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EndWar, re gross revenues and SPs:
You and falconer are on the right track. I presume you know that TGD already said what the "back of envelope" revenue would be for Rett revenue. So just work with Rett for now...ALZ/PD/ETC will take care of themselves.
Look at a standard "Cash Flow" statement, and fill in the blanks with Anavex's data, AND LISTEN TO WHAT TGD SAYS. That will project a bottom line figure, and then with shares and PE ratio one can estimate SP. Simple stuff, no rocket science.
No need to pull SP out of ones A$$, as happens so often.
Let me know what you see.
Good luck!
I respectfully disagree. DrM would go himself if there were any big news to drop. Send the rookie in to gain experience with no surprises expected.
The real question is why is Dr.M not doing it, as he has always done it in the past? Working on something more important, maybe another conference in Dec, to many meetings right now ...or just taking a vacation?
Red, I would think any sales org worth their salt would try to be first in line to be Anavex's rep, knowing Ana does not have her own sales force.
I liked the large number of analysts...lot more eyes on Ana these days. The questions themselves, got nothing revelatory from Dr.M. though imo.
Happy Thanksgiving to All
JWC3 agree! DrM either egregiously is running only one ALZ trial on the advice of his former FDA employees OR with FDA consultation he is running the one trial. Most likely it is pivotal based on the VERY GOOD PDD results.
Just as good Avatar results translates to pivotal FragileX and pivotal UNDISCLOSED trials...I think the GOOD PDD trial translates to future PD and PDD and Lewy Body and ALS trials will also be pivotal.
Dr.M very busy these days.
Nice pipeline....or GREAT pipeline.
Boi,As for Parkinsons, it could be the team is just busy as heck on the high priority item. Thanks
My two cents on the silence and expectations.
Below are/were the expectations for the second half of this year:
1 Top-line data AVATAR
1A Initiation of potentially pivotal Phase 2/3 Fragile X trial
1B Initiation of potentially pivotal Phase 2/3 for unnamed rare disease
2 Initiation of ANAVEX®2-73 imaging-focused Parkinson’s disease clinical trial – expected 2021
3 Top-line data Phase 1 ANAVEX®3-71 clinical trial
I grouped the top three items together, with two under Avatar, as I think they are subordinate to Avatar, as I will discuss.
By far the most important is Avatar top line data. Dr.M has already confirmed that they are talking with regulatory agencies, FDA implied. How can the FragileX trial and UNnamed rare disease trial be defined as PIVOTAL without any P1 or P2? They have been on the presentations for a while, so what is the holdup in getting them going? It appears that these two major trials are dependent on Avatar TLD. Only with Avatar approval or very good Avatar data for the FDA, would the FDA allow these to be defined as 'Pivotal'. So these two trials are waiting for Avatar TLD!
It is common for companies, when something big is in the works, to have a self imposed 'quiet period'. This may be what we are experiencing. Possibly related to why Dr.M skipped over the Avatar slide, in a recent presentation. So when Avatar news hits, we may hear about the 1a and 1b trials mentioned above.
The Parkinsons trials should be a big deal. I am a bit disappointed that they have not started yet. No idea what the hold up is with them.
I expect (#3) the A3-71 TLD, to be a nothing burger. It was a SAFETY trial on HEALTHY people. Imagine how long it has been since A2-73 was in that same situation, and enthusiasm for the timeline should be dampened. Now the follow on trials....!
All IMHO etc.
Guys..its a web event! Stand down.
And BIIB $269, at pre-approval price. LOL
That's interesting. There appears to be twice the sales as buy volume, yet by painting the tape, the closing price was at high of day! Terrible when the HFTs do it, but funny when the little guy can do it. Lol
bas, good idea. Maybe that will be suggested to FDA.
Cortexyme Alz GAIN Trial PR data analysis:
The Cortexyme GAIN trial was run with 643 subjects, with two primary endpoint tests ADAS-Cog and ADCS-ADL. MMSE testing was done as a secondary endpoint test, but the PR gave no MMSE data. There were three different arms, one a high dose of COR388(80mg), one a low dose of COR388(40mg), and a placebo. The thesis is that the bacteria P. gingivalis (aka PG) is the primary cause of Alzheimers, and that their drug COR388, will be efficacious in subjects that have PG.
As the PR says “In overall population, co-primary endpoints of ADAS-Cog11 and ADCS-ADL were not met”
That says a lot, but is not the whole story. Lets look at what exactly happened…
Keep in mind that the subgroup of patients WITH bacteria PG, are the primary intended subjects. Analogous to the A2-73 patients that WITH wild type genes. Comparison of these subgroups should prove interesting.
Regarding the cognitive test ADAS-COG11:
The subgroup with bacteria PG constituted 37.6% (242/643) of all the subjects. The high dose group with PG, showed a 57% slowing of cognitive decline for ADAS-COG11. This is a significant improvement, but did not meet their predicted improvement of 2.5 points. I think they actually attained ~1.71 points of improvement (57% of 2 to 4, being ~1.71 points). There was a dose improvement with the high dose over the 40mg dose, but the 40mg dose had a high p-value, emphasizing the need for the higher dose for better efficacy, but also indicating that the lower dose is likely near the bottom of the useable dose range.
In summary, if any random group of people with AD, took COR388, 37.6% of them would see a cognition decline of 43% versus placebo. This is compared to placebo and is much better than 100% decline. IIRC this high dose gives much better efficacy than the BIIB aducanumab!
Regarding the cognitive test ADCS-ADL:
There was also a primary endpoint test using Activities of Daily Living(ADL). The PR stated that this endpoint was also not met. Why? The company rightly raises the issue that many of the ADCS-ADL questions are affected by the pandemic lockdown. For example, there are questions about travel and shopping. Presumably, the company will raise this issue with the FDA. What will be the outcome?
How Does This Data Compare to A2-73
Amount of improvement:
The A2-73 super responders-----IMPROVED FROM BASELINE
COR388 super responders-------DECLINED 43% FROM BASELINE compared to placbo
This is not a numerical comparison, as A2-73 data is from the P2 trial which used ADCS-ADL. But one obviously did improve from baseline, while the other declined (though arguably much better than placebo).
How many improve?:
It is helpful to understand what percentage of a population could be expected to show improvement.
A2-73 super responders as percentage of AD population----- ~57%
COR388 super responders as percentage of AD population---~37.6%
SUMMARY
COR388 appears to be helpful with AD, but may be a victim of choosing the wrong predicted benefit value, needing a longer trial, and an endpoint affected by the pandemic! It will be interesting to see how it pans out.
Compared to A2-73, COR388 appears to help a smaller subset of AD patients, with less efficacy. However, it is probably preferable to the Biogen approved drug.
Anavex’s P3 ALZ trial also has primary endpoints using the ADAS-COG and ADCS-ADL tests. What if Anavex’s ADCS-ADL results are affected by the pandemic?
All imho.
I see what you mean. I think biogens is aducanumab. I have a hard time remembering that too! It doesn't exactly roll off your tongue.
Yeah I don't know what to say about fda. They certainly screwed up with biogen. Now all the other plaque fighters, with poor data want to get their drug approved too...well you did it for biogen!!
I don't know how Cortexymes drug will end up. There are new drugs in the works, like anavex's too. I could see a cocktail of the effective drugs used...NOT biogens. Unfortunately the pharma industry moves at a snails pace.
I don't know where the sava drug stands. I am bothered by the apparently edited pictures.
Falconer, many thanks for your continued efforts to help out this board! Please don't stop.
Hello McMagyar. Unfortunately, they did not report MMSE data and it was a secondary endpoint test only. They will probably report that at the November meeting.
They did two other tests for primary endpoints. One was called ADAS-Cog, which had the cognition improvement of 57% better than placebo. The other test they did was ADCS-ADL, which clearly failed, apparently because of the pandemic related questions.
Please allow me to rephrase my summary. The company expected the best response to be from the patients that had the P. gingivalis bacteria. And indeed these patients when given the HIGH dose, did better than the other patients that did NOT have the bacteria and the ones that got the placebo. In fact, from the start (baseline) they declined only about 43% as much as the placeboed patients, at the end (11months). These were the 'super responders'. They declined, but less than half as much as not getting anything at all. (actually 43%)
Now the question I always ask, is "How many of all the people with AD will be helped?". The answer is 37.6%. Of all the AD patients, 37.6% had the bacteria present. So, if you took 1000 people with AD and gave them 80mg COR388, 376 would perform the best, only declining 43% as much as the other 624. The 624 might be helped a little, but we cannot tell from the data the company PRed.
From what I remember of the Biogen data, this COR388 is better. COR388 works better (43% decline) and works on more people 37.6%. I would much rather try COR388 than the Biogen drug!
As a point of reference to say A2-73. If you recall the A2-73 super-responders did not decline at all, but actually improved. I also believe the A2-73 super responders will be 57%. These are the people with the wild type genes.
Hope this is clearer. All is in my humble opinion of course!
Analysis of the GAIN Trial PR data:
Regarding the cognitive tests: The subgroup with (P. gingivalis aka PG) constituted (242/643) 37.6% of all the subjects. The high dose group with PG, showed a 57% slowing of cognitive decline for ADAS-COG11. This is a significant improvement, but did not meet their predicted improvement of 2.5 points. I think they actually attained ~1.71 points of improvement ( approximately 57% of 2 to 4, being ~1.71 points). There was a dose improvement with the high dose over the 40mg dose, but the 40mg dose had a high p-value, emphasizing the need for the higher dose for better efficacy, but also indicating that the lower dose is near the bottom of the useable dose range.
In summary, if any group of people with AD, took COR388, 37.6% of them would see cognition decline of 43% (much better than 100%).
IIRC the high dose gives much better efficacy than the BIIB aducanumab!
There was also an endpoint test using Activities of Daily Living(ADL). This endpoint was also not met. Why? The company rightly raises the issue that many of these questions are affected by the pandemic lockdown. For example, there are questions about travel and shopping.
Surely, the company will raise this issue with the FDA. What will be the outcome?
I dont know if this board is active, but I thought I would pass this along.
Amateur- 174patients, 11month trial, TLD in 1month, 76Sites for the Abbvie PD trial!!!
Amazing, the whole trial was run and done WITH TLD all within one year.
When are Anavex's PD/PDD trials gonna start???
Companies with Rett P3 trials UPDATE:
About a year and a half ago, Joanne Fagg published an article "Rett failure sets up thin pipeline" on evaluate.com.
She showed the status of four companies with Rett p3 trials and their status.
Pharma is a difficult business and two companies have since stopped their Rett trials.
Anavex and Acadia's Trofinetide are still continuing. Acadia's trial is for children, and should be finishing up now, as well as Anavex's Avatar adult study. Unfortunately, the Excellence-pediatric study has slipped AT LEAST well into next year. At least a year later than the article's table above shows. Competitively, schedules do matter!
Anavex's A2-73 has been shown to be superior, per analysis shown here and per Dr.Misslings corporate presentation:
Good finds Georgejj. Thanks
Yessir. Another child of the 80s
The $1249 meme gets more conservative weekly! LOL
Kb, Not sure. Maybe he needed to cut some time from presentation. Maybe lots of behind scenes discussion with agencies, so he was 'quiet'. Not a big deal at any rate.
The big news was he again "back of the napkined" out the immediate future revenue scene.
Yep, well said
Notes from DawsonJames call:
Missed the original, but caught the rebound version.
At about 8 minutes Dr.M BOLDLY states that Rett revenue per patient would be $200k to $600k or overall revenue of $2B to $6B.
Plug those numbers into your spreadsheets and Income statements! Dr.M's numbers imply that he is expecting 10,000 patients, adjust accordingly.
Visually, Dr.M ditched his usual library/desk location, for a virtual background of a small conference room. I prefer the actual library/desk location, your mileage may vary.
Data-wise, the presentation followed the September corporate presentation with no notable changes other than one. Interestingly, when he came to the Rett Avatar Study slide, he skipped over it entirely, and went directly to the Excellence Study slide.
As noted by others, the virtual background was real-time blended with Dr.M's image, such that "his hair was perfect" (name that tune..hint Warren Zevon)
OK so three for PD. Then which one is left off the pipeline chart?? I would guess the imaging trial.
BTW I remember the imaging trial originally a go, then M said something to the effect that it was not needed, then shortly after that it was a GO again. I guess it could be part of the PD or PDD trial. Any ideas??
It may already have been discussed with fda. Avxl is up 3x so far this year. Things are coming to a head. Hold on Amateur, as we watch the price skyrocket.
The PDD is pivotal. I think Dr.M got the most data from that. You are right P2 PD trial is the imaging trial, exploratory for imaging, sort of a biomarker check.
I don't understand what the strategy is for PD. PDD is certainly a target. Maybe the data to be released will add clarity and spawn more trials.
Lots happening now. Didnt Dr.Missling say there would be a lot of BIG data coming.
The next PD will probably be pivotal. I think the previous one was just exploratory, and never set up with the FDA to be pivotal. MJFox foundation was willing to sponsor it, but Dr.M might not have expected the great outcome.
All IMO
Ripper, good news!
Check the latest Corp presentation.
Both the upcoming FragileX and the Undisclosed disease trials are both expected to be PIVOTAL P2/3 trials, and starting yet this year!
Also, I imagine they will fill quickly, as Dr.Hagerman will certainly be behind one (think the ACTUAL proverbial rolodex), and probably both.
Thanks for reminding everyone about that.
It looks like a2-73 trials may all be pivotal P2/3 trials going forward.
Nice!
Georgejj, true the fda requested more Excellence trial subjects, but even before that there were twice as many Excellence subjects needed (69) as Avatar(33). And Excellence had only 29% as many sites as Avatar.
Excellence was delaying before, not surprisingly.
The FDA has requested more Excellence subjects, now 84. So there are now 2.5 times as many subjects as Avatar. And just recently, Excellence added two more sites, but there are still only 57% as many Excellence sites as Avatar sites. With 57% of the trial sites and 2.5 times the subjects...no wonder Excellence continues delaying.
Yes, there could be covid affects also, but that would affect BOTH Avatar and Excellence.
To finish sooner...add more trial sites!
Now maybe Anavex has plans for the Avatar sites, that are not pediatric, to be converted to pediatric. I have not heard anything to that effect, but that would help.
The Excellence trial completion has slipped to June 2022. Surprise surprise
per the rettsyndromenews.com PR. I confirmed that date on clinicaltrials.com too.
The good news is that the last time the clinicaltrials.com Avatar record was updated (July29 2021) Excellence was updated also. That is, it seems that whoever updates the Rett records updates Avatar and Excellence at same time. However, this last update, September 27, was only an Excellence update. One could ASSume that Avatar September 2021 completion date is still good. Fingers fully crossed.
FYI the trial site count is 7 for Avatar, and 4 for Excellence. Excellence just opened a new trial site in Canada. Isnt there a large country, just south of Canada, that might have some Rett girls and hospitals to quickly finish up a trial?
Thanks for the post georgejj!
A2-73 IMPROVES girls with Rett, no Rett CURE!
In adults the biggest improvements are in General Mood, Nighttime Behavior, Obsessive Compulsive Behavior, and others. But there are also improvements in other areas like Breathing Problems, Face Movements, etc. This is all spelled out in the latest corporate presentation.
So when you see pics of a girl that has been through A2-73 Rett treatment, you may not be able to SEE any difference in the picture! Caregivers know!
Biomarkers are very secondary to efficacy! As Dr.Kaufmann put it, "Biomarkers can support positive signal". They are just SUPPORTIVE evidence. The proof is in the efficacy.
Korenkos salary $120000, last I checked. See annual reports...
High level execs usually get salary + incentives / shares / bonuses / warrants / options.
Cameron, the Mayo Clinic is heavily involved in many clinical trials. I suspect they are able to support Dr.K with a large part of the trial process, which he is unfamiliar with. They probably worked together on the protocol, risk analysis, and monitoring procedures. Mayo probably already has the trial managers, software, and doctors, in place to handle the monitoring process. That is a huge amount to take off of Dr.Ks plate. Mayo wants to protect their patients, foremost, so they had to work with Dr.K to establish the patient population inclusion specs, i.e. ages, severity, number of patients, etc. and then define human treatment practices.
Very exciting stuff.
Classics, I think the news MAY be better. I could be wrong, here is my proposal:
PR Language - Clue 1: "Vivos Inc....has submitted the IDE Investigational Device Exemption...as part of a pre-submission meeting process."
---Quote from Blueprint document Step 3, "In summary, this is the time where you address any issues with the test plan and investigation plan, but is before the IDE is submitted".
Note that Dr.K did NOT say he SUBMITTED any test plan, investigation plan, or sterilization validations, biocompatibility testing, animal
study protocols, and/or clinical study protocols, pre-submission package, etc. Which are all part of Step 3.
Instead he says SUBMITTED THE IDE Investigational Device Exemption and he explicitly spells out exactly what IDE means: Investigational Device Exemption.
Step 4 is the IDE Submission
Step 4 says quote "Once the interactive pre-submission is complete and your data package is complete, it is time to assemble your IDE....Once submitted, the IDE goes through a 30-day review cycle. Since the 30-day review period is highly interactive..."
This appears to be where the process is.
TO ADDRESS YOUR TWO REBUTTALS (expected??):
1) But PR says "as part of a pre-submission meeting process".
As described either the first part of the statement below is wrong or the second part is wrong:
"has submitted the IDE Investigational Device Exemption...as part of a pre-submission meeting process"
Is the second part just being technically imprecise?
OR
Did the first part really mean test plan, or investigation plan or pre-submission package---when he said "IDE Investigational Device Exemption"?
Again he did not mention any type of submission but IDE, and then explicitly defined IDE. This is being very precise in defining what was submitted.
So I lean towards, he was just being imprecise when saying "as part of a pre-submission meeting process". I think he was VERY precise in his use of IDE Investigational Device Exemption.
2) PR Language - Clue 2: This review typically takes several iterations and we will continue with biocompatibility testing in parallel.
---I suspect, they got all the ducks in a row, except biocompatibility testing, and in their discussions with FDA, FDA said something to the effect, go ahead and submit the IDE, and while we review it, finish the work on biocompatibility testing.
One final bit of logic. What is the purpose of this PR?
Is it to say that we are in the middle of an iterative FDA process, or maybe to define a specific goal that was achieved?
Lets look at the first words of the PR. Good documents always define the purpose first, whether it is a story or a paragraph.
The PR starts with:
Vivos Inc. is pleased to announce that it has submitted the IDE, Investigational Device Exemption for The Early Feasibility Medical Device Study
So, if we are in Step4, we should have IDE acceptance/denial within 30 days.
To be fair its a 35% premium forAcceleron.
Seems news of the BOut leaked out, and the price rose from 130$ to the BO price. You can check their Sp chart.
You raise a good question though...
Would 35% be a good premium for YOUR Avxl shares??
Bs manipulate avxl sp down 35% then BO!!
True, I understand, but Avatar is finally finishing up now. That is, as they say, water under the bridge. Since the US Rett trial great TLD, we have seen that Rett, will most likely lead to our first revenue. This has been understood for 9 months now, and Avatar and Excellence would be key to that first (adult) revenue and second (pediatric) revenue. Given that understanding, Excellence should have been given high priority this whole year. Ana should at least learn from past mistakes! Unnecessary delays as we sit on our growing pile of cash.
TC, the delay is a function of only having 4 trial sites, to get 84 patients. Compare that to the number of sites for Avatar and the avatar patient count, or the alz trial.
The delay was predicted.
The questions are...
How much does it cost to open trial sites?
How many years worth of cash is Ana sitting on?
How long has Ana had enough cash to fund additional sites?
What are the priorities for assigning this cash?
Who allocates this cash to projects?
How much will this Rett delay affect revenue?
What is the cost/benefit analysis for this revenue versus trial site cost?
Why is this critical Rett program Excellence not seen as a HIGH priority?
This is an example of how Ana has redefined the meaning of SOON!!
These are questions upper management should be dealing with!
Georgej, continuing your AnavexA2-73 vs SavaSimufilam comparison. Regarding your 110:8 Sigmar1:filaminA ratio of papers:
The integrity of 3 of those 8 filaminA papers are being disputed (see eliesbik's "Cassava Sciences: Of stocks and blots" at scienceintegritydigest.com). Two of those papers in dispute are all about Sava's biomarkers.
The Sava proponents say that the legal problems have only to do with the biomarker data.
While doing counts...Sava's latest slide deck (CASSAVADeck(Sept2021)b) has four slides dedicated to their biomarker findings, with only 1 dedicated to cognition findings. Which one is the beef?
I have only been able to find terse cognition top line data from Sava. No details published. FYI Peter Karol did some analysis of Anavex 2-73 and Simufilam.
Sava's Simufilam may yet prove therapeutic, but the questions have not been answered. Interesting to watch.
Georgejj, I think you're correct 69 to 84!
Dr.M actually said "from 96 to 84". He messed it up worse than me! Lol I should have double checked that.
Thanks