Anavex Life Sciences Corp (AVXL)

[TTTav66]

A couple recent perspective/review articles of interest:

An Update on Psychopharmacological Treatment of Autism Spectrum Disorder
https://link.springer.com/article/10.1007/s13311-022-01183-1?fbclid=IwAR2dYSw9_ulEwNlufoBzSziNR5odeh-KiwNqGQv7OZaSLJGX_ZyVRUaTKSU

Anavex 2–73
Anavex 2–73 (AV 2–73; Blarcamesine) is a sigma 1 receptor agonist that works between the endoplasmic reticulum and the mitochondrial membrane to normalize calcium dysregulation, oxidative stress, and mitochondrial dysfunction which is seen in many forms of ASD. It has demonstrated significant benefits in the KO mouse model of FXS where multiple behaviors were improved and deficient brain derived neurotropic factor (BDNF) levels were normalized [144]. In addition, Kaufman et al. [145] also reported significant benefits in the Rett syndrome mouse model with a rescue of behavior and BDNF levels and this work lead to patient studies in Rett syndrome that have demonstrated efficacy in a controlled trial (Anavex Life Sciences press release 2021). AV2-73 also has beneficial effects in neurodegenerative disorders because of improvement in proteostasis, autophagy, oxidative stress, prevention of protein aggregates, and improvement in mitochondrial function leading to benefits in Alzheimer’ disease and Parkinson’s disease dementia [146,147,148]. Significant potential exists for AV2-73 to improve symptoms in Fragile X-associated Tremor Ataxia (FXTAS), a neurodegenerative disease seen in approximately 40% of older carriers of the fragile X premutation, because calcium dysregulation, mitochondrial dysfunction, proteostasis, and aggregations of proteins causing inclusions occur in FXTAS [149].

Therapeutic Strategies Targeting Mitochondrial Calcium Signaling: A New Hope for Neurological Diseases?
https://www.mdpi.com/2076-3921/11/1/165

6.1.3. Blarcamesine
Blarcamesine (ANAVEX2-73) is a safe Sig-1R agonist and muscarinic receptor modulator with preliminary efficacy evidence in patients with AD and Rett syndrome [141]. Preclinically, blarcamesine exerted anticonvulsant, anti-amnesic, neuroprotective, and antidepressant effects in various animal models of Rett syndrome [141], fragile X syndrome [141], AD [142,143], and amnesia [144]. These data suggest its potential in neurodegenerative and neurodevelopmental diseases.
After demonstrating good safety, bioavailability, and tolerability in AD patients (NCT02244541) [145], blarcamesine has been tested in a phase-II, placebo-controlled studywith Rett Syndrome patients (NCT03758924) [146]. Even though the trial is completed,results are still pending. Currently, different phase-II/III trials focused on PD (NCT04575259) [147], AD (NCT04314934) [148], and Rett Syndrome (NCT03941444, NCT04304482) [149,150], which are recruiting patients to evaluate the tolerability and efficacy of blarcamesine.