Insmed Incorporated · NASDAQ:INSM
Insmed — Investor Day (October 2020)
114 slides from Insmed's investor day presentation, Oct 1, 2020
Slide 1: R&D Day September 30, 2020
R&D DAYSeptember 30, 20201
Slide 2: Agenda
AgendaSectionSpeakersWelcome & Kick-off Will Lewis Chair & Chief Executive OfficerTreprostinil Palmitil Inhalation Powder OpportunityDr. Eugene Sullivan, M.D. Chief Product Strategy Officer Dr. Ronald J. Oudiz, M.D., FACP, FACC, FCCP Professor of Medicine and Interim Chief Harbor-UCLA Medical Center
Slide 3: Forward Looking Statements
• • • Forward Looking StatementsThistation contains fotwatd.tooti,.$llltttnents that involvt- sutlstartiall rilob andties.. "kkfwarG-tooking b." as tflat termidtfint!d in tPrivate Stnritie Utigation Refonn Ad of 1995,. areu that art! not hGbOfical facts and k'l o olvt' a nutllbt!r of rills and uneer
Slide 4: Mission, Vision & Strategy
Will Lewis Chair & CEOMission, Vision & Strategy4
Slide 5: Transformational Growth Strategy
Transformational Growth StrategyWorld Class TeamResearch & Development ExpertiseGlobal Commercial PresenceBusiness Development StrengthBrensocatib NCFBEPipeline TPIP Brensocatib expansionBrensocatib NCFBEARIKAYCE EU/Japan Front LineARIKAYCE EU/Japan Front LineARIKAYCE EU/Japan Front LineARIKAYCE Ref
Slide 6: Treprostinil Palmitil Development Update
Dr. Eugene Sullivan, M.D. Chief Product Strategy OfficerDr. Ronald J. Oudiz, M.D., FACP, FACC, FCCP Professor of Medicine and Interim Chief Harbor-UCLA Medical Center Division of Cardiology Lead Investigator for Planned Phase 2a TrialTreprostinil Palmitil Development Update 7
Slide 7: Harnessing the Full Potential of the Prostanoid Pathway in PAH
Harnessing the Full Potential of the Prostanoid Pathway in Pulmonary Arterial Hypertension (PAH)Prostanoids have long been considered the cornerstone therapy for PAH but clinical use has faced challenges related to rapid metabolism and tolerability issuesTreprostinil palmitil has the potential to ad
Slide 8: Agenda
Agenda1 Pulmonary Arterial Hypertension (PAH)2 Treprostinil Palmitil Inhalation Powder (TPIP)3 Highlights of Preclinical Data4 Product Differentiation5 Path Forward9
Slide 9: Pulmonary Arterial Hypertension (PAH) Treatment Landscape
Dr. Ronald J. Oudiz, M.D., FACP, FACC, FCCP Professor of Medicine and Interim Chief Harbor-UCLA Medical Center Division of Cardiology Lead Investigator Planned Phase 2a TrialPulmonary Arterial Hypertension (PAH) Treatment Landscape10
Slide 10: Types of Pulmonary Hypertension
Types of Pulmonary Hypertension11
Slide 11: Types of Pulmonary Hypertension
Types of Pulmonary HypertensionLung disease/hypoxiaLeft-sided heart disease12
Slide 12: Types of Pulmonary Hypertension
Types of Pulmonary HypertensionLung disease/hypoxiaThromboembolic diseaseLeft-sided heart disease13
Slide 13: Types of Pulmonary Hypertension
Types of Pulmonary HypertensionThromboembolic diseaseIPAH and APAHLung disease/hypoxiaLeft-sided heart disease14
Slide 14: Pulmonary Hypertension: Diagnostic classification
Pulmonary Hypertension: Diagnostic classificationPulmonary arterial hypertension (PAH)1.1. Idiopathic PAH (IPAH) 1.2. Heritable 1.2.1. BMPR2 1.2.2. ALK1, ENG, SMAD9, CAV1, KCNK3 1.2.3. Unknown 1.3. Drug- and toxin-induced 1.4. Associated with 1.4.1. Connective tissue diseases 1.4.2. HIV infectionPH
Slide 15: Pulmonary Hypertension: Diagnostic classification
Pulmonary Hypertension: Diagnostic classificationPulmonary arterial hypertension (PAH)1.1. Idiopathic PAH (IPAH) 1.2. Heritable 1.2.1. BMPR2 1.2.2. ALK1, ENG, SMAD9, CAV1, KCNK3 1.2.3. Unknown 1.3. Drug- and toxin-induced 1.4. Associated with 1.4.1. Connective tissue diseases 1.4.2. HIV infectionPH
Slide 16: 2-year mortality untreated = 50%
2-year mortality untreated = 50%**D'Alonzo GE, Barst RJ, Ayres SM, et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med 1991;115:343–349.17
Slide 17: Progression of RV Dysfunction
Progression of RV DysfunctionChampion HC, Michelakis ED, Hassoun PM. Circulation 2009;120:992-100718
Slide 18: Algorithm for the diagnosis of PH and its causes
History, symptoms,sogns and/or laboratory tests suggestove of PHAssess probaboloty of PHEchocardiographoc probabolity of PH'Lowldentofy hogh-nsk patoentsFast-track referralof selected patientsHigh or ontermedoateConsider V/Q scan to screen for CTEPH•Consider other causes and/or follow-up•Doagnose co
Slide 19: Algorithm for the diagnosis of PH and its causes
History, symptoms,sogns and/or laboratory tests suggestove of PHAssess probaboloty of PHEchocardiographoc probabolity Low of PH'ldentofy hogh-nsk patoentsFast-track referralof selected patientsHigh or ontermedoateConsider V/Q scan to screen for CTEPH•Consider other causes and/or follow-up•Doagnose c
Slide 20: Algorithm for the diagnosis of PH (cont) / Management at PH expert centre
Algorithm for the diagnosis of PH and its causes (cont)/ Management at PH expert centreICTEPH doagnostoe)+Any m smatched -Review orNormalperfuSIOnalgonthm perlusoon defectperform f--.scan•PH not PH not confirmed Consoder other confirmed! M ttomodabty d1.1gnoshc assessment l RHC for PH doagno'' and h
Slide 21: Algorithm for the diagnosis of PH (cont) / Management at PH expert centre
Algorithm for the diagnosis of PH and its causes (cont)/ Management at PH expert centreICTEPH doagnostoe)+Any m smatched -Review orNormalperfuSIOnalgonthm perlusoon defectperform f--.scan•! M ttomodabty d1.1gnoshc assessment+PH notPHn RHC for PH doagno''confirmed Consoder other confirm d and haemody
Slide 22: Pathways Affecting PAH Treatments
Pathways Affecting PAH Treatments• Endothelin Pathway – targeted by ERAs• Nitric Oxide Pathway – targeted by PDE5 inhibitors and sGCS• Prostacylin Pathway – targeted by prostacyclin analogues and prostacyclin receptor agonists21
Slide 23: Pathways Affecting PAH Treatments
Pathways Affecting PAH Treatments• Endothelin Pathway – targeted by ERAs• Nitric Oxide Pathway – targeted by PDE5 inhibitors and sGCS• Prostacylin Pathway – targeted by prostacyclin analogues and prostacyclin receptor agonists21
Slide 24: Pathways Affecting PAH Treatments
Pathways Affecting PAH Treatments• Endothelin Pathway – targeted by ERAs• Nitric Oxide Pathway – targeted by PDE5 inhibitors and sGCS• Prostacylin Pathway – targeted by prostacyclin analogues and prostacyclin receptor agonistsParenteral prostanoids are recommended as first- line therapy for FC IV pa
Slide 25: PAH Treatments – Approved Therapies
PAH Treatments – Approved TherapiesSpecific PAH agentsProstacyclin Analogues• epoprostenol (IV)• iloprost (inh)• treprostinil (IV, SQ, inh, po)• selexipag (po)Endothelin antagonists• bosentan (po)• ambrisentan (po)• macitentan (po)PDE-5 inhibitors• sildenafil (po)• tadalafil (po)Soluble gunalylate c
Slide 26: Prostacyclin Advantages and Trade-Offs
Prostacyclin Advantages and Trade-OffsAdministration Advantage LimitationsOral Convenient • GI side effects limitSystemically administered prostanoids (oral or parenteral) are limited by the side effects:Parenteral EffectiveInhaled Targeteddosing• Systemic toxicities limit dosing • Site pain, infect
Slide 27: Prostacyclin Advantages and Trade-Offs
Prostacyclin Advantages and Trade-OffsAdministration Advantage LimitationsOral Convenient • GI side effects limitSystemically administered prostanoids (oral or parenteral) are limited by the side effects:Parenteral EffectiveInhaled Targeteddosing• Systemic toxicities limit dosing • Site pain, infect
Slide 28: A Potentially Differentiated Prostanoid
A Poten Differentiated Prostanoid 29
Slide 29: Treprostinil Palmitil Inhalation Powder (TPIP)
Treprostinil Palmitil Inhalation Powder (TPIP)• TPIP is a dry powder formulation of treprostinil prodrug, treprostinil palmitil*• The dry powder inhaler (DPI) device is the Plastiape RS01 capsule- based deviceTreprostinil Palmitil(INS1009)Lung Esterase• Once delivered to the lung, treprostinil palmi
Slide 30: Highlights of Preclinical Data
Highlights of Preclinical Data 3
Slide 31: Highlights of Preclinical Data
Highlights of Preclinical Data Preclinical data demonstrate the following features of treprostinil palmitil:Improved pharmacokinetics• Prolonged lung residence time • Lower systemic Cmax and prolonged T1/2 compared to treprostinilProlonged duration of pharmacodynamic activity compared to treprostini
Slide 32: Highlights of Preclinical Data
Highlights of Preclinical DataPotential Implications of Preclinical Data Preclinical data demonstrate the following features of treprostinil palmitil:Improved pharmacokinetics• Prolonged lung residence time • Lower systemic Cmax and prolonged T1/2 compared to treprostinilProlonged duration of pharma
Slide 33: Potential Implications of Preclinical Data
Potential Implications of Preclinical Data Preclinical data demonstrate the following features of treprostinil palmitil:Improved pharmacokinetics• Prolonged lung residence time • Lower systemic Cmax and prolonged T1/2 compared to treprostinilProlonged duration of pharmacodynamic activity compared to
Slide 34: Potential Implications of Preclinical Data
Potential Implications of Preclinical Data Preclinical data demonstrate the following features of treprostinil palmitil:Comparable effects at lower systemic exposuresImproved pharmacokinetics• Prolonged lung residence time • Lower systemic Cmax and prolonged T1/2 compared to treprostinilProlonged du
Slide 35: Potential Implications of Preclinical Data
Potential Implications of Preclinical Data Preclinical data demonstrate the following features of treprostinil palmitil:Improved pharmacokinetics• Prolonged lung residence time • Lower systemic Cmax and prolonged T1/2 compared to treprostinilProlonged duration of pharmacodynamic activity compared to
Slide 36: Potential Implications of Preclinical Data
Potential Implications of Preclinical Data Preclinical data demonstrate the following features of treprostinil palmitil:Improved pharmacokinetics• Prolonged lung residence time • Lower systemic Cmax and prolonged T1/2 compared to treprostinilProlonged duration of pharmacodynamic activity compared to
Slide 37: Highlights of Preclinical Data
Highlights of Preclinical Data Preclinical data demonstrate the following features of treprostinil palmitil:Improved pharmacokinetics• Prolonged lung residence time • Lower systemic Cmax and prolonged T1/2 compared to treprostinilProlonged duration of pharmacodynamic activity compared to treprostini
Slide 38: Improved Pharmacokinetics: Prolonged Lung Residence, Lower Cmax, Prolonged Half Life
Improved Pharmacokinetics: Prolonged Lung Residence, Lower Cmax, Prolonged Half Life (Rat and Dog)RAT Lung and Plasma LevelsDOG Plasma Levels100001000100Treprostinil Palmitil 42 μg/kg Treprostinil Palmitil 108 μg/kg Treprostinil 215 μg/kg ExtrapTreprostinil PalmitilInhaled TP Inhaled TPInhaled TP In
Slide 39: Highlights of Preclinical Data
Highlights of Preclinical Data Preclinical data demonstrate the following features of treprostinil palmitil:Improved pharmacokinetics• Prolonged lung residence time • Lower systemic Cmax and prolonged T1/2 compared to treprostinilProlonged duration of pharmacodynamic activity compared to treprostini
Slide 40: Prolonged Duration of Pharmacodynamic Activity (Telemetered Dog)
Prolonged Duration of Pharmacodynamic Activity (Telemetered Dog, Hypoxic Challenge)6 g/kg 23g/kg 57g/kg 0 138 g/kg-2-4-6-8-10-12Nose only inhalation; doses are those presented to the animals (lung dose is 1/10 of the values shown)0 2 4 6 8 10 12 14 16 18 20 22 24Time Post Dose (h)Data on file, Insme
Slide 41: Prolonged Duration of Pharmacodynamic Activity (Telemetered Dog, Hypoxic Challenge)
Prolonged Duration of Pharmacodynamic Activity (Telemetered Dog, Hypoxic Challenge)1614121086420Dose g/kg80.93522.3102.7Average right ventricular pulse pressure (RVPP) response to hypoxia challenge in two dogs following inhalation of different doses of TP; the ‘wash out’ period between doses was ≥7d
Slide 42: Highlights of Preclinical Data
Highlights of Preclinical Data Preclinical data demonstrate the following features of treprostinil palmitil:Improved pharmacokinetics• Prolonged lung residence time • Lower systemic Cmax and prolonged T1/2 compared to treprostinilProlonged duration of pharmacodynamic activity compared to treprostini
Slide 43: Local Pharmacodynamic Effect: Lower Plasma Concentrations (Rat)
Local Pharmacodynamic Effect Pulmonary Vasodilator Activity at Significantly80PBS 60 infused40200IV TreprostinilLower Plasma Treprostinil Concentrations (Rat)0.0001 0.01 0.1 1 10 10060 xRats challenged with the thromboxane mimetic U4661980PBS 60 inhaled40Inhaled Treprostinil Palmitil200 0.0001 0.01
Slide 44: Local Pharmacodynamic Effect: Lower Plasma Concentrations (Dog)
Local Pharmacodynamic Effect Pulmonary Vasodilator Activity at Significantly Lower Plasma Treprostinil Concentrations (Dog)Telemetered Dogs (Hypoxia Challenge)25PBS 20 infused15Inhaled Treprostinil PalmitilIV TreprostinilEC50 value: TP 550x lower than IV TRE10PBS 5 inhaled0-5 0.0001 0.001 0.01 0.1 1
Slide 45: Local Pharmacodynamic Effect: Inhaled vs. Infused Treprostinil in Sheep
Local Pharmacodynamic Effect Continuously Inhaled vs. Continuously Infused (IV) Treprostinil in Sheep…prostacyclin analogs are more potent pulmonary vasodilators when delivered by aerosol than when given intravenously. Systemic hemodynamic effects are also minimized by aerosol administration of the
Slide 46: Highlights of Preclinical Data
Highlights of Preclinical Data Preclinical data demonstrate the following features of treprostinil palmitil:Improved pharmacokinetics• Prolonged lung residence time • Lower systemic Cmax and prolonged T1/2 compared to treprostinilProlonged duration of pharmacodynamic activity compared to treprostini
Slide 47: Improved Hemodynamics and Vascular Remodeling in Rat Sugen-Hypoxia Model
Treprostinil Palmitil Inhalation Solution Improved Both Hemodynamics and Vascular Remodeling in the Rat Sugen-HypoxiaModel of PAHImproves Pulmonary Arterial PressureReduces Wall Thickening* significantly different from the naïve group# significantly different from the vehicle group1Fulton Index is a
Slide 48: TPIP Superior Effect on PA Pressure and RV Hypertrophy
TPIP Demonstrated Superior Effect on PA Pressure and RV Hypertrophy in the Rat Sugen-Hypoxia Model of PAHPulmonary Arterial Pressure 50 *40 *0.8Fulton Index1* * * **30 * * ## 20* # ** #0.60.4* * *#0.2 100 Nx VehicleTPIP 59 µg/kgTPIP (QD)TPIP 117 µg/kgVehicle TRE 65 µg/kgNebulized TRE (QID)Vehicle TR
Slide 49: TPIP Superior Effect on Vascular Remodeling
TPIP Demonstrated Superior Effect on Vascular Remodeling in the Sugen-Hypoxia Rat Model of PAHWall Thickness ������ �������� ������������ − ������� ����������������� �������� ������������ % = 40������ �������� ������������× ���***30 #***##******#******##1009080Non muscular Semi-muscular Muscular***
Slide 50: TPIP at High Dose Shows Superior Effect Overall
TPIP at High Dose Shows Superior Effect Overall in the Sugen-Hypoxia Rat Model for PAHParameter value = (Value – Value of Normal) / (Value of Vehicle – Value of Normal)Data on file, Insmed Inc. 51
Slide 51: Highlights of Preclinical Data
Highlights of Preclinical Data Preclinical data demonstrate the following features of treprostinil palmitil:Improved pharmacokinetics• Prolonged lung residence time • Lower systemic Cmax and prolonged T1/2Prolonged duration of pharmacodynamic activity“Local” pharmacodynamic effect• Achieves the same
Slide 52: Reduced Incidence of Cough
Reduced Incidence of Cough Threshold to Induce Cough Increased 7-Fold (guinea pig model)80 80 * 60 * 6040 40 * * 20 200 0TRE7 X HigherTPIP ***Significantly different from vehicle. **Treprostinil molar equivalent doses; TP doses are 2.3, 12.8 and 35.8 g/kg. Data on file, Insmed Inc.53
Slide 53: Product Differentiation
. wi ZX Product Differentiation
Slide 54: Treprostinil Palmitil Inhalation Solution Phase 1 Study
Treprostinil Palmitil Inhalation Solution Phase 1 StudyPlasma PK in Healthy VolunteersTreprostinil Plasma PK SummaryTyvasoTPIS 85o Substantially lower Cmax than Tyvaso®o Persistent plasma levelsCohort 1 (n = 6)TPIS 85 µgTyvaso 54 µgof drug beyond 12 hours consistent withCmax (ng/mL) 0.089 0.958AUC0-
Slide 55: TPIP a Potentially Differentiated Prostanoid
Treprostinil Palmitil Inhalation Powder (TPIP) a Potentially Differentiated ProstanoidConvenience: portable, dry powder inhalerIf the characteristics suggested by the preclinical studies are borne out in the clinical development program, TPIP could represent a differentiated productQD or BID dosing
Slide 56: TPIP a Potentially Differentiated Prostanoid
Treprostinil Palmitil Inhalation Powder (TPIP) a Potentially Differentiated ProstanoidConvenience: portable, dry powder inhalerIf the characteristics suggested by the preclinical studies are borne out in the clinical development program, TPIP could represent a differentiated productQD or BID dosing
Slide 57: Next Steps for TPIP Development
Next Steps for TPIP DevelopmentPhase 1 UnderwaySAD/MAD StudyObjective Establish PK and tolerability profileTop line results expected in Q1 2021Initiate Phase 2a in Early 2021Exploratory, single dose studyObjective Demonstrate proof of mechanism, understand PK/PD relationship, confirm tolerabilityRes
Slide 58: Next Steps for TPIP Development
Next Steps for TPIP DevelopmentPhase 1 UnderwaySAD/MAD StudyObjective Establish PK and tolerability profileTop line results expected in Q1 2021Initiate Phase 2a in Early 2021Exploratory, single dose studyObjective Demonstrate proof of mechanism, understand PK/PD relationship, confirm tolerabilityRes
Slide 59: Brensocatib NCFBE to Serve as Launch Pad for Neutrophil-mediated Portfolio
Brensocatib NCFBE to Serve as ‘Launch Pad’ for Neutrophil-mediated PortfolioSerious Unmet Need Conditions• Cystic Fibrosis • Granulomatosis with Polyangiitis • Apha-1 Antitrypsin DeficiencyNCFBE Program WILLOW + ASPENLarger MarketsResearch Pipeline• Inflammatory Bowel Disease* • Rheumatoid Arthritis
Slide 60: Brensocatib Clinical Development
Brensocatib Clinical Development 61
Slide 61: Bronchiectasis: Pathogenesis
Bronchiectasis: Pathogenesis Bronchiectasis Vicious Cycle*INFLAMMATIONPersistent inflammatory response, causing lung damageBACTERIAL COLONIZATIONIncreased susceptibility to chronic bacterial infection and colonizationAIRWAY DESTRUCTION ABNORMAL MUCOCILIARY CLEARANCEAn environmental insult or disease
Slide 62: WILLOW Study Results Underscore Potential of Brensocatib
WILLOW Study Results Underscore Potential of Brensocatib63
Slide 63: Brensocatib Phase 2 WILLOW Study Design
Brensocatib Phase 2 WILLOW Study Design6 weeksScreeningStratified by Pseudomonas1:1:1Treatment period 24 weeksBrensocatib 25 mg QD Brensocatib 10 mg QD Placebo QDOff treatment 4 weeks• Primary objective:• Time to first exacerbation over 24 weeks in patients with non-cystic fibrosis bronchiectasis (N
Slide 64: Rate of Exacerbations by Patient Subgroups
25 mg brensocatib vs. placeboRate of Exacerbations by Patient Subgroups10 mg brensocatib vs. placeboChalmers et al, ERS International Congress 2020, 7-9 September. RCT4135 BSI, bronchiectasis severity index; FEV1, forced expiratory volume in 1 second aBulgaria/Poland65
Slide 65: Dose Response Effect Across Sputum Neutrophil Serine Proteases
Dose Response Effect Seen Consistently Across Sputum Neutrophil Serine Proteases (NSPs) Mean (SE) Change from Baseline to Week 24 (log10 [mg/mL])Neutrophil ElastaseProteinase 3 Cathepsin GChalmers et al, ERS International Congress 2020, 7-9 September. RCT4135 66
Slide 66: WILLOW Safety Data
WILLOW Safety Datano. (%) Placebo (n=85)Brensocatib 10 mg (n=81)Brensocatib 25 mg (n=89)TEAE resulting in study discontinuation 3 (3.5) 3 (3.7) 4 (5.5) TEAE resulting in treatment discontinuation 9 (10.6) 6 (7.4) 6 (6.7) Serious TEAE19 (22.4) 11 13.6) 10 (11.2) Serious TEAEs in ≥ 3% of patients in a
Slide 67: Brensocatib Phase 3 Development Program
Brensocatib Phase 3 Development Program 68
Slide 68: ASPEN Study: Single Trial Designed to Support Global Filing
ASPEN Study: Single Trial Designed to Support Global FilingBreakthrough Therapy Designation for brensocatib in non-cystic fibrosis bronchiectasis (NCFBE)Robust efficacy endpoints, supported by WILLOW resultsIntegrates feedback from Health Authorities69
Slide 69: ASPEN Phase 3 Study Design
ASPEN Phase 3 Study DesignPrimary Endpoint:Treatment periodOff treatment• Rate of pulmonary exacerbations over the 52-week treatment periodKey Secondary Endpoints:• Time to first pulmonary exacerbation over the 52-week treatment period• Proportion of subjects who remain exacerbation-free over the 52
Slide 70: ASPEN Timeline Considerations
ASPEN Timeline Considerations36 Countries~480 sites6 Fast Track CountriesTargeting WILLOW study sites71
Slide 71: Brensocatib Commercial Outlook
Brensocatib Commercial Outlook 72
Slide 72: Brensocatib Strategy Builds on Successful First Launch in NCFBE
Brensocatib Strategy Builds on Successful First Launch in NCFBEN Phase 3 trial for non-cystic fibrosis onchiectasis (NCFBE)Prepare for successful global launch in NCFBEAdvance clinical programs for cystic fibrosisaluate other neutrophil-modulated eases for future research & label xpansion73
Slide 73: An Approved NCFBE Treatment Could Address Unmet Needs Across Stakeholders
An Approved NCFBE Treatment to Reduce ExacerbationsCould Address Unmet Needs Across StakeholdersPatients HealthcarePayers“It’s like waiting for• Symptoms of cough, dyspnea, fatigue interfere with daily life• Fear of exacerbations negatively impacts emotional and social well-being• Frustrated with ti
Slide 74: Bronchiectasis is a Globally Prevalent Disease
Bronchiectasis is a Globally Prevalent Disease
Slide 75: Current Prevalence Estimates May Underestimate Global Patient Population
Current Prevalence Estimates May Underestimate Global Patient Population, Given Underdiagnosis of NCFBECOPDBEAsthmaBetween 650K – 9M COPD patients in the US (4%1- 54%2) may also have NCFBEBetween 450K – 675K asthma patients in the US (2%-3%3) may also have NCFBE1. Agusti, A., Calverley, P.M., Celli,
Slide 76: Well Positioned to Support a Successful Global Launch in NCFBE
Well Positioned to Support a Successful Global Launch in NCFBEUniquely positioned to commercialize brensocatib, if approved, given theWell-developed US launch capabilities with ARIKAYCEExperience with patient finding and activationsynergies that exist between NCFBE and NTM lung diseaseGeographic and
Slide 77: Brensocatib Additional Opportunities
Brensocatib Additional Opportunities 78
Slide 78: Strategy to Build a Neutrophil-mediated Portfolio
Strategy to Build a Neutrophil-mediated PortfolioSerious Unmet Need Conditions• Cystic Fibrosis • Granulomatosis with Polyangiitis • Apha-1 Antitrypsin DeficiencyNCFBE ProgramLarger MarketsResearch Pipeline• Inflammatory Bowel Disease* • Rheumatoid Arthritis* • Lupus Nephritis* • COPD/Asthma† • Onco
Slide 79: Cystic Fibrosis and GPA Identified for Further Clinical Development
Cystic Fibrosis GPACystic Fibrosis and GPA Identified for Further Clinical DevelopmentMOA ApplicabilityValue PropositionProviding a Roadmap for Development from CF to GPAClear role for neutrophils and NE in CF; Chronic bacterial infections of CF are neutrophil-mediated, and very elevated neutrophil
Slide 80: Ongoing Investigator-Sponsored Clinical Study for Severe COVID-19
Ongoing Investigator-Sponsored Clinical Study for Treatment of Severe COVID-19 InfectionsCould brensocatib be used to treat COVID-19?Currently under investigation in multi-site UK investigator-initiated research (IIR) studyDouble-blind, prospective, placebo-controlled, randomized trialUp to 300 pati
Slide 81: ARIKAYCE
Kevin C. Mange, M.D., MSCE SVP, Clinical DevelopmentNeil Hughes General Manager, Head of EMEARoger Adsett Chief Operating OfficerARIKAYCENot for promotional use 82
Slide 82: ARIKAYCE Front Line Program
Kevin C. Mange, M.D., MSCE SVP, Clinical DevelopmentARIKAYCEFront Line Program 83 Not for promotional use 83
Slide 83: ARIKAYCE Indication and Use
ARIKAYCE® (amikacin liposomal inhalation suspension) Indication and Use• LIMITED POPULATION: ARIKAYCE is indicated in adults, who have limited or no alternative treatment options, for the treatment of Mycobacterium avium complex (MAC) lung disease as part of a combination antibacterial drug regimen
Slide 84: First-in-Disease Therapy for MAC Lung Disease
First-in-Disease Therapy for MAC Lung DiseaseMAC lung disease is a rare, progressive, and chronic condition that can cause severe, permanent damage to the lungsSymptoms often worsen over time, including chronic cough, dyspnea, fatigue, fever, weight loss, and chest painARIKAYCENovel, inhaled, once-
Slide 85: ARIKAYCE Front Line Indication – Trial Summary
ARIKAYCE Front Line Indication – Trial SummaryARISE (INS-415)Psychometric validation studySubjects: 100Start: Q4 2020ENCORE (INS-416)Double-blind PMR trialSubjects: 250Start: Q4 202086 Not for promotional use 86
Slide 86: Front Line Indication Registration Program
Front Line Indication Registration ProgramScreeningARISEARIKAYCE + AZI* + ETH*ARISEPrimary Objective Demonstrate reliability, validity and responsiveness of the PRO/symptom scoresSecondary Objective Demonstrate effect of ARIKAYCE on culture conversion, time to cultureAdults with newPsychometricR Mon
Slide 87: Developing a Symptom Score for Front Line Indication
Developing a Symptom Score for Front Line Indication Leveraging Existing Instruments to Expedite WorkRespiratory Symptom ScoreQuality of Life- Bronchiectasis (QoL-B) Patient Reported Outcome (PRO) QuestionnaireFatigue Symptom ScorePROMIS-Fatigue Short Form 7a QuestionnaireIn general, FDA requires de
Slide 88: Developing a Symptom Score: Lessons Learned
Developing a Symptom Score for Front Line Indication Lessons Learned from Prior Drug Development ProgramsDescribing longitudinal properties of questionnaires / PROs is required by FDA, in generalGlobal Blood Therapeutics incorporated describing longitudinal properties into Phase 3 study (HOPE study)
Slide 89: ARIKAYCE EU Launch Update
Neil Hughes General Manager, Head of EMEAARIKAYCEEU Launch UpdateNot for promotional use 90
Slide 90: ARIKAYCE a Blueprint for Future Success
ARIKAYCE a Blueprint for Future Success2019 $136M net salesQ2 2020 $42.5MEngaged HCP & patient populationPositive reimbursement trends• Engaged healthcare providers• Educated patient population• Focus on payers to ensure reimbursementNot for promotional useARIKAYCE was one of the Top 10 most success
Slide 91: ARIKAYCE Added to International Treatment Guidelines
ARIKAYCE Added to International Treatment Guidelines for Treatment of MAC Lung DiseaseGuidelines are a globally recognized standard for the prevention, diagnosis and treatment of NTM lung diseaseAddition of ARIKAYCE to new standard treatment regimen for adult patients with limited or no treatment op
Slide 92: ARIKAYCE Added to International Treatment Guidelines
ARIKAYCE Added to International Treatment Guidelines for Treatment of MAC Lung DiseaseGuidelines are a globally recognized standard for the prevention, diagnosis and treatment of NTM lung diseaseAddition of ARIKAYCE to new standard treatment regimen for adult patients with limited or no treatment op
Slide 93: Commercial Approach: Meaningful Opportunity in Europe
Commercial Approach Meaningful Opportunity in EuropeUS~12K – 17K total refractory MAC patients (2019E)*~80K – 90K total diagnosed NTM patients (2019E)*EU5†~1,400 total refractory MAC patients (2018E)*~14K total diagnosed NTM patients (2018E)*Japan~15K – 18K total refractory MAC patients (2018E)*~125
Slide 94: ARIKAYCE Received Positive CHMP Opinion
ARIKAYCE Received Positive CHMP Opinion July 24, 2020Committee for Medicinal Products for Human Use (CHMP)of the European Medicines Agency has adopted a positive opinion recommending ARIKAYCE for the treatment of NTM lung infections caused by MAC in non- CF Patients with limited treatment optionsNot
Slide 95: Prevalence of NTM in EU May be Greater Than Previously Reported
Prevalence of NTM in EU May be Greater Than Previously Reported…while anticipated EU indication slightly wider than only refractory MACNot for promotional use 96
Slide 96: EU Launch Strategy
EU Launch StrategyStrong but Lean InfrastructureSupport value, pricing & accessInsmed launch readinessIdentify and improve NTM lung disease treatment ecosystemsSupport for patients and HCPs for ARIKAYCE initiationOperational Excellence Not for promotional use 97
Slide 97: Insmed Projected EMEA Country Footprint
Insmed Projected EMEA Country Footprint Specific Field Force Structures Reflect Country- Specific Patient Pathways and NTM Management ProtocolsCountry KeyRegional HQ – No Local Commercial OrgInsmed Commercial OrganizationUnder Review - Insmed vs DistributorCustomer facing FTEs grow as country reimbu
Slide 98: Insmed Projected EMEA Country Footprint
Insmed Projected EMEA Country Footprint Specific Field Force Structures Reflect Country- Specific Patient Pathways and NTM Management ProtocolsCountry KeyRegional HQ – No Local Commercial OrgInsmed Commercial OrganizationUnder Review - Insmed vs DistributorCustomer facing FTEs grow as country reimbu
Slide 99: Germany First Anticipated Launch & Largest European Market
Germany First Anticipated Launch & Largest European MarketFour “3-up” territories MSL, RDM & PSP nurse cover identical geography to allow for smooth collaboration between the different parts of the FieldOffice-based PulmonologistsSchleswig- 2 HolsteinMecklenburg- Western PomeraniaBremenHamburg2Lower
Slide 100: Analytics Enable Focused Commercialization Model in Germany
Analytics Enable Focused Commercialization Model in GermanyGeographic analysis based on:• Centers of Excellence• Areas of high NTM prevalence• Existing clinical experience with ARIKAYCESplit into priority focus areas and “white space”Not for promotional use101
Slide 101: ARIKAYCE Japan Launch Update
Roger Adsett Chief Operating OfficerARIKAYCEJapan Launch UpdateNot for promotional use10210
Slide 102: Commercial Approach: Expansion to Japan
Commercial Approach: Expansion to Japan
Slide 103: On Track for Anticipated Approval, Mid-Year 2021 Japan Launch
On Track for Anticipated Approval, Mid-Year 2021 Japan Launch2020 March +12 Months ~ 3 months Mid-Year 2021ARIKAYCEJNDA FilingJDNA Approval Price Negotiation Launch2020 June JNDA Approval ~ 3 months Mid-Year 2021Lamira NebulizerNotification Form submitted; considered approvedRequest for health insur
Slide 104: Cost Plus Approach for Japanese Pricing
“Cost Plus” Approach for Japanese PricingBase Price Premiums Foreign Price AdjustmentARIKAYCEBase price includes manufacturing/transfer price, SG&A, operating profit, distribution cost, consumption taxAdjustments include innovation premium, usefulness premium.Government may adjust to a range of 75-
Slide 105: Nuances of Japanese Market
Nuances of Japanese MarketPrescriptions are limited to two-week supply for the first year drug is on the marketCo-pay market: approved drugs reimbursed at fixed ratesPhysician offices would exclusively train patients on use of ARIKAYCE with Lamira deviceNot for promotional use106
Slide 106: Building a Strong Presence in Japan
Building a Strong Presence in Japan 28 People with Japanese AffiliateNot for promotional use107
Slide 107: Engaging Major Medical Associations
Engaging Major Medical AssociationsNot for promotional use108
Slide 108: Sales Territories in Japan
Sales Territories in Japan*Greater OsakaGreater TokyoWest;;;. 7 Reps EAST;;;;. 8 Reps*Jf approvedNot for promotional use 109
Slide 109: Financial Update & Closing Remarks
Sara Bonstein Chief Financial OfficerFinancial Update & Closing Remarks110
Slide 110: Pipeline
Pipeline ` PRECLINICAL PHASE 1 PHASE 2 PHASE 3 APPROVEDARIKAYCE® (Amikacin Liposome Inhalation Suspension)*Refractory NTM: M. avium complex (MAC)ARIKAYCE® (Amikacin Liposome Inhalation Suspension) Front Line Label ExpansionBrensocatib: DPP1 Inhibitor NCFBE Brensocatib: DPP1 Inhibitor Cystic Fibrosis
Slide 111: Financial Strength to Achieve Our Objectives
Financial Strength to Achieve Our Objectives$641.9M as of 6/30/20Cash and Cash Equivalents>3 Years as of 9/30/20101M* as of 6/30/20Estimated Cash RunwayCommon Shares Outstanding*Excludes stock options, unvested RSUs and shares underlying outstanding convertible notes112
Slide 112: Transformational Growth Strategy
Transformational Growth StrategyWorld Class TeamResearch & Development ExpertiseGlobal Commercial PresenceBusiness Development StrengthBrensocatib NCFBEPipeline TPIP Brensocatib expansionBrensocatib NCFBEARIKAYCE EU/Japan Front LineARIKAYCE EU/Japan Front LineARIKAYCE EU/Japan Front LineARIKAYCE Ref
Slide 113: Questions & Answers
Questions & Answers114114
Slide 114: Thank You
We are committed to bringing forth technologies and medicines in therapeutic areas with the greatest potential to make a difference in patients’ livesThank YouInvestor Relations investor.relations@insmed.com 646-351-0954115