Anavex Life Sciences Initiates Placebo-Controlled US Phase 2 Clinical Trial of ANAVEX®3-71 in Schizophrenia

Anavex Life Sciences Corp. recently announced the first patient in its US FDA cleared placebo-controlled Phase 2 clinical study of ANAVEX3-71 for the treatment of schizophrenia has been screened ahead of schedule.

“Initiating our Phase 2 trial of ANAVEX3-71 in schizophrenia ahead of schedule is a testament to the hard work and dedication of our clinical study team,” stated Christopher 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 ANAVEX3-71’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 (ANAVEX2-73) onto a regulatory pathway for potential treatment of Alzheimer’s disease.”

ANAVEX3-71’s differentiated mechanism 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 — 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. ANAVEX3-71’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, ANAVEX3-71 demonstrated an adequate safety profile in a Phase 1 trial in healthy volunteers.

The placebo-controlled Phase 2, two-part, in-patient trial, ANAVEX3-71-SZ-001 (NCT06245213), will investigate the effects of ANAVEX3-71 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.

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 US. 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,  with an additional 50-60% experiencing only a partial improvement in symptoms or unacceptable side effects.

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, ANAVEX2-73 (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. ANAVEX2-73 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. ANAVEX2-73 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 ANAVEX2-73 for the treatment of Parkinson’s disease. ANAVEX3-71, 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, ANAVEX3-71 has shown beneficial effects on mitochondrial dysfunction and neuroinflammation. For more information, visit www.anavex.com.