Insmed Incorporated
INSMED Inc (Form: 8-K, Received: 07/19/2017 08:18:48)

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington D.C. 20549

 

FORM 8-K

 

CURRENT REPORT

PURSUANT TO SECTION 13 OR 15(d)

OF THE SECURITIES EXCHANGE ACT OF 1934

 

Date of Report (Date of Earliest Event Reported):  July 19, 2017

 

INSMED INCORPORATED

(Exact name of registrant as specified in its charter)

 

Virginia

 

000-30739

 

54-1972729

(State or other jurisdiction of
incorporation)

 

(Commission File Number)

 

(I.R.S. Employer Identification
No.)

 

10 Finderne Avenue, Building 10
Bridgewater, New Jersey

 

08807

(Address of principal executive offices)

 

(Zip Code)

 

Registrant’s telephone number, including area code: ( 908) 977-9900

 

Not Applicable

(Former name or former address, if changed since last report.)

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

 

o     Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

 

o     Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

 

o     Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

 

o     Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

 

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

 

Emerging growth company o

 

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.  o

 

 

 

 



 

Item 7.01.  Regulation FD Disclosure.

 

As previously announced, Insmed Incorporated (the “Company”) will host an Analyst and Investor Day in New York City on the date hereof, and a live webcast of the event will be available through the investor relations section of the Company’s website.  The slide presentation to be used by the Company during the Analyst and Investor Day is attached hereto as Exhibit 99.1 and incorporated herein by reference.

 

Item 9.01 Financial Statements and Exhibits.

 

(d)  Exhibits

 

Exhibit
No.

 

Description

 

 

 

99.1

 

Insmed Incorporated Analyst and Investor Day Presentation, dated July 19, 2017.

 

2



 

SIGNATURES

 

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

Dated: July 19, 2017

INSMED INCORPORATED

 

By:

/s/ Christine Pellizzari

 

Name:

Christine Pellizzari

 

Title:

General Counsel and Corporate Secretary

 

3



 

EXHIBIT INDEX

 

Exhibit
No.

 

Description

 

 

 

99.1

 

Insmed Incorporated Analyst and Investor Day Presentation, dated July 19, 2017.

 

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Exhibit 99.1

Welcome & Opening Remarks Will Lewis, President and Chief Executive Officer NTM and the Unmet Medical Need Dr. Kevin L. Winthrop, M.D., M.P.H. Professor, School of Public Health, Associate Professor, Departments of Infectious Diseases and Ophthalmology, Oregon Health & Science University Amikacin Liposome Inhalation Suspension (ALIS) as a Treatment for NTM Gina Eagle, M.D., Vice President, Clinical Development ALIS Market Opportunity and Commercialization Approach Roger Adsett, Chief Commercial Officer Understanding the NTM Patient Population Drayton Wise, General Manager - ALIS Disease Awareness and Patient Experience Colleen Silk, Senior Director, US Marketing - ALIS Patient Experience Rahul Bhatia, Senior Director, Commercial Strategy and Operations Voice of the Payer, Manufacturing, Future Opportunities and Conclusion Roger Adsett, Chief Commercial Officer Non-CF Bronchiectasis and the Unmet Medical Need Dr. Kevin L. Winthrop, M.D., M.P.H. INS1007: A Novel DPP1 Inhibitor with Potential in Anti-Inflammatory and Pulmonary Indications Eugene Sullivan, M.D., Chief Product Strategy Officer INS1007: Phase 2 Development Program Paul Streck, M.D., Chief Medical Officer Financials Paolo Tombesi, Chief Financial Officer Closing Remarks Will Lewis Question & Answer Session Break

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Insmed Analyst and Investor Day July 19, 2017

 


Safe Harbor Statement & Disclaimer This presentation contains forward-looking statements that are based on management’s current expectations regarding, among other things, the status, results and timing of our clinical trials and clinical data, the anticipated benefits of our product candidates, and the anticipated timing of regulatory submissions, and our receipt of required regulatory approvals for, and the marketing and commercialization of our product candidates. Actual results could differ materially from those projected in the forward-looking statements due to various risks and uncertainties, many of which are outside of our control. These factors include, without limitation, uncertainties in research and development related to our product candidates ALIS, or Amikacin Liposome Inhalation Suspension, INS1007, an oral reversible inhibitor of dipeptidyl peptidase, and INS1009, an inhaled treprostinil prodrug, including any delay or failure of clinical trials or other studies, the failure of clinical trial or other study results to meet expectations, or any delay in obtaining or failure to obtain approval of our product candidates from the U.S. Food and Drug Administration, European Medicines Agency or other applicable regulators; our ability to successfully commercialize our product candidates if they receive regulatory approval; competitive developments affecting our product candidates; patent disputes and other intellectual property developments relating to our product candidates; our ability to repay existing indebtedness and our need for additional financing; changes in anticipated expenses and estimates of future capital requirements, including milestone payments to AstraZeneca; the impact of litigation, such as the class action securities lawsuit against us and potential intellectual property disputes; and changes in laws and regulations affecting our business. For additional information about these and other risks and uncertainties related to our business, please see our annual report on Form 10-K for the year ended December 31, 2016 and subsequent quarterly reports on Form 10-Q, which were filed with the U.S. Securities and Exchange Commission. Investors are cautioned not to place undue reliance on any forward-looking statements herein, which speak only as of the date of this presentation. We undertake no obligation to update these forward-looking statements except as required by law. The drugs referenced in today’s presentations are investigational. Safety and efficacy have not been established. There is no guarantee that that any of these investigational drugs will be approved by the FDA or any other health authority. 2

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Welcome and Opening Remarks Will Lewis President and Chief Executive Officer

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The Cornerstones of Insmed’s Success MISSION To improve the lives of patients battling serious rare diseases VALUES Respect Passion Integrity Collaboration Accountability STRATEGY Growth International Additional products Financial responsibility • • • • • • • • • 4

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Current Efforts Underway • • CONVERT Phase 3 data – Top line results expected September +/-a month Non-branded disease education efforts for non-tuberculous mycobacteria (NTM) diagnosis and guideline based treatment • INS1007 expected to enter Phase 2 study in 2H 2017 - The Willow Study in Non-CF Bronchiectasis 5

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New Information Today • • • Amikacin Liposome Inhalation Suspension (ALIS) CONVERT Phase 3 study status ALIS market opportunity and commercialization approach • • • • • Sizing the addressable market Specifics of US sales force NTM cost burden Local understanding of the patient landscape New life cycle management opportunities in NTM • INS1007 • Willow Study Phase 2 design specifics • New talent 6

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NTMLUNGDISEASECAUSEDBY MYCOBACTERIAL AVIUM COMPLEX Unmet Medical Need Kevin L. Winthrop M.D., M.P.H. Associate Professor Divisions of Infectious Diseases, Public Health and Preventive Medicine Oregon Health and Science University

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Disclosures Consultant and/or research support: • • • • • • • • Bayer Insmed Raptor FDA NIH PCORI American NTMir Lung Association 8

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NTM Lung Disease Caused Complex (MAC) by Mycobacterial Avium • • • • • Epidemiology and disease overview Understanding the disease Identifying Treatment Treatment and treating patients – the guidelines clinical experience challenges and unmet needs 9

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What is NTM? • • NTM stands for non-tuberculous mycobacteria Environmental organisms - - - - soils, lakes, rivers municipal water (yes, including your tap at home) ability to form biofilms where water flows (live with amoeba, NTM are able to shield themselves within the airway biofilm cells like the macrophage legionella, other) as well as within certain • There are over 180 species of NTM, but the most common causing species is MAC or Mycobacterium avium complex Most common in US - M. avium complex (MAC), M. kansasii, M. abscessus lung infection-• 10

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NTM Lung Disease Overview US rate of NTM lung disease increased 1997-20071 Guidelines for treatment include therapies that have poor efficacy, safety, and adherence (i.e. macrolide, ethambutol, and rifampin)2 Refractory and cavitary patients often require IV aminoglycosides which • • • are known to cause ototoxicity, vestibular toxicity, and nephrotoxicity • Disease worsens quality of life and these patients have higher mortality 1. Adjemian, J, et.al, AJRCCM, 2012; 185:881-886 2. Griffith, DE, et.al, Am J Resp. & Crit Care Med, 2007;175:367-416 3. Mezochow, A, et.al IDSA, October 2016 Poster 11

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Prevalence of NTM Lung Disease is Rising Estimated prevalence of NTM lung disease in patients > 65 years in the USA*1 N T M P D 60 50 40 P R E V A L E N C E Increase in the annual estimated prevalence by 8.2% per year1 30 20 10 0 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 Over the last decades, an increase in the prevalence of NTM lung disease has also been observed worldwide2,3 *Based on Medicare records; NTMPD, non-tuberculous mycobacterial pulmonary disease. 1. Adapted from Adjemian J, et al. Am J Respir Crit Care Med 2012; 185:881-6; 2. Kendall BA, Winthrop KL. Semin Respir Crit Care Med 2013; 34:87-94; 3. Thomson RM, et al. Emerg Infect Dis 2010; 16:1576-83. 12 Estimated prevalence (Pop/100,000)

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Annual Age-and Sex-specific Incidence of Pulmonary NTM Disease in Oregon, 2007-2012 35.0 30.0 25.0 20.0 Males Females 15.0 10.0 5.0 0.0 0-49 50-59 60-69 70-79 80+ Age group (years) 13 Incidence per 100,000

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Why are the Rates of Increasing? NTM Lung Infections Improved quality of diagnostic methods e.g. microbiological detection techniques1 Aging population2,3 with an increase morbidities1 in the prevalence of COPD2 and other co-Increased disease awareness1 Further research on the epidemiology of NTM lung infections by international research collaborations is required4 COPD, chronic obstructive pulmonary disease; NTM, non-tuberculous mycobacteria. 1. McShane PJ, Glassroth J. Chest 2015; DOI:10.1378/chest.15-0458; 2. van Ingen J, et al. Int J Tuberc Lung Dis 2010; 14:1176-80; 3. Al-Houqani M, et al. Chest 2012; 141:190-7; 4. Ringshausen FC, et al. BMC Infect Dis 2013; 13: 231. 14

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Risk Factors for and Transmission of NTM Inhalation of NTM-laden aerosols from shower heads; hot tubs; heated pools Ingestion of soil or water1 followed by gastric Contamination of hospital water supplies and medical equipment2 Person-to-person transmission extremely rare CF, cystic fibrosis; NTM, non-tuberculous mycobacteria. 1. Falkinham JO, 3rd. J Appl Microbiol 2009; 107:356-67; 2. Johnson MM, Odell JA. J Thorac Dis 2014; 6:210-20; 15 Gastroesophageal reflux disease (GERD) has been indicated as a mediator of NTM pulmonary disease1 Swallowing of NTM reflux leading to aspiration into the lung Likely routes of infection

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Clinical Criteria May also have sputum production, fatigue, malaise, dyspnea, fever, hemoptysis, chest pain, weight loss Almost all patients have chronic or recurring cough Known underlying structural lung disease Variable and nonspecific symptoms 16 Griffith DE, et al. Am J Respir Crit Care Med 2007; 175:367-416.

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NTM Lung Disease can be Progressive If left untreated, MAC lung disease NTMPD can become a Ifclaenftruensutrlet ainteedx, tMenAsCivleuncgavditiasreyase can result in extensive lung destruction adnedsrteruscptiiroantoarynd respiratory failure2 failure2 cavitary lung lung disease1,2 progressive Decline in lung function among NTMPD patients (n=68)*3 • Mean reduction in FEV1 was 48 mL/year • Normal range = 28.4-35.6 mL/year Impaired health-related quality of life in patients with NTM lung disease is significantly associated in lung function4 with decline * Study from Taiwan (01/2000 – 04/2011). FEV1, forced expiratory volume in 1 sec; MAC, Mycobacterium avium complex; NTMPD, non-tuberculous mycobacterial pulmonary disease. 1. Weiss CH, Glassroth J. Expert Rev Respir Med 2012; 6:597-612; 2. Griffith DE, et al. Am J Respir Crit Care Med 2007; 175:367-416; 3. Lee MR, et al. PLoS One 2013; 8:e58214; 4. Mehta M, Marras TK. Respir Med 2011; 105:1718-25. 17

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I 19

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Treatment Guidelines • Treatment guidelines for patients with Mycobacterium avium complex (MAC) lung disease were published in 2007 by the American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) -based primarily on observational, small uncontrolled or non-comparative studies in patients with predominantly severe MAC disease or refractory to treatment (Griffith al. 2007) Many drugs used in the prolonged, multi-drug regimens are -expensive -poorly tolerated et • • Lack of evidence -expensive -poorly tolerated behind real life clinically-utilized treatment regimens 20 Ballarino et al. 2009.

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Treatment of MAC Pulmonary Disease • For most patients with nodular/bronchiectatic disease, regimen of a three-times-weekly - - - clarithromycin (1,000 mg) or azithromycin (500mg) rifampin (600 mg) ethambutol (25 mg/kg) is recommended • For patients with fibrocavitary MAC lung disease or severe nodular/bronchiectatic disease a daily regimen of - - - - clarithromycin (500–1,000 mg) or azithromycin(250 mg) rifampin (600 mg) or rifabutin (150–300 mg) ethambutol (15 mg/kg) consideration of three times-weekly amikacin or streptomycin early recommended in therapy is • Patients should be treated until culture negative on therapy -Generally 18-24 months of total therapy for 1 year 21

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Therapeutic Unmet Need • Efficacy -“cure” is unusual -relapse and reinfection is common (approx. Chest 2014 50% in 3 years) – Wallace & Griffith • Tolerability - - - high degree of non-serious adverse events often “lose” at least 1 drug during initial therapy serious adverse events (e.g. optic neuritis) 22

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Need Paradigm • First-line therapeutic for MDR -“Refractory” patients -all patients Can we shorten treatment? -tolerability New treatment strategies regimen • • - - suppressive post-treatment suppressive/preventive 23

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Summary • • NTM lung disease prevalence is increasing worldwide Patients typically have at least one additional lung disease, bronchiectasis or COPD (or both) NTM treatment guidelines are currently being rewritten, but based upon expert opinions and observational studies -Current multi drug regimens lack efficacy and have poor tolerability either • are primarily • If left untreated, MAC and worsen quality of There remains a high lung disease can progress, cause lung life unmet need for efficacious therapies destruction • * to be updated once new data is available. COPD, chronic obstructive pulmonary disease; MAC, Mycobacterium avium complex; NTMPD, non-tuberculous mycobacterial pulmonary disease 24

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ALIS Clinical Development Strategy Gina Eagle, MD Vice President, Clinical Development

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Overview of ALIS Clinical Development Strategy • • • Addressing an unmet medical need Leveraged insights from Phase 2 results to optimize CONVERT Phase 3 study for success Incorporated discussions with US Food and Drug Administration (FDA) to support accelerated path to potential approval in refractory population Building on the expected strength of CONVERT data to guide development in additional NTM indications • 26

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In vitro Susceptibilities to Amikacin for Slow-growing NTM For the slow-growing NTM, >89% of isolates for each slowly growing NTM species, and 92% of isolates for the slowly growing MAC NTM species, are susceptible to Amikacin 27

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Amikacin Liposome Inhalation Suspension (ALIS) • • • • Amikacin: established in vitro evidence against NTM Nebulized liposome particles directly target the lung Liposomes facilitate intra-cellular uptake by lung macrophages Low serum levels of amikacin reduce the potential for systemic toxicity 28

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Regulatory Landscape granted June 2014 *Dmitri Iarikov, MD PhD (Deputy Director, Division of Anti-infective Products) 29 FDA has granted multiple designations for ALIS in NTM lung disease •Orphan Indication Designation – granted March 2013 •Qualified Infectious Disease Product (QIDP) – granted June 2013 •Fast Track Status – granted June 2013 •Breakthrough Therapy Designation – FDA is “trying to facilitate the development of drugs to treat NTM lung disease” recognizing the increasing prevalence and that no drugs are currently approved* •Patient Focused Drug Development Workshop for NTM Lung Disease – October 2015 •Participation in Physician and Patient Conference* – May 2017 •Participation in International Society of Aerosols in Medicine – June 2017

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ALIS Development Program: Phase 12 Week Treatment Phase 2 Study 12 Week Treatment Phase 4 Week Off Treatment* R No Treatment Primary Endpoint: Efficacy • Change on Semi-Quantitative Scale for mycobacterial density at Day 84 • ALIS did not meet statistical significance for the primary efficacy endpoint although there was a positive trend (p=0.072) in favor of ALIS ALIS achieved key secondary endpoint for the proportion of patients with a negative sputum culture at Day 84 (p=0.003) ALIS achieved tertiary endpoint for 6MWT (p=0.01) In a post-hoc analysis, most patients on ALIS who achieved a negative sputum culture went on to achieve sputum culture conversion (3 consecutive negative sputum cultures) • • • Highest response in Phase 2 study observed in the subpopulation with non-CF MAC SOC: Standard of care according to guideline-based therapy; non-CF MAC = non-Cystic Fibrosis MAC *12-week off-treatment follow-up 30 Screening Period ALIS + SOC ALIS + SOC Follow-up Placebo + SOC

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Consistency of Beneficial Effect in Phase 2: Three Consecutive Negative Cultures in Non-CF MAC Sub-Population(“Culture Conversion” as Defined in Phase 3)* Percentage of patients who achieved three consecutive negative cultures at each time point (ITT population in Phase 2) 50% 40% 37.0 30% 20% 18.5 10% *The microbiologic outcomes from the 112 study were explored post hoc using a more stringent definition of culture conversion, which was defined as at least three consecutive monthly sputum samples that test negative for NTM, consistent with the definition of culture conversion in the guidelines and in clinical practice. 0% 0 28 56 84 112 140 Study Day Placebo n = 27 ALIS n = 27 31 Open-Label Phase ALIS + SOC 33.337.0 ALIS + SOC 11.1 3.7 Double-Blind Phase ALIS + SOC 25.9 14.8Placebo + SOC 3.73.7

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• 32 Phase 2 Safety Data • • Adverse events reported at >5% frequency in either arm.

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Phase 3 Study Design Based on Phase 2 Results Insmed discussed protocol with FDA for potential accelerated approval under Sub-part H for the primary endpoint of sputum culture conversion by Month 6 More homogeneous population based on subgroup of non-CF MAC that showed greatest efficacy signal Primary endpoint of culture conversion (three consecutive negative sputum cultures) 33 Key Elements

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Phase 3 INS212 CONVERT Study A Randomized, Open-Label, Multicenter Study of Amikacin Liposome Inhalation Suspension (ALIS) in Adult Patients with Nontuberculous Mycobacterial (NTM) Lung Disease caused by Mycobacterium avium complex (MAC) that are refractory to treatment • • Global 127 Clinical Trial Sites – – – – United States/Canada Europe/UK/Israel Australia/NZ Japan/South Korea/Thailand/Taiwan • • Full enrollment Q4 2016 Top-line Data expected in September 2017 +/-a month 34

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CONVERT Study Design Treatment Phase (Up to Month 16) Off Treatment Phase (Up to Month 28) Baseline Adult patients with Period longer than 12 6 Months on Treatment* Primary Endpoint: Percentage of Patients who Achieve Culture Conversion by 6 Months 3 Months off Treatment Efficacy Data Readouts Durability of Culture Conversion*** *All converters (at least 3 consecutive negative sputum cultures before and including Month 6 without relapse or recurrence) will remain in study for 12 months post first negative culture that defines culture conversion *All non-converters will be eligible to enter a separate Open-Label study. ** Patients who discontinued from the study for any reason prior to Month 12 will have a safety follow-up visit at Month 12 ***Final analysis at completion of study to support full potential approval will include sustainability of culture conversion and durability of conversion after three months off treatment for patients who convert 35 Population: MAC NTM Lung Disease that are refractory to treatment (>6 months treatment with last dose no months prior to screening) Screening End of Treatment End of Study ALIS QD + SOC 12-Month Off Treatment Follow-up R SOC 12-Month Off Treatment Follow-up

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CONVERT Study: Key Study Criteria • Amikacin-resistant (MIC>64mcg/mL) 36 Exclusion: •Patients with cystic fibrosis •Active pulmonary tuberculosis requiring treatment at screening •History of lung transplantation Inclusion: •Continually MAC+ on sputum culture while adhering to SOC for >6 months •Diagnosed with MAC NTM lung infection with evidence of underlying lung disease such as nodular bronchiectasis and/or fibrocavitary disease by chest CT •Willing to adhere to SOC regimen during the course of the study

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CONVERT Study: Key Study Endpoints for Potential Accelerated Approval* 1° Primary Efficacy Endpoint • Proportion of patients achieving culture conversion (three consecutive negative sputum cultures collected monthly) at Month 6 in the ALIS arm compared to multi-drug regimen alone 90% powered to show a 15% difference in treatment groups, assuming that 20% on ALIS will convert vs. 5% in SOC • 2° Key Secondary Endpoints • Change in 6MWT distance at Month 6 in the ALIS arm compared to multi-drug regimen alone Time to Culture Conversion Mean change from baseline at Month 6 in the SGRQ and ED-5Q • • *Final analysis at completion of study to support full potential approval will include sustainability of culture conversion and durability of conversion after three months off treatment for patients who convert SGRQ: St. George’s Respiratory Questionnaire 37

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CONVERT Study: Status • The last subject has exited Month 6 • Primary endpoint evaluated at Month 6 • Discontinuation rate slightly lower than expected • Based on original assumption of 25% • Data Monitoring Committee has met seven times to date • Recommend no changes to study conduct 38

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Phase 3 INS312 CONVERT Extension Study An Open-Label Safety Extension Study to a Multicenter Study of ALIS in Adult Patients with NTM Lung Disease Caused by MAC That are Refractory to Treatment • • Global 62 Clinical Trial Sites – – – – United States/Canada Europe/UK/Israel Australia/NZ Japan/South Korea/Thailand/Taiwan • Full enrollment expected in Q3 2017 39

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CONVERT Extension Study: Key Study Endpoints 1° Primary Safety Endpoint • To evaluate the long term safety and tolerability of ALIS in combination with standard multi-drug regimen 2° Key Secondary Efficacy Endpoints • • • • Proportion of patients achieving culture conversion at Month 6* and Month 12 Time to Culture Conversion Change in 6MWT distance at Month 6 Mean change from baseline at Month 6 in the SGRQ and ED-5Q *All available data for subjects completing Month 6 assessments 40

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Scenario Planning Around Topline Results* 02 Submission under but misses one or more secondary endpoints 04 The basis for Sub-part H approval is a surrogate endpoint (21 CFR 314.510) consistent with FDA guidance. The approval relies on the effect of the surrogate endpoint being reasonably likely to predict clinical benefit (durability of culture negativity after successful treatment) and the FDA’s concurrence on other aspects of the application (CMC, non-clinical, etc.). Specifically, the FDA takes into account the severity, rarity and/or prevalence of the condition. *Subject to the totality of the data; assumes tolerable safety profile 41 Achieves primary with less than 15% delta but misses all secondary endpoints Achieves primary with less than 15% delta03 Surrogate endpoint hit; Sub-part H Achieves primary but misses one or more secondary endpoints Achieves primary and secondary in line01 with assumptions

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Future Study Strategies: Focusing on MAC Disease Treatment Pathway Complete treatment Initiate multi-drug regimen Month 6 review Treatment Pathway for MAC Lung Disease Potential ALIS Label Indications in MAC Lung Disease 42 ALIS indicated as add-on treatment for non-converters after 6 months of multi-drug treatment ALIS as maintenance monotherapy to prevent relapse/reinfection ALIS as part of first-line multi-drug regimen ALIS as Frontline Rx ALIS as part of multi-drug regimen ALIS as monotherapy prevention Monitor for relapse/reinfection Converters continue treatment for 12 months of negative cultures

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Conclusions • • • ALIS has potential to address unmet medical needs in NTM lung disease CONVERT Phase 3 study optimized for success Positive data from CONVERT Phase 3 study may support accelerated path to potential approval in the refractory population Additional future opportunities for ALIS may include: • – – Front-line treatment Monotherapy maintenance to prevent recurrence 43

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ALIS Market Opportunity and Commercialization Approach Roger Adsett Chief Commercial Officer

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Discussion Topics • • Global addressable market for ALIS US market opportunity and go-to-market strategy • • • • • • Where do the NTM patients reside? Who is managing these patients for NTM? How are we going to reach the NTM treating healthcare providers (HCPs)? What is our approach towards disease education? How do we deliver upon a differentiated patient experience? Payer feedback • • Manufacturing capacity to fulfill anticipated global demand Life cycle possibilities 45

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US and Japan Account for Majority Addressable Market for ALIS of the Estimated Global Total Estimated NTM Patients by Country/Region 22 Source: Internal analysis of published NTM epidemiology, primary market research with treating HCPs, and anonymized patient level claims data in US 46 (2018E) ‘000s 125-1451 75-1051 Diagnosed NTM patients 1 161 61 21 221 Estimated Addressable Market (Treated MAC Patients) in 2018 ‘000s 60-70 40-50 Refractory MAC Patients 1st Line MAC Patients 45-50 ~10 30-35 10-15 15-20 ~5 ~2~1

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Refining the NTM MAC Opportunity in the US (2018 estimates) 250,000-300,0001 Patients w/ NTM Isolate Diagnosis Rate (30-35%)1 Patients w/ Diagnosed NTM Lung Disease 75,000-105,000 Rate of MAC NTMLD (~80%)2 Patients w/ NTMLD Caused by MAC 65,000-80,000 Treatment Rate (~60%)3 40,000-50,000 Patients w/ Treated NTMLD Caused by MAC “Refractory” Rate (25-30%)4 47 Patients w/ Non-responding NTMLD Caused by MAC 10,000-15,000

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Initial ALIS Opportunity in the US 250,000-300,0001 Diagnosis Rate (30-35%)1 75,000-105,000 Rate of MAC NTMLD (~80%)2 65,000-80,000 Treatment Rate (~60%)3 40,000-50,000 48 “Refractory” Rate (25-30%)4 Patients w/ Non-responding NTMLD Caused by MAC 10,000-15,000

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NTM Cases are Primarily Concentrated in Southeastern •• • Annual NTM Case Numbers c=J <500 c=J 500-1000 c=J 1001-2000 • and Coastal Regions 2001-3000 >3000 . . .. ... _.... ••• Source: Strollo,et al, The Burden of Pulmonary Nontuberculous Mycobacterial Disease in the United States, Ann Am Thorac Soc. 2015 Oct;12(10): 1458-1464 ilismed 49

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Understanding the Patient Population Drayton Wise General Manager - ALIS

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Robust Potential US Market Opportunity Triangulated Through Multiple Information Sources Pulmonologist & • Review of ~500 NTM Counties with 100+ NTM diagnosed patients Sources: Symphony Health, PatientSource™ January 2009 – March 2017; Primary Market Research 51 10,000-15,000 Refractory MAC Patients • ~ 1,000 Infectious Disease patient records Prevalence of NTM Lung Disease … • Donohue, et al, Increasing Prevalence Rate of NTM Infections … Published epidemiology research Analysis of 3 years of NTM patient level claims data Primary market and patient records research • Adjemian, et al,

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We Estimate That There are Two ‘NTM Likely’ Patients for Each Currently Diagnosed NTM Patient in the US Counties with 100+ ‘NTM Likely’ patients journey of NTM patients patients amongst national patient claims database (‘NTM Likely’ patients with a predictive likelihood score of 0.9 or above) Source: Symphony Health, PatientSource™ January 2005 – March 2017 52 Predictive modeling to identify ‘NTM Likely’ patients 1Machine learning based on profile and diagnosis 2Look-alike modeling to identify ‘NTM Likely’

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Local Market Execution of National Strategy is Key to Success Hillsborough County, FL Los Angeles County, CA NTM Diagnosed NTM Likely 1.5% 1.5% % of Total US Diagnosed Patients (approx.) 1:1 4:1 Ratio of ‘NTM-Likely’ to Diagnosed Patients ~70 HCP Targets IDN dominated market (e.g. Kaiser) ~100 HCP Targets Primarily driven by individual and group practices NTM Treatment Dynamics Source: Symphony Health, PatientSource™ January 2005 – March 2017 53

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NTM Treatment is Concentrated Among Providers • ~5K physicians manage 70% of NTM patients 8 in 10 diagnosed NTM patients managed by Pulmonologist or Infectious Disease Specialist 52% of HCPs considered themselves “aggressive treaters” • • Cumulative % of Physicians Source: Symphony Health, PatientSource™ November 2013 – October 2016 54 Cumulative % of Patients Attributed ~11.5K HCPs account for ~30% of potential ~3K HCPs account for ~20% of potential ~2.1K HCPs account for ~50% of potential

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Targeted US Go-to-Market Approach Designed Launch Success to Maximize • • • Targeted go-to-market approach with 70-75 sales representatives Vice President of US Sales hired Core requirements for sales representatives: • • • • • • Scientific aptitude Orphan Pulmonary and Infectious Disease experience Launch experience Business acumen Integrity Patient-centered 55

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Disease Awareness and Patient Experience Colleen Silk Senior Director, US Marketing - ALIS

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Patients’ Journey to NTM Diagnosis is Challenging The symptoms of NTM pulmonary disease are variable and nonspecific…Physical findings are nonspecific and reflect underlying pulmonary pathology, such as bronchiectasis and COPD - ATS/IDSA Statement on NTM 85% have a pre-existing lung condition at time of NTM diagnosis 45% have 3+ symptoms at time of NTM diagnosis 51% of patients have 2 years or more from 1st symptom to NTM diagnosis Sources: Symphony Health, PatientSource™ January 2009 – March 2017; Primary Market Research 57 “It went on for 2 years, and I felt I was partly to blame; I let it go on so long. I thought it was just a chronic nuisance... I had no idea what [NTM] was.” - Gayle [My NTM] was misdiagnosed for at least two years as asthma.-Lavinia I dismissed coughing and being tired as part of my normal world. - Jan

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Helping NTM Patients to Diagnosis through Disease Awareness “1,000 Words about NTM” NTMFacts.com Healthcare Professional Disease Awareness Campaign: Educate on the importance of timely NTM diagnosis Communicate the importance of guideline-based treatment for NTM lung disease • • “Over & Over” AboutNTM.com + Patient Disease Awareness Campaign: Educate patients on signs and symptoms of NTM Empower ‘NTM-susceptible’ patients to seek information on NTM lung disease and provide resources for productive conversations with a healthcare professional • • 58

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Patient Disease Awareness Activities Designed to Engage ‘NTM-Likely’ Patients gardening, swimming, traveling 59 Campaign Target Profile: •Age 65+ •Majority female •Diagnosed with one or more respiratory conditions: i.e. bronchiectasis, COPD, asthma •Suffering from one or more symptoms: Fatigue, cough, shortness of breath, weight loss, fever •Has an active lifestyle – hiking, Geo targeting top ten states with ‘NTM-Likely’ patients Maximize paid search Health & lifestyle combination Pilot opportunities that align with media consumption trends

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Patient Experience Rahul Bhatia Senior Director, Commercial Strategy & Operations

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Designing a Patient Support Program from a Patient’s Perspective As a non-responding NTM patient, I have … …. not achieved success in getting rid of my NTM lung disease … been on a long journey, before I got the right diagnosis (NTM), and found the right specialist …. limited income, since I retired …. a strong desire to return to my active lifestyle, that has been hampered by my incurable NTM disease 61

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Appropriate Patient Patient Needs Support Aligned to Approved Label and What to expect? (Physician office) Treatment initiation (Patient’s home) Patient off-boarding Ongoing reinforcement and adherence support Payer reimbursement & financial assistance 62

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Plan to Deliver a Differentiated Patient Experience Insmed ownership of patient interface, with back-office support from our partners Simple, flawless execution In-depth understanding of NTM patient journey Collaboration with NTM patients Predictive analytics with real-time view of each patient’s treatment status 63

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Collaboration with Patients to Create Convenient Innovative Packaging and Packaging design incorporated “voice of patient” and revealed key considerations for ALIS packaging Storage and Distribution Head 64 Tracking ProgressTravel and Mobility Replacing Aerosol Instructional MaterialsEnvironmental Concerns

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Voice of the Payer, Manufacturing, Future Opportunities and Conclusion Roger Adsett Chief Commercial Officer

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Payer Voice Source: Insmed Data on File: September 2016 Payer in-depth interviews (n=20); and April 2017 HEOR Advisors Panel (n=9) Combined organizations represent >150,000,000 lives covered 66 “CONVERT Study:Focus on Efficacy” “Do not anticipate overly restrictive management of ALIS utilization” “Interested in highest unmet need NTM Lung Disease (NTMLD) subgroups”

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First-Year Insurance/Payer Spending in NTMLD and Patient Groups of COPD, IPF, PAH, and Lung Cancer without NTMLD $48,169 $44,313 $22,901 $51,753 $69,005 COPD IPF PAH Lung Cancer NTMLD *Cost burden is calculated as first-year insurance spending after NTMLD diagnosis between 2008 and 2013, and standardized using RBRVS (Resource Based Relative Value Scale) from an U.S. national managed care claims database. Calculation is subject to sample fluctuation due to small patient numbers in subgroups. PAH = pulmonary arterial hypertension, IPF = Idiopathic pulmonary fibrosis 67 Year 1

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Burden* Payer Value Framework – First Year Payer Cost in Patient Subgroups $211,096 $80,486 $91,599 $55,120 $69,005 $51,753 $22,901 $44,313 *Cost burden is calculated as first-year insurance spending after NTMLD diagnosis between 2008 and 2013, and standardized using RBRVS (Resource Based Relative Value Scale) from an U.S. national managed care claims database. Calculation is subject to sample fluctuation due to small patient numbers in subgroups. PAH = pulmonary arterial hypertension, IPF = Idiopathic pulmonary fibrosis 68 In Lung Cancer:In PAH: Nearly Nearly 1.2X with1.8X with NTMLDNTMLD In COPD: Nearly 2.4X with NTMLD In IPF: Nearly 4.8X with NTMLD NTMLD Economic Burden IPF COPD PAH Lung Cancer NTM Lung Cancer NTM IPF NTM PAH NTM COPD

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Payer Value Framework for Urgency of Decision Up to 33% years of diagnosis² Disease Severity/ Unmet Need ¹ 2017 US national managed care insurance claims database (Insmed Data on File); ²Marras, TK, Pulmonary Nontuberculous Mycobacteria–Associated Deaths, Ontario, Canada, 2001–2013 Emerging Infectious Diseases, Vol. 23, No. 3, March 2017 69 of MAC patients die within 5 2XNTMLD risk of all cause mortality ¹ 5.1 yearsMean health plan enrollment¹ NTMLD Clinical Burden >80%Rate of background pulmonary disease1

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Supply Chain in Place for Commercial Requirements Multi-sourced drug supply chain for ALIS Expanding commercial-scale manufacturing capabilities 70 50L 200L

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Initial ALIS Opportunity 250,000-300,0001 Diagnosis Rate (30-35%)1 75,000-105,000 Rate of MAC NTMLD (~80%)2 65,000-80,000 Treatment Rate (~60%)3 40,000-50,000 71 “Refractory” Rate (25-30%)4 Patients w/ Non-responding NTMLD Caused by MAC 10,000-15,000

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Tip of the Iceberg: Unmet Needs Present Potential Life-cycle Opportunities to Conduct Additional Clinical Trials Potential Initial Indication 40,000-50,000 Patients w/ Treated NTMLD Caused by MAC Potential First Line Therapy Patients w/ NTMLD Caused by MAC 65,000-80,000 Patients w/ Diagnosed NTM Lung Disease (basis for orphan designation) 75,000-105,000 Patients w/ NTM Isolate 250,000-300,000 72 10,000-15,000 Patients w/ Non-responding NTMLD Caused by MAC

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Tip of the Iceberg: Unmet Needs Present Potential Life-cycle Opportunities to Conduct Additional Clinical Trials Initial Indication 40,000-50,000 Patients w/ treated NTMLD Caused by MAC First Line Therapy Patients w/ NTMLD Caused by MAC M. Abscessus; Increased Diagnosis 65,000-80,000 Patients w/ Diagnosed NTM Lung Disease (basis for orphan designation) 75,000-105,000 Patients w/ NTM Isolate 250,000-300,000 73 10,000-15,000 Patients w/ Non-responding NTMLD Caused by MAC

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Tip of the Iceberg: Unmet Needs Present Potential Life-cycle Opportunities to Conduct Additional Clinical Trials Patients w/ Non-responding NTMLD Caused by MAC Initial Indication 10,000-15,000 40,000-50,000 Patients w/ treated NTMLD Caused by MAC First Line Therapy Patients w/ NTMLD Caused by MAC M. Abscessus; Increased Diagnosis 65,000-80,000 Patients w/ Diagnosed NTM Lung Disease (basis for orphan designation) 75,000-105,000 Patients w/ NTM Isolate 250,000-300,000 74 Potential Maintenance Therapy

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Potential Maintenance Therapy: Prevention of Re-infection Month 0 Initiate multi-drug regimen By Month 6 Month 6 review By Month 18 Complete treatment Converters continue treatment for 12 months of negative cultures Chronic Use 3x Week 75 Potential New Indication Potential ALIS Maintenance Monotherapy to Prevent Re-infection ALIS as Part of Multi-drug Regimen Current Treatment Pathway for NTM MAC Lung Disease

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Commercial Readiness to Support Global ALIS Launches Germany, UK, France and Italy efforts underway 76 Launch Readiness • Commercial HQ leadership and teams already in place • Disease state awareness efforts underway • Go-to-market strategy and field territories defined • Account directors, field sales and patient services expected in role post 212 CONVERT trial results • Insmed KK entity expected to be formed and General Manager in role post 212 CONVERT trial results • EU commercial leadership and country managers in role • Disease state awareness

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References US 1. A) Adjemian, et al, Prevalence of Nontuberculous Mycobacterial Lung Disease in U.S. Medicare Beneficiaries, AJRCCM, Vol 185, Apr 15, 2012 B) Strollo, et al, The burden of pulmonary nontuberculous mycobacterial disease in the United States, Ann Am Thorac Soc Vol 12, No 10, pp 1459-1464, Oct 2015 C) NTM Lookalike Predictive Patient Level Modeling based on Symphony Anonymous Patient Level Data Adjemian, et al, Lack of adherence to evidence-based treatment guidelines for non tuberculous mycobacterial lung disease, Annals of the American Thoracic Society, Vol 11, No 1, January 2014 A) Adjemian, et al, Lack of adherence to evidence-based treatment guidelines for non tuberculous mycobacterial lung disease, Annals of the American Thoracic Society, Vol 11, No 1, January 2014 B) Insmed Market Research A) Adjemian, et al, Lack of adherence to evidence-based treatment guidelines for non tuberculous mycobacterial lung disease, Annals of the American Thoracic Society, Vol 11, No 1, January 2014 B) Insmed Market Research 2. 3. 4. Japan 1.Morimoto, et al, A steady increase in nontuberculous mycobacteriosis mortality and estimated prevalence in Japan, Ann Am Thorac Soc. 2014 Jan;11(1):1-8. doi: 10.1513/AnnalsATS.201303-067OC South Korea 1.Lee, et al, Changing epidemiology of nontuberculous mycobacterial lung disease in South Korea, Scandinavian Journal of Infectious Diseases, Volume 44, 2012 - Issue 10 EU 1.Ringshausen, et al, Prevalence of Nontuberculous Mycobacterial Pulmonary Disease, Germany, 2009 –2014, European Respiratory Journal 2014 44: P1067; DOI Canada 1.Marras, et al, Pulmonary Nontuberculous Mycobacterial Disease, Ontario, Canada, 1998–2010, Emerg Infect Dis. 2013 Nov; 19(11): 1889–1891 Australia 1.Thomson, et al, Changing Epidemiology of Pulmonary Nontuberculous Mycobacteria Infections, Emerg Infect Dis. 2010 Oct; 16(10): 1576–1583 77

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Break • • il\Smed

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Infectious Complications of Non-cystic Fibrosis Bronchiectasis Kevin L. Winthrop M.D., M.P.H. Associate Professor Divisions of Infectious Diseases, Public Health and Preventive Medicine Oregon Health and Science University

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Disclosures • Consultant and/or research support: Bayer Insmed Raptor FDA NIH PCORI American NTMir Lung Association 80

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Non-CF Bronchiectasis • • • • Pathophysiology Epidemiology Patient experience and current treatments Need for treatments 81

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I What is Bronchiectasis Eu r J Resir D.is 1 9&6: 69 (Su ppl 1 47): 6-15 Ch ronic bronchial sepsis, or which brouhiectasis is an example, and chronic sinusi tis di play infotmfllion a bout c he palhogenesis or chronic inllammatory disease: or the luog. 82 Inflammation: a two-edged sword-the model of bronchiectasis P. J. COLE Host Defence Unit, Depa nmenl of Thoracic Medicine, Cardiothoracic 1ns• i tute. Brompton Hospicnl, London. UK Abstract: A short-lived, controlled inflammatory respn nse by t he host is req uired to pl'olect against incursio ns by foreign malcrial into the upper and lower respi ratory tract. If this response fails l.o elimina te t he aggpesso r, inftammalion is am plified and becomes ch ron ic in a n a uempl to rectify the sit ua tion. This unsucc-essful response is poorly cont rolled and causes damage lo surrounding normal tissue, leadi ng to progressi ve disease. Hence, i nflammation can be helpful or harmful-a. lWO-<:<Iged sword. t he ha llma rks or this 'v icious ci rcle' of host-mediated.inRammatory t issue damage a nd provide a usef1.1l model in ma n i n which l o ask questions, lhe a nswers lO wnich pi'Ovide val ua ble Key u•o,·d.,·: broncl1iectasis - i nfla mma t i on - vicious circle hypothesis

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I What is Bronchiectasis Increased mucus Deslruclion of wall Normal Bronchus Broncnlectasls l:ormal 7lc:lindrical Cystic Varicose 83 _f( _}-f( !1; 4

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Interrupting the Vicious Cycle Airway Destruction and Distortion (Bronchiectasis) Neutrophil Inflammation (Proteases) Abnormal Mucus Clearance McShane, et al, Am J Resp Crit Care Med, 2013 Bacterial Colonization 84

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Non-CF Bronchiectasis • Etiology - - - - frequently idiopathic chronic lung disease (COPD, other) prior pneumonia (e.g. tuberculosis, nontuberculous mycobacteria (NTM) ) alpha-1-antitrypsin deficiency, primary ciliary dyskinesia immunodeficiency (CVID) autoimmune disease (rheumatoid arthritis (RA)) (PCD),common variable - - - allergic bronchopulmonary tumor/ obstruction aspergillosis (ABPA) 1. Bonaiti G, et al. Biomed Res Int. 2015;197950. 2. O’Donnell AE. Chest. 2008;134:815-23. 85

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Non-CF Bronchiectasis Mild • Only Severe • Daily symptoms symptoms number of flares destruction 1. Chalmers JD, et al. Am J Respir Crit Care Med. 2014;189:576-85. 2. Lonni S, et al. Ann Am Thorac Soc. 2015;12:1764-70. . 86 Disease spectrum is wide Moderate • Daily cough, sputum production • Variable and prognosis occasional• Increasing• Progressive lung exacerbations • Frequent exacerbations • Associated mortality

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Pathogens of Interest • Gram-negative organisms (Pseudomonas, Achromobacter, Stenotrophomonas, Alcaligenes,H. flu, Moraxella) Gram-positive cocci (S. aureus, S. pneumonia ) • • • • Atypical pathogens (Nontuberculous Fungal (Aspergillus) mycobacteria, Nocardia) Co-infection is common 87

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Epidemiology • • Affects up Increased to 190,000 adults >65 8.7% per year 2000-2007 Sietz et al. Chest 2012; McShane et al. AJRCCM 2013 88

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I Currently Approved Therapies in NCFB 89

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Current therapy for NCFB 1. Pasteur MC, et al. Thorax. 2010;65(suppl 1):i1-58. 2. Flude LJ, et al. Clin Chest Med. 2012 Jun;33(2):351-361. 90 Surgical management1 • Lung resection • Lung transplant Antibiotic therapy1 • To treat exacerbations • To reduce the frequency of exacerbations Airway drug therapy1 • Bronchodilation • Anti-inflammatory Exercise1 • Pulmonary rehabilitation and inspiratory muscle training Airway clearance1,2 • Airway clearance techniques (independent, device-dependent, assistive components to techniques, adjuncts to assist techniques)

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Clinical Objectives of Therapy • Make patient feel better (quality of life) -decrease inflammation and sputum -eradicate Vs. control of pathogen Mitigate progression of lung damage -improves live quality and quantity • • Lower cost and potential adverse events of care - exacerbations, hospitalization, need for antibiotics 91

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Preventive Antibiotic Studies • • • Most measure time to exacerbation or frequency Ideas extrapolated from CF (Cystic Fibrosis) of exacerbation No - - approved inhaled therapies Prior RCTs with colistin, aztreonam & gentamicin Macrolide suppressive therapy • Recently completed phase 3 studies - - Nebulized liposomal ciprofloxacin (Aradigm) Dry-powder inhaler: ciprofloxacin (Bayer) 92

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I Aradigm - ORBIT 3, 4 Figure 1. Time to First PE: (A) All Severity; (B) Required Antibiotics HR (95•;.Cl) A POOLED 0 82 (0 65-1 02) P=O 074 0 72 (0 53-0 97) P=O 032 0(0 71-1 38) P=O 97 ORBIT_. "--9 e 78 ORBIT·J I I 0 2Q 40 60 80 100 02 06 Haurd Ratlo 2 DJyl B POOLED 0 74 (0 59-0 94) P=O 0122 0 66 (0 53-0 97) P=O 0097 0 88 (0.62-1 24) P=O 46 134 ORBIT Ie ORBIT·3 25 0 50 75 100 125 150 Days 02 06 Huard R1tJo 2 PE. -.onary eucelt!Won HR 1\aunl rwt10 Cl coniIn terval • AR0-3150 significantly rncreased median tJme to flrst PE (all severities) in ORBIT·4 (Figure 1A) • AR0 3150 significantly Increased median time to first PE that required treatment with antibiotiCS in ORBIT-4 and the pooled analys1s (Figure 1B) 93

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RESPIRE 1 Results---Time to First Exacerbation Median time to first exacerbation Ciprofloxacin DPI 14 on/off >336 days (97.5% CI [290, >336]) Ciprofloxacin DPI 28 on/off 336 days (97.5% CI [206, >336]) Pooled placebo 186 days (97.5% CI [136, 282]) 94 Adjusted HR 97.5% CI P-value Ciprofloxacin DPI 14 on/off vs pooled placebo 0.53 [0.36, 0.80] 0.0005 Ciprofloxacin DPI 28 on/off vs pooled placebo 0.73 [0.50, 1.07] 0.0650

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Summary • • The prevalence of non-CF bronchiectasis is increasing Patients can have repeated exacerbations, poor quality of life, and in creased mortality decline in lung function Inhalation antibiotic therapies have shown efficacy, but failed to meet primary study outcomes • • There remains inflammation a high unmet need for therapies to control the chronic 95

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Introduction to INS1007: A Novel DPP1 Inhibitor with Inflammatory Indications Eugene J. Sullivan, MD Chief Product Strategy Officer Potential in Neutrophil-Mediated

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INS10071 New molecular entity in-licensed from Astra Zeneca in 2016 (AZD7986) Orally bioavailable, small molecule inhibitor of dipeptidyl peptidase 1 (DPP1; also known as Cathepsin C),2 the enzyme responsible for activating the neutrophil serine proteases in the maturing neutrophil Potential in treating neutrophil-driven inflammatory conditions, such as n-Cystic Fibrosis Bronchiectasis (NCFBE) 1INS1007 is an investigational compound. Safety and efficacy have not been established 2As demonstrated by in vitro testing 97

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DPP1 (Cathepsin C) Catalyzes the Activation of NSPs N-terminal dipeptide removed DPP1 Inactive Neutrophil Serine Proteases (NSPs) Cathepsin G (CatG) Proteinase 3 (Pr3) Neutrophil Elastase (NE) Activated (NSPs) 98

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INS1007 Binds to DPP1 to Prevent the Activation of NSPs DPP1 INS 1007 DPP1 Inhibitor Inactive Neutrophil Serine Proteases (NSPs) Cathepsin G (CatG) Proteinase 3 (Pr3) Neutrophil Elastase (NE) 99

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Neutrophil Serine Proteases A Family of Proteases Contained in Neutrophilic Granules • • • • Includes Neutrophil Elastase, Proteinase-3 and Cathepsin G Kill microbes and inactivate bacterial toxins Released alone or as a component of “neutrophil extracellular traps” (NETs) Also contribute to host tissue damage and inflammation when released in excess of the endogenous inhibitors 100

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Multiple Putative Damaging Effects of NSPs with Potential Relevance in NCFBE secretion from apical surface of neutrophils by macrophages and release of stored mediators) 101 Impair efferocytosis of apoptotic (resulting in neutrophil necrosis Dysregulate constitutive neutrophil apoptosis Modify pro-inflammatory cytokines to increase inflammation Activate Na channel ENaC on epithelial cells Form NETs Decrease ciliary beat frequency Stimulate mucus epithelial cells Degrade endogenous inhibitors of matrix metalloproteinases (TIMPs) Degrade extracellular matrix

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Papillon-Lefévre Syndrome Informs the Potential Safety Profile of INS1007 Very rare genetic disease caused by inactivating mutation in the DPP1 gene; provides insight into potential safety implications of DPP1 inhibition • • • Characterized by palmo-plantar keratosis and periodontitis Signs of systemic immunodeficiency are mild and uncommon Clinical manifestations appear only when DPP1 activity is absent or minimal 102

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Data from AZ’s Phase 1 Study Completed Phase 1 Study1: • • • • Single Ascending Dose (SAD) / Multiple Ascending Dose (MAD) study in healthy volunteers Well tolerated, with no major safety concerns raised PK profile supports once-daily dosing Demonstrated proof of activity, with dose-dependent inhibition of neutrophil elastase activity Phase 1 data supports advancement to Phase 2 1 Clinical Study Report, Study D6190C0001 (data on file) 103

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Initial Target Indication: Non-CF Bronchiectasis • Rare, serious, pulmonary condition with no approved therapies in the US Prominent role of the neutrophil in the “vicious cycle” of infection/inflammation/impaired mucociliary clearance and tissue destruction Extensive overlap with NTM lung disease • • Radiographic signs of bronchiectasis. A. ¼ Bronchus terminating in a cyst; B. ¼ lack of bronchial tapering as it travels to the periphery of the lung; C. ¼ signet ring sign (bronchus is larger than the accompanying vessel); D. ¼ mucus plug (mucus completely filling the airway lumen).1 1McShane P, et al, American Journal of Respiratory and Critical Care, September 2013 104

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Results from a Related Compound Neutrophil Elastase Inhibitor (AZ’s AZD9668) controlled trial in 38 patients with NCFBE 1Kuna P, et al. Respiratory Medicine, 2012 2Stockley R, et al. Respiratory Medicine, 2013 FEV1: Forced Expiratory Volume in first second 105 Phase 2 trial in NCFBE2 •4 week, randomized, double-blind, placebo-•Statistically significant improvement in FEV1 and reduction in inflammatory cytokines Phase 2 trial in COPD1 •3 month, randomized, double-blind, placebo-controlled trial in 615 patients with COPD •Failed to show benefit in the overall population •Post-hoc subgroup analysis of patients with a bronchitic phenotype showed improvement in FEV1

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• • Utilized data from an ongoing, large, prospective, cohort study of patients with NCFBE Elastase activity in sputum was associated with disease severity, dyspnea score, FEV1, and radiologic extent of bronchiectasis During a 3-year follow-up period, elevated sputum elastase activity was associated with a higher frequency of exacerbations and FEV1 decline • Conclusion: Sputum neutrophil elastase activity is a biomarker of disease severity and future risk in adults with BE American Journal of Respiratory and Critical Care Medicine, 2017 106

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Additional Diseases Where INS1007 Might Have an Impact Cystic Fibrosis Crohn’s Disease INS1007 Uveitis Lupus Nephritis Psoriasis Rheumatoid Arthritis Granulomatosis with Polyangiitis (GPA; Wegener’s Granulomatosis) Associated with auto-antibodies to Proteinase 3 (ANCA antibodies) 107

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INS1007: Phase 2 Development Program Paul D. Streck, MD, MBA Chief Medical Officer

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My Track Record in Drug Development • • • • • 25 years of clinical development, management and leadership expertise M.D. from Jefferson Medical College and surgical resident at Thomas Jefferson University Hospital Board certified in oral and maxillofacial surgery Masters of Business Administration, Duke University Fuqua School of Business Led multiple successful global regulatory submissions, launches, LCM introductions, and headed brand management for $1+billion medications. Led business development evaluations with recommendations for 30+ companies • ARANESP, VECTIBIX, SENSIPAR, NEULASTA and KEPIVANCE are trademarks or registered marks of Amgen. LIALDA, CINRYZE, NATPARA, XIIDRA, FOSRENOL, RESOLAR and XAGRID are trademarks or registered marks of Shire. BENLYSTA is a registered trademark of GSK. 109 Sirukamab

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Phase 2 Program In Non-CF Bronchiectasis Builds on Expertise in Pulmonary Rare Disease The Willow study: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multi-Center Study to Assess the Efficacy, Safety and Tolerability, and Pharmacokinetics of INS1007 Administered Once Daily for 24 Weeks in Subjects with Non-Cystic Fibrosis Bronchiectasis Key points : • • • Phase 2 study design has been extensively discussed with and endorsed by pulmonary experts FDA feedback supports progressing to phase 2 and anticipate receipt of a “study may proceed” letter in Q3 2017 Consultations with global health authorities are planned to understand clinical development path 110

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INS1007 Phase 2 Study Design 32 Week Study Duration Treatment Phase Day 1 to Day 168 (24 Week Treatment Period) Off Treatment Phase Day 169 to Day 196 (4 weeks) Day -28 to Day -1 (4 weeks) N= Patients randomized *End of Treatment 111 Visit 10 Visits 3-9: Treatment weeks: 2, 4, 8, 12, 16, 20 and 24* Visit 1 Visit 2 (Day 1, Baseline) Randomization End of Treatment End of Study Visit INS1007 25mg (N=80) Off-treatment INS1007 10mg (N=80) Off-treatment Screening Period Placebo (N=80) Off-treatment

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INS1007 Phase 2 Study: Key Endpoints Primary Endpoint • To evaluate the effect of INS1007 compared with placebo on time to first pulmonary exacerbation over the 24-week treatment period. Secondary and Key Exploratory Endpoints • Key secondary endpoints addressing FEV1, sputum neutrophil elastase, rate of exacerbations and quality of life Multiple exploratory endpoints addressing other mechanistic, outcomes and clinical measures • Safety and Pharmacokinetics 112

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INS1007 Phase 2 Study Overview • Estimated ~125 sites, 16 countries across North America, EU, and Asia Pacific Estimated 240 subjects First Patient – expected in 2H 2017 • • 113

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Financials Paolo Tombesi Chief Financial Officer

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Financial Organization Critical to Supporting Successful Global Product Launches • • • • 20 years of financial leadership in biotech/pharma Successfully built financial infrastructure to support global commercial organizations and launches International experience: US, Japan and Europe Multiple launches, including Pulmonary and Rare Diseases ENTRESTO, COSENTYX, ONBREZ, GILENYA, SEEBRI NEOHALER and ULTIBRO are trademarks or registered marks of Novartis. ORENCIA and BARACLUDE are registered trademarks of Bristol-Myers Squibb Company. ABILIFY is a trademark of Otsuka Pharmaceutical Company. 115 United States Japan Europe Europe LUCENTIS is a trademark of Genentech Inc.

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Cash-Based Operating Expenses (Non-GAAP) • • Cash Balance at 3/31/17 = $125.8M Remain disciplined with spending. Our critical spend consists of: • • 212/312 trial spend, including preparation for US regulatory filing Pre-launch investments on non-branded disease awareness and medical education Reliable product supply chain – Therapure, Pari • • Timing/pace of future spending dependent on many factors, including: • • • 212 trial top-line results Manufacturing pace/schedule INS1007 Phase 2 trial outcome • Debt $55M: interest only until 11/1/18; maturity date 10/1/20 • Able to extend interest only, by an additional 6 months, following the close of certain financing events. *A reconciliation of this non-GAAP financial measure to its most directly comparable GAAP financial measure is provided in an appendix to this presentation. 116

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Financial Planning • • • Continuing long term tax planning efforts, started in 2014 Structure supports scalable platform including Japan & EU Long term plans for manufacturing and distribution • • • Current clinical: Althea (San Diego, California, US) Current commercial launch scale: Therapure (Toronto, Canada) Future: Addition of future capacity under evaluation (post 212 data) 117

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Closing Remarks Will Lewis President and Chief Executive Officer

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Question and Answer Session

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Appendix • • il\Smed

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Non-GAAP Reconciliation Table INSMED INCORPORATED Reconci l i ati on of GAAP to Non-GAAP Resul ts (i n thousands) (Unaudi ted) Three Months Ended March 31, Si x Months Ended, 2017 2H 2016 1H 2016 2H 2015 Operati ng expenses reconci l i ati on: Total operating expenses - GAAP Stock-based compensation expense Depreciation Upfront payment to AstraZeneca related to INS1007 Cash-based operati ng expenses - Non-GAAP $ 35,969 (4,032) (716) - $ 104,200 (9,205) (1,356) (30,000) $ 69,200 (8,834) (1,082) $ 62,835 (7,629) (1,103) $ 31,221 $ 63,639 $ 59,284 $ 54,103 121

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ALIS Clinical Trials INS-212 udies 110 108 122 ONGOING COMPLETED Indication Preclinical Phase 1 Phase 2 Phase 3 Enrollment (N) Extension in CF patients with chronic Pseudomonas aeruginosa Infection – European trial TR02-206 CF patients with chronic Pseudomonas aeruginosa Infection –European trial TR02-294 NTM TR02-112 89 Pseudomonas infection in non-CF patients with bronchiectasis TR02-107 64 CF patients with Pseudomonas lung infection – US trial TR02-106 41 CF patients with Pseudomonas lung infection – European trial TR02-105 64 Indication Preclinical Phase 1 Phase 2 Phase 3 Enrollment (N) Refractory NTM caused by MAC CONVERT 336 Refractory NTM caused by MAC INS-31 2 enrolling M. abscessus Investigat or Sponsored St enrolling

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ALIS Delivers Much Higher Doses Compared to IV Administration Directly to the Lung Pharmacokinetic Data from INS112 Study: Pharmacokinetics and bronchial diffusion of single daily dose amikacin in cystic fibrosis patients1 • 35mg/kg daily dosing of IV amikacin in patients with CF1: Mean serum Cmax 121.4 µg/mL (± 37.3) Max. concentration in sputum seen at 2 hours post dose: range 0.2 – 3.8 µg/mL Similar PK parameters on Day 1 and Day 14 after daily dosing. • • • 1Canis, F et al; Journal of Antimicrobial Chemotherapy (1997) 39, 431-433 123

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Residual Amikacin in Sputum on the Growth of MAC CFU=colony-forming unit; minimal inhibitory concentration (MIC) units= µg/mL; ND=not determined. 124 MAC isolates with known MIC for amikacin incubated in sputum samples at various concentrations of amikacin for 24 hours. MAC isolates with known MIC for amikacin incubated in sputum samples at various concentrations of amikacin for 72 hours.

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Backup slides Kevin L. Winthrop M.D., M.P.H. Associate Professor Divisions of Infectious Diseases, Public Health and Preventive Medicine Oregon Health and Science University

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Nontuberculous Mycobacterium (NTM) • Slow growers -MAC, M. kansasii, M. marinum, M. xenopi Rapid growers (RGM) • -M. abscessus, M. chelonae, 100+ species and growing M. fortuitum • - - 16s Too rDNA gene sequencing many PhD candidates 126

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I NTM Disease Manifestations Table 2. Nontuberculous mycobacterium (NTM) cases by species and disease site, Oregon 2007-2012 77% of NTM disease is pulmonary 127 Mycobacterium species Pulmonary Skin/ soft tissue Disseminated Lymph Other Total N {%) N (%) N (%) N (%) N (%) N (%) M. aviumjintracel/ ulare complex 1005 (92.8%) 68 (37. 8%) 35 (79.5%) 21(87. 5%) 42 (60%) 1171(83.6%) M. abscessusj che/onae complex 46 (4.2%) 51(28.3%) 1(2.3%) 1(4.2%) 9 (12.9%) 108 (7.7%) M. fortuitumj mucogenicum 5 (0.5%) 21(11.7%) 2 (4.5%) 1(4.2%) 3 (4.3%) 32 (2.3%) M. marinum - 17 (9.4%) - - 2 (2.9%) 19 (1.4%) M. /entiflavum 6 (0.6%) 1(0.6%) - - - 7 (0.5%) M. kansasii 5 (0.5%) - - - 1(1.4%) 6 (0.4%) M. bovis - 1(0.6%) - - 3 (4.3%) 4 (0.3%) M. goodii - 4 (2.2%) - - - 4 (0.3%) M. xenopi 2 (0.2%) 1(0.6%) - - 1(1.4%) 4 (0.3%) M. aubagnense - 1(0.6%) 1(2.3%) - 1(1.4%) 3 (0.2%) M. alvei - 2 (1.1%) - - - 2 (0.1%) M. immunogenum 1(0.1%) - - - 1(1.4%) 2 (0.1%) Other (unspeciated and 13 species with a single case) 131. .2%) 12 (6.7%) 5 (11.4%) 1(4.2%) 7(10%) 38 (2.7%) TOTAL (1083') 180 44 24 70 1401

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Pulmonary MAI and M. abscessus/chelonae Incidence 6.0 (Oregon, 2007-2012) 4.8 5.0 4.4 4.3 4.2 4.1 3.9 4.0 3.0 MAI M. abscessus 2.0 1.0 0.5 0.4 0.3 0.2 0.2 0.1 0.0 2007 2008 2009 2010 2011 2012 Year 128 Henkel E et al. Ann ATS In Press Incidence per 100,000 population

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The Griffith Frustration Index (GFI) Frustration Index (GFI), • NTM respiratory pathogen 1 (no problem)-10 (big problem) • • • • • • • M. M. M. kansasii szulgai xenopi • • • • • • • 1 3 5-6 5-6 5-6 8-9 10+ (MAC) M. malmoense (M. abscessus) M. simiae 129

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MAC Therapeutic Options • Diagnosis  decision to treat -Observation vs. suppression vs. cure Treatment best defined for MAC • - - - - - Macrolide, rifampin, ethambutol Amikacin (parenteral or inhaled PRN) 18-24 months (12 month culture negative) No macrolide monotherapy TIW okay if non-cavitary or not re-infection 130

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Treatment Episodes with Initial* Intermittent or Macrolide/Azalide-Based Therapy for Nodular-Daily Bronchiectatic (NB) MAC Lung Disease 131

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I Microbiologic Results for All Patients with Clarithromycin and Azithromycin-Containing Regimens* Clarithromycin A.zithrmnycin To tal No. Patients 91 89 180 Spunun Corm:rsion-no. ( 0'o) 78191 (86°o) 76189 (85° o) 1541180 (86°'0) 0. 7•• Da ys to Convert 130.6 ± 149.7 123.2±109.8 Month5 _ ega ti...-e Cultures On TI1erapy 0.3** 12.1 ± 2.5 12.6 ± 3.5 0.9** Treatment Duration (months) 18.6 ± 8.8 18.8 ± 6.3 14191 (15o) 11189 ( l2° o) 0.4** Microbiologic Rectu-rence On Therapy t-no. (0 o)§ Microbiologic Rectu-rence Off Therapy :j:-no. (0 o)t 41177 (53°o) 33178 (42°o) 0.6** Months Microbiologic Follow-up Off Therapy 44.1 ±31.4 40 .:!:... 25.5 0.1 44.4 ± 31.3 Montlc; Clinical Follm...--up Off Therapy 407 ± 27.1 0.2 P1us-ullnus values are wean± SD. • Macrolide/azalide given at the completion of treatment. •• Clarithrowycin-containing regin1en uazitlrrowycin-containing regimeu § Microbiologic Rectu-rence: :::2 positiYe spunun AFB cultures for MAC after spunun conYers:ion ou therapy. 132 Microbiologic Rectu-rence: :::2 positive spunun AFB cultures for MAC after c;uccesc;ful completion of therapy.

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Drug-Drug Interactions • Rifampin - - - Beta-blockers, Levothyroxine, CA2+ Tacrolimus,steroids, cyclosporin Azoles, Protease inhibitors, FQs blockers, warfarin • Azithromycin -Digoxin, warfarin Clarithromycin has many of the QT issue • • above -Clari/azi, FQs, Bedaquiline, Clofaz, others 133

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M. abscessus Therapy • • • “Cure” = rare (often treat off and on forever) More rapidly progressive or relentless 3-4 drugs for 18-24 months -4-6 months “induction” phase -“suppressive strategy” thereafter than MAC • Rotational parenteral based regimen 134

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Parenteral Drugs • • Limited antibiotic options based upon susceptibility testing Parenteral agents - - - - Tigecycline 50mg daily Cefoxitin 2gm TID, Imipenam 500-1000mg BID Amikacin 10mg/kg TIW 135

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Other Adverse Events • Ethambutol – Optic neuritis, hair loss Rifampin – Hepatotoxicity, red urine/tears, thrombocytopenia, drug nephritis, cytopenias Rifabutin – Uveitis, flu-like syndrome, arthralgia, cytopenias Macrolides • interactions, interstitial • • – Foul taste, tinnitus, hearing decline, sudden cardiac Cefoxitin – Neutropenia, renal failure, rash Quinolones death • • – QT prolongation, tendinopathy, CNS (insomnia, delerium) 136

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I Inhaled Liposomal Amikacin from ) Negative* (miTT Population) Double-blind Phase -Daily Treatment 1.0000 30% t.loot •LAI+ SOC •Placebo + soc L-----------9-W-J€eB-e i 25% 20% ! N ··-C-h N 0 15% i ....oot 10% !0.20ot l 5% 0% .. .. ,. Baseline lAI (3144); PBO (3145} Day28 lAI (10142); PBO (4145) -05 Day 56 lAI (10142); PBO (3145} -OJ Day84 LAI (I I/41); PBO (3145) -01 .. .. " • n " " ,. " 3 1 " .. ".. D " " ,. " " " " " Cl "Cftt50rftg at Di!e ot U.t Contact Of Allnltlatlon Of Opel't-t.abelLAI Note: Sl.llfKUi'fllltnol.levemorcerw.omgCfftenil .lre ceMOreG a15Wtfy 'f91. Number at nu. Iii the 5-Ubjecl•remalr*lg illrtil "e correlp)I"'CCng Intervaldq. Study Day NOTe WISsf)g VillltS IEidUdecl P-\'illt kif atntifitd cocnnn..uallllf..HHI\EIIt..t of trNhtnt illl ldiultiag for ther IX!Omiution ttr.lb Olivier K eta/. ATS 2014 137 ·---------- - --- ---------- - ------------ --tf< -->1*1<-..;.!: I -LAJ-----1 -eee-Cenoored - lAI ->Pte+t Cenoored - Place Kaplan-Meier Plot of Time Study Baseline to NTM Culture Proportion of Subjects with NTM Culture Conversion to Negative (miTT Population

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I ;;.. .. S<N*nl"': .u.2:4 '"" ·-Mon<a ==:Culture Negative (Placebo) d medium 138 Olivier K et at. ATS 2014 Doubl E e Blind (LAVPiacebo)J!_PM Label (590 mg l.AJ)' J ... J _j ..... "SQS (See aiKMf!ig,ure, Bas:efme Myoobacteriiir Load by Number of Subjects (miTT Population), iar psj SAHlin• s 2 .u.2:4 .u.2.4 '"" .. Culrure Negative (LAI) Culrure Negative (Off Treatment) Note:All negative cuUures COI'Ifirmed with no grow1h inlii ....... J J --nt a,_,..,, I""O:::TM PJIIor ..-u SQS•Ift 001'1'114 211 lAI No..a !.tAt: 2 s 6 .u 2 •u·z• ]l ]l ]l ·J 6 ]l ]l _j_J .W.."JK<'HIU• 6 6 4 ]l CJI MA ltl ]l ]l UGI 6 PBO - !.tAt: 4 ]l ]l >12 4 _I_ J •12• 2:4 >12· 2:4 6 •1l: 2 ]l I ··-··· ]l 2 M.' .aMHIJ• INH INH 2 2 ]l IM•I*l"'I..LAI_!_-N...,....,<>f-nuwldt nop U..otJIIH'1 -11'1-llo + SOC 4 u _1!1_ NA !! NA _l_1_

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Acknowledgements • Close colleagues and friends at variety of institutions including: - - NJMC, Mayo,UT Tyler, NIH, Univ. Ontario, U Florida, CDC, ATS/IDSA, OHSU, OHA Oregon Clinic, Adventist Oregon Pulmonary Associates, Vancouver Clinic, Legacy, Providence, 139

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Non-CF Bronchiectasis • Etiology – – – – – – – – – frequently idiopathic chronic lung disease (COPD, other) prior pneumonia (e.g. tuberculosis, nontuberculous alpha-1-antitrypsin deficiency primary ciliary dyskinesia (PCD) common variable immunodeficiency (CVID) autoimmune disease (rheumatoid arthritis (RA)) allergic bronchopulmonary aspergillosis (ABPA) tumor/ obstruction mycobacteria (NTM) ) 140

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I Frequency of Colonization 10!;i1B rnrsms 1,11111231 ! 1 ,1111501 ! 2007 1!0191.! 1361 ! l'lill 141 Table 1 Bacter iology of brorKhiectasis 5t u:dr:X1Ytl!ar 1 0 1 Nkotra et a...s 1 1995PasteUJr 1lrt. aL"20010Kimtgl 1lrt. a 4Liet aL1. 2005 H influnza lll35 4.739 P ae:ruufnasa 31311111 M ca tarrha!is1 108.2 S e,n umoni:a@11 13 7.21 S aur us 714!4.4. NooranismNot sI!C iifid 13.21Not Sf:;!:dfid Mobacterium 17 II) l Not saedrfi1 e dl

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NTM and P. aeruginosa Co-infection is Observed Frequently in NCFB • In observational and retrospective studies, 23% to 52% of NCFB patients with NTM are co-infected with P. aeruginosa1-4 In the BRR, patients with NTM at baseline were significantly less likely to be colonized with P. aeruginosa than patients without NTM (P<0.0001)4 • – – Co-infection Co-infection rates rates were high in both the NTM (23%) and no NTM (41%) groups for other pathogens were similar in the NTM and no NTM groups 1. 2. 3. 4. Maiz L, et al. BMC Infect Dis 2016;16:437. Zoumat Z, Boutou AK, Gill SS. Respirology 2014;19:714-22. Bonaiti G, et al. Int J Mycobacteriol 2015;4:68-9. Winthrop KL, et al for the Bronchiectasis Research Registry. Respiratory microbiology of patients with nontuberculous mycobacteria from the United States Bronchiectasis Research Registry. Poster presented at ATS 2013. 142

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I Colonization and Subsequent Exacerbation bl . • u l lll P value Jrea men vs non bioi B .l(1 .7 3. ) i D 143

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Chronic Colonization and Decreased QOL UK prospective single-center cohort Colonization prevalence • • H. influenzae (29% ), P. aeruginosa (12%), M. catarrhalis (10%), S. aureus (8.4%) • Chalmers JD et al. AJRCCM 2014. 144 Colonized (n=440) Not colonized (n=168) P value 4-year mortality 11.8% 6.0% 0.03 Exacerbations (mean) 2.04 1.29 <0.0001 Hospitalizations 38.4% 12.0% <0.0001 QOL (SGRQ mean) 45.6 37.8 <0.0001

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Clinical Objectives of Antibiotic Therapy • Make patient feel better (quality of life) -Decrease inflammation and sputum -Eradicate Vs. control of pathogen Mitigate progression of lung damage -Improves live quality and quantity Lower cost and potential adverse events • • of care - Exacerbations, hospitalization, need for ABX 145

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I Time to Need for Additional Inhaled Antipseudomonal Therapy or IV -·-·-Piacebo 1!:1: Cert Ofed data - AZLI pooled " Censored data .:e..--"-1.011 "0 aJo --til-I]} l l -----,8-_.., ..,_--r:; 0 ·..;:;. ;g 0 75 -.,_ -..._ r:; iJ) Time to moo figure? 2. for additio nal in­ - -, -e:z. 5 haled or intravenous a ntip.sel.lldomonaI anti­ biotics to treat.symptomsindicative of pllllmona ry e.xacerhation _ The media n time to antibiotic need is shown for both treat.. mnt groups (aztreonam lysine for inhala... tion [AZ U] vs_ placebo,P = r0JX)7). 0 ..J.:.:. r-O 51) l:il0 L -----'--..j FHH+iiE--- '.0 (I) ..._ . 0 1!: Piacebo nt od Followup Period Mt}dian =71 rd )':5 r0.25 .2 ! 0 0.00 '-r------,---....._-- -.----sot 20 0 40 60 100 TimGo, da 'fS Day 84, .study end 146 L----AZLI/ Treatme Peri -

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A Randomized Controlled Trial of Nebulized in Non–Cystic Fibrosis Bronchiectasis Gentamicin Less sputum purulence (8.7% vs. 38.5%; P , 0.0001); greater exercise capacity (510 [350–690]mvs. [267.5–530]m; P50.03) 415 fewer exacerbations (0 [0–1] vs. 1.5 [1–2]; P , 0.0001) increased time to first exacerbation (120 [87– 161.5] d vs. 61.5 [20.7–122.7] d; P 5 0.02). Greater improvements in Leicester Cough Questionnaire (81.4% vs. 20%; P , 0.01) and St. George’s RespiratoryQuestionnaire (87.5%vs. 19.2%; P,0.004) score.N 147

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I Daily Gent Decreased Inflammation TABLE 4. SPUTUM IN FLA.MMATORV INDI,CES, VOLUME, AN D PURULE NCE BETWEE N T HE 'GROUPS THRO. ·U-Spulum Cl\ar:acro ris.Lic Month 0 Month 3. Month 6 Monlh 9 Monh 15 Spun..rn rrryelopsrox ida.s.(!, u.nits/n'ill ntamloln groLI\p Sailoo grou,p Spun..m f1"100 as,l&(!aciNity, uniWmg rltamlol.n grou:p Salloo grou;p % puruiQn'tputum ntamlol.n grou:p Sailoo grou;p 24-hputum voluiTIC!, ml ntamloln grou:p Sailoo grou;p 51.16 (29.&-13.2.6) 40.5 (17.1-104.4) 21 (3..4-:50.3.) 44.6 (13..6-114.5) 18.2 {7. 71.2)'* S2.1 (22.1-110.8) 29.7 (9.9-41.1) 13..8 (3.-34.4:r SB.2 (27-101.8) 47.7 (9.2-254.7) 67.5 (24.1-94.9) 49.8 (22.6-94. 0 (O--O) t 0 (0-20.4) 3.16 (0-17.16) 4.1 (0-19) 0(0-2.9) 0(0-29.1) 0(0-7.6) 0.9 (0-19.4) 0 (0-1.8)• 1.8 (0.17-1 6) 7.1 (0-.56) 2.8 (0.9-·18.2) 9.1• 4() 66.7 40.7 42.8 40 8.7• so 10 (2.S-1S,) 3 (3.-10) 8.7• 3.8..5 16.5,.2 44 13.5 (10-:24.S,) 8(4..5-20) 1S, (9-17.5) 4..51 (2.8-16.2) 10 (2..5-15) 15 (&-1.5.) s, (1.6-·14) 4 .5 (0..5-10) .. p.;: 0.02 I p < 0.0.5 . 148

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Inhaled Colistin in Patients with Bronchiectasis and Chronic Pseudomonas aeruginosa Infection 149

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Aztreonam for inhalation solution in patients with non-cystic fibrosis bronchiectasis (AIR-BX1 and AIR-BX2): two randomised double-blind, placebo-controlled phase 3 trials 150

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I The Use of Aerosol Penicillin and Streptomycin Bronchopulmonary Infections in JAsoN E. FARBER, M.D., and JosEPH Ross, M.D., Oakland TABLE 2. Results with Combined Antibiotic Aerosol Therapy - - - R.eduction in Cough and Sputum Number of Cases I2 13 5 II 2 - Diagnosis 50o/o More than 75% 12 11 5 10 2 Less than 25% acute or protrac · acheobronchitis........................................ 1 1 1 Chronic bronchiectasis.... ............................··-------.--·._ ···-.................. I.th respi.ratory 1.n fech.on........................... -em Bronchial ast ma with respiratory infection................................... Bronc-hopneumo-nia................................................................................... 1 Totals.................................................................................................. 2 43 40 151

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