Open-label, Single-arm, Non-controlled Trial to Evaluate Safety and Tolerability of Treprostinil Sodium in Children Below the Age of 18 Years Diagnosed With Pulmonary Arterial Hypertension (PAH)

The goal of this clinical trial is to evaluate safety and tolerability of preservative-free parenteral treprostinil in paediatric patients with PAH (PH Group 1) who are below 18 years of age. The main question it aims to answer is:
• if preservative-free parenteral treprostinil is safe and tolerable in the treatment of paediatric PAH in patients who are either treatment-naïve or have been previously treated with commercially available parenteral treprostinil formulations.
Participants will receive either subcutaneous (SC) or intravenous (IV) preservative-free treprostinil and will be observed for 5 months (20 weeks ± 1 week).

Start Date01 May 2024

Sponsor / Collaborator

Aop Orphan Pharmaceuticals GmbH

NCT06129240 / RecruitingNot Applicable

An Open-Label ProSpective MultiCENTer Study to Evaluate Safety and Tolerability of Dry Powder Inhaled Treprostinil in Pulmonary Hypertension

Study LTI-401 is an open-label, multicenter study which will evaluate the safety and tolerability of LIQ861 in subjects who have WHO Group 1 & 3 PH.

Start Date28 Dec 2023

Sponsor / Collaborator

Liquidia Technologies, Inc.

100 Clinical Results associated with Treprostinil

100 Translational Medicine associated with Treprostinil

100 Patents (Medical) associated with Treprostinil

704

Literatures (Medical) associated with Treprostinil

Thorax

Use of inhaled treprostinil in patients with interstitial lung disease and pulmonary hypertension: to boldly go where no other pulmonary vasodilator has gone before?

Author: Wort, Stephen John ; Piccari, Lucilla

01 Jan 2024·ERJ open research

Severe pulmonary hypertension–interstitial lung disease presenting as right ventricular failure: stabilisation with intravenous prostacyclin and maintenance with inhaled prostacyclin

Article

Author: Farber, Harrison W ; Moallem, Niala ; Sharofi, Aldo ; Fiscus, Garrett ; Parikh, Raj ; Thomas, Alysse

Background:

Pulmonary hypertension (PH) leads to increased morbidity and mortality in interstitial lung disease (ILD). While the INCREASE trial highlighted the use of inhaled prostacyclin in PH-ILD patients, such therapy may be inadequate when right ventricular failure (RVF) is also present. In this study, we report the use of intravenous prostacyclin in three PH-ILD patients to stabilise right ventricular (RV) function, with a subsequent transition to maintenance therapy with inhaled prostacyclin.

Methods:

We evaluated three consecutive PH-ILD patients with RVF. RV afterload and pulmonary vascular resistance (PVR) were treated with intravenous prostacyclin during the induction phase of the therapy. Patients transitioned from intravenous prostacyclin to the maintenance phase of the treatment with inhaled prostacyclin once three transition criteria were met: cardiac index (CI) >2 L·min−1·m−2, PVR <7 Wood units (WU) and tricuspid annular plane systolic excursion (TAPSE) change >1 mm or TAPSE >1.6 cm.

Results:

Pre-treatment parameters for the three patients were a mean PVR of 14.3 WU, a mean Fick CI of 1.8 L·min−1·m−2and a mean TAPSE of 1.4 cm. The average intravenous prostacyclin dose at the time of transition to maintenance therapy was 20.7 ng·kg−1·m−2of treprostinil. At 3-months follow-up, the mean PVR was 6.3 WU, Fick CI 2.2 L·min−1·m−2and TAPSE 1.7 cm.

Conclusion:

This case series of three PH-ILD patients with RVF introduces the concept of an initial intravenous prostacyclin induction phase, followed by a transition to maintenance therapy with inhaled prostacyclin. Further development of this treatment algorithm with a refinement of the transition criteria, potential testing in a clinical trial and a longer-term follow-up period is warranted to improve the outcomes of advanced PH-ILD patients with concomitant RVF.

31 Dec 2023·Journal of medical economics

Comparative evaluation of costs and healthcare resource utilization of oral selexipag versus inhaled treprostinil or oral treprostinil in patients with pulmonary arterial hypertension

Article

Author: Liu, Xing ; Tsang, Yuen ; Potluri, Ravi ; Beaudet, Amélie ; Panjabi, Sumeet ; Papademetriou, Eros

BACKGROUND:

Pulmonary arterial hypertension (PAH), a rare vasculopathy progressively leading to right heart failure and death, is associated with considerable economic burden. Oral prostacyclin pathway agents (PPAs) like selexipag and treprostinil address an underlying PAH pathway, yet are often under-utilized. Data on head-to-head cost comparison of various PPAs is lacking.

METHODS:

In this retrospective study using a large health claims database, we compared the per-patient-per-year (PPPY) costs and healthcare resource utilization (HRU) among PAH patients taking either oral selexipag, inhaled treprostinil or oral treprostinil in the United States between July 2015 and March 2020. Patients with ≥1 prescription for one of the drugs of interest, ≥1 in-patient pulmonary hypertension (PH) diagnosis, or ≥ 2 outpatient PH diagnoses were included in this study. Baseline differences between the three groups were adjusted using an inverse probability of treatment weighting approach. 411 patients were selected for the final study cohorts.

RESULTS:

All-cause hospitalization costs were highest for oral treprostinil ($39,983) compared to oral selexipag ($20,635) and inhaled treprostinil ($16,548; p = .037). Total PAH-related medical costs were 40% lower for patients on oral selexipag compared to patients on oral and inhaled treprostinil ($24,351 vs. $40,398 and $40,339, respectively; p = .006). PAH-related outpatient visits were lowest for patients on oral selexipag (14 PPPY visits) compared to oral treprostinil (16 PPPY visits) and inhaled treprostinil (22 PPPY visits; p = .001).

CONCLUSIONS:

Compared to oral and inhaled treprostinil, oral selexipag may incur lower medical costs and reduce PAH related outpatient visits for patients with PAH.

News (Medical) associated with Treprostinil

30 May 2024

·www.prnewswire.com

Insmed to Host Commercial Webinar on June 4, 2024

BRIDGEWATER, N.J., May 30, 2024 /PRNewswire/ -- Insmed Incorporated (Nasdaq:INSM), a global biopharmaceutical company on a mission to transform the lives of patients with serious and rare diseases, will host a commercial webinar on Tuesday, June 4, 2024, at 8:00 a.m. ET to discuss the market outlook for the Company's three most advanced programs, ARIKAYCE® (amikacin liposome inhalation suspension), brensocatib, and treprostinil palmitil inhalation powder (TPIP). Shareholders and other interested parties may participate in the conference call by dialing (800) 715-9871 (U.S.) and (646) 307-1963 (international) and referencing access code 7504027. The call will also be webcast live on the Company's website at . A replay of the conference call will be accessible approximately 1 hour after its completion through July 4, 2024, by dialing (800) 770-2030 (U.S.) and (609) 800-9909 (international) and referencing access code 7504027. A webcast of the call will also be archived for 90 days under the Investor Relations section of the Company's website at . About ARIKAYCE ARIKAYCE is approved in the United States as ARIKAYCE® (amikacin liposome inhalation suspension), in Europe as ARIKAYCE® Liposomal 590 mg Nebuliser Dispersion, and in Japan as ARIKAYCE® inhalation 590 mg (amikacin sulfate inhalation drug product). Current international treatment guidelines recommend the use of ARIKAYCE for appropriate patients. ARIKAYCE is a novel, inhaled, once-daily formulation of amikacin, an established antibiotic that was historically administered intravenously and associated with severe toxicity to hearing, balance, and kidney function. Insmed's proprietary PULMOVANCE® liposomal technology enables the delivery of amikacin directly to the lungs, where liposomal amikacin is taken up by lung macrophages where the infection resides, while limiting systemic exposure. ARIKAYCE is administered once daily using the Lamira® Nebulizer System manufactured by PARI Pharma GmbH (PARI). IMPORTANT SAFETY INFORMATION AND BOXED WARNING FOR ARIKAYCE IN THE U.S. Hypersensitivity Pneumonitis has been reported with the use of ARIKAYCE in the clinical trials. Hypersensitivity pneumonitis (reported as allergic alveolitis, pneumonitis, interstitial lung disease, allergic reaction to ARIKAYCE) was reported at a higher frequency in patients treated with ARIKAYCE plus background regimen (3.1%) compared to patients treated with a background regimen alone (0%). Most patients with hypersensitivity pneumonitis discontinued treatment with ARIKAYCE and received treatment with corticosteroids. If hypersensitivity pneumonitis occurs, discontinue ARIKAYCE and manage patients as medically appropriate. Hemoptysis has been reported with the use of ARIKAYCE in the clinical trials. Hemoptysis was reported at a higher frequency in patients treated with ARIKAYCE plus background regimen (17.9%) compared to patients treated with a background regimen alone (12.5%). If hemoptysis occurs, manage patients as medically appropriate. Bronchospasm has been reported with the use of ARIKAYCE in the clinical trials. Bronchospasm (reported as asthma, bronchial hyperreactivity, bronchospasm, dyspnea, dyspnea exertional, prolonged expiration, throat tightness, wheezing) was reported at a higher frequency in patients treated with ARIKAYCE plus background regimen (28.7%) compared to patients treated with a background regimen alone (10.7%). If bronchospasm occurs during the use of ARIKAYCE, treat patients as medically appropriate. Exacerbations of underlying pulmonary disease has been reported with the use of ARIKAYCE in the clinical trials. Exacerbations of underlying pulmonary disease (reported as chronic obstructive pulmonary disease (COPD), infective exacerbation of COPD, infective exacerbation of bronchiectasis) have been reported at a higher frequency in patients treated with ARIKAYCE plus background regimen (14.8%) compared to patients treated with background regimen alone (9.8%). If exacerbations of underlying pulmonary disease occur during the use of ARIKAYCE, treat patients as medically appropriate. Anaphylaxis and Hypersensitivity Reactions: Serious and potentially life-threatening hypersensitivity reactions, including anaphylaxis, have been reported in patients taking ARIKAYCE. Signs and symptoms include acute onset of skin and mucosal tissue hypersensitivity reactions (hives, itching, flushing, swollen lips/tongue/uvula), respiratory difficulty (shortness of breath, wheezing, stridor, cough), gastrointestinal symptoms (nausea, vomiting, diarrhea, crampy abdominal pain), and cardiovascular signs and symptoms of anaphylaxis (tachycardia, low blood pressure, syncope, incontinence, dizziness). Before therapy with ARIKAYCE is instituted, evaluate for previous hypersensitivity reactions to aminoglycosides. If anaphylaxis or a hypersensitivity reaction occurs, discontinue ARIKAYCE and institute appropriate supportive measures. Ototoxicity has been reported with the use of ARIKAYCE in the clinical trials. Ototoxicity (including deafness, dizziness, presyncope, tinnitus, and vertigo) were reported with a higher frequency in patients treated with ARIKAYCE plus background regimen (17%) compared to patients treated with background regimen alone (9.8%). This was primarily driven by tinnitus (7.6% in ARIKAYCE plus background regimen vs 0.9% in the background regimen alone arm) and dizziness (6.3% in ARIKAYCE plus background regimen vs 2.7% in the background regimen alone arm). Closely monitor patients with known or suspected auditory or vestibular dysfunction during treatment with ARIKAYCE. If ototoxicity occurs, manage patients as medically appropriate, including potentially discontinuing ARIKAYCE. Nephrotoxicity was observed during the clinical trials of ARIKAYCE in patients with MAC lung disease but not at a higher frequency than background regimen alone. Nephrotoxicity has been associated with the aminoglycosides. Close monitoring of patients with known or suspected renal dysfunction may be needed when prescribing ARIKAYCE. Neuromuscular Blockade: Patients with neuromuscular disorders were not enrolled in ARIKAYCE clinical trials. Patients with known or suspected neuromuscular disorders, such as myasthenia gravis, should be closely monitored since aminoglycosides may aggravate muscle weakness by blocking the release of acetylcholine at neuromuscular junctions. Embryo-Fetal Toxicity: Aminoglycosides can cause fetal harm when administered to a pregnant woman. Aminoglycosides, including ARIKAYCE, may be associated with total, irreversible, bilateral congenital deafness in pediatric patients exposed in utero. Patients who use ARIKAYCE during pregnancy, or become pregnant while taking ARIKAYCE should be apprised of the potential hazard to the fetus. Contraindications: ARIKAYCE is contraindicated in patients with known hypersensitivity to any aminoglycoside. Most Common Adverse Reactions: The most common adverse reactions in Trial 1 at an incidence ≥5% for patients using ARIKAYCE plus background regimen compared to patients treated with background regimen alone were dysphonia (47% vs 1%), cough (39% vs 17%), bronchospasm (29% vs 11%), hemoptysis (18% vs 13%), ototoxicity (17% vs 10%), upper airway irritation (17% vs 2%), musculoskeletal pain (17% vs 8%), fatigue and asthenia (16% vs 10%), exacerbation of underlying pulmonary disease (15% vs 10%), diarrhea (13% vs 5%), nausea (12% vs 4%), pneumonia (10% vs 8%), headache (10% vs 5%), pyrexia (7% vs 5%), vomiting (7% vs 4%), rash (6% vs 2%), decreased weight (6% vs 1%), change in sputum (5% vs 1%), and chest discomfort (5% vs 3%). Drug Interactions: Avoid concomitant use of ARIKAYCE with medications associated with neurotoxicity, nephrotoxicity, and ototoxicity. Some diuretics can enhance aminoglycoside toxicity by altering aminoglycoside concentrations in serum and tissue. Avoid concomitant use of ARIKAYCE with ethacrynic acid, furosemide, urea, or intravenous mannitol. Overdosage: Adverse reactions specifically associated with overdose of ARIKAYCE have not been identified. Acute toxicity should be treated with immediate withdrawal of ARIKAYCE, and baseline tests of renal function should be undertaken. Hemodialysis may be helpful in removing amikacin from the body. In all cases of suspected overdosage, physicians should contact the Regional Poison Control Center for information about effective treatment. U.S. INDICATION LIMITED POPULATION: ARIKAYCE® is indicated in adults, who have limited or no alternative treatment options, for the treatment of Mycobacterium avium complex (MAC) lung disease as part of a combination antibacterial drug regimen in patients who do not achieve negative sputum cultures after a minimum of 6 consecutive months of a multidrug background regimen therapy. As only limited clinical safety and effectiveness data for ARIKAYCE are currently available, reserve ARIKAYCE for use in adults who have limited or no alternative treatment options. This drug is indicated for use in a limited and specific population of patients. This indication is approved under accelerated approval based on achieving sputum culture conversion (defined as 3 consecutive negative monthly sputum cultures) by Month 6. Clinical benefit has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Limitation of Use : ARIKAYCE has only been studied in patients with refractory MAC lung disease defined as patients who did not achieve negative sputum cultures after a minimum of 6 consecutive months of a multidrug background regimen therapy. The use of ARIKAYCE is not recommended for patients with non-refractory MAC lung disease. Patients are encouraged to report negative side effects of prescription drugs to the FDA. Visit , or call 1‑800‑FDA‑1088. You can also call the Company at 1-844-4-INSMED. Please see Full Prescribing Information . About Insmed Insmed Incorporated is a global biopharmaceutical company on a mission to transform the lives of patients with serious and rare diseases. Insmed's first commercial product is a first-in-disease therapy approved in the United States, Europe, and Japan to treat a chronic, debilitating lung disease. The Company is progressing a robust pipeline of investigational therapies targeting areas of serious unmet need, including neutrophil-mediated inflammatory diseases and rare pulmonary disorders. Insmed is also advancing an early-stage research engine encompassing a wide range of technologies and modalities, including artificial intelligence-driven protein engineering, gene therapy, and protein manufacturing. Insmed is headquartered in Bridgewater, New Jersey, with additional offices and research locations throughout the United States, Europe, and Japan. Visit to learn more. Contact: Investors: Bryan Dunn Executive Director, Investor Relations Insmed (646) 812-4030 [email protected] Eleanor Barisser Associate Director, Investor Relations Insmed (718) 594-5332 [email protected] Media: Mandy Fahey Executive Director, Corporate Communications Insmed (732) 718-3621 [email protected] SOURCE Insmed Incorporated

Drug ApprovalAccelerated Approval

30 May 2024

·www.biospace.com

Insmed Announces Pricing of $650 Million Public Offering of Common Stock

BRIDGEWATER, N.J., May 30, 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 announced that it priced an underwritten public offering of 12,621,359 shares of its common stock at a price to the public of $51.50 per share. The gross proceeds to Insmed from the offering, before deducting underwriting discounts and commissions and other offering expenses payable by Insmed, are expected to be approximately $650 million. In addition, Insmed has granted the underwriters a 30-day option to purchase up to an additional 1,893,203 shares of common stock. Insmed intends to use the net proceeds from this offering to fund continued research and development of brensocatib as well as pre-commercial and, if approved, commercialization activities related to brensocatib, activities related to the further commercialization and development of ARIKAYCE® (amikacin liposome inhalation suspension), further research and development of treprostinil palmitil inhalation powder (TPIP) and any of the Company's other research product candidates, and for other general corporate purposes, including business expansion activities. Goldman Sachs & Co. LLC, Leerink Partners and J.P. Morgan are acting as joint book-running managers for the offering. Morgan Stanley, Cantor and Stifel are acting as co-lead managers for the offering. The offering is expected to close on May 31, 2024, subject to the satisfaction of customary closing conditions. The public offering of common stock described above is being made pursuant to Insmed's shelf registration statement on Form S-3 (File No. 333-272088) that was previously filed with the Securities and Exchange Commission (SEC) and became automatically effective on May 19, 2023. A preliminary prospectus supplement relating to and describing the terms of the offering was filed with the SEC and is available on the SEC's website at . Copies of the final prospectus supplement and the accompanying prospectus relating to this offering may be obtained, when available, from Goldman Sachs & Co. LLC, Prospectus Department, 200 West Street, New York, NY 10282, telephone: 1-866-471-2526, facsimile: 212-902-9316 or by emailing Prospectus-ny@ny.email.gs.com; or Leerink Partners LLC, Attention: Syndicate Department, 53 State Street, 40th Floor, Boston, MA 02109, by telephone at (800) 808-7525, ext. 6105, or by email at syndicate@leerink.com; or J.P Morgan Securities LLC, Attention: Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, by telephone at 1-866-803-9204, or by email at prospectus-eq_fi@jpmchase.com. This press release shall not constitute an offer to sell or a solicitation of an offer to buy, nor shall there be any sale of these securities in any jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction. About Insmed Insmed Incorporated is a global biopharmaceutical company on a mission to transform the lives of patients with serious and rare diseases. Insmed's first commercial product is a first-in-disease therapy approved in the United States, Europe, and Japan to treat a chronic, debilitating lung disease. The Company is progressing a robust pipeline of investigational therapies targeting areas of serious unmet need, including neutrophil-mediated inflammatory diseases and rare pulmonary disorders. Insmed is also advancing an early-stage research engine encompassing a wide range of technologies and modalities, including artificial intelligence-driven protein engineering, gene therapy, and protein manufacturing. Insmed is headquartered in Bridgewater, New Jersey, with additional offices and research locations throughout the United States, Europe, and Japan. Forward-looking Statements This press release 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 press release 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: the risks and uncertainties associated with market conditions and the satisfaction of customary closing conditions related to the public offering; 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; 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 full approval of ARIKAYCE from the U.S. Food and Drug Administration, including the risk that we will not successfully or in a timely manner validate a patient reported outcome tool and 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; inability of us, PARI Pharma GmbH or our other third-party manufacturers to comply with regulatory requirements related to ARIKAYCE or the Lamira® Nebulizer System (Lamira); 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; failure to obtain, or delays in obtaining, regulatory approvals for brensocatib, TPIP or our other product candidates in the U.S., Europe or Japan or regulatory approvals for potential future brensocatib or TPIP indications; failure to successfully commercialize brensocatib, TPIP or our other product candidates, if approved by applicable regulatory authorities, in the U.S., Europe or Japan, or to maintain US, European or Japanese approval for brensocatib, TPIP or our other product candidates, if approved; development of unexpected safety or efficacy concerns related to ARIKAYCE, 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; 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, if approved, brensocatib or TPIP; risk that brensocatib or TPIP does not prove to be effective or safe for patients in ongoing and future clinical studies; 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; failure to successfully predict the time and cost of development, regulatory approval and commercialization for novel gene therapy products; 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 Mycobacterium avium complex lung disease, among other things; 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; 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; 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; failure to obtain, or delays in obtaining, regulatory approvals for ARIKAYCE outside the U.S., Europe or Japan, including separate regulatory approval for Lamira in each market and for each usage; failure of third parties on which we are dependent, including Esteve Pharmaceuticals, S.A., Thermo Fisher Scientific, Inc. or the Company's other third-party manufacturers, to manufacture sufficient quantities of ARIKAYCE, brensocatib or TPIP for commercial or clinical needs, to conduct our clinical trials, or to comply with our agreements or laws and regulations that impact our business or agreements with us; 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 artificial intelligence and machine learning may not be successful; deterioration in general economic conditions in the U.S., Europe, Japan and globally, including the effect of prolonged periods of inflation, affecting us, our suppliers, third-party service providers and potential partners; the strength and enforceability of our intellectual property rights or the rights of third parties; inability to adequately protect our intellectual property rights or prevent disclosure of our trade secrets and other proprietary information and costs associated with litigation or other proceedings related to such matters; restrictions or other obligations imposed on us by agreements related to ARIKAYCE or brensocatib, including our license agreements with PARI Pharma GmbH 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 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 press release. 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. Contact: Investors: Bryan Dunn Executive Director, Investor Relations Insmed (646) 812-4030 bryan.dunn@insmed.com Eleanor Barisser Associate Director, Investor Relations Insmed (718) 594-5332 eleanor.barisser@insmed.com Media: Mandy Fahey Executive Director, Corporate Communications Insmed (732) 718-3621 amanda.fahey@insmed.com Company Codes: NASDAQ-NMS:INSM

28 May 2024

·www.prnewswire.com

Insmed Announces Positive Topline Results from Landmark ASPEN Study of Brensocatib in Patients with Bronchiectasis

—Phase 3 Study Achieves Primary Endpoint for Both Dosage Strengths of Brensocatib with Statistically Significant and Clinically Meaningful Reduction in Frequency of Pulmonary Exacerbations Versus Placebo— —Treatment with Brensocatib Also Achieves Statistical Significance on Multiple Secondary Endpoints for Both Dosage Strengths Versus Placebo— —Brensocatib Well-Tolerated at Both Dosage Strengths— —Results from ASPEN Validate DPP1 Inhibition as New Mechanism of Action with Potential to Address Range of Neutrophil-Mediated Diseases— —Insmed Plans to Advance Quickly Toward U.S. Regulatory Filing, with Anticipated U.S. Launch in Mid-2025, Pending Approval— —Insmed to Host Investor Call at 8:00 am ET on Tuesday, May 28, 2024— BRIDGEWATER, N.J., May 28, 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 announced positive topline results from the ASPEN study, a global, randomized, double-blind, placebo-controlled Phase 3 study to assess the efficacy, safety, and tolerability of brensocatib in patients with non-cystic fibrosis bronchiectasis. The study met its primary endpoint, with both dosage strengths of brensocatib demonstrating statistically significant reductions in the annualized rate of pulmonary exacerbations (PEs) versus placebo. The study also met several of its prespecified secondary endpoints with statistical significance. Based on these results, Insmed plans to file a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) for brensocatib in patients with bronchiectasis in the fourth quarter of 2024. Pending regulatory approvals, Insmed anticipates a U.S. launch for brensocatib in mid-2025 followed by launches in Europe and Japan in the first half of 2026. If approved, brensocatib would be the first approved treatment for patients with bronchiectasis as well as the first approved dipeptidyl peptidase 1 (DPP1) inhibitor—a new mechanism of action with the potential to address a range of neutrophil-mediated diseases. Topline efficacy results from the ASPEN study are as follows: "I am thrilled that the ASPEN study has demonstrated a statistically significant and clinically meaningful treatment effect for brensocatib compared with placebo, underscoring the impact this investigational therapy may have on patients with bronchiectasis," said lead study investigator James Chalmers, MBChB, Ph.D., Professor and Consultant Respiratory Physician at the School of Medicine, University of Dundee, UK. "Today, there is no approved treatment for bronchiectasis and there remains an urgent need for a therapy that can reduce exacerbations. As a DPP1 inhibitor, brensocatib would be the first treatment in its class and could offer a completely new approach to managing this difficult-to-treat patient population, heralding a new era in clinical management of bronchiectasis." As part of the ASPEN study's conduct, more than 460 trial sites were engaged in nearly 40 countries. After excluding sites that did not enroll any patients and all sites in Ukraine, the total number of active sites in ASPEN was 391 sites in 35 countries. Adult patients (ages 18 to 85 years) were randomized 1:1:1 and adolescent patients (ages 12 to <18 years) were randomized 2:2:1 for treatment with brensocatib 10 mg, brensocatib 25 mg, or placebo once daily for 52 weeks, followed by 4 weeks off treatment. The primary efficacy analysis included data from 1,680 adult patients and 41 adolescent patients. Brensocatib was well-tolerated in the study. Treatment-emergent adverse events (TEAEs) occurring in at least 5.0% of patients treated with either dose of brensocatib and more frequently than in placebo were COVID-19 (15.8%, 20.9%, 15.8%), nasopharyngitis (7.7%, 6.3%, 7.6%), cough (7.0%, 6.1%, 6.4%), and headache (6.7%, 8.5%, and 6.9%) for brensocatib 10 mg, brensocatib 25 mg, and placebo, respectively. Additional TEAEs and treatment-emergent adverse events of special interest (TEAESIs) are as follows: "We are incredibly excited about the topline results from the pivotal ASPEN study and what they may mean for patients. These findings not only underscore our belief that brensocatib has the potential to transform the treatment landscape for bronchiectasis, but they also further validate DPP1 inhibition as a mechanism that may hold promise in other neutrophil-mediated diseases," said Martina Flammer, M.D., MBA, Chief Medical Officer of Insmed. "Today's outcome is the result of years of hard work and dedication by many members of the Insmed team, and I'd like to thank them for their efforts. We are especially grateful to the clinical investigators, site staff, patients, and families who made this study possible. We now look forward to further analyzing the data while rapidly advancing toward regulatory filings in our key regions, where we believe approximately 1 million bronchiectasis patients may benefit from an approved treatment." Brensocatib has received Breakthrough Therapy Designation from the FDA and was granted access to the Priority Medicines (PRIME) scheme by the European Medicines Agency for patients with bronchiectasis. Insmed plans to present detailed results from the ASPEN study at an upcoming medical meeting. Insmed is also advancing the development of brensocatib in other neutrophil-driven inflammatory diseases with significant health burdens and limited treatment options. A Phase 2 study in patients with chronic rhinosinusitis without nasal polyps (CRSsNP) is currently underway, and Insmed plans to initiate a Phase 2 study in hidradenitis suppurativa (HS) in the second half of 2024. Insmed looks forward to hosting a commercial webinar on Tuesday, June 4, 2024, at 8:00 am ET, where the Company's commercial leadership will provide details on the market outlook for its three most advanced programs, ARIKAYCE® (amikacin liposome inhalation suspension), brensocatib, and treprostinil palmitil inhalation powder (TPIP). Conference Call Insmed management will host a conference call for investors beginning at 8:00 a.m. ET on Tuesday, May 28, to discuss the ASPEN results. Shareholders and other interested parties may participate in the conference call by dialing (800) 715-9871 (U.S.) or (646) 307-1963 (international) and referencing access code 1245105. The call will also be webcast live on the Company's website at . A replay of the conference call will be accessible approximately one hour after its completion through June 27, 2024, by dialing (800) 770-2030 (U.S.) or (609) 800-9909 (international) and referencing access code 1245105. A webcast of the call will also be archived for 90 days under the Investor Relations section of the Company's website at . About Bronchiectasis Bronchiectasis is a serious, chronic lung disease in which the bronchi become permanently dilated due to a cycle of infection, inflammation, and lung tissue damage. The condition is marked by frequent pulmonary exacerbations requiring antibiotic therapy and/or hospitalizations. Symptoms include chronic cough, excessive sputum production, shortness of breath, and repeated respiratory infections, which can worsen the underlying condition. Bronchiectasis affects approximately 450,000 patients in the U.S., 400,000 patients in Europe, and 150,000 patients in Japan, and there are currently no approved therapies specifically targeting bronchiectasis in these regions. About Brensocatib Brensocatib is a small molecule, oral, reversible inhibitor of dipeptidyl peptidase 1 (DPP1) being developed by Insmed for the treatment of patients with bronchiectasis, CRSsNP, and other neutrophil-mediated diseases. DPP1 is an enzyme responsible for activating neutrophil serine proteases (NSPs), such as neutrophil elastase, in neutrophils when they are formed in the bone marrow. Neutrophils are the most common type of white blood cell and play an essential role in pathogen destruction and inflammatory mediation. In chronic inflammatory lung diseases, neutrophils accumulate in the airways and result in excessive active NSPs that cause lung destruction and inflammation. Brensocatib may decrease the damaging effects of inflammatory diseases such as bronchiectasis by inhibiting DPP1 and its activation of NSPs. Brensocatib is an investigational drug product that has not been approved for any indication in any jurisdiction. About Insmed Insmed Incorporated is a global biopharmaceutical company on a mission to transform the lives of patients with serious and rare diseases. Insmed's first commercial product is a first-in-disease therapy approved in the United States, Europe, and Japan to treat a chronic, debilitating lung disease. The Company is progressing a robust pipeline of investigational therapies targeting areas of serious unmet need, including neutrophil-mediated inflammatory diseases and rare pulmonary disorders. Insmed is also advancing an early-stage research engine encompassing a wide range of technologies and modalities, including artificial intelligence-driven protein engineering, gene therapy, and protein manufacturing. Insmed is headquartered in Bridgewater, New Jersey, with additional offices and research locations throughout the United States, Europe, and Japan. Visit to learn more. Forward-Looking Statements This press release 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 press release 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: 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; failure to obtain, or delays in obtaining, regulatory approvals for brensocatib in the U.S., Europe or Japan; failure to successfully commercialize brensocatib, if approved by applicable regulatory authorities, in the U.S., Europe or Japan, or to maintain U.S., European or Japanese approval for brensocatib once approved; uncertainties in the degree of market acceptance of brensocatib by physicians, patients, third-party payors and others in the healthcare community; inaccuracies in the Company's estimates of the size of the potential markets for brensocatib or in data the Company has used to identify physicians; expected rates of patient uptake, duration of expected treatment, or expected patient adherence or discontinuation rates; inability of the Company, Esteve Pharmaceuticals, S.A., Thermo Fisher Scientific, Inc. or the Company's other third-party manufacturers to comply with regulatory requirements related to brensocatib; the Company's inability to obtain adequate reimbursement from government or third-party payors for brensocatib or acceptable prices for brensocatib; development of unexpected safety or efficacy concerns related to brensocatib; failure to obtain regulatory approval for potential future brensocatib indications; restrictions or other obligations imposed on us by agreements related to brensocatib, including our license agreement with AstraZeneca AB, and failure to comply with our obligations under such agreements; failure to successfully conduct future clinical trials for brensocatib, including due to the Company's potential inability to enroll or retain sufficient patients to conduct and complete the trials or generate data necessary for regulatory approval, among other things; risks that the Company's clinical studies will be delayed or that serious side effects will be identified during drug development; failure of third parties on which the Company is dependent to manufacture sufficient quantities of brensocatib 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 or agreements with the Company; the strength and enforceability of the Company's intellectual property rights or the rights of third parties; the cost and potential reputational damage resulting from litigation to which the Company may become a party, including product liability claims; changes in laws and regulations applicable to the Company's business and failure to comply with such laws and regulations; business or economic disruptions due to catastrophes or other events, including natural disasters or public health crises; and inability to repay the Company's existing indebtedness and uncertainties with respect to the Company's need and ability to access future capital. 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 press release. 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. Contact: Investors: Bryan Dunn Executive Director, Investor Relations Insmed (646) 812-4030 [email protected] Eleanor Barisser Associate Director, Investor Relations Insmed (718) 594-5332 [email protected] Media: Mandy Fahey Executive Director, Corporate Communications Insmed (732) 718-3621 [email protected] Logo -

Clinical ResultPhase 3Phase 2Drug ApprovalBreakthrough Therapy

100 Deals associated with Treprostinil

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KEGG	Wiki	ATC	Drug Bank
D06213	Treprostinil	B01AC21	DB00374

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Approved

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Indication	Country/Location	Organization	Date
Hypertension, Pulmonary	US	United Therapeutics Corp.	23 May 2022
Lung Diseases, Interstitial	US	United Therapeutics Corp.	31 Mar 2021
Chronic thromboembolic pulmonary hypertension	EU	SciPharm SARL	03 Apr 2020
Chronic thromboembolic pulmonary hypertension	IS	SciPharm SARL	03 Apr 2020
Chronic thromboembolic pulmonary hypertension	LI	SciPharm SARL	03 Apr 2020
Chronic thromboembolic pulmonary hypertension	NO	SciPharm SARL	03 Apr 2020
Pulmonary Arterial Hypertension	US	United Therapeutics Corp.	21 May 2002

Developing

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Indication	Highest Phase	Country/Location	Organization	Date
Progressive pulmonary fibrosis	Phase 3	US	United Therapeutics Corp.	30 Oct 2023
Progressive pulmonary fibrosis	Phase 3	CA	United Therapeutics Corp.	30 Oct 2023
Idiopathic Pulmonary Fibrosis	Phase 3	US	United Therapeutics Corp.	01 Jun 2021
Idiopathic Pulmonary Fibrosis	Phase 3	CA	United Therapeutics Corp.	01 Jun 2021
Pulmonary Disease, Chronic Obstructive	Phase 3	US	United Therapeutics Corp.	08 May 2018
Pulmonary Disease, Chronic Obstructive	Phase 3	AR	United Therapeutics Corp.	08 May 2018
Pulmonary Disease, Chronic Obstructive	Phase 3	IL	United Therapeutics Corp.	08 May 2018
Pulmonary Disease, Chronic Obstructive	Phase 3	PR	United Therapeutics Corp.	08 May 2018
Heart failure with normal ejection fraction	Phase 3	US	United Therapeutics Corp.	15 Aug 2017
Anemia, Sickle Cell	Phase 3	-	United Therapeutics Corp.	01 Jun 2017

Clinical Result

Indication

Phase

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04691154 (ATS2024) Manual	Phase 3	Pulmonary Arterial Hypertension	15	L606	tkcchkayoz(tuirhtczfi) = dkzjhjsdoy vxpjipcovi (xxqskvlkis ) View more	Positive	22 May 2024
NCT02261883 (CTgov)	Phase 2	Pulmonary Arterial Hypertension \| Persistent Fetal Circulation Syndrome	42	IV Remodulin (IV Remodulin)	eiznjhbffr(ifugjsoysl) = bdgvltafhy jjfqiewbzg (kckqtmwpfp, hrbzeicipx - zqrbdkcugs) View more	-	05 Mar 2024
				Placebo (Placebo)	eiznjhbffr(ifugjsoysl) = jkirnguxgz jjfqiewbzg (kckqtmwpfp, jctjhimxxu - ympaeulast) View more
NCT05067270 (CTgov)	Phase 1	Injection Site Reaction \| Diabetes Mellitus, Type 1	40	insulin+magnesium chloride+treprostinil+sodium citrate+humalog (Treatment Given to Arm Region)	urvrvufypl(mmwjjsnzmt): Geometric Least Squares Mean Ratio = 1.77 (95.0% CI, 1.3 - 2.4); Geometric Least Squares Mean Ratio = 1.49 (95.0% CI, 1.09 - 2.02); Geometric Least Squares Mean Ratio = 1.49 (95.0% CI, 1.1 - 2.03)	-	04 Oct 2023
				insulin+magnesium chloride+treprostinil (Treatment Given to Thigh)
NCT02630316 (INCREASE study, Pubmed)	Phase 2/3	Lung Diseases, Interstitial	326	Inhaled treprostinil	ddjarviyja(fnhzxtczuc) = hrutleiuvt komdnxciqz (xjkgrtxihl )	Positive	19 Jul 2023
				Placebo	wrgvifrdgr(zpzbqhatkm) = fvkwyiaeok jmutdyrcls (xtdfufoqhz )
NCT02633293 (CTgov)	Phase 2/3	Lung Diseases, Interstitial \| Hypertension, Pulmonary \| Combined pulmonary fibrosis and emphysema	243	Inhaled Treprostinil	bwsbulvsei(wmomqbitvn) = hivrzoedba usgmrtqcbq (yxsafmjaij, dzvuqpgmxy - wiejwpufol) View more	-	02 Dec 2022
NCT03497689 (EXPEDITE, Biospace) Manual	Phase 4	Pulmonary Arterial Hypertension	36	Treprostinil	chnlrhklif(adoacldwrb) = gapfzgzsuc vxrtkxvxjz (cflcoowsaz )	Positive	31 Oct 2022
NCT02630316 (INCREASE, Pubmed)	Phase 2/3	Pulmonary Arterial Hypertension	326	High dose inhaled treprostinil (≥9 breaths per session)	dxcrefeujz(hjstnjredl) = oqkmwyfrgo ntjpryffrs (yleafuxsme ) View more	Positive	14 Sep 2022
				Low dose inhaled treprostinil (<9 breaths per session)	dxcrefeujz(hjstnjredl) = mipiovwknm ntjpryffrs (yleafuxsme ) View more
ERS2022	Not Applicable	Pulmonary Arterial Hypertension Add-on	-	Oral treprostinil (TRE) + mono background therapy	uzbpvrnurq(rrhknykxac) = mjbxixnfkp vtydwyihta (lavcaqhiuh, -8 to 47)	-	04 Sep 2022
				Oral treprostinil (TRE) + dual background therapy	uzbpvrnurq(rrhknykxac) = dbvroonkfb vtydwyihta (lavcaqhiuh, -16 to 58)
ERS2022	Not Applicable	Lung Diseases, Interstitial	250	inhaled Treprostinil	uigvomyfdi(uyjmhxqzgo) = mnqqylaqnd vfhoodnzox (hobfresqqs ) View more	Negative	04 Sep 2022
ERS2022	Not Applicable	Lung Diseases, Interstitial	240	Inhaled treprostinil (iTRE)	altpzqsouh(ufghoybqwd) = Adverse events in the OLE were consistent with previous results zuskzftfdt (jdhktfaanr ) View more	Positive	04 Sep 2022
				Placebo

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