Brain Edema

European regulators on Tuesday authorized the use of Biogen and Eisai’s Alzheimer’s treatment Leqembi for some early-stage patients “under strict conditions.” The decision from the European Commission makes Leqembi the “first treatment in Europe authorized for patients in the early stages of Alzheimer’s disease,” Biogen’s head of development Priya Singhal said in a statement to Endpoints News . It also gives the companies a head start in Europe after Eli Lilly’s rival therapy Kisunla received a negative opinion from the European Medicines Agency’s human medicines committee last month. That committee, also known as CHMP, initially recommended against Leqembi’s use in a broader Alzheimer’s population last July, but reversed course in the fall after reviewing data from a subgroup of patients who had only one or no copies of a form of a gene called APOE4. The committee said that population was less likely to experience brain imaging abnormalities known as ARIA, a side effect that can lead to brain swelling or bleeding. Leqembi’s authorization on Tuesday is limited to patients who have one or no copies of APOE4 and who have amyloid beta plaques in the brain. “The authorisation is based on the positive scientific assessment of the European Medicines Agency, which concluded that the benefits of this medicine outweighed the risks in a particular population of patients with such disease and as long as risk minimisation measures are applied,” the European Commission said in an announcement . Both Leqembi and Kisunla are approved in the US to treat Alzheimer’s patients. However, bottlenecks in US health systems have created challenges for Leqembi’s rollout in the US. Eisai detailed “delayed uptake in the US market” in guidance it gave last month, citing multiple hurdles, including the length of time it takes for a patient to start treatment after their first visit with a physician. But the company said in a Q3 presentation earlier this year that infusion capacity in the US was expanding. “Together with Eisai, we are moving with urgency to make this important therapy available to patients across Europe,” Singhal said in the statement. CHMP cited ARIA as a key concern when it recommended against Kisunla last month.

SARASOTA, Fla., April 09, 2025 (GLOBE NEWSWIRE) -- Oragenics, Inc. (NYSE American: OGEN), a biotechnology company focused on developing novel intranasal therapies for brain-related conditions, today announced that it has submitted a clinical trial protocol for regulatory review to the Health and Disability Ethics Committee (HDEC) in New Zealand. This submission marks a critical milestone in advancing the Company’s Phase II clinical trial evaluating ONP-002, its proprietary neurosteroid therapy, for the treatment of mild traumatic brain injury (mTBI) or concussion. Pending approval, Oragenics expects to initiate patient enrollment in the region and expand the study’s geographic reach. The trial is expected to be conducted at Christchurch Hospital in New Zealand, the largest tertiary, teaching, and research hospital on the South Island. Christchurch Hospital provides a full range of emergency, acute, elective, and outpatient services, and its Emergency Department is one of the busiest in Australasia, treating more than 83,000 patients annually. “Submitting our HDEC application is a pivotal step toward advancing ONP-002 and addressing the critical need for effective concussion treatments,” said Janet Huffman, Interim Chief Executive Officer of Oragenics. “With patient enrollment planned in both Australia and New Zealand, including at Christchurch Hospital—one of the region’s leading research institutions—we are hoping to expand our global clinical footprint. We look forward to regulatory feedback and moving closer to bringing this much-needed therapy to patients.” No pharmaceutical therapy is available for treating concussion, an unmet medical need. These clinical trials mark the first time a novel chemical drug entity has been tested for efficacy in this patient population. ONP-002 is designed for intranasal administration, offering a non-invasive and efficient route for drug delivery to the brain. The therapy has demonstrated promising results in preclinical models, reducing inflammation, oxidative stress, and brain swelling associated with concussion. A Phase I clinical study proved the drug to be safe and well-tolerated in healthy human volunteers. Investor Contact Rich Cockrell 866.889.1972 ogen@cg.capital About Oragenics, Inc. Oragenics is a biotechnology company focused on developing intranasal therapeutics for neurological disorders, including its lead candidate, ONP-002, for the treatment of mild traumatic brain injury (mTBI) or concussion. The Company is also advancing proprietary powder formulations and intranasal delivery technology to enhance drug administration. For more information, visit www.oragenics.com. Forward-Looking Statements This communication contains “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements are based on management’s beliefs and assumptions and information currently available. The words “believe,” “expect,” “anticipate,” “intend,” “estimate,” “project” and similar expressions that do not relate solely to historical matters identify forward-looking statements. Investors should be cautious in relying on forward-looking statements because they are subject to a variety of risks, uncertainties, and other factors that could cause actual results to differ materially from those expressed in any such forward-looking statements. These factors include, but are not limited to, those described in our Form 10-K and other filings with the U.S. Securities and Exchange Commission. All information set forth in this press release is as of the date hereof. You should consider these factors in evaluating the forward-looking statements included in this press release and not place undue reliance on such statements. We do not assume any obligation to publicly provide revisions or updates to any forward-looking statements, whether as a result of new information, future developments or otherwise, circumstances should change, except as otherwise required by law. Released April 9, 2025

ATTENTION-AD trial data through 192 weeks presented at AD/PDTM 2025 Conference Prespecified delayed-start analysis indicate disease-modifying effect of oral blarcamesine and importance of early and continued long-term treatment of chronic Alzheimer’s disease Blarcamesine exhibited a favorable safety profile with no treatment-related deaths NEW YORK – April 5, 2025 Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq: AVXL), a clinical-stage biopharmaceutical company focused on developing innovative treatments for Alzheimer's disease, Parkinson's disease, schizophrenia, neurodevelopmental, neurodegenerative, and rare diseases, including Rett syndrome, and other central nervous system (CNS) disorders, today announced that over three years of continuous treatment with blarcamesine (ANAVEX®2-73) demonstrated significantly amelioration on clinical decline showing continued clinically and meaningful benefit for early Alzheimer’s disease patients. ATTENTION-AD (ANAVEX®2-73-AD-EP-004) trial result was presented at the AD/PDTM 2025 Conference. Continued blarcamesine treatment up to four (4) years demonstrated good comparative safety profile and no associated neuroimaging adverse events (no potentially fatal brain bleeding or brain swelling). There were no deaths related to the study drug. The ATTENTION-AD (ANAVEX®2-73-AD-EP-004) trial followed the 48-week ANAVEX®2-73-AD-004 double-blind (DB) clinical trial, lasting up to 192 weeks, with an open-label extension (OLE) treatment duration of 96 weeks for participants in Canada and Europe and up to 144 weeks for participants in Australia[1] to evaluate the safety and tolerability of blarcamesine and long-term effects of blarcamesine on cognition and function in participants with early Alzheimer’s disease.[2] Blarcamesine-treated patients continue to accrue benefit through up to 4 years, as measured by the clinical endpoints ADAS-Cog13 and ADCS-ADL. Delayed-start analysis of treatment with oral blarcamesine using the prespecified MMRM analysis method was significant, reflecting importance of early treatment initiation. Continued blarcamesine treatment—without interruption—is encouraged for more favorable clinical outcome that may indicate disease-modifying effect. “The long-term clinical ATTENTION-AD study results are very meaningful, demonstrating that diagnosing and treating people earlier and consistently in the continuum of Alzheimer's disease may lead to greater clinical benefit,” said Prof. Dr. Timo Grimmer, MD, member of the Anavex Scientific Advisory Board and National Coordinating Investigator for the blarcamesine Phase IIb/III ANAVEX®2-73-AD-004 study. “Overall blarcamesine could mark a shift toward more effective and patient-friendly Alzheimer’s treatments addressing disparities in Alzheimer’s care within the global healthcare systems.” Efficacy Data: The delayed-start analysis was performed using the prespecified Mixed effect Model Repeat Measure (MMRM) model, to evaluate the effect of early treatment with blarcamesine on all data collected in both DB and OLE phases as the potential indication of disease-modifying characteristics of the treatment. Comparisons were made between ‘Continued blarcamesine’ and ‘Placebo to blarcamesine’ for ADAS-Cog13 and ADCS-ADL at the scheduled visits. ‘Continued blarcamesine’ is the early start group and ‘Placebo to blarcamesine’ is the late start group. The delayed-start analysis for ADAS-Cog13 showed a significant difference between early start and late start treatment groups up to Week 192 (LS mean difference -3.83, P = 0.0165), favoring the early start group. Together these results suggest that participants who initiated treatment with blarcamesine earlier in their disease progression showed greater stability of cognitive function compared to those who did not initiate blarcamesine until ~1 year later. In addition, to place these findings in context, an ADAS-Cog13 score difference between the treatment groups at Week 192 being larger than 2 points is considered a clinically meaningful improvement.[3] Similarly, the delayed-start analysis for ADCS-ADL showed numerically favorable results for the early start group over the late start group up to Week 192 and reached statistical significance (LS mean difference +4.30, P = 0.0206). An additional analysis, evaluating the therapeutic effect of continuous drug treatment versus treatment interruption between the end of DB trial and the beginning of the OLE trial versus a longer drug interruption, confirmed the beneficial blarcamesine treatment effect. With few or no interrupted treatment days, blarcamesine treatment resulted in an improved treatment effect for both cognition, ADAS-Cog13 (LS mean difference -4.20, P = 0.0083) and function, ADCS-ADL (LS mean difference +5.75, P = 0.0015) at Week 192. This suggests that earlier initiation of treatment with blarcamesine may have a significant positive impact on disease progression and may provide continued benefits to patients with early Alzheimer’s disease over the long-term. Furthermore, continued blarcamesine treatment—without interruption—is encouraged for even more favorable clinical outcome. Safety Data: Blarcamesine exhibited a favorable safety profile with the majority of adverse events (AEs) mild to moderate in severity (Grade 1 or 2), were predominantly linked to the initial titration phase, and could be managed with adjusted titration schedules. Importantly, no severe or life-threatening adverse events were attributed to blarcamesine. There were no deaths related to blarcamesine. The ATTENTION-AD trial demonstrated the manageable nature of the most frequent treatment emergent adverse event (TEAE) of dizziness observed in the preceding ANAVEX®2-73-AD-004 trial, which was generally transient in duration (approx. 7-11 days) and mild or moderate in severity (Grade 1 or 2). The titration schedule was adjusted to a slightly longer titration period in the ATTENTION-AD trial, from previous 2-3 weeks to 10 weeks. A markedly lower frequency of the TEAE of dizziness in the respective maintenance phase was observed: from previously 25.2% in the ANAVEX®2-73-AD-004 trial to 9.6% in the ATTENTION-AD trial, demonstrating the manageable nature of the most frequent TEAE (dizziness). Furthermore, no notable findings were observed over time in vital sign, clinical laboratory test, physical examination, electrocardiogram (ECG), and no pattern of serious adverse events (SAEs) were reported. Compassionate Use: Lastly, there are currently 74 participants receiving blarcamesine within the Compassionate Use Program, who continued treatment with blarcamesine subsequent completion of respective preceding open-label-extension studies from both ANAVEX®2-73-AD-EP-004 in early AD and from ANAVEX®2-73-003 in mild-to-moderate AD. Including the start of the respective preceding studies, some participants are on oral blarcamesine once daily for over 9 years. Importantly, no severe or life-threatening adverse events were attributed to blarcamesine. “We remain excited about the scalable and convenient features of oral blarcamesine, which could be appealing because of its route of administration and good comparative safety profile. The study results demonstrate that diagnosing and treating people earlier in the progression of Alzheimer's disease may lead to greater clinical benefit,” said Juan Carlos Lopez-Talavera, MD, PhD, Head of Research and Development of Anavex. “Additionally, the comprehensive data from the blarcamesine Alzheimer’s disease program represents a solid foundation for the subsequent strategy of our Phase III and IV development plan.” “Alzheimer’s disease is a devastating chronic disease that affects tens of millions worldwide. We believe, the clinically meaningful study results combined with blarcamesine’s convenient once daily oral dosing supports long-term therapy and provide the potential for patients and their families to have a better and longer quality of life,” said Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex. “We believe the scalable and convenient features of blarcamesine could reduce crucial barriers within the currently complex healthcare ecosystem for Alzheimer's disease and provide broader access to a diverse population with early Alzheimer's disease.” The presentation is available on the Investors section of the Company’s website at www.anavex.com. This release discusses investigational uses of an agent in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that any investigational uses of such product will successfully complete clinical development or gain health authority approval. About Anavex Life Sciences Corp. Anavex Life Sciences Corp. (Nasdaq: AVXL) is a publicly traded biopharmaceutical company dedicated to the development of novel therapeutics for the treatment of neurodegenerative, neurodevelopmental, and neuropsychiatric disorders, including Alzheimer's disease, Parkinson's disease, schizophrenia, Rett syndrome, and other central nervous system (CNS) diseases, pain, and various types of cancer. Anavex's lead drug candidate, ANAVEX®2-73 (blarcamesine), has successfully completed a Phase 2a and a Phase 2b/3 clinical trial for Alzheimer's disease, a Phase 2 proof-of-concept study in Parkinson's disease dementia, and both a Phase 2 and a Phase 3 study in adult patients and one Phase 2/3 study in pediatric patients with Rett syndrome. ANAVEX®2-73 is an orally available drug candidate designed to restore cellular homeostasis by targeting SIGMAR1 and muscarinic receptors. Preclinical studies demonstrated its potential to halt and/or reverse the course of Alzheimer's disease. ANAVEX®2-73 also exhibited anticonvulsant, anti-amnesic, neuroprotective, and anti-depressant properties in animal models, indicating its potential to treat additional CNS disorders, including epilepsy. The Michael J. Fox Foundation for Parkinson's Research previously awarded Anavex a research grant, which fully funded a preclinical study to develop ANAVEX®2-73 for the treatment of Parkinson's disease. We believe that ANAVEX®3-71, which targets SIGMAR1 and M1 muscarinic receptors, is a promising clinical stage drug candidate demonstrating disease-modifying activity against the major hallmarks of Alzheimer's disease in transgenic (3xTg-AD) mice, including cognitive deficits, amyloid, and tau pathologies. In preclinical trials, ANAVEX®3-71 has shown beneficial effects on mitochondrial dysfunction and neuroinflammation. Further information is available at www.anavex.com. You can also connect with the Company on Twitter, Facebook, Instagram, and LinkedIn. Forward-Looking Statements Statements in this press release that are not strictly historical in nature are forward-looking statements. These statements are only predictions based on current information and expectations and involve a number of risks and uncertainties. Actual events or results may differ materially from those projected in any of such statements due to various factors, including the risks set forth in the Company’s most recent Annual Report on Form 10-K filed with the SEC. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement and Anavex Life Sciences Corp. undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof. For Further Information: Anavex Life Sciences Corp. Research & Business Development Toll-free: 1-844-689-3939 Email: info@anavex.com Investors: Andrew J. Barwicki Investor Relations Tel: 516-662-9461 Email: andrew@barwicki.com [1] The preceding double-blind trial (ANAVEX®2-73-AD-004) began in Australia before the other regions (Europe and Canada), leaving insufficient time for the other regions to participate in the additional OLE extension beyond the initial 96 Weeks OLE period. The extension, requested by investigators in Australia, extended the initial 96-Week OLE period to 144 Weeks. [2] The scheduled visits were [OLE Week 0 = Combined Week 48], [OLE Week 48 = Combined Week 96], [OLE Week 96 = Combined Week 144] and [OLE Week 144 = Combined Week 192]; Combined = DB (double-blind) + OLE (open-label-extension) trials. [3] Muir RT, Hill MD, Black SE, Smith EE. Minimal clinically important difference in Alzheimer's disease: Rapid review. Alzheimers Dement. 2024;20(5):3352-3363. doi:10.1002/alz.13770 A live audio webcast will be accessible through the Investors section of the Company’s website at www.anavex.com. An archived edition of the session will be available later that day.