Savara, Inc. · NASDAQ:SVRA
Savara — Mast Therapeutics — 2015 Biotech Showcase Conference
34 slides from Savara's conference presentation, Jan 12, 2015
Slide 1: 2015 Biotech Showcase Conference
NYSE MKT: MSTX 2015 Biotech Showcase Conference Brian M. Culley, CEO January 12, 2015 Exhibit 99.1
Slide 2: Forward-Looking Statements
Forward-Looking Statements NYSE MKT: MSTX 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 forwa
Slide 3: Corporate Overview
Corporate Overview NYSE MKT: MSTX Developing vepoloxamer to improve blood flow and cell membrane integrity Sickle Cell Disease (SCD) – Phase 3 enrolling (>33% complete) Acute Limb Ischemia (ALI) – Phase 2 enrolling Acute Heart Failure (ADHF) – Phase 2 initiation 2Q’15 Developing AIR001 to improve ca
Slide 4: Vepoloxamer (Purified Poloxamer)
NYSE MKT: MSTX Vepoloxamer ( Purified Poloxamer 188 )
Slide 5: Vepoloxamer Overview
Vepoloxamer Overview NYSE MKT: MSTX 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 ca
Slide 6: Vepoloxamer Mechanism of Action
Vepoloxamer Mechanism of Action NYSE MKT: MSTX Core of molecule adheres to hydrophobic domains on cell surface, such as damaged membranes and adhesive proteins. No Affinity for Healthy Cell Membranes… But Adheres to Damaged Cell Membranes
Slide 7: Vepoloxamer Pharmacodynamics
Vepoloxamer Pharmacodynamics NYSE MKT: MSTX Vepoloxamer Hemorheologic Inhibits cell adhesion, reduces aggregation; improves flow. Cytoprotective Seals membranes, restores integrity (e.g. gives cells time to heal). Simple biophysical mechanism improves flow and membrane integrity.
Slide 8: Vepoloxamer Clinical Development
Vepoloxamer Clinical Development Enrolling Planned initiation: 2Q 2015 Enrolling NYSE MKT: MSTX Preclinical Phase 1 Phase 2 Phase 3 Sickle Cell Disease (orphan) Acute Limb Ischemia (orphan) Acute Heart Failure
Slide 9: Sickle Cell Disease
NYSE MKT: MSTX Sickle Cell Disease
Slide 10: Overview of Sickle Cell Disease
Overview of Sickle Cell Disease A chronic, genetic disorder and rare (orphan) disease Hallmark of disease is a “vaso-occlusive crisis” Significant unmet need Vaso-occlusion is associated with early death Affects 90,000 to 100,000 people in the U.S. Characterized by severe deformation (i.e., “sicklin
Slide 11: Role of Vepoloxamer in Sickle Cell Disease
Role of Vepoloxamer in Sickle Cell Disease Vepoloxamer : Vaso-Occlusion : Adhesion of poorly-deformable, “sticky” cells to endothelium Entrapment of rigid, sickled cells and vessel obstruction results in ischemia and infarction Reduces aggregation and adhesion of cells to endothelium (anti-inflammat
Slide 12: Vepoloxamer Reduced Organ Pathology in Transgenic Sickle Mice
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% O ). (Asakura, et al.) Lung Pathology Vepoloxamer Control
Slide 13: Vepoloxamer Increased Survival in Transgenic Sickle Mice
Vepoloxamer Increased Survival in Transgenic Sickle Mice Transgenic mice pretreated with either vepoloxamer (400 mg/kg) or saline, subject to hypoxia (5% O ), and monitored for survival. (Asakura, et al.) Survival of Transgenic Sickle Mice Post exposure to 5% (60 - 100% ß S -Globin) Vepoloxamer Cont
Slide 14: Vepoloxamer Improves Blood Flow
Vepoloxamer Improves Blood Flow Vepoloxamer Placebo Before Infusion (Crisis Baseline) 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 2-Hours 7-Hours After Loading Infusion After Loading Infusion Source: J. Investig. Med. 2004;52(6):402-6 (p = 0.00003) Vepoloxamer improved microvascular blood flow in SCD pa
Slide 15: Phase 3 Study (Blood 1997)
Phase 2 Study Source: Blood, September 1, – Vol 90, No. 5 * Vepoloxamer is purified poloxamer 188 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 145m
Slide 16: Phase 3 Study (JAMA 2001)
Phase 3 Study Source: JAMA, November 17, 2001 – Vol 286, No. 17 Randomized, double-blind, placebo- controlled, multi-center study of vepoloxamer in 350 patients with SCD. Time-to-event analysis showed consistent trend in support of earlier crisis resolution. However, prior sponsor ended enrollment a
Slide 17: EPIC: Pivotal Phase 3 Study Design
EPIC: Pivotal Phase 3 Study Design Randomized, Double-Blind, Placebo-Controlled, Multicenter Primary Efficacy Assessment Secondary Efficacy Assessments Power Open-label extension 388 patients Standard of care +/- vepoloxamer Duration of crisis (transition off IV analgesia) No assessment of subjectiv
Slide 18: EPIC Success Factors
EPIC Success Factors Enrollment on-track. Top-line data expected Q1 2016. Most Advanced New Drug in SCD Positive Factors for Regulatory Decision-Making ~70 sites opened, >50 within the U.S. >33% enrolled as of Jan 6. Potential to be first approved drug to treat an ongoing vaso-occlusive crisis Subst
Slide 19: Acute Limb Ischemia
Acute Limb Ischemia (Vepoloxamer In Combination with Thrombolytics)
Slide 20: Overview of Occlusive Arterial Disease
Overview of Occlusive Arterial Disease A progressive circulatory problem in which obstructed arteries reduce blood flow to tissues Acute Ischemic Cerebrovascular Infarction (stroke) Acute Myocardial Infarction (heart attack) Peripheral Arterial Disease Intermittent Claudication Critical Limb Ischemi
Slide 21: Improved t-PA Effectiveness
Improved t-PA Effectiveness Animals randomized to t-PA (n = 10) or t-PA + poloxamer 188* (n = 10) Control (t-PA) Poloxamer 188* Source: Data on file * Vepoloxamer is purified poloxamer 188
Slide 22: Synergy with Thrombolytics in Heart Attack
Synergy with Thrombolytics in Heart Attack Source: Circulation 1996; 94: 298-307 *Vepoloxamer is purified poloxamer 188 Parameter Poloxamer 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 Ejecti
Slide 23: Phase 2 Study in ALI
Phase 2 Study in ALI Clinical Proof-of-Concept Study Biomarkers Clinical outcomes Study Design Randomized, double-blind, and active-controlled (t-PA) t-PA +/- low or high dose vepoloxamer 60 subjects (20 per arm) Timing Completion of enrollment anticipated 2H 2016 ALI data can be supportive of clini
Slide 24: Heart Failure
Heart Failure
Slide 25: Overview of Heart Failure
Overview of Heart Failure 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 failu
Slide 26: Heart Failure Development Rationale
Heart Failure Development Rationale In heart failure, elevated wall tension impairs lipid flow and membrane repair. This results in calcium influx and cardiac troponin leak. Vepoloxamer re-seals membranes and reduces membrane tensions, enabling lipid flow and facilitating membrane repair, thus reduc
Slide 27: Non-clinical Model of Heart Failure
Non-clinical Model of Heart Failure A single, 2h infusion improved hemodynamic parameters (LVEF, CO) and biomarkers correlated with clinical outcomes (troponin, NT-proBNP) A potentially novel mechanism, compatible with existing treatments Planning to initiate Phase 2 in acute decompensated HF in Q2
Slide 28: AIR001
AIR001 (sodium nitrite) inhalation solution
Slide 29: AIR001
AIR001 AIR001 is nitrite for intermittent inhalation (via nebulizer) AIR001 is being developed for Heart Failure with Preserved Ejection Fraction (HFpEF) Beneficial effects include dilation of blood vessels and reduced inflammation Positive hemodynamic effects; reductions observed in: Responsible fo
Slide 30: AIR001 Clinical Data
AIR001 Clinical Data Three Phase 1 studies: Established MTD and safe dose level Confirmed conversion of nitrite to nitric oxide (NO) Acute improvements in hypoxia-induced pulmonary hypertension No drug-drug interaction with sildenafil One Phase 2 study: Safety data in 124 healthy volunteers and pati
Slide 31: AIR001 Clinical Development Plan
AIR001 Clinical Development Plan Supporting three institution-sponsored Phase 2a studies to: Preliminary data anticipated 2H 2015 If positive, conduct Phase 2b proof-of-concept Evaluate acute hemodynamic effects of AIR001 Evaluate acute effects versus placebo on maximum oxygen consumption and exerci
Slide 32: Upcoming News & Events
Upcoming News & Events Initiate dosing in Phase 2a studies of AIR001 Q1 ’15 Initiate enrollment in EPIC extension study (repeat exposure) (EPIC-E) 1H ’15 Report data from nonclinical study of vepoloxamer in embolic stroke Q2 ’15 Initiate enrollment in Phase 2 study of vepoloxamer in heart failure Q2
Slide 33: MSTX Financial Overview
MSTX Financial Overview Cash/investments at 12/31/14: $57 million Market capitalization: ~$94 million* Shares outstanding: ~159 million* Average daily volume (3 mo): ~1 million* No debt * As of January 5, 2015
Slide 34: Mast Investment Summary
Mast Investment Summary A Leader in Areas of Significant Unmet Need (Vepoloxamer) AIR001 Multiple clinical readouts anticipated within 15 months Phase 2 program in heart failure with preserved ejection fraction Multiple phase 2a studies planned/ongoing Sickle cell: Phase 3 top-line Heart failure: Ph