Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
leo, No it is simple OLD math. Appears some codgers dont know how to interpret data and make a graph. Where is the error?? There isnt one! I am waiting. The Lilly results, are so poor, it is easily seen, when plotted against the AVXL data.
froll, its correct. If you think it is not, then show your work or explain why it is not correct please.
Baseline
Ray, Alz cog studies have two references, baseline and placebo. The placebo will always be close to the historical decline(which is also relative to the study baseline), because they both should have zero affect.
You could argue that there was no placebo in the anavex study, and that is correct. It is generally accepted, and I think DrM has also said, that the low/medium dose is assumed to be approximately the placebo response level. This might actually be conservative, as even those lower doses may have had a small positive response, larger than a placebo!
Remember Dr.Fadiran worked for the FDA for 24years, and is advising Dr.Missling on FDA affairs.
While I have not been happy with the apparent additional enrollments(versus published clinicaltrials.gov numbers), and longer schedules, it may be that this is due to Dr.Fadiran's advice... maybe to help solidify the phase 3 data acceptance for approvals.
Lilly donanemab versus A273 comparison. Graphically shown below!
From Lilly's PR, "Specifically, at 76 weeks compared to baseline, treatment with donanemab slowed decline by 32 percent compared to placebo as measured by the iADRS, which was statistically significant. "
Slowed decline by 32 percent compared to placebo, means it still declined 68%.
Compare this to Anavex's, peer reviewed "..Analysis of the blarcamesine (ANAVEX2-73) Phase 2a clinical study", figure 2b, where all high dose patients declined 1 ADCS-ADL point, versus the low/medium dose (assumed to be at least placebo or no dose) of -25 points at 148 weeks.
High dose patients declined 4% of what the low/medium dose patients declined.
Or as Lilly's PR would say, for high dose patients, A2-73 SLOWED declined by 96%!
Plotting Lilly's donandmab result, 68% decline (68% of 25 is 17), on the Anavex Figure 2b.
In the donanemab arm, 30.5 percent of patients discontinued treatment due to an adverse event and half of these discontinuations were due to ARIA-related events.
Microhemorrhages (7.6 percent) and superficial siderosis of central nervous system (13.7 percent), nausea (10.7 percent), and infusion-related reaction (IRR) (7.6 percent).
Superficial hemosiderosis of the central nervous system is a disease of the brain resulting from chronic iron deposition in neuronal tissues associated with cerebrospinal fluid.
A2-73 is administered as a pill, while donanemab is delivered by IV (from which 7.6% of patients discontinued because of infusion-related reaction!
The siderosis is definitely not good, and the infusion-related reaction of 7.6% seems suprisingly high.
There is a clear winner, A2-73.
Red, MAJORreason to resist takeover (must read) is this.
Ana is not like other major pharmas in these ways:
NO R&D department
No debt interest payments
No huge organization-salaries
We will have minimal sales/marketing staff.
Why is this important?
Because this means we have MINIMAL expenses!!
MAXIMUM AMOUNT OF SALES DOLLARS DROP STRAIGHT TO BOTTOM LINE!!
If we are bought out, no company will be able to produce the Return On Investment, that Ana can deliver, if she is INDEPENDENT.
nidan, totally agree. TRANSFORMATIVE YEAR, ---Dr.M called it. Just sitting back and enjoying the ride this year. Not concerned about the company's direction at all. DrM is doing a good job.
B60611, I too have wondered whether Avatar was still not fully enrolled, or whether DrM has decided not to pr it. I can't come up with a reason not to. He seems to have been very stealthy about the avatar status, like in the Dec(?) CC he updated the Alz enrollment but not Avatar. Maybe the covid spike of Nov/Dec delayed enrollments. I don't believe there is anything negative, but I am left to wonder.
Yeah, if Dr.M did not pursue all paths, he would be maligned for not doing so. Its not like the pharma industry moves to quickly...it moves at a snails pace (except operation Warp Speed)!
All the new eyes on Anavex is reflected in the nice SP response to news, that in the past, would not have moved the needle.
JWC3, good point A1066 trials should be short! How long does it take to tell if the pain is gone! So much on Ana's plate!
kund, please show a better chart from another drug. Biogen would love to have that chart. They would not have admitted failure with their huge number of patients. Keep trying LOL
Redshoulder, Thanks for the kind words. We all contribute, there are definitely many great posters here that make this board useful.
Here's the A2-73 treatment score for FragileX Syndrome:
This is the 30000 foot, non-technical, view of the results of the Murine Fragile X study. I like to evaluate efficacy by how far does a drug return the afflicted back to normal. This will be given as a percentage, with 100% being the afflicted was returned to complete normalcy(cannot do better than that!). Oh yes, the afflicted in this case were, of course, mice.
The three most significant parts of the study evaluated, EFFICACY and BIOMARKERS, IMAGING. The most significant and most revealing were the efficacy and biomarkers, so they will be discussed here.
The efficacy was based on these characteristics/measures:
1) Hyperactivity - Open Field Test.................100%
2) Freezing Response - Fear Conditioning........100%
3) Perseverance and Anxiety - Marble Burying.....50%
Also shown above is the percentage that each was improved, compared to normalcy. Hyperactivity and Freezing were totally returned to normal, while "Marble Burying" returned half way to normal.
Weighting each of the three equally (each 33.3% max), efficacy score would be:
The mice on A-73 returned 83.3% back to normal!
The biomarkers were:
1) pAkt....68.7%
2) pERK....39.3%
3) BDNF....86.9%
Also shown above is the percentage that each biomarker was moved towards normalcy. Weighting each of the three equally (each 33.3% max), efficacy score would be 64.3%. This means the biomarkers moved almost 2/3 back to normal. Biomarkers are indicators, the real proof is in the efficacy.
CONCLUSIONS:
It is clear why Fragile X expert, Dr.Hagerman, is very enthusiastic about getting A2-73 trials going for humans, with a hopeful improvements of 83.3%! As quoted in the article "...this neurodevelopment disorder continues to have an unmet therapeutic need.".
The efficacy numbers are amazingly good. The biomarker improvements support and validate the efficacy.
This study adds to the growing body of evidence, validating A2-73 as a powerful new drug.
The usual caveats exist, this is a murine study(not humans), there were not a lot of mice used, there were limited efficacy tests, all IMHO, etc.
Thanks to TTT for posting the link to the Murine Fragile X study.
Yes, approvals follow pivotal data. TRANSFORMATIONAL YEAR I think Dr.M called it!
Remember that phrase and get on board!
Shoulder, and all markets down now, Ana UP!
Magoo1, the excitement about Avatar is that it is our FIRST pivotal trial that we will approach the fda/tga. Clinicaltrials.gov says that trial should be finishing. Dr.M expects results by June.
The dosage is higher so it is expected that the signal will also be even better.
Nice comment about people checking the 2-73 Trofinetide comparison
Dr.M had great response for Trofinetide question.
He said A2-73 had a response that was multiple times better than Trofinetide and did not have the severe adverse affect, that was seen with Trofinetide.
He confirmed my Rett comparison of A2-73 and Trofinetide (sept 19,2019) that I posted where I concluded the following:
The reward side of the equation, is very positive. The technology is first class, as is Dr.K, and the potential. Currently I am looking at the risk side and competition.
Thanks for the detailed and prompt reply.
Two equations three unknowns. But I will let my uncle Fib A. Nacci explain it, as he is series ly an expert on numbers.
Look out investor, your sarcasm title is in jeopardy tonight!
I always like analysts ratings nomenclature. Like "Overweight" is one step above "Hold"...NOT a "Buy" mind you! Yet they will raise a price target from $10 to $25. A presumed gain of 250%. If I believed some stock was going up 250%, I would give that a rating of "Bloody buy all you can"!!
LOL
<rant off>
kayakwench, or anyone. I am doing DD on the company, and have a question.
Who takes over if something happens to Dr.Korenko? Like he gets sick long term, car accident, whatever. It does not look like there is an assistant that will quickly pick up the pieces.
Thanks for the post kayakwench, it helped a lot with the 'history', and I think your DD is similar to mine!
Biostock, read your post second time, and I just 'got' what you are getting at. In MY words, two tennis players using, MAYBE, equally effective racquets, play a game of tennis. If one player does NOT know how to use a racquet, he will get left behind in the dust! I.e. the player that knows how his racquet/drug works, will run circles around the other player.
You are saying, it is traditional shot in the dark pharma, versus new school precision pharma.
Anavex got top billing in MJFFoundation article, but also sounded the most exciting:
"...a drug with the potential to slow or stop Parkinson’s"
ARTICLE here
Thanks for posting georgejj
Termite, please post the link you are referring to, regarding the June 30 presentation. Thanks!
Abe, the money that was in the bank, was fine for two years of normal trial levels, but there appears to be more than the normal number of trials lining up. Suppose trial counts double, then cash would be enough for only one year. Extra cash would be wise to have, especially if available at a small dilution level.
Getting into 2-73 distribution, for Rett for starters, will require investment in space and people. This will need to be at least started, soon, before the revenue stream is present. Extra cash would be wise to have, especially if available at a small dilution level.
EVENTUALLY revenue will cover all expenses.
Going forward, whenever cash, or loans are needed, having cash in hand puts Ana in a better negotiating (think interest rate, or cost of cantor) position.
I am confident Dr.Missling would agree with one or all of the reasons above.
Loved this McM!! Adding my haha
A few more CC comments, not seen here:
Positioning 3-71 for Frontal Temporal Dementia, so it won't compete with 2-73. Good move!
3-71 trial challenge is to ascend to max dose. Dr.M said this went very well, no problems. Good!
3-71 trial results expected much earlier than June. Good!
LOTS to be discussed with FDA this year. Good!
FragileX preclinical data to be packaged and published soon. Ok soon.
I don't remember seeing ANY "analysis" of avxl. Did I miss it?
Capitalist econonomics teaches that excessive profits rarely last long, for many reasons. Foremost, excessive profits attract competition, which forces prices and profits down. Businesses have to work very hard to make any profit. Anavex will show a profit someday.
As far as the government, well the Social Security Trust Fund is a good case in point. There was such a fund once upon a time. But Pres.Johnson took it all and spent it!! Nice. 0$ left. They still talk about this "Soc Sec Trust Fund" and most of the sheep believe it.
Biogen Pipeline comparison:
Biogen shows 8 phase three trials ongoing, but two of those are Aducanumab, which may be null and void, very soon.
Leaving
6 Biogen phase three trials
as compared to little Ana's
3 Anavex phase three trials (and one being for Alz!)
David and Goliath!
Bio, followup. I checked Biogens last financial report(annual) and they had about $3Billion in cash. (I would have thought they had more, whatever.) So, yes, paying down debt for $1.75Billion is cleaning up their books, and MAY signal not anticipating good times rolling. However, that said, I think they would have little trouble raising back a few billion to make a purchase.
Thanks for the always thought provoking posts!
Totally agree Raja. The old trading range, and assumptions, have been erased with all the new eyes and interest in Ana. Assuming they are still in place is financially dangerous.
What about the trials that are 2 years late? Yeah right.
The tweets are the work of the new marketing team. They are still trying to figure out how to clean up the website. Lol
Thanks for the comments guys. According to the link power supplied, it appears to me (imo) the added trial sites are for easier approval by regulatory bodies in EU, Canada, and UK (in addition to US and Australia). Very good coverage!
A side benefit is the larger sample size N for statistics. This is imo also, as froll said we have no more details.
Power, looking at the wiki link you provided, seems to me, to imply that these 66% more sites (and patients), being added now, near the end of the 450 enrollment, would be to preclude having to run a second phase 3 trial, needed to get additional regulatory agencies on board for approval (EU/FDA/Canada). (Sorry for the run on sentence, fourth grade teacher please ignore.)
Since phase 4 is for post marketing (after approved for sales), surveillance monitoring of the drugs affects.
I suppose not having to run an extra p3 trial, is worth the extra additional months. Its just that I have been waiting a long time already lol.
Investor et al, all well and good. But why did Ana wait until the last 3 months, when we are ~80% enrolled, to finally open 66% MORE trial sites, with more on the way??
It appears that Ana could have had these sites up and running earlier, and finished up enrolling sooner, so Ana could have met the scheduled trial end with the 450 or more patients.
Instead, Ana chose to add all these sites near the end of enrollment, to enroll 450 (+++200??) patients and stretch out the trial completion from early next year to mid next year. Argghh
Agreed, more patients equals more statistical resolution, but if the FDA was good with 450, that should have been the goal. Or what changed??
Am I the only one unhappy about this? Seems like I have seen this before.
plex, and now on business channels. We knew it would happen somehow, now we know!! Strange how it played out! Outa the bag now.
Holding Long.