Savara, Inc. · NASDAQ:SVRA
Savara — Mast Therapeutics — Investor Presentation (March 2016)
48 slides from Savara's investor presentation, Mar 7, 2016
Slide 1: Corporate Overview
Corporate Overview March 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 Chronic Heart Failure Ischemic Stroke Vepoloxamer AIR001 Product Candidate Pipeline Enrolling Top-line results expected Q2 2016 Phase 2 ready
Slide 4: Vepoloxamer: A Novel Biophysical Agent
Vepoloxamer: A Novel Biophysical Agent Corrects imbalances in surface tension, an underlying feature of multiple diseases Biophysical mechanism of action offers lower development risk Targets damaged tissue; little or no activity in healthy tissue Not metabolized; no active metabolites to track, no
Slide 5: Pathologies and Conditions Related to Imbalances in Surface Tension
Pathologies and Conditions Related to Imbalances in 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 coagulat
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 90,000 – 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) Exceedingly painful condition and a leading cause of h
Slide 8: Vepoloxamer in Sickle Cell Disease (SCD)
Vepoloxamer in Sickle Cell Disease (SCD) The underlying pathology in vaso-occlusive crisis (VOC) is diminished blood flow Vepoloxamer improves blood flow by addressing multiple pathological mechanisms: Adhesion Hemolysis Aggregation Viscosity Objective of treatment with vepoloxamer: Improve blood fl
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 and appl
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 conducted 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 Duration of vaso-occlusive crisis Definition: time from randomization to last dose of parenteral opioid Advantages: Aligns with FDA recommendations Sensitive and specific data collection Objective Minimal data loss Medical expert support Clinically meaningful to experts
Slide 13: EPIC Study: Demographic Characteristics
EPIC Study: Demographic Characteristics Age Average = 15 years Range = 4 to 46 years Patients over 18 = 29% Use of Hydroxyurea (HU) = >60% Patients enrolled from U.S. = ~60% Sites that enrolled at least one patient = >80% Why are these demographics encouraging? In a prior study, patients under the a
Slide 14: 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 15: EPIC Study: Summary
EPIC Study: Summary Patient enrollment complete Top-line data anticipated Q2 2016 U.S. patients = ~60% Average patient age = 15 Hydroxyurea use = >60% At 250 patients (blinded analysis): Average duration of crisis & coefficient of variation consistent with statistical assumptions in study design Min
Slide 16: EPIC Study: Defining Success
EPIC Study: Defining Success FDA approval is based on a benefit/risk assessment Endpoints from controlled clinical trials must establish “substantial evidence” of efficacy (e.g. a statistically significant effect) How is statistical significance analyzed? p-value < 0.01 = best outcome p-value = 0.01
Slide 17: Vepoloxamer in SCD: Regulatory Considerations
Vepoloxamer in SCD: Regulatory Considerations Significant unmet need – no disease-modifying therapy for ongoing crisis Support among medical / advocacy / patient communities Orphan Drug Designation Fast Track Designation SCD is part of FDA “Patient-Focused Drug Development Initiative” Healthcare dis
Slide 18: Vepoloxamer in SCD: Key Regulatory Activities
Vepoloxamer in SCD: Key Regulatory Activities 2017 2016 Draft EU PIP EU Health Authority Meetings EPIC Top Line Data Pre-NDA Meeting NDA Review FDA Advisory Comm Meeting EMA MAA Submission US Launch NDA Preparation U.S. E.U. Submit NDA (rolling)
Slide 19: Vepoloxamer Commercial Opportunity
Vepoloxamer Commercial Opportunity
Slide 20: 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 21: 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 22: 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 23: Market Research: Physicians Report a High Percent of Patients to be Treated
Market Research: Physicians Report a High Percent of Patients to be Treated with Vepoloxamer at Peak MDs expect quick uptake and time to peak (~6 months) Source: RDS Consulting Group Research Report, 2015, n=30
Slide 24: Development Landscape in SCD
Development Landscape in SCD Stage VOC Intervention VOC Reduction SCD Corrective Treatment Marketed Hydroxyurea BMT Phase 3 vepoloxamer rivipansel L-Glutamine Phase 2 Aes-103 SANGUINATE Sevuparin SelG1 GBT440 Phase 1 NiCord NKTT120 PF-04447943 SCD-101 LentiGlobin Other gene therapy Vepoloxamer has t
Slide 25: 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 26: 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 27: Significant Potential Outside the U.S.
Significant Potential Outside the U.S. Over 12 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 stan
Slide 28: 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 29: Development of Vepoloxamer in Heart Failure
Development of Vepoloxamer in Heart Failure Objective: Restore Membrane Integrity To Improve Cardiac Performance Phase 2 Study Ongoing
Slide 30: 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 31: 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 32: 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 33: 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 34: Heart Failure Phase 2 Study Design
Heart Failure Phase 2 Study Design Randomized, double-blind, placebo-controlled, multi-center Phase 2 study in chronic heart failure ongoing N=150 patients, 3 dose arms, single 3-hour administration Efficacy assessments: Cardiac function Biomarkers Exercise tolerance Study is testing a new formulati
Slide 35: Development of Vepoloxamer in Ischemic Stroke
Development of Vepoloxamer in Ischemic Stroke Objective: Accelerate reperfusion and reduce reperfusion injury Phase 2a Ready
Slide 36: Vepoloxamer in Ischemic Stroke
Vepoloxamer in Ischemic Stroke In stroke, restoring blood flow is critical (“time is tissue”) Vepoloxamer improves blood flow as a stand-alone agent In combination with a thrombolytic, vepoloxamer shortens time to thrombolysis by up to 40% Seals and protects ischemia-injured tissue Neuronal tissue B
Slide 37: Vepoloxamer Alone or with tPA Improves Outcomes in Experimental Stroke Models
Vepoloxamer Alone or with tPA Improves 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 38: Data Generated by MAST After Acquisition of Vepoloxamer
Data Generated by MAST After 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 in QT/Q
Slide 39: 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 Filed, pending w/w Patents – New formulation HF Provisional filed Patents – Methods of use SCD, HF, IS Filed, pending w/w D
Slide 40: 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 41: 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 42: 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 43: 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 – interim data expected mid-2016 AIR001 rece
Slide 44: MSTX Financial Overview
MSTX Financial Overview Cash/investments at 12/31/2015: ~$41 million Public offering closed 2/16/2015: Net proceeds of $7.3 million Principal debt balance: $15 million $10 million prepayment on 7/31/16 if EPIC data not positive Market capitalization: $56 million* Shares outstanding: ~ 193 million* A
Slide 45: Management Team and Board of Directors
Management Team and Board of Directors Management Team Board of Directors Brian Culley, CEO Immusol, UC San Diego, Neurocrine, Scripps Research Inst. Ed Parsley, CMO Aires, Pfizer, CSL, Encysive, U. Texas Medical Brandi Roberts, CFO Alphatec, Artes, Stratagene, Pfizer, PwC Martin Emanuele, SVP Devel
Slide 46: Near-Term News and Events
Near-Term News and Events Q4 & FYE 2015 financial results & update Q1 2016 financial results & update Interim results from initial cohort in ongoing AIR001 Phase 2a study Top-line results from Phase 3 EPIC study Completion of enrollment in vepoloxamer Phase 1 special population PK study
Slide 47: Key Takeaways and Investment Highlights
Key Takeaways and Investment Highlights Mast is the leader in sickle cell disease Potential first-in-class therapy in an orphan disease with an unmet need Enrollment complete in pivotal Phase 3; data expected in Q2 2016 More than 2 years ahead of nearest competitor Extensive patient-focused activity
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