before age 8) Patient may have early signs of renal disease Multiple hospitalizations for VOC per year Avascular necrosis may start to occur as a result of ischemia Annual eye exams recommended for retinopathy, hemorrhages, and retinal detachments Multiple organ damage and failure Premature death Chronic pain Priapism and pregnancy complications Pulmonary hypertension Leg ulcers Cholelithiasis (gallstones) “Sickle cell disease is a chronic disease that is punctuated by acute events and that shortens life.” Acute papillary necrosis of the kidneys

Vaso-Occlusive Crisis is the Hallmark of SCD 80-100k hospitalizations annually in the U.S. Current treatment is palliative Consisting of hydration and IV opioids Does not treat underlying pathophysiology of the disease No VOC interventional therapy available Hospitalized on average for approximately 4-5 days 40% of patients will have acute chest syndrome complication 12-41% are re-hospitalized within 30 days of hospital discharge Shorter life expectancy due to ischemic injury to organs (~45y) Organ failure is leading cause of death Sources: Life-expectancy: Hassell, K. Am J Prev Med 2010; 38(4S): S512-521; Utilization data calculated from data in Brousseau, D., et al., Acute Care Utilization and Rehospitalizations for Sickle Cell Disease JAMA Apr 7 2010 and HCUP 2010-2012; SCD prevalent pop: Brousseau DC, Panepinto JA, Nimmer M, Hoffmann RG. The number of people with sickle-cell disease in the United States: national and state estimates. Am J Hematol 2010;85:77-8; Steinberg, M.H., Management of Sickle Cell Disease, New Eng J Med; 1999; Vol 340, No 13; Platt, et al., Mortality in Sickle Cell Disease (N Engl J Med 1994;330:1639-44)

Market Research: Expected Features and Potential Benefits Align with Unmet Needs for VOC Treatment Source: RDS Consulting Group Research Report, 2015

Market Research: Physicians Report a High Percent of Patients to be Treated with Vepoloxamer at Peak Survey-reported time to peak adoption: approx. 6 months) Source: RDS Consulting Group Research Report, 2015, n=30

Development Landscape in SCD Stage VOC Intervention VOC Reduction SCD Corrective Treatment Marketed hydroxyurea Bone Marrow Transplant Phase 3 vepoloxamer rivipansel L-glutamine Phase 2 SC-411 Sanguinate Sevuparin SelG1 GBT440 Phase 1 CXA-10 NiCord/CordLn NKTT120 PF-04447943 SCD-101 Gene therapy Vepoloxamer has the potential to be the first and only interventional treatment to reduce the duration and severity of an ongoing VOC

Concentration of SCD Treatment in the U.S. Offers an Attractive Commercial Opportunity Source: Analysis of HCUP NIS 2013 data; Dx 282.62 is 89.7% of all VOCs. Top 500 U.S. hospitals treat nearly 80% of SCD patients in crisis Effective field promotion with small hospital sales force (~30)

U.S. Sickle Cell Disease Hospital Payer Mix Inpatient prospective payment system (IPPS) Patients with public insurance have minimal share of costs Medicaid plans may seek additional funding via CHIP, per diem rates, or modified FFS rates Vepoloxamer expected to meet criteria for additional Medicare payment (NTAP) Source: ADVI analysis, 2015

Commercial Potential Outside the U.S. Over 10 million patients worldwide Europe Approximately 40,000 patients >50% reside in two countries: UK and France Most patients concentrated in large metro areas: Paris and London MENA Over 850,000 with SCD Many treatment centers provide care on par with standard of the U.S. and E.U. Sources: Hassell KL. Population estimates of sickle cell disease in the U.S. Am J Prev Med 2010;38(4 Suppl):S512-21; Data on file, Mast Therapeutics 2015; VOI Consulting analysis, 2015

Vepoloxamer Positioned for Success in SCD Novel therapy for a genetic disease with high unmet needs Unique and relevant mechanism of action No approved disease-modifying therapies available for VOC intervention Significant first-to-market advantage in multiple territories Clinical development >2 years ahead of other SCD programs Orphan Drug Designation in U.S. and E.U. Concentrated market Top 500 U.S. hospitals treat nearly 80% of SCD patients in crisis 96% of SCD patients in the U.S. have insurance coverage Research supports rapid adoption & significant market penetration Ranked 4.4 out of 5 as a “breakthrough medical innovation” by pharmacy directors at key SCD institutions KOLs and community physicians express high intent to use

Development of Vepoloxamer in Heart Failure Objective: Restore Membrane Integrity To Improve Cardiac Performance Phase 2 Study - Enrolling

Development Rationale in Heart Failure Elevated wall tension in a dilated (e.g. failing) heart impairs normal membrane repair activity Permeabilized membranes allow unregulated calcium influx and cardiac troponin leak LD = 1.5 mg/mL vepoloxamer HD = 4.5 mg/mL vepoloxamer Cardiomyocytes Isolated from Animals with Advanced Heart Failure Exhibit Reduced Intracellular Calcium 10µM Ca2+ 1.0µM Ca2+

Heart Failure Model Results Functional improvement (single administration) Vepoloxamer elicited improvements in Left Ventricle (LV) systolic and diastolic function that persisted for up to 2 weeks Ejection fraction (EF) and stroke volume (SV) increased Biomarkers (single administration) Functional improvements supported by significant reductions of NT-pro BNP for up to 2 weeks Membrane sealing supported by significant reductions in plasma troponin for up to 2 weeks Data suggests vepoloxamer can preserve cardiomyocytes by limiting calcium entry into the cell Results support clinical development of vepoloxamer for the treatment of acute and chronic heart failure

Heart Failure Model – Functional Improvement (single administration) 2 Hours Post 24 Hours Post 1 Week Post 2 Weeks Post * p < 0.05 vs. Control * * * * * * * * * * Vepoloxamer elicited improvements in LV systolic and diastolic function that lasted for up to 2 weeks Study conducted by: Hani N. Sabbah, Henry Ford Health System

Heart Failure Model – Biomarkers (single administration) * * * * * * * * * p < 0.05 vs. Control Troponin data suggests vepoloxamer can preserve cardiomyocytes by limiting calcium entry into the cell. Functional improvements supported by significant reductions of NT-proBNP for up to 2 weeks. 2 Hours Post 24 Hours Post 1 Week Post 2 Weeks Post Study conducted by: Hani N. Sabbah, Henry Ford Health System

Heart Failure Phase 2 Study Randomized, double-blind, placebo-controlled, multi-center Phase 2 study in chronic heart failure N=150 patients, 3 dose arms, single 3-hour administration of vepoloxamer Efficacy assessments: Cardiac function Biomarkers Exercise tolerance Patient enrollment ongoing First patient dosed January 2016

Development of Vepoloxamer in Ischemic Stroke Objective: Accelerate reperfusion and reduce reperfusion injury Phase 2-Ready

Vepoloxamer in Ischemic Stroke In stroke, restoring blood flow is critical (“time is tissue”) Vepoloxamer has improved blood flow as a stand-alone agent In combination with a thrombolytic, vepoloxamer has shortened time to thrombolysis by up to 40% Seals and protects ischemia-injured tissue Neuronal tissue Blood brain barrier integrity tPA alone tPA + Vepoloxamer

Vepoloxamer Alone or with tPA Improved Outcomes in Experimental Stroke Models Two hour occlusion of MCA with silicon coated nylon suture Only 27% of control mice survived vs. 52% of mice treated with poloxamer 188* (n=51) PLOS ONE 2013 (8) 4: e61641 * Vepoloxamer is purified poloxamer 188

SBIR Grant-Funded Research SBIR grant awarded by NIH in August 2016 Phase 1 nonclinical study Evaluate the effect of a combination treatment with vepoloxamer and tissue plasminogen activator (tPA) on infarct volume and functional outcome in a nonclinical model of embolic stroke

Key Data Generated by Mast Following Acquisition of Vepoloxamer Sickle Cell Disease Heart Failure / Stroke April 2013 7th Annual SCD Research & Educational Symposium MST-188 reduced aggregation of both older and younger RBC, with a greater effect on older RBC (nonclinical) July 2013 Positive results in QT/QTc clinical study (primary endpoint met)  Jan 2014 Positive data with single dose of MST-188 in nonclinical model of chronic heart failure (statistically significant improvement in key parameters of heart function)  Feb 2014 Additional positive data in nonclinical chronic heart failure model April 2014 8th Annual SCD Research & Educational Symposium MST-188 decreased inflammation/ aggregation (nonclinical) 2014 ASH MST-188 microparticle antagonism data findings presented (nonclinical) Nov 2014 2014 American Heart Association Scientific Sessions MST-188 nonclinical heart failure study biomarker data Feb 2015 2015 International Stroke Conference MST-188 showed improvements in neurologic function and reduced tissue loss (nonclinical) March 2015 Nonclinical results reproduced earlier findings in advanced heart failure and demonstrated prolonged treatment effect April 2014 – 9th Annual SCD Research & Educational Symposium MST-188 showed improvement in fragility, hemolysis, and adhesion in SCD RBCs (nonclinical) Sept 2015 19th Annual Scientific Meeting of the Heart Failure Society of America (HFSA) MST-188 showed reduction in calcium-mediated cardiomyocyte dysfunction and death (nonclinical) Nov 2015 2014 American Heart Association Scientific Sessions MST-188 showed improvements in LV systolic function (nonclinical) 2015 ASH 3 MST-188 nonclinical studies : (1) anti-adhesive effects on RBCs and protective effects on membranes/platelets, (2) reductions in adherent sickle RBCs to immobilized VCAM and hemolysis, and (3) preserved platelet function under extended storage conditions 2013 2014 2015

Vepoloxamer Market Exclusivity Form of Protection Indication Status Orphan Drug Designation (Market Exclusivity) SCD Granted (US/EU) Patents – Composition of matter SCD, HF, IS US 9,403,941 (to 2035), also pending w/w Patents – New formulation HF Filed, pending w/w Patents – Methods of use SCD, HF, IS Filed, pending w/w Data Exclusivity SCD, HF, IS Eligible (US/EU) Trade Secret & Know-How SCD, HF, IS Varies SCD = sickle cell disease HF = heart failure IS = ischemic stroke

Development of AIR001 in Heart Failure Objective: Improve exercise tolerance and hemodynamics in HFpEF patients Multiple Phase 2 Studies

AIR001 Overview AIR001 is nitrite* for intermittent inhalation Delivered via proprietary handheld nebulizer Activity includes dilation of blood vessels and reduced inflammation Not limited to role as nitric oxide donor as nitrite has direct mitochondrial oxygen-sparing activity Hemodynamic benefits include reductions in: Pulmonary capillary wedge pressure Right atrial pressure Mean pulmonary arterial pressure Safety data available in approximately 140 subjects (well-tolerated) * Note: Nitrite is a different molecule and has separate activity compared to organonitrates or nitric oxide.

AIR001 Clinical Data Three Phase 1 studies Established Maximum Tolerated Dose (MTD) Acute improvements in hypoxia-induced pulmonary hypertension No drug-drug interaction with sildenafil Phase 2a study in PAH (n=29) Well-tolerated; no treatment-related serious adverse events Improvements seen in median pulmonary vascular resistance (PVR) and median distances in 6-minute walk test Methemoglobin levels remained normal (<1.5%) Phase 2a study in HFpEF (n=30) Met primary endpoint; statistically significant decrease in pulmonary capillary wedge pressure during exercise compared to placebo Well-tolerated; no treatment-related serious adverse events

AIR001 Clinical Development Plan Heart Failure with Preserved Ejection Fraction (HFpEF) Responsible for ~50% of heart failure hospitalizations No approved medications Supporting ongoing institutional-sponsored Phase 2a study Evaluating hemodynamic effects Reported positive interim data in May 2016 AIR001 recently selected by the Heart Failure Clinical Research Network for Phase 2 study in HFpEF n=100 Multicenter, randomized, double-blind, placebo-controlled First patient enrolled July 2016

MSTX Financial Overview Cash/investments at 6/30/2016: $35.1 million Principal debt balance: $13.7 million* $10 million prepayment on 10/14/16 if EPIC data not positive or not announced Market capitalization: ~$120 million* Average daily volume (3 mo.): ~ 3.4 million* * As of September 2, 2016

Management Team and Board of Directors Management Team Board of Directors Brian Culley, CEO Neurocrine, UC San Diego, The Scripps Research Inst. Ed Parsley, CMO Aires, Pfizer, CSL, Encysive, U. Texas Medical Brandi Roberts, CFO Alphatec, Artes, Stratagene, Pfizer, PwC Martin Emanuele, SVP Development DaVita, SynthRx, Kemia, Avanir, DuPont Greg Gorgas, SVP Commercial Theragence, Biogen Idec, Chiron, Cetus, Upjohn Co. Mark Longer, VP Regulatory AstraZeneca, Amylin, Pfizer Matthew Pauls, CEO StrongBridge Biopharma Peter Greenleaf, CEO Sucampo Pharmaceuticals Brian Culley, CEO Mast Therapeutics Howard Dittrich, EIR, CMO Frazier Healthcare Partners David Ramsay, CFO (ret.) Halozyme

Key Takeaways and Investment Highlights Mast is the leader in sickle cell disease Potential first-in-class therapy for an orphan disease with high unmet need Enrollment completed in pivotal Phase 3; top-line data expected September More than 2 years ahead of nearest competitor Extensive patient-focused activity: Created the leading SCD app, VOICE Crisis Alert (>3000 downloads) Created the (5th Annual) SCD Drug Development Conference Sponsor and volunteer at charity events, SCD radio show, etc. Vepoloxamer has potential in other serious vascular diseases, including heart failure and stroke Encouraging clinical data generated from AIR001 for heart failure Met primary endpoint in 30-patient randomized blinded trial Selected by HFN as subject of 100-patient Phase 2 study in HFpEF