Anavex Life Sciences Announces Positive Topline Results from Phase 2 Study of ANAVEX®3-71 for the Treatment of Schizophrenia

Rhea-AI Summary

Anavex Life Sciences (NASDAQ:AVXL) announced positive topline results from its Phase 2 clinical study of ANAVEX®3-71 for treating schizophrenia in adults on stable antipsychotic medication. The study successfully met its primary endpoint, demonstrating safety and tolerability with no serious or severe treatment-emergent adverse events.

The trial showed encouraging trends in secondary and exploratory analyses, including positive changes in EEG and ERP biomarkers. Notably, the study revealed reduced levels of GFAP, a neuroinflammation marker, in treated participants compared to placebo, suggesting potential disease-modifying effects. ANAVEX®3-71, a dual SIGMAR1 receptor agonist and M1 positive allosteric modulator, aims to treat all symptom domains of schizophrenia without standard antipsychotic side effects.

Positive

• Study met primary endpoint demonstrating safety and tolerability
• Positive trends observed in EEG and ERP biomarkers
• Reduced GFAP levels indicating potential disease-modifying effects
• No serious treatment-emergent adverse events reported
• Potential to treat all symptom domains of schizophrenia without standard side effects

Negative

• Longer treatment duration may be needed to show pronounced effects
• Study focused primarily on safety rather than efficacy endpoints

Insights

Clinical Neuropharmacologist

Anavex's ANAVEX®3-71 showed safety in schizophrenia Phase 2 trial with promising biomarker trends despite no efficacy data yet.

Anavex Life Sciences has achieved an important milestone with ANAVEX®3-71, a dual SIGMAR1 agonist and M1 positive allosteric modulator, meeting its primary safety and tolerability endpoint in schizophrenia patients. The trial data reveals a clean safety profile with no serious or severe adverse events reported across both dosing cohorts (30mg and 60mg).

The adverse event profile appears comparable between treatment and placebo arms, with treatment-emergent adverse events occurring in 39.3% of patients on the 60mg dose versus 48.1% on placebo in Part B of the study. This favorable tolerability profile is particularly noteworthy for a CNS drug candidate in schizophrenia.

While efficacy wasn't a primary endpoint, the biomarker data provides encouraging signals. The reduction in glial fibrillary acidic protein (GFAP), a neuroinflammation marker, is particularly interesting as it suggests potential disease-modifying activity rather than merely symptomatic relief. This aligns with growing evidence that neuroinflammation plays a role in schizophrenia pathophysiology.

The positive EEG and ERP biomarker trends further support continued development, though the press release lacks specific data on the magnitude of these changes. The absence of detailed clinical outcome measures or symptom assessments is notable - we don't yet know if the treatment improved schizophrenia symptoms.

ANAVEX®3-71's dual mechanism targeting both SIGMAR1 and muscarinic receptors represents a novel approach with theoretical advantages over current antipsychotics. The company's suggestion that this could address all symptom domains (positive, negative, and cognitive) without standard side effects remains to be demonstrated in future efficacy-focused trials.

ANAVEX3-71-SZ-001 achieved its primary endpoint demonstrating safety and tolerability in adults with schizophrenia

Encouraging trends observed in biomarkers support continued development

NEW YORK, Oct. 02, 2025 (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, today announced positive topline results from its placebo-controlled Phase 2 clinical study evaluating ANAVEX®3-71 for the treatment of schizophrenia in adults on stable antipsychotic medication (ANAVEX3-71-SZ-001, NCT06245213).

The study successfully achieved its primary endpoint, demonstrating that ANAVEX®3-71 was safe and well-tolerated. The safety profile was consistent with previous studies of ANAVEX®3-71 in healthy volunteers, with no serious treatment-emergent adverse events (TEAEs) and no severe TEAEs reported in either Part A or Part B of the study.

Overview of Adverse Events (Part A)
	ANAVEX3-71 30mg (N=6)			ANAVEX3-71 60mg (N=6)			Placebo (N=4)			Total (N=16)
	n (Participants)	%	n (Events)	n (Participants)	%	n (Events)	n (Participants)	%	n (Events)	n (Participants)	%	n (Events)
AE starting before study	1	16.7	1	0	0	0	0	0	0	1	6.3	1
AEs leading to death	0	0	0	0	0	0	0	0	0	0	0	0
Treatment emergent AE (TEAE)	1	16.7	1	0	0	0	0	0	0	1	6.3	1
Related TEAE	1	16.7	1	0	0	0	0	0	0	1	6.3	1
Serious TEAE	0	0	0	0	0	0	0	0	0	0	0	0
Serious related TEAE	0	0	0	0	0	0	0	0	0	0	0	0
Non-serious TEAE	1	16.7	1	0	0	0	0	0	0	1	6.3	1
Severe TEAEs	0	0	0	0	0	0	0	0	0	0	0	0
Related severe TEAEs	0	0	0	0	0	0	0	0	0	0	0	0
TEAE leading to death	0	0	0	0	0	0	0	0	0	0	0	0
TEAE leading to discontinuation of study drug	0	0	0	0	0	0	0	0	0	0	0	0
Overview of Adverse Events (Part B)
	ANAVEX3-71 60mg (N=28)			Placebo (N=27)			Total (N=55)
	n (Participants)	%	n (Events)	n (Participants)	%	n (Events)	n (Participants)	%	n (Events)
AE starting before study	1	3.6	1	0	0	0	1	1.8	1
AEs leading to death	0	0	0	0	0	0	0	0	0
Treatment emergent AE (TEAE)	11	39.3	16	13	48.1	21	24	43.6	37
Related TEAE	5	17.9	6	4	14.8	6	9	16.4	12
Serious TEAE	0	0	0	0	0	0	0	0	0
Serious related TEAE	0	0	0	0	0	0	0	0	0
Non-serious TEAE	11	39.3	16	13	48.1	21	24	43.6	37
Severe TEAEs	0	0	0	0	0	0	0	0	0
Related severe TEAEs	0	0	0	0	0	0	0	0	0
TEAE leading to death	0	0	0	0	0	0	0	0	0
TEAE leading to discontinuation of study drug	0	0	0	2	7.4	4	2	3.6	4
Key
n (Participants) = number of study participants with at least one event in the corresponding category
n (Events) = number of events in the corresponding category and treatment group
N = total number of study participants in the corresponding treatment group
% = (number of study participants with at least one event in the corresponding category/total number of patients in the corresponding treatment group)*100

In addition to meeting the primary safety endpoint, secondary and exploratory analyses revealed encouraging trends in several outcome measures. The study demonstrated positive trends in objective electroencephalography (EEG) and event-related potential (ERP) biomarkers of schizophrenia.

Furthermore, neuroinflammatory biomarker assessments showed that glial fibrillary acidic protein (GFAP), a marker of neuroinflammation, was reduced in participants receiving ANAVEX®3-71 compared to placebo. This reduction in neuroinflammatory markers suggests a potential disease-modifying effect that may become more pronounced with longer treatment durations. GFAP is a marker of astrocyte reactivity to neuronal injury and disease¹ with known relevance to both neuropsychiatric² and neurodegenerative^3,4 disorders.

“We are encouraged that our ANAVEX3-71-SZ-001 study aligns with our expectations for safety and tolerability,” said Juan Carlos Lopez-Talavera, MD, PhD, Head of Research and Development of Anavex. “We believe we are well-positioned to advance a competitive candidate into future studies aimed at addressing the ongoing and unmet medical needs of individuals living with schizophrenia and neurodegenerative diseases.”

“We believe this study is a manifestation of Anavex’s continued platform expansion aiming to provide potential beneficial effect for patients with oral compounds,” said Christopher U Missling, PhD, President and Chief Executive Officer of Anavex. “The positive safety profile and encouraging biomarker trends support the continued development of ANAVEX®3-71 as a potential treatment for CNS disorders that could address underlying pathophysiology beyond symptomatic control.”

ANAVEX®3-71 (formerly AF710B) is a dual SIGMAR1 receptor agonist and M1 positive allosteric modulator with agonistic effects.^5,6 ANAVEX®3-71 has previously been studied in healthy volunteers prior to study ANAVEX3-71-SZ-001.^7,8 This novel mechanism of action offers the potential to treat all symptom domains (positive, negative, and cognitive) of schizophrenia without the side effects of standard of care antipsychotics.

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,⁹ with an additional 50-60% experiencing only a partial improvement in symptoms or unacceptable side effects.¹⁰

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, 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.

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 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 Abdelhak A, Foschi M, Abu-Rumeileh S, et al. Blood GFAP as an emerging biomarker in brain and spinal cord disorders. Nat Rev Neurol. 2022;18(3):158-172. doi:10.1038/s41582-021-00616-3
2 Rodrigues-Amorim D, Rivera-Baltanás T, Del Carmen Vallejo-Curto M, et al. Plasma β-III tubulin, neurofilament light chain and glial fibrillary acidic protein are associated with neurodegeneration and progression in schizophrenia. Sci Rep. 2020;10(1):14271. Published 2020 Aug 31. doi:10.1038/s41598-020-71060-4
3 Yakoub Y, Ashton NJ, Strikwerda-Brown C, et al. Longitudinal blood biomarker trajectories in preclinical Alzheimer's disease. Alzheimers Dement. 2023;19(12):5620-5631. doi:10.1002/alz.13318
4 Leipp F, Vialaret J, Mohaupt P, et al. Glial fibrillary acidic protein in Alzheimer's disease: a narrative review. Brain Commun. 2024;6(6):fcae396. Published 2024 Nov 7. doi:10.1093/braincomms/fcae396
5 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
6 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
7 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
8 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
9 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
10 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}

FAQ

What were the key results of AVXL's Phase 2 trial for ANAVEX®3-71 in schizophrenia?

The Phase 2 trial met its primary endpoint, demonstrating safety and tolerability with no serious adverse events. The study also showed encouraging trends in biomarkers and reduced GFAP levels, indicating potential disease-modifying effects.

How does ANAVEX®3-71 differ from traditional schizophrenia treatments?

ANAVEX®3-71 is a dual SIGMAR1 receptor agonist and M1 positive allosteric modulator that potentially treats all symptom domains (positive, negative, and cognitive) of schizophrenia without the side effects of standard antipsychotic medications.

What safety profile did ANAVEX®3-71 demonstrate in the Phase 2 trial?

The drug showed a strong safety profile with no serious treatment-emergent adverse events (TEAEs), no severe TEAEs, and no treatment-related deaths in either Part A or Part B of the study.

What biomarker changes were observed in AVXL's schizophrenia trial?

The study showed positive trends in EEG and ERP biomarkers and demonstrated reduced levels of GFAP (glial fibrillary acidic protein), a marker of neuroinflammation, in treated participants compared to placebo.

What are the next steps for ANAVEX®3-71 in schizophrenia treatment?

Based on the positive safety profile and encouraging biomarker trends, Anavex plans to advance development of ANAVEX®3-71 for CNS disorders, focusing on addressing underlying pathophysiology beyond symptomatic control.