Replies to post #190437 on Anavex Life Sciences Corp (AVXL)

[kevindenver]

It is very exciting to FINALLY read about S1R science someplace besides AVXL publications and SEC documents!

"Sigma-1 Agonists Offer Combination Approach to Dementia Symptoms
Research from the past decade suggests that sigma-1 receptors and their encoding gene, SIGMAR1, together act as a therapeutic target for patients with dementia."

https://www.neurologylive.com/journals/neurologylive/2019/april-2019/sigma1-agonists-offer-combination-approach-to-dementia-symptoms?fbclid=IwAR1WOu-xohYFY2MBr1eQM0hydSHatPJcsSYUb63tL0dH2-kE1vm03T4Pe2A

Also, some of the other drugs listed have horrible the side effects Fluvoxamine (Luvox), Citalopram (Celexa), and Dextromethorphan (Robitussin) in particular.

[plexrec]

Good find Mike (and TTT)---good to see we are on somebodies radar--very early innings here---the future of course is promising !!!!!

[tradeherpete]

Great find Mike!

Let me guess... North Carolina??

[Bourbon_on_my_cornflakes]

Super find, Mike! Article shows 273 far ahead of competitors.

Gee, reading this, it seems we are the only real viable Sigma 1 agonist, as well as far better than any amyloid approach. Darn near a potential real monoply on CNS diseases.

Run Secretariat run!

[nidan7500]

Mikesc….outfriggenstanding….

"The most advanced data for ANAVEX2-73 come from a completed phase 2a trial involving patients with Alzheimer disease.18,19 The study involved 32 patients with mild to moderate disease, with baseline Mini-Mental State Examination (MMSE) scores between 16 and 28. The initial 5 weeks of the study involved crossover from oral to intravenous administration, followed by a year of oral therapy. Primary endpoints focused on safety, dose, and tolerability, while secondary endpoints evaluated efficacy measured by MMSE, Alzheimer’s Disease Cooperative Study-Activities of Daily Living inventory, and electroencephalography (EEG)/event-related potentials (ERPs). After 1 year, multivariable analysis showed a strong relationship between high doses (30 mg and 50 mg) and improved responses compared with patients who received low doses (3 mg and 5 mg) and had poor responses. The agent was very well tolerated, with no serious or clinically significant adverse effects.

The extended period of this trial has been ongoing for 3 years. The most recent findings echoed earlier reports, namely that the high-dose group continued to show significantly better responses in functional and cognitive endpoints than patients treated
with low doses. The investigators also highlighted 2 genomic biomarkers that continued to be significantly associated with responses: SIGMAR1 and COMT. The former suggests that sigma-1 activation is a critical component of patient responses.
In a press release issued by Anavex, Harald Hampel, MD, PhD, professor at the Sorbonne in Paris reflected on the biomarker findings: “These results further confirm the impact of actionable genetic variants that were previously identified through a full, unbiased genomic analysis of ANAVEX2-73 in Alzheimer’s disease, raising optimism for the future of biomarker-guided precision medicine to effectively combat this devastating disease.”

In August 2018, the first patient was enrolled in an ongoing phase 2b/3 trail for ANAVEX2-73 (NCT03790709
https://www.neurologylive.com/journals/neurologylive/2019/april-2019/sigma1-agonists-offer-combination-approach-to-dementia-symptoms?fbclid=IwAR1WOu-xohYFY2MBr1eQM0hydSHatPJcsSYUb63tL0dH2-kE1vm03T4Pe2A

Sure looks solid and there can be little doubt that HH is doing the Pub which we expect to see soon. Feels like the links are established and the entire NS-AD world s getting in line...NICE. Also note, the recent patent w/AVXL and Cognision re ERP is being shown to be relevant. There can be little doubt that the entire trails game is about to pivot in our favor. Very-very-NICE.

[nidan7500]

Just in case you wake up screaming thinking you own BIIB...it was just a bad dream.

ANAVEX2-73: The leading sigma-1 agonist under development is ANAVEX2-73, an amino-tetrahydrofuran derivative and mixed muscarinic/sigma-1 receptor agonist.16 At present, 3 active clinical trials involve ANAVEX2-73: one for Parkinson disease with dementia and 2 for Alzheimer disease.17 Another clinical trial for Rett syndrome is planned, announced in October 2018 by manufacturer Anavex Life Sciences.

The most advanced data for ANAVEX2-73 come from a completed phase 2a trial involving patients with Alzheimer disease.18,19 The study involved 32 patients with mild to moderate disease, with baseline Mini-Mental State Examination (MMSE) scores between 16 and 28. The initial 5 weeks of the study involved crossover from oral to intravenous administration, followed by a year of oral therapy. Primary endpoints focused on safety, dose, and tolerability, while secondary endpoints evaluated efficacy measured by MMSE, Alzheimer’s Disease Cooperative Study-Activities of Daily Living inventory, and electroencephalography (EEG)/event-related potentials (ERPs). After 1 year, multivariable analysis showed a strong relationship between high doses (30 mg and 50 mg) and improved responses compared with patients who received low doses (3 mg and 5 mg) and had poor responses. The agent was very well tolerated, with no serious or clinically significant adverse effects.

The extended period of this trial has been ongoing for 3 years. The most recent findings echoed earlier reports, namely that the high-dose group continued to show significantly better responses in functional and cognitive endpoints than patients treated
with low doses. The investigators also highlighted 2 genomic biomarkers that continued to be significantly associated with responses: SIGMAR1 and COMT. The former suggests that sigma-1 activation is a critical component of patient responses.
In a press release issued by Anavex, Harald Hampel, MD, PhD, professor at the Sorbonne in Paris reflected on the biomarker findings: “These results further confirm the impact of actionable genetic variants that were previously identified through a full, unbiased genomic analysis of ANAVEX2-73 in Alzheimer’s disease, raising optimism for the future of biomarker-guided precision medicine to effectively combat this devastating disease.”

In August 2018, the first patient was enrolled in an ongoing phase 2b/3 trail for ANAVEX2-73 (NCT03790709).17,20

https://www.neurologylive.com/journals/neurologylive/2019/april-2019/sigma1-agonists-offer-combination-approach-to-dementia-symptoms?fbclid=IwAR1WOu-xohYFY2MBr1eQM0hydSHatPJcsSYUb63tL0dH2-kE1vm03T4Pe2A