Forward Looking Statements  This presentation contains forward-looking statements that involve substantial risks and uncertainties. “Forward-looking statements,” as that term is defined in the Private Securities Litigation Reform Act of 1995, are statements that are not historical facts and involve a number of risks and uncertainties. Words herein such as “may,” “will,” “should,” “could,” “would,” “expects,” “plans,” “anticipates,” “believes,” “estimates,” “projects,” “predicts,” “intends,” “potential,” “continues,” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) may identify forward-looking statements.  The forward-looking statements in this presentation are based upon the Company’s current expectations and beliefs, and involve known and unknown risks, uncertainties and other factors, which may cause the Company’s actual results, performance and achievements and the timing of certain events to differ materially from the results, performance, achievements or timings discussed, projected, anticipated or indicated in any forward-looking statements. Such risks, uncertainties and other factors include, among others, the following: failure to continue to successfully commercialize ARIKAYCE, our only approved product, in the U.S., Europe or Japan (amikacin liposome inhalation suspension, Liposomal 590 mg Nebuliser Dispersion, and amikacin sulfate inhalation drug product, respectively), or to maintain US, European or Japanese approval for ARIKAYCE; our inability to obtain full approval of ARIKAYCE from the FDA, including the risk that we will not successfully or in a timely manner complete the confirmatory post-marketing clinical trial required for full approval of ARIKAYCE, or our failure to obtain regulatory approval to expand ARIKAYCE’s indication to a broader patient population; failure to obtain, or delays in obtaining, regulatory approvals for brensocatib, TPIP or our other product candidates in the US, Europe or Japan or for ARIKAYCE outside the US, Europe or Japan, including separate regulatory approval for Lamira® in each market and for each usage; failure to successfully commercialize brensocatib, TPIP or our other product candidates, if approved by applicable regulatory authorities, or to maintain applicable regulatory approvals for brensocatib, TPIP or our other product candidates, if approved; uncertainties or changes in the degree of market acceptance of ARIKAYCE or, if approved, brensocatib,TPIP or our other product candidates by physicians, patients, third-party payors and others in the healthcare community; our inability to obtain and maintain adequate reimbursement from government or third-party payors for ARIKAYCE or, if approved, brensocatib, TPIP or our other product candidates, or acceptable prices for ARIKAYCE or, if approved, brensocatib, TPIP or our other product candidates; inaccuracies in our estimates of the size of the potential markets for ARIKAYCE, brensocatib, TPIP or our other product candidates or in data we have used to identify physicians, expected rates of patient uptake, duration of expected treatment, or expected patient adherence or discontinuation rates; failure of third parties on which the Company is dependent to manufacture sufficient quantities of ARIKAYCE, brensocatib, or TPIP for commercial or clinical needs, to conduct the Company's clinical trials, or to comply with the Company's agreements or laws and regulations that impact the Company's business; the risks and uncertainties associated with, and the perceived benefits of, our secured senior loan with certain funds managed by Pharmakon Advisors LP and our royalty financing with OrbiMed Royalty & Credit Opportunities IV, LP, including our ability to maintain compliance with the covenants in the agreements for the senior secured loan and royalty financing and the impact of the restrictions on our operations under these agreements; our inability to create or maintain an effective direct sales and marketing infrastructure or to partner with third parties that offer such an infrastructure for distribution of ARIKAYCE or any of our product candidates that are approved in the future; failure to successfully conduct future clinical trials for ARIKAYCE, brensocatib, TPIP and our other product candidates and our potential inability to enroll or retain sufficient patients to conduct and complete the trials or generate data necessary for regulatory approval of our product candidates or to permit the use of ARIKAYCE in the broader population of patients with MAC lung disease, among other things; development of unexpected safety or efficacy concerns related to ARIKAYCE, brensocatib, TPIP or our other product candidates; risks that our clinical studies will be delayed, that serious side effects will be identified during drug development, or that any protocol amendments submitted will be rejected; failure to successfully predict the time and cost of development, regulatory approval and commercialization for novel gene therapy products; the risk that interim, topline or preliminary data from our clinical trials that we announce or publish from time to time may change as more patient data become available or may be interpreted differently if additional data are disclosed, or that blinded data will not be predictive of unblinded data; risk that our competitors may obtain orphan drug exclusivity for a product that is essentially the same as a product we are developing for a particular indication; our inability to attract and retain key personnel or to effectively manage our growth; our inability to successfully integrate our recent acquisitions and appropriately manage the amount of management’s time and attention devoted to integration activities; risks that our acquired technologies, products and product candidates will not be commercially successful; inability to adapt to our highly competitive and changing environment; inability to access, upgrade or expand our technology systems or difficulties in updating our existing technology or developing or implementing new technology; risk that we are unable to maintain our significant customers; risk that government healthcare reform materially increases our costs and damages our financial condition; business or economic disruptions due to catastrophes or other events, including natural disasters or public health crises; risk that our current and potential future use of AI and machine learning may not be successful; deterioration in general economic conditions in the US, Europe, Japan and globally, including the effect of prolonged periods of inflation, affecting us, our suppliers, third-party service providers and potential partners; the risk that we could become involved in costly intellectual property disputes, be unable to adequately protect our intellectual property rights or prevent disclosure of our trade secrets and other proprietary information, and incur costs associated with litigation or other proceedings related to such matters; restrictions or other obligations imposed on us by agreements related to ARIKAYCE, brensocatib or our other product candidates, including our license agreements with PARI and AstraZeneca AB , and failure to comply with our obligations under such agreements; the cost and potential reputational damage resulting from litigation to which we are or may become a party, including product liability claims; risk that our operations are subject to a material disruption in the event of a cybersecurity attack or issue; our limited experience operating internationally; changes in laws and regulations applicable to our business, including any pricing reform and laws that impact our ability to utilize certain third parties in the research, development or manufacture of our product candidates, and failure to comply with such laws and regulations; our history of operating losses, and the possibility that we never achieve or maintain profitability; goodwill impairment charges affecting our results of operations and financial condition; inability to repay our existing indebtedness and uncertainties with respect to our ability to access future capital; and delays in the execution of plans to build out an additional third-party manufacturing facility approved by the appropriate regulatory authorities and unexpected expenses associated with those plans.    The Company may not actually achieve the results, plans, intentions or expectations indicated by the Company's forward-looking statements because, by their nature, forward-looking statements involve risks and uncertainties because they relate to events and depend on circumstances that may or may not occur in the future. For additional information about the risks and uncertainties that may affect the Company's business, please see the factors discussed in Item 1A, "Risk Factors," in the Company's Annual Report on Form 10-K for the year ended December 31, 2024 and any subsequent Company filings with the Securities and Exchange Commission (SEC).  The Company cautions readers not to place undue reliance on any such forward-looking statements, which speak only as of the date of this presentation. The Company disclaims any obligation, except as specifically required by law and the rules of the SEC, to publicly update or revise any such statements to reflect any change in expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. 

 Additional Disclaimers  With respect to the blended and blinded data observed from the ongoing TPIP study in pulmonary arterial hypertension, the dose titration and efficacy analyses were based on data available as of April 1, 2024, and the safety analyses were based on data available as of January 25, 2024, respectively. These findings may not be representative of results after the study is completed and all data are collected and analyzed. As a result, later interim data readouts and final data from this study may be materially different than the observations described herein, including with respect to efficacy, safety and tolerability of TPIP.  Please be aware that brensocatib and TPIP are investigational products that have not been approved for sale or found safe or effective by the FDA or any regulatory authority. In addition, ARIKAYCE has not been approved for the treatment of all patients with MAC lung disease. This presentation is not promotion or advertisement of ARIKAYCE, brensocatib, or TPIP.  Insmed and ARIKAYCE are registered trademarks of Insmed Incorporated. All other trademarks are property of their respective owner(s).  Certain information contained in this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources, as well as our own internal estimates and research. While we believe the information in these third-party sources to be reliable as of the date of this presentation, we have not independently verified any such information or the underlying assumptions relied on in such third-party sources. In addition, while we believe our internal research is reliable, such research has not been verified by any independent source. 

 Portfolio of First-in-Class and Potentially Best-in-Class* Assets Across Each Stage of Development  Pre-clinical Phase 1 Phase 2 Phase 3 Approved   ARIKAYCE®  Refractory MAC  All MAC Lung Disease  Brensocatib  Bronchiectasis  CRSsNP  HS  TPIP  PH-ILD  PAH  Pre-Clinical Research  INS1202: ALS  INS1203: Stargardt Disease  Next-Gen DPP1 Inhibitor (Multiple indications)  Other Pre-Clinical Research (Multiple indications)  Gene Therapy  INS1201: DMD  * “Best-in-disease/best-in-class" indicates a profile that could be considered more attractive than other treatment options for a particular disease. Head-to-head clinical trials are not anticipated.  TPIP: Treprostinil Palmitil Inhalation Powder; MAC / MAC LD: mycobacterium avium complex lung disease; Bronchiectasis: non-cystic fibrosis bronchiectasis; PAH: pulmonary arterial hypertension; PH-ILD: pulmonary hypertension associated with interstitial lung disease; CRSsNP: chronic rhinosinusitis without nasal polyps; HS: hidradenitis suppurativa; DMD: Duchenne muscular dystrophy; ALS: amyotrophic lateral sclerosis 

 * If pipeline of assets are approved   Bronchiectasis: non-cystic fibrosis bronchiectasis; MAC / MAC LD: Mycobacterium avium complex lung disease; CRSsNP: chronic rhinosinusitis without nasal polyps; PH-ILD: pulmonary hypertension due to interstitial lung disease; PAH: pulmonary arterial hypertension; HS: hidradenitis suppurativa  ARIKAYCE  Refractory MAC  2018 - Today  30K patients  Total Addressable Patients Has Potential to Grow 80x Through 2030*  2025 - 2030  Brensocatib  Bronchiectasis  +1.25M   ARIKAYCE  MAC LD  +275K  Brensocatib  CRSsNP   +400K  TPIP  PH-ILD  +135K  TPIP  PAH  +90K  Brensocatib  HS   +600K  Additional 2.5M+ patients* 

 Potential Value Creation Will Be Shaped by Two Distinct Drivers  * Pending regulatory approval for bronchiectasis indication; U.S. FDA target action date set for August 12, 2025  ** Guidance growth versus 2024 ARIKAYCE revenue results  † Europe/EU5 comprised of France, Germany, Italy, Spain, and the United Kingdom  ‡ Priority Review designation received; NDA: New Drug Application  (P) Indicates trial phase of respective clinical program; TLR: Topline Results  Revenue Generation  Clinical Execution  Value Creation  Mid-25  TPIP PAH   TLR (P2)  3Q:25  U.S. Launch   of Brensocatib*  YE:25  BiRCh   CRSsNP   TLR (P2)  FY:25  Double-Digit  ARIKAYCE Growth**     2H:25  TPIP PH-ILD   (P3) Initiation  YE:24  Expanded   U.S. Salesforce  1Q:26  ENCORE  MAC LD   TLR (P3)  ’25/’26  DMD First Clinical Data  2026  Brensocatib EU5†  & Japan Launch*  PAH: pulmonary arterial hypertension; PH-ILD: pulmonary hypertension associated with interstitial lung disease; Bronchiectasis: non-cystic fibrosis bronchiectasis; CRSsNP: chronic rhinosinusitis without nasal polyps; MAC / MAC LD: Mycobacterium avium complex lung disease; DMD: Duchenne muscular dystrophy  2024  2025  2026  1Q:25  FDA Accepted Brensocatib NDA Filing‡ 

 ARIKAYCE  Refractory Mycobacterium avium complex lung disease  A rare and chronic disease that can cause irreversible lung damage and is the most common form of NTM respiratory pathogen  Mycobacterium avium complex lung disease   Image source: Hendrix C, McCrary M, Hou R, Abate G. Diagnosis and Management of Pulmonary NTM with a Focus on Mycobacterium avium Complex and Mycobacterium abscessus: Challenges and Prospects. Microorganisms. 2023; 11(1):47. https://doi.org/10.3390/microorganisms11010047  ®   (amikacin liposome inhalation suspension)  

 ARIKAYCE Expected to Deliver Double-Digit Revenue Growth in 20251  1 Guidance growth vs. 2024 ARIKAYCE revenue results  EU5 comprised of France, Germany, Italy, Spain, and the United Kingdom  Double-digit   growth entering 7th year post launch  +19%   2024 vs. 2023  +14%   +39%   +33%   FY 2024  $364M   Beat $340-$360M Guidance  $255M   $21M  $88M   $405 to $425M  Full-Year 2025  +11% to 17%1   2025 vs. 2024  FY 2025E  ARIKAYCE   Revenue Guidance  

 ARIKAYCE has the Potential to be the Best in MAC LD Treatment  MAC / MAC LD: Mycobacterium avium complex lung disease; TAM: Total Addressable Market  †EU5 comprised of France, Germany, Italy, Spain, and the United Kingdom  Note: Numbered footnote references related to patient prevalence can be found at the end of this presentation.  125-145K  US  TAM  EU5†  TAM  Japan  TAM  Refractory MAC1  95-115K  14K  MAC LD1  15-18K  12-17K  1.4K  If approved, we anticipate marketing ARIKAYCE in MAC LDat same price and dosage as currently available ARIKAYCE  Phase 3 ENCORE Readout   Expected 1Q:26 

 ARIKAYCE Phase 3 Program to Potentially Expand MAC Indication  Trial summary  Key Endpoints  Screening  Double-Blind Registration PMR Trial   ARIKAYCE + AZI* + ETH*  Placebo + AZI* + ETH*  Key Endpoints   Month 13   Culture Negativity Endpoint  Month 15  R  Months 1-6  ARIKAYCE +   AZI* + ETH*  Off Treatment  Months 1-12  Adults with new MAC lung infection  (n=250+)  Psychometric Validation Study  Month 7  Placebo +   AZI + ETH  Off Treatment  Adults with new MAC lung infection  (n=100)  ENCORE  ARISE  R   ENCORE  Primary Endpoint  Change from Baseline to Month 13 (one month off treatment) in respiratory symptom score  Key Secondary Endpoint  Proportion of subjects achieving durable culture conversion at Month 15 (3 months off treatment)   ARISE  Primary Objective  Demonstrate reliability, validity and responsiveness of the PRO/symptom scores  Secondary Objective  Demonstrate effect of ARIKAYCE on culture conversion, time to culture conversion  200-220 sites across ARISE and ENCORE  Topline results from Phase 3 ENCORE trial expected in Q1:26     Aligned on Primary Endpoint (PE) with FDA (8 questions from QoL-B)  ENCORE enrollment of 425 patients (>90% powering on PE)  Positive topline results from Phase 3 ARISE trial shared in September 2023  *Azithromycin (AZI), Ethambutol (ETH) 

 Brensocatib  Image sources: 1) Fraser CS, José RJ. Insights into Personalised Medicine in Bronchiectasis. Journal of Personalized Medicine. 2023; 13(1):133. https://doi.org/10.3390/jpm13010133. | 2) Rethinkbronchiectasis.com | 3) Yang Y, Zhang N, Crombruggen KV, Lan F, Hu G, Hong S, Bachert C. Differential Expression and Release of Activin A and Follistatin in Chronic Rhinosinusitis with and without Nasal Polyps. PLoS One. 2015 Jun 1;10(6):e0128564. doi: 10.1371/journal.pone.0128564. PMID: 26030615; PMCID: PMC4451080 | 4) Z.N. Ovadja, M.M. Schuit, C.M.A.M. van der Horst, O. Lapid, Inter‐ and intrarater reliability of Hurley staging for hidradenitis suppurativa, British Journal of Dermatology, Volume 181, Issue 2, 1 August 2019, Pages 344–349, https://doi.org/10.1111/bjd.17588   Non-Cystic Fibrosis Bronchiectasis  A chronic, progressive inflammatory disease that causes permanent lung damage  Chronic Rhinosinusitis without Nasal Polyps  Hidradenitis   Suppurativa  A burdensome disease that significantly impairs quality of life  A debilitating, chronic inflammatory disease with significant treatment challenges  1)  2)  3)  4)  (DPP1 inhibitor)  

 U.S. Bronchiectasis Market Primed for a Strong Brensocatib Launch*   * Pending regulatory approval for bronchiectasis indication  ** Since website launch in November 2023 through December 2024  † From February-October 2024; Commercial lives include Veterans Affairs, Tricare, and Dept. of Defense  ‡ Highly engaged defined as those patients who have downloaded support tools or registered for Customer Relationship Management (CRM)  1 Based on US Segmentation Study (currently in field)  2 Based on US Demand Study (fieldwork: June/July 2024)  3 Patient website metrics dashboard; as of December 2024  4 Payer KPI metrics; as of October 2024  Doctors  Intend to Prescribe  64%  Indicated high unmet   need in bronchiectasis1  90%  Likely to prescribe brensocatib for   patients with 2+ exacerbations2  Patients  Are Motivated to Act3  ~900K  Unique visits to disease state website**  ~41K  Highly engaged‡ visitors who have acted**  Payors  Recognize the Disease Burden4  >90%  Medicare lives†  >90%  Commercial lives †  Lives covered by engaged accounts: 

 Brensocatib in Bronchiectasis Opportunity Could Reach >1M Patients at Launch*  * Pending regulatory approval for bronchiectasis indication  † Includes misdiagnosed, miscoded, undiagnosedNote: COPD and asthma may be comorbid with bronchiectasis and not all patients with bronchiectasis have comorbid asthma or COPD Note: Numbered footnote references related to patient prevalence can be found at the end of this presentation  † EU5 comprised of France, Germany, Italy, Spain and the United KingdomBronchiectasis refers to non-cystic fibrosis bronchiectasis  TAM: Total Addressable Market  US  TAM  EU5†  TAM  Japan  TAM  Diagnosed with Bronchiectasis2  0.8M  2.4M  2.1M  Undiagnosed† Bronchiectasis3   Asthma or COPD4  150K  500K  600K  17M  32M  27M  Bronchiectasis  NDA for Brensocatib in Bronchiectasis Accepted by FDA and Granted Priority Review with a PDUFA Target Action Date of August 12, 2025 

 Brensocatib Phase 3 in Bronchiectasis:  Trial summary  Off treatment4 weeks  Treatment period  52 weeks  Baseline  day 1  randomization  End of trial  day 364  End of studyday 392 ± 3   6 weeks  Randomization:  1:1:1 for adults  2:2:1 for adolescents  Screening  Brensocatib 10 mg once daily  Brensocatib 25 mg once daily  Placeboonce daily  Adults stratified by:  Sputum Pseudomonas aeruginosa culture status at screening (positive or negative)  Number of exacerbations in the prior 12 months (2 or ≥3)  Geographic region (Europe, Japan, North America, or ROW)  Primary endpoint:  Annualized rate of adjudicated pulmonary exacerbationsa over 52 weeks  Secondary endpoints (hierarchical):  Time to first exacerbation  Proportion of patients who remained exacerbation-free  Change from baseline in post-bronchodilator FEV1 at week 52  Annualized rate of severe exacerbations  Change from baseline in QoL-B Respiratory Symptom Domain score at week 52  ASPEN  a Defined as the presence of ≥3 of the following symptoms for at least 48 hours, resulting in a physician’s decision to prescribe systemic antibiotics: (1) increased cough, (2) increased sputum production or change in sputum consistency, (3) increased sputum purulence, (4) increased breathlessness and/or decreased exercise tolerance, (5) fatigue and/or malaise, or (6) hemoptysis.   Bronchiectasis refers to non-cystic fibrosis bronchiectasis; FEV1=forced expiratory volume in 1 second; PO=orally; QoL-B=Quality of Life-Bronchiectasis questionnaire; ROW=rest of world.  

 Phase 3 ASPEN Study a Clear Win: Primary Endpoint Achieved Statistical Significance on Both Doses  PE=Pulmonary ExacerbationFEV1=Forced Expiratory Volume Over 1 Second  QoL-B=Quality of Life-Bronchiectasis Questionnaire* Statistically significant^ Nominally significant p-value   Brensocatib 10 mg   compared to placebo  Brensocatib 25 mg compared to placebo  Primary Endpoint  Reduction in annualized rate of PEs   21.1%  p = 0.0019*  19.4%  p = 0.0046*  Secondary Endpoints  Prolongation of time to first PE   18.7%  p = 0.0100*  17.5%  p = 0.0182*  Increase in odds of remaining exacerbation free over 52 weeks   41.2%  p = 0.0059*  40.0%  p = 0.0074*  Change from baseline in post-bronchodilator FEV1 at week 52   11 mL  p = 0.3841  38 mL  p = 0.0054*  Reduction in annualized rate of severe PEs   25.8%  p = 0.1277  26.0%  p = 0.1025  Change from baseline in the QoL-B Respiratory Score at week 52   2.0 points  p = 0.0594  3.8 points  p = 0.0004^ 

 Chronic Rhinosinusitis without Nasal Polyps Represents Another Potential Large Patient Opportunity  Included in   Phase 2b  BiRCh Trial;  >75% Enrolled  Annual New Surgical Patients (Incidence)5  0.5M  3.1M  2.6M  Steroid Non-responders (Prevalence)5  40K  200K  160K  6M  29M  24M  CRSsNP  CRSsNP (Prevalence)4  US  TAM  EU5†  TAM  Japan  TAM  US  TAM  EU5†  TAM  Japan  TAM  CRSsNP: chronic rhinosinusitis without nasal polyps | TAM: Total Addressable Market  † EU5 comprised of France, Germany, Italy, Spain and the United Kingdom  Note: Numbered footnote references related to patient prevalence can be found at the end of this presentation 

 Brensocatib Phase 2b in CRSsNP: BiRCh  Brensocatib 40 mg QD  Placebo QD   Screening  BASELINE  EOT (primary analysis)  Up to 5 weeks  Brensocatib 10 mg QD  4 weeks  Treatment period  24 weeks  EOS  R  Off-treatment follow-up  N=~270 total  Key eligibility criteria:  Male or female ≥18 years old and ≤75 years old  At least a 12-week history of CRSsNP and confirmed by endoscopy at Screening  Ongoing CRS symptoms: nasal congestion score of at least 2, sTSS score of at least 5 and sino-nasal outcome test 22 score of at least 20 at screening and baseline  Blood eosinophil count of ≤750 cells/μL at Screening  Previous sinonasal surgery for CRS and/or treatment with systemic steroids or antibiotics for CRS within a year of Screening Visit  Primary Endpoint  Change in daily sinus total symptom score (sTSS)  Secondary Endpoints  Change in percentage sinus opacification  Change in modified LMK CT (Lund-MacKay computed tomography) score  Proportion of participant requiring rescue  Change in Sino-nasal Outcome Test 22 score  Exploratory Endpoint  Neutrophil serine proteases (NSPs) in blood  CRSsNP: Chronic rhinosinusitis without nasal polyps; EOS: end of study; EOT: end of treatment; QD: once daily.   Trial summary   BiRCh 

 Potential Expansion into Hidradenitis Suppurativa Could Be a New Treatment Option for >600K Patients  Hurley Stage 2 & 36  Global Diagnosed Prevalence6  30K  275K  300K  HS  1.2M – 2.6M  US  TAM  EU5†  TAM  Japan  TAM  HS: hidradenitis suppurativa | TAM: Total Addressable Market  † EU5 comprised of France, Germany, Italy, Spain and the United Kingdom  Note: Numbered footnote references related to patient prevalence can be found at the end of this presentation 

 Primary Endpoint (Week 16)  Percent change in total abscess and inflammatory nodule (AN) count  Secondary Endpoints (Week 16)  Percentage achieving HiSCR50  Percentage achieving HiSCR75  Change from baseline in draining tunnel count  Percentage remaining free from HS flare  Change from baseline in International HS Severity Score System (IHS4) score  Percentage achieving IHS-55  Change from baseline on Dermatology Life Quality Index (DLQI) Global Score  Percentage achieving Numeric Rating Scale 30 (NRS30) with Baseline NRS >3  Brensocatib Phase 2b in HS: CEDAR  Trial summary  HS: Hidradenitis suppurativa; QD: once daily; Q2W: once every 2 weeks; Q4W: once every 4 weeks; HiSCR: Hidradenitis suppurativa clinical response  Up to   35 days  Period 1  Double-Blind Placebo-Controlled  (16 weeks)  Period 2  Double-Blind Active Treatment  (36 weeks)  Follow-up  Period  (4 weeks)  No Study   Treatment  SCREENING  1:1:1  N = 204  (68/arm)  Clinic Visits Q2W  Clinic Visits Q4W  Baseline  Day 1  Randomization  Period 1  End of Treatment  Week 16  (Primary Analysis)  Period 2  End of Treatment  Week 52  End of  Study  Week 56  Tissue Biopsy (Sub-study: N=~36)  *Optional, at selected sites  Brensocatib 10 mg QD  Brensocatib 10 mg QD (n=68)  Brensocatib 40 mg QD  Brensocatib 40 mg QD (n=68)  Placebo QD  Brensocatib 10 mg QD (n=34)  Brensocatib 40 mg QD (n=34)  Interim Futility Analysis  Independent Data Monitoring Committee examines ~100 randomized participants completing 16 weeks of treatment to obtain a preliminary perspective of benefit/risk ratio in this population  CEDAR 

 TPIP  Pulmonary Hypertension due to Interstitial Lung Disease  A rapidly progressing disease associated with poor survival and decreased quality of life  Pulmonary Arterial Hypertension  A devastating and debilitating disease that   pervades all aspects of a patient’s daily life  Image source: Valentini A, Franchi P, Cicchetti G, Messana G, Chiffi G, Strappa C, Calandriello L, del Ciello A, Farchione A, Preda L, et al. Pulmonary Hypertension in Chronic Lung Diseases: What Role Do Radiologists Play? Diagnostics. 2023; 13(9):1607. https://doi.org/10.3390/diagnostics13091607  (Treprostinil Palmitil Inhalation Powder) 

 TPIP has the Potential for Clear Differentiation in PH-ILD and PAH  * No head-to-head or convenience studies have been conducted or planned** Safety analysis based on topline safety and tolerability data from the Phase 2 PH-ILD study of TPIP disclosed on May 6, 2024  †Based on most recent publicly available data  TPIP  Inhaled   (dry powder)  Once daily  Yes**  Currently being evaluated in Phase 2  Phase 2 data support advancing to Phase 3  Remodulin®  IV or subcutaneous  Continuous  Yes  Yes  No data  Tyvaso®  & Yutrepia®  Inhaled (nebulized and/or dry powder)2  4-times  per day  No  Yes  Yes  Orenitram®  & Uptravi®  Oral  2- or 3-times  per day3  No  Yes  No data  Route of administration  Dosing frequency  Favorable tolerability for dose expansion†  Efficacy in PAH  (WHO Group 1)  Efficacy in   PH-ILD  (WHO Group 3)  Potential  Differentiators  1 Yutrepia® is tentatively approved for PAH & PH-ILD; Tyvaso ® is approved in PAH & PH-ILD; all other listed products are approved in PAH   2 Tyvaso: nebulized and dry-powder | Yutrepia: dry powder   3 Orenitram: 2-3 times per day | Uptravi: 2-times per day  Approved Treprostinil Therapies1  Convenience*  Safety &   Efficacy**  Favorable safety profile & higher dosing may lead to improved outcomes  TPIP=Treprostinil Palmitil Inhalation Powder 

 PH-ILD and PAH Represent Substantial Commercial Opportunities  TPIP: A Potential Best-in-Class* Prostanoid  ‡ Wholesale acquisition cost (WAC) as of March 12, 2024  TAM: Total Addressable Market; †EU5 comprised of France, Germany, Italy, Spain and the United Kingdom   Note: Numbered footnote references related to patient prevalence can be found at the end of this presentation.  * “Best-in-disease/best-in-class" indicates a profile that could be considered more attractive than other treatment options for a particular disease. Head-to-head clinical trials are not anticipated.Note: Diagnosed pulmonary hypertension (PH) consists of pulmonary arterial hypertension (PAH), pulmonary hypertension due to left heart diseases (PH-LHD), pulmonary hypertension due to interstitial lung disease (PH-ILD), chronic thromboembolic pulmonary hypertension (CTEPH), Idiopathic PH  ~$300K  U.S. Pricing Benchmark  Tyvaso DPI   List Price‡  US  TAM  EU5†  TAM  Japan  TAM  15K  35K  40K  PAH7  PH-ILD8  20K  50K  65K  Diagnosed PH  45K  190K  150K  TPIP  TPIP=Treprostinil Palmitil Inhalation Powder 

 TPIP Phase 2 in PH-ILD  4 weeks  TPIP 80-640 µg  inhalation capsules QD   Placebo  inhalation capsules QD   Screening  Treatment period  16 weeks  Baseline  EOT  (primary analysis)  EOS  4 weeks  Primary Endpoints  Secondary Endpoints  Follow-up  Pharmacokinetics  39 participants randomized   in the study   3:1 active : placebo  Safety and tolerability  Oxygenation  Exploratory Efficacy Endpoints  Improvement in 6-Minute Walk Distance (6MWD)  Improvement in biomarkers of cardiac stress (NT-proBNP)  Improvement in lung function and pulmonary vascular volume (FRI)  Improvements in Quality of Life (CAMPHOR questionnaire)  Clinical worsening*  Steady-state period  3-week titration period; last   dose increase at   week 5 visit  * Clinical worsening is defined as one of the following: (1) Hospitalization due to a cardiopulmonary indication, (2) Lung transplantation, (3) Death from any cause, or (4) Decrease in 6MWD of at least 15% from baseline (at 2 consecutive visits at least 24 hours apart), directly related to disease  TPIP=Treprostinil Palmitil Inhalation Powder | 6MWD=six-minute walk distance | PH-ILD=pulmonary hypertension due to interstitial lung disease | QD=once daily  Trial summary  PH-ILD Trial 

 PH-ILD Phase 2 Study Met Primary Objective of Safety and Tolerability, With Lower Rates of Treatment Discontinuation and SAEs vs. Placebo  “N” = total participants randomized in specified group | “n” = number of participants within the group1 Based on investigator’s evaluation | 2 All events of cough were mild, and none led to treatment discontinuation. | 3 Includes any death that occurred on or after the first dose date. All deaths in the trial were related to disease progression or comorbid causes and none were attributed to TPIP. TEAE=Treatment emergent adverse event | SAE=Serious adverse event | TPIP=Treprostinil Palmitil Inhalation Powder | PH-ILD=pulmonary hypertension due to interstitial lung disease  TPIP (N=29)  Placebo (N=10)  Dose Titration  % Patients Titrated to Maximum 640 µg Dose of TPIP or Placebo (n)  % Patients Titrated to at least 480 µg Dose of TPIP or Placebo (n)  79.3% (23)  89.6% (26)  100.0% (10)  100.0% (10)  % Patients with Any TEAE (n)  Adverse Events (%)  93.1% (27)  90.0% (9)  % Patients with Study Drug Related1 TEAE (n)  % Patients with Study Drug Related Cough2 (n)  Adverse Events (%)  55.2% (16)  37.9% (11)  40.0% (4)  0.0% (0)  % Patients with TEAE Leading to Treatment Discontinuation (n)  Serious Adverse Events (%)  13.8% (4)  30.0% (3)  % Patients with Any SAE (n)  Serious Adverse Events (%)  20.7% (6)  40.0% (4)  % Patients with Study Drug Related1 SAE (n)  0.0% (0)  0.0% (0)  % Patient Deaths3 (n)  Deaths2  6.9% (2)  20.0% (2)  Trial was randomized 3:1 TPIP vs. placebo 

 PH-ILD Phase 2 Exploratory Efficacy Endpoints Support Advancement into Phase 3  “N” = total participants randomized in specified group; “n” = number of events, or participants within the group1 Calculation based on Hodges-Lehmann Estimate Location Shift | 2 Calculation based on geometric mean | 3 Calculation based on Fisher's Exact Test | 4 Two placebo patients each experienced two events, but this analysis counted only one event per subject | TPIP=Treprostinil Palmitil Inhalation Powder | PH-ILD=pulmonary hypertension due to interstitial lung disease  Trial was randomized 3:1 TPIP vs. placebo  TPIP (N=29)  Placebo (N=10)  Week 16  n  Week 16  n  6-Minute Walk Distance (6MWD)  Treatment effect (TPIP vs. placebo) at Week 161 (m)            Confidence interval            P-value  30  [-49.0, 171.0]  0.3484  29  N/A  10  NT-proBNP concentrations (pg/mL)2  (Baseline concentrations)  Geometric mean ratio to Baseline (Geometric SD)   Adverse Events (%)  197.50  (242.90)  0.81 (3.36)  24  382.59  (338.43)  1.13 (1.50)  7  % Patients with Clinical Worsening Event (n)     P-value (TPIP vs. placebo)3  Serious Adverse Events (%)  10.3% (3)  0.0164  29  50.0% (5)4  10  % Patients hospitalized due to cardiopulmonary indication (n)  0.0% (0)  29  30.0% (3)  10  % Patients with decrease in 6MWD ≥ 15% from Baseline (n)  3.4% (1)  29  20.0% (2)  10  % Patients who died from any cause (n)  6.9% (2)  29  20.0% (2)  10 

 TPIP Phase 2b in PAH  4 weeks  TPIP 80-640 µg  inhalation capsules QD   Placebo  inhalation capsules QD   Screening  Treatment period  16 weeks  Baseline  EOT  (primary analysis)  EOS  4 weeks  Follow-up  Approximately 100 participants randomized in the study   2:1 active : placebo  Steady-state period  3-week titration period; last dose increase at week 5 visit  Primary Endpoint  Change from baseline in pulmonary vascular resistance (PVR) at week 16  Secondary Exploratory Efficacy Endpoints  Change from baseline in exercise capacity (6MWD)  Change from baseline in WHO Functional class  Change from baseline in Quality of Life (CAMPHOR questionnaire)  Change from baseline in biomarkers of cardiac stress (NT-proBNP)  Trial summary  PAH Trial  TPIP=Treprostinil Palmitil Inhalation Powder | PAH=pulmonary arterial hypertension | 6MWD=six-minute walk distance | QD=once daily 

 Blended Blinded Phase 2 Data in PAH Indicates Potential of TPIP to Become Best-in-Class* Prostanoid  1 Dose titration analysis based on data available as of April 1, 2024. Dose titration data in PAH reflect first sets of patients in each trial who reached the Week 5 visit, which is the last possible point at which the dose can be increased in the trial.2 Efficacy analysis based on data available as of April 1, 2024. PVR data in PAH based on a review of 40 patients who had completed 16 weeks of treatment.3 6-Minute Walk Distance analysis based on data available as of April 1, 2024.  Blended/Blinded Data from Treatment and Placebo Arms (2:1 Randomization)  Dose Titration1  Patients Titrated to Maximum   Dose of 640 µg or Placebo (%)  34 (79%)  of first 43 patients who reached Week 5 visit  Most countries have approved protocol changes to increase the maximum dose of TPIP from 640 µg to up to 1,280 µg, once daily, for the open-label extension of its PAH study  Pulmonary Vascular   Resistance (PVR)2  Mean Reduction in PVR   from Baseline  19.9%  Based on first 40 patients who completed Week 16 of treatment, including active and placebo arms  6-Minute Walk Distance3  Mean Improvement in Distance  43 Meters  Based on first 40 patients who completed Week 16 of treatment, including active and placebo arms  Phase 2 PAH Trial Fully Enrolled with 102 Patients. Readout Expected in Mid-2025  * “Best-in-disease/best-in-class" indicates a profile that could be considered more attractive than other treatment options for a particular disease. Head-to-head clinical trials are not anticipated.DMC=Data Monitoring Committee 

 Gene Therapy &   Pre-Clinical Research  Gene Therapy  Duchenne Muscular Dystrophy (DMD)1  A rare genetic disorder that causes progressive muscle degeneration, primarily affecting young boys  Pre-Clinical Pipeline:  INS1202: ALS (Gene Therapy)  INS1203: Stargardt Disease (Gene Therapy)  Next Gen DPP1 (Multiple Indications)  Other Pre-Clinical Research (Multiple Indications)  1 INS1201 is Insmed’s lead gene therapy, an intrathecally-delivered treatment for patients with Duchenne muscular dystrophy (DMD); Plans to initiate a clinical trial in patients with DMD in the first half of 2025.   DMD: Duchenne muscular dystrophy; ALS: amyotrophic lateral sclerosis 

 Research Engine Has Produced First Product Candidate  Gene Therapy IND for Duchenne Muscular Dystrophy Cleared in December 20241  Our Approach  Low Upfront Costs  to acquire   the technologies  Low Ongoing Expense  <20% of   expenditures  Expect ~1-2 IND filings per year  Gene Therapy   Deimmunized Protein Engineering Using AI  Synthetic Rescue  RNA End-Joining  Our Platforms  1 INS1201 is Insmed’s lead gene therapy, an intrathecally-delivered treatment for patients with Duchenne muscular dystrophy (DMD); Plans to initiate a clinical trial in patients with DMD in the first half of 2025.  

 * 30-day safety observation period between each participant in each cohort  IDMC=Independent Data Monitoring Committee   Key Trial Information  Single dose via intrathecal administration  30-day safety monitoring period between each patient in each cohort  Patients must be ambulatory at time of screening  Primary Endpoint  Safety and Tolerability  Secondary Endpoints  Muscle dystrophin levels  Dose Finding  Exploratory Endpoints  Multiple age-appropriate functional and developmental outcomes  ASCEND  ASCEND Phase 1 in Duchenne Muscular Dystrophy (DMD)  Trial summary  Cohort 2: 3 - <5yrs  INS1201 IT  Dose Strength B  (3 patients)*  Cohort 1: 3 - <5yrs  INS1201 IT  Dose Strength A  (3 patients)*  Cohort 3: 2yrs  INS1201 IT  Dose Strength A  (3 patients)*  Cohort 4: 2yrs  INS1201 IT  Dose Strength B  (3 patients)*  The IDMC will meet after the completion of the 30-day safety period for the last participant in cohorts 1 and 3 for a safety review before initiating the next cohort(s)   SCREENING  INS1201 is Insmed’s lead gene therapy, an intrathecally-delivered treatment for patients with Duchenne muscular dystrophy (DMD); Plans to initiate a clinical trial in patients with DMD in the first half of 2025.  

 Our Culture is Our Greatest Strength  In a recent survey*  >90% of   Employees  who responded said they felt:  * The 2024 annual Insmed Pulse Survey included 89.4% participation across the organization  Proud to work at Insmed  Inspired by what we do  Confident in Insmed’s future  Driven to do their best work  No. 1 on Science’s Top BioPharma Employers List  Certified as a U.S. Great Place to Work  Four years in a row  Four years in a row 

 Strong, Long-Dated Patent Exclusivity  a Based on U.S. Patent Application No.18/024,040 and ex-U.S. counterpart applications issuing as patents. Additionally, given the complexity of drug product (liposomal inhalation with specific nebulizer), required bioequivalence testing could be difficult and lead to few generic entrants.  b Based on potential patent term extension (PTE) in the U.S. and US Application No. 16/975,292, which has been allowed, issuing in the U.S. c Based on SPC and Japan PTE being capped at 5 yearsd Based on US Application No. 18/513,377 and ex-US counterparts issuing as a patent  Brensocatib  ARIKAYCE  TPIP  Current   Exclusivity  Potential   Exclusivity  Current   Exclusivity  Potential   Exclusivity  Current   Exclusivity  Potential   Exclusivity   2034 2041d   2034 2041d   2034 2041d   2040 2040+b   2039 2040+c   2035 2040c   2035 2041a   2035 2041a   2035 2041a  US  EU  Japan 

 Manufacturing  Brensocatib  ARIKAYCE  TPIP  API  Drug Product  Spain  Canada   API  Drug Product  Taiwan   US   API  Drug Product  Italy  UK   To come online  Canada 

 ARISE: QoL-B Respiratory Score Changes* Show Clear Separation When PGI-S Category Improved vs. No Change or Decline  QoL-B: Quality of Life-Bronchiectasis Respiratory Domain questionnaire | PGI-S: Patient Global Impression of Severity | MAC: Mycobacterium avium complex   * Includes patient data from both the treatment and control arm of the ARISE study  Estimated Meaningful Score Difference Region is +12.2 to +16.7 points  ARIKAYCE  Estimated Meaningful Score Difference for QoL-B Resp. in MAC patients is +14.8 points 

 QoL-B Respiratory Domain  ALIS+AZI+ETH  N=48  ELC+AZI+ETH  N=51  Difference  # of Participants Evaluated for Change from Baseline to Month 7  43  48  # of Missing Change from Baseline to Month 7 Value  5  3  Change in PRO Score from Baseline to Month 7 (LS-Mean)  12.24  7.76  4.48   (95% Confidence Interval)   (7.96, 16.53)  (3.76, 11.77)  (-0.97, 9.93)   p-value  0.1073  ARISE: Comparison Between Treatment Arms Shows Clear Favorable Trend for ARIKAYCE Arm  ALIS: amikacin liposome inhalation suspension | AZI: azithromycin | ELC: empty liposome control | ETH: ethambutol | LS: least-squares | QoL-B: Quality of Life-Bronchiectasis Respiratory Domain questionnaire |   PRO: patient-reported outcome  ITT analysis with multiple imputation for missing data  ANCOVA model includes change from baseline as response variable and treatment, baseline Resp Score, and history of MAC lung infection as independent variables.  ARIKAYCE 

 ARISE: QoL-B Respiratory Score Changes from Baseline to Month 7   Show Clear Separation for ARIKAYCE Group  CDF: cumulative distribution function | ALIS: amikacin liposome inhalation suspension | AZI: azithromycin; ELC: empty liposome control | ETH: ethambutol |   QoL-B: Quality of Life-Bronchiectasis Respiratory Domain questionnaire | MAC: Mycobacterium avium complex  ARIKAYCE  Estimated Meaningful Score Difference for QoL-B Resp. in MAC patients is +14.8 points  Estimated Meaningful Score Difference Region is +12.2 to +16.7 points  43.8% of patients in ARIKAYCE arm achieved >14.8-point improvement   33.3% of patients in control arm achieved >14.8-point improvement 

 ARISE: Significantly* Higher, More Persistent Culture Conversion in ARIKAYCE Arm  ALIS: amikacin liposome inhalation suspension | AZI: azithromycin | ELC: empty liposome control | ETH: ethambutol  * “Nominally statistically significant” because no hierarchical testing or adjustment for multiplicity was conducted in ARISE.  Difference at Month 7 Nominally Statistically Significant*  (p-value = 0.0010)  Proportions estimated by Standardized Logistic Regression with treatment group and History of MAC Lung Infection as factors in the model with multiple imputation for missing data.  ARIKAYCE 

 ARISE: For Those Who Achieved Culture Conversion, Patients in ARIKAYCE Arm Converted Faster  ALIS: amikacin liposome inhalation suspension | AZI: azithromycin | ELC: empty liposome control | ETH: ethambutol  ~74% of converters on ARIKAYCE achieved clinical conversion at the first possible time point (Month 2) vs. ~47% for the control arm  ARIKAYCE 

 ALIS+AZI+ETH (N=48)  Culture Converted   by Month 6  Not Culture Converted   by Month 6  Difference  Change in QoL-B Resp. Score   (Baseline to Month 7)  +15.74  +3.53  +12.21    (95% Confidence Interval)   (+11.45, +20.03)  (-5.34, +12.41)  (+2.33, +22.08)    p-value   0.0167  Culture Converted   by Month 7  Not Culture Converted   by Month 7  Difference  Change in QoL-B Resp. Score   (Baseline to Month 7)  +14.89  +4.50  +10.39    (95% Confidence Interval)   (+10.47, +19.31)  (-4.40, +13.40)  (+0.42, +20.37)    p-value   0.0416  ARISE: Correlation Shown Between Culture Conversion and QoL-B Respiratory Score Changes in ARIKAYCE Arm  ALIS: amikacin liposome inhalation suspension | AZI: azithromycin | ETH: ethambutol | LS: least-squares; QoL-B: Quality of Life-Bronchiectasis Respiratory Domain questionnaire  ANCOVA model includes change from baseline as the response variable and baseline Resp Score, and culture conversion status as independent variables using observed data.  ARIKAYCE 

 ALIS+AZI+ETH  N=48  ELC+AZI+ETH  N=51  Total  N=99  Study completion (%)  44 (91.7)  48 (94.1)  92 (92.9)  Treatment completion with all 3 drugs (%)  35 (72.9)  47 (92.2)  82 (82.8)   Early ALIS/ELC discontinuation (%)  11 (22.9)  4 (7.8)  15 (15.2)  Any TEAE (%)  44 (91.7)  41 (80.4)  85 (85.9)   Dysphonia (%)  20 (41.7)  2 (3.9)  22 (22.2)   Cough (%)  13 (27.1)  4 (7.8)  17 (17.2)   Diarrhea (%)  13 (27.1)  13 (25.5)  26 (26.3)   COVID-19 (%)   6 (12.5)  5 (9.8)  11 (11.1)  # Participants with Serious TEAE (%)  7 (14.6)  3 (5.9)  10 (10.1)  ARISE: No New or Unexpected Safety Signals in ARISE  ALIS: amikacin liposome inhalation suspension | AZI: azithromycin | ELC: empty liposome control | ETH: ethambutol | TEAE: treatment-emergent adverse event; EAR: exposure adjusted incidence rate  All serious TEAEs unrelated to ARIKAYCE   ARIKAYCE 

 ASPEN: Annualized Rate of Adjudicated Pulmonary Exacerbations Over 52 Weeks  a Exacerbations were adjudicated events in the ITT analysis set analyzed using a negative binomial model b P value is statistically significant when adjusted for multiplicity control  c See Appendix for subgroup analysis | ITT=intention-to-treat  Annualized rate of exacerbationsa  21.1% Risk reduction  19.4% Risk reduction  Brensocatib 10 mgn=583  Brensocatib 25 mgn=575  Rate ratio vs. placebo  (95% CI)   0.789  (0.680–0.916)  0.806  (0.694–0.936)  P value  0.0019b  0.0046b  Primary endpoint  Risk Reduction Consistent Across Nearly All Pre-specified Subgroupsc  Brensocatib 

 ASPEN: Change From Baseline in Post-Bronchodilator FEV1 at Week 52  a % Predicted FEV1 analyzed using a linear repeated measures model in the ITT analysis set. b P value is statistically significant when adjusted for multiplicity controlc See Appendix for subgroup analysis  BD=bronchodilator | FEV1=forced expiratory volume in 1 second | ITT=intention-to-treat | LS=least squares  Secondary endpoint  Brensocatib 25 mg showed a 38 mL less FEV1 decline vs. placebo  (with similar results observed across  all prespecified subgroupsc)  Brensocatib 10 mg  Brensocatib 25 mg  Placebo  LS mean change from baseline to week 52 in post-BD FEV1 (mL)  −50  −24  −62  LS mean difference vs placebo in post-BD FEV1 (mL)  11  38  –  P value vs placebo  0.3841  0.0054b  –  LS mean (SE) change from baseline   in post-BD FEV1, mLa  1  16  28  40  52  Week  0  −20  −40  −60  579  545  529  513  475  571  529  523  494  487  563  522  513  494  468  Brensocatib 10 mg   Brensocatib 25 mg  Placebo  Placebo  Brensocatib 25 mg  Brensocatib 10 mg  Number of patients with observation  Brensocatib 

 ASPEN: Change From Baseline in QoL-B Respiratory Symptom Domain Score at Week 52  a Adult patients only. b P value vs placebo calculated using a linear repeated measures model in the ITT analysis set. c Nominally significant P value.LS=least squares | QoL-B RSS=Quality of Life-Bronchiectasis Questionnaire Respiratory Symptom Domain score.  Secondary endpoint  Brensocatib 25 mg showed a nominally significant improvement in QoL-B RSS of 3.8 points vs placebo  Brensocatib 10 mg  Brensocatib 25 mg  Placebo  LS mean change from baseline to week 52 in QoL-B RSS  6.841  8.575  4.809  LS mean difference vs placebo in QoL-B RSS  2.031  3.766  –  P value vs placebob  0.0594  0.0004c  –  1  4  8  12  16  20  24  28  32  36  40  44  48  52  0  2  4  6  8  LS mean (SE) change from baseline in QoL-B RSS  488  473  463  456  453  450  446  443  418  418  435  423  416  381  497  476  464  459  454  456  442  446  434  438  432  426  423  394  487  457  459  452  448  437  421  434  428  411  408  405  399  366  Placebo  Brensocatib 25 mg  Brensocatib 10 mg  Number of patients with observationa  Brensocatib 10 mg   Brensocatib 25 mg  Placebo  Week  Brensocatib 

 ASPEN: TEAEs and Treatment Discontinuations Were Comparable in Brensocatib and Placebo Arms  TEAE=treatment-emergent adverse event * As reported by study investigators  Brensocatib 10 mgn=582  Brensocatib 25 mgn=574  Placebon=563  Any TEAE, n (%)  452 (77.7)  440 (76.7)  448 (79.6)  Severe TEAE, n (%)   74 (12.7)  67 (11.7)  90 (16.0)  Serious TEAE, n (%)   101 (17.4)  97 (16.9)  108 (19.2)  TEAE leading to death, n (%)  3 (0.5)  4 (0.7)  7 (1.2)  TEAE leading to treatment discontinuation, n (%)   25 (4.3)  22 (3.8)  23 (4.1)  TEAEs of special interest*, n (%)  42 (7.2)  56 (9.8)  53 (9.4)  Hyperkeratosis, n (%)  8 (1.4)  17 (3.0)  4 (0.7)  Periodontal/gingival event, n (%)  8 (1.4)  12 (2.1)  15 (2.7)  Severe infection, n (%)  4 (0.7)  7 (1.2)  4 (0.7)  Pneumonia, n (%)  23 (4.0)  27 (4.7)  33 (5.9)  Rates of TEAEs of Special Interest* Were Comparable Between Treatment Arms and Placebo  Brensocatib 

 ASPEN: Change From Baseline in Post-Bronchodilator FVC at Week 52  Brensocatib  aFVC analyzed using a linear repeated measures model in the ITT analysis set. bNominally significant P value.BD=bronchodilator; FVC=forced vital capacity; ITT=intention-to-treat; LS=least squares.  Exploratory endpoint  Brensocatib 10 mg  Brensocatib 25 mg  Placebo  LS mean change from baseline to week 52 in post-BD FVC (mL)  -51  -12  -87  LS mean difference vs placebo in post-BD FVC (mL)  36  75  –  P value vs placebo  0.0331b  <0.0001b  –  Placebo  Brensocatib 25 mg  Brensocatib 10 mg  Number of patients with observation  545  529  513  475  529  523  494  487  522  513  494  468  579  571  563  1  16  28  40  52  20  0  −40  −80  Brensocatib 10 mg   Brensocatib 25 mg  Placebo  −100  −20  −60  LS mean (SE) change from baseline   in post-BD FVC, mLa  Week 

 ASPEN: Change From Baseline in Average Daily BEST Score  Brensocatib  a Average daily change in the BEST score analyzed with an analysis of covariance model in adult patients in the ITT analysis set. | b Nominally significant P value.BEST, Bronchiectasis Exacerbation and Symptoms Tool.  Exploratory endpoint  Brensocatib 10 mg  Brensocatib 25 mg  Placebo  LS mean change from baseline in 52-week average daily BEST score  −0.594  −0.999  −0.426  LS mean difference vs placebo in BEST score  −0.168  −0.572  –  P value vs placebo  0.1696  <0.0001b  –  Mean change from baseline in BEST scorea  Week  Number of patients with observationa  Placebo  Brensocatib 25 mg  Brensocatib 10 mg  558  553  555  547  544  534  528  520  515  506  504  505  497  488  557  552  542  540  534  529  517  520  522  513  507  505  499  494  549  549  541  534  527  520  517  508  505  499  493  490  485  477  1  4  8  12  16  20  24  28  32  36  40  44  48  52  −1.5  −1.0  −0.5  0.0  Brensocatib 10 mg   Brensocatib 25 mg   Placebo 

 Subgroup  Brensocatib 10 mg  (N=583)  n (%)  Brensocatib 25 mg  (N=575)  n (%)  Placebo (N=563)  n (%)  Brensocatib 10 mg  Rate ratio  (95% CI)  Brensocatib 10 mg  Rate ratio  (95% CI)  Brensocatib 25 mg  Rate ratio  (95% CI)  Brensocatib 25 mg  Rate ratio  (95% CI)  Overall  583 (100.0)  575 (100.0)  563 (100.0)  0.79 (0.68-0.92)  0.81 (0.69-0.94)  Age  12 to <18 years  17 (2.9)  16 (2.8)  8 (1.4)  0.41 (0.11-1.58)  0.73 (0.20-2.68)  18 to <65 years  289 (49.6)  257 (44.7)  295 (52.4)  0.81 (0.66-0.99)  0.70 (0.57-0.86)  ≥65 years  277 (47.5)  302 (52.5)  260 (46.2)  0.79 (0.63-0.99)  0.93 (0.74-1.15)  <75 years  500 (85.8)  491 (85.4)  470 (83.5)  0.81 (0.69-0.95)  0.79 (0.68-0.93)  ≥75 years  83 (14.2)  84 (14.6)  93 (16.5)  0.61 (0.40-0.94)  0.89 (0.59-1.34)  ≥18 years  566 (97.1)  559 (97.2)  555 (98.6)  0.80 (0.69-0.93)  0.80 (0.69-0.93)  Sex  Female  385 (66.0)  360 (62.6)  362 (64.3)  0.81 (0.68-0.96)  0.83 (0.70-1.00)  Male  198 (34.0)  215 (37.4)  201 (35.7)  0.75 (0.57-0.99)  0.75 (0.57-0.98)  Race  American Indian or Alaska Native  8 (1.4)  6 (1.0)  9 (1.6)  NE  NE  Asian  63 (10.8)  64 (11.1)  64 (11.4)  0.40 (0.23-0.67)  0.41 (0.24-0.70)  Black or African American  2 (0.3)  5 (0.9)  3 (0.5)  NE  NE  Native Hawaiian or Other Pacific Islander  1 (0.2)  0 (0.0)  1 (0.2)  NE  NE  White  431 (73.9)  430 (74.8)  405 (71.9)  0.79 (0.67-0.94)  0.79 (0.67-0.93)  Othera  15 (2.6)  13 (2.3)  11 (2.0)  NE  NE  Ethnicity  Hispanic or Latino  177 (30.4)  164 (28.5)  170 (30.2)  0.94 (0.70-1.26)  0.92 (0.69-1.24)  Not Hispanic or Latino  391 (67.1)  397 (69.0)  373 (66.3)  0.73 (0.61-0.87)  0.77 (0.64-0.92)  Number of PEs in prior 12 months  2  411 (70.5)  412 (71.7)  396 (70.3)  0.73 (0.60-0.89)  0.78 (0.65-0.95)  ≥3  172 (29.5)  163 (28.3)  167 (29.7)  0.89 (0.72-1.11)  0.85 (0.67-1.07)  PE=pulmonary exacerbationaOther races were Asian/Maori, Australian Aboriginal, Brown Race, Latin, Latino, Maori, Mestizo, Mexican, mixed, mixed race, New Zealand Maori, other mixed, and Puerto Rican.  Metersky ML, et al. CHEST Annual Meeting, Boston, MA, USA, October 6-9, 2024. Poster 3186.  0.1  1  Brensocatib 10 mg better  Placebo better  10  0.1  1  Brensocatib 25 mg better  Placebo better  10  ASPEN: Annualized Rate of Adjudicated Pulmonary Exacerbations Over 52 Weeks Among Prespecified Subgroups (1 of 3)  Brensocatib 

 Subgroup  Brensocatib 10 mg  (N=583)  n (%)  Brensocatib 25 mg  (N=575)  n (%)  Placebo (N=563)  n (%)  Brensocatib 10 mg  Rate ratio  (95% CI)  Brensocatib 10 mg  Rate ratio  (95% CI)  Brensocatib 25 mg  Rate ratio  (95% CI)  Brensocatib 25 mg  Rate ratio  (95% CI)  Chronic use of antibiotics  Yes  146 (25.0)  154 (26.8)  133 (23.6)  0.76 (0.59-0.97)  0.74 (0.57-0.96)  No  437 (75.0)  421 (73.2)  430 (76.4)  0.80 (0.66-0.96)  0.82 (0.68-0.98)  Maintenance use of macrolides  Yes  110 (18.9)  114 (19.8)  105 (18.7)  0.79 (0.58-1.06)  0.79 (0.58-1.08)  No  473 (81.1)  461 (80.2)  458 (81.3)  0.78 (0.66-0.93)  0.80 (0.67-0.95)  P. aeruginosa colonization status  Positive  203 (34.8)  205 (35.7)  199 (35.3)  0.75 (0.59-0.95)  0.88 (0.70-1.10)  Negative  380 (65.2)  370 (64.3)  364 (64.7)  0.81 (0.67-0.98)  0.77 (0.64-0.94)  BSI score  ≤4  136 (23.3)  150 (26.1)  148 (26.3)  0.77 (0.55-1.07)  0.69 (0.50-0.95)  5-8  275 (47.2)  239 (41.6)  220 (39.1)  0.71 (0.56-0.89)  0.77 (0.60-0.97)  ≥9  168 (28.8)  182 (31.7)  195 (34.6)  0.92 (0.72-1.17)  0.92 (0.73-1.17)  <Median  286 (49.1)  278 (48.3)  275 (48.8)  0.77 (0.61-0.97)  0.74 (0.59-0.92)  ≥Median  293 (50.3)  293 (51.0)  288 (51.2)  0.80 (0.66-0.97)  0.86 (0.70-1.04)  BE-CT score  <Median  274 (47.0)  273 (47.5)  255 (45.3)  0.78 (0.62-0.98)  0.91 (0.73-1.14)  ≥Median  309 (53.0)  302 (52.5)  308 (54.7)  0.81 (0.67-0.98)  0.74 (0.61-0.91)  Post-BD FEV1 (% predicted)  <50%  101 (17.3)  102 (17.7)  98 (17.4)  1.01 (0.70-1.46)  1.23 (0.86-1.75)  ≥50%  478 (82.0)  469 (81.6)  465 (82.6)  0.74 (0.62-0.87)  0.72 (0.61-0.85)  BD=bronchodilator; BE-CT=bronchiectasis computed tomography; BSI=Bronchiectasis Severity Index;   FEV1=forced expiratory volume in 1 second  Metersky ML, et al. CHEST Annual Meeting, Boston, MA, USA, October 6-9, 2024. Poster 3186.  0.1  1  Brensocatib 10 mg better  Placebo better  10  0.1  1  Brensocatib 25 mg better  Placebo better  10  ASPEN: Annualized Rate of Adjudicated Pulmonary Exacerbations Over 52 Weeks Among Prespecified Subgroups (2 of 3)  Brensocatib 

 COPD=chronic obstructive pulmonary disease; PE=pulmonary exacerbationbIncludes the United States and Canada. cIncludes Austria, Belgium, Bulgaria, Denmark, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Latvia, Netherlands, Poland, Portugal, Serbia, Slovakia, Spain, Turkey, and United Kingdom. dIncludes Argentina, Australia, Brazil, Chile, Colombia, Korea (the Republic of), Malaysia, Mexico, New Zealand, Peru, Taiwan, and Thailand. eIncludes Argentina, Brazil, Chile, Colombia, Mexico, and Peru. fIncludes Bulgaria, Greece, Hungary, Latvia, Poland, Serbia, Slovakia, and Turkey. gIncludes Austria, Belgium, Canada, Denmark, France, Germany, Ireland, Italy, Netherlands, Portugal, Spain, United Kingdom, and United States. hIncludes Israel, Japan, Korea (the Republic of), Malaysia, Taiwan, and Thailand. iIncludes Australia and New Zealand.   Metersky ML, et al. CHEST Annual Meeting, Boston, MA, USA, October 6-9, 2024. Poster 3186.  Subgroup  Brensocatib 10 mg  (N=583)  n (%)  Brensocatib 25 mg  (N=575)  n (%)  Placebo (N=563)  n (%)  Brensocatib 10 mg  Rate ratio  (95% CI)  Brensocatib 10 mg  Rate ratio  (95% CI)  Brensocatib 25 mg  Rate ratio  (95% CI)  Brensocatib 25 mg  Rate ratio  (95% CI)  Stratification region  North Americab  84 (14.4)  83 (14.4)  81 (14.4)  0.66 (0.45-0.97)  0.83 (0.59-1.18)  Europec  231 (39.6)  221 (38.4)  221 (39.3)  0.90 (0.72-1.14)  0.86 (0.70-1.08)  Japan  30 (5.1)  28 (4.9)  29 (5.2)  0.37 (0.16-0.87)  0.32 (0.14-0.75)  Rest of Worldd  238 (40.8)  243 (42.3)  232 (41.2)  0.79 (0.63-0.99)  0.83 (0.65-1.06)  Geographic region  South Americae  174 (29.8)  157 (27.3)  157 (27.9)  0.91 (0.68-1.23)  0.92 (0.67-1.26)  Eastern Europef  75 (12.9)  68 (11.8)  72 (12.8)  0.54 (0.29-0.99)  0.62 (0.35-1.08)  Western countriesg  216 (37.0)  205 (35.7)  201 (35.7)  0.86 (0.70-1.07)  0.86 (0.69-1.06)  Asian countriesh  81 (13.9)  91 (15.8)  88 (15.6)  0.62 (0.41-0.94)  0.62 (0.41-0.94)  Oceaniai  37 (6.3)  54 (9.4)  45 (8.0)  0.79 (0.54-1.17)  0.77 (0.51-1.18)  Blood eosinophil count  ≥300/mm3  115 (19.7)  111 (19.3)  106 (18.8)  0.72 (0.52-0.99)  0.86 (0.62-1.20)  <300/mm3  465 (79.8)  461 (80.2)  452 (80.3)  0.81 (0.68-0.95)  0.79 (0.67-0.94)  Smoking status  Former smoker  164 (28.1)  163 (28.3)  183 (32.5)  0.83 (0.64-1.07)  0.75 (0.58-0.97)  Never smoked  419 (71.9)  412 (71.7)  380 (67.5)  0.78 (0.65-0.93)  0.84 (0.70-1.01)  Use of inhaled steroids  Yes  324 (55.6)  324 (56.3)  352 (62.5)  0.83 (0.69-0.99)  0.76 (0.63-0.92)  No  259 (44.4)  251 (43.7)  211 (37.5)  0.78 (0.60-1.01)  0.93 (0.73-1.20)  History of asthma  Yes  101 (17.3)  109 (19.0)  111 (19.7)  0.96 (0.71-1.30)  0.99 (0.72-1.34)  No  482 (82.7)  466 (81.0)  452 (80.3)  0.75 (0.63-0.89)  0.76 (0.64-0.90)  History of COPD  Yes  77 (13.2)  83 (14.4)  102 (18.1)  0.70 (0.44-1.13)  0.81 (0.56-1.18)  No  506 (86.8)  492 (85.6)  461 (81.9)  0.80 (0.68-0.93)  0.80 (0.68-0.95)  Hospitalized in prior 24 months for PE  Yes  146 (25.0)  133 (23.1)  142 (25.2)  0.89 (0.68-1.16)  0.81 (0.61-1.07)  No  437 (75.0)  442 (76.9)  421 (74.8)  0.76 (0.63-0.90)  0.81 (0.68-0.96)  0.1  1  Brensocatib 10 mg better  Placebo better  10  0.1  1  Brensocatib 25 mg better  Placebo better  10  ASPEN: Annualized Rate of Adjudicated Pulmonary Exacerbations Over 52 Weeks Among Prespecified Subgroups (3 of 3)  Brensocatib 

 Subgroup  Brensocatib 10 mg  (N=583)  n (%)  Brensocatib 25 mg  (N=575)  n (%)  Placebo (N=563)  n (%)  Brensocatib 10 mg  LS mean difference  (95% CI)  Brensocatib 10 mgLS mean difference  (95% CI)  Brensocatib 25 mg  LS mean difference  (95% CI)  Brensocatib 25 mg  LS mean difference  (95% CI)  Overall  583 (100.0)  575 (100.0)  563 (100.0)  11 (–14 to 37)  38 (11 to 65)  Age  12 to <18 years  17 (2.9)  14 (2.4)  8 (1.4)  287 (–134 to 707)  324 (–96 to 745)  18 to <65 years  281 (48.2)  243 (42.3)  280 (49.7)  –4 (–43 to 35)  31 (–11 to 74)  ≥65 years  266 (45.6)  294 (51.1)  251 (44.6)  21 (–12 to 55)  42 (9 to 75)  <75 years  482 (82.7)  470 (81.7)  448 (79.6)  10 (–19 to 39)  40 (10 to 70)  ≥75 years  82 (14.1)  81 (14.1)  91 (16.2)  23 (–35 to 80)  29 (–26 to 83)  ≥18 years  547 (93.8)  537 (93.4)  531 (94.3)  8 (–18 to 34)  36 (10 to 63)  Sex  Female  371 (63.6)  342 (59.5)  347 (61.6)  –3 (–32 to 26)  32 (2 to 62)  Male  193 (33.1)  209 (36.3)  192 (34.1)  42 (–9 to 94)  50 (–1 to 102)  Race  American Indian or Alaska Native  8 (1.4)  6 (1.0)  8 (1.4)  256 (–233 to 746)  256 (34 to 478)  Asian  63 (10.8)  63 (11.0)  58 (10.3)  18 (–27 to 63)  69 (24 to 114)  Black or African American  1 (0.2)  5 (0.9)  2 (0.4)  NE  NE  Native Hawaiian or Other Pacific Islander  1 (0.2)  0 (0.0)  1 (0.2)  NE  NE  White  416 (71.4)  409 (71.1)  392 (69.6)  11 (–19 to 40)  27 (–4 to 58)  Othera  14 (2.4)  13 (2.3)  10 (1.8)  30 (–118 to 178)  152 (–96 to 399)  Ethnicity  Hispanic or Latino  171 (29.3)  156 (27.1)  164 (29.1)  19 (–36 to 75)  29 (–26 to 84)  Not Hispanic or Latino  378 (64.8)  382 (66.4)  355 (63.1)  6 (–23 to 35)  40 (9 to 70)  Number of PEs in prior 12 months  2  395 (67.8)  392 (68.2)  375 (66.6)  11 (–21 to 44)  38 (7 to 70)  ≥3  169 (29.0)  159 (27.7)  164 (29.1)  12 (–30 to 55)  35 (–16 to 87)  FEV1=forced expiratory volume in 1 second; LS=least squares; PE=pulmonary exacerbationa Other races were Asian/Maori, Australian Aboriginal, Brown Race, Latin, Latino, Maori, Mestizo, Mexican, mixed, mixed race, New Zealand Maori, other mixed, and Puerto Rican.   Aksamit TR, et al. CHEST Annual Meeting, Boston, MA, USA, October 6-9, 2024. Poster 3185.  Placebo better  Brensocatib 10 mg better  -300  -200  -100  0  100  200  300  400  500  600  700  800  Placebo better  Brensocatib 25 mg better  -300  -200  -100  0  100  200  300  400  500  600  700  800  ASPEN: Change From Baseline in Post-Bronchodilator FEV1 at Week 52 Among Prespecified Subgroups (1 of 3)  Brensocatib 

 Subgroup  Brensocatib 10 mg  (N=583)  n (%)  Brensocatib 25 mg  (N=575)  n (%)  Placebo (N=563)  n (%)  Brensocatib 10 mg  LS mean difference  (95% CI)  Brensocatib 10 mgLS mean difference  (95% CI)  Brensocatib 25 mg  LS mean difference  (95% CI)  Brensocatib 25 mg  LS mean difference  (95% CI)  Chronic use of antibiotics  Yes  141 (24.2)  147 (25.6)  128 (22.7)  –22 (–75 to 30)  40 (–9 to 89)  No  423 (72.6)  404 (70.3)  411 (73.0)  22 (–8 to 52)  37 (5 to 68)  Maintenance use of macrolides  Yes  106 (18.2)  110 (19.1)  104 (18.5)  –15 (–70 to 39)  44 (–16 to 104)  No  458 (78.6)  441 (76.7)  435 (77.3)  17 (–12 to 47)  35 (2 to 73)  P. aeruginosa colonization status  Positive  199 (34.1)  194 (33.7)  190 (33.7)  4 (–32 to 39)  40 (2 to 78)  Negative  365 (62.6)  357 (62.1)  349 (62.0)  16 (–19 to 51)  37 (2 to 73)  BSI score  ≤4  131 (22.5)  144 (25.0)  144 (25.6)  –7 (–68 to 54)  23 (–33 to 80)  5-8  270 (46.3)  231 (40.2)  208 (36.9)  23 (–15 to 61)  22 (–17 to 60)  ≥9  163 (28.0)  176 (30.6)  187 (33.2)  17 (–22 to 56)  74 (28 to 121)  <Median  277 (47.5)  268 (46.6)  261 (46.4)  0 (–40 to 40)  18 (–21 to 58)  ≥Median  287 (49.2)  283 (49.2)  278 (49.4)  26 (–8 to 59)  58 (22 to 94)  BE-CT score  <Median  266 (45.6)  261 (45.4)  249 (44.2)  8 (–33 to 50)  30 (–13 to 72)  ≥Median  298 (51.1)  290 (50.4)  290 (51.5)  17 (–15 to 49)  48 (15 to 81)  Post-BD FEV1 (% predicted)  <50%  98 (16.8)  96 (16.7)  92 (16.3)  –10 (–60 to 40)  32 (–23 to 87)  ≥50%  466 (79.9)  455 (79.1)  447 (79.4)  16 (–13 to 46)  39 (9 to 69)  BD=bronchodilator; BE-CT=bronchiectasis computed tomography; BSI=Bronchiectasis Severity Index; FEV1=forced expiratory volume in 1 second; LS=least squares  Aksamit TR, et al. CHEST Annual Meeting, Boston, MA, USA, October 6-9, 2024. Poster 3185.  Placebo better  Brensocatib 10 mg better  -300  -200  -100  0  100  200  300  400  500  600  700  800  Placebo better  Brensocatib 25 mg better  -300  -200  -100  0  100  200  300  400  500  600  700  800  ASPEN: Change From Baseline in Post-Bronchodilator FEV1 at Week 52 Among Prespecified Subgroups (2 of 3)  Brensocatib 

 COPD=chronic obstructive pulmonary disease; FEV1=forced expiratory volume in 1 second; LS=least squares; PE=pulmonary exacerbationbIncludes the United States and Canada. cIncludes Austria, Belgium, Bulgaria, Denmark, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Latvia, Netherlands, Poland, Portugal, Serbia, Slovakia, Spain, Turkey, and United Kingdom. dIncludes Argentina, Australia, Brazil, Chile, Colombia, Korea (the Republic of), Malaysia, Mexico, New Zealand, Peru, Taiwan, and Thailand. eIncludes Argentina, Brazil, Chile, Colombia, Mexico, and Peru. fIncludes Bulgaria, Greece, Hungary, Latvia, Poland, Serbia, Slovakia, and Turkey. gIncludes Austria, Belgium, Canada, Denmark, France, Germany, Ireland, Italy, Netherlands, Portugal, Spain, United Kingdom, and United States. hIncludes Israel, Japan, Korea (the Republic of), Malaysia, Taiwan, and Thailand. iIncludes Australia and New Zealand.   Aksamit TR, et al. CHEST Annual Meeting, Boston, MA, USA, October 6-9, 2024. Poster 3185.  Subgroup  Brensocatib 10 mg  (N=583)  n (%)  Brensocatib 25 mg  (N=575)  n (%)  Placebo (N=563)  n (%)  Brensocatib 10 mg  LS mean difference  (95% CI)  Brensocatib 10 mgLS mean difference  (95% CI)  Brensocatib 25 mg  LS mean difference  (95% CI)  Brensocatib 25 mg  LS mean difference  (95% CI)  Stratification region  North Americab  79 (13.6)  81 (14.1)  75 (13.3)  20 (–44 to 85)  77 (–5 to 159)  Europec  223 (38.3)  211 (36.7)  214 (38.0)  5 (–36 to 46)  35 (–8 to 78)  Japan  30 (5.1)  28 (4.9)  29 (5.2)  47 (–20 to 115)  97 (32 to 162)  Rest of Worldd  232 (39.8)  231 (40.2)  221 (39.3)  11 (–32 to 54)  20 (–20 to 60)  Geographic region  South Americae  169 (29.0)  149 (25.9)  151 (26.8)  10 (–46 to 67)  13 (–41 to 66)  Eastern Europef  74 (12.7)  65 (11.3)  67 (11.9)  48 (–23 to 120)  41 (–50 to 131)  Western countriesg  206 (35.3)  196 (34.1)  193 (34.3)  1 (–42 to 44)  56 (8 to 104)  Asian countriesh  79 (13.6)  90 (15.7)  84 (14.9)  –1 (–44 to 42)  39 (–4 to 82)  Oceaniai  36 (6.2)  51 (8.9)  44 (7.8)  28 (–51 to 108)  32 (–44 to 109)  Blood eosinophil count  ≥300/mm3  110 (18.9)  110 (19.1)  101 (17.9)  0 (–57 to 57)  43 (–24 to 110)  <300/mm3  452 (77.5)  438 (76.2)  434 (77.1)  16 (–13 to 46)  37 (7 to 66)  Smoking status  Former smoker  159 (27.3)  159 (27.7)  177 (31.4)  11 (–33 to 55)  51 (8 to 93)  Never smoked  405 (69.5)  392 (68.2)  362 (64.3)  12 (–20 to 44)  33 (–1 to 66)  Use of inhaled steroids  Yes  314 (53.9)  312 (54.3)  337 (59.9)  13 (–21 to 47)  41 (6 to 76)  No  250 (42.9)  239 (41.6)  202 (35.9)  10 (–29 to 49)  37 (–4 to 78)  History of asthma  Yes  96 (16.5)  105 (18.3)  106 (18.8)  –23 (–89 to 42)  24 (–41 to 90)  No  468 (80.3)  446 (77.6)  433 (76.9)  20 (–8 to 48)  42 (12 to 71)  History of COPD  Yes  77 (13.2)  80 (13.9)  96 (17.1)  10 (–45 to 65)  39 (–12 to 90)  No  487 (83.5)  471 (81.9)  443 (78.7)  10 (–19 to 39)  37 (7 to 67)  Hospitalized in prior 24 months for PE  Yes  141 (24.2)  130 (22.6)  134 (23.8)  58 (4 to 113)  110 (53 to 166)  No  423 (72.6)  421 (73.2)  405 (71.9)  –3 (–32 to 26)  15 (–15 to 44)  Placebo better  Brensocatib 10 mg better  -300  -200  -100  0  100  200  300  400  500  600  700  800  Placebo better  Brensocatib 25 mg better  -300  -200  -100  0  100  200  300  400  500  600  700  800  ASPEN: Change From Baseline in Post-Bronchodilator FEV1 at Week 52 Among Prespecified Subgroups (3 of 3)  Brensocatib 

 TPIP showed substantially lower Cmaxand longer half-life  Supports the potential for improved tolerability, efficacy and convenience  Safety profile was generally well tolerated, AEs were mild and consistent with inhaled prostanoid  Tolerability was improved with an up-titration approach  Findings suggest TPIP may be safely dosed at nominal doses far in excess of Tyvaso  PK supports development of TPIP with once daily dosing  TPIP showed substantially lower Cmax and longer half-life than that of Tyvaso  Future studies would use an up-titration dosing schedule to the maximum individual tolerated dose exceeding 600 µg once daily  TPIP  TPIP Phase 1 Study: Key Takeaways  TPIP=treprostinil palmitil inhalation powder; AES=adverse events; Cmax=highest concentration of a drug in blood, fluid, or target organ after dosing; PK=pharmacokinetics 

 TPIP  TPIP: Change From Baseline in Small and Large Blood Vessels  aEffect size was calculated as a percentage of the treatment effect divided by the placebo arm baseline mean.   SD=standard deviation; TPIP=treprostinil palmitil inhalation powder; BV5A=volume of pulmonary arteries smaller than 5 mm2 in cross-sectional area; BV10A=volume of pulmonary arteries larger than 10 mm2 in cross-sectional area  There was a consistent increase of blood volume in small arteries observed with TPIP vs. placebo  Baseline, mean (SD)  Change from baseline, %  Effect size,a %  P value  TPIP(n=9)  Placebo(n=5)  TPIP(n=9)  Placebo(n=5)  BV5A (mL)  volume of pulmonary arteries <5 mm2  19.5 (7.3)  33.6 (21.1)  +14.0  –7.5  +13.0  0.24  BV5A PR (%)  volume of small arteries (<5 mm2) as a fraction of total pulmonary vessel volume  24.1 (5.0)  27.6 (8.2)  +8.4  –5.5  +13.7  0.02  BV5A PRA (%)  volume of small arteries (<5 mm2) as a fraction of total pulmonary artery volume  44.4 (8.1)  47.1 (13.2)  +8.0  –3.8  +13.6  0.05  BV10A (mL)  volume of pulmonary arteries >10 mm2  11.9 (6.5)  15.8 (6.4)  –7.1  +16.3  –25.7  0.14  BV10A PR (%)  volume of large arteries (>10 mm2) as a fraction of total pulmonary vessel volume  14.0 (4.3)  14.6 (5.2)  –10.8  +16.4  –23.2  0.08  BV10A PRA (%)  volume of large arteries (>10 mm2) as a fraction of total pulmonary artery volume  25.7 (7.0)  25.0 (8.5)  –12.0  +18.7  –24.8  0.07  BV5A:BV10A RATIO  2.0 (1.1)  2.6 (2.5)  +31.4  –10.5  +49.4  0.17  Lung imaging results from the Phase 2 PH-ILD study 

 TPIP  TPIP: Change From Baseline in High Attenuation Abnormality Scorea   bThe HAA score is expressed as a percentage of total lung volume.  cEffect size was calculated as a percentage of the treatment effect divided by the placebo arm baseline mean.  HAA=high-attenuation abnormality; SD=standard deviation; TPIP=treprostinil palmitil inhalation powder  A numerical decrease from baseline in the HAA score observed with   TPIP and slight increase with placebo  aA deep-learning algorithm was trained to distinguish between patches of voxels from scans of subjects with IPF and healthy subjects using automatically extracted high-attenuation textural features, excluding segmented blood vessels and airway walls, and to output a probability that a given patch is "fibrotic.” The algorithm is applied to overlapping patches, calculating the attenuation probability for a given voxel as an average probability of all the patches which cover that voxel. The HAA score is that volume of high-attenuation voxels with a greater than 50% chance of being "fibrotic.“  Change from baseline, mean (SD)  Effect size,c %  P value  TPIP (n=9)  Placebo (n=5)  HAA score,b %  –0.7 (2.7)  0.3 (1.8)  –10.5  0.54  Lung imaging results from the Phase 2 PH-ILD study 

 Color indicates vessel size. Small vessels with cross-sectional area (CSA) <5 mm2 are colored in red (●), vessels with CSA 5-10 mm2 – in yellow (●), and CSA >10 mm2 – in blue (●). Parameters indicated as BV5 and BV10 represent the total volume of vessels with CSA <5 mm2 and >10 mm2, respectively. Note the increase of small vessels colored in red (●) in patients treated with TPIP at week 16, compared with placebo.   TPIP  TPIP: FRI in Representative Patients Treated with TPIP (A) vs. Placebo (B)  TPIP treatment resulted in a significant increase in the fraction of blood volume in small arteries and a directional improvement in small-to-large artery volume ratio versus placebo  Results suggestive of small vessel vasodilation and improved pulmonary arteriole recruitment  A numerical decrease in HAA score was observed with TPIP  Limitations included the small sample size, which may limit the generalizability of the results and may increase the risk of random variation  Further evaluation of FRI in a larger trial may provide additional insights and support the strength and potential increased generalizability of these findings  FRI=functional respiratory imaging; CSA=cross-sectional area; BV5A=volume of pulmonary arteries smaller than 5 mm2 in cross-sectional area; BV10A=volume of pulmonary arteries larger than 10 mm2 in cross-sectional area; TPIP=treprostinil palmitil inhalation powder; HAA=high-attenuation abnormality  TPIP  Change from baseline, mL (%)  BV5A:BV10A RATIO  +0.45 (+29.7%)  Placebo  Change from baseline, mL (%)  BV5A:BV10A RATIO  -0.11 (-8%)  TPIP (A)  Placebo (B)  Lung imaging results from the Phase 2 PH-ILD study 

 Epidemiological Footnotes (1 of 3)  1. Internal analysis of published NTM epidemiology, including internal market research and US patient level claims data analysis:   Jennifer Adjemian, Kenneth N Olivier, Amy E Seitz, Steven M Holland, D Rebecca Prevots: Prevalence of nontuberculous mycobacterial lung disease in U.S. Medicare beneficiaries Am J Respir Crit Care Med. 2012 Apr 15; 185(8):881-6 DOI: 10.1164/rccm.201111-2016OC  Jennifer Adjemian, D Rebecca Prevots, Jack Gallagher, Kylee Heap, Renu Gupta, David Griffith: Lack of adherence to evidence-based treatment guidelines for nontuberculous mycobacterial lung disease Ann Am Thorac Soc. 2014 Jan; 11(1): 9–16 DOI: 10.1513/AnnalsATS.201304-085OC  Sara E. Strollo , Jennifer Adjemian, Michael K. Adjemian, and D. Rebecca Prevots: The Burden of Pulmonary Nontuberculous Mycobacterial Disease in the United States Ann Am Thorac Soc Vol 12, No 10, pp 1458–1464, Oct 2015 DOI: 10.1513/AnnalsATS.201503-173OC  https://www.kff.org/medicare/state-indicator/total-medicare-beneficiaries/?currentTimeframe=0&sortModel=%7B%22colId%22:%22Location%22,%22sort%22:%22asc%22%7D  Felix C. Ringshausen, Dirk Wagner, Andrés de Roux, Roland Diel, David Hohmann, Lennart Hickstein, Tobias Welte, Jessica Rademacher: Prevalence of Nontuberculous Mycobacterial Pulmonary Disease, Germany, 2009–2014 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 22, No. 6, June 2016 DOI: http://dx.doi.org/10.3201/eid2206.151642  Jonathan E Moore, Michelle E Kruijshaar, L Peter Ormerod, Francis Drobniewski , Ibrahim Abubakar: Increasing reports of non-tuberculous mycobacteria in England, Wales and Northern Ireland, 1995-2006 BMC Public Health 2010, 10:612 http://www.biomedcentral.com/1471-2458/10/612  Hoefsloot, Van Ingen et al, The geographic diversity of nontuberculous mycobacteria isolated from pulmonary samples, AN NTM-NET collaborative study; 2013, European Respiratory Journal 2013 42: 1604-1613; DOI: 10.1183/09031936.00149212   Kozo Morimoto , Kazuro Iwai , Kazuhiro Uchimura , Masao Okumura , Takashi Yoshiyama , Kozo Yoshimori, Hideo Ogata , Atsuyuki Kurashima , Akihiko Gemma, and Shoji Kudoh: A Steady Increase in Nontuberculous Mycobacteriosis Mortality and Estimated Prevalence in Japan Ann Am Thorac Soc Vol 11, No 1, pp 1–8, Jan 2014, DOI: 10.1513/AnnalsATS.201303-067OC   2. Internal analysis of published BE epidemiology, including internal market research and US patient level claims data analysis:  Weycker, et al. Prevalence and incidence of NCFBE among US adults in 2013. Chronic Respiratory Disease. 2017   BE Patient Level Claims Data Analysis. Source: swoop/ipm.ai  Trinity Epidemiology Assessment; 2020 (for Japan epi)  Ringausen et al 2019 Growth (Germany)  Aliberti 2016; quality standards for the management of bronchiectasis in Italy  Snell et al. United Kingdom; 2019  Internal Insmed NCFBE market sizing EU5 report   3. Internal analysis and estimations based on internal market research and US patient level claims data analysis:  Insmed Analysis 2022: Potential Undiagnosed or Misdiagnosed (with COPD, Asthma) BE patients in US estimated based on Medical Experts driven insights, applied to Patient Level Claims Data -using advanced analytics / statistical methods Potential Undiagnosed or Co-morbid (with COPD) BE patients in US derived based on internal Insmed meta-analysis of 16 epi studies that look at BE prevalence in COPD patients; Ex-US estimates are based on extrapolation of US focused claims and epi data analysis   4 

 Epidemiological Footnotes (2 of 3)  4. Internal analysis and estimations based on published epidemiology studies:  National Health Interview Survey (NHIS) Data (2021)  Alshabanat A, Zafari Z, Albanyan O, Dairi M, FitzGerald JM (2015) Asthma and COPD Overlap Syndrome (ACOS): A Systematic Review and Meta Analysis. PLoS ONE 10(9): e0136065. doi:10.1371/ journal.pone.0136065  OECD/European Union (2016), “Asthma and COPD prevalence”, in Health at a Glance: Europe 2016: State of Health in the EU Cycle, OECD Publishing, Paris.   Hosseini, M., Almasi-Hashiani, A., Sepidarkish, M. et al. Global prevalence of asthma-COPD overlap (ACO) in the general population: a systematic review and meta-analysis. Respir Res 20, 229 (2019). https://doi.org/10.1186/s12931-019-1198-4  Blanco I, Diego I, Bueno P, et al. Geographic distribution of COPD prevalence in the world displayed by Geographic Information System maps. Eur Respir J 2019; 54: 1900610 [https://doi.org/ 10.1183/13993003.00610-2019].   R. de Marco et al. Eur Respir J 2012; 39:883-892. DOI: 10.1183/09031936.000611.  Iwanaga T, Tohda Y. [Epidemiology of asthma in Japan]. Nihon Rinsho. 2016 Oct;74(10):1603-1608. Japanese. PMID: 30551268  Massoth L, Anderson C, McKinney KA. Asthma and Chronic Rhinosinusitis: Diagnosis and Medical Management. Med Sci (Basel). 2019 Mar 27;7(4):53. doi: 10.3390/medsci7040053. PMID: 30934800; PMCID: PMC6524348.  Hashimoto S, Yoshida Y, Makita N, Sorimachi R, Sugaya S, Arita Y, Hayashi N, Tashiro N, Ichinose M. Real-World Evidence on the Diagnostic and Clinical Characteristics of Asthma in Japanese Patients with COPD: The ACO Japan Cohort Study. Int J Chron Obstruct Pulmon Dis. 2023;18:37-46   Awad MT, Sankari A. Asthma and COPD Overlap. [Updated 2023 Jun 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK592422/  https://www.cdc.gov/asthma/most_recent_national_asthma_data.htm  https://www.cdc.gov/copd/php/case-reporting/national-trends-in-copd.html  Minakata Y, Ichinose M. [Epidemiology of COPD in Japan]. Nihon Rinsho. 2011 Oct;69(10):1721-6. Japanese. PMID: 22073563   5. Internal assessment of published epidemiology and US patient level claims data analysis:  Cho et. al, Chronic Rhinosinusitis without Nasal Polyps J Allergy Clin Immunol Pract. 2016 ; 4(4): 575–582. doi:10.1016/j.jaip.2016.04.015  Benjamin et. al, Clinical Characteristics of Patients with Chronic Rhinosinusitis without Nasal Polyps in an Academic Setting, J ALLERGY CLIN IMMUNOL PRACT VOLUME 7, NUMBER 3, MARCH 2019  Komodo Health: CRS patient level claims data analysis 2022 - US only, Extrapolated to Europe5 and Japan  Palmer JN, Messina JC, Biletch R, Grosel K, Mahmoud RA. A cross-sectional, population-based survey of U.S. adults with symptoms of chronic rhinosinusitis. Allergy Asthma Proc. 2019 Jan 14;40(1):48-56. doi: 10.2500/aap.2019.40.4182. PMID: 30582496   6. Internal assessment of market research, published epidemiology and US patient level claims data analysis:   Hidradenitis Suppurativa (HS) - Market Insights, Epidemiology, and Market Forecast Report (2019-2032). Source: DelveInsight  Komodo Health: HS patient level claims data analysis 2024: Potential HS Patients (1+ HS Dx in claims history 2016-23) - US only, Extrapolated to Europe5 and Japan 

 Epidemiological Footnotes (3 of 3)  7. Internal assessment of published epidemiology and US patient level claims data analysis, including:  Kirson, N. Y., Birnbaum, H. G., Ivanova, J. I., Waldman, T., Joish, V., & Williamson, T. (2011). Prevalence of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension in the United States. Current Medical Research and Opinion, 27(9), 1763–1768. https://doi.org/10.1185/03007995.2011.604310  2019 National Audit of Pulmonary Hypertension Great Britain; Humbert M et al, “Pulmonary arterial hypertension in France: results from a national registry”, Feb 2006  Ling Y, Johnson MK, Kiely DG, Condliffe R, Elliot CA, Gibbs JS, Howard LS, Pepke-Zaba J, Sheares KK, Corris PA, Fisher AJ, Lordan JL, Gaine S, Coghlan JG, Wort SJ, Gatzoulis MA, Peacock AJ. Changing demographics, epidemiology, and survival of incident pulmonary arterial hypertension: results from the pulmonary hypertension registry of the United Kingdom and Ireland. Am J Respir Crit Care Med. 2012 Oct 15;186(8):790-6. doi: 10.1164/rccm.201203-0383OC. Epub 2012 Jul 12. PMID: 22798320.  Escribano-Subias P, Blanco I, López-Meseguer M, Lopez-Guarch CJ, Roman A, Morales P, Castillo-Palma MJ, Segovia J, Gómez-Sanchez MA, Barberà JA; REHAP investigators. Survival in pulmonary hypertension in Spain: insights from the Spanish registry. Eur Respir J. 2012 Sep;40(3):596-603. doi: 10.1183/09031936.00101211. Epub 2012 Feb 23. PMID: 22362843.  Hoeper MM, Huscher D, Pittrow D. Incidence and prevalence of pulmonary arterial hypertension in Germany. Int J Cardiol. 2016 Jan 15;203:612-3. doi: 10.1016/j.ijcard.2015.11.001. Epub 2015 Nov 9. PMID: 26580339.  Humbert M, Sitbon O, Chaouat A, Bertocchi M, Habib G, Gressin V, Yaici A, Weitzenblum E, Cordier JF, Chabot F, Dromer C, Pison C, Reynaud-Gaubert M, Haloun A, Laurent M, Hachulla E, Simonneau G. Pulmonary arterial hypertension in France: results from a national registry. Am J Respir Crit Care Med. 2006 May 1;173(9):1023-30. doi: 10.1164/rccm.200510-1668OC. Epub 2006 Feb 2. PMID: 16456139.  Secondary research: Japan’s Intractable Disease Database 2021  Diagnosed prevalence for PH-LHD, CTEPH and PH-Idiopathic sourced from “Patient-Based Forecast Model Pulmonary Hypertension”, Datamonitor, September 2023.   8. Internal assessment of published epidemiology, including:  Andersen, C. U., Mellemkjær, S., Hilberg, O., Nielsen-Kudsk, J. E., Simonsen, U., & Bendstrup, E. (2012). Pulmonary hypertension in interstitial lung disease: prevalence, prognosis and 6 min walk test. Respiratory medicine, 106(6), 875-882.  Ryu, Jay H., et al. "Pulmonary hypertension in patients with interstitial lung diseases." Mayo Clinic Proceedings. Vol. 82. No. 3. Elsevier, 2007  Duchemann et al., “Prevalence and incidence of interstitial lung diseases in a multi-ethnic county of Greater Paris.” European Respiratory Journal, 2017  Diagnosed prevalence for PH-LHD, CTEPH and PH-Idiopathic sourced from “Patient-Based Forecast Model Pulmonary Hypertension”, Datamonitor, September 2023.