Savara, Inc. · NASDAQ:SVRA
Savara — Mast Therapeutics — Investor Presentation (September 2016)
45 slides from Savara's investor presentation, Sep 7, 2016
Slide 1: Corporate Overview
Corporate Overview September 7, 2016 Exhibit 99.1
Slide 2: Safe Harbor Statement
Safe Harbor Statement 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 state
Slide 3: Product Candidate Pipeline
Preclinical Phase 1 Phase 2 Phase 3 Heart Failure (HFpEF) Preclinical Phase 1 Phase 2 Phase 3 Sickle Cell Disease Heart Failure (HFrEF) Ischemic Stroke Vepoloxamer* AIR001* Product Candidate Pipeline Enrolling Top-line results expected Sep. 2016 Phase 2-ready Enrolling *Investigational new drug
Slide 4: Vepoloxamer: A Novel Biophysical Agent
Vepoloxamer: A Novel Biophysical Agent Mechanism hypothesis: Vepoloxamer adheres to damaged cell membranes, correcting defects in membrane surface tension, an underlying feature of multiple diseases Potential benefits of “biophysical” mechanism of action: Targets damaged tissue; little or no activit
Slide 5: Pathologies and Conditions Related to Defects in Membrane Surface Tension
Pathologies and Conditions Related to Defects in Membrane Surface Tension Sickle Cell Disease Chronic & Acute Heart Failure Ischemic Stroke Surface Tension Pathologies Elevated blood viscosity Cellular aggregation Cellular adhesion Loss of membrane barrier function / repair capacity Dysfunctional co
Slide 6: Vepoloxamer in Sickle Cell Disease
Vepoloxamer in Sickle Cell Disease Objective: Improve blood flow to prevent ischemic injury and shorten duration of crisis Phase 3 Study – Enrollment Complete
Slide 7: Overview of Sickle Cell Disease
Overview of Sickle Cell Disease A chronic genetic disorder and rare (orphan) disease Affects ~100,000 people in the U.S. and is characterized by severe deformation of red blood cells Hallmark of disease is a “vaso-occlusive crisis” (VOC) Reduces blood flow and causes ischemic injury to tissues and o
Slide 8: Vepoloxamer in Sickle Cell Disease (SCD)
Vepoloxamer in Sickle Cell Disease (SCD) The underlying pathology of vaso-occlusive crisis is reduced blood flow Studies suggest vepoloxamer improves blood flow by addressing multiple pathological mechanisms: Adhesion Hemolysis Aggregation Viscosity Objective of treatment with vepoloxamer: Improve b
Slide 9: Vepoloxamer Improved Blood Flow in Sickle Cell Patients
Vepoloxamer Improved Blood Flow in Sickle Cell Patients Source: J. Investig. Med. 2004;52(6):402-6 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 Double-blind assessment of red cell velocit
Slide 10: Vepoloxamer Development History
Vepoloxamer Development History Over 100 nonclinical studies completed Phase 2 SCD – statistically significant shorter crisis and less opioid use Phase 2 ACS* – ~50% shorter hospitalization stay vs. historical control Phase 3 SCD – shorter duration of crisis (p-value = 0.07) Lessons learned from pri
Slide 11: The Phase 3 EPIC Study
The Phase 3 “EPIC” Study Evaluation of Purified Poloxamer 188 In Vaso-Occlusive Crisis Largest placebo-controlled study in sickle cell disease ever concluded Double-Blind, Placebo-Controlled, International (~75 sites) 388 patients, randomized 1:1 to standard of care +/- vepoloxamer 1hr loading dose
Slide 12: EPIC Study: Primary Endpoint
EPIC Study: Primary Endpoint Assessment: Duration of vaso-occlusive crisis Definition: Time from randomization to last dose of parenteral opioid (LPO) Advantages: Aligns with FDA recommendations Sensitive and specific data collection Objective Minimal data loss Medical expert support Clinically mean
Slide 13: EPIC Study: Safety
EPIC Study: Safety DSMB Evaluations Independent, unblinded DSMB (4 clinicians and 1 statistician) Meetings at 25, 58, 145 and 250 patients DSMB meeting held at 250 patients No unexpected safety signals identified DSMB members deemed no additional meetings were necessary
Slide 14: EPIC Study: Key Characteristics
EPIC Study: Key Characteristics U.S. patients = ~60% Average patient age = 15 years (range 4-46, ~30% adults) Hydroxyurea use = >60% Blinded analysis at 250 patients: Average duration of crisis (pooled) & coefficient of variation consistent with statistical assumptions in study design (79h and ~50%)
Slide 15: Vepoloxamer in SCD: Regulatory Considerations
Vepoloxamer in SCD: Regulatory Considerations Significant unmet need – no disease-modifying therapies for an ongoing crisis Support among medical / advocacy / patient communities Orphan Drug Designation Fast Track Designation SCD is part of FDA “Patient-Focused Drug Development Initiative” Healthcar
Slide 16: Vepoloxamer: Commercial Opportunity in Sickle Cell Disease
Vepoloxamer: Commercial Opportunity in Sickle Cell Disease
Slide 17: SCD: A Lifetime of Complications
SCD: A Lifetime of Complications Source: Martin H. Steinberg, M.D., Management of Sickle Cell Disease, New Eng J Med; 1999; Vol 340, No 13 Infant Adolescent Transition Childhood Young Adult Mature Adult Adult Senior Diagnosis (at birth) Daily penicillin prophylaxis (through age 5) Transfusions may b
Slide 18: Vaso-Occlusive Crisis is the Hallmark of SCD
Vaso-Occlusive Crisis is the Hallmark of SCD 80-100k hospitalizations annually in the U.S. Current treatment is palliative Consisting of hydration and IV opioids Does not treat underlying pathophysiology of the disease No VOC interventional therapy available Hospitalized on average for approximately
Slide 19: Market Research: Expected Features and Potential Benefits Align with Unmet Needs
Market Research: Expected Features and Potential Benefits Align with Unmet Needs for VOC Treatment Source: RDS Consulting Group Research Report, 2015
Slide 20: Market Research: Physicians Report a High Percent of Patients Treated
Market Research: Physicians Report a High Percent of Patients to be Treated with Vepoloxamer at Peak Survey-reported time to peak adoption: approx. 6 months) Source: RDS Consulting Group Research Report, 2015, n=30
Slide 21: Development Landscape in SCD
Development Landscape in SCD Stage VOC Intervention VOC Reduction SCD Corrective Treatment Marketed hydroxyurea Bone Marrow Transplant Phase 3 vepoloxamer rivipansel L-glutamine Phase 2 SC-411 Sanguinate Sevuparin SelG1 GBT440 Phase 1 CXA-10 NiCord/CordLn NKTT120 PF-04447943 SCD-101 Gene therapy Vep
Slide 22: Concentration of SCD Treatment in the U.S.
Concentration of SCD Treatment in the U.S. Offers an Attractive Commercial Opportunity Source: Analysis of HCUP NIS 2013 data; Dx 282.62 is 89.7% of all VOCs. Top 500 U.S. hospitals treat nearly 80% of SCD patients in crisis Effective field promotion with small hospital sales force (~30)
Slide 23: U.S. Sickle Cell Disease Hospital Payer Mix
U.S. Sickle Cell Disease Hospital Payer Mix Inpatient prospective payment system (IPPS) Patients with public insurance have minimal share of costs Medicaid plans may seek additional funding via CHIP, per diem rates, or modified FFS rates Vepoloxamer expected to meet criteria for additional Medicare
Slide 24: Commercial Potential Outside the U.S.
Commercial Potential Outside the U.S. Over 10 million patients worldwide Europe Approximately 40,000 patients >50% reside in two countries: UK and France Most patients concentrated in large metro areas: Paris and London MENA Over 850,000 with SCD Many treatment centers provide care on par with stand
Slide 25: Vepoloxamer Positioned for Success in SCD
Vepoloxamer Positioned for Success in SCD Novel therapy for a genetic disease with high unmet needs Unique and relevant mechanism of action No approved disease-modifying therapies available for VOC intervention Significant first-to-market advantage in multiple territories Clinical development >2 yea
Slide 26: Development of Vepoloxamer in Heart Failure
Development of Vepoloxamer in Heart Failure Objective: Restore Membrane Integrity To Improve Cardiac Performance Phase 2 Study - Enrolling
Slide 27: Development Rationale in Heart Failure
Development Rationale in Heart Failure Elevated wall tension in a dilated (e.g. failing) heart impairs normal membrane repair activity Permeabilized membranes allow unregulated calcium influx and cardiac troponin leak LD = 1.5 mg/mL vepoloxamer HD = 4.5 mg/mL vepoloxamer Cardiomyocytes Isolated from
Slide 28: Heart Failure Model Results
Heart Failure Model Results Functional improvement (single administration) Vepoloxamer elicited improvements in Left Ventricle (LV) systolic and diastolic function that persisted for up to 2 weeks Ejection fraction (EF) and stroke volume (SV) increased Biomarkers (single administration) Functional i
Slide 29: Heart Failure Model – Functional Improvement
Heart Failure Model – Functional Improvement (single administration) 2 Hours Post 24 Hours Post 1 Week Post 2 Weeks Post * p < 0.05 vs. Control * * * * * * * * * * Vepoloxamer elicited improvements in LV systolic and diastolic function that lasted for up to 2 weeks Study conducted by: Hani N. Sabbah
Slide 30: Heart Failure Model – Biomarkers
Heart Failure Model – Biomarkers (single administration) * * * * * * * * * p < 0.05 vs. Control Troponin data suggests vepoloxamer can preserve cardiomyocytes by limiting calcium entry into the cell. Functional improvements supported by significant reductions of NT-proBNP for up to 2 weeks. 2 Hours
Slide 31: Heart Failure Phase 2 Study
Heart Failure Phase 2 Study Randomized, double-blind, placebo-controlled, multi-center Phase 2 study in chronic heart failure N=150 patients, 3 dose arms, single 3-hour administration of vepoloxamer Efficacy assessments: Cardiac function Biomarkers Exercise tolerance Patient enrollment ongoing First
Slide 32: Development of Vepoloxamer in Ischemic Stroke
Development of Vepoloxamer in Ischemic Stroke Objective: Accelerate reperfusion and reduce reperfusion injury Phase 2-Ready
Slide 33: Vepoloxamer in Ischemic Stroke
Vepoloxamer in Ischemic Stroke In stroke, restoring blood flow is critical (“time is tissue”) Vepoloxamer has improved blood flow as a stand-alone agent In combination with a thrombolytic, vepoloxamer has shortened time to thrombolysis by up to 40% Seals and protects ischemia-injured tissue Neuronal
Slide 34: Vepoloxamer Alone or with tPA Improved Outcomes in Experimental Stroke Models
Vepoloxamer Alone or with tPA Improved Outcomes in Experimental Stroke Models Two hour occlusion of MCA with silicon coated nylon suture Only 27% of control mice survived vs. 52% of mice treated with poloxamer 188* (n=51) PLOS ONE 2013 (8) 4: e61641 * Vepoloxamer is purified poloxamer 188
Slide 35: SBIR Grant-Funded Research
SBIR Grant-Funded Research SBIR grant awarded by NIH in August 2016 Phase 1 nonclinical study Evaluate the effect of a combination treatment with vepoloxamer and tissue plasminogen activator (tPA) on infarct volume and functional outcome in a nonclinical model of embolic stroke
Slide 36: Key Data Generated by Mast Following Acquisition of Vepoloxamer
Key Data Generated by Mast Following Acquisition of Vepoloxamer Sickle Cell Disease Heart Failure / Stroke April 2013 7th Annual SCD Research & Educational Symposium MST-188 reduced aggregation of both older and younger RBC, with a greater effect on older RBC (nonclinical) July 2013 Positive results
Slide 37: Vepoloxamer Market Exclusivity
Vepoloxamer Market Exclusivity Form of Protection Indication Status Orphan Drug Designation (Market Exclusivity) SCD Granted (US/EU) Patents – Composition of matter SCD, HF, IS US 9,403,941 (to 2035), also pending w/w Patents – New formulation HF Filed, pending w/w Patents – Methods of use SCD, HF,
Slide 38: Development of AIR001 in Heart Failure
Development of AIR001 in Heart Failure Objective: Improve exercise tolerance and hemodynamics in HFpEF patients Multiple Phase 2 Studies
Slide 39: AIR001 Overview
AIR001 Overview AIR001 is nitrite* for intermittent inhalation Delivered via proprietary handheld nebulizer Activity includes dilation of blood vessels and reduced inflammation Not limited to role as nitric oxide donor as nitrite has direct mitochondrial oxygen-sparing activity Hemodynamic benefits
Slide 40: AIR001 Clinical Data
AIR001 Clinical Data Three Phase 1 studies Established Maximum Tolerated Dose (MTD) Acute improvements in hypoxia-induced pulmonary hypertension No drug-drug interaction with sildenafil Phase 2a study in PAH (n=29) Well-tolerated; no treatment-related serious adverse events Improvements seen in medi
Slide 41: AIR001 Clinical Development Plan
AIR001 Clinical Development Plan Heart Failure with Preserved Ejection Fraction (HFpEF) Responsible for ~50% of heart failure hospitalizations No approved medications Supporting ongoing institutional-sponsored Phase 2a study Evaluating hemodynamic effects Reported positive interim data in May 2016 A
Slide 42: MSTX Financial Overview
MSTX Financial Overview Cash/investments at 6/30/2016: $35.1 million Principal debt balance: $13.7 million* $10 million prepayment on 10/14/16 if EPIC data not positive or not announced Market capitalization: ~$120 million* Average daily volume (3 mo.): ~ 3.4 million* * As of September 2, 2016
Slide 43: Management Team and Board of Directors
Management Team and Board of Directors Management Team Board of Directors Brian Culley, CEO Neurocrine, UC San Diego, The Scripps Research Inst. Ed Parsley, CMO Aires, Pfizer, CSL, Encysive, U. Texas Medical Brandi Roberts, CFO Alphatec, Artes, Stratagene, Pfizer, PwC Martin Emanuele, SVP Developmen
Slide 44: Key Takeaways and Investment Highlights
Key Takeaways and Investment Highlights Mast is the leader in sickle cell disease Potential first-in-class therapy for an orphan disease with high unmet need Enrollment completed in pivotal Phase 3; top-line data expected September More than 2 years ahead of nearest competitor Extensive patient-focu
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