ANAVEX 3-71 / Anavex - LARVOL DELTA

SZ-001: A Study of ANAVEX3-71 in Adults With Schizophrenia (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Anavex Life Sciences Corp. | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Psychiatry • Schizophrenia

SZ-001: A Study of ANAVEX3-71 in Adults With Schizophrenia (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: Anavex Life Sciences Corp.

New P2 trial • CNS Disorders • Psychiatry • Schizophrenia

Anavex Life Sciences Reports Publication of ANAVEX3-71 in Clinical Journal Confirming Pharmacokinetic Dose Proportionality of ANAVEX3-71 in Humans (GlobeNewswire) - P=NA | N=NA | "Anavex Life Sciences Corp...announced a peer-reviewed publication in Clinical Pharmacology in Drug Development, findings from the ANAVEX 3-71 first-in-human study which achieved its safety objectives....The results from this PK evaluation demonstrated that ANAVEX3-71, at single ascending doses of 5 to 200 mg, is linear, dose proportional, and time invariant. Food had no effect on the PK of ANAVEX3-71. This data also expands the safety objectives met in this first-in-human study of ANAVEX3-71, further supporting its drug development program."

Clinical data • PK/PD data • Alzheimer's Disease • CNS Disorders • Dementia • Parkinson's Disease

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. (PubMed, Clin Pharmacol Drug Dev) - "Age, weight, and creatinine clearance were not explanatory of the variability in apparent clearance and apparent volume of the central compartment of ANAVEX3-71. Food had no effect on the PK of ANAVEX3-71 and its M8 metabolite."

Journal • PK/PD data • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Psychiatry • Schizophrenia

Early treatment with an M1 and sigma-1 receptor agonist prevents cognitive decline in a transgenic rat model displaying Alzheimer-like amyloid pathology. (PubMed, Neurobiol Aging) - "Lastly, AF710B treatment rescued the conversion of brain-derived neurotrophic factor precursor to its mature and biologically active form. Overall, these results suggest preventive and disease-modifying properties of the compound."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Inflammation • Aβ42 • BDNF

Anavex Life Sciences Reports New Publication in Scientific Journal Demonstrating the Potential of ANAVEX3-71 to Prevent Cognitive Decline in Alzheimer’s Disease (GlobeNewswire) - "Anavex Life Sciences Corp...reported a new peer-reviewed publication in the journal Neurobiology of Aging...featuring the orally available small molecule ANAVEX^®3-71 (AF710B)....Notably, the reduction in amyloid pathology was accompanied by a reduction in inflammatory glial activity which is connected to the disease cascade in AD and other dementias. ANAVEX^®3-71 treatment downregulated the proinflammatory IL-1β and IL-6 cytokines, which are known to be associated with AD. Additionally, ANAVEX^®3-71 treatment boosted brain derived neurotrophic factor (BDNF) which reinforces the evidence that ANAVEX^®3-71 protects neurons."

Preclinical • Alzheimer's Disease • CNS Disorders

Anavex Life Sciences Reports Publication of ANAVEX 3-71 in Clinical Journal Confirming ANAVEX 3-71 Clinical Cardiovascular Safety (GlobeNewswire) - P1 | N=36 | NCT04442945 | Sponsor: Anavex Life Sciences Corp. | "Anavex Life Sciences Corp...announced a peer-reviewed publication in Clinical Pharmacology in Drug Development, findings from the ANAVEX®3-71 first-in-human study which achieved its cardiovascular safety objectives....The publication reports the cardiodynamic evaluation part of the single ascending dose study in healthy participants with the primary objective of assessing the effect of ANAVEX®3-71 on ECG (electrocardiogram) parameters. The results from this cardiodynamic evaluation demonstrated that ANAVEX®3-71 at single ascending doses of 5 to 200 mg had no clinically relevant effects on any of the studied ECG parameters and hence confirmed the ANAVEX®3-71 preclinical cardiovascular safety findings. These data also expand the safety objectives met in this first-in-human study of ANAVEX®3-71, further supporting its drug development program."

P1 data • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Parkinson's Disease • Schizophrenia • Tauopathies And Synucleinopathies

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. (PubMed, Clin Pharmacol Drug Dev) - "An effect on the placebo-corrected, change-from-baseline QTc exceeding 10 ms can be excluded within the full observed ranges of plasma concentrations of ANAVEX3-71 and M8 up to ∼996 and ∼58 µg/L, respectively. The results from this cardiodynamic evaluation demonstrated that ANAVEX3-71 at single ascending doses of 5-200 mg had no clinically relevant effects on any of the studied ECG parameters."

Journal • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Psychiatry • Schizophrenia

Anavex Life Sciences Reports New Publication in Medical Journal Highlighting the Relevance of SIGMAR1 Activation to Compensate for Early Alzheimer's Disease (GlobeNewswire) - "Anavex Life Sciences Corp...reported a relevant new peer-reviewed publication in the journal Science Translational Medicine...In this publication, position emission tomography (PET) and magnetic resonance imaging (MRI) markers were utilized to show that impaired mitochondrial oxidative phosphorylation and synaptic loss are central to neurodegeneration in the cellular pathology of Alzheimer's disease (AD). One of the featured observations was an increase in SIGMAR1 expression in the early stages of AD. Increased SIGMAR1 expression may be an endogenous, compensatory mechanism for the loss of other receptors and proteostasis. However, PET scans of patients with more advanced AD diagnoses show a reduction of SIGMAR1 expression....Recent studies with ANAVEX®2-73 and ANAVEX®3-71 show that SIGMAR1 activation also involves mitochondrial performance, an intricate phenomenon that provides energy for cellular functions..."

Preclinical • Alzheimer's Disease • CNS Disorders

Anavex Announces Long-lasting Effect of ANAVEX 3-71 Preventing Cognitive Decline in a Transgenic Rat Model of Alzheimer’s Disease at AAIC 2022 (Yahoo Finance) - “Anavex Life Sciences Corp…announced long-lasting effect of clinical drug candidate ANAVEX®3-71 in preventing cognitive decline in a transgenic rat model of Alzheimer’s disease at the Alzheimer’s Association International Conference (AAIC), taking place in San Diego, CA and virtually on July 31 – August 4, 2022….Biomarker analysis revealed that ANAVEX^®3-71 prevents McGill-APP transgenic rats from increasing cortical (p ≤ 0.05) and hippocampal (p ≤ 0.01) extracellular Aβ deposition. ANAVEX^®3-71 also significantly reduces microglia (p ≤ 0.05) and astrocytes (p ≤ 0.05) recruitment towards Aβ-burdened neurons in the hippocampus….In the Novel Object Recognition behavioral test, Tg control rats explored the novel object significantly less than wt control rats (p ≤ 0.01).”

Biomarker • Preclinical • Alzheimer's Disease • CNS Disorders • Dementia

Anavex Life Sciences Provides Business Update and Reports Fiscal 2022 Second Quarter Financial Results (GlobeNewswire) - "Pipeline expansion of the ANAVEX platform using gene biomarkers of response, applying precision medicine for neurological disorders with unmet medical need are expected 2022:...Planned initiation of ANAVEX®3-71 Phase 2 clinical trials for FTD, schizophrenias and Alzheimer’s disease indications."

New P2 trial • Alzheimer's Disease • CNS Disorders

Novel Therapeutic Target for Prevention of Neurodegenerative Diseases: Modulation of Neuroinflammation with Sig-1R Ligands. (PubMed, Biomolecules) - "Activation of Sig-1R provides neuroprotection in cell cultures and animal studies. Clinical trials demonstrated that several Sig-1R agonists (pridopidine, ANAVEX3-71, fluvoxamine, dextrometorphan) and their combinations have a neuroprotective effect and slow down the progression of distinct NDDs."

Journal • Review • Alzheimer's Disease • CNS Disorders • Immunology • Inflammation

M1 MUSCARINIC STIMULATION OF POST-SYNAPTIC RECEPTORS FOR THE POTENTIAL TREATMENT AND PREVENTION OF COGNITIVE DECLINE (ADPD 2022) - "Positive effects on some of the neuropathological hallmarks of AD were also reported in preclinical studies with EUK1001, VU0364572, a bitopic M1 agonist, VU0486846, an M1 PAM, and AF710B, a mixed M1 allosteric/sigma-1 agonist...Ref: E. Giacobini, AC Cuello and A. Fisher. REIMAGINING CHOLINERGIC THERAPY FOR ALZHEIMER DISEASE, Brain, in press."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Psychiatry • Schizophrenia • Sjogren's Syndrome • Xerostomia

Phase 1 Study of ANAVEX3-71 (clinicaltrials.gov) - P1; N=36; Completed; Sponsor: Anavex Life Sciences Corp.; Recruiting ➔ Completed

Clinical • Trial completion

Anavex Life Sciences Reports Positive Results from Phase 1 Clinical Trial of ANAVEX 3-71 (GlobeNewswire) - P1, N=36; NCT04442945; Sponsor: Anavex Life Sciences Corp.; “Anavex Life Sciences Corp...announced positive top-line results from its Phase 1 clinical trial of ANAVEX®3-71…for the treatment of neurodegenerative diseases including Frontotemporal Dementia (FTD), for which ANAVEX®3-71 has been granted Orphan Drug Designation (ODD) by the FDA….ANAVEX®3-71 was well tolerated in all cohorts receiving ANAVEX®3-71 in single doses ranging from 5 mg to 200 mg daily with no serious adverse events (SAEs) and no significant lab abnormalities in any subject….Based on these results, and ANAVEX®3-71 pre-clinical profile, the Company intends to advance ANAVEX®3-71 into a biomarker-driven clinical development dementia program for the treatment of FTD, schizophrenias and Alzheimer’s disease, evaluating longitudinal effect of treatment with ANAVEX®3-71 initiating in 2022.”

New trial • P1 data • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Parkinson's Disease • Schizophrenia

Phase 1 Study of ANAVEX3-71 (clinicaltrials.gov) - P1; N=36; Recruiting; Sponsor: Anavex Life Sciences Corp.; Trial completion date: Mar 2021 ➔ Aug 2021; Trial primary completion date: Mar 2021 ➔ Aug 2021

Clinical • Trial completion date • Trial primary completion date

Anavex Life Sciences Reports New Publication in Medical Journal Elucidating the Mechanism of ANAVEX 2-73 (blarcamesine) and ANAVEX 3-71 (AF710B) related to the Treatment of Alzheimer's Disease (GlobeNewswire) - "Anavex Life Sciences...today reported that ANAVEX 2-73 (blarcamesine) and ANAVEX 3-71 (AF710B) are featured in a new peer-reviewed publication in the journal of Expert Opinion on Therapeutic Targets, titled 'The emerging role of the sigma-1 receptor in autophagy: Hand-in-hand targets for the treatment of Alzheimer's'....Sigma-1 receptor (SIGMAR1)’s expression increases with age, however in Alzheimer’s disease (AD) it decreases...The decrease in SIGMAR1 expression during AD coincides with an age-related decrease in autophagy...The SIGMAR1 may compensate for loss of receptors and autophagic machinery during healthy aging...SIGMAR1 is activated by ANAVEX-compounds...ANAVEX®2-73 has been shown to induce autophagy..."

Preclinical • Alzheimer's Disease • CNS Disorders

The emerging role of the sigma-1 receptor in autophagy: Hand-in-hand targets for the treatment of Alzheimer's. (PubMed, Expert Opin Ther Targets) - "AF710B, T-817MA and ANAVEX2-73 are some of the σ-1R agonists which have shown promising results and have entered clinical trials...The future of AD treatment could involve the combined targeting the σ-1R and autophagy activation. We suggest that future studies investigate the link between autophagy the σ-1R and AD."

Journal • Alzheimer's Disease • CNS Disorders • APP

Anavex Life Sciences Reports Fiscal 2021 First Quarter Financial Results And Business Outlook (GlobeNewswire) - "Potential accelerated approval strategy planning underway as Phase 2 U.S. Rett syndrome trial clinical data showed positive clinical activity and safety data with progress within ongoing Phase 2/3 AVATAR adult Rett syndrome and Phase 2/3 EXCELLENCE pediatric Rett syndrome studies...U.S. Food and Drug Administration (FDA) approved extension of ANAVEX®2-73 U.S. Rett syndrome Phase 2 open-label extension study...New clinical pipeline compound ANAVEX®3-71 Phase 1 study is on track: Independent Data Safety Monitoring Board (DSMB) for the Company’s Phase 1 study of its new investigational compound ANAVEX®3-71..."

DSMB • FDA event • Trial status • CNS Disorders

Phase 1 Study of ANAVEX3-71 (clinicaltrials.gov) - P1; N=36; Recruiting; Sponsor: Anavex Life Sciences Corp.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

Anavex Life Sciences Announces First Participant Enrolled in Phase 1 Study of ANAVEX 3-71 (AF710B) (GlobeNewswire) - "Anavex Life Sciences Corp....today announced the enrollment of the first participant in a Phase 1 clinical trial of ANAVEX®3-71 (AF710B)...with topline data anticipated in the first half of 2021....Anavex is developing ANAVEX®3-71 initially for the treatment of Frontotemporal Dementia (FTD), for which ANAVEX®3-71 was previously granted orphan drug designation by the FDA. ANAVEX®3-71 demonstrated disease-modifying activity against the major hallmarks of Alzheimer’s disease in transgenic (3xTg-AD) mice..."

Enrollment status • P1 data • Alzheimer's Disease • CNS Disorders • Frontotemporal Lobar Degeneration • Parkinson's Disease

Phase 1 Study of ANAVEX3-71 (clinicaltrials.gov) - P1; N=36; Not yet recruiting; Sponsor: Anavex Life Sciences Corp.

Clinical • New P1 trial

Anavex Life Sciences reports newly published data on Alzheimer's disease research demonstrate the neuroprotective features of the sigma-1 receptor (GlobeNewswire) - "New data published in the current issue of the peer-reviewed scientific journal Neurotoxicity Research1 confirm that sigma-1 agonists, including multiple investigational compounds from Anavex Life Sciences...induce an anti-oxidant effect and protect mitochondrial function in pathological central nervous system conditions. In addition, another recent publication in the peer-reviewed scientific journal, Behavioural Brain Research2, confirms that the absence of sigma-1 receptor function exacerbates amyloid toxicity and increases learning impairments in pharmacologic and genetic mouse models of Alzheimer’s disease....The Neurotoxicity Research publication provides further insight on the mechanism of three Anavex sigma-1 receptor (S1R) agonists, ANAVEX®2-73, ANAVEX®1-41, and ANAVEX®3-71, which are all being studied in neurodegenerative diseases..."

Preclinical • Alzheimer's Disease • CNS Disorders • Parkinson's Disease

Anavex Life Sciences Reports Fiscal 2020 First Quarter Financial Results and Provides Clinical Study Updates (GlobeNewswire, Anavex Life Sciences Corp.) - "We announced January 8, 2020 that the United States Patent and Trademark Office (USPTO) granted U.S. Patent No. 10,507,196...ANAVEX®2-73 (blarcamesine) for the treatment of...Rett syndrome, and multiple sclerosis. This patent is expected to remain in force at least until 2037, not including any patent term extensions....Enrollment for the Phase 2b/3 ANAVEX®2-73 (blarcamesine) Alzheimer’s disease (AD) study2 is 50% complete. Recruitment is expected to accelerate given the anticipated international expansion of the study, which will increase the total number of sites from 15 to approximately 45 in 2020. ANAVEX®3-71 successfully completed IND-enabling toxicology studies and drug product manufacturing....Initiation of the first Phase 1 clinical trial of ANAVEX®3-71 is expected in 2020."

Enrollment status • New P1 trial • Patent

Pridopidine stabilizes mushroom spines in mouse models of Alzheimer's disease by acting on the sigma-1 receptor. (PubMed, Neurobiol Dis) - "Pridopidine stabilizes mushroom spines in mouse models of AD and this requires S1R, endoplasmic reticulum calcium leakage through PS1/2 and nSOC. Thus, pridopidine may be useful to explore for the treatment of AD."

Journal • Preclinical