Anavex Life Sciences Corp. 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. 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. 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 omeostasis 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. 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. 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.