Savara, Inc. · NASDAQ:SVRA
Savara — Mast Therapeutics — Investor Day (October 2015)
70 slides from Savara's investor day presentation, Oct 7, 2015
Slide 1: Investor & Analyst Day
_ eee MAST | INC. Investor & Analyst Day October 7, 2015
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 AIROO! 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
Product Candidate Pipeline Vepoloxamer Preclinical Phase 1 Phase2 Phase3 Sickle Cell Disease Chronic Heart Failure Ischemic Stroke AIROO1 Preclinical Phase1 2a ab Phase3 Heart Failure (HFpEF)
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 met
Slide 5: Pathologies and Conditions Related to Imbalances in Surface Tension
——————eoOO—CSt—~s Pathologies and Conditions Related to Imbalances in Surface Tension Silecelbissse Elevated blood viscosity Heart Failure Cellular aggregation F Cellularadhesion IschomleStroke Loss of membrane barrier function / repair Other Diseases capacity Dysfunctional coagulation
Slide 6: Vepoloxamer in Sickle Cell Disease (SCD)
——o CC Vepoloxamerin Sickle Cell Disease (SCD) > The underlying pathology in vaso-occlusive crisis (VOC) is diminished blood flow > Vepoloxamerimproves blood flow by addressing multiple pathological mechanisms: * Adhesion + Hemolysis + Aggregation + Viscosity Objective of treatmentwith vepoloxamer:
Slide 7: Vepoloxamer Improves Blood Flow
—_ @ & Vepoloxamer Improves Blood Flow Vepoloxamerimproved microvascular blood flowin SCD patients during vaso-occlusive crisis (prior Phase 3 sub-study) as = Vepoloxamer as: e Placebo g we | Double blind assessmentof z al red cell velocity (mm/s) 3 measured by video microscopyin ninesickle cell pat
Slide 8: Development of Vepoloxamer in Sickle Cell Disease
Development of Vepoloxamer in Sickle Cell Disease
Slide 9: Vepoloxamer Development History
—— VVVV Vv 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
Slide 10: The EPIC Study
——— > Vv v 10 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 Se
Slide 11: EPIC Study: Primary Endpoint
——————“‘_—(_mré EPIC Study: Primary Endpoint > Duration of vaso-occlusive crisis > Definition: time from randomization to last dose of parenteral opioid > Advantages: * Aligns with FDA recommendations and guidance ~ Sensitive and specific data collection ~ Objective ~ Minimal data loss + Medical exp
Slide 12: EPIC Study: Enrollment Progress
nc, EPIC Study: Enrollment Progress (as of September30, 2015) “> Approx.80%enrolled i» > Top-line data anticipated duringQ1.2016 2
Slide 13: EPIC Study: Demographic Characteristics
7, EPIC Study: Demographic Characteristics* (As of September30, 2015) > Age + Average= 15 years + Range= 4 to 46 years + Patients over 18 = 28% v Use of Hydroxyurea (HU) = 61% > U.S. patients > 50% > ~80% ofall sites have enrolled at least one patient Vv Why are these demographics encouraging? + Int
Slide 14: Interim Statistical Considerations for The EPIC Study
Interim Statistical Considerations for The EPIC Study Bruce A. Barton, Ph.D. Research Professor, Biostatistics U Mass Medical School October 7, 2015
Slide 15: Interim Statistical Considerations for EPIC
Interim Statistical Considerations for EPIC Review original assumptions of sample size in EPIC protocol and the performance of these assumptions Review variability of primary efficacy outcome measurement across regions Reviews performed WITHOUT treatment group information to preserve statistical int
Slide 16: Sample Size Assumptions
Sample Size Assumptions * Protocol sample size for EPIC was set at a total of 388 patients (194/treatment group) based on the following assumptions about the primary outcome (time from randomization to last dose of parenteral opioid analgesic): — Mean duration: 96 hours (placebo) — Standard Deviatio
Slide 17: Sample Size Assumptions
Sample Size Assumptions Without treatment group information, look for “consistency” between current data and assumptions for initial sample size Major factor is the S.D. - that determines ability to detect differences At two-thirds of recruitment (250 subjects), mean duration across ALL subjects is
Slide 18: Analysis of Variability Among Regions
Analysis of Variability Among Regions * With clinical sites in numerous (i.e., non-U.S.) geographic regions, there could be increased variability due to systematic regional differences in treatment of pain crises * What does the primary outcome look like at this point for ALL subjects across regions
Slide 19: Boxplot for Time from Randomization to Last Parenteral Opioid Dose by Region
Boxplot for Time from Randomization to Last Parenteral Opioid Dose by Region
Slide 20: Boxplot Interpretation
Boxplot Interpretation Each box and its “whiskers” represents the distribution of times within that group of clinics The ‘*’ in each box is the mean (average) The line inside the box is the median The bottom border of the box itself is the 25" percentile and the top is the 75" percentiles of the tim
Slide 21: Analysis of Variability Among Regions
Analysis of Variability Among Regions * Conclusion: The non-U.S. regions have substantial overlap with the U.S. for the primary outcome - means, medians, and S.D. almost identical — Because of small sample size in other countries/regions, the effect of any single non-U.S. site or country on the main
Slide 22: Conclusions about Interim Blinded Statistical Assessments for EPIC
Conclusions about Interim Blinded Statistical Assessments for EPIC * Current data support sample size estimates and confirm the study is performing to preconceived assumptions * Current data support similar variability for primary outcome across U.S./non-U.S. regions and expect minimal impact on mai
Slide 23: EPIC Study: Safety
——————“‘_—(_mré 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 safety signals identified + DSMB members deemed no additional meetings were necessary 23
Slide 24: EPIC Study: Summary
——o— CC EPIC Study: Summary > Enrollmenton track > Safetyassumptionsas predicted > Age consistentwith expectations > HU use higherthan expected > Study design assumptions consistentwith original plan (patient#s, avg. duration of crisis, coefficientof variation) > Minimal regional variability
Slide 25: Vepoloxamer in SCD: Regulatory Considerations
———— Vepoloxamerin SCD: Regulatory Considerations > Significantunmetneed - still no disease-modifying therapy for ongoing VOC > Supportamong medical / advocacy / communities > Orphan Drug Designation > FastTrack Designation > SCDis partof FDA “Patient-Focused Drug Development Initiative” > Healthcar
Slide 26: Vepoloxamer in SCD: Key Regulatory Activities
—oo— tM Vepoloxamer in SCD: Key Regulatory Activities FDAAdvisory Committee Meeting US. EU. DraftEUPIP EU Nation: EMAMAA Authority Meet Submission
Slide 27: Sickle Cell Disease Commercial Opportunity and Strategy
27 Sickle Cell Disease Commercial Opportunity and Strategy MAST
Slide 28: SCD: A Lifetime of Complications
——o— SCD: A Lifetime of Complications “Sickle cell disease is a chronic disease thatis punctuated by acute events and that shortens life.” + Premature death ‘Multiple organ damage and ature ‘+ Mult hospatzations forVOC per year ‘+ Arascalr necrosis may stato oecar as ares of sehen + Piapism and preg
Slide 29: Significant Costs to Treat SCD
————aa— Significant Costs to Treat SCD Average Annual Cost of Care: U.S. Population v. SCD Patients (2011 $ in Thousands) $987 \Non-S0D Casts $4 $35 ‘Direct SoD Costs $10. ae $199 $15.2 $72 $6.1. $8.8 a | | $5 USPop pes a ‘ScD Co oa ‘scp | Patients Patients Patients Patients ows 191044 451054 551064
Slide 30: Vaso-Occlusive Crisis is the Hallmark of SCD
Vaso-Occlusive Crisis 20 is the Hallmark of SCD 80-100k hospitalizations annually inthe U.S. Currenttreatmentis palliative Consisting of hydration andIV opioids Does nottreat underlying pathophysiology ofthe disease No VOC interventional therapy available Hospitalized on average for approximately 4-
Slide 31: Physicians Report a High Correlation of VOC with Organ Damage and Mortality
Physicians Reporta High Correlation of VOC with Organ Damage and Mortality Frequency, Severity, and Duration of VOC Correlates with Morbidity and Mortality (# of mentions) uiWeak Moderate Strong oo TT “My older patients have more organ issues than my younger patients” -IM “It's ikea heartattack- the
Slide 32: Physicians Recognize the Value of a New Treatment that Would Reduce the Duration of VOC
- Physicians Recognize the Value of a New Treatmentthat Would Reduce the Duration of VOC Desired Benefits of ‘Ideal’ Treatment for VOC (# of mentions, unaided) Rede spon 5 Ree ii se ws Hem/One (n=18) 1a IM, PED (n=12)
Slide 33: Expected Features and Potential Benefits
eC Expected Features and Potential Benefits Align with Unmet Needs for VOC Treatment Key Advantages/Features of Vepoloxamer (# of ranked mentions, unaided) ‘Unique MOA/Targets undertying cause Of\OC EE] S Reducengh fos Rich sii. ——————<——" Potentially preventoga age — a 5 Improve blood iow —— Ts 4 V
Slide 34: Incremental Value
Incremental Value u Potential to Drive Value According to Multiple Near-Term Outcomes & Long-Term Expectations ©, ctor a. e@ damage Lowersrateof | a Reduces ry ‘e-hospitalization Shortens durationof VOC (painful crisis) Value Drivers Launch platform: > New treatment approach specific for VOC > Reduc
Slide 35: Physicians Report a High Percent of Patients to be Treated with Vepoloxamer at Peak
oO Physicians Report a High Percent of Patients to be Treated with Vepoloxamer at Peak Average % of Patients Treated with Vepoloxamer at Peak 100% kts 94% 89% 20% 60% 40% 20% on Hem/Onc iM Ped MDs expect quick uptake and time to peak (~6 months)
Slide 36: Development Landscape in SCD
——oo OM Development Landscape in SCD Vepoloxamer has the potential to be the firstand only treatment to reduce the duration of an ongoing VOC VOC Reduction Stage 36
Slide 37: Concentration of SCD Treatment in the U.S.
ee. Concentration of SCD Treatmentin the U.S. Offers an Attractive Commercial Opportunity hwo > ~50% of SCD patientsintheU.S. are ey — treated in thetop 16 metropolitan areas scsiaisani —_ = Piospia > Topfourmetropolitanareasaccountfor = Wastingonde 24% of the market = Detroit lenee, e A¥anta > <200
Slide 38: U.S. Sickle Cell Disease Hospital Payer Mix
—————eaoOOCSt—~s U.S. Sickle Cell Disease Hospital Payer Mix Sickle Cell Disease, Payer Mix 2012 HCUP data Other, Missing, Uninsured, 2,720, 3% . 150, 0% 3,385, 4% > Inpatient prospective payment system (IPPS) > Patients with public insurance have minimal share of costs Medicare, 8 > Medicaid plans
Slide 39: Vepoloxamer's Adoption & Growth Guided by the Development Strategy
~ Vepoloxamer’s Adoption & Growth Guided by the Development Strategy Expandusein other ForED setting, early ‘SCD complications intervention trial For IP stays, initial regulatory success driven byThe EPIC Study Rate of Acute Care Encounters by Age {or Patients with Sickte Cell Disease inthe U.S. com
Slide 40: Significant Potential Outside the U.S.
—_ & Significant Potential Outside the U.S. > Over 12 million patients worldwide . > Europe F ¢ + Approximately 40,000 patients & 2 Fp | £ aa > MENA 4) fe SS + Over850,000 with ScD ~ 2 + Many treatment centers provide care on par with standard of the U.S, and E.U. 40
Slide 41: Vepoloxamer Positioned for Success in SCD
———— St Vv Vepoloxamer Positioned for Success in SCD Novel therapy fora geneticdisease with high unmetneeds + Unique and relevant mechanism of action + No approved disease-modifying therapies available for VOC intervention Significantfiretto-marketadvantage in multiple tertores Clinical development
Slide 42: Development of Vepoloxamer in Heart Failure
2 Development of Vepoloxamerin Heart Failure Objective: Restore Membrane Integrity To Improve Cardiac Performance MAST
Slide 43: Development Rationale in Heart Failure
———— St 3 Development Rationale in Heart Failure Elevated wall tension in dilated (failing) heartimpairs normal 1 on membrane repair process | Permeabilized membranes allow i unregulated calcium influxand cardiactroponin leak al Vepoloxamer reduces surface tension, inal facilitating membrane repair
Slide 44: Heart Failure Model - Functional Improvement
“4 bon seed BE art Failure Model - Functional Improvement (single administration) ALV Ejection Fraction (%) | a mi 2HoursPost Im 24 HoursPost " 1Week Post - lm 2Weeks Post ato 7 *p<0.05vs. Control Controt ‘ow DoseVepolaamer High DeseVepolxamer AStroke Volume (mL) > Vepoloxamerelicited improvements i
Slide 45: Heart Failure Model - Biomarkers
— " Heart Failure Model - Biomarkers (single administration) ‘Plasma Troponin-I(ng/ml) li 2HoursPost lm 24 Hours Post ~ 1WeekPost ll 2Weeks Post oo ot ie *p<0.05vs.Control > Troponin data suggests vepoloxamercan preserve cardiomyocytes by limiting calciumentryintothecell. > Functional improvements s
Slide 46: Heart Failure Model - Repeat Administration
—_ &2& 27 4 Heart Failure Model - Repeat Administration so LW Ejection Fraction (%) ash 30h 25h 40h , a = ae a5 Coe ee Venticulography 20 ea 25h 20F 15 Time (0 to 6 Weeks) go Stroke Volume (mL) pop Time (0 to 6 Weeks) 46 Vepoloxamer Placebo Control > Repeat administration of vepoloxamer (0 and 3 wks
Slide 47: Heart Failure Phase 2 Study Design
——————“‘_—(_mré Heart Failure Phase 2 Study Design v Randomized, double-blind, placebo-controlled, multi-center Phase 2 studyin chronic heart failure > 150 patients, 3 dose arms, single dose (3-hourlV administration) > Efficacy assessments: + Biomarkers * Cardiacfunction > Anticipated start: October
Slide 48: Development of Vepoloxamer in Ischemic Stroke
Development of Vepoloxamerin Ischemic Stroke Objective: Accelerate time to reperfusion and reduce reperfusion injury
Slide 49: Vepoloxamer in Ischemic Stroke
——————“‘_—(_mré Vepoloxamerin Ischemic Stroke > Instroke, restoring blood flowis critical (“time is tissue”) + Vepoloxamer improves blood flow as a stand-alone agent + Incombination with a thrombolytic, vepoloxamer shortens time to thrombolysis by up to 40% + Seals and protects ischemia-injured tiss
Slide 50: Vepoloxamer Alone or with tPA Improves Outcomes in Experimental Stroke Models
Vepoloxamer Alone or with tPA Improves Outcomes in Experimental Stroke Models 2 hr. occlusion of MCA with silicon coated nylon suture Delayed intervention MCA thrombotic occlusion ‘model. Contralateral brain tissue salvage at day 7 ‘Only 27% of control mice survived vs. 52% of mice treated postinjur
Slide 51: Vepoloxamer Market Exclusivity
eo Vepoloxamer Market Exclusivity Femernenaes | ines | sate Orphan Drug Designation (Market Exclusivity) scD Granted (US/EU) Patents - Composition of matter SCD, HF,IS Filed, pendingw/w Patents - Newformulation HF Provisional filed Patents - Methods of use SCD, HF,IS Filed, pendingw/w Data Exclusivi
Slide 52: Development of AIR001 in Heart Failure
Development of AIRO01 in Heart Failure Objective: Improve hemodynamics and exercise tolerance in HFpEF patients MAST
Slide 53: AIR001 Overview
——————“‘_—(_mré AIROO1 Overview > AIROO1is nitrite* forintermittent inhalation + Deliveredviaa proprietary handheld nebulizer + Activityincludes dilation of blood vessels and reduced inflammation + Hemodynamic benefits include reductions in: ~ Pulmonary capillary wedge pressure ~ Right atrial pressu
Slide 54: AIR001 Clinical Data
———“‘—‘—FOm AIRO01 Clinical Data > ThreePhase 1 studies Established MTD Acute improvements in hypoxia-induced pulmonary hypertension No drug-drug interaction with sildenafil > OnePhase 2 study 54 Well-tolerated; no treatment-related serious adverse events Improvements seen in median pulmonary vascul
Slide 55: AIR001 Clinical Development
——o— —t~* - AIRO01 Clinical Development > Heart Failure with Preserved Ejection Fraction (HFpEF) + Responsible for ~50% of heart failure hospitalizations * 80% develop pulmonary hypertension + No approved medications v Supporting two institutional-sponsored Phase 2a studies to: + Evaluate hemodynami
Slide 56: Financial Overview
Financial Overview
Slide 57: MSTX Financial Overview
———“‘—‘—FOm MSTX Financial Overview > Cash/investmentsat 9/30/2015: ~$50M > Marketcapitalization: ~ $95 million* > Shares outstanding: ~ 164 million* > Average daily volume (3 mo.): ~ 900,000 37
Slide 58: Major Planned Activities
_—_—_—— 38 —_ Major Planned Activities Vepoloxamer Commercial/Regulatory Completion of EPIC enrollment SCD NDA Preparation SCD US Launch ‘SCD EU Launch Cli al Vepoloxamer Phase 2 HF study Vepoloxamer Phase 2 Stroke study AIROO1 Phase 2 HF study Vepoloxamer SCD Label-Expansion studies
Slide 59: Year Plan
——————“‘_—(_mré 3 Year Plan > Assumes vepoloxameron the marketin 2017, becoming standard of care in SCD > Areas offocus: + Regulatory ~ U.S. NDA preparations - E.U.MAA preparations + Commercial Operations - Launch preparation, pricing studies Identify third party logistic (3PL) partner Hire approxim
Slide 60: Financing Update
———“‘—‘—FOm Financing Update > Debtagreementwith Hercules Technology Growth Capital + $15M facility + Extensive due diligence completed + Amendment completed September 28 = Capital raise requirement moved from 12/31/15 to 4/30/16 and removed if EPIC data positive > ATMAgreementwith Cowen & Co. + $30
Slide 61: Mast Therapeutics: Key Takeaways
——o— CC Mast Therapeutics: Key Takeaways > EPICaverageageis 15, majority of patients are fromU.S., and hydroxyurea useis ~60% > Blinded statistical analysis suggests EPIC s performingas itwas designed > Nosafety signals after250 patients and no further DSMB meetings needed > Vepoloxamerhas the poten
Slide 62: Slide 62
Slide 63: Executive Team Backgrounds
63 Executive Team Backgrounds
Slide 64: Brian Culley, CEO
———S—“‘i‘ OO Brian Culley, CEO Mast CEO since 2010 > MAin biochemistry & molecularbiology, MBA > Experience: + Gyears CEO + 8years Business Development + Tyears bench scientist (Neurocrine Biosciences, The Scripps Research Inst) v ‘Acquisitions: + Aires (A/R00D + SynthRx (vepoloxame’) + SD Pharma (m
Slide 65: Marty Emanuele, SVP Development
———S—“‘i‘ OO Marty Emanuele, SVP Development Joined Mast in 2011 > PhD (Pharmacology & Experimental Therapeutics), MBA > Overall experience: 6 30 years Pharma / Biotech (20+ Sr. Executive Management) 15 yearsResearch & Development ~ Awarded NIH and FDA grants primary investigator ~ warded 4 U.S. pat
Slide 66: Ed Parsley, CMO
———S—“‘i‘ OO Ed Parsley, CMO Joined Mast in 2014 > Doctor of Osteopathic Medicine and Surgery; Pulmonary, Critical Care, Sleep, and Internal Medicine certifications > Overall experience: 10 years Pharma/Biotech; 20+ years patientcare Clinical Development. Ctinical trial design and execution across m
Slide 67: Bruce Barton, Statistician
———— Bruce Barton, Statistician Joined Mast asa consultant in 2015 > PhD in Biostatistics > Current positions: + Research Professor, UMass Medical School's Department of Quantitative Health Sciences, Division of Biostatistics (5+ years) * Director, Quantitative Methods Core (5+ years) * Adjunct Prof
Slide 68: Greg Gorgas, SVP Commercial
———— St Greg Gorgas, SVP Commercial Joined Mast in 2011 >» MBA Overall experience: + ~30 years of successful commercial leadership * Global marketing, business development, sales, operations * Built commercial infrastructure for several companies + 4 first-in-class product launches, including Rituxa
Slide 69: Brandi Roberts, CFO
——————“‘_—(_mré Brandi Roberts, CFO Joined Mast in 2011 > CPA,MBA > Overall experience: + ~20 years of accounting and finance experience + 17years of life sciences experience, including 7 years at Agouron/Pfizer > Revenue related experience: + Stratagene/Agilent + Artes Medical + Alphatec Spine > M&
Slide 70: Mark Longer, VP Regulatory
———— Mark Longer, VP Regulatory Joined Mast in 2015 > PhD, Pharmaceutical Sciences; Post-docin biochemistry > Drug Development and Regulatory experience: + 25years of industry experience in PhRMA and biotech, including 18 yearsin the Regulatory Affairs functions with Agouron/ Pfizer, Amylin, and Ard