Anavex Life Sciences Corp (AVXL)

[MycroftHolmes]

Re: AAIC Notes - Dr Hampel

Here are my notes from the AAIC conference. As I mentioned, Dr. Hampel read directly from the slides but the few places he departed were interesting.

I've tried to bold the points of greatest interest below:


Sigma Receptor
• Sigma Protein modulates function at ER, Nuclease and Cell Membrane
• Under chronic cellular pathological stress the endogenous ligands which agonize the Sigma deplete.
• Anavex 2-73 acts to replace the depleted endogenous ligands
• Cell can regain neuroplasticity to restore function
• Evidence that sigma impacts neuro-degenerative pathways
• Some studies have shown Sigma is involved in reduction of beta amyloid, hyperphosphorylated tau, oxidative stress, neuroinflammation-leading thus leading to synaptic dysfunction and neuronal loss

2-73
• Significant relation between ANAVEX 2-73 concentration and (ADCS-ADL) (26 patients at 57 weeks)

Genetics:
• Full NGS exome (DNA) and transcriptome (RNA) sequencing using Next Generation sequencing methods
• KEM is used successfully in oncology to avoid over fitting of hypothesis
• KEM has proven successful in oncology with even smaller samples
• 20,000,000 relations led to 33,000 relevant genes extracted that had relation to study data; about 800 pathways were identified.
• Out of possible genes, 2 had strong, robust and significant association to exploratory outcome measures like cognition & function. (COMT gene for memory, SIGMAR codes target)
• The presence of specific variants results in worse outcomes, and that of others in improved outcomes for MMSE and ADCS-ADL
• RNA expression analyses show concordance with results
• AD patients with wild-type SIGMAR1 gene were found to have improved benefit from treatment
• Focus on 102 Genes. In particular, genes associated with measures MMSE & ADCS-ADL and other relevant genes. (SIGMAR, APOE, BDNF, COMT, INPP5D, MAPT)

Summary

• Confirmed safety & dose-dependent target engagement with SIGMAR1 using PET
• Exome sequencing showed response-linked gene variants using formal concept analyses (FCA)
• SIGMAR1/COMT variants shown to be linked to limited clinical response
• Confirmation through high SIGMAR1 RNA expression levels linked to clinical response
• Results consistent across cognition (MMSE) and activities of daily living (ADCS-ADL)
• genetic biomarkers have been identified and much like oncology studies can be used to enrich the clinical development of ANAVEX 2-73
• Informative for a larger trial targeted therapy studies are already approved for Alzheimer’s and Parkinson’s

Apologize in advance for all typos.

Cheers

Mycroft