Savara, Inc. · NASDAQ:SVRA
Savara — Mast Therapeutics — Investor Presentation (March 2015)
55 slides from Savara's investor presentation, Mar 2, 2015
Slide 1: Corporate Overview March 2015
Exhibit 99.1 NYSE 2,, Corporate March MKT:2015 Overview MSTX
Slide 2: Forward-Looking Statements
Forward-Looking This statement are pending material; releases We 2presentation NYSE difficult caution presentation and MKT: our ofyou to our to historical future ability predict. reflect MSTX not filings includes Statements clinical toplace toevents fact Actual raise with forward-looking should stud
Slide 3: Corporate Overview
3?Corporate Publicly-traded Rare Sickle Large Developing Heart NYSE (“orphan”) Failure? failure market Cell MKT: Overview Disease AIR001 vepoloxamer with opportunities: MSTX Stroke biopharmaceutical diseases: preserved ?for: Acute (MST-188) Limb ejection Ischemia company fraction? for: based Commerc
Slide 4: Pipeline
Product Vepoloxamer Acute (orphan) Preclinical AIR001 Heart 4Enrolling Planned NYSEFailure Limb Candidate MKT: Enrolling Phase Ischemia Planned (“HFpEF”) Preclinical MSTX 1 Pipeline PhasePhase Enrolling 2 Phase 1 Phase 3 2 Phase 3 Sickle Cell Disease
Slide 5: Lead Program: Vepoloxamer
5Lead Program Vepoloxamer
Slide 6: Vepoloxamer: Biophysical Agent
Vepoloxamer: 6?Poiseuille’s Want How?lower Reduce NYSE friction surface Law viscosity? AMKT: Biophysical describes tension by lowering MSTX with Newtonian Agent adhesion vepoloxamer flow and improving the deformability of cells
Slide 7: Vepoloxamer Structure
Vepoloxamer HO API Large, Composition Rapidly 7Ether NYSE –Structure: linkages (CH2CH2O)79– synthesized and MKT:predominantly of Overview cannot | MSTX matter CH3 polymer be claims (CH2CHO)30– cleaved; cleared with pending extraction nobydrug kidneys Administration: (CH2CH2O)79– metabolites process
Slide 8: Vepoloxamer Core Mechanism of Action
Vepoloxamer Core No 8ButAffinity Adheres of molecule NYSEfor toMechanism Damaged Healthy MKT: adheres MSTX Cell Cell to of hydrophobic Action Membranes… Membranesdomains on a cell surface, such as damaged membranes and adhesive proteins.
Slide 9: Vepoloxamer Pharmacodynamics
Lowers Vepoloxamer Intracellular Ratio 60 50 CPS) (Saline Viscosity 3.0 30 010 2.5 9Shear Poloxamer 2.0 NYSE 4.0 2.5 5 10 40 340/380 Rate adhesion 20 MKT: 35 20(1/sec) 40 .Ca2+ 188 Pharmacodynamics adheres 80 MSTX Cell 0Level Lowto integrity hydrophobic Dose High maintained Dose domains Improves on
Slide 10: Vepoloxamer Pharmacodynamics by Indication
Vepoloxamer Viscosity Lowers Improves Cell Ca2+ Acute Heart 10 NYSE integrity influx Failure: Limb adhesion is flow MKT: reduced Ischemia: reduced maintained Pharmacodynamics adheres Lower Membranes MSTXSickle viscosity, toFaster hydrophobic are Cell thrombolysis, sealed more Disease: membrane domai
Slide 11: Sickle Cell Disease
Sickle CellImprove Objective 11 Diseaseblood flow and shorten the duration of crisis
Slide 12: Sickle Cell Disease Overview
?Overview 12 A Affects Vaso-occlusion Characterized Hallmark Exceedingly Significant No Standard Obstructed NYSE chronic, approved 90,000 MKT: of of ofgenetic Sickle blood unmet care disease painful agents by MSTX to is(hydration severe 100,000 flow associated Cell need disorder is to condition? aDi
Slide 13: Role of Vepoloxamer in Vaso-Occlusive Crisis
Role ?Vaso-Occlusive Vepoloxamer: 13 Adhesion Lowers NYSE of Vepoloxamer viscosity, MKT: of poorly-deformable, Crisis: MSTXreduces in Sickle adhesion Cell“sticky” Disease of cells cells to endothelium, to endothelium lowers and to RBC eachaggregation, other leads to improves vessel obstruction? RBC
Slide 14: Vepoloxamer Reduces RBC Aggregation
Vepoloxamer 1Dose-dependent 1.2 Aggre 0.8 ?0Relative *Vepoloxamer 14 .25 The Results gation NYSE 0.5 effect 0.6 Aggregate 10.4 represent MKT: Aggregate 2 of 50.2 Reduces Poloxamer five iseffect MSTX purified the extent concentrations strength RBC on mean 188* poloxamer redAggregation ofblood (mg/mL)
Slide 15: Vepoloxamer Reduces Sickle Cell Aggregation
Vepoloxamer Dose-dependent 1A Aggrega ?00.4 *Vepoloxamer 15The ggregate 0.25 NYSE lative effect 0.50.6 0.2 MKT: 1extent of Poloxamer Aggregate Re Reduces poloxamer iseffect MSTX purified tion 0.8 RBC on strength 188* poloxamer sickle 188Aggregation (mg/mL) oncell sickle red 188cell blood (sickle RBC
Slide 16: Vepoloxamer Decreases Blood Viscosity
Vepoloxamer ?Poloxamer *Vepoloxamer 16 Poloxamer Results NYSErepresent MKT: 188* 188 188 Decreases isconcentration MSTX decreased purified added the mean to Blood poloxamer whole viscosity of(mg/mL) Viscosity samples blood of 188 sickle (40% from Underhematocrit) 11 cell Low SCD whole Shear patients
Slide 17: Vepoloxamer Effect on Sickle Cells
Vepoloxamer Lower Before 17 NYSEsurface vepoloxamer MKT:Effect tension MSTXon After improves Sickle vepoloxamer Cells flow and deformability (video)
Slide 18: Vepoloxamer Improves Blood Flow
Vepoloxamer 1.8 2.0 1.4 (mm/sec) 0.8 02. 0.4 0B (Crisis Source: 18efore NYSE Vepoloxamer (p =Baseline) Red vaso-occlusive Infusion J. cell 0.00003) 1.2 MKT: Investig. velocity ty Improves improved 2-Hours 1.0 MSTX After 1.6 crisis. Med. (mm/s) Placebo Loading Blood microvascular 7-Hours 2004;52(6):4
Slide 19: Phase 3 Study Results
Phase Randomized, Subjects (n=18) Duration ± excluded *±± Source: 19 Vepoloxamer Excludes NYSE Proportional 2(n=13) Blood, Study Who of equally MKT: patients Crisis Hospitalization double-blind, Received September ishazards MSTX (n=9) purified 44who hours between Full model had poloxamer 1,placebo-c
Slide 20: Acute Chest Syndrome Clinical Data
?•Acute Duration 12 8714 9.9 4610 20N Standard *Source: 20 .9 A Serious Acute Vepoloxamer EJM 7.2 4.1 12.8 NYSE leading 6.3 Chest 2000* Adults Chest of NEJM, complication MKT: cause Hospitalization Lo Syndrome Vepoloxamer? Syndrome Children Dose reduced MSTX June of death (40-80 22, of Clinical dura
Slide 21: Prior Phase 3 Study and Lessons Learned
Prior ENROLLMENT? 350 255 ?(actual)? *Average trial Flawed Lessons Incorporate patients (EPIC) Sponsor’s Responder’s endpoint age learned as conducted FDA, of ofPhase patients Jan for First selection expert, 2015: Mast analysis 3(intended) large Study in Phase and Mast’s 14 and trial highly years pa
Slide 22: Current Phase 3 EPIC Study Design
Current (Mast ?loss 22Double-Blind, 388 Primary Duration Secondary Re-hospitalization Power 90% NYSE (PCA patients, study) power Phase Calculations MKT: Endpoint: device) ofEndpoints to crisis 3randomized detect Study Placebo-Controlled, MSTX from fora“EPIC” and crisis 16-hour randomization 1:1 Othe
Slide 23: EPIC Enrollment and Success Factors
?EPIC designation? 23 Enrollment ~70 Most Potential Considerations Significant NYSE Success trial Advanced MKT: sites toHealthcare unmet on-track be Factors open 1st MSTX for Newneed drug Regulatory (>50 Drug disparity –ever in standard in U.S.)? approved SCD Decision-Making concerns? Top-line of ca
Slide 24: Commercial Opportunity
Commercial ?United Europe 24 Approximately NYSEStates MKT: Opportunity MSTX 100,000patients? 40,000 hospitalizations ~50% ofannually? patients reside ~50%inof2events cities:?occur Parisinand justLondon 16 metropolitan areas? Effective coverage with small, targeted field force
Slide 25: Arterial Disease: Acute Limb Ischemia and Stroke
Arterial ?Vepoloxamer Objective 25 Acute Limb Disease Accelerate in Ischemia? Combination timeStroke to thrombolysis with Thrombolytics and restore tissue perfusion
Slide 26: Arterial Disease Overview
Overview Acute (stroke) (heart ?Peripheral Development 26 A Thrombolytic Intermittent NYSE progressive attack) Ischemic Myocardial MKT: of Arterial Arterial Strategy:? Claudication? circulatory agents Cerebrovascular MSTX Infarction Disease Disease (tPA) Develop problem Critical are used Infarction
Slide 27: Vepoloxamer is Antithrombotic
Vepoloxamer is Antithrombotic Vepoloxamer 27 NYSE ? Juvenile MKT: is pigs purified MSTX were subjected poloxamerto188 balloon (P188) angioplastyinfusion using excessive of 25 mg/kg/hr) pressureorand a comparable placement of volume a wireofstent Heparin ? Animals in normal weresaline randomized (p <
Slide 28: Accelerated Thrombolysis in Animals
Accelerated Animals 28 (tPA) NYSEsubjected MKT: tPA Activity MSTX to femoral Minutes thrombotic Poloxamer occlusion 188 control randomized (tpa) Time to tPA to or Reperfusion tPA + poloxamer Time to188* re-Occlusion (n=10), then monitored for blood flow Time to Reperfusion Time to Re-Occlusion Minut
Slide 29: Effect on Reperfusion Injury
Effect Poloxamer ut 35 36 40 Outp 9(30 5Cardi ?Blood *Vepoloxamer 29 %Rat 0)NYSE 1025 hearts 4.4 on Superoxide normal Reperfusion MKT: 188* perfused is20 MSTX protected purified dismutase acwith fInjury 15poloxamer human against o P188packed no-reflow 188 red and cellsreperfusion and heparininjury s
Slide 30: Synergy with Thrombolytics in Heart Attack Trial
Synergy with Thrombolytics in Heart Attack Clinical Trial Infarct Myocardial Ejection (median) 13% Incidence Reinfarction *Vepoloxamer 30 NYSE Size Fraction 52% MKT: of16% 1% 46% is MSTX 13% 26% purified 0.020 92% 38%poloxamer improvement reduction reduction188 0.016 0.031 Source: (median) Circulati
Slide 31: Phase 2 Study in Acute Limb Ischemia
?Phase 31 Timing Clinical Biomarkers? Study Dose-finding, Completion Data NYSE 2can Design Study Proof-of-Concept MKT: be supportive of in Clinical randomized, enrollment MSTX Acute outcomes Limb of clinical anticipated Study double-blind, Ischemia development 2H and 2016active-controlled? in stroke
Slide 32: Vepoloxamer in Stroke Model
Vepoloxamer alone in Stroke or inModel combination with tPA improved neurological outcomes ? Vepoloxamer administration Conducted Data 32 NYSE presented MKT: by Michael occurred at alone MSTX 2015orChopp, International in 4 hours combination Ph.D. following Stroke Henry with MCAO Conference Ford tPA
Slide 33: Vepoloxamer Stroke Model Data
?nVepoloxamer Conducted Data 33 Panelsare Bar =NYSE 10/group presented graph MKT: by H&E shows in alone Michael atStroke MSTX stained 2015 that or inChopp, treatments International Model combination coronal Ph.D. sections with Stroke Henry with vepoloxamer obtained tPA Conference Ford reduced Health
Slide 34: Heart Failure (Chronic and Acute)
Heart Failure (Chronic Objective 34 and Preserve Acute)heart cells and improve cardiac function
Slide 35: Chronic Heart Failure Overview
?Overview 35 Vepoloxamer Chronic Heart Primary Significant Leading Substantial > $21 NYSE 5 million billion cannot MKT: clinical condition of healthcare Heart of Unmet and individuals pump direct ?MSTX Growing symptom Membrane-sealing Failure characterized Medical cost enough costs with inMarket for
Slide 36: Membrane Injury and Repair in Cardiomyocytes
?Background: Membrane In healthy rat injury Membrane hearts, andadrenergic repair Injuryisand a stimulation constitutive Repair in Cardiomyocytes increases event in healthy myocytecells, wounding especially 3-fold. those subjected to increased wall tensions from mechanical stress, such as cardiomyoc
Slide 37: Development Rationale
Development leak. Displaceme calcium ?ad Be (no hemodynamic and had *Vepoloxamer 37Vepoloxamer Elevated 0.05 NYSE treatment) biomarkers significantly (µm) damage MKT: nwall n=Rationale =parameters (1.0 15 isled seals tension (troponin, 7and MSTX reduced purified ntto mg/mL) 0.15 membranes preserving
Slide 38: Chronic Heart Failure Model Study 1
Chronic ?Study by Conducted 38 The intracoronary NYSEprimary 1: Heart Single-administration MKT: by Hani objective Failure MSTX microembolizations N.Model Sabbah, of this study Ph.D.,was Henry to examine Ford Health the effects SystemofData acutepresented intravenous at American administration Heart
Slide 39: Study 1 Protocol: Single Administration
21 Heart Study 1 –Failure Single Dogs Administration (LV EF ~30%) Protocol Randomized 1FOLLOW-UP 2 NYSEWeek 39 Weeks MKT:AllMSTX Groups Low Dose 24 hours High Dose Placebo – Control 2 hours infusion 2 hours infusion 2 hours infusion vepoloxamer vepoloxamer of normal saline (225 mg/kg) (450 mg/kg) (n
Slide 40: Study 1 Results
2610 Study ?**500 1 –Hours p Single *<**100Post 0.05 Administration vs.24 Hours Control Post Results 1 Volume Week Post 2 Weeks Post 5*15 ? LV *10Ejection nt-pro 0.1 Control 40 NYSE 8 ** * 4 300 BNP LowMKT: Fraction (pg/mL) 00. DoseMSTX High?(%) -100 ? Stroke Plasma -300 Dose -0.1 Troponin-I Control
Slide 41: Study 1 Conclusions
?Study 41 The Intravenous NYSE functional decline 1: Single MKT:in vepoloxamer Administration plasma improvement MSTX troponin-I elicits isConclusions supported improvements level suggest by significant that in LV vepoloxamer systolic reductions andmay diastolic of act NT-proBNP tofunction limit ong
Slide 42: Chronic Heart Failure Model Study 2
Chronic ?Study failure Conducted 42The NYSE primary 2: produced Heart Repeat-administration MKT: by Hani objective Failure MSTX by N. intracoronary Model Sabbah, of this study Ph.D. microembolizations was Henry to examine Ford Health the effects Systemof acute intravenous administration of multiple
Slide 43: Study 2 Protocol: Repeat Administration
14 Heart Study 2 –Failure RepeatDogs Administration (LV EF ~30%) Protocol Randomized 6Total Follow-Up 43 NYSE Weeks All Groups MKT: MSTX Placebo – Control High Dose 2 hours infusion 2 hours infusion of normal saline vepoloxamer (450 mg/kg) on week 0 and on week 0 and week 3 week 3 (n=7) (n=7)
Slide 44: Study 2 Repeat Administration Results
Study Placebo *Preliminary 44 NYSE 2 –Control Repeat MKT: data. Vepoloxamer MSTX Administration Arrows indicate Results dose events.
Slide 45: Study 2 Left Ventricle Ejection Fraction
845 Study Placebo Vepoloxamer 10??L 2 4 2V 2h NYSE -2 Dose-1 –Control 61ERepeat 4je22c0W hDose-2 MKT: W tioMSTX Administration 3n W F r3aW c tio + 2n???? h Focus 3 W + On 2 4hLeft 4WVentricle 5W 6 W Ejection TIME Fraction
Slide 46: Study 2 Conclusions
?Study 46 Reproduced InNYSE addition, 2 – Repeat MKT:intravenous Study MSTX Administration 1 findings vepoloxamer Conclusions pulsed once every 3 weeks elicits improvements in LV systolic and diastolic function that can be sustained for at least 6 weeks.
Slide 47: Supplemental Findings Protocol
Study ?Sealing Conducted 47 Protocol: ?NYSE Cells 2 membranes – were Repeat MKT: by Isolated Hani then MSTX Administration cardiomyocytes N. washed with Sabbah, intensity vepoloxamer andPh.D. treated Supplemental readings were Henry with treated were Ford 10 Findings uM obtained with Health Fura-2 v
Slide 48: Vepoloxamer Seals Cardiomyocyte Membranes
Vepoloxamer Cardiomyocytes Intracellular 1.50 n=4 1.25 00.50 LD 48LD NYSE =10µM 4.0 3.5 2.0 HD 1.51.00 mg/mL 0MKT: Ca2+ LD Ca2+ 3.0 Seals HDIsolated MSTX n=4 0.75 vepoloxamer Level Cardiomyocyte 1.0mM 2.5Intracellular fromCa2+ Animals HD =Membranes 4.5 Ca2+ with mg/mL Level Advanced vepoloxamer Rati
Slide 49: Vepoloxamer Repairs Disrupted Membranes
Vepoloxamer ?(Yasuda 49Seals Restores Prevents NYSE skeletal et.MKT: Ca contraction action al.,Repairs overload Nature, muscle MSTX potentials Disrupted induced 2005, cells in Lysophospatidylcholine and against 436:1025 membrane prevents Membranes carboxyfluorescein – Ca++ 1029) injurymediated and i
Slide 50: AIR001 (sodium nitrite)
(sodium nitrite) AIR001 Objective 50 Improveinhalation hemodynamics solution and exercise tolerance of patients with heart failure
Slide 51: AIR001 Overview
?AIR001 51 Nitrite Different pulmonary Safety NYSEOverview data for MKT: molecule intermittent vascular available MSTXand resistance? ininhalation activity 124 subjects than pulmonary (viaorganonitrates (well-tolerated) nebulizer) capillaryorwedge including nitric pressure oxide? exposures Beneficia
Slide 52: AIR001 Clinical Data
?AIR001 52 Acute Three Well-tolerated; Established One Showed NYSE Phase Phase improvements Clinical MKT: improvement 2MTD 1study: studies: MSTX Data no and treatment-related insafe inhypoxia-induced median dose level pulmonary serious pulmonary adverse vascularevents hypertension? resistance (PVR)
Slide 53: AIR001 Development Plan
?AIR001 53 AIR001 Responsible Supporting Evaluate Preliminary NYSEClinical for MKT: thethree Heart data for acute MSTX Development ~50% announcements institutional-sponsored Failure hemodynamic effects of heart with versus Plan Preserved failure placebo 2H effects 2015 hospitalizations? Phase Ejecti
Slide 54: MSTX Financial Overview
*?MSTX 54 Cash/investments AsNYSE of Financial February MKT: MSTX 25, Overview at2015 12/31/14: $57.3 million? Market capitalization: ~$89 million*? Shares outstanding: ~159 million*? Average daily volume (3 mo): ~1.0 million*? No debt
Slide 55: Mast Therapeutics Summary
?Mast 55 A Sickle Mast NYSE Leader Therapeutics Therapeutics Cell MKT: inDisease: Areas MSTX Summary of isMost Significant committed advanced to Unmet showing newNeed drug theinclinical development? benefit of Acute improving Limb Ischemia: blood flow Phase and 2sealing ongoing; cellgateway membrane
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