Anavex Announces First Entire Clinical Gene Pathway Data of ANAVEX2-73 from AVATAR Study in Patients with Rett Syndrome

Significant activation of key developmental and metabolic gene pathways and potential compensatory mechanism with ANAVEX2-73 in Rett syndrome patients

NEW YORK, Dec. 20, 2023 (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 and neurodevelopmental disorders including Alzheimer’s disease, Parkinson’s disease, Rett syndrome and other central nervous system (CNS) diseases, today announced the first entire clinical gene pathway data from the ANAVEX2-73-RS-002 AVATAR Rett syndrome trial.

A whole genome and exome analysis comparing drug and placebo in patients with Rett syndrome was performed. We believe the results confirm that Rett syndrome is indeed a neurodevelopmental disorder with a key metabolic component, which can be addressed with therapeutic intervention and is likely relevant for other neurodevelopmental disease indications.

AVATAR study was a randomized, placebo-controlled clinical trial in 33 patients with Rett syndrome which included prespecified biomarkers of response as well as Whole Exome Sequencing (WES) DNA data and full RNA exome expression (RNA-seq) data collection. The study included analysis of gene expression changes in each treatment group as well as analysis of the impact of single nucleotide polymorphisms/variants (SNPs/SNVs) on treatment response.

ANAVEX2-73 transcriptomics analysis (RNAseq) identified gene networks that are differentially expressed in Rett syndrome patients treated with ANAVEX2-73 compared to placebo. Patient samples that were analyzed contained on average over 20 million unique reads in both placebo and ANAVEX2-73 treated patients. Biological relevance of this pool of genes was assessed through pathway analysis and confirmed the impact of ANAVEX2-73 treatment on pathways involved in neurodevelopmental diseases.

The results highlight many significant differences between active treatment group and placebo, such as the differential expression of several genes in response to ANAVEX2-73 treatment as shown in the following heatmap figure:

Pathway analysis of the differentially expressed genes suggests ANAVEX2-73 may, among other functions, correct metabolic alterations in patients with Rett syndrome through enhanced mitochondrial energy production and increased expression of genes involved in oxidative phosphorylation, fatty acid metabolism, developmental signaling pathways, transcription/translation, membrane trafficking, and branched-chain amino acid catabolism as shown in the following table: