M1 receptor

First patient screened ahead of schedule Trial to investigate positive, negative, and cognitive domains of schizophrenia ANAVEX®3-71’s differentiated dual novel mechanism of action offers the potential to synergistically activate both SIGMAR1 and M1 muscarinic receptors and treat all symptom domains of schizophrenia without the side effects of standard of care antipsychotics NEW YORK, March 18, 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 psychiatric disorders, including Alzheimer's disease, Parkinson's disease, Rett syndrome, schizophrenia, and other central nervous system (CNS) diseases, today 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 has been screened ahead of schedule. “Initiating our Phase 2 trial of ANAVEX®3-71 in schizophrenia ahead of schedule is a testament to the hard work and dedication of our clinical study team,” stated Christopher U Missling, PhD, President and Chief Executive Officer of Anavex. “Schizophrenia is a challenging disorder that can impair social and occupational functions and overall quality of life for the nearly 24 million people affected worldwide. Following on from our positive initial Phase 1 results in healthy volunteers, our Phase 2 study will apply novel neuroinflammatory, metabolomic, and transcriptomic biomarkers at the intersection of schizophrenia pathophysiology and ANAVEX®3-71’s novel, dual mechanism of action, with the goal of addressing the large unmet need in this patient population. We are excited to build on our diverse Precision Medicine Platform, which advanced blarcamesine (ANAVEX®2-73) onto a regulatory pathway for potential treatment of Alzheimer’s disease.” ANAVEX®3-71’s differentiated mechanism is a dual SIGMAR1 receptor agonist and M1 positive allosteric modulator with agonistic effects.1,2 This novel mechanism of action offers the potential to treat all symptom domains of schizophrenia -- positive symptoms (hallucinations and delusions), negative symptoms (difficulty enjoying life and withdrawal from others), and cognitive impairment (deficits in memory, concentration, and decision-making) -- without the side effects of standard of care antipsychotics, which do not adequately address all symptom domains in schizophrenia. ANAVEX®3-71’s ability to modulate both SIGMAR1 and M1 receptors is expected to potentially address disruptions to neuronal homeostasis observed in individuals with schizophrenia, upstream of the targets leveraged by standard of care medications. Preceding this study, ANAVEX®3-71 demonstrated an adequate safety profile in a Phase 1 trial in healthy volunteers.3,4 ANAVEX®3-71 Phase 2 Program Outline The placebo-controlled Phase 2, two-part, in-patient trial, ANAVEX®3-71-SZ-001 (NCT06245213), will investigate the effects of ANAVEX®3-71 in patients with schizophrenia. Part A is a double-blind, placebo-controlled, multiple ascending dose trial. The results of Part A will be used to select a dose for Part B, a proof-of-concept efficacy, double-blind, placebo-controlled trial.Participants will undergo either 10 or 28 days of dosing (Part A and Part B, respectively).Standard clinical outcome measures, including the Positive and Negative Syndrome Scale (PANSS), and novel fluid and electrophysiological biomarkers will be assessed. Anavex is leveraging several advances in electroencephalography/event-related potential (EEG/ERP) biomarkers in schizophrenia developed in collaboration with the industry-led ERP Biomarker Qualification Consortium.5 This includes a validated, and automated data analysis pipeline for quantitative EEG and ERP biomarkers, as well as normative EEG/ERP data in patients with schizophrenia and matched healthy volunteers. These advances also include recently established relationships between EEG/ERP biomarkers and clinically important measures in schizophrenia. In addition to the electrophysiological biomarkers, Anavex is applying novel neuroinflammatory, metabolomic, and transcriptomic biomarkers at the intersection of schizophrenia pathophysiology and ANAVEX®3-71’s novel, dual mechanism of action. About Schizophrenia Schizophrenia is a persistent and often disabling mental illness impacting how a person thinks, feels, and behaves, and affects nearly 24 million people worldwide, including 2.8 million people in the U.S. It is characterized by three symptom domains: positive symptoms (hallucinations and delusions), negative symptoms (difficulty enjoying life and withdrawal from others), and cognitive impairment (deficits in memory, concentration, and decision-making). In part due to limitations with current treatments, people living with schizophrenia often struggle to maintain employment, live independently, and manage relationships. While current treatments can be effective in managing select symptoms, approximately 34% of people do not respond to therapy, 6 with an additional 50-60% experiencing only a partial improvement in symptoms or unacceptable side effects.7 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 and neurodevelopmental 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. 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 DevelopmentToll-free: 1-844-689-3939Email: info@anavex.com Investors:Andrew J. BarwickiInvestor RelationsTel: 516-662-9461Email: andrew@barwicki.com 1 Fisher A, Bezprozvanny I, Wu L, et al. AF710B, a Novel M1/σ1 Agonist with Therapeutic Efficacy in Animal Models of Alzheimer’s Disease. Neurodegener Dis. 2016;16(1-2):95-110. doi:10.1159/0004408642 Hall H, Iulita MF, Gubert P, et al. AF710B, an M1/sigma-1 receptor agonist with long-lasting disease-modifying properties in a transgenic rat model of Alzheimer's disease. Alzheimers Dement. 2018;14(6):811-823. doi:10.1016/j.jalz.2017.11.0093 Fadiran EO, Hammond E, Tran J, et al. Concentration-QTc Relationship from a Single Ascending Dose Study of ANAVEX3-71, a Novel Sigma-1 Receptor and Allosteric M1 Muscarinic Receptor Agonist in Development for the Treatment of Frontotemporal Dementia, Schizophrenia, and Alzheimer's Disease. Clin Pharmacol Drug Dev. 2023;12(9):888-901. doi:10.1002/cpdd.13034 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.13235 Cecchi M, Adachi M, Basile A, et al. Validation of a suite of ERP and QEEG biomarkers in a pre-competitive, industry-led study in subjects with schizophrenia and healthy volunteers. Schizophr Res. 2023;254:178-189. doi:10.1016/j.schres.2023.02.0186 Potkin SG, Kane JM, Correll CU, et al. The neurobiology of treatment-resistant schizophrenia: paths to antipsychotic resistance and a roadmap for future research. NPJ Schizophr. 2020;6(1):1. Published 2020 Jan 7. doi:10.1038/s41537-019-0090-z7 Nucifora FC Jr, Woznica E, Lee BJ, Cascella N, Sawa A. Treatment resistant schizophrenia: Clinical, biological, and therapeutic perspectives. Neurobiol Dis. 2019;131:104257. doi:10.1016/j.nbd.2018.08.016

Contineum Therapeutics has thrown its hat into the ring for a spring public debut. The neurology and inflammation-focused company filed for an IPO last week to fund clinical trials of its two lead programmes, including a multiple sclerosis (MS) and depression candidate that’s partnered with Johnson & Johnson. Formerly Pipeline Therapeutics, Contineum joins Boundless Bio in the IPO queue, which was the first biotech in March to signal its public interest following the rapid-fire offerings of late January and early February. The mid-stage oncology company has yet to set terms for its offering.Also in line for public offerings are several biotechs seeking sub-$30 million debuts: Aprinoia Therapeutics, Lirum Therapeutics, and Jyong Biotech.  MS, depression in the pipelineContineum’s clinical pipeline comprises two oral small molecules: LPA1R antagonist PIPE-791, and M1 muscarinic receptor antagonist PIPE-307.The former is a brain penetrant compound that’s completed Phase I studies for idiopathic pulmonary fibrosis (IPF) and progressive multiple sclerosis (MS). With the IPO proceeds, Contineum expects to start this year a Phase Ib PET imaging trial to measure the relationship of pharmacokinetics to lung and brain receptor occupancy, which will help inform dosing for Phase II trials for each indication.Johnson & Johnson has an exclusive, worldwide licence to the latter candidate, which is in development for relapsing/remitting MS and depression.Last year Contineum received $50 million upfront for rights to PIPE-307 and is eligible for up to $1 billion in milestones, plus low-double digit to high-teen tiered royalties. The company also received a $25 million equity investment from the US pharma’s venture capital arm, JJDC. Muscarinic receptor modulators have gained steam as of late for their potential in mood disorders, particularly schizophrenia. For more, see KOL Views Q&A: Leading psychiatrist sees a muscarinic revolution coming in schizophrenia and beyond.“To our knowledge, PIPE-307 is the most clinically advanced selective M1R antagonist in development,” the company said in the filing.  Contineum is in charge of a Phase II trial of PIPE-307 in relapsing/remitting MS; IPO proceeds are expected to help the biotech wrap up the study. Johnson & Johnson plans to start a Phase II trial this year of the candidate to treat depression.

NEW YORK, Feb. 26, 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 and neurodevelopmental disorders including Alzheimer’s disease, Parkinson’s disease, Rett syndrome, schizophrenia and other central nervous system (CNS) diseases, today announced that it will present at the 44th Annual TD Cowen Health Care Conference, March 4-6, 2024. Christopher U Missling, PhD, President & Chief Executive Officer will present the Company in a session scheduled at 1:30 PM (ET) on Monday, March 4th, 2024, at the Boston Marriott Copley Place in Boston, MA. 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. 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 and neurodevelopmental 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. 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 DevelopmentToll-free: 1-844-689-3939Email: info@anavex.com Investors:Andrew J. BarwickiInvestor RelationsTel: 516-662-9461Email: andrew@barwicki.com