Savara, Inc. · NASDAQ:SVRA
Savara — Mast Therapeutics — Investor Presentation (January 2016)
44 slides from Savara's investor presentation, Jan 11, 2016
Slide 1: Corporate Overview
Corporate Overview January 11, 2016 Brian M. Culley, Chief Executive Officer 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 Candidate Pipeline
Preclinical Phase 1 2a 2b Phase 3 Heart Failure (HFpEF) (Two studies) Preclinical Phase 1 Phase 2 Phase 3 Sickle Cell Disease Chronic Heart Failure Ischemic Stroke Vepoloxamer AIR001 Product Candidate Pipeline
Slide 4: Vepoloxamer: A Novel Proprietary Biophysical Agent
Vepoloxamer: A Novel Proprietary 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 t
Slide 5: Pathologies and Conditions Related to Imbalances in Surface Tension
Pathologies and Conditions Related to Imbalances in Surface Tension Sickle Cell Disease Heart Failure Ischemic Stroke Other Diseases Surface Tension Pathologies Elevated blood viscosity Cellular aggregation Cellular adhesion Loss of membrane barrier function / repair capacity Dysfunctional coagulati
Slide 6: Development of Vepoloxamer in Sickle Cell Disease
Development of Vepoloxamer in Sickle Cell Disease Objective: Improve blood flow to prevent ischemic injury and shorten the duration of crisis Phase 3 (“EPIC”) Study Ongoing
Slide 7: 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 8: 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 9: 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* - approx. 50% shorter hospitalization stay vs. historical control Phase 3 SCD – shorter duration of crisis (p-value = 0.07) Lessons learned f
Slide 10: The EPIC Study
The EPIC Study Evaluation of Purified Poloxamer 188 In Vaso-Occlusive Crisis Double-Blind, Placebo-Controlled, Multicenter 388 patients, randomized to standard of care +/- vepoloxamer Primary Endpoint Duration of crisis from time of randomization to last dose of parenteral opioid Secondary Endpoints
Slide 11: 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
Slide 12: EPIC Study: Demographic Characteristics
EPIC Study: Demographic Characteristics (As of December 31, 2015) Age Average = 15 years Range = 4 to 46 years Patients over 18 = 29% Use of Hydroxyurea (HU) = 62% U.S. patients > 50% More than 80% of all sites have enrolled at least one patient Why are these demographics encouraging? In the prior s
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: Summary
EPIC Study: Summary >90% enrolled; enrollment completion anticipated Feb 2016 Top-line data anticipated Q2 2016 Safety assumptions as predicted Age consistent with expectations Hydroxyurea use higher than expected At 250 patients, study performance consistent with statistical assumptions in study de
Slide 15: Vepoloxamer in SCD: Regulatory Considerations
Vepoloxamer in SCD: Regulatory Considerations Significant unmet need –no disease-modifying therapy for ongoing VOC Support among medical / advocacy / patient communities Orphan Drug Designation Fast Track Designation SCD is part of FDA “Patient-Focused Drug Development Initiative” Healthcare dispari
Slide 16: 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 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
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 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 21: 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 Phase 1 GBT440 NiCord NKTT120 PF-04447943 SCD-101 LentiGlobin Vepoloxamer has the potential to be
Slide 22: Concentration of SCD Treatment in the U.S.
Concentration of SCD Treatment in the U.S. Offers an Attractive Commercial Opportunity ~50% of SCD patients in the U.S. are treated in the top 16 metropolitan areas Top four metropolitan areas account for 24% of the market <200 hospitals in the U.S. serve the majority of SCD patients Target audience
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: Significant Potential Outside the U.S.
Significant Potential Outside the U.S. Over 12 million patients worldwide Europe Approximately 40,000 patients 54% 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 Ongoing
Slide 27: Development Rationale in Heart Failure
Development Rationale in Heart Failure Elevated wall tension in dilated (failing) heart impairs normal membrane repair process Permeabilized membranes allow unregulated calcium influx and cardiac troponin leak Vepoloxamer reduces surface tension, facilitating membrane repair and inhibiting unregulat
Slide 28: 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 at least one week Study conducted by: Hani N. Sa
Slide 29: 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 30: 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 initiated Q4 2015 N=150 patients, 3 dose arms, single dose (3-hour IV administration) Efficacy assessments: Cardiac function Biomarkers Study is testing a new formulat
Slide 31: Development of Vepoloxamer in Ischemic Stroke
Development of Vepoloxamer in Ischemic Stroke Objective: Accelerate time to reperfusion and reduce reperfusion injury Phase 2a Ready
Slide 32: 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 33: 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 34: Vepoloxamer Data Announcements Following Acquisition by MAST
Vepoloxamer Data Announcements Following Acquisition by MAST 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
Slide 35: 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 36: Development of AIR001 in Heart Failure
Development of AIR001 in Heart Failure Objective: Improve exercise tolerance and hemodynamics in HFpEF patients Phase 2a Studies Ongoing
Slide 37: AIR001 Overview
AIR001 Overview AIR001 is nitrite* for intermittent inhalation Delivered via a proprietary handheld nebulizer Activity includes dilation of blood vessels and reduced inflammation Hemodynamic benefits include reductions in: Pulmonary capillary wedge pressure Right atrial pressure Mean pulmonary arter
Slide 38: 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 One Phase 2 study Well-tolerated; no treatment-related serious adverse events Improvements seen in median pulmonar
Slide 39: AIR001 Clinical Development
AIR001 Clinical Development Heart Failure with Preserved Ejection Fraction (HFpEF) Responsible for ~50% of heart failure hospitalizations 80% develop pulmonary hypertension No approved medications Supporting two institutional-sponsored Phase 2a studies to: Evaluate acute effects versus placebo on su
Slide 40: MSTX Financial Overview
MSTX Financial Overview Cash/investments at 12/31/2015: ~$41M Market capitalization: $70 million* Shares outstanding: ~ 164 million* Average daily volume (3 mo.): ~ 1.1 million * As of January 6, 2016
Slide 41: 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, CLS, Encysive, U. Texas Medical Brandi Roberts, CFO Alphatec, Artes, Stratagene, Pfizer, PWC Martin Emanuele, SVP Devel
Slide 42: Mast Therapeutics: Key Takeaways
Mast Therapeutics: Key Takeaways Vepoloxamer has the potential to be a first-in-class disease-modifying therapy for SCD EPIC average age is 15, majority of patients are from U.S., and hydroxyurea use is >60% Blinded analysis suggests EPIC actual performance is consistent with statistical assumptions
Slide 43: Investment Highlights: Anticipated Milestones in 1H 2016
Investment Highlights Anticipated milestones in 1H 2016 Top-line results from first of two ongoing AIR001 Phase 2a studies Completion of enrollment in EPIC study Q4 & FYE 2015 financial results & update EPIC study final patient’s 30-day observation period & follow-up Q1 2016 financial results & upda
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