ENCORE success positions Insmed (Nasdaq: INSM) to seek ARIKAYCE label expansion

Rhea-AI Filing Summary

Insmed Incorporated reported positive topline results from its Phase 3b ENCORE study of ARIKAYCE in patients with newly diagnosed MAC lung infection not previously treated with antibiotics. ARIKAYCE plus multidrug therapy improved Respiratory Symptom Score at Month 13 by 17.77 points versus 14.66 with placebo, a 3.11‑point advantage (p=0.0299), and achieved culture conversion by Month 6 in 87.8% of patients versus 57.0% with placebo. By Month 15, a significantly greater proportion of ARIKAYCE patients maintained durable culture conversion, and overall study completion exceeded 90% in both arms, with a safety profile consistent with known risks such as dysphonia, cough and bronchospasm. These results fulfill the U.S. FDA post‑marketing requirement, and Insmed plans a supplemental NDA in the second half of 2026 to seek U.S. label expansion and conversion of ARIKAYCE’s existing refractory indication to traditional approval, as well as a parallel submission to Japan’s PMDA.

Positive

• Phase 3b ENCORE trial met primary and all key secondary endpoints, with ARIKAYCE plus multidrug therapy showing statistically significant improvements in Respiratory Symptom Score and culture conversion versus placebo in newly diagnosed MAC lung disease.
• High culture conversion and durability, including 87.8% culture conversion by Month 6 versus 57.0% with placebo and significantly higher durable conversion at Month 15, strengthens ARIKAYCE’s efficacy package in MAC lung disease.
• FDA post‑marketing requirement fulfilled with a large, global study of 425 patients, supporting Insmed’s plan to file a supplemental NDA in the U.S. and a parallel submission to Japan’s PMDA in the second half of 2026 for label expansion and traditional approval.

Negative

• None.

Insights

Biopharmaceutical clinical and regulatory analyst

ENCORE success strengthens ARIKAYCE’s clinical case and supports key label expansion filings.

The ENCORE trial showed ARIKAYCE plus standard multidrug therapy produced better symptom relief and higher culture conversion than placebo plus multidrug therapy in newly diagnosed MAC lung disease. The primary Respiratory Symptom Score endpoint and all multiplicity‑controlled culture conversion endpoints reached statistical significance.

Culture conversion by Month 6 was 87.8% with ARIKAYCE versus 57.0% with placebo, and durable conversion by Month 15 also favored ARIKAYCE. Safety findings, including higher rates of dysphonia, cough and bronchospasm, were broadly consistent with the established profile, and no deaths were attributed to study drug.

Completion of this study fulfills the FDA post‑marketing requirement, a pivotal regulatory milestone. Insmed plans a supplemental NDA in the U.S. and a submission to Japan’s PMDA in the second half of 2026 to pursue label expansion and traditional approval, which could materially broaden the addressable MAC lung disease population if regulators agree with these results.

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UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d) of

The Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): March 23, 2026

INSMED INCORPORATED

(Exact name of registrant as specified in its charter)

Virginia		000-30739		54-1972729
(State or other jurisdiction		(Commission		(IRS Employer
of incorporation)		File Number)		Identification No.)

700 US Highway 202/206 Bridgewater, New Jersey		08807 (Zip Code)
(Address of principal executive offices)

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

Not Applicable

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

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

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

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

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

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

Securities registered pursuant to Section 12(b) of the Act:

Title of each class	Trading Symbol(s)	Name of each exchange on which registered
Common Stock, par value $0.01 per share	INSM	Nasdaq Global Select Market

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (17 CFR 230.405) or Rule 12b-2 of the Securities Exchange Act of 1934 (17 CFR 240.12b-2).

Emerging growth company ☐

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

ITEM 7.01 — Regulation FD Disclosure.

On March 23, 2026, Insmed Incorporated (the “Company”) issued a press release announcing positive topline results from its Phase 3b ENCORE study of ARIKAYCE^® (amikacin liposome inhalation suspension) plus multidrug therapy (azithromycin 250 mg + ethambutol 15 mg/kg) once-daily versus placebo plus multidrug therapy once-daily in diagnosed patients with a new occurrence of Mycobacterium avium complex (“MAC”) lung infection who had not received antibiotics (the “ENCORE Study”). A copy of the press release is attached hereto as Exhibit 99.1 and incorporated herein by reference.

The Company will host a conference call to discuss the positive topline results of the ENCORE Study on March 23, 2026, at 8:00 a.m., Eastern Time, and a live webcast of the call will be available through the investor relations section of the Company’s website. A copy of the slide presentation to be used by the Company during the conference call is attached hereto as Exhibit 99.2 and incorporated herein by reference.

The information contained in this Item 7.01, including Exhibits 99.1 and 99.2, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as shall be expressly set forth by specific reference in such a filing.

ITEM 8.01 — Other Events.

On March 23, 2026, the Company issued a press release announcing positive topline results from the ENCORE Study. Topline efficacy results from the ENCORE Study are as follows:

	ARIKAYCE 590 mg plus azithromycin 250 mg + ethambutol 15 mg/kg once-daily (N=213)	Placebo plus azithromycin 250 mg + ethambutol 15 mg/kg once-daily (N=212)	Treatment difference, p-value
Primary Endpoint
Change from Baseline in Respiratory Symptom Score at Month 13	17.77 points	14.66 points	3.11 points, p=0.0299*
Multiplicity-Controlled Secondary Endpoints
Culture Conversion by Month 6	87.8%	57.0%	30.8%, p<0.0001*
Culture Conversion by Month 12	84.7%	61.3%	23.3%, p<0.0001*
Culture Conversion by Month 13	82.4%	55.6%	26.8%, p<0.0001*
Durable Culture Conversion at Month 15	76.2%	47.6%	28.6%, p<0.0001*
Change from Baseline in PROMIS Fatigue T-score at Month 13	-5.07	-4.27	-0.81, p=0.2900
Other Secondary & Exploratory Endpoints
Meeting the Meaningful Within-Patient Change (“MWPC”) Threshold as Reflected in the Change in Respiratory Symptom Scores Computed from Baseline to Month 13	MWPC=16.67 53.4%	MWPC=16.67 45.4%	MWPC=16.67 8.0%, p=0.0570**
	MWPC=20.83 43.5%	MWPC=20.83 35.3%	MWPC=20.83 8.2%, p=0.0390**
Change from Baseline in Respiratory Symptom Score at Month 15	16.63 points	11.83 points	4.80 points, p=0.0015**
Time to Culture Conversion	Median:  Month 2***	Median:  Month 3***	Hazard ratio:  2.03, p<0.0001**

 * Statistically significant

 ** Nominal p-value not adjusted for multiplicity control

 *** The second month of two consecutive negative cultures after applying adjustment rules as specified in the statistical analysis plan

Patients were screened and enrolled at 177 sites globally, and a total of 425 patients were randomized 1:1 to receive ARIKAYCE plus multidrug therapy (n=213) or placebo plus multidrug therapy (n=212) once daily for 12 months. Patients then discontinued all study treatments and remained in the trial for three months for the assessment of durability of culture conversion.

The most common treatment-emergent adverse events (“TEAEs”) occurring in 10% or more of patients in a treatment arm and higher in the ARIKAYCE arm compared to the active comparator arm were in line with expectations. Overall TEAEs were as follows:

	ARIKAYCE 590 mg plus azithromycin 250 mg + ethambutol 15 mg/kg once-daily (N=213)	Placebo plus azithromycin 250 mg + ethambutol 15 mg/kg once-daily (N=212)
Any TEAE, n (%)	209 (98.1)	206 (97.2)
Severe TEAE, n (%)	32 (15.0)	22 (10.4)
Serious TEAE, n (%)	30 (14.1)	24 (11.3)
TEAE Leading to Death, n (%)	1 (0.5)	1 (0.5)
TEAE Leading to ARIKAYCE/Comparator Discontinuation, n (%)	31 (14.6)	18 (8.5)
TEAEs ≥10% and Higher in the ARIKAYCE Arm
Dysphonia, n (%)	125 (58.7)	18 (8.5)
Cough, n (%)	70 (32.9)	31 (14.6)
Fatigue, n (%)	37 (17.4)	24 (11.3)
Dyspnea, n (%)	35 (16.4)	12 (5.7)
Nausea, n (%)	33 (15.5)	27 (12.7)
Headache, n (%)	27 (12.7)	25 (11.8)

 n = number of patients with at least one event

Among TEAEs of special interest, only bronchospasm (n=49, 23.0% vs n=25, 11.8%) and hypersensitivity pneumonitis (n=5, 2.3% vs n=0) occurred in notably more patients receiving ARIKAYCE than patients in the comparator arm. Comparable rates between treatment arms were observed for ototoxicity (n=55, 25.8% vs n=48, 22.6%), exacerbation of underlying pulmonary disease (n=23, 10.8% vs n=21, 9.9%), hemoptysis (n=22, 10.3% vs n=22, 10.4%), neuromuscular disorders (n=5, 2.3% vs n=6, 2.8%), and nephrotoxicity (n=1, 0.5% vs n=0). No death was considered related to ARIKAYCE or placebo. The treatment discontinuation rate was 18.3% in the ARIKAYCE arm and 11.8% in the comparator arm. Study completion rates were 90.6% in the ARIKAYCE arm and 93.4% in the comparator arm.

With these results, the Company has completed the study intended to fulfill the U.S. Food and Drug Administration (the “FDA”) post-marketing requirement. The Company plans to file a supplemental new drug application for ARIKAYCE in patients with MAC lung disease in the second half of 2026 to support potential label expansion and to obtain traditional approval for the existing refractory indication in the U.S. Additionally, the Company plans to submit the data to the Pharmaceuticals and Medical Devices Agency in the second half of 2026 to support potential label expansion in Japan.

Forward-Looking Statements

The forward-looking statements in this Current Report on Form 8-K 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: risk that topline data from the Company’s clinical trials, including the ENCORE Study, that the Company announces or publishes from time to time may change as more patient data become available or may be interpreted differently if additional data are disclosed; failure to continue to successfully commercialize ARIKAYCE in the U.S., Europe or Japan, or to maintain U.S., European or Japanese approval for ARIKAYCE; the Company’s inability to obtain full approval of ARIKAYCE from the FDA, or the Company’s failure to obtain regulatory approval to expand ARIKAYCE's indication to a broader patient population; failure to obtain, or delays in obtaining, regulatory approvals for ARIKAYCE outside of the U.S., Europe and Japan, including separate regulatory approval for the Lamira^® Nebulizer System in each market and for each usage; failure to successfully commercialize ARIKAYCE in a broader patient population, if approved by applicable regulatory authorities; uncertainties or changes in the degree of market acceptance of ARIKAYCE by physicians, patients, third-party payors and others in the healthcare community; the Company’s inability to obtain and maintain adequate reimbursement from government or third-party payors for ARIKAYCE in a broader patient population, if approved, or acceptable prices for ARIKAYCE; inaccuracies in the Company’s estimates of the size of the potential markets for ARIKAYCE 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; failure of third parties on which the Company is dependent to manufacture sufficient quantities of ARIKAYCE for commercial needs, or to comply with the Company’s agreements or laws and regulations that impact the Company’s business; the Company’s 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; development of unexpected safety or efficacy concerns related to ARIKAYCE; restrictions or other obligations imposed on the Company by agreements related to ARIKAYCE, including the Company’s license agreement with PARI, and failure to comply with the Company’s obligations under such agreements; the cost and potential reputational damage resulting from litigation to which the Company is or may become a party, including product liability claims; 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, 2025 and any subsequent Company filings with the Securities and Exchange Commission (the “SEC”).

The Company cautions readers not to place undue reliance on any such forward-looking statements, which speak only as of the date hereof. 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.

ITEM 9.01 – Financial Statements and Exhibits.

(d) Exhibits

Exhibit No.		Description
99.1		Press release issued by Insmed Incorporated on March 23, 2026.
99.2		Insmed Incorporated March 23, 2026 ENCORE Presentation.
104		Cover Page Interactive Date File (embedded within the Inline XBRL document).

SIGNATURES

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

Dated: March 23, 2026	INSMED INCORPORATED
	By:	/s/ Michael A. Smith
	Name:	Michael A. Smith
	Title:	Chief Legal Officer and Corporate Secretary

Exhibit 99.1

Insmed Announces Positive Topline Results from Phase 3b ENCORE Study of ARIKAYCE^® (Amikacin Liposome Inhalation Suspension) in Patients with MAC Lung Disease

—The Study Met Primary and All Multiplicity-Controlled Secondary Culture Conversion Endpoints, Demonstrating Statistically Significant and Clinically Meaningful Improvements in Respiratory Symptom Score and Culture Conversion Rates—

—In the Second Half of 2026, Insmed Plans to File a Supplemental NDA for ARIKAYCE with the FDA and Submit the Data to the PMDA in Japan to Support Potential Label Changes—

—Insmed to Host Investor Conference Call on Monday, March 23, 2026, at 8:00 AM ET—

BRIDGEWATER, N.J., Mar. 23, 2026 -- Insmed Incorporated (Nasdaq: INSM), a people-first global biopharmaceutical company striving to deliver first- and best-in-class therapies to transform the lives of patients facing serious diseases, today announced positive topline results from the Phase 3b ENCORE study. This study evaluated ARIKAYCE^® (amikacin liposome inhalation suspension) plus multidrug therapy (azithromycin 250 mg + ethambutol 15 mg/kg) once-daily versus placebo plus multidrug therapy once-daily in diagnosed patients with a new occurrence of Mycobacterium avium complex (MAC) lung infection who had not received antibiotics.

Topline efficacy results from the ENCORE study are as follows:

	ARIKAYCE 590 mg plus azithromycin 250 mg + ethambutol 15 mg/kg (N=213)	Placebo plus azithromycin 250 mg + ethambutol 15 mg/kg (N=212)	Treatment difference, p-value
Primary Endpoint
Change from Baseline in Respiratory Symptom Score at Month 13	17.77 points	14.66 points	3.11 points, p=0.0299*
Multiplicity-Controlled Secondary Endpoints
Culture Conversion by Month 6	87.8%	57.0%	30.8%, p<0.0001*
Culture Conversion by Month 12	84.7%	61.3%	23.3%, p<0.0001*
Culture Conversion by Month 13	82.4%	55.6%	26.8%, p<0.0001*
Durable Culture Conversion at Month 15	76.2%	47.6%	28.6%, p<0.0001*
Change from Baseline in PROMIS Fatigue T-score at Month 13	-5.07	-4.27	-0.81, p=0.2900

 *Statistically significant

“These results are an exciting win for patients living with MAC lung disease and a powerful validation of ARIKAYCE's ability to deliver real clinical benefit as part of a multidrug treatment regimen,” said Martina Flammer, M.D., MBA, Chief Medical Officer of Insmed. “We are energized by the potential for patients with a new MAC infection to see benefit with ARIKAYCE earlier in their treatment journey and look forward to exploring the expansion of the ARIKAYCE indication in the U.S. and Japan, with the ultimate goal of improving outcomes for an even greater number of patients fighting this difficult disease."

With these results, Insmed has completed the study intended to fulfill the U.S. Food and Drug Administration (FDA) post-marketing requirement, further strengthening the clinical foundation supporting ARIKAYCE. Insmed plans to file a supplemental new drug application (sNDA) for ARIKAYCE in patients with MAC lung disease in the second half of 2026 to support potential label expansion and to obtain traditional approval for the existing refractory indication in the U.S. Additionally, Insmed plans to submit the data to the Pharmaceuticals and Medical Devices Agency (PMDA) in the second half of 2026 to support potential label expansion in Japan. Insmed also plans to present these data at a future medical congress.

“These groundbreaking results show that patients may have significant clinical benefit from including ARIKAYCE as part of their multidrug treatment earlier in their MAC lung disease journey,” said David Griffith, M.D., ENCORE Steering Committee Member, Professor of Medicine, National Jewish Health. “The improvements in Respiratory Symptom Score alongside durable culture conversion highlight the potential for this medicine to make a substantial difference in outcomes for patients facing this serious and often progressive infection.”

The safety profile was consistent with the known safety profile of ARIKAYCE, and no new safety signals were observed. The most common treatment-emergent adverse events (TEAEs) occurring in 10% or more of patients in a treatment arm and higher in the ARIKAYCE arm compared to the active comparator arm were in line with expectations. Overall TEAEs were as follows:

	ARIKAYCE 590 mg plus azithromycin 250 mg + ethambutol 15 mg/kg (N=213)	Placebo plus azithromycin 250 mg + ethambutol 15 mg/kg (N=212)
Any TEAE, n (%)	209 (98.1)	206 (97.2)
Severe TEAE, n (%)	32 (15.0)	22 (10.4)
Serious TEAE, n (%)	30 (14.1)	24 (11.3)
TEAE Leading to Death, n (%)	1 (0.5)	1 (0.5)
TEAE Leading to ARIKAYCE/Comparator Discontinuation, n (%)	31 (14.6)	18 (8.5)
TEAEs ≥10% and Higher in the ARIKAYCE Arm
Dysphonia, n (%)	125 (58.7)	18 (8.5)
Cough, n (%)	70 (32.9)	31 (14.6)
Fatigue, n (%)	37 (17.4)	24 (11.3)
Dyspnea, n (%)	35 (16.4)	12 (5.7)
Nausea, n (%)	33 (15.5)	27 (12.7)
Headache, n (%)	27 (12.7)	25 (11.8)

n = number of patients with at least 1 event

Among TEAEs of special interest, only bronchospasm (n=49, 23.0% vs n=25, 11.8%) and hypersensitivity pneumonitis (n=5, 2.3% vs n=0) occurred in notably more patients receiving ARIKAYCE than patients in the comparator arm. Comparable rates between treatment arms were observed for ototoxicity (n=55, 25.8% vs n=48, 22.6%), exacerbation of underlying pulmonary disease (n=23, 10.8% vs n=21, 9.9%), hemoptysis (n=22, 10.3% vs n=22, 10.4%), neuromuscular disorders (n=5, 2.3% vs n=6, 2.8%), and nephrotoxicity (n=1, 0.5% vs n=0). No death was considered related to ARIKAYCE or placebo. The treatment discontinuation rate was 18.3% in the ARIKAYCE arm and 11.8% in the comparator arm. Study completion rates were 90.6% in the ARIKAYCE arm and 93.4% in the comparator arm.

Conference Call

Insmed management will host a conference call for investors beginning at 8:00 AM ET on Monday, March 23, 2026, to discuss the ENCORE results. Shareholders and other interested parties may participate in the conference call by dialing (800) 715-9871 (U.S.) or +1 (646) 307-1963 (International) and referencing access code 2033335. 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 one hour after its completion through March 30, 2026, by dialing (800) 770-2030 (U.S. and Canada) or +1 (609) 800-9909 (International) and referencing access code 2033335. 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.

About the Phase 3b ENCORE Study

ENCORE was a randomized, double-blind, placebo-controlled, Phase 3b study to evaluate the efficacy and safety of ARIKAYCE plus multidrug therapy in diagnosed patients with a new occurrence of MAC lung infection who have not received antibiotics. Among enrolled patients, 82.4% were experiencing their first MAC infection, while this was the second or third infection for 17.6% of patients. Patients were screened and enrolled at 177 sites globally, and a total of 425 patients were randomized 1:1 to receive once-daily regimens of either ARIKAYCE plus multidrug therapy (azithromycin 250 mg + ethambutol 15 mg/kg; n=213) or placebo (inhaled empty liposome control) plus multidrug therapy (azithromycin 250 mg + ethambutol 15 mg/kg; n=212) for 12 months. Patients then discontinued all study treatments and remained in the trial for three months for the assessment of durability of culture conversion.

The primary endpoint is change from baseline in Respiratory Symptom Score at Month 13 based on eight items from the Quality of Life – Bronchiectasis (QoL-B) Respiratory Domain. The multiplicity-controlled secondary endpoints are the proportion of patients achieving culture conversion by Months 6, 12, and 13, and durable culture conversion at Month 15, and change from baseline in PROMIS Fatigue T-score at Month 13. The Japan-specific primary endpoint is the proportion of patients who achieved both culture conversion by Month 6 and durable culture conversion at Month 15.

About MAC Lung Disease

Mycobacterium avium complex (MAC) lung disease is a rare and serious disease that can significantly increase morbidity and mortality. Patients with MAC lung disease can experience a range of symptoms that often worsen over time, including chronic cough, dyspnea, fatigue, fever, weight loss, and chest pain. In some cases, MAC lung disease can cause severe, even permanent damage to the lungs, and can be fatal. MAC lung disease is an emerging public health concern worldwide with significant unmet need.

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).

About PARI Pharma and the Lamira^® Nebulizer System

ARIKAYCE is delivered by a novel inhalation device, the Lamira^® Nebulizer System, developed by PARI. Lamira^® is a quiet, portable nebulizer that enables efficient aerosolization of ARIKAYCE via a vibrating, perforated membrane. Based on PARI's 100-year history working with aerosols, PARI is dedicated to advancing inhalation therapies by developing innovative delivery platforms to improve patient care.

IMPORTANT SAFETY INFORMATION FOR ARIKAYCE IN THE U.S.

WARNING: RISK OF INCREASED RESPIRATORY ADVERSE REACTIONS

ARIKAYCE has been associated with an increased risk of respiratory adverse reactions, including hypersensitivity pneumonitis, hemoptysis, bronchospasm, and exacerbation of underlying pulmonary disease that have led to hospitalizations in some cases. 

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 www.fda.gov/medwatch, 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 people-first global biopharmaceutical company striving to deliver first- and best-in-class therapies to transform the lives of patients facing serious diseases. The Company is advancing a diverse portfolio of approved and mid- to late-stage investigational medicines as well as cutting-edge drug discovery focused on serving patient communities where the need is greatest. Insmed's most advanced programs are in pulmonary and inflammatory conditions, including two approved therapies to treat chronic, debilitating lung diseases. The Company's early-stage programs encompass a wide range of technologies and modalities, including gene therapy, AI-driven protein engineering, protein manufacturing, RNA end-joining, and synthetic rescue.

Headquartered in Bridgewater, New Jersey, Insmed has offices and research locations throughout the United States, Europe, and Japan. Insmed is proud to be recognized as one of the best employers in the biopharmaceutical industry, including spending five consecutive years as the No. 1 Science Top Employer. Visit www.insmed.com to learn more or follow us on LinkedIn, Instagram, YouTube, and X.

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: risk that topline data from the Company’s clinical trials, including the ENCORE trial, that the Company announces or publishes from time to time may change as more patient data become available or may be interpreted differently if additional data are disclosed; failure to continue to successfully commercialize ARIKAYCE in the U.S., Europe or Japan, or to maintain U.S., European or Japanese approval for ARIKAYCE; the Company’s inability to obtain full approval of ARIKAYCE from the FDA, or the Company’s failure to obtain regulatory approval to expand ARIKAYCE's indication to a broader patient population; failure to obtain, or delays in obtaining, regulatory approvals for ARIKAYCE outside of the U.S., Europe and Japan, including separate regulatory approval for the Lamira^® Nebulizer System in each market and for each usage; failure to successfully commercialize ARIKAYCE in a broader patient population, if approved by applicable regulatory authorities; uncertainties or changes in the degree of market acceptance of ARIKAYCE by physicians, patients, third-party payors and others in the healthcare community; the Company’s inability to obtain and maintain adequate reimbursement from government or third-party payors for ARIKAYCE in a broader patient population, if approved, or acceptable prices for ARIKAYCE; inaccuracies in the Company’s estimates of the size of the potential markets for ARIKAYCE 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; failure of third parties on which the Company is dependent to manufacture sufficient quantities of ARIKAYCE for commercial needs, or to comply with the Company’s agreements or laws and regulations that impact the Company’s business; the Company’s 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; development of unexpected safety or efficacy concerns related to ARIKAYCE; restrictions or other obligations imposed on the Company by agreements related to ARIKAYCE, including the Company’s license agreement with PARI, and failure to comply with the Company’s obligations under such agreements; the cost and potential reputational damage resulting from litigation to which the Company is or may become a party, including product liability claims; 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, 2025 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

Vice President, Investor Relations

(646) 812-4030

investor.relations@insmed.com

Media:

Claire Mulhearn

Vice President, Corporate Communications

(862) 842-6819

media@insmed.com

Exhibit 99.2

 March 23, 2026  Topline Results of Phase 3b ENCORE Study of ARIKAYCE® in Patients with Newly Diagnosed MAC Lung Infection Not Yet Treated With Antibiotics  MAC: Mycobacterium avium complex lung disease | ARIKAYCE is approved in the U.S. 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)  

 Opening Remarks  Closing Remarks  Q&A Session  4-6  7-16  17  18  Will Lewis  Chair & CEO  Martina Flammer  Chief Medical Officer  Study Results 

 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: risk that topline data from the Company’s clinical trials, including the ENCORE trial, that the Company announces or publishes from time to time may change as more patient data become available or may be interpreted differently if additional data are disclosed; failure to continue to successfully commercialize ARIKAYCE® in the U.S., Europe or Japan, or to maintain U.S., European or Japanese approval for ARIKAYCE; the Company’s inability to obtain full approval of ARIKAYCE from the FDA, or the Company’s failure to obtain regulatory approval to expand ARIKAYCE's indication to a broader patient population; failure to obtain, or delays in obtaining, regulatory approvals for ARIKAYCE outside of the U.S., Europe and Japan, including separate regulatory approval for the Lamira® Nebulizer System in each market and for each usage; failure to successfully commercialize ARIKAYCE in a broader patient population, if approved by applicable regulatory authorities; uncertainties or changes in the degree of market acceptance of ARIKAYCE by physicians, patients, third-party payors and others in the healthcare community; the Company’s inability to obtain and maintain adequate reimbursement from government or third-party payors for ARIKAYCE in a broader patient population, if approved, or acceptable prices for ARIKAYCE; inaccuracies in the Company’s estimates of the size of the potential markets for ARIKAYCE 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; failure of third parties on which the Company is dependent to manufacture sufficient quantities of ARIKAYCE for commercial needs, or to comply with the Company’s agreements or laws and regulations that impact the Company’s business; the Company’s 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; development of unexpected safety or efficacy concerns related to ARIKAYCE; restrictions or other obligations imposed on the Company by agreements related to ARIKAYCE, including the Company’s license agreement with PARI, and failure to comply with the Company’s obligations under such agreements; the cost and potential reputational damage resulting from litigation to which the Company is or may become a party, including product liability claims; 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, 2025 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.  Additional Disclaimers: ARIKAYCE has not been approved for the treatment of all patients with MACLD. This presentation is not promotion or advertisement of ARIKAYCE. Insmed and ARIKAYCE are registered trademarks of Insmed Incorporated. All other trademarks are property of their respective owner(s).   FDA: Food & Drug Administration | U.S.: United States | MACLD: Mycobacterium avium complex lung disease 

 Opening Remarks  Will Lewis | Chair & CEO 

 ENCORE Demonstrates Clear Success  PRO: patient reported outcome | MAC: Mycobacterium avium complex lung disease | 1 ARIKAYCE + macrolide-based background regimen consisting of Azithromycin (AZI) and Ethambutol (ETH) | 2 Empty liposome placebo control + AZI + ETH  Statistically significant improvement in Respiratory Symptom Score at Month 13   Statistically significant greater rate of culture conversion by Months 6, 12, 13, and 15  Earlier, greater, and more durable culture conversion throughout the entire study period  Patients on ARIKAYCE® showed1…  …versus patients on active multidrug comparator therapy2  Using a validated PRO, results demonstrate that ARIKAYCE improves respiratory symptoms and effectively clears MAC infection from the lungs 

 Next Steps: Results Support Actions to Seek Expansion of ARIKAYCE’s Label in the U.S. and Japan   Plan to file sNDA with FDA for potential U.S. label expansion in MACLD patients in 2H:26  Will also request conversion of ARIKAYCE’s current U.S. conditional label to traditional approval  Intend to submit data to PDMA to support potential Japanese label expansion in 2H:26  sNDA: supplemental new drug application | U.S.: United States | FDA: Food & Drug Administration | PDMA: Pharmaceuticals & Medical Device Agency | H: half | MAC / MACLD: Mycobacterium avium complex lung disease | TAM: total addressable market | * if expanded label for ARIKAYCE is approved | † Total addressable Refractory MAC patients in the U.S., Europe (France, Germany, Italy, Spain, and United Kingdom), and Japan | ‡ Additional addressable MAC patients in the U.S. and Japan if expanded ARIKAYCE label is approved | Note: References related to patient TAMs can be found in the Company's Investor Presentation  Potential Label Expansion*  Current TAM 30K† (Refractory MAC only)  ~+200K‡ Patients* (MACLD)  Addressable   Patient Population 

 Study Results  Martina Flammer | Chief Medical Officer 

 Phase 3b Registrational PMR Trial in Patients With A New Occurrence of MAC Lung Infection  PMR: post-marketing requirement | MAC: Mycobacterium avium complex | AZI: Azithromycin | ETH: Ethambutol | EOT: end of treatment | QD: once-daily | U.S.: United States | DCC: durable culture conversion | * A predefined sequential testing approach was applied to control the overall type I error rate (α=0.05) | 1 ARIKAYCE (590 mg) + macrolide-based background regimen consisting of AZI (250 mg) and ETH (15 mg/kg) | 2 Empty liposome control placebo + macrolide-based background regimen consisting of AZI and ETH | 3 RSS ranges from 0 to 100, with positive change indicating improvement | Culture conversion was defined as no MAC growth on agar and broth media in all sputum cultures at 2 consecutive visits (8 total samples). Durable culture conversion defined as no MAC growth (culture negative) at Months 11, 12, 13, and 15  Key Secondary Endpoint  (DCC)  425 adults with new occurrence of MAC lung infection who have not received antibiotics (randomized)  ARIKAYCE Arm1  ARIKAYCE + AZI + ETH | QD  Comparator Arm2  Placebo + AZI + ETH | QD  Primary   Endpoint  (RSS)  Month 13  Month 15  active : placebo  Screening  1:1  One Month   Off Treatment  Three Months Off Treatment  Off   Treatment  Months 1-12  Baseline  EOT   ENCORE  Primary Endpoint  Change from baseline in Respiratory Symptom Score (RSS)3 at Month 13 (one month off treatment)  Multiplicity-Controlled Secondary Endpoints*  Proportion of patients achieving culture conversion by Month 13 (one month off treatment)  Proportion of patients achieving durable culture conversion by Month 15 (three months off treatment)  Proportion of patients achieving culture conversion by Months 12 and Month 6  Change from baseline fatigue symptom score at Month 13 (PROMIS Fatigue T-score)  Other Secondary & Exploratory Endpoints  Change from baseline in RSS at Month 15  Proportion of participants meeting the meaningful within-patient change (MWPC) threshold as reflected in the change in RSS computed from baseline to Month 13   Time to culture conversion  Additional data to be presented at   future medical meetings 

 ARIKAYCE Arm1N=213  Comparator Arm2N=212  Total  N=425  Age: Median at Screening, Years  68.0  69.0  68.0  ≥65, % (n)  67.1% (143)  70.3% (149)  68.7% (292)  Sex: Female, % (n)  80.3% (171)  78.3% (166)  79.3% (337)  Geographic Region: % (n)*  North America  24.4% (52)  25.5% (54)  24.9% (106)  Japan  20.2% (43)  19.3% (41)  19.8% (84)  Europe  26.8% (57)  25.9% (55)  26.4% (112)  Rest of the World  28.6% (61)  29.2% (62)  28.9% (123)  Race: % (n)  White  62.9% (134)  62.7% (133)  62.8% (267)  Asian  32.4% (69)  35.4% (75)  33.9% (144)  Other  4.7% (10)  1.9% (4)  3.3% (14)  History of MAC Lung Infection3: Initial,% (n)*  82.2% (175)  82.5% (175)  82.4% (350)  Mean Baseline† Respiratory Symptom Score4 (RSS), Points  63.91  61.52  62.72  Mean Baseline PROMIS Fatigue T-Score, Points  55.23  54.88  55.05  Baseline Characteristics Were Well-Balanced Across Arms  MAC: Mycobacterium avium complex | AZI: Azithromycin | ETH: Ethambutol | n/N: number of participants | 1 ARIKAYCE (590 mg) + macrolide-based background regimen consisting of AZI (250 mg) and ETH (15 mg/kg) | 2 Empty liposome control placebo + macrolide-based background regimen consisting of AZI and ETH | 3 Initial diagnosis defined as a patient being diagnosed with MAC lung infection for the first time. Subsequent diagnosis defined as a previously infected MAC patient being reinfected with the disease (new infection). A reinfected patient is not the same as a refractory patient, who did not culture convert on initial therapy and must add or switch therapies to treat the same infection | 4 RSS ranges from 0 to 100, with positive change indicating improvement | † Baseline value is the last non-missing value prior to the first dose of ARIKAYCE or empty liposomal control placebo | * randomization stratification factors 

 MAC: Mycobacterium avium complex | AZI: Azithromycin | ETH: Ethambutol | RSS: Respiratory Symptom Score | LS: least-squares | SE: standard error | CI: confidence interval | SAP: statistical analysis plan | N: number of participants | 1 RSS ranges from 0 to 100, with positive change indicating improvement | 2 ARIKAYCE (590 mg) + macrolide-based background regimen consisting of AZI (250 mg) and ETH (15 mg/kg) | 3 Empty liposome control placebo + macrolide-based background regimen consisting of AZI and ETH | 4 LS mean changes from baseline RSS to Month 15 for the ARIKAYCE and Comparator arms were 16.63 points and 11.83 points, respectively | † ANCOVA (analysis of covariance) model includes change from baseline as the dependent variable and treatment, baseline RSS, history of MAC lung infection (initial or subsequent), and region as independent variables. Multiple imputations are applied to impute the missing RSS scores in the analysis using ANCOVA according to the type of incurrent events and the assumptions of mission data mechanism described in the SAP | * statistically significant | ^ nominal not adjusted for multiplicity control  Symptom benefit at Month 15 expands to a 4.80 point difference4,†, favoring the ARIKAYCE arm (p=0.0015^)  Exploratory Endpoint  RSS: Statistically Significant Improvement in RSS1 Observed With ARIKAYCE at Month 13  PRIMARY ENDPOINT  LS Mean Change From Baseline   RSS to Month 13†  ARIKAYCE Arm2  N=213  Comparator Arm3  N=212  3.11 points, p=0.0299*  95% CI [0.30, 5.92]  SE (1.01)  SE (1.01)  Change From Baseline RSS to Month 15 

 Responder Analysis: ARIKAYCE Arm Showed Higher Rates of Clinically Meaningful Improvement in RSS1 at Month 13   Meaningful Within-Patient Change in RSS  Secondary Endpoint  Separation observed between arms consistently favored ARIKAYCE across a range of possible   RSS improvement thresholds that could be determined clinically meaningful by the FDA  CDF (%)  16.67  — ARIKAYCE Arm2  — Comparator Arm3  8.0%  Difference at lower threshold favoring ARIKAYCE arm  p=0.0570^  8.2%  Difference at higher threshold favoring ARIKAYCE arm  p=0.0390^   Predicted Change in RSS (Points)  I M P R O V E M E N T  D E T E R I O R A T I O N  Estimated Range of Meaningful Within-Patient RSS Improvement†  20.83  AZI: Azithromycin | ETH: Ethambutol | RSS: Respiratory Symptom Score | CDF: covariate-adjusted cumulative distribution function | FDA: Food and Drug Administration | MWPC: meaningful within-patient change | 1 RSS ranges from 0 to 100, with positive change indicating improvement | 2 ARIKAYCE (590 mg) + macrolide-based background regimen consisting of AZI (250 mg) and ETH (15 mg/kg) | 3 Empty liposome control placebo + macrolide-based background regimen consisting of AZI and ETH | Note: 53.4% of ARIKAYCE arm participants achieved the 16.67 MWPC in RSS threshold (vs. 45.4% in the Comparator arm) and 43.5% of ARIKAYCE arm participants achieved the 20.83 MWPC in RSS threshold (vs. 35.5% in the Comparator arm); using the standardized logistic regression (SLR); analysis includes treatment group, baseline, region, and history of MAC lung infection (initial or subsequent) as factors in model | ^ nominal not adjusted for multiplicity control | † Estimated threshold range established using data (prior to unblinding) from the Phase 3 ARISE and ENCORE studies  

 MAC: Mycobacterium avium complex | AZI: Azithromycin | ETH: Ethambutol | SAP: statistical analysis plan | SE: standard error | | N: number of participants | 1 Conversion by Month 13 was defined as negative MAC cultures at Month 12 and Month 13 after applying adjustment rules as specified in the SAP | 2 ARIKAYCE (590 mg) + macrolide-based background regimen consisting of AZI (250 mg) and ETH (15 mg/kg) | 3 Empty liposome control placebo + macrolide-based background regimen consisting of AZI and ETH | † standardized logistic regression (SLR); analysis includes treatment group, region, and history of MAC lung infection (initial or subsequent) as factors in model. Multiple imputations are applied to impute the missing culture conversion results in the analysis using SLR model according to the type of incurrent events and the assumptions of missing data mechanism as described in the SAP | * statistically significant  26.8%, p<0.0001*  95% CI [18.3%, 35.3%]  Rate of Culture Conversion (%) by Month 13†  ARIKAYCE Arm2  N=213  Comparator Arm3  N=212  Culture Conversion: Statistically Significant Greater Proportion of ARIKAYCE Patients Achieved Culture Conversion1 by Month 13  SECONDARY ENDPOINT  SE (2.7%)  SE (3.4%) 

 MAC: Mycobacterium avium complex | AZI: Azithromycin | ETH: Ethambutol | SAP: statistical analysis plan | SE: standard error | N: number of participants | 1 Durable converters at Month 15 are participants who achieved and maintained negative MAC cultures by Months 11, 12, 13 and 15 after applying adjustment rules as specified in the SAP | 2 ARIKAYCE (590 mg) + macrolide-based background regimen consisting of AZI (250 mg) and ETH (15 mg/kg) | 3 Empty liposome control placebo + macrolide-based background regimen consisting of AZI and ETH | † standardized logistic regression (SLR); analysis includes treatment group, region, and history of MAC lung infection (initial or subsequent) as factors in model. Multiple imputations are applied to impute the missing culture conversion results in the analysis using SLR model according to the type of incurrent events and the assumptions of missing data mechanism as described in the SAP | * statistically significant  28.6%, p<0.0001*  95% CI [19.7%, 37.5%]  Rate of Durable Culture Conversion (%) by Month 15†  ARIKAYCE Arm2  N=213  Comparator Arm3  N=212  Statistically Significant Greater Proportion of ARIKAYCE Patients Achieved Durable Culture Conversion1 by Month 15  KEY SECONDARY ENDPOINT  SE (3.0%)  SE (3.4%) 

 Earlier and Greater Culture Conversion1 Rates Were Achieved in ARIKAYCE Arm at Every Measured Timepoint  Proportion of Patients with Culture Conversion, ±SE (%)†  Month  ARIKAYCE Arm3  Comparator Arm4  MAC: Mycobacterium avium complex | AZI: Azithromycin | ETH: Ethambutol | SE: standard error | SAP: statistical analysis plan | EOT: end of treatment | DCC: durable culture conversion | 1Culture conversion rate at each visit from Month 2 to Month 13 is displayed as the second month of 2 consecutive negative cultures after applying adjustment rules as specified in the SAP | 2 Durable converters at Month 15 are participants who achieved and maintained negative MAC cultures by Months 11, 12, 13 and 15 after applying adjustment rules as specified in the SAP | 3 ARIKAYCE (590 mg) + macrolide-based background regimen consisting of AZI (250 mg) and ETH (15 mg/kg) | 4 Empty liposome control placebo + macrolide-based background regimen consisting of AZI and ETH | † standardized logistic regression (SLR); analysis includes treatment group, region, and history of MAC lung infection (initial or subsequent) as factors in model. Multiple imputations are applied to impute the missing culture conversion results in the analysis using SLR model according to the type of incurrent events and the assumptions of missing data mechanism as described in the SAP | ‡ ARIKAYCE arm achieved median time to culture conversion at Month 2 vs. Month 3 for the active comparator arm (Hazard Ratio of 2.03, suggesting that patients treated with ARIKAYCE were roughly twice as likely to achieve culture conversion (nominal p<0.0001, not adjusted for multiplicity control)  Time to Culture Conversion  Exploratory Endpoint  ARIKAYCE patients were roughly twice as likely to achieve earlier culture conversion vs. active comparator patients‡  (EOT)  (DCC)2 

 Safety: No New Or Unexpected Safety Signals Observed   ​ARIKAYCE Arm1  N=213  Comparator Arm2  N=212  DISPOSITION  %  n  %  n  Study Completion**  90.6%  193  93.4%  198  ARIKAYCE/Comparator Treatment Completion  81.7%  174  88.2%  187  ARIKAYCE/Comparator Discontinuation  18.3%  39  11.8%  25  SAFETY  TEAES  98.1%  209  97.2%  206   Serious  14.1%  30  11.3%  24   Severe  15.0%  32  10.4%  22   Leading to ARIKAYCE/Comparator Discontinuation  14.6%  31  8.5%  18   Leading to Death  0.5%  1  0.5%  1  Most Common TEAEs Reported*   Dysphonia  58.7%  125  8.5%  18   Cough  32.9%  70  14.6%  31   Fatigue  17.4%  37  11.3%  24   Dyspnea  16.4%  35  5.7%  12   Nausea  15.5%  33  12.7%  27   Headache  12.7%  27  11.8%  25  AZI: Azithromycin | ETH: Ethambutol | 1 ARIKAYCE (590 mg) + macrolide-based background regimen consisting of AZI (250 mg) and ETH (15 mg/kg) | 2 Empty liposome control placebo + macrolide-based background regimen consisting of AZI and ETH | n/N: number of participants | TEAEs: treatment-emergent adverse effects | * TEAEs that occurred in ≥10% of the ARIKAYCE arm and were elevated compared to the Comparator arm | ** Patients may discontinue one or more of the treatments in the study, but not discontinue the entire study  Tolerability profile of ARIKAYCE + multidrug therapy was consistent with known profiles of these therapies  >90% completion observed for both study arms**   No deaths were considered ARIKAYCE- or placebo-related 

 RSS  Improvement  Statistically significant at Month 13*  Strengthening of improvement at Month 15^  Greater proportion of clinically meaningful RSS responders at Month 13  Culture Conversion  Statistically significant greater conversion by Months 6, 12, 13 and 15*  Earlier, greater, and more durable conversion  Results Show That Early Treatment with ARIKAYCE + Multidrug Therapy Can Significantly Improve Outcomes For MACLD Patients  Treatment with ARIKAYCE1 vs. Comparator2 showed…  Safety & Tolerability  >90% completion in both study arms  No new or unexpected safety signals observed  AZI: Azithromycin | ETH: Ethambutol | 1 ARIKAYCE (590 mg) + macrolide-based background regimen consisting of AZI (250 mg) and ETH (15 mg/kg) | 2 Empty liposome control placebo + macrolide-based background regimen consisting of AZI and ETH | MAC / MACLD: Mycobacterium avium complex lung disease | RSS: Respiratory Symptom Score | * statistically significant | ^ not multiplicity controlled; nominally statistically significant 

 Results bring new hope to patients and providers battling MACLD  Early treatment with ARIKAYCE may improve patient respiratory symptoms, achieve culture conversion sooner, and maintain conversion for longer  Expect to file a sNDA for ARIKAYCE in patients with MACLD with the FDA in 2H:26  MAC / MACLD: Mycobacterium avium complex lung disease | sNDA: supplemental new drug application | FDA: Food and Drug Administration | H: half  Clear Success Unlocks Pathway to Engage with Regulatory Authorities 

 Q&A Session  Will Lewis  Chair & CEO  Sara Bonstein  Chief Financial Officer  Kevin Mange  Chief Development Officer  Martina Flammer  Chief Medical Officer  Thank you to the patients and investigators who participated in this study! 

FAQ

What did Insmed (INSM) announce about the Phase 3b ENCORE study?

Insmed announced positive topline results from the Phase 3b ENCORE trial of ARIKAYCE in newly diagnosed MAC lung disease. The study met its primary symptom endpoint and all multiplicity‑controlled culture conversion endpoints, demonstrating statistically significant and clinically meaningful benefits versus placebo plus multidrug therapy.

What were the key efficacy results for ARIKAYCE in ENCORE for Insmed (INSM)?

ARIKAYCE plus multidrug therapy improved Respiratory Symptom Score at Month 13 more than placebo and achieved 87.8% culture conversion by Month 6 versus 57.0% with placebo. A significantly higher proportion of patients maintained durable culture conversion through Month 15.

How did the safety profile of ARIKAYCE look in Insmed’s ENCORE trial?

The safety profile was consistent with known ARIKAYCE risks. Common treatment‑emergent adverse events included dysphonia, cough, fatigue, dyspnea and nausea, occurring more often with ARIKAYCE than placebo. Serious events and deaths occurred at similar low rates, and no death was considered related to ARIKAYCE or placebo.

What regulatory steps will Insmed (INSM) take after the ENCORE results?

Insmed plans to file a supplemental new drug application for ARIKAYCE in MAC lung disease in the second half of 2026 to seek U.S. label expansion and conversion to traditional approval. The company also intends to submit ENCORE data to Japan’s PMDA for potential label expansion.

Did ENCORE fulfill any FDA requirements for Insmed’s ARIKAYCE?

Yes. Insmed stated that ENCORE completed the study intended to fulfill the U.S. Food and Drug Administration post‑marketing requirement for ARIKAYCE. This strengthens the overall clinical package supporting the drug and underpins the planned supplemental NDA for broader MAC lung disease use.

What does the ENCORE outcome mean for ARIKAYCE’s market opportunity for Insmed (INSM)?

ENCORE supports pursuing label expansion from refractory to broader MAC lung disease, potentially adding a large population of newly diagnosed patients. Insmed highlighted an incremental addressable MAC patient pool if regulators approve expanded labeling in the U.S. and Japan based on these data.

Filing Exhibits & Attachments

5 documents

Press Releases

• EX-99.1 EXHIBIT 99.1 60.9 KB
• EX-99.2 EXHIBIT 99.2 45.1 KB

Other Documents

• EX-101 XBRL TAXONOMY EXTENSION SCHEMA 3.8 KB
• EX-101 XBRL TAXONOMY EXTENSION LABEL LINKBASE 21.5 KB
• EX-101 XBRL TAXONOMY EXTENSION PRESENTATION LINKBASE 15.7 KB