Exhibit 99.2
January 13, 2025 JPMorgan Healthcare Conference Presentation
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; the risk that the full data set from the ASPEN study or data generated in further clinical trials of brensocatib will not be consistent with the topline results of the ASPEN study or any additional data published from the ASPEN study; 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 or TPIP 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 or TPIP, or acceptable prices for ARIKAYCE or, if approved, brensocatib or TPIP; 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 L.P. 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; risks that interim or partial data sets are not representative of a complete or larger data set or that blinded data will not be predictive of unblinded data; 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; 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 are not 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, 2023 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. 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. 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).
2025: Building on Our Momentum * If approved † Preliminary unaudited cash, cash equivalents, and marketable securities position as of December 31, 2024 Continued double-digit growth in ARIKAYCE for refractory MAC Execution of the largest commercial launch* in our history Late-stage clinical data readouts to catalyze the next wave of growth Expanded clinical breadth with start of first gene therapy program 1 2 3 4 Enabled by >$1.4B of cash on our balance sheet†
Portfolio of First-in-Class and Potentially Best-in-Class* Assets Across Each Stage of Development Preclinical Phase 1 Phase 2 Phase 3 Approved ARIKAYCE® Refractory NTM 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 Early-Stage 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: Deschene 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; assumes priority review ** 2025 ARIKAYCE revenue guidance as of January 2025; Growth vs. 2024 preliminary unaudited revenue results † Europe/EU5 comprised of France, Germany, Italy, Spain, and the United Kingdom (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: Deschene muscular dystrophy 2024 2025 2026
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 * Preliminary unaudited revenue results for 12-months ended December 31, 2024 1 Growth vs. 2024 preliminary unaudited 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 a Best in MAC LD Treatment Regimen 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
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)
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
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:
Chronic Rhinosinusitis without Nasal Polyps Represents Another Potential Large Patient Opportunity Included in Phase 2 BiRCh Trial 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
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
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: Topline Results Moved Forward to Mid-2025 for Phase 2 PAH Trial 102 Participants Enrolled 2:1 Randomization Primary Endpoint: Change from baseline in pulmonary vascular resistance (PVR) at 16 weeks
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
Early-Stage Research Engine Has Produced First Product Candidate Gene Therapy IND for Duchenne Muscular Dystrophy Cleared in December 20241 Our Approach High Potential Impact Multiple preclinical programs 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.
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
Multiple Catalysts Fuel Our Next Era * If approved under priority review TPIP PAH Topline Data Mid-25 U.S. Launch of Brensocatib in Bronchiectasis* 3Q:25 Brensocatib CRSsNP Topline Data YE:25 Initial Clinical Data from DMD Gene Therapy Late- ’25/’26 › › Supported by our unique culture & strong balance sheet ‹ ‹ ARIKAYCE ENCORE Topline Data 1Q:26
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.
Appendix Late-Stage Trial Designs
ARIKAYCE Phase 3 Clinical 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) ARIKAYCE
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 Brensocatib
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 Brensocatib
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