Vascular Malformations

-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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New five-year data reinforce long-term safety and efficacy of SPRAVATO® (esketamine) in patients with inadequate response to two or more oral antidepressants (treatment-resistant depression) 23 abstracts highlight data from Company's robust portfolio and pipeline, including clinical insights on major depressive disorder and the significant burden of anhedonia and insomnia symptoms Large real-world analysis highlights the link between reducing relapse and improving survival in schizophrenia TITUSVILLE, N.J., Oct. 24, 2024 /PRNewswire/ -- Johnson & Johnson (NYSE: JNJ) announced today that 23 abstracts featuring new real-world and clinical trial data from across its neuropsychiatry portfolio and pipeline will be presented at the annual U.S. Psychiatric and Mental Health Congress (Psych Congress), taking place October 29 to November 2 in Boston, Massachusetts. Presentations include new data supporting the safety and efficacy of SPRAVATO® (esketamine) CIII nasal spray and the Company's innovative portfolio of long-acting injectables (LAIs) for schizophrenia, as well as data highlighting the significant burden people living with major depressive disorder (MDD) and schizophrenia often face. "For nearly seven decades, J&J has been at the forefront of driving scientific progress and innovation in neuroscience," said Bill Martin, Ph.D., Global Neuroscience Therapeutic Area Head, Johnson & Johnson Innovative Medicine. "It is our responsibility and privilege to help advance research and understanding of MDD and schizophrenia so we can continue to deliver transformational therapies that address the greatest unmet patient needs." Key presentations include: New five-year, real-world safety data from nearly 35,000 adults treated with SPRAVATO®, building on more than a decade of research and reinforcing its well-studied, consistent safety profile (Poster 151). Novel insights into the clinical, humanistic and economic burden of anhedonia in adults with MDD (Poster 113). Results from an analysis of more than 30,000 adults with schizophrenia highlighting the link between symptom relapse and risk of death, which can occur 15‐20 years prematurely for adults living with schizophrenia compared to the general population due to many different causes.1 (Poster 42). "Serious mental illness is one of the most complex health challenges of our time," said Pearl Pugh, President, U.S. Neuroscience, Johnson & Johnson Innovative Medicine. "Understanding the patient experience is at the core of our mission to develop breakthrough solutions that can help improve care and make a difference in the lives of those living with challenging-to-treat mental illnesses." J&J will present the following posters at Psych Congress on October 31 from 1:30-3:30 p.m. ET and November 1 from 1:30-3:30 p.m. ET in the Exhibit Hall. ABOUT TREATMENT-RESISTANT DEPRESSION Depression is a common mental health disorder that impacts an estimated 280 million people worldwide.2 In the U.S., approximately 21 million adults have had at least one major depressive episode, and approximately one-third of medication-treated adults are considered to have TRD.3,4 People living with MDD are often considered to have TRD if they have not responded adequately to at least two different antidepressants of adequate dose and duration in the current depressive episode.4 TRD has a significant negative impact on the lives of those affected and has one of the highest economic burdens of all psychiatric disorders.4 ABOUT SPRAVATO® SPRAVATO® (esketamine) CIII nasal spray is approved by the U.S. Food and Drug Administration in combination with an oral antidepressant for adults with TRD and depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior. It is the first treatment to use a new mechanism of action in decades for the treatment of TRD. SPRAVATO® is a non-selective, non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor and is believed to work differently by acting on a pathway in the brain that affects glutamate. To date, SPRAVATO® has been approved in 79 countries and administered to more than 100,000 patients worldwide. ABOUT MAJOR DEPRESSIVE DISORDER WITH INSOMNIA SYMPTOMS MDD is one of the most common psychiatric disorders and leading causes of disability worldwide,5 with an estimated 280 million people living with the disorder around the world.2 MDD is often accompanied by sleep disturbances such as insomnia or hypersomnia, affecting up to 60 percent of patients with MDD.6 Disturbed sleep and insomnia symptoms have a significant impact on a patient's quality of life and exacerbate the risk of depressive relapse and suicide.7,8 ABOUT SELTOREXANT Seltorexant, an investigational potential first-in-class therapy, is a selective antagonist of the human orexin-2 receptor currently being developed as an adjunctive treatment for adults with MDD with insomnia symptoms. Seltorexant is believed to selectively antagonize the orexin-2 receptors, potentially improving mood and sleep symptoms associated with depression. When orexin-2 receptors are stimulated for too long or at inappropriate times, their activation can cause hyperarousal manifestations, including insomnia and excessive cortisol release, which may contribute to depression and insomnia. ABOUT SCHIZOPHRENIA Schizophrenia is a chronic and severe brain disorder affecting approximately 20 million people worldwide and an estimated 2.4 million adults in the U.S.9-11 The disease is characterized by distortions in thinking, perception, emotions, language, sense of self, and behavior.9 It can also lead to neurological impairment and severe disability.12 Antipsychotic medication is recognized as an essential component in the treatment of schizophrenia, and adherence to medication plays a critical role in controlling symptoms and costly relapses.13 ABOUT J&J'S U.S. LONG-ACTING INJECTABLES The J&J U.S. portfolio of long-acting injectable treatments for adults with schizophrenia provides the most varied range of dosing options and the longest-lasting schizophrenia treatments with each dose available. Our portfolio includes INVEGA SUSTENNA® (1-month paliperidone palmitate), INVEGA TRINZA® (3-month paliperidone palmitate), and INVEGA HAFYERA® (6-month paliperidone palmitate), all of which are administered in a clinical setting by a medical professional. Long-acting injectables (LAIs) allow for the slow release of medicine into the bloodstream and have been available and studied for more than 50 years. Based on clinical guidance, the National Council for Mental Wellbeing and the American Psychiatric Association have updated their guidance and practice guidelines to recommend the use of LAIs for appropriate patients.14-16 SPRAVATO® IMPORTANT SAFETY INFORMATION What is SPRAVATO® (esketamine) CIII nasal spray? SPRAVATO® is a prescription medicine, used along with an antidepressant taken by mouth to treat: Adults with treatment-resistant depression (TRD) Depressive symptoms in adults with major depressive disorder (MDD) with suicidal thoughts or actions SPRAVATO® is not for use as a medicine to prevent or relieve pain (anesthetic). It is not known if SPRAVATO® is safe or effective as an anesthetic medicine. It is not known if SPRAVATO® is safe and effective for use in preventing suicide or in reducing suicidal thoughts or actions. SPRAVATO® is not for use in place of hospitalization if your healthcare provider determines that hospitalization is needed, even if improvement is experienced after the first dose of SPRAVATO®. It is not known if SPRAVATO® is safe and effective in children. IMPORTANT SAFETY INFORMATION Do not take SPRAVATO® if you: have blood vessel (aneurysmal vascular) disease (including in the brain, chest, abdominal aorta, arms and legs) have an abnormal connection between your veins and arteries (arteriovenous malformation) have a history of bleeding in the brain are allergic to esketamine, ketamine, or any of the other ingredients in SPRAVATO®. If you are not sure if you have any of the above conditions, talk to your healthcare provider before taking SPRAVATO®. Before you take SPRAVATO®, tell your healthcare provider about all of your medical conditions, including if you: have heart or brain problems, including: high blood pressure (hypertension) slow or fast heartbeats that cause shortness of breath, chest pain, lightheadedness, or fainting history of heart attack history of stroke heart valve disease or heart failure history of brain injury or any condition where there is increased pressure in the brain have liver problems have ever had a condition called "psychosis" (see, feel, or hear things that are not there, or believe in things that are not true). are pregnant or plan to become pregnant. SPRAVATO® may harm your baby. You should not take SPRAVATO® if you are pregnant. Tell your healthcare provider right away if you become pregnant during treatment with SPRAVATO®. If you are able to become pregnant, talk to your healthcare provider about methods to prevent pregnancy during treatment with SPRAVATO®. There is a pregnancy registry for women who are exposed to SPRAVATO® during pregnancy. The purpose of the registry is to collect information about the health of women exposed to SPRAVATO® and their baby. If you become pregnant during treatment with SPRAVATO®, talk to your healthcare provider about registering with the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or online at . are breastfeeding or plan to breastfeed. You should not breastfeed during treatment with SPRAVATO®. Tell your healthcare provider about all the medicines that you take, including prescription and over-the-counter medicines, vitamins and herbal supplements. Taking SPRAVATO® with certain medicine may cause side effects. Especially tell your healthcare provider if you take central nervous system (CNS) depressants, psychostimulants, or monoamine oxidase inhibitors (MAOIs) medicine. Keep a list of them to show to your healthcare provider and pharmacist when you get a new medicine. How will I take SPRAVATO®? You will take SPRAVATO nasal spray yourself, under the supervision of a healthcare provider in a healthcare setting. Your healthcare provider will show you how to use the SPRAVATO® nasal spray device. Your healthcare provider will tell you how much SPRAVATO® you will take and when you will take it. Follow your SPRAVATO® treatment schedule exactly as your healthcare provider tells you to. During and after each use of the SPRAVATO® nasal spray device, you will be checked by a healthcare provider who will decide when you are ready to leave the healthcare setting. You will need to plan for a caregiver or family member to drive you home after taking SPRAVATO®. If you miss a SPRAVATO® treatment, your healthcare provider may change your dose and treatment schedule. Some people taking SPRAVATO® get nausea and vomiting. You should not eat for at least 2 hours before taking SPRAVATO® and not drink liquids at least 30 minutes before taking SPRAVATO®. If you take a nasal corticosteroid or nasal decongestant medicine take these medicines at least 1 hour before taking SPRAVATO®. What should I avoid while taking SPRAVATO? Do not drive, operate machinery, or do anything where you need to be completely alert after taking SPRAVATO®. Do not take part in these activities until the next day following a restful sleep. See "What is the most important information I should know about SPRAVATO® ?" What are the possible side effects of SPRAVATO®? SPRAVATO® may cause serious side effects including: See "What is the most important information I should know about SPRAVATO?" Increased blood pressure. SPRAVATO® can cause a temporary increase in your blood pressure that may last for about 4 hours after taking a dose. Your healthcare provider will check your blood pressure before taking SPRAVATO® and for at least 2 hours after you take SPRAVATO®. Tell your healthcare provider right away if you get chest pain, shortness of breath, sudden severe headache, change in vision, or seizures after taking SPRAVATO®. Problems with thinking clearly. Tell your healthcare provider if you have problems thinking or remembering. Bladder problems. Tell your healthcare provider if you develop trouble urinating, such as a frequent or urgent need to urinate, pain when urinating, or urinating frequently at night. The most common side effects of SPRAVATO when used along with an antidepressant taken by mouth include: If these common side effects occur, they usually happen right after taking SPRAVATO and go away the same day. These are not all the possible side effects of SPRAVATO®. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1‑800‑FDA‑1088. Please see full Prescribing Information , including Boxed WARNINGS, and Medication Guide for SPRAVATO® and discuss any questions you may have with your healthcare provider. cp-170363v3 INVEGA® IMPORTANT SAFETY INFORMATION INDICATIONS INVEGA HAFYERA® (6-month paliperidone palmitate) is a prescription medicine given by injection every 6 months by a healthcare professional and used to treat schizophrenia. INVEGA HAFYERA® is used in adults who have been treated with either: INVEGA SUSTENNA® (paliperidone palmitate) a 1-time-each-month paliperidone palmitate extended-release injectable suspension for at least 4 months INVEGA TRINZA® (paliperidone palmitate) a 1-time-every-3-months paliperidone palmitate extended-release injectable suspension for at least 3 months INVEGA TRINZA® is a prescription medicine given by injection every 3 months by a healthcare professional and used to treat schizophrenia. INVEGA TRINZA® is used in people who have been adequately treated with INVEGA SUSTENNA® for at least 4 months. INVEGA SUSTENNA® is a prescription medicine given by injection by a healthcare professional. INVEGA SUSTENNA® is used to treat schizophrenia in adults. IMPORTANT SAFETY INFORMATION Do not receive INVEGA HAFYERA®, INVEGA TRINZA® or INVEGA SUSTENNA® if you are allergic to paliperidone, paliperidone palmitate, risperidone, or any of the ingredients in INVEGA HAFYERA®, INVEGA TRINZA® or INVEGA SUSTENNA®. See the end of the Patient Information leaflet in the full Prescribing Information for a complete list of INVEGA HAFYERA®, INVEGA TRINZA® and INVEGA SUSTENNA® ingredients. Before you receive INVEGA HAFYERA®, INVEGA TRINZA® or INVEGA SUSTENNA®, tell your healthcare professional about all your medical conditions, including if you: have had Neuroleptic Malignant Syndrome (NMS) have or have had heart problems, including a heart attack, heart failure, abnormal heart rhythm, or long QT syndrome have or have had low levels of potassium or magnesium in your blood have or have had uncontrolled movements of your tongue, face, mouth, or jaw (tardive dyskinesia) have or have had kidney or liver problems have diabetes or have a family history of diabetes have Parkinson's disease or a type of dementia called Lewy Body Dementia have had a low white blood cell count have had problems with dizziness or fainting or are being treated for high blood pressure have or have had seizures or epilepsy have any other medical conditions are pregnant or plan to become pregnant. It is not known if INVEGA HAFYERA®, INVEGA TRINZA® or INVEGA SUSTENNA® will harm your unborn baby If you become pregnant while taking INVEGA HAFYERA®, INVEGA TRINZA® or INVEGA SUSTENNA®, talk to your healthcare professional about registering with the National Pregnancy Registry for Atypical Antipsychotics. You can register by calling 1-866-961-2388 or visit . Infants born to women who are treated with INVEGA HAFYERA®, INVEGA TRINZA® or INVEGA SUSTENNA® may experience symptoms such as tremors, irritability, excessive sleepiness, eye twitching, muscle spasms, decreased appetite, difficulty breathing, or abnormal movement of arms and legs. Let your healthcare professional know if these symptoms occur. are breastfeeding or plan to breastfeed. INVEGA HAFYERA®, INVEGA TRINZA® or INVEGA SUSTENNA® can pass into your breast milk. Talk to your healthcare professional about the best way to feed your baby if you receive INVEGA HAFYERA®, INVEGA TRINZA® or INVEGA SUSTENNA®. Tell your healthcare professional about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. INVEGA HAFYERA®, INVEGA TRINZA® and INVEGA SUSTENNA® may affect the way other medicines work, and other medicines may affect how INVEGA HAFYERA®, INVEGA TRINZA® and INVEGA SUSTENNA® works. Your healthcare provider can tell you if it is safe to receive INVEGA HAFYERA®, INVEGA TRINZA® or INVEGA SUSTENNA® with your other medicines. Do not start or stop any medicines during treatment with INVEGA HAFYERA®, INVEGA TRINZA® or INVEGA SUSTENNA® without talking to your healthcare provider first. Know the medicines you take. Keep a list of them to show to your healthcare professional or pharmacist when you get a new medicine. Patients (particularly the elderly) taking antipsychotics with certain health conditions or those on long-term therapy should be evaluated by their healthcare professional for the potential risk of falls. How will I receive INVEGA HAFYERA®, INVEGA TRINZA® or INVEGA SUSTENNA®? Follow your treatment schedule exactly as your healthcare provider tells you to. Your healthcare provider will tell you how much you will receive and when you will receive it. What should I avoid while receiving INVEGA HAFYERA®, INVEGA TRINZA® or INVEGA SUSTENNA®? INVEGA HAFYERA®, INVEGA TRINZA® and INVEGA SUSTENNA® may affect your ability to make decisions, think clearly, or react quickly. Do not drive, operate heavy machinery, or do other dangerous activities until you know how INVEGA HAFYERA®, INVEGA TRINZA® or INVEGA SUSTENNA® affects you. Avoid getting overheated or dehydrated. INVEGA HAFYERA® , INVEGA TRINZA® and INVEGA SUSTENNA® may cause serious side effects, including: See "What is the most important information I should know about INVEGA HAFYERA® , INVEGA TRINZA® and INVEGA SUSTENNA®?" stroke in elderly people (cerebrovascular problems) that can lead to death Neuroleptic Malignant Syndrome (NMS). NMS is a rare but very serious problem that can happen in people who receive INVEGA HAFYERA®, INVEGA TRINZA® or INVEGA SUSTENNA®. NMS can cause death and must be treated in a hospital. Call your healthcare professional right away if you become severely ill and have any of these symptoms: high fever; severe muscle stiffness; confusion; loss of consciousness; changes in your breathing, heartbeat, and blood pressure. problems with your heartbeat. These heart problems can cause death. Call your healthcare professional right away if you have any of these symptoms: passing out or feeling like you will pass out, dizziness, or feeling as if your heart is pounding or missing beats. uncontrolled movements of your tongue, face, mouth, or jaw (tardive dyskinesia) metabolic changes. Metabolic changes may include high blood sugar (hyperglycemia), diabetes mellitus and changes in the fat levels in your blood (dyslipidemia), and weight gain. low blood pressure and fainting changes in your blood cell counts high level of prolactin in your blood (hyperprolactinemia). INVEGA HAFYERA®, INVEGA TRINZA® or INVEGA SUSTENNA® may cause a rise in the blood levels of a hormone called prolactin (hyperprolactinemia) that may cause side effects including missed menstrual periods, leakage of milk from the breasts, development of breasts in men, or problems with erection. problems thinking clearly and moving your body seizures difficulty swallowing that can cause food or liquid to get into your lungs prolonged or painful erection lasting more than 4 hours. Call your healthcare professional or go to your nearest emergency room right away if you have an erection that lasts more than 4 hours. problems with control of your body temperature, especially when you exercise a lot or spend time doing things that make you warm. It is important for you to drink water to avoid dehydration. The most common side effects of INVEGA HAFYERA® include: injection site reactions, weight gain, headache, upper respiratory tract infections, feeling restlessness or difficulty sitting still, slow movements, tremors, stiffness and shuffling walk. The most common side effects of INVEGA TRINZA® include: injection site reactions, weight gain, headache, upper respiratory tract infections, feeling restlessness or difficulty sitting still, slow movements, tremors, stiffness and shuffling walk. The most common side effects of INVEGA SUSTENNA® include: injection site reactions; sleepiness or drowsiness; dizziness; feeling of inner restlessness or needing to be constantly moving; abnormal muscle movements, including tremor (shaking), shuffling, uncontrolled involuntary movements, and abnormal movements of your eyes. Tell your healthcare professional if you have any side effect that bothers you or does not go away. These are not all the possible side effects of INVEGA HAFYERA®, INVEGA TRINZA® or INVEGA SUSTENNA®. For more information, ask your healthcare professional or pharmacist. Call your healthcare professional for medical advice about side effects. You may report side effects of prescription drugs to the FDA at 1-800-FDA-1088. General information about the safe and effective use of INVEGA HAFYERA®, INVEGA TRINZA® or INVEGA SUSTENNA® Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use INVEGA HAFYERA®, INVEGA TRINZA® or INVEGA SUSTENNA® for a condition for which it was not prescribed. You can ask your pharmacist or healthcare professional for information about INVEGA HAFYERA®, INVEGA TRINZA® or INVEGA SUSTENNA® that is written for healthcare professionals. For more information, go to , or or call 1-800-526-7736. Please click to read the full Prescribing Information, including Boxed WARNING, for INVEGA HAFYERA ® , INVEGA TRINZA ® and INVEGA SUSTENNA® and discuss any questions you have with your healthcare professional. cp-256259v4 ABOUT JOHNSON & JOHNSON At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and where solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at or at . Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC and Janssen Biotech, Inc. are Johnson & Johnson companies. Cautions Concerning Forward-Looking Statements This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of nipocalimab. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, Janssen Biotech, Inc. and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 31, 2023, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at , or on request from Johnson & Johnson. None of Janssen Research & Development, LLC, Janssen Biotech, Inc. nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. Correll C, Solmi, M, Croatto G, et al. Mortality in people with schizophrenia: a systematic review and meta-analysis of relative risk and aggravating or attenuating factors. World Psychiatry. 21(2),248–271. doi:10.1002/wps.20994 World Health Organization. Depressive disorder (depression). Accessed October 2024. who.int/news-room/fact-sheets/detail/depression National Institute of Mental Health. Major depression. Accessed October 2024. nimh.nih.gov/health/statistics/major-depression Zhdanava M, Pilon D, Ghelerter I, et al. The prevalence and national burden of treatment-resistant depression and major depressive disorder in the United States. J Clin Psychiatry. (2021);82(2):20m13699. World Health Organization. "Depression: let's talk" says WHO, as depression tops list of causes of ill health. Accessed October 2024. Sakurai, H, Suzuki, T, Yoshimura, K, et al. Predicting relapse with individual residual symptoms in major depressive disorder: a reanalysis of the STAR*D data. Psychopharmacology. (2017);234(16): 2453–2461 . Psychopharmacology Institute. Understanding the relationship between insomnia disorder and MDD.. Accessed October 2024. Taddei-Allen, P. Economic burden and managed care considerations for the treatment of insomnia. Am J Manag Care. (2020);26:S91-S96. doi.org/10.37765/ajmc.2020.43008 World Health Organization. Schizophrenia. Accessed October 2024. Regier DA, Farmer ME, Rae DS, et al. One–month prevalence of mental disorders in the United States and sociodemographic characteristics: the epidemiologic catchment area study. Acta Psychiatr Scand. (1993);88(1):35-47. doi:10.1111/j.1600-0447.1993.tb03411.x US Census Bureau. 2010 US Census. Accessed October 2024. Andreasen N, Nopoulos P, Magnotta V, et al. Progressive brain change in schizophrenia: a prospective longitudinal study of first-episode schizophrenia. Biol Psychiatry. (2011);70(7):672-679. doi:10.1016/j.biopsych.2011.05.017 Higashi K, Medic G, Littlewood K, et al. Medication adherence in schizophrenia: factors influencing adherence and consequences of nonadherence, a systemic literature review. Ther Adv Psychopharmacol. (2013);3(4):200-218. doi:10.1177/2045125312474019 American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia. Accessed October 2024. American Psychiatric Association. APA releases new practice guideline on treatment of patients with schizophrenia. Accessed October 2024. National Council for Mental Wellbeing. Guide to long-acting medications. Accessed October 2024. © Johnson & Johnson 2024. All rights reserved. SOURCE Johnson & Johnson WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Poster presentations include data supporting QTORIN™ rapamycin 3.9% anhydrous gel as a potential targeted therapy for the treatment of microcystic lymphatic malformations and a review of the Phase 3 SELVA studyWAYNE, PA., Oct. 15, 2024 (GLOBE NEWSWIRE) -- Palvella Therapeutics, Inc., a clinical-stage biopharmaceutical company focused on developing and commercializing novel therapies to treat patients suffering from serious, rare genetic skin diseases for which there are no FDA-approved therapies, today announced two poster presentations at the upcoming 12th Pediatric Dermatology Research Alliance (PeDRA) Annual Conference, taking place October 24-26, 2024, in Phoenix, AZ. The presentations include data supporting QTORIN™ rapamycin 3.9% anhydrous gel (QTORIN™ rapamycin) as a potential targeted therapy for microcystic lymphatic malformations (microcystic LMs) and a review of the Phase 3 SELVA study, a 24-week, single-arm, baseline-controlled clinical trial of QTORIN™ rapamycin for the treatment of microcystic LMs. The details are as follows: 12th PeDRA Annual Conference AbstractsTitle: SELVA: A Phase 3 Study with a Fit-For-Purpose Primary Endpoint Evaluating QTORIN 3.9% Rapamycin Anhydrous Gel in the Treatment of Microcystic Lymphatic MalformationsPresenter: Joyce Teng, M.D., Ph.D.; Professor of Dermatology and Pediatrics, Stanford University Session Date: Thursday, October 24, 2024 Session Time: 4:00-5:25 PM MST Title: QTORIN™ rapamycin 3.9% anhydrous gel: A Novel, Dermal-Targeted Topical mTOR inhibitor in Phase 3 for treatment of Microcystic Lymphatic MalformationsPresenter: Jeff Martini, Ph.D., Chief Scientific Officer, Palvella TherapeuticsSession Date: Thursday, October 24, 2024Session Time: 4:00-5:25 PM MST PeDRA will publish abstracts from the 12th annual conference in the journal Pediatric Dermatology. For more details about the 12th PeDRA Annual Conference please visit https://pedraresearch.org/2024-annual-conference. About Microcystic Lymphatic MalformationsMicrocystic LMs is a rare, chronically debilitating genetic disease caused by dysregulation of the phosphatidylinositol 3-kinase (PI3K)/mTOR pathway. The disease is characterized by malformed lymphatic vessels that protrude through the skin and persistently leak lymph fluid (lymphorrhea) and bleed, often leading to recurrent serious infections and cellulitis that can cause hospitalization. The natural history of microcystic LMs are persistent and progressive without spontaneous resolution, with symptoms generally worsening during life, including increases in the number and size of malformed vessels that lead to complications and lifetime morbidity. There are currently no FDA-approved treatments for the estimated more than 30,000 diagnosed patients with microcystic LMs in the United States. About QTORIN™ Platform and QTORIN™ rapamycinPalvella's research team developed QTORIN, a patented and versatile platform designed to generate novel topical therapies that penetrate the deep layers of the skin to locally treat a broad spectrum of serious, rare genetic skin diseases. Well-accepted mechanisms of action of rapamycin and other therapeutic agents represent potential therapies for rare genetic skin diseases. However, the adverse event profile of those agents through systemic exposure poses significant barriers to patient adoption. Palvella’s QTORIN product candidates are designed for targeted, localized delivery of therapeutic agents to pathogenic tissue of interest while minimizing systemic absorption and thereby reducing the risk of unwanted adverse events associated with systemic therapy. QTORIN rapamycin is the lead product candidate from Palvella's QTORIN platform. QTORIN rapamycin is a novel, patented 3.9% rapamycin anhydrous gel, which aims to harness the potential therapeutic benefits of rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, while minimizing systemic exposure of rapamycin and potential adverse reactions associated with systemic therapy. QTORIN rapamycin is currently under development for the treatment of microcystic LMs, cutaneous venous malformations, and other serious, functionally debilitating skin diseases driven by the overactivation of the mTOR pathway. QTORIN rapamycin has received FDA Breakthrough Therapy Designation, Fast Track Designation, and Orphan Drug Designation for microcystic LMs, and Fast Track Designation for venous malformations. QTORIN rapamycin is protected by multiple issued composition patents in the U.S. and Japan and has several pending patent applications covering anhydrous gel formulations of rapamycin in the U.S., Europe, and Japan. In the third quarter of 2024, Palvella initiated SELVA, a 24-week, Phase 3, single-arm, baseline-controlled clinical trial of QTORIN rapamycin for the treatment of microcystic LMs. The study's primary and key secondary endpoints are clinician-reported outcomes. The study is expected to enroll 40 subjects at leading vascular anomaly centers across the U.S. QTORIN rapamycin is for investigational use only and has not been approved or cleared by the FDA or by any other regulatory agency. About Palvella TherapeuticsFounded and led by rare drug disease drug development veterans, Palvella Therapeutics is a clinical-stage biopharmaceutical company focused on developing and commercializing novel therapies to treat patients suffering from serious, rare genetic skin diseases for which there are no FDA-approved therapies. Palvella is developing a broad pipeline of product candidates based on its patented QTORIN™ platform, with an initial focus on serious, rare genetic skin diseases, many of which are lifelong in nature. Palvella's lead product candidate, QTORIN 3.9% rapamycin anhydrous gel (QTORIN™ rapamycin), is currently in clinical development for microcystic lymphatic malformations (microcystic LMs) and cutaneous venous malformations. In July 2023, Palvella and Pieris Pharmaceuticals, Inc. (Nasdaq: PIRS) announced they have entered into a definitive merger agreement to combine the companies in an all-stock transaction. Forward-Looking StatementsThis press release contains forward-looking statements concerning the development and commercialization of Palvella’s products, the potential benefits and attributes of such products, and the company’s expectations regarding its prospects, including the potential merger with Pieris Pharmaceuticals. Forward-looking statements are subject to risks, assumptions and uncertainties that could cause actual future events or results to differ materially from such statements. These statements are made as of the date of this press release. Actual results may vary. Palvella undertakes no obligation to update any forward-looking statements for any reason. No Offer or SolicitationThis press release is not intended to and does not constitute an offer to sell or the solicitation of an offer to subscribe for or buy or an invitation to purchase or subscribe for any securities or the solicitation of any vote in any jurisdiction pursuant to the proposed transaction or otherwise, nor shall there be any sale, issuance or transfer of securities in any jurisdiction in contravention of applicable law. No offer of securities shall be made except by means of a prospectus meeting the requirements of the Securities Act. Subject to certain exceptions to be approved by the relevant regulators or certain facts to be ascertained, the public offer will not be made directly or indirectly, in or into any jurisdiction where to do so would constitute a violation of the laws of such jurisdiction, or by use of the mails or by any means or instrumentality (including without limitation, telephone and the internet) of interstate or foreign commerce, or any facility of a national securities exchange, of any such jurisdiction. NEITHER THE SEC NOR ANY STATE SECURITIES COMMISSION HAS APPROVED OR DISAPPROVED OF THE SECURITIES OR DETERMINED IF THIS PRESS RELEASE IS TRUTHFUL OR COMPLETE. Important Additional Information About the Proposed Transactions Will be Filed with the SECIn connection with the proposed transaction between Pieris and Palvella, Pieris intends to file relevant materials with the SEC, including a registration statement on Form S-4 that will contain a proxy statement and prospectus of Pieris and an information statement of Palvella. PIERIS URGES INVESTORS AND STOCKHOLDERS TO READ THESE MATERIALS CAREFULLY AND IN THEIR ENTIRETY WHEN THEY BECOME AVAILABLE, AS WELL AS ANY AMENDMENTS OR SUPPLEMENTS TO THESE MATERIALS, BECAUSE THEY WILL CONTAIN IMPORTANT INFORMATION ABOUT PIERIS, PALVELLA, THE PROPOSED TRANSACTION AND RELATED MATTERS. Investors and stockholders will be able to obtain free copies of the proxy statement/prospectus/information statement and other documents filed by Pieris with the SEC (when they become available) through the website maintained by the SEC at www.sec.gov. In addition, investors and stockholders will be able to obtain free copies of the proxy statement/prospectus/information statement and other documents filed by Pieris with the SEC free of charge on Pieris’ website at www.pieris.com, or by contacting Investor Relations by email at info@pieris.com. Investors and stockholders are urged to read the proxy statement/prospectus/information statement and the other relevant materials when they become available before making any voting or investment decision with respect to the proposed transaction. Participants in the Solicitation Palvella, Pieris and their respective directors and executive officers may be considered participants in the solicitation of proxies in connection with the proposed transaction. Information about Pieris’ directors and executive officers is included in Pieris’ most recent Annual Report on Form 10-K, as amended, including any information incorporated therein by reference, as filed with the SEC on March 29, 2024, and amended on April 29, 2024. Additional information regarding the persons who may be deemed participants in the solicitation of proxies will be included in the proxy statement/prospectus/information statement relating to the proposed transaction when it is filed with the SEC. These documents can be obtained free of charge from the sources indicated above. Contact InformationInvestorsWesley H. KaupinenFounder and CEO, Palvella Therapeuticswes.kaupinen@palvellatx.com MediaStephanie JacobsonManaging Director, Argot Partnerspalvella@argotpartners.com