Neurobehavioral Manifestations

—ARIKAYCE® (amikacin liposome inhalation suspension) Total Revenue of $93.4 Million for the Third Quarter of 2024, Reflecting 18% Growth Over the Third Quarter of 2023— —NDA Submission for Brensocatib in Bronchiectasis Remains on Track for the Fourth Quarter of 2024 with Potential U.S. Launch Still Expected in Mid-2025— —Expanded U.S. Sales Force is Now Fully Deployed; Focusing on Bronchiectasis Disease-State Awareness and Supporting the Growth of ARIKAYCE Prior to the Anticipated Launch of Brensocatib— —Ends the Third Quarter with ~$1.5 Billion in Cash, Cash Equivalents, and Marketable Securities— —Renegotiates Term Loan with Pharmakon Resulting in a Lower Cost of Capital and an Additional $150 Million in Proceeds to be Received in the Fourth Quarter— —Reiterates 2024 Global ARIKAYCE Revenue Guidance in the Range of $340 Million to $360 Million, Reflecting Double-Digit Growth Compared to 2023— BRIDGEWATER, N.J., Oct. 31, 2024 /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 third quarter ended September 30, 2024, and provided a business update. "I am pleased with the progress the Company is making across multiple ongoing initiatives this quarter." said Will Lewis, Chair and Chief Executive Officer of Insmed. "We remain on track to file our NDA for brensocatib in the fourth quarter of 2024 and continue to expect a potential U.S. launch in the middle of 2025. We have also made great progress on the clinical side, with the ENCORE and PAH studies nearing full enrollment. All of this has been accomplished while delivering yet another quarter of double-digit growth for ARIKAYCE in each of our three commercial regions. With our demonstrated ability to execute both clinically and commercially, and a strengthened balance sheet due to actions we have taken to lower our cost of capital while adding to our cash balance, we believe we are well-positioned to deliver on the tremendous opportunities ahead." Recent Pillar Highlights Pillar 1: ARIKAYCE ARIKAYCE global revenue grew 18% in the third quarter of 2024 compared to the third quarter of 2023, reflecting an all-time revenue high and double-digit year-over-year growth in the U.S., Japan, and Europe and rest of world. Insmed has closed screening of new patients for the ENCORE study and is now expected to exceed its target enrollment of 400 patients with newly diagnosed or recurrent Mycobacterium avium complex (MAC) lung infection who have not started antibiotics. The Company is scheduled to meet with the U.S. Food and Drug Administration (FDA) during the fourth quarter to discuss the possibility of an accelerated approval to expand the label for ARIKAYCE to include all patients with MAC lung infection, based on the positive Phase 3 ARISE trial data. Insmed continues to expect that the full data from the ongoing ENCORE trial will be required for approval. Pillar 2: Brensocatib Insmed remains on track to file a New Drug Application (NDA) with the FDA for brensocatib in patients with bronchiectasis in the fourth quarter of 2024. If priority review is granted and brensocatib is approved, Insmed anticipates a U.S. launch in mid-2025. Launches in Europe and Japan are expected in the first half of 2026, pending approvals. New subpopulation data from 19 pre-specified categories of patients in the ASPEN study were presented in October 2024 at the American College of Chest Physicians Annual Meeting in Boston. The annualized rate of pulmonary exacerbations favored brensocatib at both the 10 mg and 25 mg doses over placebo for almost all subgroups. In a separate analysis, least squares mean difference for brensocatib 25 mg demonstrated a reduced decline in post-bronchodilator forced expiratory volume in 1 second (FEV1) at Week 52 versus placebo for all prespecified subgroups. Insmed is advancing launch readiness activities in the U.S. and has hired, trained, and deployed 120 additional therapeutic sales specialists in advance of launch, focused on bronchiectasis disease-state awareness with an expanded group of pulmonologists while also supporting the growth of ARIKAYCE. The Company continues to enroll patients in the Phase 2b BiRCh trial of brensocatib in patients with chronic rhinosinusitis without nasal polyps (CRSsNP) and anticipates providing top-line data from the study in the second half of 2025. The Company is preparing to activate the first U.S. clinical site for its Phase 2 study of brensocatib in patients with hidradenitis suppurativa (HS) by the end of 2024. Pillar 3: TPIP Enrollment remains ongoing in the Phase 2 study of treprostinil palmitil inhalation powder (TPIP) in patients with pulmonary arterial hypertension (PAH), with more than 90% of the target enrollment currently complete. Insmed remains on track to report topline results from the PAH study in the second half of 2025. The Company continues to anticipate initiating a Phase 3 study of TPIP in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD) in the second half of 2025. Pillar 4: Early-Stage Research Insmed's early-stage research efforts include more than 30 identified pre-clinical programs in development, all of which have the potential to become first-in-class or best-in-class therapies. The Company continues to anticipate the totality of its early-stage research programs will comprise less than 20% of overall spend. Corporate Updates Insmed has taken the following actions intended to further strengthen its balance sheet and financial position: (i) During the third quarter of 2024, the Company completed the redemption of its $225 million convertible notes due in January 2025. Insmed issued approximately 5.7 million shares of common stock in connection with the redemption and earlier conversions of notes. (ii) The Company raised an additional $371 million in net proceeds under its at-the-market equity offering program during the third quarter, at an average sales price of $75.64 per share. (iii) In October 2024, Insmed entered into an agreement to amend its $350 million term loan with investment funds managed by Pharmakon Advisors, LP. Under the terms of the amended agreement, investment funds managed by Pharmakon Advisors, LP will provide an additional $150 million in proceeds, to be received in the fourth quarter of 2024. The maturity date for the full principal amount was extended to 2029, and will carry a reduced fixed-interest rate in the high-single digits. In October 2024, Insmed announced that it has earned the No. 1 ranking in Science's 2024 Top Employers Survey, marking the fourth consecutive year in which Insmed achieved the top ranking. The annual survey polls employees in biotechnology, pharmaceutical, and related industries to determine the 20 best employers, as well as their driving characteristics. Third-Quarter 2024 Financial Results Total revenue for the quarter ended September 30, 2024, was $93.4 million, reflecting 18% year-over-year growth compared to total revenue of $79.1 million for the third quarter of 2023. Total revenue for third-quarter 2024 included ARIKAYCE net sales of $66.9 million in the U.S., $21.0 million in Japan, and $5.6 million in Europe and rest of world. Third-quarter 2024 sales demonstrated year-over-year growth of 13% in the U.S., 31% in Japan, and 45% in Europe and rest of world, reflecting continued growth trends for ARIKAYCE in these regions. Cost of product revenues (excluding amortization of intangibles) was $21.2 million for the third quarter of 2024, compared to $16.7 million for the third quarter of 2023, primarily reflecting increased sales volumes of ARIKAYCE. Research and development (R&D) expenses were $150.8 million for the third quarter of 2024, compared to $109.1 million for the third quarter of 2023. The year-over-year increase in R&D expenses was primarily driven by increases in manufacturing and compensation and benefit-related expenses. Selling, general and administrative (SG&A) expenses for the third quarter of 2024 were $118.9 million, compared to $90.6 million for the third quarter of 2023. The year-over-year increase in SG&A expenses resulted primarily from increases in compensation and benefit-related expenses and stock-based compensation costs due to an increase in headcount associated with launch readiness activities for brensocatib. For the third quarter of 2024, Insmed reported a net loss of $220.5 million, or $1.27 per share, compared to a net loss of $158.9 million, or $1.11 per share, for the third quarter of 2023. Balance Sheet, Financial Guidance, and Planned Investments As of September 30, 2024, Insmed had cash, cash equivalents, and marketable securities totaling $1,467.9 million. Insmed is reiterating its guidance for full-year 2024 global ARIKAYCE revenues in the range of $340 million to $360 million, representing 15% year-over-year growth at the midpoint compared to 2023. Insmed continues to anticipate that over 80% of total expenditures will be on its clinical and commercial programs, and that less than 20% of overall spend will be on its early-stage research programs, reflecting the Company's historical approach to spending. The Company plans to continue to invest in the following key activities in 2024: (i) commercialization and continued growth of ARIKAYCE in its current indication globally, as well as advancement of the clinical trial program intended to potentially support label expansion to include all patients with a MAC lung infection and to satisfy the post-marketing requirement for full approval of its current indication; (ii) advancement of brensocatib, including: a. activities related to regulatory filing and commercial launch readiness for bronchiectasis and b. the ongoing Phase 2 BiRCh trial in patients with CRSsNP and the anticipated Phase 2 program in HS; (iii) advancement of its clinical development programs for TPIP; and (iv) development of its early-stage research programs. Conference Call Insmed will host a conference call beginning today at 8:00 AM Eastern Time. Shareholders and other interested parties may participate in the conference call by dialing (888) 210-2654 (U.S.) and (646) 960-0278 (international) and referencing access code 7862189. The call will also be webcast live on the Company's website at . A replay of the conference call will be accessible approximately 1 hour after its completion through November 7, 2024, by dialing (800) 770-2030 (U.S.) and (609) 800-9909 (international) and referencing access code 7862189. A webcast of the call will also be archived for 90 days under the Investor Relations section of the Company's website at . 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, CRSsNP, and other neutrophil-mediated diseases. DPP1 is an enzyme responsible for activating neutrophil serine proteases (NSPs), such as neutrophil elastase, in neutrophils when they are formed in the bone marrow. Neutrophils are the most common type of white blood cell and play an essential role in pathogen destruction and inflammatory mediation. In chronic inflammatory lung diseases, neutrophils accumulate in the airways and result in excessive active NSPs that cause lung destruction and inflammation. Brensocatib may decrease the damaging effects of inflammatory diseases such as bronchiectasis by inhibiting DPP1 and its activation of NSPs. Brensocatib is an investigational drug product that has not been approved for any indication in any jurisdiction. About 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 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. 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 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. 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 US, 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 US, 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 or TPIP 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 or TPIP, or acceptable prices for ARIKAYCE or, if approved, brensocatib or TPIP; 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 L.P. 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 and our other product candidates and our potential inability to enroll or retain sufficient patients to conduct and complete the trials or generate data necessary for regulatory approval of our product candidates or to permit the use of ARIKAYCE in the broader population of patients with 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; 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 are not commercially successful; inability to adapt to our highly competitive and changing environment; inability to access, upgrade or expand our technology systems or difficulties in updating our existing technology or developing or implementing new technology; risk that we are unable to maintain our significant customers; risk that government healthcare reform materially increases our costs and damages our financial condition; business or economic disruptions due to catastrophes or other events, including natural disasters or public health crises; risk that our current and potential future use of 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; 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, 2023 and any subsequent Company filings with the Securities and Exchange Commission (SEC). The Company cautions readers not to place undue reliance on any such forward-looking statements, which speak only as of the date of this press release. The Company disclaims any obligation, except as specifically required by law and the rules of the SEC, to publicly update or revise any such statements to reflect any change in expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. Contact: Investors: Bryan Dunn Executive Director, Investor Relations (646) 812-4030 [email protected] Michael V. Morabito, Ph.D. Director, Investor Relations (917) 936-8430 [email protected] Gianna De Palma Manager, Investor Relations (873) 886-2236 [email protected] Media: Mandy Fahey Vice President, Corporate Communications (732) 718-3621 [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

-New testing method highlights link between protofibrils and biomarkers for neurodegeneration- -Patient and caregiver perspectives on five-year treatment with lecanemab - - Utilization of blood biomarkers to predict brain amyloid accumulation in AHEAD study of preclinical AD- TOKYO and CAMBRIDGE, Mass., Oct. 30, 2024 /PRNewswire/ -- Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") and Biogen Inc. (Nasdaq: BIIB, Corporate headquarters: Cambridge, Massachusetts, CEO: Christopher A. Viehbacher, "Biogen") announced today that the latest findings for lecanemab-irmb (U.S. brand name: LEQEMBI®), an anti-amyloid beta (Aβ) protofibril* antibody for the treatment of early Alzheimer's disease (AD), were presented at the Clinical Trials for Alzheimer's Disease Conference (CTAD), held in Madrid, Spain, and virtually. Benefits of Continued Treatment with Lecanemab for People with Early AD In July 2024 at the Alzheimer's Association International Conference (AAIC) 2024, results from the open-label long-term extension study (OLE) following the core study of the lecanemab Phase 3 Clarity AD study were presented, showing that the mean change from baseline in CDR-SB (global cognitive and functional scale) in the lecanemab treated group relative to the placebo group was -0.45 at 18 months, and at 36 months, this expanded to -0.95 compared to a prespecified natural history** cohort of AD. There was a 30% reduction in the relative risk of progressing to the next disease stage In addition, the tau PET substudy of the lecanemab Phase 3 Clarity AD clinical study showed that with three (3) years of continuous treatment with lecanemab, 59% of patients with no or low tau accumulation in the brain (no tau/low tau) at baseline showed improvement or no decline, and 51% showed improvement from baseline on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) global cognitive and functional scale.1 Clarity AD data presented at CTAD expand on these initial results to include additional measurements resulting from three (3) years of continuous lecanemab treatment in patients with low levels of amyloid accumulation in the brain at baseline (less than 60 Centiloids: low amyloid). These data show that 46% of patients improved or had no decline, and 33% showed improvement from baseline on the CDR-SB. On the ADAS-Cog14 measurement scale, 46% of patients showed improvement or no decline and 43% showed improvement. On the ADCS MCI-ADL, 51% of patients showed improvement or no decline and 48% showed improvement. These results – from no tau/low tau population and low amyloid populations – suggest that earlier initiation of lecanemab treatment may have a positive impact on disease progression of early AD patients and may provide continued benefits to patients with early AD over the long term.2 No new safety findings were observed with continued lecanemab treatment over three (3) years. Most amyloid-related imaging abnormalities (ARIA) occurred in the first six (6) months of treatment. After the first six (6) months, ARIA rates were low and similar to ARIA rates on placebo during the placebo-controlled period. With regards to the incidence of ARIA by ApoEε4 status during the continuous treatment, the incidence was higher in ApoE4 homozygotes than in heterozygotes or non-carriers, but rates of new ARIA were decreased after the completion of the 18 months core study as treatment continued, regardless of ApoEε4 status.2 Correlation between Protofibrils and Biomarkers for Neurodegenerative Disease i n the AD Brain Dual-acting lecanemab is the only early AD treatment available to support neuronal function by clearing the highly toxic protofibrils that continue to cause neuronal injury and death even after plaques have been cleared from the brain. Protofibrils accumulate early in the AD brain and lead to nerve cell function loss, abnormal nerve processes, inflammation, and memory loss. In non-clinical studies, antibodies against protofibrils prevented protofibril-mediated neuronal dysfunction and memory loss. Accurately quantifying the amount of protofibrils in human cerebrospinal fluid (CSF) has been challenging due to their low concentration. As such, a new measurement method was developed by researchers at Eisai to accurately quantify protofibrils in CSF. Utilizing this new method of measurement, the amount of protofibrils in AD CSF correlated more strongly with neurodegenerative disease biomarkers (CSF total tau and neurogranin) than with CSF Aβ42, a biomarker associated with Aβ plaques accumulation, indicating that protofibrils are closely related to synaptic dysfunction. Furthermore, it was observed that protofibrils, unlike plaques, are diffusible. These results suggest that protofibrils induce synaptic dysfunction, playing an important role in neurodegeneration in AD brains.3 Lecanemab Treatment for Early AD: Insights from Long-Term U.S. Clinical Studies Dr. Marwan Noel Sabbagh, Moreno Family Chair for Alzheimer's Research and Vice Chairman for Research and Professor, Department of Neurology, Barrow Neurological Institute, presented outcomes of an analysis of the use of lecanemab treatment between January 6, 2023, and July 30, 2024, based on payment claims data from the Komodo Research Database, a medical database in the U.S. In the U.S., lecanemab is used in accordance with the US FDA-approved indication, dosing, and monitoring guidelines. The analysis found that access to lecanemab treatment is expanding and highlighted opportunities to improve access in rural areas and educational outreach for underserved populations.4 Dr. David Watson of the Alzheimer's Research and Treatment Center reported on patients who continued to receive lecanemab treatment following the Phase II Study 201 and Phase III Clarity AD study. A total of 136 patients participated in both studies at this center, and 66 patients chose to continue lecanemab therapy, with 13 patients receiving treatment for more than five (5) years and 40 patients receiving treatment for more than three (3) years. More than half of the patients (15/24) who continued treatment with lecanemab for more than three (3) years after the core phase remained in their initial stage of disease. Further, in a survey of 11 patients (or their caregivers) who received lecanemab treatment for more than five (5) years, all patients responded that they were "very satisfied" or "satisfied" with lecanemab treatment. In addition, between 45% and 73% of patients responded that lecanemab treatment made them feel more positive about their daily life, social activities, memory, etc. "frequently" or "very often."5 No new long-term safety findings were observed in these multi-year studies.5 Progress in the AHEAD 3-45 Study: Improving Screening Eligibility Using Blood Biomarkers and Completing Patient Enrollment AHEAD 3-45 is a Phase 3 clinical study for individuals with preclinical AD, meaning they are clinically unimpaired but have intermediate or elevated levels of amyloid in their brains. In the study, blood tests, cognitive function tests (PACC-5***), amyloid PET, MRI, and tau PET were used for screening. Based on the amount of Aβ accumulation in the brain as determined by amyloid PET, subjects were assigned to two (2) trials with different dose settings: the A3 trial, for those with borderline Aβ levels in the brain, and the A45 trial, for those with positive Aβ levels in the brain.6 Screening with blood biomarker tests was important to improve eligibility for amyloid PET testing in subjects without cognitive impairment. Using plasma Aβ42/40 ratio and p-tau217/tau217 ratio in the initial screening reduced screening failure on amyloid PET from more than 70% to less than 30%. In particular, plasma p-tau217 was shown to correlate with amyloid PET, supporting its role as a useful blood biomarker to identify elevated amyloid in the brain.6 Enrollment for the AHEAD 3-45 study was completed in October 2024. Lifetime Achievement Award Presented to Professor Lannfelt Professor Emeritus Lars Lannfelt of Uppsala University received the CTAD Lifetime Achievement Award in recognition of his pioneering work in scientific discovery and drug development in AD. As part of this award ceremony, he delivered a keynote speech outlining the discovery of the arctic mutation in familial AD, its application to therapeutic strategies targeting protofibrils for AD treatment, and the development of lecanemab. Eisai serves as the lead for lecanemab's development and regulatory submissions globally with both Eisai and Biogen co-commercializing and co-promoting the product and Eisai having final decision-making authority. *Protofibrils are believed to contribute to the brain injury that occurs with AD and are considered to be the most toxic form of Aβ, having a primary role in the cognitive decline of this progressive, debilitating condition.7 Protofibrils cause injury to neurons in the brain which, in turn, can negatively impact cognitive function through multiple mechanisms, not only increasing the development of insoluble Aβ plaques but also increasing direct damage to brain cell membranes and the connections that transmit signals between nerve cells or nerve cells and other cells. It is believed the reduction of protofibrils may prevent the progression of AD by reducing damage to neurons in the brain and cognitive dysfunction.8 **ADNI is a clinical research project launched in 2005 to develop methods to predict the onset of AD and to confirm the effectiveness of treatments. The ADNI observational cohort was pre-specified and used during the design of Clarity AD. The cohort represents the exact population of those in Clarity AD study; matched ADNI participants show similar degree of decline to placebo group out to 18 months. ***PACC-5 is a composite measure that provides a highly sensitive measure of changes in cognitive function in individuals with preclinical AD. Please see full Prescribing Information for LEQEMBI, including Boxed WARNING. U.S. INDICATION LEQEMBI® [(lecanemab-irmb) 100 mg/mL injection for intravenous use] is indicated for the treatment of Alzheimer's disease (AD). Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment (MCI) or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. IMPORTANT SAFETY INFORMATION CONTRAINDICATION LEQEMBI is contraindicated in patients with serious hypersensitivity to lecanemab-irmb or to any of the excipients of LEQEMBI. Reactions have included angioedema and anaphylaxis. WARNINGS AND PRECAUTIONS AMYLOID-RELATED IMAGING ABNORMALITIES LEQEMBI can cause ARIA-E and ARIA-H, which can occur together. ARIA-E can be observed on magnetic resonance imaging (MRI) as brain edema or sulcal effusions and ARIA-H as microhemorrhage and superficial siderosis. ARIA can occur spontaneously in patients with AD. With this class of medications, ARIA-H generally occurs in association with ARIA-E. Reported ARIA symptoms may include headache, confusion, visual changes, dizziness, nausea, and gait difficulty. Focal neurologic deficits may also occur. Symptoms usually resolve over time. Incidence of ARIA Symptomatic ARIA occurred in 3% (29/898) and serious ARIA symptoms in 0.7% (6/898) with LEQEMBI. Clinical ARIA symptoms resolved in 79% (23/29) of patients during the period of observation. ARIA, including asymptomatic radiographic events, was observed: LEQEMBI, 21% (191/898); placebo, 9% (84/897). ARIA-E was observed: LEQEMBI, 13% (113/898); placebo, 2% (15/897). ARIA-H was observed: LEQEMBI, 17% (152/898); placebo, 9% (80/897). No increase in isolated ARIA-H was observed for LEQEMBI vs placebo. ApoE ε4 Carrier Status and Risk of ARIA Of the patients taking LEQEMBI, 16% (141/898) were ApoE ε4 homozygotes, 53% (479/898) were heterozygotes, and 31% (278/898) were noncarriers. With LEQEMBI, the incidence of ARIA was higher in ApoE ε4 homozygotes (LEQEMBI: 45%; placebo: 22%) than in heterozygotes (LEQEMBI: 19%; placebo: 9%) and noncarriers (LEQEMBI: 13%; placebo: 4%). Symptomatic ARIA-E occurred in 9% of ApoE ε4 homozygotes vs 2% of heterozygotes and 1% of noncarriers. Serious ARIA events occurred in 3% of ApoE ε4 homozygotes and in ~1% of heterozygotes and noncarriers. The recommendations on management of ARIA do not differ between ApoE ε4 carriers and noncarriers. Radiographic Findings The majority of ARIA-E radiographic events occurred within the first 7 doses, although ARIA can occur at any time, and patients can have >1 episode. Maximum radiographic severity of ARIA-E with LEQEMBI was mild in 4% (37/898), moderate in 7% (66/898), and severe in 1% (9/898) of patients. Resolution of ARIA-E on MRI occurred in 52% of patients by 12 weeks, 81% by 17 weeks, and 100% overall after detection. Maximum radiographic severity of ARIA-H microhemorrhage with LEQEMBI was mild in 9% (79/898), moderate in 2% (19/898), and severe in 3% (28/898) of patients; superficial siderosis was mild in 4% (38/898), moderate in 1% (8/898), and severe in 0.4% (4/898) of patients. With LEQEMBI, the rate of severe radiographic ARIA-E was highest in ApoE ε4 homozygotes (5%; 7/141) vs heterozygotes (0.4%; 2/479) or noncarriers (0%; 0/278). With LEQEMBI, the rate of severe radiographic ARIA-H was highest in ApoE ε4 homozygotes (13.5%; 19/141) vs heterozygotes (2.1%; 10/479) or noncarriers (1.1%; 3/278). Intracerebral Hemorrhage Intracerebral hemorrhage >1 cm in diameter was reported in 0.7% (6/898) with LEQEMBI vs 0.1% (1/897) with placebo. Fatal events of intracerebral hemorrhage in patients taking LEQEMBI have been reported. Concomitant Antithrombotic Medication: In Clarity AD, baseline use of antithrombotic medication (aspirin, other antiplatelets, or anticoagulants) was allowed if the patient was on a stable dose. The majority of exposures to antithrombotic medications were to aspirin. Antithrombotic medications did not increase the risk of ARIA with LEQEMBI. The incidence of intracerebral hemorrhage was 0.9% (3/328) in patients taking LEQEMBI with a concomitant antithrombotic medication at the time of the event vs 0.6% (3/545) in those who did not receive an antithrombotic. Patients taking LEQEMBI with an anticoagulant alone or combined with an antiplatelet medication or aspirin had an incidence of intracerebral hemorrhage of 2.5% (2/79) vs none in patients receiving placebo. Caution should be exercised when considering the administration of anticoagulants or a thrombolytic agent (e.g., tissue plasminogen activator) to a patient already being treated with LEQEMBI. Other Risk Factors for Intracerebral Hemorrhage: Patients were excluded from enrollment in Clarity AD for findings on neuroimaging that indicated an increased risk for intracerebral hemorrhage. These included findings suggestive of cerebral amyloid angiopathy (prior cerebral hemorrhage >1 cm in greatest diameter, >4 microhemorrhages, superficial siderosis, vasogenic edema) or other lesions (aneurysm, vascular malformation). The presence of an ApoE ε4 allele is also associated with cerebral amyloid angiopathy. Caution should be exercised when considering the use of LEQEMBI in patients with factors that indicate an increased risk for intracerebral hemorrhage and in patients who need to be on anticoagulant therapy. ARIA Monitoring and Dose Management Guidelines Obtain a recent baseline brain MRI prior to initiating treatment with LEQEMBI and prior to the 5th, 7th, and 14th infusions. Enhanced clinical vigilance for ARIA is recommended during the first 14 weeks of treatment with LEQEMBI. Depending on ARIA-E and ARIA-H clinical symptoms and radiographic severity, use clinical judgment when considering whether to continue dosing or to temporarily or permanently discontinue LEQEMBI. If a patient experiences ARIA symptoms, clinical evaluation should be performed, including MRI if indicated. If ARIA is observed on MRI, careful clinical evaluation should be performed prior to continuing treatment. HYPERSENSITIVITY REACTIONS Hypersensitivity reactions, including angioedema, bronchospasm, and anaphylaxis, have occurred with LEQEMBI. Promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity reaction and initiate appropriate therapy. INFUSION-RELATED REACTIONS (IRRs) IRRs were observed—LEQEMBI: 26% (237/898); placebo: 7% (66/897)—and the majority of cases with LEQEMBI (75%, 178/237) occurred with the first infusion. IRRs were mostly mild (69%) or moderate (28%) in severity. IRRs resulted in discontinuation of LEQEMBI in 1% (12/898). Symptoms of IRRs included fever and flu-like symptoms (chills, generalized aches, feeling shaky, and joint pain), nausea, vomiting, hypotension, hypertension, and oxygen desaturation. In the event of an IRR, the infusion rate may be reduced or the infusion may be discontinued and appropriate therapy initiated as clinically indicated. Consider prophylactic treatment prior to future infusions with antihistamines, acetaminophen, nonsteroidal anti-inflammatory drugs, or corticosteroids. ADVERSE REACTIONS The most common adverse reaction leading to discontinuation of LEQEMBI was ARIA-H microhemorrhages that led to discontinuation in 2% (15/898) with LEQEMBI vs <1% (1/897) with placebo. The most common adverse reactions reported in ≥5% with LEQEMBI (N=898) and ≥2% higher than placebo (N=897) were IRRs (LEQEMBI: 26%; placebo: 7%), ARIA-H (LEQEMBI: 14%; placebo: 8%), ARIA-E (LEQEMBI: 13%; placebo: 2%), headache (LEQEMBI: 11%; placebo: 8%), superficial siderosis of central nervous system (LEQEMBI: 6%; placebo: 3%), rash (LEQEMBI: 6%; placebo: 4%), and nausea/vomiting (LEQEMBI: 6%; placebo: 4%). [Notes to editors] 1. About lecanemab (LEQEMBI®) Lecanemab is the result of a strategic research alliance between Eisai and BioArctic. It is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibril) and insoluble forms of amyloid-beta (Aβ). Lecanemab is approved in the U.S.,9 Japan,10 China,11 South Korea,12 Hong Kong,13 Israel,14 the United Arab Emirates15 and Great Britain.16 Eisai has also submitted applications for approval of lecanemab in 10 countries and regions, including the European Union (EU). LEQEMBI's approvals in these countries were based on Phase 3 data from Eisai's, global Clarity AD clinical trial, in which it met its primary endpoint and all key secondary endpoints with statistically significant results. The primary endpoint was the global cognitive and functional scale, Clinical Dementia Rating Sum of Boxes (CDR-SB). In the Clarity AD clinical trial, treatment with lecanemab reduced clinical decline on CDR-SB by 27% at 18 months compared to placebo.17,18 The mean CDR-SB score at baseline was approximately 3.2 in both groups. The adjusted least-squares mean change from baseline at 18 months was 1.21 with lecanemab and 1.66 with placebo (difference, −0.45; 95% confidence interval [CI], −0.67 to −0.23; P<0.001). In addition, the secondary endpoint from the AD Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL), which measures information provided by people caring for patients with AD, noted a statistically significant benefit of 37% compared to placebo. The adjusted mean change from baseline at 18 months in the ADCS-MCI-ADL score was −3.5 in the lecanemab group and −5.5 in the placebo group (difference, 2.0; 95% CI, 1.2 to 2.8; P<0.001). The ADCS MCI-ADL assesses the ability of patients to function independently, including being able to dress, feed themselves and participate in community activities. The most common adverse events (>10%) in the lecanemab group were infusion reactions, ARIA-H (combined cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis), ARIA-E (edema/effusion), headache, and fall. In July 2024 Eisai presented 36-month data from the Phase 3 Clarity AD Open-Label Extension Study demonstrating that LEQEMBI-treated patients continued to show benefit at 36 months of treatment. In the 18-month core study of Clarity AD, there was a statistically significant difference in global cognition and function as measured by CDR-SB between the LEQEMBI and placebo groups. The separation in CDR-SB between the group that continued to receive LEQEMBI (early start group) and the group who switched from placebo to LEQEMBI (delayed start group) was maintained during the 6-month OLE following the core study. This indicates that similar disease trajectory for both early and delayed start groups occurred with LEQEMBI administration. The blood biomarker results (plasma Aβ42/40 ratio, ptau181, GFAP and NfL) showed improvement even after delayed initiation of treatment with LEQEMBI. Since July 2020 the Phase 3 clinical study (AHEAD 3-45) for individuals with preclinical AD, meaning they are clinically normal and have intermediate or elevated levels of amyloid in their brains, is ongoing. AHEAD 3-45 is conducted as a public-private partnership between the Alzheimer's Clinical Trial Consortium that provides the infrastructure for academic clinical trials in AD and related dementias in the U.S, funded by the National Institute on Aging, part of the National Institutes of Health, Eisai, and Biogen. Since January 2022, the Tau NexGen clinical study for Dominantly Inherited AD (DIAD), that is conducted by Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU), led by Washington University School of Medicine in St. Louis, is ongoing and includes lecanemab as the backbone anti-amyloid therapy. 2 . About the Collaboration between Eisai and Biogen for AD Eisai and Biogen have been collaborating on the joint development and commercialization of AD treatments since 2014. Eisai serves as the lead of lecanemab development and regulatory submissions globally with both companies co-commercializing and co-promoting the product and Eisai having final decision-making authority. 3 . About the Collaboration between Eisai and BioArctic for AD Since 2005, Eisai and BioArctic have had a long-term collaboration regarding the development and commercialization of AD treatments. Eisai obtained the global rights to study, develop, manufacture and market lecanemab for the treatment of AD pursuant to an agreement with BioArctic in December 2007. The development and commercialization agreement on the antibody back-up was signed in May 2015. 4 . About Eisai Co., Ltd. Eisai's Corporate Concept is "to give first thought to patients and people in the daily living domain, and to increase the benefits that health care provides." Under this Concept (also known as human health care (hhc) Concept), we aim to effectively achieve social good in the form of relieving anxiety over health and reducing health disparities. With a global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to create and deliver innovative products to target diseases with high unmet medical needs, with a particular focus in our strategic areas of Neurology and Oncology. In addition, we demonstrate our commitment to the elimination of neglected tropical diseases (NTDs), which is a target (3.3) of the United Nations Sustainable Development Goals (SDGs), by working on various activities together with global partners. For more information about Eisai, please visit (for global headquarters: Eisai Co., Ltd.), and connect with us on X, LinkedIn and Facebook. The website and social media channels are intended for audiences outside of the UK and Europe. For audiences based in the UK and Europe, please visit and Eisai EMEA LinkedIn. 5 . About Biogen Founded in 1978, Biogen is a leading biotechnology company that pioneers innovative science to deliver new medicines to transform patients' lives and to create value for shareholders and our communities. We apply deep understanding of human biology and leverage different modalities to advance first-in-class treatments or therapies that deliver superior outcomes. Our approach is to take bold risks, balanced with return on investment to deliver long-term growth. The company routinely posts information that may be important to investors on its website at . Follow Biogen on social media – Facebook, LinkedIn, X, YouTube. Biogen Safe Harbor This news release contains forward-looking statements, including about the potential clinical effects of lecanemab; the potential benefits, safety and efficacy of lecanemab; potential regulatory discussions, submissions and approvals and the timing thereof; the treatment of Alzheimer's disease; the anticipated benefits and potential of Biogen's collaboration arrangements with Eisai; the potential of Biogen's commercial business and pipeline programs; including lecanemab; and risks and uncertainties associated with drug development and commercialization. These statements may be identified by words such as "aim," "anticipate," "believe," "could," "estimate," "expect," "forecast," "intend," "may," "plan," "possible," "potential," "will," "would" and other words and terms of similar meaning. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early-stage clinical studies may not be indicative of full results or results from later stage or larger scale clinical studies and do not ensure regulatory approval. You should not place undue reliance on these statements. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including without limitation unexpected concerns that may arise from additional data, analysis or results obtained during clinical studies; the occurrence of adverse safety events; risks of unexpected costs or delays; the risk of other unexpected hurdles; regulatory submissions may take longer or be more difficult to complete than expected; regulatory authorities may require additional information or further studies, or may fail or refuse to approve or may delay approval of Biogen's drug candidates; including lecanemab; actual timing and content of submissions to and decisions made by the regulatory authorities regarding lecanemab; uncertainty of success in the development and potential commercialization of the medicine; failure to protect and enforce Biogen's data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; product liability claims; and third party collaboration risks, results of operations and financial condition. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from Biogen's expectations in any forward-looking statement. Investors should consider this cautionary statement as well as the risk factors identified in Biogen's most recent annual or quarterly report and in other reports Biogen has filed with the U.S. Securities and Exchange Commission. These statements speak only as of the date of this news release. Biogen does not undertake any obligation to publicly update any forward-looking statements. References Sperling, R., Selkoe, D., Reyderman, L., Youfang, C., Van Dyck, C. (2024, July 28 - August 1). Does the Current Evidence Base Support Lecanemab Continued Dosing for Early Alzheimer's Disease? [Perspectives Session] Alzheimer's Association International Conference, Philadelphia, PA, United States. Van Dyck, C. (2024, October 29-November 1). Does the Current Evidence Base Support Lecanemab Continued Dosing for Early Alzheimer's Disease? [Symposium on Lecanemab Continued Dosing] Clinical Trials for Alzheimer's Disease, Madrid, Spain. De Simone, F., Buitrago, L., Benina, N., et al. (2024, October 29-November 1). The use of plasma biomarkers for the prediction of Amyloid positivity. [Oral Presentation] Clinical Trials for Alzheimer's Disease, Madrid, Spain. Sabbagh, M., Zhao, C., Mahendran, M. et al. (2024, October 29-November 1). Lecanemab Treatment in Real World Settings in the United States. [Late Breaking Symposium 2]. Clinical Trials for Alzheimer's Disease, Madrid, Spain. Watson, D., Neam, M., Stafford, M. et al. (2024, October 29-November 1). Transitioning from Clinical Trial to Clinical Practice for Long-Term Lecanemab Treatment in Early Alzheimer's Disease: Perspectives from an Alzheimer's Disease Treatment Center. [Poster Presentation]. Clinical Trials for Alzheimer's Disease, Madrid, Spain. Sperling, RA., Rissman, R., Johnson, KA., et al. (2024, October 29-November 1). Screening Plasma Biomarkers, Amyloid and Tau PET Imaging in the AHEAD 3-5 Study. [Late Breaking Symposium 1]. Clinical Trials for Alzheimer's Disease, Madrid, Spain. Amin L, Harris DA. Aβ receptors specifically recognize molecular features displayed by fibril ends and neurotoxic oligomers. Nat Commun. 2021;12:3451. doi:10.1038/s41467-021-23507-z Ono K, Tsuji M. Protofibrils of Amyloid-β are Important Targets of a Disease-Modifying Approach for Alzheimer's Disease. Int J Mol Sci. 2020;21(3):952. doi: 10.3390/ijms21030952. PMID: 32023927; PMCID: PMC7037706. U.S. Food and Drug Administration. 2023. FDA Converts Novel Alzheimer's Disease Treatment to Traditional Approval. Last accessed: October 2024. Reuters. 2023. Japan approves Alzheimer's treatment Leqembi by Eisai and Biogen. Last accessed: October 2024. The Pharma Letter. 2024. Brief - Alzheimer drug Leqembi now approved in China. Last accessed: October 2024. Pharmaceutical Technology. 2024. South Korea's MFDS approves Eisai-Biogen's LEQEMBI for Alzheimer's. Last accessed: October 2024. Pharmaceutical Technology. 2024. Hong Kong approves Leqembi for Alzheimer's treatment. Last accessed: October 2024. BioSpace. 2024. Leqembi approved for the treatment of Alzheimer's disease in Israel. Last accessed: October 2024. United Arab Emirates Ministry of Health & Prevention. 2024. Registered Medical Product Directory. Leqembi. Last accessed: October 2024. BioSpace. 2024. Leqembi authorized for early Alzheimer's disease in Great Britain. Last accessed: October 2024. Eisai presents full results of lecanemab Phase 3 confirmatory Clarity AD study for early Alzheimer's disease at Clinical Trials on Alzheimer's Disease (CTAD) conference. Available at: van Dyck, C., et al. Lecanemab in Early Alzheimer's Disease. New England Journal of Medicine. 2023;388:9-21. . SOURCE Eisai Inc. 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Wholly owned first-in-class program anticipated to enter clinical trials in first half of 2025 THOUSAND OAKS, Calif., Oct. 30, 2024 /PRNewswire/ -- Capsida Biotherapeutics ("Capsida") today announced the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to Capsida for CAP-002. CAP-002 is the company's lead investigational gene therapy for the treatment of developmental and epileptic encephalopathy (DEE) due to syntaxin-binding protein 1 (STXBP1) mutations. CAP-002 is a novel, first-in-class IV-administered gene therapy using one of Capsida's proprietary engineered capsids designed to achieve brain-wide neuronal expression of the STXBP1 protein while significantly detargeting the liver. CAP-002 is currently in IND-enabling studies. "FDA's granting Orphan Drug Designation signals the significant potential that CAP-002 demonstrates based upon our preclinical data," said Peter Anastasiou, Chief Executive Officer of Capsida Biotherapeutics. "There are no disease-modifying therapies available for STXBP1 developmental and epileptic encephalopathy and CAP-002 could be the first, bringing hope for patients and families affected by this devastating disorder." The STXBP1 protein is present in every neuron in the brain and is essential for normal neurotransmission. A mutation in the STXBP1 gene is associated with treatment-resistant seizures, severe developmental delay and intellectual disability, motor abnormalities, and sudden unexpected death in epilepsy (SUDEP). Preclinical pharmacology studies have established the potential to treat and even fully correct the disease through gene supplementation. These studies demonstrated rescue of these neurological phenotypes was dependent on supplementation of STXBP1 in neurons throughout the brain at levels not achievable by wild-type serotypes, such as AAV9. Capsida conducted these studies with a proprietary murine disease model in collaboration with Mingshan Xue, Ph.D., associate professor of neuroscience and molecular and human genetics at Baylor College of Medicine, as well as a member of the Cain Foundation Laboratories and the Duncan Neurological Research Institute at Texas Children's Hospital. "Receiving Orphan Drug Designation moves us one step closer to our goal of transforming the lives of people living with STXBP1 developmental and epileptic encephalopathy," said Swati Tole, M.D., Chief Medical Officer at Capsida. "We are committed to advancing CAP-002, with our IND filing in the first half of 2025, and bringing novel gene therapies to people with high unmet medical needs." The FDA's Orphan Drug Designation is intended to encourage the development of treatments for rare diseases, defined as those affecting fewer than 200,000 people in the United States. Orphan Drug Designation may shorten the clinical development path through closer FDA collaboration and potential qualification for expedited development programs. This designation also provides the company with certain benefits, including tax credits for qualified clinical trials, exemption from user fees, and potential seven-year market exclusivity upon FDA approval. About STXBP1 Developmental and Epileptic Encephalopathy Developmental and epileptic encephalopathy caused by STXBP1 mutations is estimated to affect up to one in 26,000 children globally. It is associated with treatment resistant seizures, severe developmental delay and intellectual disability, motor abnormalities, and sudden unexpected death in epilepsy (SUDEP). There are no approved treatments. About Capsida Biotherapeutics Capsida Biotherapeutics is a fully integrated gene therapy company with a central nervous system (CNS) pipeline consisting of disease modifying and potentially curative treatments for rare and more common diseases across all ages. Capsida's intravenously (IV) administered gene therapies utilize proprietary engineered capsids that enable high transduction levels to desired tissues and cells, while limiting tropism to non-target organs, such as the liver. Capsida has three wholly owned programs, including a potential -first-in-class treatment for STXBP1 developmental and epileptic encephalopathy and a best-in-class treatment Parkinson's disease associated with GBA mutations, both of which are in IND-enabling studies and on track to enter the clinic in the first half of 2025. In addition to its wholly owned programs, the Company has validating CNS partnerships with AbbVie, Lilly, CRISPR Therapeutics, and the AbbVie partnership was expanded to include ophthalmology disorders. Capsida was founded in 2019 by lead investors Versant Ventures and Westlake Village BioPartners and originated from groundbreaking research in the laboratory of Viviana Gradinaru, Ph.D., a neuroscience professor at Caltech. Visit us at . SOURCE Capsida Biotherapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED