Exhibit 99.1
Corporate Overview
February 24, 2014
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 quarterly report on Form 10-Q filed with the SEC on August 5, 2013.
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.
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Corporate Overview
Ø Publicly-traded biopharmaceutical company based in San Diego
Ø Developing MST-188 for diseases with high unmet need;
n Near-term focus on rare (“orphan”) diseases
Ø Sickle Cell Disease (SCD)Ø Acute Limb Ischemia (ALI)
n Longer-term growth into larger markets
Ø Heart FailureØ Stroke
Ø Recently acquired Aires Pharmaceuticals (AIR001)
n Phase 2 asset in Pulmonary Hypertension (PH)
n Complementary to MST-188
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Lead Program MST-188
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MST-188 Overview
HO – (CH2CH2O)79– (CH2CHO)30– (CH2CH2O)79– H
API Structure: |
CH3
Large polymer (8,500 Daltons) manufactured by CMC: chemical synthesis and proprietary purification process
Drug Product: Formulated as a clear, buffered solution
Administration: IV infusion
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MST-188 Mechanism of Action
Hydrophobic core adheres to hydrophobic domains in circulation (e.g., damaged cell membranes)
No Affinity for Healthy Cell Membranes…
But Adheres to Damaged Cell Membranes
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MST-188 Pharmacodynamics
Biophysical mechanism confers multiple pharmacodynamic features
Hemorheologic Anti-Inflammatory
Inhibits adhesion of Inhibits cell aggregation; inflammatory cells and improves blood flow molecules to endothelium
MST-188
Antithrombotic/ Cytoprotective Pro-Fibrinolytic
Restores membrane Reduces thrombosis; integrity; gives cells time improves vessel patency to heal
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MST-188 Clinical Development
Preclinical Phase 1 Phase 2 Phase 3 2014 Sickle Cell Disease
Enrolling
(orphan)
Acute Limb Ischemia*
Trial initiation Q1 2014
(orphan)
Acute Heart Failure Positive nonclinical data: developing clinical strategy
Stroke* Planned initiation: 2H 2014
*In combination with thrombolytics
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Sickle Cell Disease
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Overview of Sickle Cell Disease
Ø A chronic, genetic disorder and rare (orphan) disease
n Affects 90,000 to 100,000 people in the U.S.*
n Characterized by severe deformation (i.e., “sickling”) of red blood cells
Ø Hallmark of disease is a “vaso-occlusive crisis”
n Exceedingly painful conditionn Leading cause of hospitalization
Ø Significant unmet need
n No approved agents to shorten duration or severity of crisis
n Standard of care (hydration and analgesics) unchanged for >10 years
Ø Vaso-occlusion is associated with early death
n Obstructed blood flow -> hypoxia -> tissue death -> organ failure*n Average age at death; 42 years (males), 48 years (females)*
*Sources: Centers for Disease Control and Prevention, Powars, D.R., et al., Outcome of Sickle Cell Anemia A 4-Decade Observational Study of 1056 Patients, Medicine, Vol. 84, No. 6, Nov. 2005: 363-376; Panepinto, J.A., Variation in Hospitalizations and Hospital Length of Stay in Children With Vaso-Occlusive Crises in Sickle Cell Disease, Pediatric Blood Cancer, 2005; 44:182-186 10
Role of MST-188 in Sickle Cell Disease
Vaso-Occlusion:
n Adhesion of poorly-deformable, “sticky” cells to endotheliumn Physical entrapment of rigid, sickled cells and vessel obstruction
cannot traverse occlusion to deliver oxygen to tissue, g in ischemia, hypoxia and infarction
MST-188:
n Reduces adhesion of cells to endothelium (anti-inflammatory)
n Reduces RBC aggregation, improves RBC deformability, lowers viscosity, and restores flow (rheologic)
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MST-188 Improves Blood Flow
MST-188 improved microvascular blood flow in SCD patients in crisis
2.0
1.8 MST-188
1.6 Placebo
1.4 (p = 0.00003)
(mm/sec) 1.2
1.0
ci
0.8 Red cell velocity (mm/s) el measured by video
0.6 microscopy in nine sickle cell patients with
0.4 vaso-occlusive crisis.
0.2
0
Before Infusion 2-Hours 7-Hours
(Crisis Baseline) After Loading After Loading Infusion Infusion
Source: J. Investig. Med. 2004;52(6):402-6
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Phase 2 Study
Ø Randomized, double-blind, placebo-controlled, multi-center study of MST-188* in SCD patients hospitalized for crisisØ MST-188 significantly improved important efficacy parameters
Subjects Who Received Full Dose±
MST-188* Placebo p value±±
(n=18) (n=13)
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.
Source: Blood, September 1, 1997 – Vol 90, No. 5
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| 1st generation (non-purified) formulation |
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Phase 3 Study
Ø Randomized, double-blind, placebo- ts controlled, multi-center study of MST-188 in 255 patients with SCD
Ø Time-to-event analysis demonstrates consistent trend in achievement of crisis resolution FunctionØ Original statistical plan, which required
Children (<16 years)
350 patients, was reduced by almost Distribution (n=73)
30% by prior sponsor (capital constraints), lowering statistical power. p = 0.007
Ø Observation period was stopped at 168 hours (“right censoring”), diminishing observable treatment differences
Hours After Randomization
Source: JAMA, November 17, 2001 – Vol 286, No. 17
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Phase 3 Study
Ø Responders analysis (proportion of patients responding at a point in time) is not impacted by “right-censoring” (discontinuation of observation period)
Ø MST-188 significantly increased the proportion of patients achieving crisis resolution at 168 hours (end of the observation period)
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
Source: JAMA, November 17, 2001 – Vol 286, No. 17
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Evaluation of Purified 188 In Crisis (EPIC): Pivotal Phase 3 Study Design
Ø Randomized, Double-Blind, Placebo-Controlled, Multicenter
n 388 patients
n Standard of care +/- MST-188
Ø Primary Efficacy Assessment
n Duration of crisis (from randomization to last dose of parenteral opioid)
Ø Secondary Efficacy Assessments
n Re-hospitalization for crisis within 14 daysn Occurrence of acute chest syndrome
Ø Power
n 90% power to detect a 16-hour difference (p=0.05)n 85% power to detect a 24-hour difference (p=0.01)
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EPIC Success Factors
Ø Enrollment on-track at 6-months (announced Jan 2014)
n 40 U.S. sites opened in 2013n First ex-U.S. sites opened Q1 2014
Ø Most Advanced New Drug in SCD
n Potential to be first approved drug to treat an on-going vaso-occlusive crisisn Substantial head start versus other SCD drugs in development
Ø Positive Factors for Regulatory Decision-Making
n Significant unmet need – standard of care unchanged for yearsn Increased reliance on disease experts in rare diseasen Support for MST-188 among medical / advocacy communitiesn Fast Track designationn Orphan Drug designationn Healthcare disparity
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Arterial Disease
(MST-188 In Combination with Thrombolytics)
Ø Acute Limb IschemiaØ Stroke
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Overview of Arterial Disease
Ø A progressive circulatory problem in which obstructed arteries reduce blood flow to tissues
n Thrombolytic agents (tPA) are used to treat acute complicationsn Significant morbidity and mortality
Acute Ischemic Cerebrovascular Infarction
(stroke)
Acute Myocardial Infarction
(heart attack)
Peripheral Arterial Disease
n Intermittent Claudicationn Critical Limb Ischemia
Development Strategy:n Develop initially in ALIn Expand into other markets
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MST-188 Improved t-PA Effectiveness
Animals randomized to t-PA (n = 10) or t-PA + MST-188 (n = 10)
Time to Reperfusion Time to Re-Occlusion
60 70
60
50 MST-188
40 50
Control (t-PA)
40 30
Minutes Minutes 30
20 20
10 10
0 0
Source: Data on file
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MST-188 Showed Synergy with
Thrombolytics in Heart Attack
Parameter MST-188* Control Difference p Value
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
Source: Circulation 1996; 94: 298-307
• 1st generation (non-purified) formulation
• N=114
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Planned Phase 2 Study in ALI
Ø Clinical Proof-of-Concept Study
n Biomarkersn Clinical outcomes
Ø Study Design
n Dose-finding, randomized, double-blind, and active-controlledn Rutherford Class 2A / 2B and catheter-directed thrombolysisn t-PA +/- low or high dose MST-188n 60 subjects (20 per arm)
Ø Timing
n Protocol submitted to FDAn Initiation: Q1 2014n Enrollment: ~18 months
Ø Data can be supportive of clinical development in stroke
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Heart Failure
(Acute Decompensation)
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Overview of Heart Failure
Ø Chronic condition characterized by decreasing heart function
n Heart cannot pump enough blood to meet the body’s needs
n Cardiac deterioration following myocardial injury (e.g., heart attack) or increased cardiac workload (e.g., high blood pressure or valve disease)
n Primary clinical symptom is difficulty breathing (fluid in lungs – “congestive”)
Ø Significant Unmet Medical Need
n Leading cause of hospitalization of elderlyn Leading healthcare cost in U.S. and Europen High rates of re-hospitalization and mortality
Ø Substantial and Growing Market Opportunity
n > 5 million individuals with heart failure in the U.S.n $32 billion to treat heart failure in the U.S.
Ø Acute Decompensation
n Each decompensation contributes to a downward spiral of worsening heart failure and damage to vital organs, decreasing survival probability following the next event
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MST-188 Data in Heart Failure
Ø MST-188 Improved Cardiac Function in an Established Animal Model of Chronic Heart Failure
Ø Immediate and durable reductions in troponin and NT-proBNP
n Statistically significant at 2-weeks post administration
Ø Potentially Novel Mechanism of Action
n Durable effect may indicate direct improvement in cardiac functionn MST-188’s membrane-sealing activity may restore weakened cardiac cell membranes, minimizing calcium overload injury
Ø Next Steps
n Conferring with experts on clinical development strategy
Source: Data on file
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AIR001
(sodium nitrite) inhalation solution
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AIR001
Ø Intermittently delivers nebulized formulation of nitrite
n AIR001 converted to nitric oxide
n Beneficial effects include dilation of blood vessels, reduction of inflammation and undesirable cell growth
Ø Orphan drug status in U.S. and EU for treatment of Pulmonary Arterial Hypertension (PAH)
Ø Development to date has been focused primarily in PAH
n Safety data in more than 120 subjects (well-tolerated)
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Pulmonary Hypertension
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Overview of Pulmonary Hypertension
Ø High blood pressure affecting the blood vessels in the lungs
n Leads to shortness of breath, dizziness, fainting, leg swelling, etc.n May result in heart failure
Ø World Health Organization (WHO) defined classifications1
n WHO Group 1 (Pulmonary arterial hypertension or PAH)
n Idiopathic, familial, or associated with other diseases
n WHO Group 2 (PH associated with left heart disease)
n WHO Group 3 (PH associated with lung disease and/or hypoxemia)n WHO Group 4 (PH due to chronic thrombotic and/or embolic tissue)
n WHO Group 5 (PH due to unclear multifactorial mechanisms)
Ø PAH is a rare/orphan disease
n Approximately 100,000 patients in U.S. & Europen Significant market opportunity (~$3Bn sales)
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| Simonneau G, Robbins I, Beghetti M. et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2009; 54: S43-S54. |
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AIR001 for Pulmonary Hypertension
Ø A phase 2 study in PAH was discontinued just prior to acquisition (capital constraints)
• Results will supplement AIR001 safety data and provide insight into PAH opportunity
• Data expected Q2 2014
Ø Planned expansion of an ongoing Phase 2a study in PH
n Evaluate whether AIR001 can reduce wedge pressure and right atrial pressure in WHO Group 2 patientsn Data expected summer 2015
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MSTX Financial Overview
Ø Cash/investments at 12/31/13: >$44 millionØ Market capitalization: ~$85 million*Ø Shares outstanding: ~103 million*Ø Average daily volume (3 mo): ~3.5 million*Ø No debtØ Evaluating strategic partnerships
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| As of February 18, 2014 |
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Upcoming News & Events
Open First EPIC Site Outside the U.S. Q1 ’14
Initiate Phase 2 Study in Acute Limb Ischemia Q1 ’14
Outcome from U.S. Adopted Names Council Review of Unique
Q1 ’14
Designation for Purified Poloxamer 188
Submit Abstract with Heart Failure Study Biomarker Data to Major
Q2 ’14
Medical Conference
Request Orphan Designation for ALI in EU (Received in U.S.) Q2 ‘14 Initiate Nonclinical POC Study in Stroke Q2 ’14 Report Results from Phase 2 study of AIR001 in PAH Q2 ’14
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Mast Investment Summary
Ø A Leader in Areas of Significant Unmet Need
n Sickle Cell Disease: Most advanced new drug in development
(Phase 3)
n Acute Limb Ischemia: Initiating Phase 2 study in Q1 2014n Heart Failure: potential new mechanism with durable effects
Ø Recently acquired Aires Pharmaceuticals (AIR001)
n New opportunities in pulmonary hypertension & PH with left heart disease
Ø Cash and marketable securities
• Over $44 million at 12/31/13
Ø Non-Dilutive Financing Opportunities
n Strategic partnerships
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