Savara, Inc. · NASDAQ:SVRA
Savara — Mast Therapeutics — 4th Annual SCD Therapeutics Conference (September 2015)
26 slides from Savara's conference presentation, Sep 3, 2015
Slide 1: 4th Annual SCD Therapeutics Conference
NYSE MKT: MSTX 4th Annual SCD Therapeutics Conference September 3, 2015 Exhibit 99.1
Slide 2: Forward-Looking Statements
Forward-Looking Statements 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
Slide 3: Product Pipeline
Preclinical Phase 1 2a 2b Phase 3 Heart Failure (“HFpEF”) Product Pipeline Preclinical Phase 1 Phase 2 Phase 3 Sickle Cell Disease (orphan) Chronic Heart Failure Ischemic Stroke Initiation planned for Sep 2015 Planned for 2016 >75% Enrolled Vepoloxamer AIR001 Data expected fall 2015 Data expected 20
Slide 4: Vepoloxamer: A Biophysical Agent
Poiseuille’s Law describes Newtonian flow with = flow (volume/time) = length of the capillary = viscosity of the media = pressure drop over the length = radius of the capillary Vepoloxamer: A Biophysical Agent Want lower viscosity? Reduce friction by lowering adhesion and improving the deformability
Slide 5: Vepoloxamer: A Biophysical Agent
Poiseuille’s Law describes Newtonian flow with = flow (volume/time) = length of the capillary = viscosity of the media = pressure drop over the length = radius of the capillary Vepoloxamer: A Biophysical Agent Want lower viscosity? Reduce friction by lowering adhesion and improving the deformability
Slide 6: Vepoloxamer Overview
API Structure: CMC: Large, synthesized polymer with extraction process to remove undesirable (toxic) components Composition of matter claims pending Administration: IV infusion ADME: Rapidly and predominantly cleared by kidneys (4-8h) Ether linkages cannot be cleaved; no drug metabolites Vepoloxamer
Slide 7: Vepoloxamer Mechanism of Action
No Affinity for Healthy Cell Membranes… But Adheres to Damaged Cell Membranes Core of molecule adheres to hydrophobic domains on a cell surface, such as damaged membranes and adhesive proteins. Vepoloxamer Mechanism of Action
Slide 8: Vepoloxamer Pharmacodynamics
Vepoloxamer Pharmacodynamics Vepoloxamer adheres to hydrophobic domains on cells and lowers surface tensions Viscosity is reduced Lowers adhesion Improves flow Membranes are sealed Cell integrity maintained Ca2+ influx reduced Sickle Cell Disease: Less occlusion, reduced hemolysis Heart Failure: Mem
Slide 9: SCD Pathophysiology (multiple points of intervention)
SCD Pathophysiology (multiple points of intervention) sRBC Adherence to Endothelium VASO-OCCLUSION ORGAN DAMAGE/FAILURE ANEMIA PAIN INTRAVASCULAR Hemolysis NITRIC OXIDE DEPLETION VASOCONSTRICTION INFLAMMATION ACTIVATION OF COAGULATION TISSUE ISCHEMIA LOCAL HYPOXIA STRESS LARGE VESSEL DAMAGE Microvas
Slide 10: Vepoloxamer Effect on Sickle Cells
Vepoloxamer Effect on Sickle Cells Before vepoloxamer Lower surface tension improves flow and deformability (video) After vepoloxamer
Slide 11: Role of Vepoloxamer in Sickle Cell Disease
Role of Vepoloxamer in Sickle Cell Disease Vaso-Occlusive Crisis: Adhesion of poorly-deformable, “sticky” cells to endothelium and to each other leads to vessel obstruction Occluded RBC’s cannot deliver oxygen, leading to ischemia, pain, organ damage Vepoloxamer: Lowers viscosity, reduces adhesion o
Slide 12: Vepoloxamer Lowers Pathologic Blood Viscosity Under Low Shear Rates
Vepoloxamer Lowers Pathologic Blood Viscosity Under Low Shear Rates *Vepoloxamer is purified poloxamer 188 Shear Rate (1/sec) 2.5 5 10 20 40 80
Slide 13: Vepoloxamer Reduces RBC Aggregation
Vepoloxamer Reduces RBC Aggregation (sickle cell patients) RBCs represent 99.9% of the volume of blood cells Poloxamer 188* (mg/mL) Aggregate extent Aggregate strength *Vepoloxamer is purified poloxamer 188 The effect of poloxamer 188 on sickle cell RBC aggregation determined by a Myrenne aggregomet
Slide 14: Vepoloxamer Reduced Organ Pathology in Transgenic Sickle Mice
Lung pathology was compared in transgenic mice pretreated with either vepoloxamer (400 mg/kg) or saline and subject to hypoxia (5% O2). (Asakura, et al.) Vepoloxamer Reduced Organ Pathology in Transgenic Sickle Mice Vepoloxamer Control
Slide 15: Vepoloxamer Increased Survival in Transgenic Sickle Mice
Transgenic mice pretreated with either vepoloxamer (400 mg/kg) or saline, subject to hypoxia (5% O2), and monitored for survival. (Asakura, et al.) Vepoloxamer Increased Survival in Transgenic Sickle Mice Vepoloxamer Control
Slide 16: Vepoloxamer Improves Blood Flow
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 Source: J. Investig. Med. 2004;52(6):402-6 (p = 0.00003) Vepoloxamer improved microvascular blood flow in SCD patients during vaso-occlusive c
Slide 17: Phase 2 Study in SCD Vaso-Occlusive Crisis
Phase 2 Study Source: Blood, September 1, 1997 – Vol 90, No. 5 Subjects Who Received Full Dose± Poloxamer 188* (n=18) Placebo (n=13) p value±± 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
Slide 18: Acute Chest Syndrome Clinical Study
Acute Chest Syndrome Clinical Study Vepoloxamerⱡ Hi Dose (100-120mg/kg/hr) (n=7) Vepoloxamerⱡ Lo Dose (40-80mg/kg/hr) (n=20) NEJM 2000* Standard of care (n=409) Vepoloxamerⱡ Hi Dose (100-120 mg/kg/hr) (n=4) Vepoloxamerⱡ Lo Dose (40-80 mg/kg/hr) (n=10) NEJM 2000* Standard of care (n=128) Children (≤1
Slide 19: Prior Sponsor's Phase 3 Study
Flawed endpoint selection and premature termination led to loss of power Proportional analysis positive: All ages: 52% vs. 37% (n=249, p=0.02) Under 16y*: 60% vs. 28% (n=73, p=0.009) Lessons learned for Mast’s Phase 3 study: Vepoloxamer has activity in SCD Incorporate FDA, physician, and patient inp
Slide 20: Current Phase 3 Study EPIC
Largest Interventional SCD Trial Ever Conducted 388 patients, randomized 1:1 (standard of care +/- vepoloxamer) Double-blind, placebo-controlled, international (2/3rd U.S. sites) Primary Endpoint: Duration of crisis Assessed from randomization to last dose of parenteral opioid Clinically relevant (n
Slide 21: EPIC Success Factors
Enrollment on-track Enrollment >75% complete Top-line data anticipated Q1 2016 Most Advanced New Drug in SCD Potential to be 1st drug ever approved to treat on-going vaso-occlusive crisis Substantial head start versus other drugs in development Considerations for Regulatory Decision-Making Significa
Slide 22: SCD Market Opportunity
SCD Market Opportunity United States Approximately 100,000 hospitalizations annually ~50% of events occur in just 16 metropolitan areas Effective coverage with small, targeted field force Europe Approximately 40,000 patients ~50% of patients reside in 2 cities: Paris and London
Slide 23: Vepoloxamer Market Opportunity
Addressable market for vepoloxamer is substantially larger than for current gene corrective approaches (e.g. not limited to just “severe” patients) Vepoloxamer Market Opportunity Approximately 100,000 Hospitalizations Annually for Crisis (U.S.) * Estimated research analyst consensus (range 5-25%)
Slide 24: Vepoloxamer Positioned for Success in SCD
Vepoloxamer Positioned for Success in SCD Novel Therapy for Rare Disease with High Unmet Need Unique mechanism Orphan Drug Designation (U.S. and EU) New composition of matter patent application pending No approved therapies available for crisis intervention First-To-Market Advantage Clinical develop
Slide 25: Mast Therapeutics Summary
An Emerging Cardiovascular Company Sickle Cell Disease Most clinically-advanced new drug in development Heart Failure Two distinct programs with novel mechanisms Stroke Encouraging nonclinical data, phase 2 planned for 2016 Mast Therapeutics is committed to: Bringing the first new SCD therapy to mar
Slide 26: MSTX Financial Overview
Cash/investments at 6/30/15: $43.4 million Market capitalization: ~$72 million* Shares outstanding: 164 million* Average daily volume (3 mo): ~700,000* * As of August 26, 2015 MSTX Financial Overview
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