Savara, Inc. · NASDAQ:SVRA
Savara — Mast Therapeutics — Investor Presentation (June 2014)
32 slides from Savara's investor presentation, Jun 5, 2014
Slide 1: Corporate Overview
NYSE MKT: MSTX Corporate Overview Brian M. Culley, CEO June 5, 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 with high unmet need Near-term focus on rare ("orphan") diseases Sickle Cell Disease (SCD) Acute Limb Ischemia (ALI) Longer-term growth into larger markets Heart Failure Stroke Recently acquired Aires Pharma
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 Drug Product: Formulated as a clear, buffered solution 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* Trial initiated Q1 2014 Positive nonclinical data: developing clinical strategy Planned initiation: 2H 2014 *In combinati
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 un
Slide 11: The Complex Pathophysiology of Sickle Cell Disease Requires Multiple Sites of Intervention
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
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 (proportion of patients responding at a point in time) is not impacted by "right-censoring" (
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 (from randomization to last dose of parenteral opioid) Secondary Efficacy Assessments Re-hospitalization for crisis within 14 days Occurrence of acute ch
Slide 18: EPIC Success Factors
Enrollment on-track at 6 months (announced Jan 2014) 40 U.S. sites opened in 2013 First ex-U.S. sites opened Q1 2014 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 SCD drugs in development Positive Fact
Slide 19: Mechanistic Approaches to Treating SCD
Pathophysiological Activity MST-188 Selectin inhibitors Platelet inhibitors Anti-sickling agents Heparin(s) Vaso-occlusion / cell adherence X X X X Intravascular hemolysis X X Nitric oxide depletion X X Inflammation X X X Blood flow (independent of adhesion) X Dysfunctional coagulation X X X Platele
Slide 20: Arterial Disease (MST-188 In Combination with Thrombolytics)
20 Arterial Disease (MST-188 In Combination with Thrombolytics) Acute Limb Ischemia Stroke
Slide 21: 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 21 Acute Ischemic Cerebrovascular Infarction (stroke) Acute Myocardial Infarction (heart attack) Peripheral
Slide 22: 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 Oy ust-28 [BB controt (t-PA) ‘Source: ata onto 2 NYSE MKT: MSTX
Slide 23: MST-188 Showed Synergy with Thrombolytics in Heart Attack
23 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 24: Phase 2 Study in ALI
24 Clinical Proof-of-Concept Study Biomarkers Clinical outcomes Study Design Dose-finding, 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
Slide 25: Heart Failure (Acute Decompensation)
25 Heart Failure (Acute Decompensation)
Slide 26: Overview of Heart Failure
Overview of Heart Failure 26 Chronic condition characterized by decreasing heart function Heart cannot pump enough blood to meet the body's needs Primary clinical symptom is difficulty breathing (fluid in lungs - "congestive") Significant Unmet Medical Need Leading healthcare cost in U.S. and Europe
Slide 27: Proof-of-Concept in Heart Failure
Proof-of-Concept in Heart Failure (nonclinical model of chronic heart failure) 27 Single 2h infusion resulted in statistically significant improvements in hemodynamic parameters (LVEF, CO) and biomarkers (troponin, NT-proBNP) Troponin associated with 180-day all-cause mortality Elevated NT-proBNP as
Slide 28: AIR001 (sodium nitrite) inhalation solution
28 AIR001 (sodium nitrite) inhalation solution
Slide 29: AIR001
Nitrite for intermittent inhalation via nebulizer Beneficial effects include dilation of blood vessels and reduction of inflammation and undesirable cell growth Positive hemodynamic effects Observed reductions in: pulmonary vascular resistance pulmonary capillary wedge pressure right atrial pressure
Slide 30: 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 potential in World Health Organization (WHO) Group 2 Patients (PH associated with left heart disease) Planned expansion of a
Slide 31: MSTX Financial Overview
Cash/investments at 3/31/14: $49.6 million Market capitalization: ~$73 million* Shares outstanding: ~116 million* Average daily volume (3 mo): ~2.1 million* No debt Evaluating strategic partnerships 31 * As of May 27, 2014 MSTX Financial Overview
Slide 32: Mast Investment Summary
A Leader in Areas of Significant Unmet Need Sickle Cell Disease: Most advanced new drug in development (Phase 3) Acute Limb Ischemia: Initiated Phase 2 study in Q1 2014 Heart Failure: potential new mechanism with durable effects Recently acquired Aires Pharmaceuticals (AIR001) New opportunities in p
Mast Therapeutics — Investor Presentation (June 2014) on 6ix