Brensocatib

—ARIKAYCE® (amikacin liposome inhalation suspension) Total Revenue of $92.8 Million for the First Quarter of 2025, Reflecting 23% Growth Over the First Quarter of 2024— —NDA for Brensocatib in Patients with Bronchiectasis Remains on Track, with a PDUFA Target Action Date of August 12, 2025— —Phase 2b Study of TPIP in Patients with PAH Completed; Topline Data Expected in June 2025— —Enrollment Completed for Phase 2b BiRCh Study of Brensocatib in Patients with CRSsNP; Topline Data Anticipated By the End of 2025— —MAA Filings for Brensocatib in Patients with Bronchiectasis Accepted by EMA and MHRA— —Company Reiterates 2025 Global ARIKAYCE Revenue Guidance Range of $405 Million to $425 Million, Reflecting Double-Digit Growth Compared to 2024— BRIDGEWATER, N.J., May 8, 2025 /PRNewswire/ -- 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 reported financial results for the first quarter ended March 31, 2025 and provided a business update. "In the first quarter of 2025, Insmed demonstrated executional excellence across our commercial and clinical programs, while simultaneously preparing for critical near-term milestones, including our Phase 2 data readout of TPIP in PAH, and our anticipated FDA approval of brensocatib for bronchiectasis," said Will Lewis, Chair and Chief Executive Officer of Insmed. "Against the backdrop of an evolving regulatory environment, brensocatib's FDA review process remains on track, and we are relentlessly focused on preparing for a frictionless launch for the patients counting on us to succeed. This momentum is anticipated to continue as we expect to unveil data from our Phase 2 BiRCh study of brensocatib in chronic rhinosinusitis without nasal polyps by year-end 2025 and our Phase 3 ENCORE study of ARIKAYCE in all MAC lung disease patients in the first half of 2026. As I reflect on these upcoming catalysts, I couldn't be prouder of the Insmed team working tirelessly to achieve our ambitious vision." Recent Progress and Anticipated Milestones by Program: ARIKAYCE ARIKAYCE global revenue grew 23% in the first quarter of 2025 compared to the first quarter of 2024, reflecting double-digit year-over-year growth in the U.S., Japan, and Europe. The Company anticipates the topline readout of the Phase 3 ENCORE trial in the first half of 2026 in patients with newly diagnosed or recurrent Mycobacterium avium complex (MAC) lung disease who have not started antibiotics, which will include the change from baseline in respiratory symptom score at Month 13 and the percentage of patients achieving durable culture conversion at Month 15. The Company plans to submit a supplementary new drug application (sNDA) to the U.S. Food and Drug Administration (FDA) for ARIKAYCE in all patients with MAC lung disease in the U.S. in the second half of 2026. Brensocatib In February 2025, the FDA accepted the Company's New Drug Application (NDA) for brensocatib for patients with bronchiectasis, granting the application Priority Review designation with a Prescription Drug User Fee Act (PDUFA) target action date of August 12, 2025. If approved, Insmed expects to immediately launch brensocatib in the U.S. Regulatory submissions for brensocatib in the EU and UK have been accepted, with submission in Japan planned for 2025. Insmed anticipates commercial launches for each territory in 2026, pending approval. Insmed completed enrollment in the Phase 2b BiRCh study of brensocatib in patients with chronic rhinosinusitis without nasal polyps (CRSsNP) with 288 patients. The Company remains on track to report topline results by the end of 2025. The Company continues to enroll patients in the Phase 2b CEDAR study of brensocatib in patients with hidradenitis suppurativa (HS). Based on current enrollment rates, the Company anticipates the interim futility analysis from the first 100 patients to complete Week 16 of the trial in the first half of 2026. TPIP Insmed completed the Phase 2b study of treprostinil palmitil inhalation powder (TPIP) in pulmonary arterial hypertension (PAH), with topline data anticipated in June of 2025. The Company plans to initiate a Phase 3 study of TPIP in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD) in the second half of 2025. Gene Therapy Insmed initiated the Phase 1 ASCEND clinical study of INS1201, an intrathecally-delivered gene therapy for patients with Duchenne muscular dystrophy (DMD), in the first quarter of 2025, and expects to dose the first patient in the second quarter of 2025. The Company's next two gene therapy candidates, which target amyotrophic lateral sclerosis (ALS) and Stargardt disease, are currently advancing toward the clinic. Pre-Clinical Programs Insmed's research efforts include more than 30 identified pre-clinical programs in development, all of which have the potential to become first-in-class or best-in-class therapies for the indications being pursued. The Company anticipates submitting an average of one to two INDs per year from its pre-clinical research programs. Insmed continues to anticipate that the totality of its pre-clinical research programs will comprise less than 20% of overall expenditures. Corporate Updates In April 2025, data from the Phase 3 ASPEN study of brensocatib in patients with bronchiectasis were published in the New England Journal of Medicine. In April 2025, the Company issued a notice of redemption for all $569.5 million aggregate principal amount of its remaining outstanding 0.75% Convertible Senior Notes Due 2028, with a redemption date of June 6, 2025. Insmed plans to present eleven abstracts from across its respiratory portfolio (ARIKAYCE, brensocatib, and TPIP) at the American Thoracic Society (ATS) 2025 International Conference, taking place May 18-21, 2025. Insmed intends to expand its U.S. manufacturing footprint and has a project underway to establish a secondary source of brensocatib manufacturing in the U.S. First-Quarter 2025 Financial Results The following table summarizes first-quarter 2025 and 2024 revenues and revenue growth for ARIKAYCE across all commercial regions: Cost of product revenues (excluding amortization of intangibles) was $21.3 million for the first quarter of 2025, compared to $17.5 million for the first quarter of 2024. The increase in cost of product revenues primarily reflects growth in ARIKAYCE sales. Research and development (R&D) expenses were $152.6 million for the first quarter of 2025, compared to $121.1 million for the first quarter of 2024. The increase in R&D expenses was primarily related to increases in compensation and benefit-related expenses and stock-based compensation costs, due to an increase in headcount, as well as an increase in manufacturing expenses. Selling, general and administrative (SG&A) expenses for the first quarter of 2025 were $147.5 million, compared to $93.1 million for the first quarter of 2024. The increase in SG&A expenses was primarily related to increases in compensation and benefit-related expenses, as well as stock-based compensation costs, predominantly due to an increase in headcount in preparation for the anticipated launch of brensocatib in the U.S., pending regulatory approval. For the first quarter of 2025, Insmed reported a net loss of $256.6 million, or $1.42 per share, compared to a net loss of $157.1 million, or $1.06 per share, for the first quarter of 2024. Balance Sheet, Financial Guidance, and Planned Investments As of March 31, 2025, Insmed had cash, cash equivalents, and marketable securities totaling approximately $1.2 billion. Insmed continues to anticipate full-year 2025 global ARIKAYCE revenues in the range of $405 million to $425 million, representing between 11% and 17% year-over-year growth compared to 2024. The Company plans to continue to invest in the following key activities in 2025: (i) commercialization and expansion of ARIKAYCE globally; (ii) commercial launch of brensocatib in the U.S., if approved, with advancement of regulatory submissions and interactions in the EU, UK, and Japan; (iii) advancement of clinical trial programs for brensocatib, including the ongoing Phase 2b BiRCh study in patients with CRSsNP and the Phase 2b CEDAR study in patients with HS; (iv) advancement of the Phase 3 ENCORE study for ARIKAYCE, which is intended to satisfy the post-marketing requirement for full approval of its current indication and potentially support label expansion to include all patients with a MAC lung disease; (v) advancement of the clinical development programs for TPIP, including the Phase 2b study in patients with PAH and the initiation of a Phase 3 study in patients with PH-ILD; (vi) advancement of the Phase 1 ASCEND study for INS1201 in DMD; and (vii) continued development of its pre-clinical research programs. Conference Call Insmed will host a conference call beginning today, May 8, 2025, at 8:00 AM Eastern Time. Shareholders and other interested parties may participate in the conference call by dialing (888) 210-2654 (U.S. and international) and referencing access code 7862189. The call will also be webcast live on the Company's website at . A replay of the conference call will be accessible approximately 1 hour after its completion through May 15, 2025, by dialing (800) 770-2030 (U.S. and international) and referencing access code 7862189. A webcast of the call will also be archived for 90 days under the Investor Relations section of the Company's website at . 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. About Brensocatib Brensocatib is a small molecule, oral, reversible inhibitor of dipeptidyl peptidase 1 (DPP1) being developed by Insmed for the treatment of patients with bronchiectasis, chronic rhinosinusitis without nasal polyps, hidradenitis suppurativa, and other neutrophil-mediated diseases. DPP1 is an enzyme responsible for activating neutrophil serine proteases (NSPs), such as neutrophil elastase, in neutrophils when they are formed in the bone marrow. Neutrophils are the most common type of white blood cell and play an essential role in pathogen destruction and inflammatory mediation. In chronic inflammatory lung diseases, neutrophils accumulate in the airways and result in excessive active NSPs that cause lung destruction and inflammation. Brensocatib may decrease the damaging effects of inflammatory diseases such as bronchiectasis by inhibiting DPP1 and its activation of NSPs. Brensocatib is an investigational drug product that has not been approved for any indication in any jurisdiction. About TPIP Treprostinil palmitil inhalation powder (TPIP) is a dry powder formulation of treprostinil palmitil, a treprostinil prodrug consisting of treprostinil linked by an ester bond to a 16-carbon chain. Developed entirely in Insmed's laboratories, TPIP is a potentially highly differentiated prostanoid being evaluated for the treatment of patients with pulmonary arterial hypertension (PAH), PH-ILD, and other rare and serious pulmonary disorders. TPIP is administered in a capsule-based inhalation device. TPIP is an investigational drug product that has not been approved for any indication in any jurisdiction. About INS1201 INS1201 is an investigational micro-dystrophin adeno-associated virus gene replacement therapy that Insmed is developing as a potential treatment for patients with Duchenne muscular dystrophy. Administered intrathecally, this approach has the potential to target both skeletal and cardiac muscles at lower doses. INS1201 is an investigational drug product that has not been approved for any indication in any jurisdiction. IMPORTANT SAFETY INFORMATION AND BOXED WARNING FOR ARIKAYCE IN THE U.S. Hypersensitivity Pneumonitis has been reported with the use of ARIKAYCE in the clinical trials. Hypersensitivity pneumonitis (reported as allergic alveolitis, pneumonitis, interstitial lung disease, allergic reaction to ARIKAYCE) was reported at a higher frequency in patients treated with ARIKAYCE plus background regimen (3.1%) compared to patients treated with a background regimen alone (0%). Most patients with hypersensitivity pneumonitis discontinued treatment with ARIKAYCE and received treatment with corticosteroids. If hypersensitivity pneumonitis occurs, discontinue ARIKAYCE and manage patients as medically appropriate. Hemoptysis has been reported with the use of ARIKAYCE in the clinical trials. Hemoptysis was reported at a higher frequency in patients treated with ARIKAYCE plus background regimen (17.9%) compared to patients treated with a background regimen alone (12.5%). If hemoptysis occurs, manage patients as medically appropriate. Bronchospasm has been reported with the use of ARIKAYCE in the clinical trials. Bronchospasm (reported as asthma, bronchial hyperreactivity, bronchospasm, dyspnea, dyspnea exertional, prolonged expiration, throat tightness, wheezing) was reported at a higher frequency in patients treated with ARIKAYCE plus background regimen (28.7%) compared to patients treated with a background regimen alone (10.7%). If bronchospasm occurs during the use of ARIKAYCE, treat patients as medically appropriate. Exacerbations of underlying pulmonary disease has been reported with the use of ARIKAYCE in the clinical trials. Exacerbations of underlying pulmonary disease (reported as chronic obstructive pulmonary disease (COPD), infective exacerbation of COPD, infective exacerbation of bronchiectasis) have been reported at a higher frequency in patients treated with ARIKAYCE plus background regimen (14.8%) compared to patients treated with background regimen alone (9.8%). If exacerbations of underlying pulmonary disease occur during the use of ARIKAYCE, treat patients as medically appropriate. Anaphylaxis and Hypersensitivity Reactions: Serious and potentially life-threatening hypersensitivity reactions, including anaphylaxis, have been reported in patients taking ARIKAYCE. Signs and symptoms include acute onset of skin and mucosal tissue hypersensitivity reactions (hives, itching, flushing, swollen lips/tongue/uvula), respiratory difficulty (shortness of breath, wheezing, stridor, cough), gastrointestinal symptoms (nausea, vomiting, diarrhea, crampy abdominal pain), and cardiovascular signs and symptoms of anaphylaxis (tachycardia, low blood pressure, syncope, incontinence, dizziness). Before therapy with ARIKAYCE is instituted, evaluate for previous hypersensitivity reactions to aminoglycosides. If anaphylaxis or a hypersensitivity reaction occurs, discontinue ARIKAYCE and institute appropriate supportive measures. Ototoxicity has been reported with the use of ARIKAYCE in the clinical trials. Ototoxicity (including deafness, dizziness, presyncope, tinnitus, and vertigo) were reported with a higher frequency in patients treated with ARIKAYCE plus background regimen (17%) compared to patients treated with background regimen alone (9.8%). This was primarily driven by tinnitus (7.6% in ARIKAYCE plus background regimen vs 0.9% in the background regimen alone arm) and dizziness (6.3% in ARIKAYCE plus background regimen vs 2.7% in the background regimen alone arm). Closely monitor patients with known or suspected auditory or vestibular dysfunction during treatment with ARIKAYCE. If ototoxicity occurs, manage patients as medically appropriate, including potentially discontinuing ARIKAYCE. Nephrotoxicity was observed during the clinical trials of ARIKAYCE in patients with MAC lung disease but not at a higher frequency than background regimen alone. Nephrotoxicity has been associated with the aminoglycosides. Close monitoring of patients with known or suspected renal dysfunction may be needed when prescribing ARIKAYCE. Neuromuscular Blockade: Patients with neuromuscular disorders were not enrolled in ARIKAYCE clinical trials. Patients with known or suspected neuromuscular disorders, such as myasthenia gravis, should be closely monitored since aminoglycosides may aggravate muscle weakness by blocking the release of acetylcholine at neuromuscular junctions. Embryo-Fetal Toxicity: Aminoglycosides can cause fetal harm when administered to a pregnant woman. Aminoglycosides, including ARIKAYCE, may be associated with total, irreversible, bilateral congenital deafness in pediatric patients exposed in utero. Patients who use ARIKAYCE during pregnancy, or become pregnant while taking ARIKAYCE should be apprised of the potential hazard to the fetus. Contraindications: ARIKAYCE is contraindicated in patients with known hypersensitivity to any aminoglycoside. Most Common Adverse Reactions: The most common adverse reactions in Trial 1 at an incidence ≥5% for patients using ARIKAYCE plus background regimen compared to patients treated with background regimen alone were dysphonia (47% vs 1%), cough (39% vs 17%), bronchospasm (29% vs 11%), hemoptysis (18% vs 13%), ototoxicity (17% vs 10%), upper airway irritation (17% vs 2%), musculoskeletal pain (17% vs 8%), fatigue and asthenia (16% vs 10%), exacerbation of underlying pulmonary disease (15% vs 10%), diarrhea (13% vs 5%), nausea (12% vs 4%), pneumonia (10% vs 8%), headache (10% vs 5%), pyrexia (7% vs 5%), vomiting (7% vs 4%), rash (6% vs 2%), decreased weight (6% vs 1%), change in sputum (5% vs 1%), and chest discomfort (5% vs 3%). Drug Interactions: Avoid concomitant use of ARIKAYCE with medications associated with neurotoxicity, nephrotoxicity, and ototoxicity. Some diuretics can enhance aminoglycoside toxicity by altering aminoglycoside concentrations in serum and tissue. Avoid concomitant use of ARIKAYCE with ethacrynic acid, furosemide, urea, or intravenous mannitol. Overdosage: Adverse reactions specifically associated with overdose of ARIKAYCE have not been identified. Acute toxicity should be treated with immediate withdrawal of ARIKAYCE, and baseline tests of renal function should be undertaken. Hemodialysis may be helpful in removing amikacin from the body. In all cases of suspected overdosage, physicians should contact the Regional Poison Control Center for information about effective treatment. U.S. INDICATION LIMITED POPULATION: ARIKAYCE® is indicated in adults, who have limited or no alternative treatment options, for the treatment of Mycobacterium avium complex (MAC) lung disease as part of a combination antibacterial drug regimen in patients who do not achieve negative sputum cultures after a minimum of 6 consecutive months of a multidrug background regimen therapy. As only limited clinical safety and effectiveness data for ARIKAYCE are currently available, reserve ARIKAYCE for use in adults who have limited or no alternative treatment options. This drug is indicated for use in a limited and specific population of patients. This indication is approved under accelerated approval based on achieving sputum culture conversion (defined as 3 consecutive negative monthly sputum cultures) by Month 6. Clinical benefit has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Limitation of Use : ARIKAYCE has only been studied in patients with refractory MAC lung disease defined as patients who did not achieve negative sputum cultures after a minimum of 6 consecutive months of a multidrug background regimen therapy. The use of ARIKAYCE is not recommended for patients with non-refractory MAC lung disease. Patients are encouraged to report negative side effects of prescription drugs to the FDA. Visit , or call 1‑800‑FDA‑1088. You can also call the Company at 1-844-4-INSMED. Please see  Full Prescribing Information . About Insmed Insmed Incorporated is a 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 a therapy approved in the United States, Europe, and Japan to treat a chronic, debilitating lung disease. 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 four consecutive years as the No. 1 Science Top Employer. Visit to learn more. Forward-looking Statements This press release contains forward-looking statements that involve substantial risks and uncertainties. "Forward-looking statements," as that term is defined in the Private Securities Litigation Reform Act of 1995, are statements that are not historical facts and involve a number of risks and uncertainties. Words herein such as "may," "will," "should," "could," "would," "expects," "plans," "anticipates," "believes," "estimates," "projects," "predicts," "intends," "potential," "continues," and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) may identify forward-looking statements. The forward-looking statements in this press release are based upon the Company's current expectations and beliefs, and involve known and unknown risks, uncertainties and other factors, which may cause the Company's actual results, performance and achievements and the timing of certain events to differ materially from the results, performance, achievements or timings discussed, projected, anticipated or indicated in any forward-looking statements. Such risks, uncertainties and other factors include, among others, the following: failure to continue to successfully commercialize ARIKAYCE, our only approved product, in the U.S., Europe or Japan (amikacin liposome inhalation suspension, Liposomal 590 mg Nebuliser Dispersion, and amikacin sulfate inhalation drug product, respectively), or to maintain U.S., European or Japanese approval for ARIKAYCE; our inability to obtain full approval of ARIKAYCE from the FDA, including the risk that we will not successfully or in a timely manner complete the confirmatory post-marketing clinical trial required for full approval of ARIKAYCE, or our failure to obtain regulatory approval to expand ARIKAYCE's indication to a broader patient population; failure to obtain, or delays in obtaining, regulatory approvals for brensocatib, TPIP or our other product candidates in the U.S., Europe or Japan or for ARIKAYCE outside the US, Europe or Japan, including separate regulatory approval for Lamira® in each market and for each usage; failure to successfully commercialize brensocatib, TPIP or our other product candidates, if approved by applicable regulatory authorities, or to maintain applicable regulatory approvals for brensocatib, TPIP or our other product candidates, if approved; uncertainties or changes in the degree of market acceptance of ARIKAYCE or, if approved, brensocatib, TPIP or our other 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 ARIKAYCE or, if approved, brensocatib, TPIP or our other product candidates, or acceptable prices for ARIKAYCE or, if approved, brensocatib, TPIP or our other product candidates; inaccuracies in our estimates of the size of the potential markets for ARIKAYCE, brensocatib, TPIP or our other product candidates or in data we have used to identify physicians, expected rates of patient uptake, duration of expected treatment, or expected patient adherence or discontinuation rates; failure of third parties on which the Company is dependent to manufacture sufficient quantities of ARIKAYCE, brensocatib, or TPIP for commercial or clinical needs, to conduct the Company's clinical trials, or to comply with the Company's agreements or laws and regulations that impact the Company's business; the risks and uncertainties associated with, and the perceived benefits of, our secured senior loan with certain funds managed by Pharmakon Advisors LP and our royalty financing with OrbiMed Royalty & Credit Opportunities IV, LP, including our ability to maintain compliance with the covenants in the agreements for the senior secured loan and royalty financing and the impact of the restrictions on our operations under these agreements; our inability to create or maintain an effective direct sales and marketing infrastructure or to partner with third parties that offer such an infrastructure for distribution of ARIKAYCE or any of our product candidates that are approved in the future; failure to successfully conduct future clinical trials for ARIKAYCE, brensocatib, TPIP or our other product candidates and our potential inability to enroll or retain sufficient patients to conduct and complete the trials or generate data necessary for regulatory approval of our product candidates or to permit the use of ARIKAYCE in the broader population of patients with MAC lung disease, among other things; development of unexpected safety or efficacy concerns related to ARIKAYCE, brensocatib, TPIP or our other product candidates; risks that our clinical studies will be delayed, that serious side effects will be identified during drug development, or that any protocol amendments submitted will be rejected; failure to successfully predict the time and cost of development, regulatory approval and commercialization for novel gene therapy products; the risk that interim, topline or preliminary data from our clinical trials that we announce or publish from time to time may change as more patient data become available or may be interpreted differently if additional data are disclosed, 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 recent acquisitions and appropriately manage the amount of management's time and attention devoted to integration activities; risks that our acquired technologies, products and product candidates 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 government healthcare reform materially increases our costs and damages our financial condition; business or economic disruptions due to catastrophes or other events, including natural disasters or public health crises; risk that our current and potential future use of AI and machine learning may not be successful; deterioration in general economic conditions in the U.S., Europe, Japan and globally, including the effect of prolonged periods of inflation, affecting us, our suppliers, third-party service providers and potential partners; the risk that we could become involved in costly intellectual property disputes, be unable to adequately protect our intellectual property rights or prevent disclosure of our trade secrets and other proprietary information, and incur costs associated with litigation or other proceedings related to such matters; restrictions or other obligations imposed on us by agreements related to ARIKAYCE, brensocatib or our other product candidates, including our license agreements with PARI and AstraZeneca AB, and failure to comply with our obligations under such agreements; the cost and potential reputational damage resulting from litigation to which we are or may become a party, including product liability claims; risk that our operations are subject to a material disruption in the event of a cybersecurity attack or issue; our limited experience operating internationally; changes in laws and regulations applicable to our business, including any pricing reform and laws that impact our ability to utilize certain third parties in the research, development or manufacture of our product candidates, and failure to comply with such laws and regulations; our history of operating losses, and the possibility that we never achieve or maintain profitability; goodwill impairment charges affecting our results of operations and financial condition; inability to repay our existing indebtedness and uncertainties with respect to our ability to access future capital; and delays in the execution of plans to build out an additional third-party manufacturing facility approved by the appropriate regulatory authorities and unexpected expenses associated with those plans. The Company may not actually achieve the results, plans, intentions or expectations indicated by the Company's forward-looking statements because, by their nature, forward-looking statements involve risks and uncertainties because they relate to events and depend on circumstances that may or may not occur in the future. For additional information about the risks and uncertainties that may affect the Company's business, please see the factors discussed in Item 1A, "Risk Factors," in the Company's Annual Report on Form 10-K for the year ended December 31, 2024 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 [email protected] Media: Claire Mulhearn Vice President, Corporate Communications (862) 842-6819 [email protected] SOURCE Insmed Incorporated WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

编者按：今年初，行业媒体Evaluate发布报告，梳理了预计于2025年上市的关键创新疗法。随着2025年进程已过三分之一，我们也对这些潜在重磅疗法的最新进展进行回顾。在报告列出的十项疗法中，有五款为小分子药物，充分体现了小分子药物在2025年生物医药创新格局中所占据的重要地位。在这五款小分子潜力疗法中，药明康德化学业务平台很高兴为其中两款提供了赋能服务，助力合作伙伴加速创新成果转化。面向未来，药明康德将持续发挥平台优势，携手全球客户，推动更多创新疗法早日惠及全球患者。图片来源：123RF在这份报告中所提到的10款潜在重磅疗法当中，已有5款率先获得美国FDA批准，包含由Vertex Pharmaceuticals所开发，在去年底获批用以治疗囊性纤维化（CF）患者的Alyftrek；由阿斯利康（AstraZeneca）与第一三共（Daiichi Sankyo）联合开发用以治疗乳腺癌的Trop2靶向抗体偶联药物（ADC）Datroway（datopotamab deruxtecan），以及同样由Vertex Pharmaceuticals所开发、用于治疗急性疼痛的Journavx（suzetrigine）则在今年1月分别接连获得FDA批准；而由GSK所开发的脑膜炎球菌疫苗Penmenvy（MenABCWY）则在2月获批；强生开发的抗体疗法Imaavy（nipocalimab）在4月底获批治疗全身性重症肌无力（gMG）。值得注意的是，在这些潜在重磅疗法当中，有不少具有显著的创新性。例如，由GSK所开发的depemokimab是在3期试验中进行评估的首个白细胞介素5（IL-5）靶向超长效生物制品。根据新闻稿，该疗法可能成为仅须每6个月给药一次、用于治疗严重哮喘的首个获批超长效生物制品。而Vertex Pharmaceuticals的新闻稿则指出，其NaV1.8抑制剂suzetrigine为二十多年来首个用于治疗急性疼痛的新机制药物。此外，强生（Johnson & Johnson）旗下新生儿Fc受体（FcRn）靶向单抗nipocalimab具有治疗多种免疫疾病的潜力，获批治疗gMG之外，它还是在干燥综合征（Sjögren’s disease，SjD）领域获得突破性疗法认定（BTD）的首款疗法。▲2025年10款潜在重磅疗法一览（图表来源：根据参考资料[1]整理制表）在列出的10款潜在重磅疗法中，小分子药物占据一半（5款，占比50%）；单克隆抗体疗法占据2款（占比20%）；而抗体偶联药物（ADC）、多肽药物及疫苗各自占据1款（各占比10%）。这一分布进一步印证了小分子药物在2025年生物医药创新版图中举足轻重的地位。2025年的十款潜在重磅疗法疗法：Alyftrek（vanzacaftor/tezacaftor/deutivacaftor）公司：Vertex Pharmaceuticals研发状态：2024年12月20日获美国FDA批准Alyftrek是一款下一代囊性纤维化跨膜电导调节因子（CFTR）调节剂三联疗法，该疗法在去年12月获FDA批准用于治疗6岁及以上、携带至少一个F508del突变或其他对Alyftrek有应答的CFTR基因突变的囊性纤维化患者。在两项随机双盲3期临床试验中，接受治疗24周后，基于一秒用力呼气量百分比（ppFEV1）数值的评估，Alyftrek的疗效与获批CF疗法Trikafta相当，达到试验的主要终点。此外，Alyftrek在降低汗液氯化物（SwCl）水平方面与活性对照药物相比表现出优效性，这是两项3期试验的关键次要终点之一。▲Alyftrek在SKYLINE 102和SKYLINE 103试验中达到主要终点（图片来源：Vertex公司官网）疗法：Datroway（datopotamab deruxtecan，Dato-DXd）公司：阿斯利康、第一三共研发状态：2025年1月17日获美国FDA批准Datroway是一款由人源化、靶向Trop2的单克隆抗体与创新DNA拓扑异构酶I抑制剂（DXd），通过可裂解的四肽连接子偶联生成的ADC。该疗法在今年1月获FDA批准上市，用于治疗无法切除或转移性HR阳性、HER2阴性的成年乳腺癌患者，这些患者曾接受过内分泌疗法和化疗。美国FDA的批准主要基于TROPION-Breast01临床3期试验的结果。分析显示，Datroway治疗组的中位无进展生存期（PFS）为6.9个月（95% CI：5.7，7.4），化疗组为4.9个月（95% CI：4.2，5.5），即Datroway相较于化疗，可将患者的疾病进展或死亡风险降低37%（HR=0.63，95% CI：0.52，0.76，p<0.0001）。Datroway与化疗组患者的确认客观缓解率（ORR）分别为36%（95% CI：31，42）和23%（95% CI：19，28）。今年1月，美国FDA授予Datroway优先审评资格用于治疗局部晚期或转移性表皮生长因子受体突变（EGFRm）的非小细胞肺癌（NSCLC）成人患者，预计将在2025年第三季度完成审评。疗法：Journavx（suzetrigine）公司：Vertex Pharmaceuticals研发状态：2025年1月30日获美国FDA批准Suzetrigine是一种口服选择性NaV1.8抑制剂，与其它NaV离子通道相比，它对NaV1.8具有高度选择性。根据关键性3期临床试验的积极结果，suzetrigine在急性疼痛治疗中表现出显著效果。具体来说，在接受腹部整形手术（abdominoplasty）患者中进行的3期临床试验结果显示，suzetrigine达到了试验的主要终点，与安慰剂相比，药物组患者48小时内疼痛强度差异的时间加权总和评分（SPID48）显著降低，SPID48的平均差异为48.4（95% CI：33.6，63.1；P<0.0001）。此外，患者在手术48小时后的数值疼痛评分量表（NPRS）评分与基线相比也显著降低。而在接受拇囊炎切除手术（bunionectomy）的患者中，该疗法亦达成主要终点，SPID48的平均差异为29.3（95% CI：14.0，44.6；P=0.0002）。▲Suzetrigine达成试验主要终点（图片来源：Vertex官网）疗法：Aficamten公司：Cytokinetics研发状态：PDUFA日期为2025年12月26日Aficamten是一种下一代心肌球蛋白抑制剂，用于治疗梗阻性肥厚型心肌病（HCM）。该药物的上市申请主要基于关键性3期临床试验SEQUOIA-HCM结果。分析显示，与安慰剂相比，aficamten治疗24周显著提高了患者的运动能力。通过心肺运动试验（CPET）测得的峰值氧气摄取量（pVO2）与基线相比，在aficamten治疗组增加了1.8 ml/kg/min，而安慰剂组为0.0 ml/kg/min。此外，接受aficamten治疗的患者在10个预先设定的次要终点中，均观察到了统计学上显著的改善。FDA曾于2021年12月授予aficamten治疗梗阻性HCM的突破性疗法认定。▲Aficamten达到SEQUOIA-HCM试验的主要终点（图片来源：Cytokinetics官网）疗法：Brensocatib公司：Insmed研发状态：PDUFA日期为2025年8月12日Brensocatib是一种口服、可逆性DPP1小分子抑制剂。DPP1是一种酶，负责激活中性粒细胞中的中性粒细胞丝氨酸蛋白酶（NSPs）。Brensocatib可通过抑制DPP1降低NSPs的活化，从而降低炎症性疾病（如支气管扩张）的组织损伤。这款疗法已经获得美国FDA授予的突破性疗法认定，用于治疗非囊性纤维化支气管扩张。一项包含1680名成人和41名青少年非囊性纤维化支气管扩张症患者的临床试验结果显示，试验达到主要终点，10 mg和25 mg剂量的brensocatib分别将患者的年化肺部症状恶化（PE）率降低21.1%和19.4%，统计学显著并具有临床意义。▲Brensocatib的3期临床试验疗效数据（图片来源：参考资料[4]）疗法：Tolebrutinib公司：赛诺菲（Sanofi）研发状态：PDUFA日期为2025年9月28日Tolebrutinib是一款在研口服、能穿越血脑屏障且具有生物活性的布鲁顿氏酪氨酸激酶（BTK）抑制剂，它能够达到足以调节B淋巴细胞和疾病相关小胶质细胞的脑脊液浓度。临床3期试验结果表明，tolebrutinib与安慰剂相比，可将非复发性继发进展型多发性硬化（nrSPMS）出现6个月确认残疾进展（CDP）的时间延缓31%（HR=0.69；95% CI，0.55-0.88；p=0.0026）。进一步的次要终点分析显示，接受tolebrutinib治疗的参与者中，确认残疾获得改善的患者比例（10%）是安慰剂组（5%）的两倍（HR=1.88；95% CI，1.10-3.21）。Tolebrutinib目前正在多个3期临床试验中评估其治疗多种类型多发性硬化的潜力。该疗法在2024年12月获得FDA授予突破性疗法认定，用于治疗nrSPMS成年患者。▲Tolebrutinib分子结构（图片来源：PubChem）疗法：玛仕度肽（Mazdutide，IBI362）公司：信达生物（Innovent）、礼来（Eli Lilly and Company）研发状态：在中国用于治疗肥胖与2型糖尿病治疗的监管申请结果预定分别在2025年上半年与下半年公布玛仕度肽是信达生物与礼来共同推进的一款胰高血糖素样肽-1受体（GLP-1R）和胰高血糖素受体（GCGR）双重激动剂。之前发布于eClinicalMedicine期刊上的一篇研究结果显示，接受每周一次9 mg玛仕度肽皮下注射治疗的受试者从基线至第12周体重的平均百分比变化为-11.7%，接受安慰剂治疗的受试者为-1.8%（估计治疗差异：-9.8%；95% CI：-14.4，-5.3；P=0.0002）。安全性方面，玛仕度肽的耐受性良好，并具有良好的安全性。未报告严重不良事件。所有治疗相关不良事件均为轻度或中度。疗法：Depemokimab公司：GSK研发状态：PDUFA日期为2025年12月16日Depemokimab是在3期试验中进行评估的首个白细胞介素5（IL-5）靶向超长效生物制品。SWIFT-1和SWIFT-2临床3期试验结果显示，试验达主要终点，depemokimab可显著降低严重哮喘患者的哮喘发作率达54%（HR=0.46，95% CI：0.36–0.59，p<0.001），这些患者具有2型炎症特征（以血液嗜酸性粒细胞计数为标志）。此外，试验亦达成次要终点。与安慰剂相比，患者需要住院或急诊救治的临床显著恶化减少达72%（HR=0.28，95% CI：0.13–0.61，p=0.002）。GSK预计在2025年启动该疗法用于治疗慢性阻塞性肺病（COPD）患者的3期临床试验。根据新闻稿，depemokimab可能成为仅须每6个月给药一次、用于治疗严重哮喘的首个获批超长效生物制品。疗法：Penmenvy（MenABCWY）公司：GSK研发状态：2025年2月14日获美国FDA批准五种脑膜炎球菌血清群（A，B，C，W和Y）占全球大部分地区的几乎所有侵袭性脑膜炎球菌病病例。GSK的五合一MenABCWY疫苗结合已获批的脑膜炎疫苗Bexsero和Menveo的抗原成分，可针对这五种血清群的脑膜炎球菌保护接种者。将两种有效疫苗合并为一种的目的是帮助简化免疫接种计划，进而增加疫苗覆盖率，帮助减少疾病的总负担。在3期试验中，MenABCWY疫苗成功达到所有主要终点，包括在免疫原性方面不劣于一剂GSK的A、C、Y和W群脑膜炎球菌疫苗，以及在对110种不同的B群脑膜炎球菌侵袭性菌株产生的免疫反应上，不劣于两剂GSK的B群脑膜炎球菌疫苗。此外，该疫苗显示出良好的耐受性，其安全性与上述两种疫苗一致。疗法：Nipocalimab公司：强生研发状态：2025年4月29日获美国FDA批准Nipocalimab是一款潜在“best-in-class”，靶向新生儿Fc受体的抗体疗法。它通过与FcRn结合，让被单核细胞和内皮细胞摄入的自身抗体不会重新释放到血液中，而是在细胞内被降解。已有研究显示，它可以将血液循环中包括致病自身抗体在内的IgG水平降低超过75%。它在4月29日获FDA批准，治疗抗AChR、抗MuSK抗体阳性的全身性重症肌无力（gMG）成人与12岁以上儿童患者。强生公司还在罕见自身抗体疾病、母体同种抗体介导的母胎疾病和风湿病领域探索nipocalimab的潜力。它在去年11月获得FDA授予突破性疗法认定，用于治疗中度至重度SjD成人患者。根据新闻稿，nipocalimab是在SjD领域获得突破性疗法认定的首个疗法。DAHLIAS临床2期试验结果显示，nipocalimab达到主要终点，从第4周开始，15 mg/kg nipocalimab组患者就开始获得缓解，并在整个24周的治疗期间持续增加。在第24周，与安慰剂相较，15 mg/kg组受试者在主要终点上，显示出平均系统性疾病活动程度相对于安慰剂超过70%的改善。▲DAHLIAS研究疗效结果摘要（图片来源：参考资料[5]）参考资料：[1] Top 10 most anticipated drug launches of 2025. Retrieved April 27, 2025 from https://www.fiercepharma.com/marketing/top-10-most-anticipated-drug-launches-2025[2] Insmed Provides Business Update at 43rd Annual J.P. Morgan Healthcare Conference. Retrieved January 21, 2025 from https://filecache.investorroom.com/mr5ir_insmed/371/2025-01-10-Insmed-Provides-Business-Update-at-43rd-Annual-J-P-Morgan-Healthcare-Conference.pdf[3] Delivering strong and sustained momentum. Retrieved January 21, 2025 from https://www.gsk.com/media/11750/gsk-2025-jpm-conf-presentation-14-january-2025.pdf[4] Insmed  Announces Positive Topline Results from Landmark ASPEN Study of  Brensocatib in Patients with Bronchiectasis. Retrieved May 28, 2024,  from  https://www.prnewswire.com/news-releases/insmed-announces-positive-topline-results-from-landmark-aspen-study-of-brensocatib-in-patients-with-bronchiectasis-302156279.html[5] LBA0010 EFFICACY AND SAFETY OF NIPOCALIMAB, AN ANTI-FcRn MONOCLONAL ANTIBODY, IN PRIMARY SJOGREN’S DISEASE: RESULTS FROM A PHASE 2, MULTICENTER, RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE-BLIND STUDY (DAHLIAS). Retrieved November 12, 2024 from https://ard-bmj-com.libproxy1.nus.edu.sg/content/83/Suppl_1/240.2免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新