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Part A of the placebo-controlled Phase 2 study has been completed ANAVEX®3-71 demonstrates a dose-dependent pharmacodynamic effect on objective EEG biomarkers of schizophrenia Patients are currently being dosed in Part B of the Phase 2 study which will investigate a longer treatment duration Oct. 17, 2024 -- Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq: AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of Alzheimer's disease, Parkinson's disease, schizophrenia, neurodevelopmental, neurodegenerative, and rare diseases, including Rett syndrome, and other central nervous system (CNS) diseases, today announced encouraging preliminary electroencephalography (EEG) biomarker results from the Part A of the ongoing placebo-controlled Phase 2 clinical study of ANAVEX®3-71 for the treatment of schizophrenia. Part A of the Phase 2 study ANAVEX®3-71-SZ-001 (NCT06245213), was a multiple ascending dose study in 16 participants treated with either oral placebo, oral ANAVEX®3-71 90 mg daily, or oral ANAVEX®3-71 180 mg daily for 10 days. Preliminary results demonstrated a dose-dependent effect of ANAVEX®3-71 on two key EEG biomarkers in patients with schizophrenia. Treatment with ANAVEX®3-71 compared to placebo resulted in improvements in 40 Hz Auditory Steady-State Response (ASSR) Inter Trial Coherence (ITC) and Resting State Alpha Power, both of which were increased. These effects were most pronounced in the higher dose group demonstrating a dose-dependent pharmacodynamic effect. These results provide evidence of CNS target engagement and potential therapeutic effects of ANAVEX®3-71 in schizophrenia. The observed changes reversed known EEG and ERP biomarker abnormalities associated with schizophrenia1. These EEG biomarkers correlate with positive, negative, and cognitive symptoms of schizophrenia. Individuals with schizophrenia typically have reduced neural synchrony as measured by 40 Hz ASSR ITC. Improvements in 40 Hz ASSR ITC indicate enhanced neural synchronization, potentially leading to reduced auditory hallucinations (positive symptom), improved executive function, and working memory (cognitive symptoms).2 Individuals with schizophrenia also typically have decreased resting state alpha power correlating with sensory and behavioral problems. Increases in Resting State Alpha Power reflect improvements in thalamocortical circuits and sensory gating, potentially resulting in reduced irritability and anxiety (negative symptoms).3 “We are pleased to see an initial effect of biomarkers changing in people with schizophrenia treated with our oral M1/SIGMAR1 therapy ANAVEX®3-71, which could eventually help patients address both positive, negative, and cognitive symptoms of schizophrenia,” said Christopher U Missling, PhD, President and Chief Executive Officer of Anavex. “The results are encouraging for further development of ANAVEX®3-71 for people with schizophrenia.” ANAVEX®3-71 was well tolerated, with no serious adverse events reported. Oral ANAVEX®3-71 is a dual SIGMAR1 receptor agonist and M1 positive allosteric modulator with agonistic effects. This novel mechanism of action offers the potential to treat all symptom domains of schizophrenia without the side effects of standard of care antipsychotics. ANAVEX®3-71 has previously demonstrated long-lasting, pro-cognitive effects and behavioral improvements in animal models of neurodegenerative diseases4,5, an ability to prevent cognitive decline in animal models6,7, and has shown robust safety signals in healthy volunteers at single doses ranging from 5 to 200 mg once daily.8,9 Recent research into the genetic underpinnings of schizophrenia has revealed links between this psychiatric disorder and neurodegenerative disease, suggesting the disorders may share certain mechanisms.10 Oral ANAVEX®3-71, in addition to the M1 muscarinic receptor activity, the combined SIGMAR1 receptor activity might offer a novel mechanism of action that may address multiple symptom domains without the motor side effects associated with traditional antipsychotics. The currently ongoing Part B of the placebo-controlled Phase 2 study, which includes more participants and a longer treatment duration, will provide more comprehensive data on the efficacy and safety of ANAVEX®3-71 in schizophrenia. Anavex expects data from Part B of the placebo-controlled Phase 2 study in the first half of 2025. 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, 11 with an additional 50-60% experiencing only a partial improvement in symptoms or unacceptable side effects.12 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. 1 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.2023.02.018 2 Parker DA, Hamm JP, McDowell JE, et al. Auditory steady-state EEG response across the schizo-bipolar spectrum. Schizophr Res. 2019;209:218-226. doi:10.1016/j.schres.2019.04.014 3 Newson JJ, Thiagarajan TC. EEG Frequency Bands in Psychiatric Disorders: A Review of Resting State Studies. Front Hum Neurosci. 2019;12:521. Published 2019 Jan 9. doi:10.3389/fnhum.2018.00521 4 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:10.1159/000440864 5 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.2017.11.009 6 https://www.anavex.com/post/anavex-life-sciences-reports-new-publication-in-scientific-journal-demonstrating-the-potential-of 7 Orciani C, Do Carmo S, Foret MK, et al. Early treatment with an M1 and sigma-1 receptor agonist prevents cognitive decline in a transgenic rat model displaying Alzheimer-like amyloid pathology [published online ahead of print, 2023 Sep 26]. Neurobiol Aging. 2023;132:220-232. doi:10.1016/j.neurobiolaging.2023.09.010 8 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.1303 9 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 10 Guo P, Meng C, Zhang S, et al. Network-based analysis on the genes and their interactions reveals link between schizophrenia and Alzheimer's disease. Neuropharmacology. 2024;244:109802. doi:10.1016/j.neuropharm.2023.109802 11 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-z 12 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 The content above comes from the network. if any infringement, please contact us to modify.

None By Dr. L. Alison McInnes and Jimmy QianWe’re finally moving towards a causality-based nosology for psychiatry: specific symptoms with defined biological underpinnings can now be targeted by new therapies. But how do we bridge clinical development with real-world care? How do we ensure trial endpoints are synchronized with real-world measures, payer requirements, and clinical society guidelines? Below, we dig into the widening gap between research and clinical care. No consensus on how to measure transdiagnostic symptomsExcitingly, researchers have been able to characterize underlying neural circuitry for certain symptoms. The NIMH Fast-Fail Trials initiative, which stipulated that a drug candidate should alter a biomarker in an objectively measurable fashion, accelerated this movement. For anhedonia, investigators identified ventral striatum abnormalities during reward anticipation that normalized in response to kappa opioid receptor (KOR) antagonists. Despite this advancement, there has yet to be consensus on how to measure anhedonia in the clinic. Many clinicians do not practice measurement-based care, and even amongst those who do, measurement of anhedonia is typically confined to the first question of the PHQ-9. Moreover, anhedonia is a transdiagnostic symptom that should be measured across multiple diagnoses, not just depression.Progress has also been made in elucidating the neurocircuitry of cognition in depression. Leanne Williams’ group has identified biotypes with distinct fMRI signatures and associated cognitive abnormalities that may predict differential response to treatment. Meanwhile, Alto Neuroscience is developing cognitive profiling tools to subtype patients for enriched response to its pipeline agents. However, there is no consensus approach to measure cognition in the real-world. Furthermore, tools for characterizing cognitive deficits in depression do not necessarily capture the deficits observed in other disorders. Today, real-world clinicians often miss subtle but disabling cognitive symptoms for lack of appropriate measurement tools.Researchers have made additional advancements in precision measurement spanning EEG, fMRI, digital phenotyping, proteomics, and more. Yet as research progresses, the gap to real-world care widens. New mechanisms of action require more from cliniciansNovel mechanisms of action are also being developed, often enabling precise targeting of pharmacotherapies to specific symptoms. Continuing the anhedonia example, the phase 3 KOR antagonists aticaprant and navacaprant leverage the fact that elevated levels of dynorphin, which activates KORs, are associated with stress, anhedonia, and dysregulation of reward processing.Seltorexant, a selective orexin-2 receptor antagonist, is being studied specifically for depression with insomnia symptoms. Xanomeline-trospium, a dual M1/M4 muscarinic agonist, has shown promise in treating positive, negative, and cognitive symptoms of schizophrenia, with scientists speculating that dual agonism confers broad activity while M1 agonism may be more involved in cognitive improvements.Additional novel mechanisms are being studied or have been recently approved, spanning NMDA and AMPA receptor modulators, dual orexin receptor antagonists, 5HT2a receptor antagonists, GABAA receptor modulators, digital therapeutics, and more. New treatment options coupled with the complexity of treatment pathways and symptom clusters mean clinicians will need to know how to prioritize different mechanisms, measure success, and monitor side effects.Most patients have constellations of symptoms, so how are clinicians to make decisions about which to treat first with these targeted therapies? A hospitalist has objective physiological measures to help prioritize interventions to stabilize an inpatient; similarly, psychiatrists need novel objective measures to select the best treatment pathway for individual patients. Diagnosing and measuring previously untreatable conditions is a challengeIt is wonderful to see therapies for hitherto untreatable indications. Tardive dyskinesia is an example of a historically-neglected condition as there were no effective therapeutics. Why should clinicians and patients spend time measuring symptoms if there is no solution? Though valbenazine and deutetrabenazine have recently been approved for tardive dyskinesia, it is under-diagnosed in the real-world. The symptom measures used in trials are not typically used – or even known – by real-world clinicians. Similar dynamics exist for negative symptoms of schizophrenia, cognitive impairment, and other conditions. Our solution: a Learning Health SystemWe appreciate an analogy by one of the leaders of precision psychiatry, “You wouldn't want to launch electric vehicles without building an EV charging network first.” With breakthroughs in drug development comes an increased need for connectivity across biopharma, regulators, clinicians, payers, and clinical societies.At Osmind, our Learning Health System approach lowers barriers between research and patient care. By building consensus around the same precision measurements, we align evidence goalposts and generate cohorts of well-characterized patients for research. We deploy these measures directly at the point of care through our technology and EHR. Our collaboration with the American Psychiatric Association is an example of this approach.“As we advance in understanding the biological underpinnings of mental illness, an important challenge – and opportunity – will be to ensure that these insights translate into improvements in patient care,” says Husseini Manji, MD, a Strategic Advisor at Osmind. “We must work collaboratively across sectors to create a seamless integration of precision diagnostics and targeted therapeutics into everyday practice and real-world outcomes.” 

SAN DIEGO--( BUSINESS WIRE )--Contineum Therapeutics, Inc. (Nasdaq: CTNM), a clinical-stage biopharmaceutical company focused on discovering and developing novel, oral small molecule therapies that target biological pathways associated with specific clinical impairments for the treatment of neuroscience, inflammation and immunology (NI&I) indications, today announced encouraging preclinical data on PIPE-307, a potentially first-in-class M1 receptor antagonist in development for patients with relapse-remitting multiple sclerosis (RRMS), were published online in the peer-reviewed journal, Proceedings of the National Academy of Science ( PNAS ). The published data provide early evidence that PIPE-307 is a potentially first-in-class, novel, small molecule, selective inhibitor of the muscarinic type 1 M1 receptor. The full manuscript is titled “ Targeting the muscarinic M1 receptor with a selective, brain-penetrant antagonist to promote remyelination in multiple sclerosis” . “We believe that PIPE-307 represents a differentiated and clinically validated approach for the treatment of RRMS, and we are pleased to have our innovative science validated by a high-quality journal like PNAS,” said Carmine Stengone, President and CEO of Contineum Therapeutics. RRMS is the most common form of multiple sclerosis (MS). The pathological hallmark of all forms of MS is the accumulation of demyelinating lesions that occur in the brain and spinal cord. In healthy neurons, myelin, which is a specialized extension of the plasma membrane of oligodendrocytes, serves as an insulator that allows for rapid and efficient conduction of electrochemical signals along the axon. In demyelinating diseases, such as MS, loss of myelin leads to slower signal transmission through the axon and eventual permanent loss of neuronal function. “As observed in our preclinical studies, we believe that the immune-mediated effects of RRMS drive M1 signaling by increasing the local concentration of acetylcholine which in turn, limits OPC maturation and remyelination,” said Stephen Huhn, M.D., Chief Medical Officer and Senior Vice President of Clinical Development of Contineum Therapeutics. “The M1 receptor is highly expressed on OPCs and, by blocking M1 and lifting this inhibitory brake on maturation, we believe that PIPE-307 can lead to OPC maturation and axon remyelination. We are pleased to have published these data in PNAS and to have advanced into a multi-center Phase 2 study investigating PIPE-307’s efficacy and safety in patients.” The published data highlight the foundational preclinical profile of PIPE-307 that supports Contineum’s ongoing Phase 2 clinical trial in RRMS. To date, Contineum has completed two Phase 1 clinical trials of PIPE-307 in healthy volunteers and has initiated a Phase 2 multi-center, randomized, double-blind, placebo-controlled proof-of-concept clinical trial in RRMS patients (NCT06083753). This trial, named VISTA, will assess efficacy and safety in patients with RRMS and is designed to measure multiple clinical and imaging endpoints sensitive to changes in remyelination in RRMS. PIPE-307 is being developed pursuant to a global license and development agreement with Janssen Pharmaceutica NV, one of the Janssen Pharmaceutical Companies of Johnson & Johnson. About Contineum Therapeutics Contineum Therapeutics (Nasdaq: CTNM) is a clinical stage biopharmaceutical company focused on discovering and developing novel, oral small molecule therapies for NI&I indications with high unmet need. Contineum is focused on targeting biological pathways associated with specific clinical impairments, that Contineum believes, once modulated, may demonstrably impact the course of disease. Contineum has a pipeline of internally-developed programs to address multiple NI&I disorders. Contineum has two drug candidates in clinical trials, PIPE-791, an LPA1 receptor antagonist in clinical development for idiopathic pulmonary fibrosis and progressive multiple sclerosis (MS) and PIPE-307, a selective inhibitor of the M1 receptor, in clinical development for relapse remitting MS. PIPE-307 is being developed pursuant to a global license and development agreement between Contineum and Janssen Pharmaceutica NV, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, who plans to initiate a Phase 2 clinical trial of PIPE-307 in depression in 2024. Contineum is headquartered in San Diego, CA. For more information, please visit www.contineum-tx.com . Forward-Looking Statements Certain statements contained in this press release, other than historical information, constitute forward-looking statements within the meaning of the federal securities laws. Forward-looking statements include, but are not limited to, the status and potential of PIPE-307 as a differentiated, first-in-class, novel approach for the treatment of RRMS, statements regarding the Company’s plans for and the anticipated benefits of its drug candidates, including PIPE-791 and PIPE-307, the timing, objectives and results of the clinical trials, and the quotations of Contineum’s management. These statements involve known and unknown risks, uncertainties and other important factors that are in some cases beyond the Company’s control and may cause its actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. These risks and uncertainties, include, but are not limited to, the following: the Company is heavily dependent on the success of PIPE-791 and PIPE-307, both of which are in the early stages of clinical development, and neither of these drug candidates may progress through clinical development or receive regulatory approval; the results of earlier preclinical studies and clinical trials, including those conducted by third parties, may not be predictive of future results and unexpected adverse side effects or inadequate efficacy of the Company’s drug candidates may limit their development, regulatory approval and/or commercialization; clinical studies and preclinical studies may not proceed at the time or in the manner expected, or at all; the timing and outcome of research, development and regulatory review is uncertain; risks associated with reliance on third parties to successfully conduct clinical trials and, in the case of PIPE-307, the Company’s reliance, after completion of the VISTA trial, upon Johnson and Johnson Innovative Medicine’s decision, in its sole discretion, whether or not to further develop PIPE-307 for RRMS; the Company has incurred significant operating expenses since inception and it expects that its operating expenses will continue to significantly increase for the foreseeable future; the Company’s license agreement with an affiliate of Johnson & Johnson may not result in the successful development of PIPE-307; and the Company may be unable to obtain, maintain and enforce intellectual property protection for its technology and drug candidates. Additional risks and uncertainties that could affect the Company’s business, operations and results are included under the captions, “Risk Factors” and "Management’s Discussion and Analysis of Financial Condition and Results of Operations” in its most recent filing on Form 10-Q and in other filings that it makes with the SEC from time to time. These documents are available on the Company’s website at www.contineum-tx.com under the Investor section and on the SEC’s website at www.sec.gov . Accordingly, readers should not rely upon forward-looking statements as predictions of future events. Except as required by applicable law, the Company undertakes no obligation to update publicly or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.