Alzheimer Disease, Familial, Type 3

Company to host a webcast today at 8:30 a.m. Eastern Time NEW YORK, May 09, 2024 (GLOBE NEWSWIRE) -- Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq: AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative, neurodevelopmental and neuropsychiatric disorders including Alzheimer’s disease, Parkinson’s disease, Rett syndrome, schizophrenia, and other central nervous system (CNS) diseases, today reported financial results for its fiscal quarter ended March 31, 2024. “We are encouraged by the very recently issued FDA guidance for Early Alzheimer’s disease, which states that one cognitive measurement alone, like ADAS-Cog13, could be a sufficient primary endpoint for early Alzheimer’s disease.1 We appreciate this new guidance and believe this opens another possible pathway for us to move forward in parallel to the initiated process of Marketing Authorisation application to the European Medicines Agency (EMA) for blarcamesine related to the treatment of Alzheimer’s disease, which is underway. We are also pleased to report that the first cohort of schizophrenia patients in the ongoing ANAVEX®3-71-SZ-001 Phase 2 trial of ANAVEX®3-71 has been fully enrolled,” said Christopher U Missling, PhD, President and Chief Executive Officer of Anavex. “Moreover, we remain committed to the development of our programs within neurodegenerative, neurodevelopmental disorders, which could further expand our portfolio of transformative investigational therapies and utilizing our differentiated precision medicine platform to deliver easy access and scalable treatment options for brain disorders.” Key Pipeline Updates: Alzheimer’s disease: Full data from the blarcamesine in Alzheimer’s disease Phase 2b/3 placebo-controlled clinical trial will be published in an upcoming peer-reviewed journal. The initiated process for submitting a Marketing Authorisation application to the European Medicines Agency (EMA) under the Centralised Procedure is underway. The Marketing Authorisation would allow direct market access throughout the European Union for oral blarcamesine for the treatment of Alzheimer’s disease. There are an estimated 7 million people in Europe with Alzheimer’s disease, a number expected to double by 2030, according to the European Brain Council.2Analysis of RNA sequencing (RNA-seq) of the placebo-controlled Phase 2b/3 blarcamesine trial in early Alzheimer’s disease is underway. Interim data expected by mid 2024.Ongoing ATTENTION-AD open-label extension 96-week trial. Interim data expected in the second half of 2024. Schizophrenia: The placebo-controlled ANAVEX®3-71-SZ-001 Phase 2 clinical study of ANAVEX®3-71 for the treatment of schizophrenia is well underway with the first cohort of schizophrenia patients fully enrolled.Parkinson’s disease: Initiation of ANAVEX®2-73 imaging-focused trial and Phase 2b/3 6 month trial is expected in the second half of 2024.Rett syndrome: Continued positive Real World Evidence (RWE) feedback from Rett syndrome patients and caregivers from the ongoing open-label extension trial and Compassionate Use Program for patients who participated in the Phase 2/3 EXCELLENCE trial encourages us to continue our partnership with the Rett syndrome community and to proceed with a Phase 3 12-week efficacy study. An educational presentation will be provided at the 2024 IRSF Rett Syndrome Scientific Meeting, taking place June 18 – June 19, 2024. ANAVEX®2-73 had previously received Fast Track designation, Rare Pediatric Disease designation and Orphan Drug designation from the FDA for the treatment of Rett syndrome.Fragile X: New disease-specific, translatable, and objective biomarker data generated with ANAVEX®2-73, supporting the initiation of the potentially pivotal ANAVEX®2-73 Phase 2/3 clinical trial will be presented at the 19th National Fragile X Foundation Conference, taking place July 25 – July 28, 2024.New Rare disease: Initiation of potentially pivotal ANAVEX®2-73 Phase 2/3 clinical trial.Publications: Continued clinical publications involving ANAVEX®2-73 and ANAVEX®3-71. Recent Business Highlights: On March 18, 2024, the Company announced that the first patient in its U.S. FDA cleared placebo-controlled Phase 2 clinical study of ANAVEX®3-71 for the treatment of schizophrenia had been screened, ahead of schedule.On January 24, 2024, the Company announced a peer-reviewed publication in Clinical Pharmacology in Drug Development, findings from the ANAVEX®3-71 first-in-human study which achieved its safety objectives. The publication is entitled, ‘Population-Based Characterization of the Pharmacokinetics and Food Effect of ANAVEX3-71, a Novel Sigma-1 Receptor and Allosteric M1 Muscarinic Receptor Agonist in Development for Treatment of Frontotemporal Dementia, Schizophrenia, and Alzheimer Disease’.3 The publication reports pharmacokinetic (PK) dose proportionality of ANAVEX®3-71 in humans and food had no effect on the PK of ANAVEX®3-71. This data also expands the safety objectives met in this first-in-human study of ANAVEX®3-71, further supporting its drug development program.On January 8, 2024, the Company announced that the United States Patent and Trademark Office (USPTO) granted U.S. Patent No. 11,839,600 entitled “NEURODEVELOPMENTAL DISORDER THERAPY” from the United States Patent and Trademark Office (USPTO) for its patent application number 17/890,083. Anavex’s newest patent expands coverage of ANAVEX®2-73 (blarcamesine) therapy to ameliorate various conditions associated with loss-of-function mutations of the gene encoding methyl-CpG binding protein (MeCP2). Financial Highlights: Cash and cash equivalents of $139.4 million at March 31, 2024 compared to $151.0 million at fiscal yearend September 30, 2023. The Company anticipates at the current cash utilization rate a runway of approximately 4 years.General and administrative expenses for the quarter of $2.8 million compared to $2.9 million for the comparable quarter of fiscal 2023.Research and development expenses for the quarter of $9.7 million compared to $11.3 million for the comparable quarter of fiscal 2023.Net loss for the quarter of $10.5 million, or $0.13 per share, compared to a net loss of $13.1 million, or $0.17 per share for the comparable quarter of fiscal 2023. The financial information for the fiscal quarter ended March 31, 2024, should be read in conjunction with the Company’s condensed consolidated interim financial statements, which will appear on EDGAR, www.sec.gov and will be available on the Anavex website at www.anavex.com. Webcast / Conference Call Information: The live webcast of the conference call will be available on Anavex’s website at www.anavex.com. The conference call can be also accessed by dialing 1 929 205 6099 for participants in the U.S. using the Meeting ID# 815 2682 8440 and reference passcode 121725. A replay of the conference call will also be available on Anavex’s website for up to 30 days. 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, Rett syndrome, schizophrenia 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 in pediatric patients with Rett syndrome. ANAVEX®2-73 is an orally available drug candidate that restores 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. Anavex Life Sciences Corp.Condensed Consolidated Interim Statements of Operations and Comprehensive Loss(in thousands, except share and per share amounts) Three months ended March 31, 20242023Operating Expenses General and administrative$2,790 $2,883 Research and development 9,729 11,307 Total operating expenses 12,519 14,190 Operating loss (12,519) (14,190) Other income Research and development incentive income 472 750 Interest income, net 1,756 1,465 Other financing expense - (964)Foreign exchange gain (loss), net (150) (118)Total other income, net 2,078 1,133 Net loss before provision for income taxes (10,441) (13,057)Income tax expense, current (105) (50)Net loss and comprehensive loss$ (10,546)$ (13,107) Net loss per share Basic and diluted$(0.13)$(0.17) Weighted average number of shares outstanding Basic and diluted 82,464,226 78,304,363 Anavex Life Sciences Corp.Condensed Consolidated Interim Statements of Operations and Comprehensive Loss(in thousands, except share and per share amounts) Six months ended March 31, 20242023Operating Expenses General and administrative$5,399 $6,200 Research and development 18,413 23,373 Total operating expenses 23,812 29,573 Operating loss (23,812) (29,573) Other income Grant income - 25 Research and development incentive income 1,064 1,483 Interest income, net 3,764 2,733 Other financing expense - (964)Foreign exchange gain (loss), net 7 247 Total other income, net 4,835 3,524 Net loss before provision for income taxes (18,977) (26,049)Income tax expense, current (191) (30)Net loss and comprehensive loss$ (19,168)$ (26,079) Net loss per share Basic and diluted$(0.23)$(0.33) Weighted average number of shares outstanding Basic and diluted 82,269,965 78,138,940 Anavex Life Sciences Corp.Condensed Consolidated Interim Balance Sheets(in thousands, except share and per share amounts) March 31, September 30, 20242023Assets Current Cash and cash equivalents$139,386 $151,024 Incentive and tax receivables3,785 2,709 Prepaid expenses and other current assets1,345 653 Total Assets$144,516 $154,386 Liabilities and stockholders' equity Current Liabilities Accounts payable$3,726 $4,322 Accrued liabilities4,915 7,295 Deferred grant income917 917 Total Liabilities9,558 12,534 Capital Stock84 82 Additional paid-in capital447,345 434,839 Share proceeds receivable(234)- Accumulated deficit(312,237)(293,069)Total Stockholders' Equity134,958 141,852 Total Liabilities and Stockholders' Equity$144,516 $154,386 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 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/early-alzheimers-disease-developing-drugs-treatment 2 https://www.braincouncil.eu/projects/rethinking-alzheimers-disease/ 3 Fadiran EO, Hammond E, Tran J, Missling CU, Ette E. Population-Based Characterization of the Pharmacokinetics and Food Effect of ANAVEX3-71, a Novel Sigma-1 Receptor and Allosteric M1 Muscarinic Receptor Agonist in Development for Treatment of Frontotemporal Dementia, Schizophrenia, and Alzheimer Disease. Clin Pharmacol Drug Dev. 2024;13(1):21-31. doi:10.1002/cpdd.1323

New analyses suggest REXULTI was associated with reductions in overall neuropsychiatric symptoms and in agitation symptoms REXULTI was associated with reductions in occupational disruptiveness/caregiver distress as early as four weeks Efficacy of REXULTI for agitation symptoms confirmed across dementia severity, care setting, concomitant/prior medication use, and co-occurring neuropsychiatric symptoms REXULTI was associated with improvement in agitation symptoms in patients with and without psychosis symptoms at baseline PRINCETON, N.J. & DEERFIELD, Ill.--(BUSINESS WIRE)-- Otsuka Pharmaceutical Development & Commercialization, Inc. (Otsuka) and Lundbeck U.S., the U.S. subsidiaries of H. Lundbeck A/S, (Lundbeck) presented new post hoc pooled analyses of two pivotal Phase 3 trials evaluating the safety and efficacy of REXULTI® (brexpiprazole) in patients with agitation associated with dementia due to Alzheimer’s disease.1 The posters were presented on March 16 at the American Association for Geriatric Psychiatry (AAGP) 2024 Annual Meeting in Atlanta. This press release features multimedia. View the full release here: REXULTI is the first treatment approved by the U.S. Food and Drug Administration (FDA) for agitation associated with dementia due to Alzheimer’s disease.2 Agitation associated with dementia due to Alzheimer’s disease is a common neuropsychiatric condition reported in approximately half of all patients with dementia due to Alzheimer’s disease and one of the most complex and stressful aspects of caring for people living with dementia due to Alzheimer’s disease.3 Agitation symptoms include behaviors such as pacing, gesturing, profanity, shouting, shoving, and hitting.4 Otsuka and Lundbeck presented three practice-relevant posters containing post hoc analyses on the efficacy of REXULTI in patients with agitation associated with dementia due to Alzheimer’s disease, and caregiver impact at the meeting. One poster utilized the Neuropsychiatric Inventory (NPI) to explore the relationship of REXULTI on neuropsychiatric symptoms relating to agitation and occupational disruptiveness/caregiver distress related to patients’ behavior. The NPI, which is administered through a structured caregiver interview, is comprised of 12 domains of neuropsychiatric symptoms including agitation/aggression, irritability/lability, and disinhibition. Each domain is scored from best to worst based on frequency, severity, and occupational disruptiveness/caregiver distress. The analysis demonstrated that REXULTI was associated with reductions in overall neuropsychiatric symptoms and in agitation symptoms (as captured by the NPI) compared with placebo over 12 weeks. In addition, REXULTI was associated with a greater reduction in occupational disruptiveness/caregiver distress total score compared to placebo, with separation observed as early as Week 4.1 Another poster explored the efficacy of REXULTI on symptoms of agitation across different patient characteristic subgroups that are common in clinical practice, including baseline dementia severity, care setting, concomitant/prior medication use, and baseline co-occurring NPI symptoms (excluding agitation). A responder analysis based on a meaningful within-patient change threshold of ≥20-point reduction from baseline to Week 12 in the CMAI Total score was also conducted. The post-hoc analysis demonstrated that REXULTI was associated with greater improvement in symptoms of agitation than placebo across all subgroups as measured by the change from baseline in Cohen-Mansfield Agitation Inventory (CMAI) total score at Week 12.5 The final poster looked at the efficacy and safety of REXULTI in patients grouped by baseline psychosis status (with psychosis and without psychosis), with approximately a quarter of patients presenting with psychosis symptoms at baseline. The analysis showed fixed-dose REXULTI 2 or 3 mg/day was associated with greater improvements in agitation symptoms compared with placebo in both subgroups, as measured by the change in CMAI total score at Week 12. In addition, the safety and tolerability of REXULTI 0.5-3mg/day was similar between the subgroups.6 “It’s well known that the effects of dementia due to Alzheimer’s disease extend beyond the patient to caregivers whose lives are often disrupted in order to meet the significant demands of care,” said George T. Grossberg, MD, Department of Psychiatry and Behavioral Neuroscience at Saint Louis University School of Medicine. “These new analyses are important because they are the first to explore the potential impact of addressing agitation symptoms with brexpiprazole on caregiver-reported distress.” “These data reinforce the urgency to treat agitation separately from dementia due to Alzheimer’s disease and gives prescribers further confidence to choose an FDA-approved therapy to help address these symptoms,” said John Kraus, M.D., Ph.D., executive vice president and chief medical officer, Otsuka. “We greatly appreciate the efforts of the caregivers and their families that participated in these important clinical trials.” “Family caregivers typically spend more than 20 hours a week caring for a loved one with Alzheimer’s disease,”7 said Johan Luthman, executive vice president, Lundbeck Research & Development. “The breadth of data presented at AAGP represents our continued commitment to understanding the full potential of REXULTI on agitation associated with dementia due to Alzheimer’s disease.” About Agitation Associated with Dementia Due to Alzheimer’s Disease Agitation associated with dementia due to Alzheimer’s disease is a common neuropsychiatric symptom that is reported in approximately half of all patients with dementia due to Alzheimer’s disease.3 The condition has a large impact on the quality of life for the patients, family members, and caregivers.3,8 Agitation associated with dementia due to Alzheimer’s disease covers a large group of behaviors occurring in patients with dementia due to Alzheimer’s disease, such as pacing, gesturing, profanity, shouting, shoving, and hitting.8 Symptoms of agitation are also a consistent predictor of nursing home admission in patients with dementia, including those with Alzheimer’s disease.9-11 About Brexpiprazole Brexpiprazole was approved in the U.S. in 2015 as an adjunctive therapy to antidepressants in adults with major depressive disorder (MDD) and as a treatment for schizophrenia in adults. Brexpiprazole was also approved by Health Canada for schizophrenia and adjunctive treatment of MDD in 2017 and 2019, respectively. It was approved by the Ministry of Health, Labour and Welfare in Japan and by the European Medicines Agency (EMA) in 2018 for the treatment of schizophrenia. Brexpiprazole was discovered by Otsuka and is being co-developed by Otsuka and Lundbeck. The mechanism of action of brexpiprazole is unknown, however the efficacy of brexpiprazole may be mediated through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, and antagonist activity at serotonin 5-HT2A receptors. INDICATIONS and IMPORTANT SAFETY INFORMATION for REXULTI® (brexpiprazole) INDICATIONS: REXULTI is a prescription medicine used: along with antidepressant medicines to treat major depressive disorder (MDD) in adults to treat schizophrenia in adults and children ages 13 years and older to treat agitation that may happen with dementia due to Alzheimer’s disease REXULTI should not be used as an “as needed” treatment for agitation that may happen with dementia due to Alzheimer’s disease. It is not known if REXULTI is safe and effective in children with MDD. It is not known if REXULTI is safe and effective in children under 13 years of age with schizophrenia. IMPORTANT SAFETY INFORMATION: Increased risk of death in elderly people with dementia-related psychosis. Medicines like REXULTI can raise the risk of death in elderly people who have lost touch with reality (psychosis) due to confusion and memory loss (dementia). REXULTI is not approved for the treatment of people with dementia-related psychosis without agitation that may happen with dementia due to Alzheimer’s disease. Increased risk of suicidal thoughts and actions. REXULTI and antidepressant medicines may increase suicidal thoughts and actions in some people 24 years of age and younger, especially within the first few months of treatment or when the dose is changed. Depression and other mental illnesses are the most important causes of suicidal thoughts and actions. Patients on antidepressants and their families or caregivers should watch for new or worsening depression symptoms, especially sudden changes in mood, behaviors, thoughts, or feelings. Report any change in these symptoms immediately to the doctor. Do not take REXULTI if you are allergic to brexpiprazole or any of the ingredients in REXULTI. REXULTI may cause serious side effects, including: Cerebrovascular problems, including stroke, in elderly people with dementia-related psychosis that can lead to death. Neuroleptic malignant syndrome (NMS) is a serious condition that can lead to death. Call your healthcare provider or go to the nearest hospital emergency room right away if you have some or all of the following signs and symptoms of NMS: high fever; changes in your pulse, blood pressure, heart rate, and breathing; stiff muscles; confusion; increased sweating Uncontrolled body movements (tardive dyskinesia). REXULTI may cause movements that you cannot control in your face, tongue, or other body parts. Tardive dyskinesia may not go away, even if you stop taking REXULTI. Tardive dyskinesia may also start after you stop taking REXULTI. Problems with your metabolism such as: high blood sugar (hyperglycemia) and diabetes. Increases in blood sugar can happen in some people who take REXULTI. Extremely high blood sugar can lead to coma or death. Your healthcare provider should check your blood sugar before you start, or soon after you start REXULTI and then regularly during long term treatment with REXULTI. Call your healthcare provider if you have any of these symptoms of high blood sugar during treatment with REXULTI: feel very thirsty feel very hungry feel sick to your stomach need to urinate more than usual feel weak or tired feel confused, or your breath smells fruity increased fat levels (cholesterol and triglycerides) in your blood. Your healthcare provider should check the fat levels in your blood before you start, or soon after you start REXULTI, and then periodically during treatment with REXULTI. weight gain. You and your healthcare provider should check your weight before you start and often during treatment with REXULTI. Unusual and uncontrollable (compulsive) urges. Some people taking REXULTI have had strong unusual urges, to gamble and gambling that cannot be controlled (compulsive gambling). Other compulsive urges include sexual urges, shopping, and eating or binge eating. If you or your family members notice that you are having new or unusual strong urges or behaviors, talk to your healthcare provider. Low white blood cell count. Your healthcare provider may do blood tests during the first few months of treatment with REXULTI. Decreased blood pressure (orthostatic hypotension) and fainting. You may feel dizzy, lightheaded or pass out (faint) when you rise too quickly from a sitting or lying position. Falls. REXULTI may make you sleepy or dizzy, may cause a decrease in your blood pressure when changing position (orthostatic hypotension), and can slow your thinking and motor skills which may lead to falls that can cause fractures or other injuries. Seizures (convulsions). Problems controlling your body temperature so that you feel too warm. Do not become too hot or dehydrated during treatment with REXULTI. Do not exercise too much. In hot weather, stay inside in a cool place if possible. Stay out of the sun. Do not wear too much clothing or heavy clothing. Drink plenty of water. Difficulty swallowing that can cause food or liquid to get into your lungs. Sleepiness, drowsiness, feeling tired, difficulty thinking and doing normal activities. Do not drive a car, operate machinery, or do other dangerous activities until you know how REXULTI affects you. REXULTI may make you feel drowsy. Before taking REXULTI, tell your healthcare provider about all of your medical conditions, including if you: have or have had heart problems or a stroke have or have had low or high blood pressure have or have had diabetes or high blood sugar or a family history of diabetes or high blood sugar. Your healthcare provider should check your blood sugar before you start REXULTI and during treatment with REXULTI. have or have had high levels of total cholesterol, LDL cholesterol, or triglycerides, or low levels of HDL cholesterol have or have had seizures (convulsions) have or have had kidney or liver problems have or have had a low white blood cell count are pregnant or plan to become pregnant. REXULTI may harm your unborn baby. Taking REXULTI during your third trimester of pregnancy may cause your baby to have abnormal muscle movements or withdrawal symptoms after birth. Talk to your healthcare provider about the risk to your unborn baby if you take REXULTI during pregnancy. Tell your healthcare provider if you become pregnant or think you are pregnant during treatment with REXULTI. There is a pregnancy exposure registry for women who are exposed to REXULTI during pregnancy. If you become pregnant during treatment with REXULTI, talk to your healthcare provider about registering with the National Pregnancy Registry for Atypical Antipsychotics. You can register by calling 1-866-961-2388 or visit . are breastfeeding or plan to breastfeed. It is not known if REXULTI passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with REXULTI. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. REXULTI and other medicines may affect each other causing possible serious side effects. REXULTI may affect the way other medicines work, and other medicines may affect how REXULTI works. Your healthcare provider can tell you if it is safe to take REXULTI with your other medicines. Do not start or stop any medicines during treatment with REXULTI without first talking to your healthcare provider. The most common side effects of REXULTI include weight gain, sleepiness, dizziness, common cold symptoms, and restlessness or feeling like you need to move (akathisia). These are not all the possible side effects of REXULTI. For more information, ask your healthcare provider or pharmacist. You are encouraged to report side effects of REXULTI (brexpiprazole). Please contact Otsuka America Pharmaceutical, Inc. at 1-800-438-9927 or FDA at 1-800-FDA-1088 ( ). Please read FULL PRESCRIBING INFORMATION, including BOXED WARNING, and MEDICATION GUIDE for REXULTI. About Otsuka Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the corporate philosophy: Otsuka–people creating new products for better health worldwide. Otsuka researches, develops, manufactures, and markets innovative products, with a focus on pharmaceutical products to meet unmet medical needs and nutraceutical products for the maintenance of everyday health. In pharmaceuticals, Otsuka is a leader in the challenging areas of mental, renal, and cardiovascular health and has additional research programs in oncology and on several under-addressed diseases including tuberculosis, a significant global public health issue. These commitments illustrate how Otsuka is a “big venture” company at heart, applying a youthful spirit of creativity in everything it does. Otsuka established a presence in the U.S. in 1973 and today its U.S. affiliates include Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC) and Otsuka America Pharmaceutical, Inc. (OAPI). These two companies’ 2,000 employees in the U.S. develop and commercialize medicines in the areas of mental health and nephrology, using cutting-edge technology to address unmet healthcare needs. OPDC and OAPI are indirect subsidiaries of Otsuka Pharmaceutical Company, Ltd., which is a subsidiary of Otsuka Holdings Co., Ltd. headquartered in Tokyo, Japan. The Otsuka group of companies employed 47,000 people worldwide and had consolidated sales of approximately USD 14.2 billion in 2023. All Otsuka stories start by taking the road less traveled. Learn more about Otsuka in the U.S. at and connect with us on LinkedIn and Twitter at @OtsukaUS. Otsuka Pharmaceutical Co., Ltd.’s global website is accessible at About Lundbeck Lundbeck US refers to the wholly owned US subsidiaries of H. Lundbeck A/S (HLUNa / HLUNb, HLUNA DC / HLUNB DC), a global pharmaceutical company specialized in brain diseases, including Lundbeck LLC and Lundbeck Pharmaceuticals LLC. For more than 70 years, we have been at the forefront of neuroscience research. We are tirelessly dedicated to restoring brain health, so every person can be their best. We have approximately 5,400 employees in more than 50 countries, and our products are available in more than 100 countries. Our research programs tackle some of the most complex challenges in neuroscience, and our pipeline is focused on bringing forward transformative treatments for brain diseases for which there are few, if any therapeutic options. We have research facilities in Denmark and the United States, and our production facilities are located in Denmark, France and Italy. In the United States, H. Lundbeck A/S subsidiaries, including Lundbeck LLC and Lundbeck Pharmaceuticals LLC, employ more than 1,000 people focused solely on accelerating therapies for brain disorders. With a special commitment to the lives of patients, families and caregivers, Lundbeck US actively engages in a broad range of initiatives each year that support patient communities. For additional information, we encourage you to visit us at lundbeck.com/us and connect with us on LinkedIn and Twitter at @LundbeckUS. References Brubaker M, Wang D, Chumki S, et al. Efficacy of Brexpiprazole Across Agitation Behaviors in Alzheimer’s Disease, Including Impact on Caregivers, Analyzed Using the Neuropsychiatric Inventory: a Post Hoc Pooled Analysis of Randomized, Fixed-dose, Placebo-controlled Trials. American Association for Geriatric Psychiatry (AAGP), Atlanta, Ge., March-15-18, 2024. FDA News Release. FDA Approves First Drug to Treat Agitation Symptoms Associated with Dementia due to Alzheimer’s Disease. Published: May 11, 2023. Last accessed: Feb 20, 2024. Available at: Halpern R, Seare J, Tong J, Hartry A, Olaoye A, Aigbogun MS. Using electronic health records to estimate the prevalence of agitation in Alzheimer disease/dementia. Int J Geriatr Psychiatry. 2019;34(3):420-431. Cummings J, Mintzer J, Brodaty H, et al. Agitation in cognitive disorders: International Psychogeriatric Association provisional consensus clinical and research definition. Int Psychogeriatr. 2015;27(1):7-17. Brubaker M, Wang D, Chumki S, et al. Efficacy of Brexpiprazole in Patients With Agitation Associated With Dementia Due to Alzheimer’s Disease Analyzed by Patient Characteristics: a Post Hoc Pooled Analysis of Randomized, Fixed-dose, Placebo-controlled Trials. American Association for Geriatric Psychiatry (AAGP), Atlanta, Ge., March-15-18, 2024. Behl S, Chang D, Chen D, et. al. Efficacy of Brexpiprazole in Patients with Agitation Associated With Alzheimer’s Dementia Analyzed by Presence or Absence of Psychosis: a Pooled Analysis. American Association for Geriatric Psychiatry (AAGP), Atlanta, Ge., March-15-18, 2024. Alzheimer’s Association. 2015 Alzheimer’s Disease Facts and Figures. Alzheimer’s & Dementia 2015;11(3)332. Last accessed: 07 Mar, 2024. Available at: Fillit H, Aigbogun MS, Gagnon-Sanschagrin P, et al. Impact of agitation in long-term care residents with dementia in the United States. Int J Geriatr Psychiatry. 2021;36(12):1959-1969. Gaugler JE, Yu F, Krichbaum K, Wyman JF. Predictors of nursing home admission for persons with dementia [published correction appears in Med Care. 2009 May;47(5):606]. Med Care. 2009;47(2):191-198. Kales HC, Chen P, Blow FC, Welsh DE, Mellow AM. Rates of clinical depression diagnosis, functional impairment, and nursing home placement in coexisting dementia and depression. Am J Geriatr Psychiatry. 2005;13(6):441-449. Yaffe K, Fox P, Newcomer R, et al. Patient and caregiver characteristics and nursing home placement in patients with dementia. JAMA. 2002;287(16):2090-2097.

Baseline Data from Phase 3 Trial of NE3107 Presented as Poster at the American Diabetes Association Annual MeetingCARSON CITY, Nev., June 26, 2023 (GLOBE NEWSWIRE) -- BioVie Inc., (NASDAQ: BIVI) (“BioVie” or the “Company”) a clinical-stage company developing innovative drug therapies for the treatment of neurological and neurodegenerative disorders and advanced liver disease, today announced that baseline data from its multicenter, randomized, placebo-controlled Phase 3 study (NCT04669028) of NE3107 in patients with mild to moderate Alzheimer’s Disease (AD) was presented as a poster at the 83rd Scientific Sessions of the American Diabetes Association, to be held June 23-26, 2023 in San Diego, CA. NE3107 is an oral small molecule, blood-brain permeable anti-inflammatory insulin sensitizer that binds extracellular signal-regulated kinase. BioVie’s Phase 3 trial is the largest study to date to evaluate the safety and efficacy of NE3107 in patients with AD. NE3107 is the only anti-inflammatory agent currently in phase 3 development for AD. Consistent with the proposed anti-inflammatory and insulin-sensitizing properties of NE3107, this phase 3 study was designed to confirm the efficacy and safety of NE3107 treatment in patients with probable AD. The poster, Metabolic Dysregulation in Probable Alzheimer’s Disease (Christopher Reading, et al), discussed the role of insulin resistance and neuroinflammation in the risk of mild cognitive impairment, and details baseline metabolic and inflammation characteristics from the Phase 3 study (see Table 1), including data on the regulation of glycemia. Presenters noted that at baseline, the majority of patients had a high WHR (85%), hypertension (61%), and impaired glucose metabolism (IFG/T2D; 52%); almost half of all patients (47%) had some degree of insulin resistance; 40% and 30% of patients had hypertriglyceridemia and hypercholesterolemia, respectively; and patients had elevated inflammatory markers. Both Aβ+ and Aβ− patients with AD were enrolled in the study and had comparable CDR-SB scores indicative of mild dementia, but while Aβ+ patients had worse ADAS-Cog12 and MMSE scores, indicating lower cognitive functioning, Aβ− patients had significantly higher inflammation, insulin resistance, IFG, and hypertension, compared to their Aβ+ counterparts. Additional subgroup analysis revealed higher degrees of impaired glucose metabolism and insulin resistance among the APOE ε4− patients compared to their APOE ε4+ counterparts and comparable baseline MMSE scores, indicating that both groups had mild to moderate cognitive impairment. Investigators concluded that in the absence of classical risk markers, such as Aβ+ and APOE ε4+, central obesity (high WHR) and age-related systems dysregulation, involving inflammation (elevated CRP, RANTES, and C1q), hyperglycemia, insulin resistance, dyslipidemia, and hypertension, may contribute to probable AD and disease progression. Table 1. Baseline CharacteristicsCharacteristic AllAβ+aAβ−bPAPOE ε4+APOE ε4−PN=378n=57n=77 n=97n=259Age, mean (SE) y73 (0.3)76 (0.8)72 (0.6)**73 (0.6)73 (0.4)-Female, %555367-6464-High WHRc, %858484-8182-FPG, mean, mg/dL112100112*106115* IFG, %321835#2536- T2D, %201422-1725 Fasting insulin, mean (SE), µlU/mL16 (1.1)10 (1.0)15 (2.4)*12 (1.1)17 (1.6)* High (>23), %15915-1017-HOMA2-IR, mean (SE)1.8 (0.1)1.3 (0.2)1.9 (0.2)*1.5 (0.1)1.9 (0.1)* 1.4-2.5, %271329##2427- >2.5, %201521-1522-MAGE, mean (SE), mg/dL70 (2.5)62 (3.4)68 (4.6)-68 (4.2)71 (3.1)-CRP, mean (SE), mg/L4.1 (0.4)1.8 (0.2)6.3 (1.2)**3.6 (0.8)4.3 (0.4)- >3, %671328#2032 >10, %18018##421C1q, mean (SE), mg/dL22 (0.2)21 (0.4)44 (0.5)-21 (0.3)22 (0.2)- High (>22), %322833-3431-RANTES, mean (SE), pg/mL28 (1.6)23 (2.0)33 (2.8)**26 (2.8)29 (2.0)-Cholesterol,189 (4)174 (5)175 (5)-183 (4)180 (3)-mean (SE), mg/dL302226-3030- High (>199), % Triglycerides,143 (4)130 (9)143 (8)-132 (5)148 (5)-mean (SE), mg/dL402736-3641- High (>149), % High BP (>130/80), %614771##5463-Low BP (<66 diastolic), %13122.5##154.1##CDR-SB, mean (SE)6.3 (0.1)6.6 (0.3)6.2 (0.2)-6.6 (0.2)6.1 (0.1)**MMSE, mean (SE)20 (0.1)20 (0.1)21 (0.2)**20 (0.2)20 (0.1)-ADAS-Cog12,28 (0.4)31 (1.4)25 (0.7)**30 (0.9)27 (0.5)**mean (SE)ADCS-ADL, mean (SE)55 (0.6)57 (1.4)57 (1.2)-56 (1.0)55 (0.5)-Aβ42/40 ratio,0.0950.085 (0.001)0.107 (0.001)**0.0890.098**mean (SE)-0.001-0.002-0.001aPositive Precivity test; bNegative Precivity test; cFor females WHR>0.8 and for males WHR>0.95; Mann-Whitney *P <0.05, **P<0.01; Fisher’s Exact Test #<0.05, ## <0.01. About BioVie BioVie Inc. (NASDAQ: BIVI) is a clinical-stage company developing innovative drug therapies for the treatment of neurological and neurodegenerative disorders and advanced liver disease. In neurodegenerative disease, the Company’s drug candidate NE3107 inhibits inflammatory activation of ERK and NFkB (e.g., TNF signaling) that leads to neuroinflammation and insulin resistance, but not their homeostatic functions (e.g., insulin signaling and neuron growth and survival). Both are drivers of Alzheimer’s and Parkinson’s diseases. The Company is conducting a potentially pivotal Phase 3 randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate NE3107 in patients who have mild to moderate Alzheimer's disease (NCT04669028). Results of a Phase 2 investigator initiated trial (NCT05227820) showing NE3107-treated patients experienced improved cognition and biomarker levels were presented at the Clinical Trial in Alzheimer’s Disease (CTAD) annual conference in December 2022. An estimated six million Americans suffer from Alzheimer’s. A Phase 2 study of NE3107 in Parkinson’s disease (NCT05083260) has completed, and data presented at the International Conference on Alzheimer's and Parkinson's Disease and Related Neurological Disorders conference in Gothenburg, Sweden in March 2023 showed significant improvements in “morning on” symptoms and clinically meaningful improvement in motor control in patients treated with a combination of NE3107 and levodopa vs. patients treated with levodopa alone, and no drug-related adverse events. In liver disease, the Company’s Orphan drug candidate BIV201 (continuous infusion terlipressin), with FDA Fast Track status, is being evaluated in a US Phase 2b study for the treatment of refractory ascites due to liver cirrhosis. BIV201 is administered as a patent-pending liquid formulation. The active agent is approved in the U.S. and in about 40 countries for related complications of advanced liver cirrhosis. For more information, visit http://www.bioviepharma.com/. Forward-Looking Statements This press release contains forward-looking statements, including statements regarding the Company’s strategy, plans and objectives, such as statements regarding the Company’s anticipated timeline for announcing results from the NE3107 Phase 3 potential pivotal trials. Forward-looking statements may generally be identified by words such as "expect," "look forward to," "anticipate" "intend," "plan," "believe," "seek," "estimate," "will," "project" or words of similar meaning. Although BioVie Inc. believes such forward-looking statements are based on reasonable assumptions, it can give no assurance that its expectations will be attained. Actual results may vary materially from those expressed or implied by the statements herein due risks associated with conducting and completing clinical trials, including our reliance on third parties to conduct our clinical trials, to successfully defend potential future litigation, our ability to raise capital when needed on reasonable terms, changes in local or national economic conditions as well as various additional risks, many of which are now unknown and generally out of the Company's control, and which are detailed from time to time in reports filed by the Company with the SEC, including quarterly reports on Form 10-Q, reports on Form 8-K and annual reports on Form 10-K. BioVie Inc. does not undertake any duty to update any statements contained herein (including any forward-looking statements), except as required by law.  For Investor Relations Inquiries: Contact: Bruce Mackle Managing Director LifeSci Advisors, LLC bmackle@lifesciadvisors.com