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It's not just the Sigma-1R that is efficacious. It's the way the Sigma-1R binds and synergizes with the M1 - M4 ligands that makes Anavex's drugs so unique and powerful.
Anavex has numerous patents to protect their drugs.
If the FDA is going to require a P3 confirmatory trial, why is Anavex preparing for commercialization?
So, are you saying that a company can commercialize their product with a P3 confirmatory trial running simultaneously?
That's not my understanding.
The only way to do that is with a P4 confirmatory trial.
Yes. I read all of the information that you put forward this morning. What am I missing?
I get what you're trying to convey with a P3 confirmatory trial, but your theory doesn't explain why Anavex is preparing for commercialization.
The only confirmatory trial that allows a company to commercialize their product is a P4 trial.
So, taking all of the evidence that has been conveyed to us thus far, the verdict is more likely to be a P4...in my opinion, of course.
As always, time will tell us which path Anavex is heading down.
Thanks for all of your DD.
Read this other post by Steady.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=171874266
Nice article.
As I recall, Dr. Missling said that recognition of the S1-r is at an all-time high right now because the medical establishment is finally waking up to its MOA.
This is exactly what you want to see when you're invested in a biotech company that is 10 years ahead of everyone else.
I see tremendous growth ahead for Anavex's two main drugs...A2-73 and 3-71.
Excellent post Steady. Thanks for the great DD.
Also appreciate the links to back up your DD!
A nice Caddy is a lot easier on the eyes. Thanks Bourbon!
P4 = AA = commercialization of your product while the confirmatory trial is going on.
I don't believe a P3 confirmatory trial allows the company to commercialize their product while the trial is going on.
The fact that we are preparing for commercialization of our product tells me that we are requestng a P4...that's why TGD is talking about AA and commercialization at the same time.
I do not agree with your assessment that a P3 confirmatory trial is 100% likely.
This goes against Dr. Missling, Dr. Jin Kun, and Tom Bishop's outlook.
I'll take their expertise over yours.
Bourbon...Love your posts, but that cartoon of kim jong-un rising in the background sure does get annoying.
Good to hear. Thanks for clarifying.
And don't forget about Dr. Jin Kun.
As the former lead statistician for the FDA, I'm sure he is the one recommending this submission without needing another P3 trial.
All comments are just my opinion and should not be used to buy or sell AVXL shares.
As per your own post, and I quote: "70% had confirmatory trials started before approval"
So, that means that 30% did not need to have a confirmatory trial started before the FDA gave them AA.
Additionally, one of the more critical posters on this MB (Anshu2) stated the following:
Anshu2
Wednesday, May 10, 2023
Post#414869
No. AA can be granted irrespective of the timing of confirmation trial. SRPT’s first drug (Exondys) got the AA in 2016 and the confirmation trial only started in mid-2020 with readout in 2026 (?). There were trials running during AA approval process, but FDA asked for a newly designed confirmation trial.
From a site: US data show that, of 23 accelerated approvals granted in 2010-20 to non-oncology drugs, only four had converted to full approvals through clinical confirmation as at the end of 2020, taking an average of 3.5 years to do so.
However, FDA does like to see the promise of completion of the confirmation trial — in ongoing case of SRPT’s gene therapy AA (AdCom panel on Friday and decision on 5/29), the confirmation trial is fully enrolled and finishing in a few months. I think FDA likes that.
Yes. In addition to those comments from Dr. Missling, we have the comments from Tom Bishop...who spoke with TGD just after the CC. (See below)
Tom Bishop talked to Anavex post CC. Here are his comments.
Anavex’s (AVXL $9.20, +9%) (… and wow, Aris is up 25% this morning, I’ll hit that next!) quarterly release and conference call was this morning. And after speaking with the Company and clarifying a few issues, there were some exciting revelations. First and foremost, the Company now believes, after 5 months of evaluating the data, that the data from the resent Phase 2b/3 Alzheimer’s trial, and especially the data from the improvement in surrogate biomarkers that are associated with the pathology of Alzheimer’s are strong enough that it intends to apply to the FDA for approval of A2-73 based on the “Accelerated Approval Pathway.” Now this doesn’t just mean the process moves along more quickly while it now does a full phase 3 trial. This means conditional approval for commercial sale of A2-73 based on the data already collected from the Phase 2b/3 trial, especially that based on improvement in the various Alzheimer’s disease pathology biomarkers, along with the cognitive and other improvements in functional data itself. And then a confirmatory study would be done while the drug is already approved. Recent Alzheimer’s drug approvals (Biogen and Lilly) have all utilized this pathway and evidence of improvement of various biomarkers for Alzheimer’s disease. So this is rather exciting as there is a reasonable chance now that the Company could get approval relatively soon without waiting to first conduct a full blown Phase 3 trial. No guarantees on this, but very encouraging re the potential time line to market acceleration. Here is something more on this pathway–
“The pathway specifically allows FDA to approve drugs based on a determination that the product has an effect on certain surrogate endpoints or intermediate clinical endpoints. Surrogate or intermediate endpoint can be based on a laboratory measurement (like blood glucose level for diabetes), radiographic image (like tumor size reduction), physical sign (like blood pressure for cardiovascular disease) or other measure. For instance, reduction of viral load in HIV patients, reduced tumor size in cancer patients or alleviation of symptoms can all be used to show a treatment’s benefit to patients. Congress has clarified, through statute, that the accelerated approval pathway does not alter the standards of evidence required for approval.
After a medicine is granted accelerated approval, companies are required to conduct, and provide updates on, confirmatory trials and the FDA is required to make this information publicly available.
Companies are required to conduct confirmatory studies of medicines granted accelerated approval and are subject to reporting requirements on the status of these studies. The FDA is required to track, and make publicly available, progress of confirmatory trials.”
Remember that the safety data is much better than those Alzheimer’s drugs recently approved that can cause brain swelling/bleeding (maybe even death) and the need for periodic/expensive MRI’s to monitor this. AND A2-73 is an oral formulation not infusion therapy. So all things being equal, what are you gonna take?
Now the other cool thing here is, as announced in a press release last week, the Company has filed for a patent covering A2-73’s use to lower high blood pressure. As you might expect, when patients came in for periodic trial evaluations, they got their blood pressure taken. And the Company noticed that those coming in with high blood pressure saw that drop back into the normal range! So while the Company is a ways off from pursuing this indication on its own, if it can claim this side benefit, in addition to the Alzheimer’s benefits above … like I said, which one are you gonna choose? Duh. (I also recall some potential benefits regarding improved sleep, I hope we get data on that also.) It’s like how they have discovered lately that some of the diabetes drugs (Eli Lilly’s in particular)) cause significant weight loss! So now these diabetes drugs are in short supply because other people are taking them just for weight loss. So A2-73, if approved, could then potentially be prescribed off label for blood pressure, or at least more likely advertised as a side benefit. The blood pressure data has not been disclosed but perhaps will be in the full release in a medical journal that will cover all the things we have been waiting for (30 vs. 50 mg, ADL and COG, sigma1 normal gene vs. the variant, all the other biomarker data … ).
Elsewhere, I believe they are at last getting very close to announcing the Phase 3 Parkinson’s disease trial initiation, in addition to the full A2-73 data release, plus in H2 the Rett Pediatric data. While this seems to move very slowly the Company is meticulous in its approach, avoiding the pitfalls so many companies fall into with their failed clinical trials and I would remind everybody once again that they have never failed one of their clinical trials. They have all been successful in showing efficacy, and that consistency itself tells you something. Small wonder Dr. Missling reiterated in closing that “… looking forward we’re very excited about the Company’s potential as well as to build the bio-marker driven precision medicine studies…”
There was more meat on the bone than today’s stock market reaction gives credit for (it was down in the pre-market but I see as I finish this that it is now up 8%, still … plenty of room ahead)- Buy.
Yes...especially now that Anavex has $153 Million in the bank. They're done selling shares on the open market.
The Shorts cannot count on the company selling anymore shares.
I anticipate a steady rise for AVXL as the Shorts start to cover.
Plus, I think we'll get several sharp spikes upward when the company announces Rett TLR...Parkinson's P3 Trial...updated TLR for AD P2b/3...and other surprises TBA.
Good post, Steady.
Quote: "Looks like Missling is using all possible approaches to obtaining approval."
Exactly what Nidan had requested last night.
From your lips to God's ears, Nidan. Your brother is in good hands. Rest easy, my friend.
OK chief. If that makes you sleep better at night.
Chill out. It's just a hypothetical game after hours.
No need for derogatory insults.
Me too, Nidan. Condolences.
I'll say a prayer for the soul of your twin brother tonight.
I take it back, Hoskuld. You have to play with the cards that you're holding...which means that you have to decide if you're going to Buy, Sell, or Hold the shares that you currently have.
(Me? I'm holding)
Sure. It's a hypothetical scenario. I was just curious as to what Mikey would do.
Your response is interesting.
But note that I never gave the closing price. I said there was two minutes left and the MMs were pushing the price back down.
Fast forward to tomorrow morning's quarterly report...
TGD clarifies that pre-commercialization is based on the excellent results from the P2b/3 AD trial...and that he intends to file an NDA first with Australia's TGA. (Hypothetically speaking, of course)
The market likes what he says and AVXL shoots up to $22/share. The price continues to bounce around throughout the day between $21 and $25. But in the last 10 minutes of trading it shoots up to $31/share!
Everyone is dancing in the street. Except...there's still ten minutes before the market closes...and the MMs are starting to push the price back down.
$30
$29
$28
Two minutes left before the market closes...
Are you going to Buy, Sell, or Hold?
I'm curious as to what you'd do, Mikey?
Hmm...now you've got me thinking...which is a dangerous game, LOL.
If we're hiring 280 new employees over the next 10 years, we should be conducting new trials. So, it begs the following question:
I'd like to know how many new trials Anavex will be conducting over the next 10 years based on the number of trials we've conducted since 2017?
This should be interesting!
Yup. If they hadn't hired Dr Missling back in 2013, there is a very good chance that Anavex wouldn't even be here today.
Here is the statement from their accounting firm:
"The accompanying consolidated financial statements have been prepared assuming that the Company will continue as a going concern. As described in Note 1 to the consolidated financial statements, the Company had an accumulated deficit of $41,204,972 and negative working capital of $1,559,211 at September 30, 2013 and incurred a net loss of $3,700,046 for the year then ended. These conditions raise substantial doubt about the Company’s ability to continue as a going concern. Management’s plans in regard to these matters are also described in Note 1. The consolidated financial statements do not include any adjustments that might result from the outcome of this uncertainty. Our opinion is not modified with respect to this matter."
/s/ BDO USA, LLP
New York, NY
December 30, 2013
https://www.sec.gov/Archives/edgar/data/1314052/000106299313006497/form10k.htm#page_33
Thank God they found Dr. Chris Missling...
When Dr. Missling came aboard in 2013 there were only 1 or 2 employees.
Since then the company has had tremendous (employment) growth in preparation for the commercialization of their new drug, Blarcamesine. (See below)
2013...Dr. Missling is hired
2014 = 4 employees
2015 = 7 employees
2016 = 10 employees
2017 = 10 employees
2018 = 13 employees
2019 = 16 employees
2020 = 20 employees
2021 = 25 employees
2022 = 37 employees
https://www.macrotrends.net/stocks/charts/AVXL/anavex-life-sciences/number-of-employees
Better check your research.
YoY employees was not 10 to 37. (See the actual numbers below)
It took 5 years to go from 10 to 37 employees.
2013...Dr. Missling is hired
2014 = 4 employees
2015 = 7 employees
2016 = 10 employees
2017 = 10 employees
2018 = 13 employees
2019 = 16 employees
2020 = 20 employees
2021 = 25 employees
2022 = 37 employees
https://www.macrotrends.net/stocks/charts/AVXL/anavex-life-sciences/number-of-employees
Wow...I can't remember the last time the XBI has been up over 5% in a single day.
Wow...you sure have become optimistic lately.
What changed your tune?
Which is exactly what the manipulators want you to feel. They're hoping that you'll get so frustrated that you'll sell your shares.
Remember, there's a buyer at the other side of each sell.
In retrospect, it may not boil down to whether one believes TGD is lying or not...it may be that some are waiting for additional data. (Just like we were waiting for the initial data for the TLR).
We accept the initial data that has been presented thus far - along with the CEO's assurance that all endpoints have been met. They, on the other hand, are still waiting for additional data to confirm their inquisitiveness.
Nothing wrong with that as long as each side respects the others position.
I agree. I like Joseph because he seems to be a level-headed guy and goes out of his way to search for the truth...and that's why it doesn't make sense for him to be invested if he believes the CEO is lying about the P2b/3 results. (It just goes against his level-headedness)
A few days ago I asked him why he was invested and this was his answer:
"I believe Anavex very likely has a great drug platform. I believe blarcamesine will be approved for Rett after the Excellence trial. I think the Excellence trial will have good results based on the prior Rett trials, and that the big, and widely spread, AF to-do over changed endpoints in Avatar was dishonest or mistaken.
I may nonetheless have considered greatly paring my shares but for Jin joining the company. He doubtless had lots of employment options besides Anavex. It's probable he saw the AD data (though I don't know for a fact whether Anavex legally could share it at the time he was being recruited) and unquestionable he would have reviewed the publicly-available data and analyses of the earlier trials for all indications before accepting a position. I don't think someone with his background, options, and expertise would join a company that didn't have a drug he believed would get approval. I'm happy to invest where Jin has chosen to work.
I also think Anavex will probably get approval for Alzheimer's, though I'm not sure it won't require another P3. I'd feel way better if Anavex had released a convincing TLR. Apart from the blanket statement that All Endpoints Were Met, it's really not in itself convincing, and I wish other longs would just admit it. If SAVA or some other little-known biotech or Biogen released a TLR with such a gaping hole in the stats, would basparks and the Likers ignore (and create apologies for) the hole so long as the CEO said endpoints were met? I doubt it. I wouldn't. (BTW, I have no gripe with basparks or anyone else on this board who appears honest and doesn't do things like say he teaches med school while proving be couldn't.) Back to the positives on blarcamesine for Alzheimer's, and why I'm "deep" in Anavex shares, I believe that if it wins approval it will blow away the mabs (which I think are junk and hope never get CMS coverage) and be huge.
Without going into my politics, I can say that I'm more disturbed when people "on my side" spread pro-my-side bullsh*t than I am when it's the "other side" (of whom I expect it) doing it. I am unhappy and feel less secure in my Anavex investment when it seems I'm among a coterie of True Believers who are impervious to reasonable skepticism and argue that the only reason for the low share price is short-seller manipulation. I'd rather invest in something honest skeptics believe in than in something that has what looks to me like unquestioning support. (Hence the signature I've chosen for this post. Look up the history of the stock mentioned there.)
I think the skeptics bring at least as much utility as the true believers to this board, but the skeptics are given short shrift while true believers can post any well-articulated rah-rah cheer (even posts like that one of basparks which is made, IMO, with great faith and eyes closed) and get inundated with Likes. I'm going to keep fighting for clear-eyed analysis even though I'm deeply long."
Well, if Anavex (or any biotech company) were to conduct a trial for HTN, would they ask the participants to stop taking their meds?
Yes. December 2nd (Friday) was the day after the presentation...and the price increased $3.18 in a single day...which contradicts your original claim that people sold their shares after they heard the presentation.
And yes, November 28th was the 4Q earnings presentation...but the selloff on that day had nothing to do with your claim that "companies usually announce TLD days to weeks before an approaching conference (then going into more detail at the meeting)"
Oh c'mon, doc. You originally claimed that "Playing Devil's advocate to one's position is important in any investment."
Now you're going to avoid your own thesis?
Give it another try.
Furthermore, I asked you to play Devil's advocate to prove Dr. Missling's claim that the P2b/3 AD trial had achieved their endpoints.
All you did was (basically) re-confirm your position as to how it didn't achieve them.
Can you try again?
Thanks
No Doc. You got it wrong. December 2nd was a Friday.
The sell off happened BEFORE the conference call...which was on Monday, NOVEMBER 28th. You see, the AF team of manipulators had already prepared to sell AVXL shares before the results were even announced.
(If that's not manipulation I don't know what is!)
Your post is interesting in that you claim both sides of the "manipulation" argument at the same time.
Good for you.