Insmed Incorporated (INSM) — Agentic Tribune

ITEM 1. BUSINESS

Business Overview

We are a people-first global biopharmaceutical company striving to deliver first- and best-in-class therapies to transform the lives of patients facing serious diseases. Our commercial portfolio and clinical pipeline are organized around three therapeutic areas: Respiratory, Immunology & Inflammation, and Neuro & Other Rare. To complement our internal research and development, we also actively evaluate in-licensing and acquisition opportunities for commercial products, product candidates and technologies.

Our two commercial products, ARIKAYCE® and BRINSUPRI®, are both part of the Respiratory therapeutic area. ARIKAYCE is approved in the US as ARIKAYCE (amikacin liposome inhalation suspension), in Europe as ARIKAYCE Liposomal 590 mg Nebuliser Dispersion and in Japan as ARIKAYCE inhalation 590mg (amikacin sulfate inhalation drug product). ARIKAYCE received accelerated approval in the US in September 2018 for the treatment of MAC lung disease as part of a combination antibacterial drug regimen for adult patients with limited or no alternative treatment options in a refractory setting. In October 2020, the European Commission (EC) approved ARIKAYCE Liposomal for the treatment of nontuberculous mycobacterial (NTM) lung infections caused by MAC in adults with limited treatment options who do not have cystic fibrosis (CF). In March 2021, Japan's Ministry of Health, Labour and Welfare (MHLW) approved ARIKAYCE for the treatment of patients with NTM lung disease caused by MAC who did not sufficiently respond to prior treatment with a multidrug regimen. NTM lung disease caused by MAC (which we refer to as MAC lung disease) is a rare and often chronic infection that can cause irreversible lung damage and can be fatal.

Our Respiratory therapeutic area also includes the clinical-stage programs TPIP and INS1148. TPIP is an inhaled dry powder formulation of the treprostinil prodrug treprostinil palmitil which may offer a differentiated product profile for pulmonary hypertension associated with interstitial lung disease (PH-ILD), pulmonary arterial hypertension (PAH), progressive pulmonary fibrosis (PPF), and idiopathic pulmonary fibrosis (IPF). INS1148 is a monoclonal antibody targeting a specific isoform of Stem Cell Factor, called Stem Cell Factor 248 (SCF248).

The clinical-stage program in our Inflammation & Immunology therapeutic area is brensocatib, a small molecule, oral, reversible inhibitor of dipeptidyl peptidase 1 (DPP1), for the treatment of patients with hidradenitis suppurativa (HS).

The clinical-stage programs in our Neuro & Other Rare therapeutic area are INS1201, an intrathecally delivered gene therapy for patients with Duchenne muscular dystrophy (DMD), and INS1202, an intrathecally delivered gene therapy for patients with amyotrophic lateral sclerosis (ALS).

Our pre-clinical research programs encompass a wide range of technologies and modalities, including gene therapy, AI-driven protein engineering, protein manufacturing, RNA end-joining, and synthetic rescue.

A summary of our commercial products and clinical-stage pipeline is shown below:

The information below summarizes our updates and anticipated near-term milestones across our therapeutic areas.

Respiratory

BRINSUPRI

•In August 2025, BRINSUPRI (brensocatib 25 mg and 10 mg tablets), an oral, once-daily treatment for NCFB in adults and children 12 years and older, was approved in the US by the FDA. We launched BRINSUPRI in the US in the third quarter of 2025.

•In November 2025, the EC approved BRINSUPRI (brensocatib 25 mg tablets) for the treatment of NCFB in patients 12 years of age and older with two or more exacerbations in the prior 12 months.

•We anticipate regulatory decisions for brensocatib for the treatment of NCFB in the United Kingdom (UK) and Japan in 2026.

•We continue to evaluate the potential effect of evolving US policies which will then impact the timing for future potential international commercial launches.

ARIKAYCE

•Following the announcement of positive topline results from the ARISE trial, in June 2024, we met and aligned with the FDA on the primary endpoint for the ENCORE trial. If the data are positive, ENCORE may support a label expansion to include all MAC lung disease as well as support full approval for the current refractory indication.

•We completed enrollment in the ENCORE trial with 425 patients in the fourth quarter of 2024.

•We anticipate reporting topline data from the ENCORE trial by April 2026, with the submission of a US supplementary new drug application (sNDA) for ARIKAYCE in all patients with MAC lung disease projected for the second half of 2026. We also plan to review the data with the Pharmaceuticals and Medical Devices Agency to support potential label expansion in Japan.

TPIP

•In January 2026, the Office of Orphan Products Development of the FDA granted orphan drug designation to treprostinil palmitil for the treatment of patients with PAH. We plan to initiate a Phase 3 study of TPIP in patients with PAH in the first half of 2026.

•We initiated PALM-ILD, a Phase 3 study of TPIP in patients with PH-ILD in the fourth quarter of 2025 and are actively enrolling patients.

•We expect to report data from the open-label extension (OLE) of our Phase 2b study of TPIP in PAH in the second half of 2026.

•Additional Phase 3 studies of TPIP are anticipated to be initiated in patients with PPF and IPF in the second half of 2026.

INS1148

•In December 2025, we acquired INS1148, a Phase 2-ready monoclonal antibody targeting SCF248.

•We plan to advance Phase 2 development programs for INS1148 initially in interstitial lung disease and moderate to severe asthma.

We are exploring additional opportunities utilizing our various technologies within the Respiratory therapeutic area.

Immunology & Inflammation

Brensocatib

•In October 2025, we completed enrollment in the Phase 2b CEDAR study of brensocatib in patients with HS. We anticipate reporting topline data in the second quarter of 2026.

We are exploring additional opportunities utilizing our various technologies within the Immunology & Inflammation therapeutic area.

Neuro & Other Rare

INS1201

•We continue to enroll patients in the Phase 1 ASCEND clinical study of INS1201 for patients with DMD.

INS1202

•We continue to enroll patients in the Phase 1 ARMOR clinical study of INS1202 for patients with ALS.

We are exploring additional opportunities utilizing our various technologies within the Neuro & Other Rare therapeutic area.

Our Strategy

We strive to develop and commercialize first- and best-in-class therapies that serve patient communities where the need is greatest. Our commercial portfolio and clinical pipeline are organized around three therapeutic areas: Respiratory, Immunology & Inflammation, and Neuro & Other Rare. Our Respiratory therapeutic area includes our commercial products ARIKAYCE and BRINSUPRI and the clinical-stage product candidates TPIP and INS1148. Our first product, ARIKAYCE, is approved in the US as ARIKAYCE (amikacin liposome inhalation suspension), in Europe as ARIKAYCE Liposomal 590 mg Nebuliser Dispersion and in Japan as ARIKAYCE inhalation 590mg (amikacin sulfate inhalation drug product). We are not aware of any other approved inhaled therapies specifically indicated to treat MAC lung disease in North America, Europe or Japan. We believe that ARIKAYCE has the potential to prove beneficial in other patients with refractory MAC lung disease. Our second commercial product, BRINSUPRI, was approved in the US and EU in August 2025 and November 2025, respectively, for the treatment of NCFB. Regulatory submissions for brensocatib in the UK and Japan have been accepted. TPIP is our product candidate that may offer a differentiated product profile for patients with PH-ILD, PAH, PPF, and IPF. INS1148 is a monoclonal antibody targeting SCF248. Our Immunology & Inflammation therapeutic area includes brensocatib, which we are developing for HS. Our Neuro & Other Rare therapeutic area includes INS1201, our intrathecally delivered gene therapy product candidate for patients with DMD, and INS1202, our intrathecally delivered gene therapy product candidate for patients with ALS. We are also advancing pre-clinical research programs encompassing a wide range of technologies and modalities, including gene therapy, AI-driven protein engineering, protein manufacturing, RNA end-joining, and synthetic rescue.

Our key priorities are as follows:

•Ensure successful US commercial launch of BRINSUPRI;

•Continue to provide ARIKAYCE to appropriate patients and expand our label;

•Advance our pipeline and produce topline clinical data readouts in the near and long term; and

•Control spending, prudently deploying capital to support the best return-generating opportunities.

Respiratory

BRINSUPRI

BRINSUPRI (brensocatib 25 mg and 10 mg tablets), an oral, once-daily treatment for NCFB in adults and children 12 years and older, was approved in the US by the FDA in August 2025. In November 2025, BRINSUPRI (brensocatib 25 mg tablets), an oral, once-daily treatment for NCFB in adults and children 12 years and older with two or more exacerbations in the prior 12 months, was approved by the EC. Regulatory submissions for brensocatib in the UK and Japan have been accepted.

Brensocatib is a small molecule, reversible inhibitor of DPP1, which we licensed from AstraZeneca in October 2016. DPP1 is an enzyme responsible for activating neutrophil serine proteases (NSPs) 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. Neutrophils contain the NSPs (including neutrophil elastase, proteinase 3, and cathepsin G) that have been implicated in a variety of inflammatory diseases. 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.

In June 2020, the FDA granted breakthrough therapy designation for brensocatib for the treatment of adult patients with NCFB for reducing exacerbations. In November 2020, brensocatib was granted access to the PRIME scheme from the EMA for patients with NCFB. In October 2021, the EMA’s Paediatric Committee approved the brensocatib Pediatric Investigational Plan (the PIP) for the treatment of patients with NCFB. As a result, the ASPEN trial included 41 adolescent patients between ages 12 to 17, which trial design satisfied the pediatric study requirements to support marketing applications in this patient population in the US, Europe and Japan. As a condition of BRINSUPRI’s approval in the US, we agreed with the FDA to conduct a pediatric post marketing study of BRINSUPRI in children between ages 6 and 11. We are also required to continue to progress the PIP notwithstanding BRINSUPRI’s approval in the EU.

The ASPEN Study

Based on positive results of our Phase 2b study of brensocatib in patients with NCFB (the WILLOW study), in December 2020 we commenced the ASPEN study, a global, randomized, double-blind, placebo-controlled Phase 3 study to assess the efficacy, safety, and tolerability of brensocatib in adult patients with bronchiectasis. Patients with bronchiectasis due to CF were not enrolled in the study. The primary endpoint was the rate of adjudicated pulmonary exacerbations (PEs) over the 52-week treatment period. Secondary endpoints included the time to first adjudicated PE, the proportion of subjects free of adjudicated PE by 52 weeks, the absolute change from baseline in post-bronchodilator FEV1, the reduction in annualized rate of severe adjudicated PE, and the change from baseline in the Bronchiectasis QOL-B Respiratory Symptoms Domain Score.

As part of the ASPEN study, 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, due to the ongoing conflict, 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.

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Financial statements

data from SEC XBRL filings. Values are as-reported; restatements supersede originals. Values reported in .

From 10-Q filed 2026-05-07 (period ending 2026-03-31).

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ITEM 2. MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS

Cautionary Note Regarding Forward-Looking Statements

This Quarterly Report on Form 10-Q 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, Section 27A of the Securities Act of 1933, as amended (the "Securities Act") and Section 21E of the Securities Exchange Act of 1934, as amended (the "Exchange Act"), 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) identify forward-looking statements.

Forward-looking statements are based on our current expectations and beliefs, and involve known and unknown risks, uncertainties and other factors, which may cause our actual results, performance and achievements and the timing of certain events to differ materially from the results, performance, achievements or timing discussed, projected, anticipated or indicated in any forward-looking statements. Such risks, uncertainties and other factors include, among others, the following:

•failure to continue to successfully commercialize ARIKAYCE in the US, Europe or Japan (amikacin liposome inhalation suspension, Liposomal 590 mg Nebuliser Dispersion, and amikacin sulfate inhalation drug product, respectively) or failure to successfully commercialize BRINSUPRI in the US or Europe, or to maintain US, European or Japanese approval for ARIKAYCE or US or European approval for BRINSUPRI;

•our inability to obtain full approval of ARIKAYCE from the FDA, or our failure to obtain regulatory approval to expand ARIKAYCE’s indication to a broader patient population;

•failure to obtain, or delays in obtaining, regulatory approvals for our product candidates in the US, Europe or Japan, for ARIKAYCE outside of the US, Europe and Japan, including separate regulatory approval for Lamira in each market and for each usage, or for BRINSUPRI outside of the US and Europe;

•failure to successfully commercialize our product candidates, if approved by applicable regulatory authorities, or to maintain applicable regulatory approvals for such product candidates, if approved;

•uncertainties or changes in the degree of market acceptance of our marketed products or, if approved, our product candidates, by physicians, patients, third-party payors and others in the healthcare community;

•our inability to obtain and maintain adequate reimbursement from government or third-party payors for our marketed products or, if approved, our product candidates, or acceptable prices for our marketed products or, if approved, our product candidates;

•inaccuracies in our estimates of the size of the potential markets for our marketed products and our product candidates or in data we have used to identify physicians, expected rates of patient uptake, duration of expected treatment, or expected patient adherence or discontinuation rates;

•failure of third parties on which we are dependent to manufacture sufficient quantities of our marketed products and our product candidates for commercial or clinical needs, as applicable, to conduct our clinical trials, or to comply with our agreements or laws and regulations that impact our business;

•risks and uncertainties associated with, and the perceived benefits of, our senior secured loan with certain funds managed by Pharmakon and our royalty financing with OrbiMed, 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 our marketed products or any of our product candidates that are approved in the future;

•failure to successfully conduct future clinical trials for our marketed products or our 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;

•development of unexpected safety or efficacy concerns related to our marketed products or our product candidates;

•risks that our clinical studies will be delayed, that serious side effects will be identified during drug development, or that any protocol amendments submitted will be rejected;

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•failure to successfully predict the time and cost of development, regulatory approval and commercialization for novel gene therapy products;

•risk that interim, topline or preliminary data from our clinical trials that we announce or publish from time to time may change as more patient data become available or may be interpreted differently if additional data are disclosed, or that blinded data will not be predictive of unblinded data;

•risk that our competitors may obtain orphan drug exclusivity for a product that is essentially the same as a product we are developing for a particular indication;

•our inability to attract and retain key personnel or to effectively manage our growth;

•our inability to successfully integrate our acquisitions and appropriately manage the amount of management’s time and attention devoted to integration activities;

•risks that our acquired technologies, products and product candidates will not be commercially successful;

•inability to adapt to our highly competitive and changing environment;

•inability to access, upgrade or expand our technology systems or difficulties in updating our existing technology or developing or implementing new technology;

•risk that we are unable to maintain our significant customers;

•risk that healthcare legislation or other government action materially adversely affects our business;

•business or economic disruptions due to catastrophes or other events, including natural disasters or public health crises;

•risk that our current and potential future use of AI and machine learning may not be successful;

•deterioration in general economic conditions in the US, Europe, Japan and globally, including the effect of prolonged periods of inflation, affecting us, our suppliers, third-party service providers and potential partners;

•risk that we could become involved in costly intellectual property disputes, be unable to adequately protect our intellectual property rights or prevent disclosure of our trade secrets and other proprietary information, and incur costs associated with litigation or other proceedings related to such matters;

•restrictions or other obligations imposed on us by agreements related to our marketed products or our product candidates, including our license agreements with PARI and AstraZeneca, 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;

•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.

We caution readers not to place undue reliance on any such forward-looking statements, which speak only as of the date they are made. Any forward-looking statement is based on information current as of the date of this Quarterly Report on Form 10-Q and speaks only as of the date on which such statement is made. Actual events or results may differ materially from the results, plans, intentions or expectations anticipated in these forward-looking statements as a result of a variety of factors, many of which are beyond our control. More information on factors that could cause actual results to differ materially from those anticipated is included from time to time in our reports filed with the Securities and Exchange Commission (SEC), including, but not limited to, those described in the sections titled “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” in this Quarterly Report on Form 10-Q and included in our Annual Report on Form 10-K for the fiscal year ended December 31, 2025. We disclaim 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 our expectations or in events,

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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.

The following discussion should be read in conjunction with our consolidated financial statements and related notes thereto included elsewhere in this Quarterly Report on Form 10-Q and the consolidated financial statements and related notes thereto in our Annual Report on Form 10-K for the year ended December 31, 2025.

OVERVIEW

Our two commercial products, ARIKAYCE and BRINSUPRI, are both part of the Respiratory therapeutic area. ARIKAYCE is approved in the US as ARIKAYCE (amikacin liposome inhalation suspension), in Europe as ARIKAYCE Liposomal 590 mg Nebuliser Dispersion and in Japan as ARIKAYCE inhalation 590mg (amikacin sulfate inhalation drug product). ARIKAYCE received accelerated approval in the US in September 2018 for the treatment of MAC lung disease as part of a combination antibacterial drug regimen for adult patients with limited or no alternative treatment options in a refractory setting. In October 2020, the EC approved ARIKAYCE Liposomal for the treatment of NTM lung infections caused by MAC in adults with limited treatment options who do not have CF. In March 2021, Japan's MHLW approved ARIKAYCE for the treatment of patients with NTM lung disease caused by MAC who did not sufficiently respond to prior treatment with a multidrug regimen. NTM lung disease caused by MAC (which we refer to as MAC lung disease) is a rare and often chronic infection that can cause irreversible lung damage and can be fatal. We are not aware of any other approved inhaled therapies specifically indicated to treat MAC lung disease in North America, Europe, or Japan.

BRINSUPRI (brensocatib 25 mg and 10 mg tablets), an oral, once-daily treatment for non-cystic fibrosis bronchiectasis (referred to as bronchiectasis or NCFB) in patients 12 years of age and older, was approved in the US in August 2025. In November 2025, the EC approved BRINSUPRI (brensocatib 25 mg tablets) for the treatment of NCFB in patients 12 years of age and older with two or more exacerbations in the prior 12 months. In February 2026, the MHRA granted a marketing authorisation for BRINSUPRI to treat patients 12 years and older with NCFB who have experienced two or more flare-ups or worsening of symptoms in the past 12 months. 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. We are not aware of any other approved therapies in the US, Europe, or Japan for the treatment of patients with bronchiectasis.

Our Respiratory therapeutic area also includes the clinical-stage programs TPIP and INS1148. TPIP is an inhaled dry powder formulation of the treprostinil prodrug treprostinil palmitil which may offer a differentiated product profile for PH-ILD, PAH, PPF, and IPF. INS1148 is a monoclonal antibody targeting SCF248, which we plan to initially develop for PPF and IPF.

Our Immunology & Inflammation therapeutic area is exploring opportunities utilizing our various technologies.

The clinical-stage programs in our Neuro & Other Rare therapeutic area are INS1201, an intrathecally delivered gene therapy for patients with DMD, and INS1202, an intrathecally delivered gene therapy for patients with ALS.

Our pre-clinical research programs encompass a wide range of technologies and modalities, including gene therapy, AI-driven protein engineering, RNA end-joining, and synthetic rescue.

Prior to 2019, we had not generated significant revenue and, through March 31, 2026, we had an accumulated deficit of $5.8 billion. We have financed our operations primarily through the public offerings of our equity securities, debt financings and revenue interest financings. Although it is difficult to predict our future funding requirements, based upon our current operating plan, we anticipate that our cash and cash equivalents and marketable securities as of March 31, 2026 will enable us to fund our operations for at least the next 12 months.

Our ability to reduce our operating loss and begin to generate positive cash flow from operations depends on the continued success in commercializing our marketed products and obtaining full approval of ARIKAYCE in the US. Our continued success also depends on bringing additional clinical stage products, such as TPIP, INS1148, INS1201, and INS1202, to market, and advancing our pre-clinical research programs. We expect to continue to incur substantial expenses related to our research and development activities as we conduct trials of TPIP in PH-ILD, PAH, PPF, and IPF, and fund development of our clinical and pre-clinical programs. We also expect to continue to incur significant costs related to the commercialization of our marketed products. Our financial results may fluctuate from quarter to quarter and will depend on, among other factors, the net sales of our marketed products; the scope and progress of our research and development efforts; and the timing of certain expenses. We cannot predict whether or when new products or new indications for marketed products will receive regulatory

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approval or, if any such approval is received, whether we will be able to successfully commercialize such products and whether or when we may become profitable.

The information below summarizes our updates and anticipated near-term milestones for our marketed products and our product candidates.

Respiratory

BRINSUPRI

•In November 2025, the EC approved BRINSUPRI (brensocatib 25 mg tablets) for the treatment of NCFB in patients 12 years of age and older with two or more exacerbations in the prior 12 months.

•In February 2026, the MHRA granted marketing authorisation for BRINSUPRI (brensocatib 25 mg tablets) for the treatment of NCFB in patients 12 years of age and older with two or more flare-ups or worsening of symptoms in the past 12 months.

•We anticipate a regulatory decision for brensocatib for the treatment of NCFB in Japan in 2026.

•We continue to evaluate the potential effect of evolving US policies which will then impact the timing for future potential international commercial launches.

ARIKAYCE

•In March 2026, we reported positive topline results from the Phase 3b ENCORE study, which met its primary and all multiplicity-controlled secondary culture conversion endpoints.

•We anticipate submitting a US supplemental new drug application (sNDA) for ARIKAYCE in all patients with MAC lung disease in the second half of 2026. We also plan to review the data with the Pharmaceuticals and Medical Devices Agency (PMDA) to support potential label expansion in Japan in the second half of 2026.

TPIP

•We initiated PALM-ILD, a Phase 3 study of TPIP in patients with PH-ILD, in the fourth quarter of 2025 and are actively enrolling patients.

•In January 2026, the Office of Orphan Products Development of the FDA granted orphan drug designation to treprostinil palmitil for the treatment of patients with PAH. In April 2026, we initiated the Phase 3 PALM-PAH study of TPIP in patients with PAH.

•We expect to report data from the open-label extension (OLE) of our Phase 2b study of TPIP in PAH in the third quarter of 2026.

•We anticipate initiating a Phase 3 study of TPIP in patients with PPF in the second half of 2026 and a Phase 3 study in patients with IPF in the first half of 2027.

INS1148

•In December 2025, we acquired INS1148, a Phase 2-ready monoclonal antibody targeting SCF248.

•We plan to advance a Phase 2 development program for INS1148, initially targeting PPF and IPF, and we are exploring other diseases where inhibition of the inflammatory functions of SCF248 may be beneficial.

We are exploring additional opportunities utilizing our various technologies within the Respiratory therapeutic area.

Immunology & Inflammation

We are exploring opportunities utilizing our various technologies within the Immunology & Inflammation therapeutic area.

Neuro & Other Rare

INS1201

•We continue to enroll patients in the Phase 1 ASCEND clinical study of INS1201 for patients with DMD.

INS1202

•We continue to enroll patients in the Phase 1 ARMOR clinical study of INS1202 for patients with ALS.

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We are exploring additional opportunities utilizing our various technologies within the Neuro & Other Rare therapeutic area.

Our Strategy

We strive to develop and commercialize first- and best-in-class therapies that serve patient communities where the need is greatest. Our commercial portfolio and clinical pipeline are organized around three therapeutic areas: Respiratory, Immunology & Inflammation, and Neuro & Other Rare. Our Respiratory therapeutic area includes our commercial products ARIKAYCE and BRINSUPRI and the clinical-stage product candidates TPIP and INS1148. Our first product, ARIKAYCE, is approved in the US as ARIKAYCE (amikacin liposome inhalation suspension), in Europe as ARIKAYCE Liposomal 590 mg Nebuliser Dispersion and in Japan as ARIKAYCE inhalation 590mg (amikacin sulfate inhalation drug product). Our second commercial product, BRINSUPRI, was approved in the US, EU, and UK in August 2025, November 2025, and February 2026, respectively, for the treatment of NCFB. The regulatory submission for brensocatib in Japan has been accepted. TPIP is our product candidate that may offer a differentiated product profile for patients with PH-ILD, PAH, PPF, and IPF. INS1148 is a monoclonal antibody targeting SCF248, which we plan to initially develop for PPF and IPF. Our Immunology & Inflammation therapeutic area is exploring opportunities utilizing our various technologies. Our Neuro & Other Rare therapeutic area includes INS1201, our intrathecally delivered gene therapy product candidate for patients with DMD, and INS1202, our intrathecally delivered gene therapy product candidate for patients with ALS. We are also advancing pre-clinical research programs encompassing a wide range of technologies and modalities, including gene therapy, AI-driven protein engineering, RNA end-joining, and synthetic rescue.

Our key priorities are as follows:

•Ensure successful US commercial launch of BRINSUPRI;

•Continue to provide ARIKAYCE to appropriate patients and expand our label;

•Advance our pipeline and produce topline clinical data readouts in the near and long term; and

•Control spending, prudently deploying capital to support the best return-generating opportunities.

Respiratory

BRINSUPRI

BRINSUPRI (brensocatib 25 mg and 10 mg tablets), an oral, once-daily treatment for NCFB in adults and children 12 years and older, was approved in the US by the FDA in August 2025. In November 2025, BRINSUPRI (brensocatib 25 mg tablets), an oral, once-daily treatment for NCFB in adults and children 12 years and older with two or more exacerbations in the prior 12 months, was approved by the EC. In February 2026, the MHRA granted a marketing authorisation for BRINSUPRI to treat patients 12 years and older with NCFB who have experienced two or more flare-ups or worsening of symptoms in the past 12 months. A regulatory submission for brensocatib in Japan has been accepted.

The ASPEN Study

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of severe adjudicated PE, and the change from baseline in the Bronchiectasis QOL-B Respiratory Symptoms Domain Score.

ASPEN Safety Information and Efficacy Data

We announced positive topline results from the ASPEN trial in May 2024. Results from the ASPEN trial were published in the New England Journal of Medicine in April 2025. The primary efficacy analysis included data from 1,680 adult patients and 41 adolescent patients. Brensocatib was well-tolerated in the study. In addition, the study met its primary endpoint, with both dosage strengths of brensocatib demonstrating statistically significant reductions in the annualized rate of adjudicated PEs versus placebo. The study also met several of its prespecified secondary endpoints with statistical significance.

Topline efficacy results from the ASPEN study were as follows:

Brensocatib 10 mg compared to placebo

Brensocatib 25 mg
compared to placebo

Primary Endpoint

Reduction in annualized rate of PEs

21.1%

p=0.0019*

19.4%

p=0.0046*

Secondary Endpoints

Prolongation of time to first PE

18.7%

p=0.0100*

17.5%

p=0.0182*

Increase in odds of remaining exacerbation free over 52 weeks

41.2%

p=0.0059*

40.0%

p=0.0074*

Change from baseline in post-bronchodilator forced expiratory volume in 1 second (FEV1) at week 52

11 mL

p=0.3841

38 mL

p=0.0054*

Reduction in annualized rate of severe PEs

25.8%

p=0.1277

26.0%

p=0.1025

Change from baseline in the Quality of Life – Bronchiectasis (QOL-B) Respiratory Score at week 52

2.0 points

p=0.0594

3.8 points

p=0.0004^

* - Statistically significant

^ - Nominally significant p-value

ARIKAYCE for Patients with MAC Lung Disease

ARIKAYCE is our first approved product. ARIKAYCE received accelerated approval in the US in September 2018 for the treatment of refractory MAC lung disease as part of a combination antibacterial drug regimen for adult patients with limited or no alternative treatment options. In October 2020, ARIKAYCE received approval in Europe for the treatment of NTM lung infections caused by MAC in adults with limited treatment options who do not have CF. In March 2021, ARIKAYCE received approval in Japan for the treatment of patients with NTM lung disease caused by MAC who did not sufficiently respond to prior treatment with a multidrug regimen. MAC lung disease is a rare and often chronic infection that can cause irreversible lung damage and can be fatal. Amikacin solution for parenteral administration is an established drug that has activity against a variety of NTM; however, its use is limited by the need to administer it intravenously and by toxicity to hearing, balance, and kidney function. Unlike amikacin solution for intravenous administration, our proprietary Pulmovance™ technology uses charge-neutral liposomes to deliver amikacin directly to the lungs where liposomal amikacin is taken up by the lung macrophages where the MAC infection resides. This technology also prolongs the release of amikacin in the lungs, while minimizing systemic exposure, thereby offering the potential for decreased systemic toxicities. ARIKAYCE's ability to deliver high levels of amikacin directly to the lung and sites of MAC infection via the use of our Pulmovance technology distinguishes it from intravenous amikacin. ARIKAYCE is administered once-daily using Lamira, an inhalation device developed and manufactured by PARI. Lamira is a portable nebulizer that enables aerosolization of liquid medications via a vibrating, perforated membrane, and was designed specifically for ARIKAYCE delivery.

The FDA has designated ARIKAYCE as an orphan drug and a Qualified Infectious Disease Product (QIDP) for NTM lung disease. Orphan designated drugs are eligible for seven years of exclusivity for the orphan indication. QIDP designation provides an additional five years of exclusivity for the designated indication. The FDA granted a total of 12 years of exclusivity in the indication for which ARIKAYCE was approved.

ARIKAYCE also has been included in the international treatment guidelines for NTM lung disease. The evidence-based guidelines, issued by the American Thoracic Society (ATS), European Respiratory Society (ERS), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), and Infectious Diseases Society of America (IDSA), strongly

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recommend the use of ARIKAYCE for MAC lung disease as part of a combination antibacterial drug regimen for adult patients with limited or no alternative treatment options who have failed to convert to a negative sputum culture after at least six months of treatment.

In October 2020, the FDA approved an sNDA for ARIKAYCE, adding important efficacy data regarding the durability and sustainability of culture conversion to the ARIKAYCE label. The data, which are from the Company's Phase 3 study of ARIKAYCE (the CONVERT study), demonstrate that the addition of ARIKAYCE to guideline-based therapy (GBT) was associated with sustained culture conversion through the end of treatment as well as durable culture conversion three months post-treatment compared with GBT alone.

Accelerated Approval and Post-Marketing Confirmatory Clinical Trial

In September 2018, the FDA granted accelerated approval for ARIKAYCE under the Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD) for the treatment of refractory MAC lung disease as part of a combination antibacterial drug regimen for adult patients with limited or no alternative treatment options. LPAD, which was enacted as part of the 21st Century Cures Act, serves to advance the development of new antibacterial drugs to treat serious or life-threatening infections in limited populations of patients with unmet needs. As required for drugs approved under the LPAD pathway, labeling for ARIKAYCE includes certain statements to convey that the drug has been shown to be safe and effective only for use in a limited population.

As a condition of accelerated approval, we must conduct a post-marketing confirmatory clinical trial. In December 2020, we commenced the post-marketing confirmatory clinical trial program for ARIKAYCE in patients with MAC lung disease consisting of the ARISE trial, an interventional study designed to validate cross-sectional and longitudinal characteristics of a patient-reported outcome (PRO) tool in MAC lung disease, and the ENCORE trial, designed to establish the clinical benefits and evaluate the safety of ARIKAYCE in patients with newly diagnosed or recurrent MAC lung infection who have not started antibiotics using the PRO tool validated in the ARISE trial. In September 2023, we announced positive topline results from the ARISE trial. The study met its primary objective of demonstrating that the QOL-B respiratory domain works effectively as a PRO tool in patients with MAC lung disease. Based on feedback and in alignment with the FDA, we determined that the primary endpoint for the ENCORE study would include eight questions from the QOL-B respiratory domain PRO.

The ARISE Study

The ARISE trial was a global, randomized, double-blind, placebo-controlled Phase 3b study in adult patients with newly diagnosed or recurrent MAC infections that aimed to generate evidence demonstrating the domain specification, reliability, validity, and responsiveness of PRO-based scores, including a respiratory symptom score. The ARISE study met its primary objective of demonstrating that the QOL-B respiratory domain works effectively as a PRO tool in patients with MAC lung disease.

Patients in ARISE (N=99) were randomized 1:1 to treatment with ARIKAYCE plus macrolide-based background regimen (ARIKAYCE arm) or placebo plus macrolide-based background regimen (comparator arm) once daily for six months, followed by one month off treatment. ARIKAYCE-treated patients performed better than those in the comparator arm as measured by the QOL-B instrument, with 43.8% of patients achieving an improvement in QOL-B respiratory score above the estimated meaningful within-subject score difference of 14.8, compared with 33.3% of patients in the comparator arm. While the study was not powered to show a statistically significant difference between treatment arms, a strong trend toward significance was observed for improvement from baseline at Month 7 (12.24 vs. 7.76, p=0.1073). Patients in the ARIKAYCE arm also achieved nominally statistically significantly higher culture conversion rates at Month 7 versus patients in the comparator arm (78.8% vs. 47.1%, p=0.0010), and culture conversion was faster and more likely to persist through Month 7 for the ARIKAYCE arm, suggesting that ARIKAYCE-treated patients are more likely to remain negative.

Consistent with our expectations, the FDA and the PMDA in Japan confirmed that they would not consider a label expansion for ARIKAYCE based on data from the ARISE study alone.

ARISE Culture Conversion

Consistent with prior clinical studies, a higher proportion of patients in the ARIKAYCE arm achieved culture conversion by Month 6 (defined as negative cultures at Months 5 and 6) compared to patients in the comparator arm (80.6% vs. 63.9%, p=0.0712). Among patients who achieved culture conversion by Month 6, more patients in the ARIKAYCE arm achieved the first of their two required monthly negative cultures for clinical conversion at Month 1 versus the comparator arm (74.3% vs. 46.7%). As reported above, at Month 7 (one month following the cessation of treatment), 78.8% of patients in the ARIKAYCE arm vs. 47.1% of patients in the comparator arm were culture-converted, suggesting that ARIKAYCE-treated patients are more likely to remain negative.

Correlation Between ARISE Culture Conversion and QOL-B Performance

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Patients in the ARIKAYCE arm who achieved culture conversion at both Month 6 and Month 7 had nominally statistically significantly greater improvements in QOL-B respiratory domain scores at Month 7 compared to patients in the ARIKAYCE arm who did not achieve culture conversion (15.74 vs. 3.53, p=0.0167 at Month 6 and 14.89 vs. 4.50, p=0.0416 at Month 7).

ARISE Safety and Tolerability

The discontinuation rate of ARIKAYCE or the placebo used in the comparator arm was 22.9% in the ARIKAYCE arm and 7.8% in the comparator arm. Study completion rates were 91.7% in the ARIKAYCE arm and 94.1% in the comparator arm. No new safety events were observed in the ARIKAYCE arm, and the safety profile in general was as expected in both treatment arms. Treatment-emergent adverse events (TEAEs) were reported by 91.7% of patients in the ARIKAYCE arm and 80.4% of patients in the comparator arm. The most common TEAEs were dysphonia (41.7% for the ARIKAYCE arm vs. 3.9% for the comparator arm), cough (27.1% vs. 7.8%), diarrhea (27.1% vs. 25.5%), and COVID-19 (12.5% vs. 9.8%). Of the treatment-emergent serious adverse events observed in the trial, none were determined to be related to ARIKAYCE by investigators.

The ENCORE Study

The ENCORE study was a randomized, double-blind, placebo-controlled Phase 3b study to evaluate the efficacy and safety of an ARIKAYCE-based regimen in patients with newly diagnosed or recurrent MAC infection who had not started antibiotics. Patients were screened and enrolled at 177 sites globally, and a total of 425 patients were randomized 1:1 to receive ARIKAYCE plus background regimen or placebo plus background regimen 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 primary endpoint was change from baseline to Month 13 in respiratory symptom score. The key secondary endpoint was the proportion of subjects achieving durable culture conversion at Month 15. Based on feedback and in alignment with the FDA, the primary endpoint for the ENCORE study included eight questions from the QOL-B respiratory domain PRO.

We announced positive topline results from the ENCORE study in March 2026. Topline efficacy results from the ENCORE study 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)	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**

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* 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

The most common 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, we have completed the study intended to fulfill the FDA post-marketing requirement. We plan to file an 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 US. Additionally, we plan to submit the data to the PMDA in the second half of 2026 to support potential label expansion in Japan.

Regulatory Approval Outside of the US

In October 2020, the EC granted marketing authorization for ARIKAYCE for the treatment of NTM lung infections caused by MAC in adults with limited treatment options who do not have CF. ARIKAYCE can now be prescribed for patients across the EU countries as well as in the UK. ARIKAYCE is reimbursed nationally in France, Belgium, the Netherlands, the UK and Ireland. To date, we have been unable to reach an acceptable agreement of a nationally reimbursed price with the Italian Medicines Agency; however, ARIKAYCE remains commercially available for physicians to prescribe in Italy under Class C, where we set the price and funding is agreed locally.

In March 2021, Japan's MHLW approved ARIKAYCE for the treatment of patients with NTM lung disease caused by MAC who did not sufficiently respond to prior treatment with a multidrug regimen. In July 2021, we launched ARIKAYCE in Japan.

Further Research and Lifecycle Management

We are currently exploring and supporting research and lifecycle management programs for ARIKAYCE beyond treatment of refractory MAC lung disease as part of a combination antibacterial regimen for adult patients who have limited or no treatment options. As noted above, we have completed the post-marketing confirmatory MAC lung disease clinical trial program for ARIKAYCE, through the completed ARISE and ENCORE trials, which are intended to fulfill the FDA's post-

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marketing requirement to allow for the full approval of ARIKAYCE in the US, as well as to support the use of ARIKAYCE as a treatment for patients with MAC lung disease.

Treprostinil Palmitil Inhalation Powder

TPIP is an investigational inhaled dry powder formulation of treprostinil palmitil that has the potential to address certain of the current limitations of existing prostanoid therapies. We believe that TPIP prolongs duration of effect and may provide patients with greater consistency in pulmonary arterial pressure reduction over time. Current inhaled prostanoid therapies must be dosed four to nine times per day. Reducing dose frequency has the potential to ease treatment burden for patients and improve compliance. Additionally, we believe that TPIP may be associated with fewer side effects, including severity and/or frequency of cough, headache, throat irritation, nausea, flushing, and dizziness that are associated with high initial drug levels and local upper airway exposure when using current inhaled prostanoid therapies. We believe TPIP may offer a differentiated product profile for PH-ILD, PAH, PPF and IPF. In January 2026, the FDA granted an orphan drug designation for treprostinil palmitil for the treatment of PAH, based on a plausible hypothesis that it may be clinically superior to treprostinil already approved for the treatment of the same indication.

In February 2021, we announced topline results from the Phase 1 study of TPIP in healthy volunteers. The objective of this first-in-human single ascending dose and multiple ascending dose study was to assess the pharmacokinetics and tolerability profile of TPIP. Data from the study demonstrated that TPIP was generally well tolerated, with a pharmacokinetic profile that supports continued development with once-daily dosing. The most common AEs across all cohorts in the study were cough, dizziness, headache, and nausea. Most AEs were mild in severity and consistent in nature with those typically seen with other inhaled prostanoid therapies. There were few moderate AEs and no severe or serious AEs. Subjects in the multiple dose panel that incorporated an up-titration approach beginning at 112.5 µg once-daily and progressing to 225 µg once-daily reported fewer AEs compared to the panel dosed with 225 µg once-daily from the first dose.

Overall pharmacokinetic results demonstrated that treprostinil exposure (AUC and Cmax) was dose-proportional, with low to moderate inter-subject variability. Treprostinil was detected in the plasma at 24 hours at all doses and throughout the 48-hour sampling period for the two highest doses. Compared with currently available inhaled treprostinil therapy, TPIP showed substantially lower Cmax and longer half-life.

In May 2024, we reported positive topline safety data and certain exploratory efficacy endpoints from the Phase 2a study of TPIP in patients with PH-ILD. A total of 39 patients were randomized 3:1 to receive either TPIP (n=29) or placebo (n=10) for 16 weeks. Patients started at a dose of 80 µg once-daily (TPIP or matching placebo) and were titrated up to their maximum tolerated dose, or to the maximum allowable dose of 640 µg, once daily over a three-week period, with the possibility of a final dose increase occurring at Week 5. Of the patients treated with TPIP, 79.3% of patients were able to reach the maximum 640 µg dose by Week 5, compared to 100.0% of patients in the placebo arm. TEAEs which led to treatment discontinuation were reported in 13.8% of patients in the active treatment arm and 30.0% of patients in the placebo arm. Adverse events related to study drug were reported in 55.2% of TPIP patients and 40.0% of placebo patients. Serious adverse events were reported in 20.7% of TPIP-treated patients and 40.0% of placebo-treated patients. Deaths were reported in 6.9% of patients taking TPIP and 20.0% of patients taking placebo. All deaths were attributed to disease progression or comorbid causes, none of which were deemed related to study drug.

There were no meaningful changes in oxygenation levels compared to baseline for TPIP-treated patients at rest or at the lowest point during or after exercise. There was also no change in the use of supplemental oxygen for patients taking TPIP. There was a small decrease in oxygenation levels observed after exercise for patients on TPIP, compared to a slight increase for patients taking placebo.

On the exploratory endpoint of change from baseline in 6-minute walk distance (6MWD), TPIP-treated patients demonstrated a 30-meter improvement compared to patients treated with placebo. However, this result was associated with a wide confidence interval. In addition, there was a directional improvement observed in N-terminal pro b-type natriuretic peptide (NT-proBNP) levels from baseline for patients taking TPIP and a directional worsening observed in patients on placebo, although no meaningful separation was observed between groups. Events of clinical worsening were reported in 10.3% of patients taking TPIP, compared to 50.0% of patients taking placebo. This difference was nominally significant (p=0.0164).

We initiated PALM-ILD, a Phase 3 study of patients with PH-ILD, in the fourth quarter of 2025 and are actively enrolling patients.

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In June 2025, we announced positive topline results from the Phase 2b study of TPIP in patients with PAH. The study met its primary endpoint and secondary efficacy endpoints. For the primary endpoint, the placebo-adjusted reduction from baseline in pulmonary vascular resistance (PVR) was 35% with Least Squares (LS) mean ratio of 0.65 (95% Confidence Interval (CI): 0.54, 0.79; p<0.001). For the secondary efficacy endpoints, the placebo-adjusted improvement in 6MWD was 35.5 meters (95% CI: 11.2, 60.7; p=0.003) and the placebo-adjusted reduction from baseline in NT-proBNP concentrations, a biomarker for cardiac stress, was 60% with LS mean ratio of 0.40 (95% CI: 0.27, 0.59; p<0.001). Efficacy of TPIP was evaluated approximately 24 hours after therapy was administered.

The TPIP PAH study was conducted at 44 sites globally, and a total of 102 patients were randomized 2:1 to receive either TPIP (n=69) or placebo (n=33) for 16 weeks. Demographics and baseline characteristics were similar in both study arms. Patients started at a dose of 80 µg once daily (TPIP or matching placebo) and were titrated up to their maximum tolerated dose, or to the maximum allowable dose of 640 µg, once daily over a three-week period, with the possibility of a final dose increase occurring at Week 5. Of the patients treated with TPIP, 84% titrated to at least 480 µg once daily (n=58) and 75% titrated to the maximum allowed dose of 640 µg once daily (n=52). Overall, 90% of patients receiving TPIP (n=62) and all patients receiving placebo completed the study.

Once-daily TPIP therapy was well-tolerated in the study. TEAEs occurred in 88.4% of patients who received TPIP versus 75.8% of patients who received placebo; serious TEAEs were observed in 7.2% of patients who received TPIP versus 3.0% of patients who received placebo; and severe TEAEs were observed in 5.8% of patients who received TPIP versus 3.0% of patients who received placebo. TEAEs leading to treatment discontinuation were experienced by 5.8% of patients taking TPIP; there were none in the placebo arm. There were no deaths in the study. The most common TEAEs occurring in at least 5.0% of patients in any study arm, and more frequently with TPIP than with placebo, were cough (40.6%, 21.2%), headache (31.9%, 15.2%), fatigue (10.1%, 3.0%), chest discomfort (8.7%, 0.0%), flushing (8.7%, 3.0%), upper respiratory tract infection (7.2%, 3.0%), and non-cardiac chest pain (5.8%, 3.0%) for TPIP and placebo, respectively.

In April 2026, we initiated a Phase 3 study of TPIP in patients with PAH.

All patients who completed the Phase 2b study were eligible to enroll in the long-term OLE, which will evaluate TPIP up to a maximum allowable dose of 1,280 µg once daily. Of the patients who completed the Phase 2b study (n=95), 95% enrolled in the OLE. We expect to report data from the OLE of our Phase 2b study of TPIP in PAH in the third quarter of 2026.

We anticipate initiating a Phase 3 study of TPIP in patients with PPF in the second half of 2026 and a Phase 3 study in patients with IPF in the first half of 2027.

INS1148

INS1148 is an investigational monoclonal antibody that we are developing as a potential first-in-class therapy to address respiratory and immunological and inflammatory diseases with high unmet need. Through its novel mechanism of action, INS1148 preferentially targets SCF248. Binding to SCF248 induces clearance of this SCF isoform and interrupts only the inflammatory cascade downstream of c-Kit signaling, while leaving the homeostatic and tissue healing c-Kit pathways intact. We plan to advance a Phase 2 development program for INS1148 initially in PPF and IPF.

Immunology & Inflammation

Brensocatib

In April 2026, we completed the Phase 2b CEDAR study of brensocatib in patients with hidradenitis suppurativa (HS). The study did not meet its primary or secondary efficacy endpoints and we have discontinued our development program for brensocatib in HS.

Neuro & Other Rare

INS1201

INS1201 is a micro-dystrophin adeno-associated virus gene therapy for patients with DMD. Administered intrathecally, this approach has the potential to target both skeletal and cardiac muscles at lower doses than intravenous DMD gene therapies. The FDA granted INS1201 orphan drug designation in August 2025 for the treatment of DMD. The FDA granted INS1201 Rare Pediatric Disease Designation in August 2024. We have initiated a Phase 1 study of INS1201, which we refer to as the ASCEND trial, and continue to enroll patients.

INS1202

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INS1202 is an investigational adeno-associated virus (AAV9) short hairpin RNA (shRNA) construct targeting the human superoxide dismutase type 1 (SOD1) gene. We are developing INS1202 as a potential treatment for patients with ALS who carry the SOD1 genetic mutations and those who do not have any genetic mutations. INS1202 is administered intrathecally as a one-time fixed (non-weight-based) dose. We have initiated a Phase 1 study of INS1202, which we refer to as the ARMOR trial, and continue to enroll patients.

Corporate Development

We plan to continue to develop, acquire, in-license, or co-promote other commercial products, product candidates, and technologies, including those that address serious diseases that currently have significant unmet needs. We are focused broadly on serious disease therapeutics and prioritizing those within our three therapeutic areas.

KEY COMPONENTS OF OUR RESULTS OF OPERATIONS

Product Revenues, Net

Product revenues, net, consist of net sales of ARIKAYCE and BRINSUPRI. We recognize revenue for product received by our customers net of allowances for customer credits, including prompt pay discounts, service fees, estimated rebates, including government rebates, such as Medicaid rebates and Medicare Part D reimbursements in the US, and chargebacks.

Cost of Product Revenues (Excluding Amortization of Intangible Assets)

Cost of product revenues (excluding amortization of intangible assets) consist primarily of direct and indirect costs related to the manufacturing of ARIKAYCE and BRINSUPRI sold, including third-party manufacturing costs, packaging services, freight, and allocation of overhead costs, in addition to royalty expenses.

Research and Development Expenses

R&D expenses consist of salaries, benefits and other related costs, including stock-based compensation, for personnel serving in our research and development functions. R&D expenses also include other internal operating expenses, the cost of manufacturing product candidates, including the medical devices for drug delivery, for clinical study, the cost of conducting clinical studies, and the cost of conducting pre-clinical and research activities. In addition, R&D expenses include payments to third parties for the license rights to products in development (prior to marketing approval), and may include the cost of asset acquisitions. Our R&D expenses related to manufacturing our product candidates and medical devices for clinical study are primarily related to activities at CMOs that manufacture our product candidates and early-stage research activities. Our R&D expenses related to clinical trials are primarily related to activities at contract research organizations (CROs) that conduct and manage clinical trials on our behalf. These contracts with CROs set forth the scope of work to be completed at a fixed fee or billed at a per-unit cost, and increase proportionally to the volume of services rendered. Payments under these contracts with CROs primarily depend on performance criteria such as the successful enrollment of patients or the completion of clinical trial milestones as well as time-based fees. Expenses are accrued based on contracted amounts applied to the level of patient enrollment and to activity according to the clinical trial protocol. Deposits for goods or services that will be used or rendered for future research and development activities are deferred and capitalized. Such amounts are then recognized as an expense as the related goods are delivered or the services are performed.

Selling, General and Administrative (SG&A) Expenses

SG&A expenses consist of salaries, benefits and other related costs, including stock-based compensation, for our non-employee directors and personnel serving in our executive, finance and accounting, legal and compliance, commercial and pre-commercial, corporate development, field sales, information technology and human resource functions. SG&A expenses also include professional fees for legal services, consulting services, including commercial activities, insurance, board of director fees, tax and accounting services.

Amortization of Intangible Assets

Upon commercialization of each of ARIKAYCE and BRINSUPRI, the related intangible assets began to be amortized over their estimated useful lives. The fair values assigned to our intangible assets are based on estimates and assumptions we believe are reasonable based on available facts and circumstances. Unanticipated events or circumstances may occur that require us to review the assets for impairment.

Change in Fair Value of Contingent Consideration

In connection with the Business Acquisition, we recorded contingent consideration liabilities related to potential future milestone payments. Adjustments to the fair value are due to changes in the probability of achieving milestones, our stock price,

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or certain other estimated assumptions. The change in fair value of contingent consideration is calculated quarterly with gains and losses recorded in the consolidated statements of comprehensive loss.

Investment Income and Interest Expense

Investment income consists of interest and dividend income earned on our cash and cash equivalents and marketable securities. Interest expense consists primarily of contractual interest costs, Royalty Financing Agreement non-cash interest expense and the amortization of debt issuance costs related to our debt. Debt issuance costs were amortized to interest expense using the effective interest rate method over the term of the debt. Our consolidated balance sheets reflect debt, net of the debt issuance costs paid to the lender, and other third-party costs.

RESULTS OF OPERATIONS

Comparison of the Three Months Ended March 31, 2026 and 2025

Product Revenues, Net

Product revenues, net, consists of net sales of ARIKAYCE and BRINSUPRI. The following table summarizes revenue by product and geography for the three months ended March 31, 2026 and 2025 (in thousands):

	Three Months Ended March 31,				Increase (decrease)
	2026		2025		$		%
ARIKAYCE
US	$	62,884	$	64,275	$	(1,391)	(2.2)	%
International	35,226		28,548		6,678		23.4	%
Total	$	98,110	$	92,823	$	5,287	5.7	%
BRINSUPRI
US	$	207,182	$	—	$	207,182	NA
International	672		—		672		NA
Total	$	207,854	$	—	$	207,854	NA
Total
US	$	270,066	$	64,275	$	205,791	320.2	%
International	35,898		28,548		7,350		25.7	%
Total product revenues, net	$	305,964	$	92,823	$	213,141	229.6	%

Product revenues, net, for the three months ended March 31, 2026 were $306.0 million as compared to $92.8 million for the same period in 2025, an increase of $213.1 million, or 229.6%. This increase was a result of $207.2 million of US commercial sales of BRINSUPRI following approval in August 2025 and a 5.7% growth in sales of ARIKAYCE, driven by growth in international sales of 23.4%. In the first quarter of 2026, we began recognizing international BRINSUPRI revenue related to EAPs in Europe, consisting of sales to the French National Agency for Medicines and Health Products Safety, which has granted BRINSUPRI a Compassionate Access Authorisation (Autorisation d'accès compassionnel or AAC) and sales through the NPP in other countries.

Cost of Product Revenues (excluding amortization of intangible assets)

Cost of product revenues (excluding amortization of intangible assets) for the three months ended March 31, 2026 and 2025 were comprised of the following (in thousands):

	Three Months Ended March 31,						Increase (decrease)
	2026			2025			$		%
Cost of product revenues (excluding amortization of intangible assets)	$	47,420		$	21,278		$	26,142	122.9	%
Cost of product revenues, as % of revenues	15.5		%	22.9		%

Cost of product revenues (excluding amortization of intangible assets) were $47.4 million for the three months ended March 31, 2026 as compared to $21.3 million for the same period in 2025, an increase of $26.1 million, or 122.9%. This increase was primarily attributable to the increase in total product revenues discussed above. Cost of product revenues as a percent of revenues decreased in the current period due to sales of BRINSUPRI, which has lower manufacturing costs than ARIKAYCE.

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All product costs for BRINSUPRI incurred prior to FDA approval on August 12, 2025 were expensed as R&D expenses. We expect our cost of product revenues (excluding amortization of intangible assets) to benefit 2026 and beyond, as we sell through inventory that was expensed prior to FDA approval of BRINSUPRI.

R&D Expenses

R&D expenses for the three months ended March 31, 2026 and 2025 were comprised of the following (in thousands):

	Three Months Ended March 31,				Increase (decrease)
	2026		2025		$		%
External Expenses
Clinical development and research	$	47,956	$	40,537	$	7,419	18.3	%
Manufacturing	38,136		21,809		16,327

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Held by

holders ( registered funds via N-PORT, institutional investors via 13F). Showing top by dollar value.

Holder	Type	ETF	MF	Position ($)	% of holder	Δ % of holder	Holder AUM

Recent insider activity

Last 90 days. Open-market trades (purchases & sales) by directors, officers, and 10%+ owners. 22 transactions across 5 insiders. Net: -270,467 shares, -$36,782,907.

Date	Insider	Role	Action	Shares	Price	Value
2026-06-08	Lewis William	Chair and CEO	Sell	-6,515	$94.03	-$612,605
2026-06-03	Adsett Roger	Chief Operating Officer	Sell	-2,370	$102.27	-$242,380
2026-06-03	Smith Michael Alexander	Chief Legal Officer	Sell	-2,159	$102.27	-$220,801
2026-06-03	Bonstein Sara	Chief Financial Officer	Sell	-2,404	$102.27	-$245,857
2026-06-05	Flammer Martina M.D.	Chief Medical Officer	Sell	-1,858	$103.78	-$192,823
2026-06-03	Flammer Martina M.D.	Chief Medical Officer	Sell	-2,566	$102.27	-$262,425
2026-06-03	Lewis William	Chair and CEO	Sell	-7,605	$102.27	-$777,763
2026-05-22	Smith Michael Alexander	Chief Legal Officer	Sell	-6,149	$108.47	-$666,982
2026-05-18	Lewis William	Chair and CEO	Sell	-25,564 ×3	$106.33	-$2,718,224
2026-05-13	Adsett Roger	Chief Operating Officer	Sell	-5,837	$116.18	-$678,143
2026-05-13	Bonstein Sara	Chief Financial Officer	Sell	-8,272	$116.18	-$961,041
2026-05-13	Lewis William	Chair and CEO	Sell	-13,283	$116.18	-$1,543,219
2026-05-13	Smith Michael Alexander	Chief Legal Officer	Sell	-4,109	$116.18	-$477,384
2026-05-14	Flammer Martina M.D.	Chief Medical Officer	Sell	-10,479	$117.54	-$1,231,702
2026-05-13	Flammer Martina M.D.	Chief Medical Officer	Sell	-7,854 ×2	$114.23	-$897,190
2026-05-11	Flammer Martina M.D.	Chief Medical Officer	Sell	-12,949 ×2	$100.40	-$1,300,121
2026-05-04	Lewis William	Chair and CEO	Sell	-10,699 ×6	$137.34	-$1,469,442
2026-04-16	Lewis William	Chair and CEO	Sell	-10,699 ×4	$143.97	-$1,540,332
2026-04-06	Lewis William	Chair and CEO	Sell	-10,699 ×3	$163.22	-$1,746,336
2026-04-01	Adsett Roger	Chief Operating Officer	Sell	-88,060 ×3	$164.63	-$14,497,651
2026-03-30	Smith Michael Alexander	Chief Legal Officer	Sell	-19,638	$150.98	-$2,964,945
2026-03-19	Lewis William	Chair and CEO	Sell	-10,699 ×3	$143.52	-$1,535,542

Source: SEC Form 4 filings.

Next expected filings

~2026-08-06 10-Q expected by 2026-08-12 (in 52 days)
~2026-10-29 10-Q expected by 2026-11-04 (in 136 days)
~2027-02-18 10-K expected by 2027-02-25 (in 248 days)
~2027-05-06 10-Q expected by 2027-05-12 (in 325 days)

Predicted from historical filing cadence; not an SEC commitment.

Recent SEC filings

2026-05-15 S-3ASR S-3ASR
2026-05-07 8-K Earnings Release; Financial Statements and Exhibits
2026-05-07 10-Q Quarterly Report
2026-04-07 8-K Regulation FD Disclosure; Other Events; Financial Statements and Exhibits
2026-03-23 8-K Regulation FD Disclosure; Other Events; Financial Statements and Exhibits
2026-02-19 10-K Annual Report
2026-02-19 8-K Earnings Release; Officer/Director Change; Financial Statements and Exhibits
2025-12-17 8-K Regulation FD Disclosure; Other Events; Financial Statements and Exhibits
2025-11-18 8-K Regulation FD Disclosure; Other Events; Financial Statements and Exhibits
2025-10-30 10-Q Quarterly Report
2025-10-30 8-K Earnings Release; Financial Statements and Exhibits
2025-08-12 8-K Regulation FD Disclosure; Other Events; Financial Statements and Exhibits
2025-08-07 10-Q Quarterly Report
2025-08-07 8-K Earnings Release; Financial Statements and Exhibits
2025-06-13 8-K Regulation FD Disclosure; Other Events; Financial Statements and Exhibits

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