— ARIKAYCE® (amikacin liposome inhalation suspension) Total Revenue of $75.5 Million for the First Quarter of 2024, Reflecting 16% Annual Growth Over the First Quarter of 2023— —Company Reports Positive Topline Safety and Tolerability Data from the Phase 2 PH-ILD Study of TPIP with 79.3% of Patients Reaching the Maximum Dose of 640 µg by Week 5, with an Unexpectedly Positive and Robust Signal on the Exploratory Endpoint of Clinical Worsening— —Encouraging Blinded Data from First 40 Patients in Phase 2 PAH Study of TPIP, with Combined Active Treatment and Placebo Arms Showing Mean PVR Reduction of 19.9% and 6-Minute Walk Distance Improvement of 43 Meters— —Topline Data from the Phase 3 ASPEN Trial of Brensocatib in Patients with Bronchiectasis Remains on Track to Read Out in the Latter Part of Second-Quarter 2024— —Company Reiterates 2024 Global ARIKAYCE Revenue Guidance in the Range of $340 Million to $360 Million, Reflecting Double-Digit Growth Compared to 2023— BRIDGEWATER, N.J., May 9, 2024 /PRNewswire/ -- Insmed Incorporated (NASDAQ:INSM), a global biopharmaceutical company on a mission to transform the lives of patients with serious and rare diseases, today reported financial results for the first quarter ended March 31, 2024 and provided a business update. "Today, Insmed kicked off a series of crucial data readouts, starting with TPIP, where we continue to observe a favorable safety and tolerability profile from the Phase 2 PH-ILD trial results as well as encouraging additional blinded PVR data from the Phase 2 PAH trial. Together, we believe these results continue to position TPIP as a potential best-in-class prostanoid," said Will Lewis, Chair and Chief Executive Officer of Insmed. "We now await with great anticipation the ASPEN trial results, which are expected in the latter half of this quarter. Supporting our research efforts is the ARIKAYCE commercial engine, which produced double-digit revenue growth this quarter, keeping us on track to meet our 2024 revenue guidance." Recent Pillar Highlights Pillar 1: ARIKAYCE  ARIKAYCE global revenue grew 16% in the first quarter of 2024 compared to the first quarter of 2023, reflecting double-digit year-over-year growth in the U.S., Japan, and Europe. The Company received notification that the National Agency for the Safety of Medicines and Health in France plans to proceed with a program to allow for the compassionate prescribing of ARIKAYCE for the treatment of adult patients with mycobacterium abscessus lung infection. The Company is scheduled to meet with the U.S. Food and Drug Administration (FDA) in late June to gain additional insights and guidance on the patient-reported outcome tool to be used in the Phase 3 ENCORE study, after which it will finalize its statistical plan for ENCORE. The Data Safety Monitoring Committee for the ongoing ENCORE trial held its fourth safety review meeting in April of 2024 and recommended that the study progress unchanged. The Company continues to expect topline data from ENCORE in 2025. Pillar 2: Brensocatib Insmed continues to expect topline data from the Phase 3 ASPEN study of brensocatib in patients with non-cystic fibrosis bronchiectasis (NCFBE) in the latter part of the second quarter of 2024. As of the end of the first quarter of 2024, all adult patients in ASPEN had completed their 52-week visit, the point in the trial at which the primary and secondary efficacy endpoints are measured. If ASPEN is successful and regulatory approval is obtained, the Company anticipates a launch in the U.S. in mid-2025, followed by launches in Europe and Japan in the first half of 2026. Insmed continues to advance its launch readiness activities in preparation for these potential launches. In the first quarter of 2024, Insmed received notification from the Medicines and Healthcare products Regulatory Agency in the United Kingdom regarding a positive outcome for the Company's Innovative Licensing and Access Pathway (ILAP) passport application, granting Innovation Passport designation for brensocatib in the treatment of NCFBE in patients aged 12 years and older. The ILAP and the Innovation Passport are intended to accelerate time to market, facilitating patient access for important new medicines in the United Kingdom. The Company continues to enroll patients in the Phase 2b BiRCh trial of brensocatib in patients with chronic rhinosinusitis without nasal polyps (CRSsNP) and anticipates providing topline data from the study in 2025. The Company expects to initiate a Phase 2 study of brensocatib in patients with hidradenitis suppurativa (HS) in the second half of 2024, pending positive results from the ASPEN study. Pillar 3: TPIP PH-ILD Today, Insmed reported topline safety and tolerability data as well as certain exploratory efficacy endpoints from the Phase 2 study of treprostinil palmitil inhalation powder (TPIP) in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD). In the TPIP arm, 79.3% of patients were successfully able to reach the maximum 640 microgram (µg) dose by Week 5, compared to 100.0% of patients in the placebo arm. Treatment-emergent adverse events which led to treatment discontinuation occurred in 13.8% of patients in the active treatment arm and 30.0% of patients in the placebo arm. Adverse events of any kind were observed in 93.1% of patients in the TPIP arm and 90.0% of patients in the placebo arm. Adverse events related to study drug occurred in 55.2% of TPIP patients and 40.0% of placebo patients. Study drug-related cough was observed in 37.9% of patients in the TPIP arm and 0.0% of patients in the placebo group. All events of cough were mild, and none led to treatment discontinuation. Serious adverse events occurred in 20.7% of TPIP-treated patients and 40.0% of placebo-treated patients. Deaths occurred in 6.9% of patients taking TPIP and 20.0% of patients taking placebo. All deaths were attributed to disease progression or comorbid causes, none of which were deemed related to study drug. There were no meaningful changes in oxygenation levels compared to baseline for TPIP-treated patients at rest or at the lowest point during or after exercise. There was also no change in the use of supplemental oxygen for patients taking TPIP. There was a small decrease in oxygenation levels observed after exercise for patients on TPIP, compared to a slight increase for patients taking placebo. However, there was variability in the timing of when this endpoint was measured in the study, which could make the results less interpretable than the measurements taken at rest or at the lowest point during or after exercise. On the exploratory endpoint of change from baseline in 6-minute walk distance, TPIP-treated patients demonstrated a 30-meter improvement compared to patients treated with placebo. However, this result was associated with a wide confidence interval. There was a directional improvement observed in NT-proBNP levels from baseline for patients taking TPIP and a directional worsening observed in patients on placebo, although no meaningful separation was observed between groups. Events of clinical worsening occurred in 10.3% of patients taking TPIP, compared to 50.0% of patients taking placebo. This difference was nominally significant (p=0.0164). Due to the small size of the study, the Company interprets these results with appropriate caution. Insmed looks forward to the opportunity to present pharmacokinetic results and additional safety and exploratory endpoints from this trial at an upcoming medical conference later this year. Based on these Phase 2 results in PH-ILD, the Company is advancing toward discussions with global regulatory authorities on the design of a Phase 3 study in PH-ILD, which the Company anticipates initiating in 2025. PAH Today, the Company also shared updated blinded and blended data from the first 40 patients who completed the full 16 weeks of treatment in the ongoing Phase 2 study of TPIP in pulmonary arterial hypertension (PAH). Of those 40 patients, including those on placebo, the average reduction in pulmonary vascular resistance (PVR) at Week 16 compared to baseline levels was 19.9%. Among the 40 patients across the treatment and placebo arms, the average improvement in 6-minute walk distance from baseline was 43 meters. Among the first 43 patients to complete the Week 5 visit, 79.1% were able to reach the maximum dose of 640 µg or matching placebo. Insmed has received the necessary regulatory approvals in 10 of 17 countries where the study is taking place to amend the protocol to allow for an increase in the maximum dose of TPIP from 640 µg to up to 1,280 µg, once a day, in the open label extension study for certain PAH patients based on investigator decision. Enrollment remains ongoing in the Phase 2 PAH study, with more than half of the target enrollment currently complete. In March of 2024, the second meeting of the Data Monitoring Committee took place for the Phase 2 trial in PAH, resulting in the committee's recommendation to continue the trial without changes. Topline results from the Phase 2 PAH study continue to be expected in 2025. Pillar 4: Early-Stage Research Insmed's early-stage research efforts include more than 30 identified pre-clinical programs in development, all of which have the potential to become first-in-class or best-in-class therapies. The Company continues to anticipate the totality of its early-stage research programs will comprise less than 20% of overall spend. Corporate Updates Insmed plans to present nine abstracts from across its respiratory portfolio (ARIKAYCE, brensocatib, and TPIP) at the American Thoracic Society (ATS) 2024 International Conference, taking place May 17-22, 2024. The Company served as the founding sponsor of the COPD Foundation's new Care Center Network for patients with bronchiectasis and nontuberculous mycobacterial lung disease. Through this initiative, the COPD Foundation aims to create 150 multi-disciplinary centers of excellence across the U.S. to establish consistent standards of care coming from expert-led academic centers and share them with the broader community in an effort to bring more comprehensive care to patients as they strive to meet treatment goals. Insmed's Chief Medical Officer, Martina Flammer, M.D., M.B.A., has been appointed Chair of the New Jersey Rare Disease Advisory Council (RDAC) by Governor Phil Murphy. In an effort established by the National Organization for Rare Disorders (NORD), RDACs bring together a unified, multidisciplinary network of state-wide experts focused on raising awareness of rare diseases and funding much-needed new research. Martina was nominated by BioNJ, the life sciences trade association for New Jersey, to represent the biopharma industry in New Jersey's RDAC. First-Quarter 2024 Financial Results Total revenue for the first quarter ended March 31, 2024 was $75.5 million, reflecting 16% growth compared to total revenue of $65.2 million for the first quarter of 2023. Total revenue for first-quarter 2024 was comprised of ARIKAYCE net sales of $56.3 million in the U.S., $14.9 million in Japan, and $4.3 million in Europe and rest of world. First-quarter 2024 sales demonstrated year-over-year growth of 15% in the U.S., 13% in Japan, and 42% in Europe and rest of world, reflecting continued growth trends for ARIKAYCE in these regions. Cost of product revenues (excluding amortization of intangibles) was $17.5 million for the first quarter of 2024, compared to $13.8 million for the first quarter of 2023, primarily reflecting increased sales volumes of ARIKAYCE. Research and development (R&D) expenses were $121.1 million for the first quarter of 2024, compared to $127.9 million for the first quarter of 2023, a decrease that reflects a non-cash charge of $10.3 million related to the acquisition of Vertuis Bio, Inc. in the first quarter of 2023. Selling, general and administrative (SG&A) expenses for the first quarter of 2024 were $93.1 million, compared to $79.9 million for the first quarter of 2023. The year-over-year increase in SG&A expenses resulted primarily from increases in compensation and benefit-related expenses. For the first-quarter 2024, Insmed reported a net loss of $157.1 million, or $1.06 per share, compared to a net loss of $159.8 million, or $1.17 per share, for the first-quarter 2023. Balance Sheet, Financial Guidance, and Planned Investments As of March 31, 2024, Insmed had cash and cash equivalents totaling $595.7 million. Insmed is reiterating its sales guidance for full-year 2024 global ARIKAYCE revenues in the range of $340 million to $360 million, representing 15% year-over-year growth at the midpoint compared to 2023. Insmed continues to anticipate that over 80% of total expenditures will be on its mid- to late-stage and commercial programs (ARIKAYCE, brensocatib, and TPIP), and that less than 20% of overall spend will be on its early-stage research programs, reflecting the Company's historical approach to spending. The Company plans to continue to invest in the following key activities in 2024: (i) commercialization and expansion of ARIKAYCE globally;(ii) advancement of brensocatib, including the Phase 3 ASPEN study in patients with bronchiectasis, commercial launch readiness activities, the ongoing Phase 2 trial in patients with CRSsNP, and the Phase 2 program in HS to be initiated in the second half of the year if the ASPEN result is positive;(iii) advancement of the clinical trial program for ARIKAYCE, which is intended to satisfy the post-marketing requirement for full approval of its current indication and potentially support label expansion to include all patients with a MAC lung infection;(iv) advancement of its clinical development programs for TPIP; and(v) development of its early-stage research programs. Conference Call Insmed will host a conference call beginning today at 8:00 AM Eastern Time. Shareholders and other interested parties may participate in the conference call by dialing (888) 210-2654 (U.S.) and (646) 960-0278 (international) and referencing access code 7862189. The call will also be webcast live on the Company's website at www.insmed.com. A replay of the conference call will be accessible approximately 1 hour after its completion through June 8, 2024, by dialing (800) 770-2030 (U.S.) and (609) 800-9909 (international) and referencing access code 7862189. A webcast of the call will also be archived for 90 days under the Investor Relations section of the Company's website at www.insmed.com. INSMED INCORPORATED Consolidated Statements of Net Loss (in thousands, except per share data) (unaudited)  Three Months Ended March 31,  2024 2023 Product revenues, net $     75,500 $     65,214