Savara, Inc. · NASDAQ:SVRA
Savara — Mast Therapeutics — Canaccord Genuity 34th Annual Growth Conference (August 2014)
32 slides from Savara's conference presentation, Aug 14, 2014
Slide 1: Canaccord Genuity 34th Annual Growth Conference
NYSE MKT: MSTX Canaccord Genuity 34th Annual Growth Conference Brian M. Culley, CEO August 14, 2014
Slide 2: Forward-Looking Statements
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 st
Slide 3: Corporate Overview
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 Fa
Slide 4: Lead Program
Lead Program MST-188 MAST : weer MTX as
Slide 5: MST-188 Overview
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
Slide 6: MST-188 Mechanism of Action
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
Slide 7: MST-188 Pharmacodynamics
7 Biophysical mechanism confers multiple pharmacodynamic features MST-188 Pharmacodynamics
Slide 8: MST-188 Clinical Development
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
Slide 9: Sickle Cell Disease
Sickle Cell Disease 9 NYSEMKT: MSTX
Slide 10: Overview of 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 unm
Slide 11: Complex Pathophysiology 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 HYPOXI
Slide 12: Role of MST-188 in Sickle Cell Disease
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 v
Slide 13: MST-188 Improves Blood Flow
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
Slide 14: Phase 2 Study Results
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 Du
Slide 15: Phase 3 Study
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,
Slide 16: Phase 3 Study Responders Analysis
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 signific
Slide 17: EPIC: Pivotal Phase 3 Study Design
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 differ
Slide 18: EPIC Success Factors
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
Slide 19: Arterial Disease
19 Arterial Disease (MST-188 In Combination with Thrombolytics) Acute Limb Ischemia Stroke
Slide 20: Overview of Arterial Disease
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
Slide 21: MST-188 Improved t-PA Effectiveness
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 BB vst-s8 [BB controt (t-PA) Souce: ois on te a NYSE MKT: MSTX
Slide 22: MST-188 Showed Synergy with Thrombolytics in Heart Attack
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 Syne
Slide 23: Phase 2 Study in ALI
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 an
Slide 24: Heart Failure (Acute Decompensation)
24 Heart Failure (Acute Decompensation)
Slide 25: Overview of Heart Failure
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 fa
Slide 26: Proof-of-Concept in Heart Failure
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 prognos
Slide 27: AIR001 (sodium nitrite) inhalation solution
27 AIR001 (sodium nitrite) inhalation solution
Slide 28: AIR001
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
Slide 29: AIR001 for Pulmonary Hypertension
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
Slide 30: Upcoming News & Events
Upcoming News & Events ReportResults from Phase 2 study of AIR001 in PAH 314 Reach Agreement with FDA on Phase 2 study of MST-188 in Heart Failure 41d Report Data from Nonclinical Study of MST-188 in Heart Failure 14s ReportData from Non! I Study of MST-188 in Embolic Stroke 215 Initiate Enrollmenti
Slide 31: MSTX Financial Overview
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
Slide 32: Mast Investment Summary
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 opportunit
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