Slide 1: Corporate Overview
© 2012, Insmed, Inc. All rights reserved. Corporate Overview Improving the Lives of Patients Battling Serious Orphan Lung Diseases Using Targeted Inhalation Therapies December, 2012
Slide 2: Safe Harbor Statement
Safe Harbor Statement This presentation contains forward-looking statements which are made pursuant to provisions of Section 21E of the Securities Exchange Act of 1934. Words, and variations of words, such as “intend”, “expect”, “will”, “anticipate”, “believe”, “continue”, “propose” and similar expr
Slide 3: Near Term Goal: Approval and Commercial Launch of ARIKACE in Europe and the US
Cystic Fibrosis Non-Tuberculous Mycobacteria (NTM) Lung Disease ARIKACE Being developed to treat rare lung infections in patients with limited options for treatment. Near Term Goal: The Approval and Commercial Launch of ARIKACE ® in Europe and the US § Life expectancy 37 years 1 § 30,000 US 2 § 35,0
Slide 4: Orphan Disease #1: Cystic Fibrosis Patients with Pseudomonas Lung Infections
Orphan Disease #1 Cystic Fibrosis (CF) Patients with Pseudomonas Lung Infections
Slide 5: Urgent Need for Therapies: Cystic Fibrosis - Fatal Genetic Disease
Urgent Need for Therapies With Better Efficacy, Safety and Durability Orphan Disease #1: Cystic Fibrosis - Fatal Genetic Disease § Life expectancy of 37 years 1 § No existing cure § Mucous buildup impairs lung function § 70% of adults have chronic infection due to Pseudomonas aeruginosa 1 § Infectio
Slide 6: Urgent Need for Therapies: Current Treatment Options
Urgent Need for Therapies With Better Efficacy, Safety and Durability Orphan Disease #1: Cystic Fibrosis - Current Treatment Options § Up to 3 hours per day of medications and treatments § Current inhaled antibiotics all require 2X or 3X / day dosing § Most common is ≈20 minutes each treatment § Res
Slide 7: Proprietary Formulation AND Delivery System
Proprietary Formulation AND Delivery System concentrates Amikacin antibiotic near bacteria w/ potential for: ü Improved Compliance ( first- ever 1X daily dosing via inhalation ) ü Increased Efficacy (concentrated at site of bacteria) ü Increased Durability of effect (benefits when off treatment) ü I
Slide 8: ARIKACE Achieves Access to Bacteria in Infected Tissues and Macrophages
Aerosol Delivery ( e Flow ® Nebulizer) ARIKACE: Achieves Access to Bacteria in Infected Tissues and Macrophages Conceptual diagram for illustration purposes only. Liposomal Formulation (DPPC and Cholesterol)
Slide 9: Gilead Cayston vs. Novartis TOBI: Both Show Decline In Lung Function
AZLI / TIS 28 Days AZLI / TIS 28 Days AZLI / TIS 28 Days Gilead Cayston vs. Novartis TOBI: Both Show Decline In Lung Function Source: 2010 North American CF Conference Poster 305 and Slide Presentation, 10/10. AZLI = Cayston; TIS = TOBI CF Phase 3 Gilead Sponsored Open Label Trial Results (ON) (OFF)
Slide 10: ARIKACE: Phase 2 Pooled Results: Pulmonary Function
§ ARIKACE demonstrated statistically significant and clinically meaningful improvement in pulmonary function throughout the 28-day treatment period. § Improvement was sustained through the off-treatment period. ARIKACE: Treatment of Pseudomonas Lung Infections in CF Phase 2 Pooled Results (560mg 1X
Slide 11: Demonstrated Sustained Efficacy of ARIKACE During and Between Multiple Cycles
Demonstrated Sustained Efficacy of ARIKACE During and Between Multiple Cycles of Therapy ARIKACE: Treatment of Pseudomonas Lung Infections in CF Open Label Extension (TR02-105): Durability of Response * Significance at end of treatment over 6 cycles ** Significance 56 days off-treatment over 6 cycle
Slide 12: ARIKACE: Phase 3 Study Design Europe and Canada
Screening Period Day -18 to Day -4 ARIKACE: Cystic Fibrosis Phase 3 Study Design Europe and Canada The registration trial for Europe is a comparator study vs. TOBI and will evaluate FEV 1 improvement at week 24 as the primary efficacy endpoint. R 28 Day Daily Dosing 28 Days Follow-Up 28 Days Off Inh
Slide 13: Orphan Disease #2: Non-TB Mycobacteria (NTM) Lung Infections
Orphan Disease #2 Non-TB Mycobacteria (NTM) Lung Infections § No approved treatments
Slide 14: Orphan Disease #2: Non-TB Mycobacteria (NTM) Lung Infections
Orphan Disease #2: Non-TB Mycobacteria (NTM) Lung Infections “Current treatment for NTM lung disease requires lengthy multi-drug regimens that can be poorly tolerated and have limited efficacy, especially in patients with severe disease or in those who have failed prior treatment attempts.” David E.
Slide 15: NTM Lung Infections - Debilitating and Wide Spread
Orphan Disease #2: Non-TB Mycobacteria (NTM) Lung Infections - Debilitating and Wide Spread 1 Incidence of TB from Center for Disease Control and Prevention Morbidity and Mortality Weekly Report (March, 2012). 2 Clarity Pharma Research, Patient Chart Study, 2012. 3 Adjemian et al. Prevalence of Pulm
Slide 16: NTM Lung Infections - Current Treatment Options
Orphan Disease #2: Non-TB Mycobacteria (NTM) Lung Infections - Current Treatment Options § No approved treatment; all treatments are off label § Off label treatments carry significant toxicities and limitations § Avg. 7.6 antibiotic courses/yr 1 § Chronic, debilitating, progressive § Lengthy, repeat
Slide 17: ARIKACE: Positioned to Become the First Drug Approved for NTM Lung Infections
ARIKACE: Positioned to Become the First Drug Approved for Non-TB Mycobacteria Lung Infections Conceptual diagram for illustration purposes only. 1. Study conducted by L. E. Bermudez at Oregon State University (data on file). (2010) ü ARIKACE once-daily treatment ü ARIKACE is taken up by lung macroph
Slide 18: ARIKACE: NTM Phase 2 Study Design: TR02-112
Abbreviations: CT - computed tomography. FEV 1 - forced expiratory volume in 1 second. NTM - non-TB mycobacterium. SGRQ - Saint George’s respiratory questionnaire. Screening Period Day -42 to Day -4 ARIKACE: Non-TB Mycobacteria Lung Infections Phase 2 Study Design: TR02-112 Primary Endpoints: Effica
Slide 19: Phase III Pivotal Trial Investigator Sites
Phase III Pivotal Trial Investigator Sites Are Laying the Groundwork for Strong Commercial Launch = Activated Investigator with Screened Patients (75) CLEAR-108 European Sites CLEAR-108 Canadian Sites
Slide 20: Manufacturing
Manufacturing § CGMP Facility § Currently 3-4 batches/month § 2+ years of stability on 25l capacity § 12-month extractables and leachables (E&L) study underway § Planned scale up program underway § Selection of 2nd source supplier progressing
Slide 21: Extensive Patent Coverage and Other Exclusive Arrangements
Insmed Has Extensive Patent Coverage and Other Exclusive Arrangements Protecting Composition, Use, and Delivery Of ARIKACE ARIKACE IP and Exclusivity § US Composition-of-matter patent, with an added 6 months of pediatric exclusivity, provides coverage through Feb 2029 § Additional global application
Slide 22: 2013 Is Focused On Advancing Our European Filing and Pre-Commercial Preparation
2013 2012 2013 Is Focused On Advancing Our European Filing and Pre-Commercial Preparation ü EU Phase III pivotal underway ü US Phase II NTM underway ü Senior Team build out ü $20M Hercules debt facility ü $25M+ capital raised § Plan to launch compassionate use program in NTM patients § Phase III piv
Slide 23: Management Has Extensive Experience with Anti-Infective Development
Management Has Extensive Experience with Anti-Infective Development, Regulatory, and Commercial
Slide 24: Strong Cash Position
Strong Cash Position Capital Structure and Key Figures Present Capital Structure (NASDAQ: INSM) § 33.9 million fully diluted shares: § 31.4 million common shares § 2.5 million options, restricted stock units, and warrants Balance Sheet § Cash of $91.9 million as of September 30, 2012 § $10M of debt
Slide 25: Thank You
© 2012, Insmed, Inc. All rights reserved. Thank You Improving the Lives of Patients Battling Serious Orphan Lung Diseases Using Targeted Inhalation Therapies www.INSMED.com
Slide 26: Appendix: Additional Clinical Data
Appendix Additional Clinical Data
Slide 27: Resistance
Resistance “ Most resistance to aminoglycosides is caused by bacterial inactivation by intracellular enzymes. Because of structural differences, amikacin is not inactivated by the common enzymes that inactivate gentamicin and tobramycin . Therefore, a large proportion of the gram-negative aerobes th
Slide 28: ARIKACE: Cystic Fibrosis Phase 2 Pooled Results
Weekly Safety Evaluation Assessments of PFT, CFU, Exacerbations, Time to Rescue Antibiotics, CFQ-R and PK ARIKACE: Cystic Fibrosis Phase 2 Pooled Results N = 64 Placebo (1.5% saline ) ARIKACE 280mg ARIKACE 560mg TR02-105* (Europe) The Phase 2 program was prospectively designed to analyze pooled coho
Slide 29: ARIKACE: TR02-105 - Patient Characteristics
No significant differences assessed by ANOVA for continuous variables, chi-square test for categorical variables 29 ARIKACE: TR02-105 - Patient Characteristics
Slide 30: Percent Change in FEV1 - ITT Phase II Study
ARIKACE 560 * 15.4% (16.5) 18.4% (21.3) 13.2% (15.3) 13.2% (16.2) 11.5% (16.4) 13.2% (24.3) ARIKACE 280 * 10.9% (10.6) 9.4% (12.6) 9.6% (12.5) 10.1% (12.8) 1.7% (9.0) 2.0% (8.6) Placebo * 0.6% (11.7) -3.2% (12.2) 1.8% (10.9) 2.2% (11.9) -0.3% (12.0) -4.4% (13.0) Visit Day * Mean (SD) Percent Change
Slide 31: Change in FEV1 (% predicted) - ITT Phase II Study
P=0.009 P=0.019 P=0.124 P=0.021 ARIKACE 560 * 12.9% (17.2) 15.8% (22.5) 10.5% (15.6) 11.0% (16.4) 8.6% (17.7) 13.8% (26.2) ARIKACE 280 * 10.8% (10.8) 9.2% (13.1) 9.4% (12.9) 9.6% (13.7) 1.6% (9.6) 1.8% (8.8) Placebo * -0.9% (10.7) -4.4% (11.3) 0.3% (9.9) 0.5% (10.5) 0.7% (9.6) -3.8% (13.5) Visit Day
Slide 32: 105&106 - Pooled Pulmonary Exacerbations
No significant differences assessed by ANOVA for continuous variables, chi-square test for categorical variables 32 105&106 - Pooled Pulmonary Exacerbations ≈560 mg Cohort
Slide 33: Prior Use of Inhalation Antibiotic: Relative Change FEV1
No significant differences assessed by ANOVA for continuous variables, chi-square test for categorical variables 33 Prior Use of Inhalation Antibiotic Relative Change FEV 1 (ml)
Slide 34: Results - Safety
No significant differences assessed by ANOVA for continuous variables, chi-square test for categorical variables 34 Results - Safety
Slide 35: ARIKACE: Phase 1/2 Clinical Research Program
ARIKACE: Cystic Fibrosis Phase 1/2 Clinical Research Program: N=208 § Scintigraphy study - normal volunteers: N = 6 § Phase I Single Dose: N = 24 § 2 Phase1b/2a, 14 Days Dosing Open Label Studies: N = 24 § 1 European Phase 2, 28 Days Dosing, Randomized, Placebo Comparative Study: N=64 § 1 US Phase 2
Slide 36: Phase 2 Pooled Results: Pulmonary Function
Day 7 Day 14 Day 21 Day 28 Day 56 ARIKACE 560 - Mean (Std Dev) 12.2% (14.9) 13.1% (19.7) 8.8% (15.8) 8.1% (16.1) 9.3% (20.3) Placebo - Mean (Std Dev) 1.0% (10.6) -1.9% (11.5) 0.7% (10.3) 1.1% (10.1) -3.2% (11.9) ARIKACE: Cystic Fibrosis Phase 2 Pooled Results: Pulmonary Function ARIKACE demonstrated
Slide 37: Phase 2 Pooled Results: Pulmonary Function by Baseline FEV1
ARIKACE * 9.2% (16.3) 10.1% (19.3) Placebo * 2.1% (11.7) -4.5% (13.1) ARIKACE * 5% (16.2) 7.5% (23.5) Placebo * -0.6% (6.6) -1% (9.6) ARIKACE: Cystic Fibrosis Phase 2 Pooled Results: Pulmonary Function * Mean (SD) ARIKACE 560 Placebo Visit Day Visit Day 560mg Cohort FEV 1 % >75% 560mg Cohort FEV 1 %
Slide 38: Phase 2 Pooled Results: Microbiology
Day 7 Day 14 Day 21 Day 28 Day 35 ARIKACE 560 - Mean (Std Dev) -1.294 (1.881) -1.413 (1.928) -1.789 (2.512) -1.536 (1.768) -1.523 (2.707) Placebo - Mean (Std Dev) 0.171 (1.447) -0.248 (1.370) -0.363 (1.183) -0.434 (1.170) -0.238 (1.098) ARIKACE: Cystic Fibrosis Phase 2 Pooled Results: Microbiology [
Slide 39: Phase 2 Pooled Results: Microbiology by Baseline FEV1
ARIKACE * -1.38 (1.9) -1.38 (2.08) -1.93 (2.67) -1.66 (1.77) -1.75 (2.71) Placebo * 0.37 (1.35) -0.01 (1.46) -0.3 (1.04) -0.4 (1.19) -0.26 (0.83) ARIKACE * -1.05 (1.91) -1.49 (1.52) -1.37 (2.1) -1.08 (1.82) -0.86 (2.76) Placebo * -0.27 (1.63) -0.76 (1.04) -0.49 (1.48) -0.52 (1.18) -0.19 (1.54) ARIKA
Slide 40: Phase Pooled Results: Safety Summary
ARIKACE: Cystic Fibrosis Phase 2 Pooled Results: Safety Summary Overall, ARIKACE 560 mg, administered once daily for 28 days is well-tolerated § No unexpected AEs were observed § There were no appreciable changes in acute tolerability § There was improvement in oxygen saturation § No significant dif
Slide 41: In Vitro Bactericidal Effect of ARIKACE
In Vitro Bactericidal Effect of ARIKACE On Mycobacterium Avium Complex 1 Summary § ARIKACE at 10 µg/ml and 4 µg/ml is active against intracellular Mycobacterium avium (MAC). Liposome by itself did not show any anti-mycobacterial activity. § ARIKACE at equivalent concentration to free amikacin (10 µg