Filing

 

 

 

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): March 7, 2016

 

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):

 

 

 

 

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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, including at the Cowen and Company 36^th Annual Health Care Conference on March 7, 2016.  

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 and furnishing 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 24, 2015, Quarterly Report on Form 10-Q filed on November 12, 2015, 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

The Company 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 within the meaning of the Private Securities Litigation Reform Act of 1995 that are based on the Company’s current expectations and assumptions. Such forward-looking statements may be identified by the use of forward-looking words such as “intend,” “plan,” anticipate,” “believe,” “expect,” among others, and include, but are not limited to, statements regarding the Company’s development, regulatory and commercialization strategies and plans for its investigational 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. 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 inherent uncertainty of outcomes in ongoing and future studies of the Company’s product candidates and the risk that its product candidates may not demonstrate adequate safety, efficacy or tolerability in one or more such studies, including vepoloxamer in the ongoing EPIC study; delays in the commencement or completion of clinical studies, including the Phase 2 study of vepoloxamer in heart failure, and the ongoing and planned Phase 2 studies of AIR001, 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; delays in clinical study closeouts, including blinded data review and quality assurance procedures, that may delay announcement of study results; risks associated with the fact that the Company is not the sponsor of the ongoing or currently planned Phase 2 studies of AIR001 in heart failure and has no control over the protocol for or conduct of the studies, including whether the ongoing study will be completed or the planned study be commenced on anticipated timelines, or at all; the risk that, even if the EPIC study achieves statistical significance in the primary endpoint, the FDA or another regulatory authority may determine it does not demonstrate sufficient magnitude of clinical relevance or provide adequate safety and tolerability data to provide the basis for submission of a new drug application; the potential for institutional review boards or the FDA or other regulatory agencies to require additional clinical or nonclinical studies prior to initiation of a planned clinical study; 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 dependence on third parties to assist with important aspects of development of its product candidates, including conduct of its clinical studies and supply and manufacture of clinical trial material, and, if approved, commercial product and the risk that such third parties may fail to perform as expected; the risk that the Company may be required to repay its outstanding debt obligations on an accelerated basis and/or at a time that could be harmful to its financial

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condition and/or ability to pursue its business strategy; risk associated with the Company’s ability to manage operating expenses and/or obtain additional funding to support its operations, if needed, 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 or partner its product candidates 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 and obtains regulatory approval for a product candidate, 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 and other market exclusivity protections for its products, if approved, without infringing the proprietary rights of others; 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.

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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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Corporate Overview March 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 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 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 reports on Form 10-Q filed with the SEC on August 12, 2015 and November 12, 2015. 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 Chronic Heart Failure Ischemic Stroke Vepoloxamer AIR001 Product Candidate Pipeline Enrolling Top-line results expected Q2 2016 Phase 2 ready

Vepoloxamer: A Novel Biophysical Agent Corrects imbalances in surface tension, an underlying feature of multiple diseases Biophysical mechanism of action offers lower development risk 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 Bound Healthy Cell Membrane = Vepoloxamer Inactive

Pathologies and Conditions Related to Imbalances in 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

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 90,000 – 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) 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 in vaso-occlusive crisis (VOC) is diminished blood flow 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 (mm/s) measured in nine sickle cell patients with vaso-occlusive crisis (p = .00003) Vepoloxamer improved microvascular blood flow in sickle cell disease patients during vaso-occlusive crisis (prior Phase 3 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 and applied to Mast’s Phase 3 study “EPIC”: 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 conducted Double-Blind, Placebo-Controlled, International (~75 sites) 388 patients, randomized 1:1 to standard of care +/- vepoloxamer 1hr loading dose followed by 47h 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 Duration of vaso-occlusive crisis Definition: time from randomization to last dose of parenteral opioid 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: Demographic Characteristics Age Average = 15 years Range = 4 to 46 years Patients over 18 = 29% Use of Hydroxyurea (HU) = >60% Patients enrolled from U.S. = ~60% Sites that enrolled at least one patient = >80% Why are these demographics encouraging? In a prior study, patients under the age of 16 had a benefit of 22 hours (p = 0.01) and those on HU had a benefit of 16 hours (p = 0.02).

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: Summary Patient enrollment complete Top-line data anticipated Q2 2016 U.S. patients = ~60% Average patient age = 15 Hydroxyurea use = >60% At 250 patients (blinded analysis): Average duration of crisis & coefficient of variation consistent with statistical assumptions in study design Minimal regional variability (U.S. vs ex-U.S.)

EPIC Study: Defining Success FDA approval is based on a benefit/risk assessment Endpoints from controlled clinical trials must establish “substantial evidence” of efficacy (e.g. a statistically significant effect) How is statistical significance analyzed? p-value < 0.01 = best outcome p-value = 0.01 - 0.05 = good outcome p-value > 0.05 = likely insufficient to support an NDA What supporting evidence can be provided? Secondary endpoints Pharmacodynamic endpoints (laboratory biomarkers) Data from additional studies Prior phase 2/3 trials Ongoing repeat-dose (EPIC-E) and special population studies Next step = pre-NDA meeting

Vepoloxamer in SCD: Regulatory Considerations Significant unmet need – no disease-modifying therapy for 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 has already received three doses of vepoloxamer

Vepoloxamer in SCD: Key Regulatory Activities 2017 2016 Draft EU PIP EU Health Authority Meetings EPIC Top Line Data Pre-NDA Meeting NDA Review FDA Advisory Comm Meeting EMA MAA Submission US Launch NDA Preparation U.S. E.U. Submit NDA (rolling)

Vepoloxamer Commercial Opportunity

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 (~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)

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 MDs expect quick uptake and time to peak (~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 BMT Phase 3 vepoloxamer rivipansel L-Glutamine Phase 2 Aes-103 SANGUINATE Sevuparin SelG1 GBT440 Phase 1 NiCord NKTT120 PF-04447943 SCD-101 LentiGlobin Other gene therapy Vepoloxamer has the potential to be the first and only treatment to reduce the duration 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

Significant Potential Outside the U.S. Over 12 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 Ongoing

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 Design Randomized, double-blind, placebo-controlled, multi-center Phase 2 study in chronic heart failure ongoing N=150 patients, 3 dose arms, single 3-hour administration Efficacy assessments: Cardiac function Biomarkers Exercise tolerance Study is testing a new formulation of vepoloxamer designed to be more suitable for a heart failure patient population Patent applications filed on formulation and methods of use in heart failure

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

Vepoloxamer in Ischemic Stroke In stroke, restoring blood flow is critical (“time is tissue”) Vepoloxamer improves blood flow as a stand-alone agent In combination with a thrombolytic, vepoloxamer shortens 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 Improves 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

Data Generated by MAST After 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 Filed, pending w/w Patents – New formulation HF Provisional filed 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 124 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 – interim data expected mid-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 Initiation expected Q3 2016

MSTX Financial Overview Cash/investments at 12/31/2015: ~$41 million Public offering closed 2/16/2015: Net proceeds of $7.3 million Principal debt balance: $15 million $10 million prepayment on 7/31/16 if EPIC data not positive Market capitalization: $56 million* Shares outstanding: ~ 193 million* Average daily volume (3 mo.): ~ 1.4 million* * As of March 1, 2016

Management Team and Board of Directors Management Team Board of Directors Brian Culley, CEO Immusol, UC San Diego, Neurocrine, 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 Lew Shuster, CEO Shuster Capital Howard Dittrich, EIR, CMO Frazier Healthcare Partners David Ramsay, CFO (ret.) Halozyme NEW NEW

Near-Term News and Events Q4 & FYE 2015 financial results & update Q1 2016 financial results & update Interim results from initial cohort in ongoing AIR001 Phase 2a study Top-line results from Phase 3 EPIC study Completion of enrollment in vepoloxamer Phase 1 special population PK study

Key Takeaways and Investment Highlights Mast is the leader in sickle cell disease Potential first-in-class therapy in an orphan disease with an unmet need Enrollment complete in pivotal Phase 3; data expected in Q2 2016 More than 2 years ahead of nearest competitor Extensive patient-focused activity: Created the leading SCD app, VOICE Crisis Alert (>3000 downloads) Created the (4th Annual) SCD Drug Development Conference Sponsor and volunteer to charity events, SCD radio show, etc. Vepoloxamer has potential in other serious vascular diseases, including heart failure and stroke Encouraging clinical data emerging 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 (INDIE-HFpEF)