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You nailed it. Thanks, as you saved me a lot of time trying to explain!
The only thing is Missling dodged the question when he had the perfect opportunity to clear up the matter entirely. Why wouldn’t he want to make it clear that 50mgs was one of the arms? I don’t understand the rationale.
Could it be possible that the 10 and 20 mg concentrations listed on the EU site were simply two separate pill forms that Anavex had manufactured and each had to be registered separately? It seems possible, but if that’s the case registering the trial in the US as only “high” and “medium” was just dumb. Everyone knew 50 was the highest dose possible, so what would be the purpose of keeping that a secret?
Expecting 4.20 by EOD and 5.80 by EOW.
Likely to see above $7 soon. A lot of funny money was pumped into the system. Gotta go somewhere.
“Dizziness was the most common adverse event (20 incidents in 15 patients), followed by headache (16 in 10 patients). Most (94%) occurred in the first week of treatment. All were mild or moderate. Headache and dizziness are considered signs that patients are approaching their maximum tolerated dose, Dr. Missling said.
The company’s task now is to find a standard minimum dose that is strong enough to get patients to at least 4 ng/mL plasma level, without inducing these side effects.
https://www.mdedge.com/neurology/article/152595/alzheimers-cognition/development-sigma-1-receptor-agonist-alzheimers
“Patients Treated with Higher ANAVEX®2-73 Concentration Show Higher MMSE* Performance Compared to Lower Concentration
High Concentration cohort shows 64 % less decline than low concentration cohort
“High plasma concentration of ANAVEX®2-73 [>4.0 ng/ml] is correlated with the clinically administered dose
Observed adverse events at doses above the maximum tolerated single dose included headache and dizziness, which were moderate in severity and reversible.
75 neurological AE’s at 57 weeks and only 13 at 148 weeks.
“Nearly all patients (98%) had some sort of adverse event, but most of them were mild transitory dizziness or headache; 76% of the events were grade 1, and 2% were grade 2. There were no serious adverse events. Three subjects dropped out because of adverse events (delirium, dizziness, and a combination of confusion, disorientation, and lethargy)”
followed by an 11-day washout period, and then 30 or 50 mg/day oral ANAVEX 2-73 for 11 days. This was followed by a 52-week, open-label, extension trial of 10-50 mg/day orally, titrating each patient to the maximum tolerated dose. “
76 + 2 = 78
https://www.mdedge.com/neurology/article/120066/alzheimers-cognition/sigma-1-agonist-presses-forward-after-positive-results
https://www.anavex.com/wp-content/uploads/2019/03/Anavex-Presentation-March-2019-1.pdf
“securities and the exchange on which it is registered and the number of shares outstanding of each of the issuer's classes of common stock, as of the latest practicable date (date is commonly the filing date, NOT the time period covered ...”
By Jove your right.
“Indicate the number of shares outstanding of each of the issuer’s classes of common stock, as of the latest practicable date: 58,664,946 shares of common stock outstanding as of February 6, 2020.
1 “
Well he probably doesn’t need money because Anavex and Biogen have already inked a coequal partnership deal that includes upfront cash! Exciting times!!!
No
“For the quarterly period ended: March 31, 2020”
How exactly do you know how many shares he sold to Lincoln Park in April and May?
There should be approx 58,664,946 shares outstanding.....there were 57,080,365 on Dec 31 2019.
Your not paranoid if they really are out to get you! There was nothing in that video other than the truth. Just like book burning.
Apparently, the key to getting a drug approved is allowing the corrupt upper echelon to take the credit and royalties. Perhaps Dr. M should offer Dr. Fauci a position on the BOD?
“There were no clinically significant treatment-related adverse events and no serious adverse events. “
So seriously misworded as you be a material misstatement?
Why put “treatment-related” in the first part but not after the “and”?
Needs to be corrected imho.
2) The denominator is based on 58,664,946 shares outstanding as of April 27, 2020
As of July 2, 2019, we had 51,661,413 shares of Common Stock outstanding.
So looks like ~7 million shares sold in ~9 months.
Observed adverse events at doses above the maximum tolerated single dose included headache and dizziness, which were moderate in severity and reversible.
75 neurological AE’s at 57 weeks and only 13 at 148 weeks. Must have reduced dosing or the folks with headaches dropped out?
Through 57 weeks, Alzheimer’s patients taking a daily oral dose between 10mg and 50mg of ANAVEX®2-73 was well tolerated. There were no clinically significant treatment-related adverse events and no serious adverse events.
Strange because the supplements to the latest paper seem to indicate 5 SAE’s at 57 weeks and either 6 or 9 at 148 weeks. Not clear if they were treatment related but doesn’t matter because they appear to be stating there were none at all. ????
Additionally, we will only be able to sell or issue to Lincoln Park 10,076,680 shares in total, which is equal to 19.99% of the shares of common stock outstanding on the date of the Purchase Agreement unless we obtain shareholder approval or the average price of such sales exceeds the price of our common stock on June 7, 2019 as determined under NASDAQ rules.
(2) The denominator is based on 58,664,946 shares outstanding as of April 27, 2020
On July 3, 2019, we filed the registration statement of which this prospectus supplement is a part, registering up to $250 million in securities utilizing a shelf registration process and on September 13, 2019 following the deregistration of all shares remaining registered under the 2016 Registration Statement, we filed a prospectus supplement to cover the issuance and sale of up to $15,514,532 of shares of our common stock. As of May 1, 2020 all of such shares have been sold and/or issued to Lincoln Park.
I believe he may be referring to the fact that posts on this board about this paper seem to have a negative spin.
https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/trc2.12013
[Quote] High concentration of 2-73 results in greater effect and small concentration causes little or no effect!
Isn't that what we want to see ??
Well then, you must expect failure in Anavex’s 2b/3 Alzheimer’s trial because everyone taking A2-73 in the trial is on the “small” concentration. The 2a trial doses were 10,20,30,40 and 50 mgs daily. The 2b/3 doses are only 10 or 20 mgs. Why would they run a trial that excludes the only doses that were effective?
Yes but no sense showing it again.
The beauty and also possibly the weakness of the strategy (if that’s what they are trying) imho will be proving that A2-73 is the reason for the improvements and not that they just figured out which patients are most likely to benefit from donepezil because it also binds to S1.
It could depend on how many patients in the current trial are only taking A2-73 w/o also taking one of the other SOC’s.
“This observed heterogeneity is also seen in other therapeutic areas such as oncology. In oncology, multiple small, open-label clinical trials are run in which a broad range of biomarker candidates are identified and hypotheses generated and tested iteratively, serving as foundation for the design of follow-up controlled studies. Crizotinib is a good example of accelerated approval in oncology following an open-label Phase 1a study, where a novel biomarker (ALK+) was first identified based on 2 of 11 patients with non-small cell lung cancer enrolled in a Phase 1 dose escalation trial.54 The biomarker was validated through an amended Phase 2a study including 19 patients, with 10 out of 19 patients being labeled as responders, which ultimately led to a preliminary drug registration. Subsequently, a confirmatory trial enrolled 82 ALK+ patients and showed 57% partial response and 1% complete response. “
That is probably the basis for the job description Anavex posted which included a preference for oncology experience.
So it seems to me the plan is to look at the small number of improved patients that should predictably show up in the current AD trial and see if they share some common markers that enhance response and then run a confirmatory trial with those parameters.
https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/trc2.12013
https://alzres.biomedcentral.com/articles/10.1186/alzrt210/tables/2
“Super responders” was a term made up here to describe the group of patients who’s scores improved. This group of patients should have been expected even if A2-73 did absolutely nothing, because many in Anavex’s trial are still taking the SOC that produced the results above.
Change my mind!!!
https://alzres.biomedcentral.com/articles/10.1186/alzrt210#Tab2
Had Dr. Missling been in charge of Neurotrope, they would not have failed their blinded trial so quickly. When they finally did fail their blinded trial, there would have been more money in the bank. No one should be calling for Dr. M’s removal here. He is doing a fantastic job with the finances.
Never said it would affect the blinded doses.
I said this:
If bioavailability is improved due to reformulation then 50 mg would probably be well beyond MTD imho.
“ 97% Consistency: MMSE, ADCS-ADL and EEG/ERPs: Identified relations show that high dose (concentration) is linked to improved response
and low dose (concentration) to poor response “
https://www.anavex.com/wp-content/uploads/2018/05/Anavex-ANAVEX2-73-CTAD-Phase-2a-November-2017.pdf
Review this:
https://www.nuventra.com/resources/blog/what-is-steady-state-concentration/
If I recall correctly, the half life of the metabolite is roughly twice that of A2-73.
The half life of the drug is different for young vs older patients.
Imho, something is being hidden about the reason why the lower doses were chosen.
My opinion:
65% probability that regulatory agencies forced Anavex to use the lower doses for some reason.
35% that management knew they would suffer too many dropouts if they tried the higher doses.
Conclusion imho: The company prepared a presentation that showed that high doses had the best chance of succeeding and then they used the low doses instead.
They started referring to “concentration” instead of dose, they appear to have put some effort into hiding the doses in the 2b/3 trial from investors.
Imho someone should put the CEO on the spot and demand an explanation.
Low Concentration ....MMSE decreases
Low Concentration....
ADCS-ADL decreases
Anyone bother to consider why management would plan the 2b3 trial with the doses that failed the 2a Alzheimer’s trial? Look a pages 23 and 24. https://www.anavex.com/wp-content/uploads/2018/05/Anavex-ANAVEX2-73-CTAD-Phase-2a-November-2017.pdf
The doses on the left are 10 and 20 mgs. There must be a significant reason that they were forced to use those ineffective doses from the 2a trial in the 2b/3 Alzheimer’s and PDD trial.
Look at slide 22. https://www.anavex.com/wp-content/uploads/2018/05/Anavex-ANAVEX2-73-CTAD-Phase-2a-November-2017.pdf
54%
High dose -> Improved response
Low dose -> Improved response
3%
43%
Low dose -> Poor response
Imho only a significant toxicity problem would explain the seemingly inexplicable choice to use 10 and 20 mgs in the current trials.
I think the US (southern at least) may have the benefit of timing.
“The “virus is highly sensitive to high temperature”, which could prevent it from spreading in warmer countries, while the opposite appeared to be true in colder climes, the study said.”
https://www.scmp.com/news/china/science/article/3074131/coronavirus-highly-sensitive-high-temperatures-dont-bank-summer
The human body’s reaction to infection is often “fever” that because it slows or kills viruses. No guarantee but a strong possibility.
“Does high temperature kill viruses?
A fever kills the virus by making your body hotter than normal. That also helps germ-killing proteins in your blood get where they need to be more quickly. So if you run a slight fever for a day or two, you could get well faster.”
So if anyone gets sick it might be prudent not to rush to prevent fever immediately. And folks should not arrive unannounced to a doctors office if they suspect infection. If you give it to the healthcare workers then the situation magnifies exponentially.