Insmed Incorporated · NASDAQ:INSM
Insmed — Investor Day (May 2023)
146 slides from Insmed's investor day presentation, May 8, 2023
Slide 1: The Future of Rare at Insmed: Functional Genes, AI-Enhanced Proteins, Glowing Algae, and More
The Future of Rare at Insmed: Functional Genes, AI-Enhanced Proteins, Glowing Algae, and More 6
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation contains forward-looking statements that involve substantial risks and uncertainties. “Forward-looking statements,” as that term is defined in the Private Securities Litigation Reform Act of 1995, are statements that are not historical facts and involve a
Slide 3: Will Lewis, Chair and Chief Executive Officer
Will Lewis Chair and Chief Executive Officer 6
Slide 4: Insmed is Assembling the Key Pieces from Which All Successful Biotechnology Companies are Made
Insmed is Assembling the Key Pieces from Which All Successful Biotechnology Companies are Made Culture 6 Disciplined Business Development Research Engine Core Commercial Engine Commercial Engine: Global scale with ability to support business (Pillars 1 – 3) Research Engine: Technologies, platforms,
Slide 5: Accelerating the Transformation of Insmed
Accelerating the Transformation of Insmed 3 1 2 4 6 TPIP ARIKACE® Brensocatib Early-Stage Research
Slide 6: Near-term readouts for ARIKAYCE and brensocatib potentially unlock commercial value
Near-term readouts for ARIKAYCE and brensocatib potentially unlock the commercial value of these assets, steer the company towards profitability, and fund early-stage research Potential Addressable Patient Populations: Pillars 1 & 2 Refractory MAC lung disease All MAC Lung Disease + All Bronchiectas
Slide 7: Few Have Accomplished Our Proven Success at Each Stage of Drug Development
Few Have Accomplished Our Proven Success at Each Stage of Drug Development Research Clinical Regulatory Commercial ARIKAYCE developed in our labs TPIP developed in our labs Brensocatib diligence by research team Advanced ARIKAYCE through all stages Advanced brensocatib into pivotal Phase 3 Advanced
Slide 8: Our Drug Development is Focused on Having the Highest Impact to Patients
8 Our Drug Development is Focused on Having the Highest Impact to Patients Refractory MAC Lung Disease (Ref MAC) All MAC Lung Disease (All MAC) First-In- Disease First-In- Class Best-In- Class** Non-CF Bronchiectasis (NCFBE) Chronic Rhinosinusitis without Nasal Polyps (CRSsNP) Cystic Fibrosis (CF) H
Slide 9: Pillar 4 Aims to Bring First-in-Class & Best-in-Class Gene Therapies and Proteins
9 Pillar 4 Aims to Bring ‘First-in-Class’ & ‘Best-in-Class’ Gene Therapies and Therapeutic Proteins to Patients* First-In- Disease First-In- Class Best-In- Class** Duchenne Muscular Dystrophy1 (DMD) Stargardt Disease1 (STGD) Chronic Refractory Gout2 (CRG) Argininosuccinic Aciduria1 (ASA) Early-Stage
Slide 10: Our Principles for Business Development Have Guided How We Built our Pillar 4
Our Principles for Business Development Have Guided How We Built our Pillar 4 Potential for First- or Best-in-Class Therapies & Technologies Asymmetric Return Potential Low Up-Front Cost Success-Driven Milestones Consensus on the Final Decision Disciplined Business Development 10
Slide 11: Recent Acquisitions Potentially Position Us to Bring Gene Therapies and Proteins to Market Faster
Acquired DbD Platform Acquired RNA End Joining (REJ) Technology Recent Acquisitions Potentially Position Us to Bring Gene Therapies and Therapeutic Proteins to Market Faster and Cheaper 2022 2023 AlgaeneX Vertuis Deimmunized by Design (DbD) Began AI-protein engineering Acquired Next Generation Gene
Slide 12: Our Next-generation Gene Therapies Could Leapfrog Current Approaches
Our Next-generation Gene Therapies Could Leapfrog Current Approaches Inconsistency between batches and dose measurements Cannot target genes >4kbs 10 to 50-fold dose reduction Insmed’s Next Generation Gene Therapies CHALLENGES High doses – linked to adverse safety outcomes P O T E N T I A L B E N E
Slide 13: Deimmunized Therapeutic Proteins Could Overcome Immunogenicity and Cost Challenges
Deimmunized Therapeutic Proteins Could Overcome Immunogenicity and Cost Challenges Facing Biologics Reduced efficacy (49% of drugs) and safety (60%) due to Immunogencity1 Difficult and expensive to manufacture Innovative drugs with low immunogenicity Insmed’s Deimmunized Therapeutic Proteins 1 Wang
Slide 14: Brian Kaspar, PhD, Chief Scientific Officer
Brian Kaspar, PhD Chief Scientific Officer 10
Slide 15: Next-Generation Gene Therapy
Next-Generation Gene Therapy 10 World-leading expertise and differentiated approach in GTx
Slide 16: Gene Therapy Can Have a Truly Transformational Impact on Patients
Gene Therapy Can Have a Truly Transformational Impact on Patients, as Past Success Has Shown Spinal muscular atrophy (SMA): genetic neuromuscular disease affecting children Children born with SMA rarely reach the age of 2 Evelyn’s story: Now 7 ½ years post- treatment with gene therapy Evelyn, shown
Slide 17: 70+ Years of Biotech Experience
70+ Years of Biotech Experience T H E I N S M E D S A N D I E G O F O U N D I N G T E A M Former CEO and Co Founder of Celenex (acquired by Amicus) Investor & Board member of Advanced Cell Technology (ACTC) (acquired by Astellas) Investor & Board member of Cynvenio Founder and Managing Director - Tr
Slide 18: Insmed Is Uniquely Positioned To Address Challenges In GTx Landscape
Insmed Is Uniquely Positioned To Address Challenges In GTx Landscape With Game Changing, Novel, Proprietary Technologies Rare and debilitating genetic disorders with no effective treatment options Gap in expertise and experience bringing GTx programs to market Challenges in manufacturing at scale wi
Slide 19: Targeted Up-Front Investment And Focus On CMC, Quality, And Analytics
Insmed’s Targeted Up-Front Investment And Focus On CMC, Quality, And Analytics Designed to Ensure A Locked Commercial Process To Supply The Market with Control And Understanding Of The Product In House GMP QC Lab with 25 state-of-the-art assays to ensure quality and robust analytical understanding o
Slide 20: Insmed is Uniquely Positioned to Address Challenges in GTx Landscape
Insmed is Uniquely Positioned to Address Challenges in GT x Landscape with Game-Changing, Novel, Proprietary Technologies transduction requiring redosing Next Generation Gene Therapies HWighitDhosTesa, irngheeretnetd systemDicetolixviceitireys, low efficacy, and off-target Enhanced safety profile wi
Slide 21: Duchenne Muscular Dystrophy: John W. Day, M.D., PhD
Duchenne Muscular Dystrophy 10 John W. Day, M.D., PhD Professor of Neurology, Pediatrics, and Pathology Stanford University
Slide 22: Duchenne Muscular Dystrophy (DMD)
Duchenne Muscular Dystrophy (DMD) 10 Duchenne is caused by a genetic mutation that prevents the body from producing dystrophin, a protein that muscles need to work properly. Without dystrophin, muscle cells become damaged and weaken. Duchenne muscular dystrophy is inherited in an X-linked recessive
Slide 23: Targeted Delivery System To Circumvent Challenges Within The DMD Landscape
Insmed Has Developed A Targeted Delivery System To Circumvent Challenges Within The DMD Landscape Competitor High doses Inherent systemic toxicities Low efficacy Off-target transduction 10
Slide 24: Placeholder Slide for Dr. Day
[Placeholder Slide for Dr. Day] 10
Slide 25: Brian Kaspar, PhD, Chief Scientific Officer
Brian Kaspar, PhD Chief Scientific Officer 10
Slide 26: Targeted Delivery System To Circumvent Challenges Within The DMD Landscape
Insmed Has Developed A Targeted Delivery System To Circumvent Challenges Within The DMD Landscape High doses Inherent systemic toxicities Low efficacy Off-target transduction Next Generation Gene Therapies With Targeted Delivery 10 Enhanced safety profile with similar/better efficacy 10 to 50-fold r
Slide 27: Insmed's IT-Delivery of AAV9-GFP Shows Greatly Improved Muscle Targeting
Robust expression & tactical targeting Minimal expression & limited targeting No dose NovaRed immunostaining for GFP expression (Vector® HRP substrate) *Doses are expressed as total vector genomes administered per animal Intravenous (IV) Delivery Intrathecal (IT) Delivery 10 Insmed’s IT-Delivery of
Slide 28: IT Delivery Shows Enhanced Targeting Of Skeletal And Cardiac Muscles
Insmed’s IT Delivery Shows Enhanced Targeting Of Skeletal And Cardiac Muscles With Lower Liver Expression Relative To Systemic (IV) Delivery NovaRed immunostaining for GFP expression (Vector® HRP substrate) *Doses are expressed as total vector genomes administered per animal Intravenous (IV) Deliver
Slide 29: IT-Delivery Shows Efficient DNA Biodistribution in Skeletal And Cardiac Muscles
Insmed’s IT-Delivery Shows Efficient DNA Biodistribution in Skeletal And Cardiac Muscles O N E - T I M E I N T R A T H E C A L D E L I V E R Y P L A T F O R M : N H P A A V 9 - G F P d d P C R 10
Slide 30: Innovative Gene Construct (INS1201) Specifically Designed for DMD
Treatment involves a one-time administration of AAV9-Micro- Dystrophin in human DMD patients to replace missing dystrophin protein and promote muscle function Recombinant AAV9 Capsid Shell scAAV ITR shRNA SOD1 H1 Stuffer Sequence scAAV ITR The constructs contain unique promoter, enhancer, intron, an
Slide 31: Preclinical Proof of Concept Study of INS1201 ICV Injections
Preclinical Proof of Concept Study Intracerebroventricular (ICV) Injections of INS1201 ICV injection of INS1201 at P28 (postnatal day 28) in mdx mice Tissue analyzed for dystrophin expression and correction of histopathological DMD features at various time points The goal of this study is to evaluat
Slide 32: INS1201-Treated mdx Mice Show Improvement of Dystrophic Pathology (Gastrocnemius)
INS1201-Treated mdx Mice Demonstrate Substantial Improvement of Dystrophic Pathology in a Dose-Dependent Manner (Muscle: Gastrocnemius) 10
Slide 33: Reduced Fibrosis and Increased Fiber Size, Dystrophin Expression in up to 84% of cells
Reduced Fibrosis and Increased Fiber Size 10 Dystrophin Expression in up to 84% of cells INS1201-Treated mdx Mice Demonstrate Substantial Improvement of Dystrophic Pathology in a Dose-Dependent Manner (Muscle: Gastrocnemius)
Slide 34: INS1201 Improves Dystrophic Pathology (Tibialis Anterior)
INS1201 Treated mdx Mice Demonstrate Substantial Improvement of Dystrophic Pathology in a Dose-Dependent Manner (Muscle: Tibialis Anterior) 10
Slide 35: Dystrophin Expression in up to 89% of cells
Reduced Fibrosis and Increased Fiber Size Dystrophin Expression in up to 89% of cells INS1201-Treated mdx Mice Demonstrate Substantial Improvement of Dystrophic Pathology in a Dose-Dependent Manner 10 (Muscle: Tibialis Anterior)
Slide 36: INS1201 Improves Dystrophic Pathology (Diaphragm)
INS1201 Treated mdx Mice Demonstrate Substantial Improvement of Dystrophic Pathology in a Dose-Dependent Manner (Muscle: Diaphragm) 10
Slide 37: Dystrophin Expression in up to 81% of cells
Reduced Fibrosis and Increased Fiber Size Dystrophin Expression in up to 81% of cells INS1201-Treated mdx Mice Demonstrate Substantial Improvement of Dystrophic Pathology in a 10 Dose-Dependent Manner (Muscle: Diaphragm)
Slide 38: INS1201 Improves Dystrophic Pathology (EDL)
INS1201 Treated mdx Mice Demonstrate Substantial Improvement of Dystrophic Pathology in a Dose- Dependent Manner (Muscle: EDL) 10
Slide 39: Dystrophin Expression in up to 74% of cells
Reduced Fibrosis and Increased Fiber Size Dystrophin Expression in up to 74% of cells INS1201-Treated mdx Mice Demonstrate Substantial Improvement of Dystrophic Pathology in a Dose-Dependent Manner 10 (Muscle: EDL)
Slide 40: 10 To 50-fold Reduction In Dose Compared To Systemic Delivery In mdx Mouse
40 Consistent Functional & Histopathological Effects Observed Following Intrathecal Administration Of INS1201 With 10 To 50-fold Reduction In Dose Compared To Systemic Delivery In mdx Mouse High Dose Low Dose Relative Dose in mdx mouse (in Total vg) Mid Dose INS1201 Intrathecal Administration Sarept
Slide 41: Brief Study Design: ICV Injections of INS1201 in Wild Type Mice
41 Intracerebroventricular (ICV) Injections of INS1201 ICV injection of INS1201 at P28 (postnatal day 28) in wild type (C57BL/6J) mice Protocol Group Dosing Group Dose (total vg) Group 1 vehicle 0.0E+00 Group 2 Dose 1 8.0E+11 Group 3 Dose 2 4.0E+11 Group 4 Dose 3 2.0E+11 Group 5 Naïve/untreated 0.0E
Slide 42: INS1201 Mouse GLP Toxicology Study Shows Clean Safety Profile
42 INS1201 Mouse GLP Toxicology Study Shows Clean Safety Profile With No Off-Target Transduction Normal Body Weight Gain Normal Clinical Observations No Concerning Histopathology Associated With INS1201 Delivery Observed mono-nuclear cell infiltrates around blood vessels in the brain, associated wit
Slide 43: Muscle Biodistribution of INS1201 in 3-week GLP Toxicology Study
Muscle Biodistribution of INS1201 Demonstrates a Dose Response and Robust Muscle Targeting in 3-week GLP Toxicology Study in Wild Type Mice 43
Slide 44: Muscle Biodistribution of INS1201 in 6-week GLP Toxicology Study
Muscle Biodistribution of INS1201 Demonstrates a Dose Response and Robust Muscle Targeting in 6-week GLP Toxicology Study in Wild Type Mice 43
Slide 45: Muscle Biodistribution of INS1201 in 12-week GLP Toxicology Study
Muscle Biodistribution of INS1201 Demonstrates a Dose Response and Robust Muscle Targeting in 12-week GLP Toxicology Study in Wild Type Mice 43
Slide 46: INS1201 Demonstrates Durability Throughout Twelve Weeks and Heart Targeting
Muscle Biodistribution of INS1201 Demonstrates Durability Throughout Twelve Weeks and Effective Targeting of the Heart 43
Slide 47: Brief Study Design: IT Injections of INS1201 in NHP
Brief Study Design Intrathecal (IT) Injections of INS1201 IT injection of INS1201 in 10 NHP between 2-3 years Tissue analyzed at 21 days post treatment The overall goal of this study is to evaluate the Biodistribution of INS1201 in Non-Human Primates (NHP) Using GMP Produced Engineering Lot of INS12
Slide 48: Muscle Biodistribution of INS1201 in Non-Human Primates
Muscle Biodistribution of INS1201 Demonstrates a Dose Response and Robust Muscle Targeting in Non- Human Primates Normal Body Weight Gain Normal Clinical Observations No mortality or moribundity in any NHPs dosed with INS1201 Normal Blood Chemistry/Hematology 43
Slide 49: Brief Study Design: ICV Injections in Newborn mdx Mice
Brief Study Design Intracerebroventricular (ICV) Injections of INS1201 ICV injection of INS1201 at P1 (postnatal day 1) in mdx mice EDL muscle analyzed by physiology The overall goal of this study is to evaluate INS1201 efficacy in newborn mdx mice 43
Slide 50: Improvement in Muscle Physiology by Early Intervention in P1 mdx Mice
WT e9 0 1 le 15 e1 e1 ic 00 15 1.5 h Ve X+ 00 01 + MD X+ 0 X MD X+ MD MD 0 20 40 60 80 ) 1 C E / 0 1 C E ( s s e r t s C E f o % %EC Post/Pre ✱ 40 60 80 100 Eccentric Contraction Profile Contraction e s a e r c e D e c r o F % WT MDX + Vehicle MDX+001 1.5e11 MDX+001 5e10 MDX+001 5e9 Substantial Impr
Slide 51: Insmed Plans to Initiate a Clinical Trial for INS1201 in 2H2023
Recombinant AAV9 Capsid Shell scAAV ITR shRNA SOD1 H1 Stuffer Sequence scAAV ITR micro-dystrophin gene MHCK7 promoter 5’ ITR SV40 intron SV40 pol 3’ 43 y (A) signal ITR Insmed Plans to Initiate a Clinical Trial for INS1201 in 2H2023
Slide 52: Phase 1 Study of INS1201 in Male Toddlers with DMD
52 Insmed Will Initiate A Phase 1, Multicenter, Open-Label, Study to Investigate the Safety and Biodistribution of INS1201 in Male Toddlers for the Treatment of Duchenne Muscular Dystrophy Muscle Biopsy and Biomarker Data Expected To Be Available 1H2024 Screening Safety, Proof Of Concept Study (up t
Slide 53: Jessica Eisner, M.D.
Jessica Eisner, M.D. has over 20 years of leadership experience in regulated medical product development in both industry and the government. She has worked in multiple therapeutic areas including rare diseases, infectious diseases, cardiology, and oncology. Dr. Eisner’s previous positions include S
Slide 54: Insmed is Uniquely Positioned to Address Challenges in GTx Landscape
Insmed is Uniquely Positioned to Address Challenges in GTx Landscape with Game-Changing, Novel, Proprietary Technologies transduction High production costs with low yields Immunogenicity and inability to target diseases requiring redosing Next Generation Gene Therapies HWighitDhosTesa, irngheeretnet
Slide 55: RNA End Joining Technology: Value Proposition & Solution
Insmed is Uniquely Positioned to Address Challenges in GTx Landscape with Game-Changing, Novel, Proprietary Technologies Insmed Value Proposition & Solution RNA End Joining Technology (REJ) Unlocks new GTx market opportunities with no competition Large size gene delivery through traditional AAVs Ina
Slide 56: RNA End Joining Enables Treatment With Larger Mid-Dystrophin Variants
I N T R A M U S C U L A R D E L I V E R Y O F A A V 8 - R E J - M I D - D Y S T R O P H I N Novel RNA End Joining Technology Enables Treatment With Larger Mid- Dystrophin Variants AAV8-REJ-mid-dystrophin An ~8kb/253kDa truncated dystrophin; improved efficacy/functionality, particularly for cardiac f
Slide 57: Intrathecal Dual REJ-AAV9 Mid-Dystrophin Results in Widespread Gene Replacement
Intrathecal Dual REJ-AAV9 Mid-Dystrophin250kDa Results in Widespread Gene Replacement N E X T - G E N E R A T I O N D Y S T R O P H I N R E P L A C E M E N T Approach: Combination of two of Insmed’s key inventions: (1) Intrathecal AAV administration for widespread distribution and (2) RNA-end joinin
Slide 58: Full-Length Dystrophin Replacement With Triple REJ-AAV Approach
Full-Length Dystrophin Replacement With Triple REJ-AAV Approach T R I P L E R E J - A A V A P P R O A C H F O R U L T R A - L A R G E G E N E R E P L A C E M E N T Reconstitution of full length YFP from three vectors using REJ technology Three vector approach allows for ~12kb CDS 53
Slide 59: Full-Length Dystrophin Replacement With Triple REJ-AAV Approach
Full-Length Dystrophin Replacement With Triple REJ-AAV Approach T R I P L E R E J - A A V A P P R O A C H F O R U L T R A - L A R G E G E N E R E P L A C E M E N T Reconstitution of full length Dystrophin from three vectors using REJ technology Three vector approach allows for ~12kb CDS 53
Slide 60: Cure Duchenne: Michael G. Kelly, PhD
Cure Duchenne 53 Michael G. Kelly, PhD Chief Scientific Officer CureDuchenne
Slide 61: CureDuchenne Ventures
CureDuchenne Ventures was established to find, fund and de-risk innovative research programs, advance them to the clinic to accelerate the approval of life-changing treatments for all Duchenne/Becker patients. Early funder, substantial due diligence and de-risk projects to attract further investment
Slide 62: Supporting Innovation - Growing a Pipeline of Therapeutic Opportunities
Supporting Innovation - Growing a Pipeline of Therapeutic Opportunities Our investments are targeted and impactful: We invest with an emphasis on treatments that restore dystrophin in addition to approaches that provide a “stand-alone” benefit for Duchenne and Becker muscular dystrophy patients. “Co
Slide 63: Activating Private Capital & Public Markets
Activating Private Capital & Public Markets We've invested alongside many VC and biotech funds to drive innovation. New technologies targeting DNA/RNA have emerged that will dramatically impact many monogenetic diseases. The “next-generation” cell-penetrating muscle-targeted exon-skipping approach's
Slide 64: We Still Need Breakthroughs To Get Closer To Our Goal
We Still Need Breakthroughs To Get Closer To Our Goal Gaps and opportunities exist within the current gene therapy pipeline. Delivery & cost: improved muscle targeting for AAV and non-viral approaches. Lower AAV dose - reduce manufacturing burden & cost of goods and improve safety Gene size: larger
Slide 65: CureDuchenne Ventures/Insmed Meetings with Motus Bio & Vertuis Bio
CureDuchenne Ventures/Insmed 87 CD Ventures held separate meetings over the past few years with Motus Bio & Vertuis Bio. Vertuis Bio: utilized RNA end joining technology to deliver larger dystrophin transcripts - efficiently produced mid-length (ca. 8kb, 253 kDa) BMD constructs and full-length dystr
Slide 66: Brian Kaspar, PhD, Chief Scientific Officer
Brian Kaspar, PhD Chief Scientific Officer 87
Slide 67: Insmed is Uniquely Positioned to Address Challenges in GTx Landscape
High production costs with low yields Immunogenicity and inability to target diseases requiring redosing Insmed is Uniquely Positioned to Address Challenges in GTx Landscape with Game-Changing, Novel, Proprietary Technologies Next Generation Gene Therapies With Targeted HighDDeoslievs,einrhyerent sy
Slide 68: Lukas Bachmann, PhD, Director, Research
Lukas Bachmann, PhD Director, Research 87
Slide 69: RNA End Joining Technology: Value Proposition & Solution
Insmed is Uniquely Positioned to Address Challenges in GTx Landscape with Game-Changing, Novel, Proprietary Technologies Insmed Value Proposition & Solution Inability to treat diseases requiring delivery of large genes RNA End Joining Technology (REJ) 87 Unlocks new GTx market opportunities with no
Slide 70: Proprietary RNA-End Joining Technology Could Enable Large Gene Delivery Using AAV
Insmed’s Proprietary RNA-End Joining (REJ) Technology Could Enable Large Gene Delivery Using AAV O V E R C O M I N G T H E C A P A C I T Y C H A L L E N G E : A N R N A P L A T F O R M F O R N E X T G E N E R A T I O N G E N E T H E R A P Y CHALLENGE POTENTIAL SOLUTION Current challenge in AAV gene
Slide 71: REJ Platform Designed to Allow Two Vector Delivery Of Split Genes
Insmed’s Proprietary REJ Platform is Designed to Allow For Two Vector Delivery Of Split Genes With Efficient, Precise Reconstitution Of RNA While Maintaining Suppression Of Un-joined Protein Fragment Expression REJ Technology in Action: Gene can be split anywhere Split-gene is packaged in two AAVs;
Slide 72: REJ Platform Is ~15x More Efficient At Gene Reconstitution Than DNA Hybrid
Insmed’s Proprietary REJ Platform Is ~15x More Efficient At Gene Reconstitution Than DNA Hybrid Technology 1 2 3 120 100 80 60 40 20 0 -20 % YFP Signal relative to REJ RNA joining DNA hybrid vehicle Hybrid dual AAV RNA end joining 87
Slide 73: REJ Platform Produces High Levels of Functional Protein Across Tissue and Cell Types
Insmed’s Proprietary REJ Platform Produces High Levels of Functional Protein Across Tissue and Cell Types Systemic delivery Local delivery Liver Diaphragm Di Li Heart Skeletal Muscle Neurons Retinal Photoreceptors 87
Slide 74: REJ Platform Could Unlock Gene Therapy Whitespace
Insmed’s Proprietary REJ Platform Could Unlock Gene Therapy Whitespace Retinal Disease Respiratory Muscular/Cardiac Nervous System Other Systems REJ Platform is designed to enable delivery of large genes with AAV 87
Slide 75: Stargardt Disease overview
1 National Eye Institute. Stargardt Disease, Available at: https://www.nei.nih.gov/learn -about-eye-health/ eye-conditions-and-diseases/ stargardt -disease (Accessed: 31 March 2023) 2 https://doi.org/10.1167/iovs.0 9-3611 87 Caused by mutations in the ABCA4 gene - gene affects how body uses vitamin
Slide 76: Stargardt Disease: REJ Produces a Full Length Abca4 Protein in vitro
Stargardt Disease: REJ Produces a Full Length Abca4 Protein in vitro Experimental Setup A Full Length Abca4 by REJ 87 B
Slide 77: Stargardt Disease: REJ Produces a Full Length Abca4 Protein in vivo
Stargardt Disease: REJ Produces a Full Length Abca4 Protein in vivo S U B R E T I N A L D E L I V E R Y O F A A V 8 - R E J - A b c a 4 REJ dual AAV8 Abca4 generates (more than) physiological levels of Abca4 in photoreceptors when injected sub- retinally in the Stargardt’s Disease model mouse In con
Slide 78: Insmed Plans To Submit An IND For Stargardt Disease by the end of 2024
Insmed Plans To Submit An IND For The Treatment Of Stargardt Disease by the end of 2024 87
Slide 79: 10-Minute Intermission
10-Minute Intermission 87
Slide 80: Karl Griswold, PhD and Chris Bailey-Kellogg, PhD
Karl Griswold, PhD Executive Director, Biologics Research & NH Site Lead 87 Chris Bailey-Kellogg, PhD Executive Director, Computational Biology
Slide 81: Insmed is Uniquely Positioned to Address Challenges in GTx Landscape
High production costs with low yields Insmed is Uniquely Positioned to Address Challenges in GTx Landscape with Game-Changing, Novel, Proprietary Technologies Next Generation Gene Therapies With Targeted HighDDeoslievs,einrhyerent systemic toxicities, low efficacy, and off-target Enhtrancsedducsatif
Slide 82: Deimmunized by Design (DbD) Platform: Value Proposition & Solution
Insmed is Uniquely Positioned to Address Challenges in GTx Landscape with Game-Changing, Novel, Proprietary Technologies Immunogenicity Inability to target diseases requiring redosing Insmed Value Proposition & Solution Deimmunized by Design (DbD) platform 87 Redosable viral vectors Deimmunized biob
Slide 83: A Deep Bench of Multidisciplinary Scientists and Engineers Empower Insmed Research
Chris Bailey-Kellogg Executive Director, Computational Biology Karl Griswold Executive Director, Biologics Research Franziska Leifer Director, Biologics Research A Deep Bench of Multidisciplinary Scientists and Engineers Empower Insmed Research PhD, Computer & Information Science, Ohio State Univers
Slide 84: Transforming Immunogenic Biotherapies into Immunologically Stealthy Drugs
Transforming Potent but Immunogenic Biotherapies into High- Performance, Immunologically Stealthy Drugs proteases toxins mAbs non-mAb binding scaffolds viral vectors metabolic enzymes metabolic enzymes non-mAb binding scaffolds viral vectors mAbs proteases toxins Our proprietary Deimmunized by Desig
Slide 85: Immune Surveillance Can Undermine Biotherapeutic Efficacy
88 (Abbreviations: DC-dendritic cell; MHC-major histocompatibility complex; TCR-T cell receptor; BCR-B cell receptor, Ag-antigen) Immune Surveillance Can Undermine Biotherapeutic Efficacy C H A L L E N G E “Wild-type” Biotherapeutic DC BCR Naïve B cell Plasma cells Induced antidrug antibodies Neutra
Slide 86: Deleting T Cell Epitopes Blunts Development of Antidrug Antibodies
89 (Abbreviations: iDC-immature dendritic cell; mDC-mature dendritic cell; MHC-major histocompatibility complex; TCR-T cell receptor; BCR-B cell receptor, ADA-antidrug antibodies) Deleting T Cell Epitopes of Immunogenic Biotherapies Blunts Development of Antidrug Antibodies, Enabling Effective Redos
Slide 87: Deleting B Cell Epitopes Enables Treatment With Pre-Existing Antidrug Immunity
(Abbreviations: ADA-antidrug antibodies) Deleting B Cell Epitopes of Immunogenic Biotherapies Enables Effective Treatment in the Context of Pre-Existing Antidrug Immunity CHALLENGE “Wild-type” biotherapeutic Antibody-drug complex Pre-existing ADAs Neutralized biotherapeutic * * Pre-existing ADAs B c
Slide 88: Deimmunized by Design: An AI-driven Protein Engineering Platform
Deimmunized by Design® An AI-driven protein engineering platform designed to enable functional deimmunization of therapeutic proteins Machine learning methods learn models from prior data regarding protein function and immunogenicity AI methods map the complex design space of protein variants, balan
Slide 89: Deimmunized Lysostaphin for MRSA Infections
92 Deimmunized Lysostaphin for MRSA Infections 90 P R O O F O F P R I N C I P L E :
Slide 90: Transforming Potent but Immunogenic Biotherapies: Next-generation Anti-infectives
Transforming Potent but Immunogenic Biotherapies into High- Performance, Immunologically Stealthy Drugs proteases next-generation anti-infectives Our proprietary Deimmunized by Design® platform represents a unique technology for engineering safer and more effective biotherapeutic candidates, with re
Slide 91: Lysostaphin is a Potent Anti-Staphylococcal Agent, but Limited by Immunogenicity
Lysostaphin is a Potent Anti-Staphylococcal Agent, but its Clinical Potential is Limited by Immunogenicity Issues Rapid Bacterial Lysis Rapid onset of action and potent killing of S. aureus Effective against MSSA, MRSA, VISA, VRSA, LRSA, DRSA Synergy with other conventional antibiotics; re-sensitize
Slide 92: The DbD AI Design Platform has Generated LYT100
Radial Diffusion Screen In vitro potency assays Ex vivo PBMC Assays In vivo efficacy & immunogenicity Design Space Experiments Data Models Lysostaphin 96 The DbD AI Design Platform has Generated LYT100, a High- Performance, Deimmunized Antibiotic for MRSA Goal: T cell epitope deletion Blunt developm
Slide 93: LYT100 Evades Human T cell Surveillance
97 LYT100 Evades Human T cell Surveillance D E I M M U N I Z E D L Y S O S T A P H I N L Y T 1 0 0 S I L E N C E S H U M A N T C E L L A C T I VA T I O N Schematic of the Human PBMC Assay Human PBMC Assays Matched Antigen Expansion and Restimulation Donor DRB1* HLA Genotype Wild type lysostaphin act
Slide 94: LYT100 Dampens Antidrug Antibody Response
98 WT LST Antigen/Plasma LYT100 Antigen/Plasma LYT100 Dampens Antidrug Antibody (ADA) Response D E I M M U N I Z E D L Y S O S T A P H I N L Y T 1 0 0 D A M P E N S A N T I D R U G A N T I B O D Y R E S P O N S E S I N H U M A N I Z E D H L A T R A N S G E N I C M I C E DR4 mice express human MHC II
Slide 95: LYT100 Enables Efficacious Repeat Dosing for Recurrent MRSA Infections
99 LYT100 Enables Efficacious Repeat Dosing for Recurrent MRSA Infections Deimmunized LYT100 enables highly efficacious repeat dosing in humanized HLA transgenic mice 0 7 14 21 28 35 42 49 Days Science Advances (2020) Vol. 6, no. 36, eabb9011 Percent survival *** LYT100 (N=6) WT LST (N=10) MRSA Chal
Slide 96: Initial Studies Demonstrated Animal Proof-of-Concept for LYT100
Initial Studies Demonstrated Animal Proof-of-Concept for LYT100 T cell epitopes can be depleted while maintaining function T cell epitope deletion does lead to reduced antibody titers Reduced antibody titers do lead to improved efficacy Further data available in the following LYT100 publications: El
Slide 97: DbD Therapeutic Proteins Example: Uricase
DbD Therapeutic Proteins Example: Uricase 101 101
Slide 98: Transforming Potent But Immunogenic Biotherapies: Metabolic Enzymes
Transforming Potent But Immunogenic Biotherapies into High- Performance, Immunologically Stealthy Drugs metabolic enzymes rheumatology Our proprietary Deimmunized by Design® platform represents a unique technology for engineering safer and more effective biotherapeutic candidates, with relevance to
Slide 99: Pegloticase is a Marketed Protein Where Immunogenicity Limits its Utility
Pegloticase (a Pegylated Uricase) is an Example of a Marketed Therapeutic Protein Where Immunogenicity Limits its Utility Sources: Schlesinger. Semin Arthritis Rheum. 2020; Nyborg. PLoS One. 2016; Lipsky. Arthritis Res Ther. 2014; Horizon Therapeutics Press Release 3/1/23; Evaluate Pharma; Insmed ma
Slide 100: DbD AI Design Platform Generated Deimmunized Uricase Variants
Design Space Experiments Data Models uricase Ex vivo PBMC Assays Halo Screen 104 kinetics The DbD AI Design Platform has Generated High-Performance, Deimmunized Uricase Variants for Refractory Gout Goal: T cell epitope deletion Blunt development of ADAs in naïve subjects, enabling effective redosing
Slide 101: Round 1 Candidates Exhibit Wild Type or Better Activity
Reaction Velocity (arbitrary units) KM (µM) 43 ±2 700 ±100 40 ±2 600 ±70 34 ±1 470 ±60 30 ±1 400 ±50 28.0 ±0.5 350 ±20 Round 1 Candidates Exhibit Wild Type or Better Activity (Abbreviations: WT-wild type Krystexxa enzyme; v1/v2/v3/v4-deimmunized Krystexxa variants) 0 20 40 60 80 F U N C T I O N A L
Slide 102: Round 1 Candidates Evade Human T Cell Surveillance
Round 1 Candidates Evade Human T Cell Surveillance P R E L I M I N A R Y S T U D Y W I T H A S M A L L P A N E L O F H E A L T H Y H U M A N P B M C D O N O R S WT v1 v2 v3 v4 -2 0 2 4 6 8 Day 7 Expansion (- background) + 7 6 i K + 3 D C % Responder Threshold Day 7 Expansion (-background) %CD3+Ki67+
Slide 103: Peer-Reviewed Papers Demonstrate the Breadth of DbD Utility
Peer-Reviewed Papers Demonstrate the Breadth of DbD Utility for Engineering Deimmunized Biotherapies 107 P A R T I A L L I S T O F T E A M ’ S P E E R - R E V I E W E D P A P E R S O N P R O T E I N D E I M M U N I Z A T I O N B Y T C E L L E P I T O P E D E L E T I O N Salvat…Bailey-Kellogg, Griswo
Slide 104: We are Currently Deimmunizing Three Therapeutic Proteins in Parallel
Uricase Therapeutic protein 3 We are Currently Deimmunizing Three Therapeutic Proteins in Parallel and Have Additional Opportunities in Queue IND-enabling CMC & toxicology Design & engineering Iterative AI-driven library design and screening Candidate evaluation Detailed in vitro and in vivo analysi
Slide 105: Deimmunizing AAV Capsids for Gene Therapy
Deimmunizing AAV Capsids for Gene Therapy 109 109
Slide 106: Transforming Immunogenic Biotherapies: Viral Vectors and Gene Therapy
Transforming Potent but Immunogenic Biotherapies into High- Performance, Immunologically Stealthy Drugs viral vectors gene therapy Our proprietary Deimmunized by Design® platform represents a unique technology for engineering safer and more effective biotherapeutic candidates, with relevance to a br
Slide 107: Enabling Redosable AAV Gene Therapy Can Unlock New High Unmet Need Disease Targets
Enabling Redosable AAV Gene Therapy Can Unlock New High Unmet Need Disease Targets for Gene Therapy Diseases requiring high doses of transgene High doses of currently available AAV capsids entail significant safety risks Redosable gene therapy can enable doses to be spread out over time Diseases wit
Slide 108: Next-Gen DbD Viral Capsids for Multi-Dose Gene Therapy
#1 Delete CD4+ T cell epitopes from AAV capsids Enable repeat dosing of AAV- vectored gene therapies for AAV- naïve patients Next-Gen DbD Viral Capsids for Multi-Dose Gene Therapy P R I O R I T I Z E D E N G I N E E R I N G O B J E C T I V E S https://pubmed. ncbi. nl m. nih. gov/ 23596044/ #2 #2 De
Slide 109: AI-Driven AAV T Cell Epitope Depletion to Enable Repeat Dosing
AI-Driven AAV T Cell Epitope Depletion to Enable Repeat Dosing of Naïve Patients Each learn-map-design-test round employs multiple experimental screening cycles to select the fittest variants Results shown from first round’s experimental cycles Design Space Experiments Data Models AAV AAV Library ca
Slide 110: Capsids with Deimmunizing Mutations are Functionally Enriched Over Screening Cycles
Theoretical Plasmid Packaged Cycle 1 Cycle 2 Cycle 3 Cycle 4 Cycle 5 107 106 105 104 103 Max Sequence Diversity Screening Stringency Capsids with Combinations of Deimmunizing Mutations are Functionally Enriched Over Screening Cycles Cycle 114 Relative frequency Population-wide Sequence Diversity AAV
Slide 111: AI-Driven AAV B Cell Epitope Deletion to Enable Treatment of Seropositive Patients
AI-Driven AAV B Cell Epitope Deletion to Enable Treatment of Seropositive Patients Each learn-map-design-test round employs multiple experimental screening cycles to select the fittest variants Results shown from first round’s experimental cycles Design Space Experiments Data Models AAV Pre-incubate
Slide 112: Functional Screening Identifies Highly Fit, Antibody-Evading Capsids
116 Functional Screening Identifies Highly Fit, Antibody-Evading Capsids (Abbreviations: Nab-neutralizing antibody; WT-wild-type) Fitness, relative to wild-type * Iterative library selection yields highly- mutated individual capsids with up to 600- fold greater fitness (*) under NAb pressure that ne
Slide 113: Multiple Staged Programs Aim to Create Redosable AAV Gene Therapies
AAVi Other Serotypes AAVii Multiple Staged Programs Aim to Create Redosable AAV Gene Therapies for Diverse Indications and Patient Populations B cell epitope depleted capsids To enable dosing of gene therapy for seropositive patients T cell epitope depleted capsids To enable redosable gene therapy f
Slide 114: Franziska Leifer, PhD, Director, Biologics Research
Franziska Leifer, PhD Director, Biologics Research 118
Slide 115: Argininosuccinic Aciduria is Ideally Suited to Demonstrate Redosable Gene Therapy
119 Argininosuccinic Aciduria is Ideally Suited to Demonstrate the Expected Benefit of Redosable Gene Therapy As AAV capsid reengineering proceeds, we are developing therapeutic transgene constructs for target diseases to streamline later development Our hASL therapeutic transgene construct shows st
Slide 116: ASA Mice Recapitulate Human Disease
120 “ASA Mice” Recapitulate Human Disease 18 days old ASA mouse WT 15% residual argininosuccinate lyase (ASL) activity1 Hyperammonemia1 Elevation of urea cycle intermediates argininosuccinic acid and citrulline1 Abnormal hair patterning1 Severely stunted growth1 Dramatically shortened life span1 ASA
Slide 117: ASA AAV GTx Nearly Normalizes Metabolic Parameters of ASA Mice
121 WT pre-dose High 0 100 200 300 400 41.3 200.7 Plasma Citrulline (mole/L) 0 50 100 150 105.1 Plasma Argininosuccinic Acid (mole/L) Error bars = SEM WT pre-dose High 700 600 500 400 300 200 100 0 46.6 483.1 Whole blood Ammonia (mole/L) ** * **** ** 188.1 80.8 65.6 se se se Do Do Do d w Mi Lo *
Slide 118: ASA AAV GTx Results in Strong Survival and Growth Benefit
122 0 50 150 200 0 50 100 100 Age (Days) Survival (%) Vehicle median = 19 d ASA AAV GTx Results in Strong Survival and Growth Benefit in ASA Mice
Slide 119: ASA AAV GTx Results in Strong Survival and Growth Benefit
median = 106 d median = 124 d 0 50 0 50 100 100 150 200 Age (Days) Survival (%) High Dose (1e14 vg/kg, 7e11 vg/mouse) Mid Dose (5e13 vg/kg, 3.5e11 vg/mouse) Low Dose (1e13 vg/kg, 7e10 vg/mouse) Vehicle 25 75 100 0 10 20 50 Age (Days) Body Weight (g) vehicle median = 19 d Error bars = STDEV 123 ASA A
Slide 120: ASA AAV GTx Results in Strong Survival and Growth Benefit
ASA AAV GTx Results in Strong Survival and Growth Benefit in ASA Mice median = 106 d median = 124 d 0 50 0 50 100 100 150 200 Age (Days) Survival (%) High Dose (1e14 vg/kg, 7e11 vg/mouse) Mid Dose (5e13 vg/kg, 3.5e11 vg/mouse) Low Dose (1e13 vg/kg, 7e10 vg/mouse) Vehicle 25 75 100 0 10 20 50 Age (Da
Slide 121: ASA AAV GTx Shows Clinical Effect Lasting More Than 100 Days
ASA AAV GTx Shows Remarkable Clinical Effect Lasting More Than 100 Days in ASA Mice WT vehicle GTx HD WT GTx HD GTx LD 125 Video of 19-day-old ASA mice treated at birth Video of 100-day-old ASA mice treated at birth GTx HD = 3 dashes WT = clean tail vehicle = clean tail GTx HD = 1 dash GTx LD = 3 da
Slide 122: hASL Transgene Construct Shows Therapeutic Efficacy in a Mouse Model of ASA
This data provides strong support for the potential utility of AAV gene therapy in the treatment of ASA. Delivering the hASL transgene construct with a redosable deimmunized AAV capsid could lead to a durable and highly effective treatment for even the youngest ASA patients. A similar strategy could
Slide 123: DbD - Key Takeaways
DbD - Key Takeaways Immunogenicity is a major challenge with many biotherapeutics. Deimmunized by Design® is a proprietary AI-driven platform for reengineering immunogenic biotherapies into immunologically stealthy drugs. The platform has been validated preclinically with lysostaphin and several oth
Slide 124: Brian Kaspar, PhD, Chief Scientific Officer
Brian Kaspar, PhD Chief Scientific Officer 128
Slide 125: Insmed is Uniquely Positioned to Address Challenges in GTx Landscape
Insmed is Uniquely Positioned to Address Challenges in GTx Landscape with Game-Changing, Novel, Proprietary Technologies Next Generation Gene Therapies With Targeted HighDDeoslievs,einrhyerent systemic toxicities, low efficacy, and off-target Enhtrancsedducsatifoenty profile with similar/better effi
Slide 126: AlgaeneX: New, Proprietary Manufacturing Value Proposition
Insmed is Uniquely Positioned to Address Challenges in GTx Landscape with Game-Changing, Novel, Proprietary Technologies Insmed Value Proposition & Solution High production costs with low yields AlgaeneX New, Proprietary Manufacturing Lowest cost of goods for Insmed’s gene therapy portfolio Opportun
Slide 127: The Arduous Process of AAV Gene Therapy Manufacturing
The Arduous Process of AAV Gene Therapy Manufacturing Creating functional genes for specific disease targeting is extremely slow & expensive… 1 3 Development Create a gene construct for an appropriate disease target 2 Construction Production of AAV recombinant plasmid containing gene construct Stora
Slide 128: Anthony Berndt, PhD, Senior Scientist
Anthony Berndt, PhD Senior Scientist 132
Slide 129: The AlgaeneX Solution: Algae for Mass Gene Therapy Production
The AlgaeneX Solution: A L G A E F O R M A S S G E N E T H E R A P Y P R O D U C T I O N Algae Cell Production Potential future of GTx production Algae cells take ~11 hours to double one-time P O T E N T I A L B E N E F I T S Rapid scalability to larger volumes No transfection required Low productio
Slide 130: Use Simple Algae Cell For Mass Production
Use Simple Algae Cell For Mass Production O U R S O L U T I O N Microalgae have been successfully utilized to produce human recombinant proteins Transformation Inherent low cost of goods and capitalization costs Simple production process and fast growth rate AAV9-GFP Injection Overview of AAV9 produ
Slide 131: Minimum Necessary Components To Make An Infectious AAV
Minimum Necessary Components To Make An Infectious AAV ITR VP1 135 VP2 VP3 Viral coat proteins: VP1, VP2, VP3 Replication Factors: Rep78, Rep52 ITR-flanked gene (payload)
Slide 132: Insmed Has Successfully Expressed GFP Protein Using AlgaeneX
Insmed Has Successfully Expressed GFP Protein Using The AlgaeneX Next Generation Manufacturing Solution 136
Slide 133: Insmed Has Successfully Expressed AAV9 VP1, VP2, and VP3 Using AlgaeneX
Insmed Has Successfully Expressed AAV9 VP1, VP2, and VP3 Using The Algaenex Next Generation Manufacturing Solution A n t i - V P 1 / 2 / 3 a n t i b o d y o n a l g a e l y s a t e s 80 65 50 kDa VP1 137 VP2 VP3
Slide 134: Building A Differentiated, Next-Generation Production Platform And Genetic Tool Kit
Insmed Is Building A Differentiated, Next- Generation Production Platform And Genetic Tool Kit That is Intended to Allow For Low-Cost Cultivation While Maintaining High Yield Bright Field tdTomato Wild Type Random Integration (Bi-Directional, GFP& tdTomato) Site-directed (tdTomato reporter) Generati
Slide 135: Roger Adsett, Chief Operating Officer
Roger Adsett Chief Operating Officer 139
Slide 136: Insmed Strategically Positioned to Answer What's Next?
Insmed Strategically Positioned to Answer “What’s Next?” Potential ‘First-in- Disease’ or ‘Best-in- Disease’ Rare Disease Focus Faster to Market and Durable Revenue Potential First-in-Disease/Best-in-Disease medicines in areas of significant unmet need Solving key issues facing gene therapy – safety
Slide 137: Game-Changing Platform Technologies with Multiple Revenue Stream Opportunities
Game-Changing Platform Technologies with Multiple Revenue Stream Opportunities Unlocks GTx for diseases caused by large gene mutations Redosable viral vectors Biobetter versions of biologics with known immunogenicity issues Innovative drugs with low immunogenicity Potentially improved safety profile
Slide 138: Initial GTx INDs Targeting Potential First-in-Disease or Best-in-Disease
Initial GTx INDs Targeting Potential First-in-Disease or Best-in- Disease Duchenne Muscular Dystrophy (DMD) Stargardt Disease Source: cureduchenne.org Source: fightingblindness.org Argininosuccinic Aciduria (ASA) Source: gosh.nhs.uk 142
Slide 139: $1+B Potential Annual Market Opportunity for Newly Diagnosed Patients with DMD
$1+B Potential Annual Market Opportunity for Newly Diagnosed Patients with DMD Source: Insmed analysis based on published epi (2019) and UN population estimates (2022) 10,500-13,000 10,000-10,500 3,000-4,000 23,500-27,500 Estimated DMD Prevalence US EU4+UK Japan TOTAL (7 major markets) 400-600 300-4
Slide 140: Substantial Stargardt Disease Opportunity
Substantial Stargardt Disease Opportunity: Large Eligible Patient Pool Addressed with Potentially the Only Approved Gene Therapy 1 Runhart, et. al, Stargardt disease: monitoring incidence and diagnostic trends in the Netherlands using a nationwide disease registry, Acta Ophthalmol. 2022 Jun; 100(4):
Slide 141: GTx Redosing for Babies Born with ASA is a Paradigm Shift
GTx Redosing for Babies Born with ASA is a Paradigm Shift Towards Lifelong Gene Therapy 145 1 Based on prevalence of 1:70,000-218,000 newborns, and UN 2023 population estimate 2 Assuming median life expectancy of 50 years Estimated Argininosuccinic Aciduria Incidence1 Estimated Argininosuccinic Acid
Slide 142: Gene Therapies will Transform Patient Outcomes While Reducing Costs
0.9 2.1 2.8 3.0 3.5 Dec 2017) (SMA, May 2019) Luxturna (IRD, Zolgensma Zynteglo (TDT, Aug 2022) Skysona (CALD, Sep 2022) Hemgenix (Hem B, Nov 2022) Gene Therapies will Transform Patient Outcomes While Reducing Costs to Healthcare System US List Price (WAC) $ Million US prices for approved GTxs* anch
Slide 143: Anticipated Upcoming Milestones from Pillar 4
Anticipated Upcoming Milestones* from Pillar 4 S U B S E T O F P I L L A R 4 P I P E L I N E 1 Next Generation Gene Therapies 2 Deimmunized Therapeutic Protein Duchenne Muscular Dystrophy1 (DMD) Stargardt Disease1 (STGD) Chronic Refractory Gout2 (CRG) Argininosuccinic Aciduria1 (ASA) 2H 2023 2024 20
Slide 144: Key Takeaways
Key Takeaways First in Disease/Best in Disease medicines in areas of significant unmet need Focus on rare diseases, BLAs – ensures patient access under the IRA ≥ 6 INDs by end of 2025, with potentially shortened time from IND to approval Insmed strategically positioned for success 3 Potentially game
Slide 145: Infinite potential. One patient at a time.
Infinite potential. One patient at a time. 149
Slide 146: Upcoming milestones across brensocatib, ARIKAYCE, TPIP and early-stage research
Brensocatib ARIKAYCE TPIP Early-Stage Research 2023 2024 2025 Label Expansion ARISE topline ENCO readout enrollm RE ent comple tion Bronchiectasis ASPEN topline readout CRSsNP Ph2 trial initiation Pulmonary Hypertension associated with Interstitial Lung Diseases (PH-ILD) Interim dose titration & saf