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I agree with you. I'm being very conservative with regard to multiple aspects of the potential revenue stream. % patients, cost per year, 50% revenue sharing with BP. Many more multiples available depending on how things go. I'm investing in this as I believe Rett approval is >80% probable. But it is nice to dream about all the other possibilities.
Maybe sooner. Who knows. I'm being very conservative with the number of patients treated (20%), $600 per month cost for the large indications and 50% revenue sharing for a partner. If AVXL can get a revenue stream going (Rett, Fragile X) and a partnership there would be plenty of $$$ to support multiple PH3 trials across all the indications in parallel.
Nice to dream
GO AVXL
It has been noted that once AVXL has (when/if?) approval for 2-73 for Rett only one trial is required to repurpose an already approved drug for another indication. The other target being noted on the board is AZ as AVXL is furthest along with trials and data for AZ.
However, as much as I would love to see AVXL get approval for AZ using the repurposed path I'm actually holding because of my belief that the EXCELLENCE trial will be successful and lead to repurposing of A2-73 for a multiple of orphan diseases.
approximate number of US patients by indication
US Rett 11,000
US Fragile X 88,000
US Infantile Spasms 10,000
US Angelman Syndrome 27,000
@20,000 treated patients * $10,000 per month = $200,000,000 per month, $2.4B per year. 5x to 10x to get market cap. Nice.
GO AVXL
It will be interesting to see if the MMs can hold the price below $8 through tomorrow and even the Oct 20 option expiry date.
1333 open Sept calls @ $8
450 open Sept calls @ $8.5
935 open Sept calls @ $9
For October the open interest is huge
10433 open Oct calls @ $8
859 open Oct calls @ $9
3713 open Oct calls @ $10
I believe the big players like to sell options and look for them to expire. Looks like they are having a little bit of a battle holding AVXL underneath $8 as I type this. My suspicion is that we will close very near $8 tomorrow. Then run up to 9ish between Sept and Oct expiry dates but then settle back to $8 again at the Oct expiry date.
However if we shoot to $20-$30 on great EXCELLANCE news I'll be ready to unload some holdings and sell out the calls at this higher price.
I feel its finally going to get exciting.
There are 444 open call contracts at the $8 strike, 92 at the $8.5 strike and 1022 @ the $9 strike expiring this Friday. The goal for the MM is to have options expire worthless. Therefore, I expect we will see a dip to the $8 area for the close Friday. Then I'll look to sell cash covered puts around the $7-$8 strikes.
I've been selling options on AVXL over the past three years to lower my cost basis. Selling cash covered puts in the $7-$8 area and covered calls in the $9-$10 area when there is excitement about an upcoming conf or something. I keep a significant baseline of shares for the potential spike when we move to approval on Rett Syndrome. Best financial decision / tactic I've every done. ~4-6% per month on the cash and stock value when selling options near the current price.
GO AVXL
not trading advice
I would love to see Anavex charge ~$50K per year for A2-73 for Rett. @10000 patients this would be $500M per year, 5x to 10x revenue to market cap of $2.5B to $5B, easily $25 to $50 pps. More than enough to fund all the other indications. I would suspect that the EU countries will not accept the ACADs $400K+ price for a drug which shows marginal improvement and some issues with quality of life.
Probably the main reason for the tight non-overlapping ranges for the liquid dose is that it is given by IV. No gut biome or digestive tract getting in the way of the concentration in the blood stream. The smaller range of the liquid IV dose is most likely related to how quickly each individual metabolizes the drug.
I don't think the following would happen but I ran the numbers just for grins.
At $100K per year.
15000 Rett patients, assume 75% can get insurance coverage. This might be high but this would be 11,250 patients treated. Revenue to AVXL of $1.125B. Very nice. Virtually no off label prescriptions written or filled because very very few could afford the out of pocket $100K.
But
At $12K per year, $1K per month.
AZ, Parkinson's, dementia patient population of 6M. Assume 10% of these families can afford the $1K per month. If doctors will prescribe off label there could be a significant pool of patient families that would pay the out of pocket drug cost. Now the total patients treated are Rett + 10% of 6M or 611,250 patients. At $12K per year the revenue to AVXL is $7.335B.
Here's an analysis which says Anavex is correct on their calcs and p values.
https://www.investorvillage.com/groups.asp?mb=20622&mn=1054&pt=msg&mid=23759087
The lineup....
Tuesday
4:50 pm Clarity AD: A Phase 3 Placebo-Controlled, Double-Blind, Parallel-Group, 18-Month Study Evaluating Lecanemab in Early Alzheimer's Disease (BIIB, Eisai)
Wednesday
3:00pm: TRAILBLAZER-ALZ 4: Topline study results directly comparing donanemab to aducanumab on amyloid lowering in early, symptomatic Alzheimer’s disease (Lilly)
4:15: Topline Results of Phase III GRADUATE I & II Pivotal Trials with Subcutaneous Gantenerumab (Roche)
Thursday
4:30 pm Top Line Data of ANAVEX®2-73 (blarcamesine) Randomized, Double-blind, Multicenter, Placebo-controlled Phase 2b/3 in Patients with Early Alzheimer’s Disease (Anavex)
I find it very difficult to believe that Missling is going to walk Anavex into that lineup with anything less than stellar results. If he does jump into that spotlight with so-so results then every disparaging word typed regarding his management skill will be justified AND I will have severely misjudged his fitness for a CEO position.
Thanks for the info. I was wondering what happened.
Any thoughts on why they would up the requirements right now? Too much speculation and potential overextension by individuals?
I've been selling puts and some calls on AVXL for about a year now.
There is an uncanny ability for the price to be at a point where almost all the calls written expire worthless on the monthly options. I know that this behavior is not "new" info for those experienced in option trading.
This seemly coordinated price movement is why I believe that there is actually a cabal or maybe an unstated but in place agreement between the large trading firms as to where the price should be on a given day.
Based on this history I've got to believe we will be somewhere just under $20 a share on the close this Friday.
Cheers.
GO AVXL
Sounds remarkably like DCVAX. Not exact and they don't talk about maturation of dendritic cells... but overall similarities apparent.
https://news.mit.edu/2021/new-cancer-treatment-may-reawaken-immune-system-1019
Regarding drug trial recruitment...
One item people need to be aware of is that patient enrollment is deliberately spread across multiple sites without having any one site having a preponderance of patients in the trial. In order to avoid any bias by site or investigator trials will proportion approximately how many patients are required at each site.
A trial targeting 450 patients across 30 sites and 98% enrolled might seem like it should only take another week to be fully enrolled. The reality is that the last couple of sites that opened for recruitment will need to be the sites that fill the last spots. This could take several weeks or a month.
The frequency and accuracy of the trial info on .gov will not show this. I've see many times where trials have dozens of sites recruiting for the last 10 patients, which seems like it should only take a week but takes much longer. Then the PR finally comes out that the trial is fully enrolled and then the trial data - status at clinical trials is updated after the fact.
A potential long position which would pay off handsomely would be a vertical put position 30/35 in the July or Oct strike month.
Pricing right now, after hours is not reliable. You will not get what is currently quoted for these verticals.
You might be able to get a credit for each July +30/-35 vertical of $440 or so per contract. Risk is $60 per contract. Reward / risk of 7.3.
Or the Oct +30/-35 vertical.. If you sell this you might be able to get $420 credit or so... risk $80. Reward / risk of 5.25.
The Oct strikes give more time for CVM to release data. I've placed my vertical in Oct. I was able to get a credit of $440 per contract about a month ago.
If you purchase 100 shares right now you will need ~$2000 to do so. A 6x profit would require the stock to be at $140 per share. Certainly could happen.
But if you do the vertical
$2030 will allow you to sell ~29 contracts. With a credit premium of $430 per contract x 29 contract, profit $430 x 29 = $12470. IF THE STOCK IS ABOVE $35 per share at the Oct expiration date. If the stock is below $30 per share you lose all.
Just another way to play the potential surge in price. Have to be right though. If the stock stays where its at you will lose all unless you close the position (purchase the credit spread) before expiration to minimize loss.
Just something to think about. If you are not familiar with options this is not a play for you. But if you understand options and are willing to lose whatever you would purchase the stock for it is a way to generate a large return with a smaller stock price movement than if you were to purchase the stock or a call option.
NOT INVESTMENT ADVICE. I'M WRONG MORE OFTEN THAN I AM RIGHT...
added thought... Everything in biotech takes longer than anyone expects. So in Dec 2020 it seemed like a very safe bet that data would be out by July. Now... Hmmmm... data could still show up in Aug or Sept and the July verticals sold in Dec 2020 would be a total loss. There was a post with a study link on the NWBO board that full trial data for cancer trials takes a median of 300 days to be published. 10 months and this is the median. So make sure you are far enough out in time to allow whatever event you are investing (betting) on to happen.
Thanks to CherryTree1 on the NWBO board for the information I've copied.
How Long It Takes to Publish Clinical Trial Data - Oncology Times
https://journals.lww.com/oncology-times/fulltext/2018/09200/3_questions_on____how_long_it_takes_to_publish.16.aspx
Quote:
Oncologists and other members of the cancer care team would presumably want that information sooner rather than later to be able to more appropriately prescribe those drugs and take care of their patients. But new data that reviewed 100 pharmaceutical company-sponsored clinical trials shows that the median delay from when results are available to publication of complete data was 300 days . . .
No way of knowing if non-oncology trial data would be a shorter time frame...
Thanks for the summary information.
I was reviewing the model presented by the Ladenburg Thalmann analyst.
I appreciate that an analyst at this time would lowball estimates but this seems really low especially for 2023 and 2024.
COGS of 20%???? One pill probably doesn't even cost $1 to make. A month's supply would be $30 COGS. For Rett a revenue figure of $1000 per patient per month is probably low. $30/$1000 ~ 3% COGS.
Also there is no revenue for any other orphan disease modeled. Hmmm... I'm thinking that if Rett is successful then the potential for Fragile X, Frontal Lobe Dementia, Infantile Spasms, etc.. becomes that much more de-risked and we will see revenue in at least one other orphan disease by 2024.
And as Red Shoulder has posted on; PD & PDD. That's huge.
Exciting times.
GO AVXL
Completely agree that the potential revenue projections for Anavex are staggering.
I believe what we as investors must do now is focus on this statement in your post;
"Not the kind of thing that should guide the taking of an AVXL ownership position right now. There are lots of more relevant and controlling other data on that presently available for intelligent investments in AVXL equity positions."
Given that the potential revenue streams to Anavex are staggering, what is the possibility that those revenue streams will be realized. Just because I can return $10M or more for each dollar invested (gambled) in the lottery doesn't mean I should risk any significant sum of money. In fact, for a lottery investment I should consider the invested money the same as if I used the cash for fire kindling.
For Anavex, as you've pointed out and as I believe the continuing pre-clinical and clinical data continues to prove, is that the company is being rapidly de-risked. Each data set and latest lab experiments build a higher and higher base of understand and effectiveness for the company's pipeline.
Looking forward to the next few years.
Cheers
ps. GO AVXL
Yes. Future share count
Actually this spreadsheet is on my computer so I don't have a URL for it.
The revenue I estimated is yearly.
Rett patient total; = 30K
40% treated; = 12K
$24000 yearly revenue; = $288M
I'm being very conservative. The treatment cost may be much higher.
Alexion's drug Soliris is listed at $500K per year. This is probably negotiated to be much lower but still points to the conservative nature of the estimates.
Thanks for checking.
NWDR
go AVXL... actually wait another week till I'm fully loaded...
Hmmm... How do I link the spreadsheet. Can't upload like an image.
If the Rett trials confirm and improve (higher dose, younger patients) the first trial results then I firmly believe A2-73 will be approved for Rett treatment. If this happens then the market will begin to price in the other rare disease treatment approvals (highlighted in light blue). Not the full value but some percentage of possible approval which will increase as more trial data is completed, scrubbed and released.
The shares outstanding, percentage of patients treated, revenue per patient per year are all conservative.
Thank you. I shall read up. Cheers
Anyone have a good link about the implications of owning EPD or other MLC, LLCs that use K9s in a 401K? Someone told me that you couldn't own the MLC or LLCs in 401Ks. Trying to get to the truth. I'm willing to do the reading but a Google search didn't turn up anything special.
Thanks
Right there with you.
I am really looking forward to the results of the PDD and Rett Anavex A2-73 trials. I believe there is a strong possibility of significant improvement in patients. However, as a long time stock investor (>30yrs) I have learned that there is no sure thing. With that being said consider...
(1) Sleep improvement in AZ patients was universal in all patients who initially reported problems. I believe the initial baseline had 8 patients with sleep issues and after 12 weeks or so no patients had sleep issues. I could be off by a couple of patients either way.
As a long time care giver and guardian for my Mom who suffers from mental illness I have seen first hand the compounding effects of lack of sleep as well as sleep issues being the early signs of a mental break. As I have posted before the assisted living facility where my Mom is at has instructions to immediately notify me at any sign of sleep issues. When this occurs I call the psych doc and he agrees to up the dose of meds to get her to sleep. The meds are much better now than 20 years ago but do cause drowsiness throughout the day and can aggravate heart issues. The improvement in sleep is what initially attracted my attention to A2-73.
(2) The anecdotal reports of improvement in AZ patients including several news videos. When has this improvement been seen in AZ patients before? And a not insignificant number of patients reporting improvement... golf, Ern, painting, piano, using public transport... Sheez, I can barely figure out public transport. Gonna have to get some of that A2-73.
(3) GABA increase and glutamate decrease in Rett patients. I've spent some time reading papers about GABA and glutamate and these biomarkers as targets for Parkinson's treatment. ALL the papers I have seen and read discuss either trying to increase GABA or decrease glutamate. A2-73 apparently does both without specifically targeting the generation or modulation of GABA and glutamate. Apparently A2-73 works by restoring normal brain function, homeostasis.
(4) Relatively benign safety profile. Probably easy to manage by increasing dosage slowly and lowering when necessary.
Sleep, GABA & glutamate improvements, care giver reports on AZ patients plus the multiple research papers over the last 4 years on Sigma 1 targets. Something positive happens to patients / people taking A2-73.
The Parkinson's trial primary endpoint is improvement in patients with Parkinson's Disease Dementia. A2-73 doesn't have to solve all the physical issues with Parkinson's... just reduce the dementia (think sleep improvement).
Bottom line for me;
Is the company smart enough to be able to put together trials that show significant improvement in AZ, PDD and Rett given the data that they have?
I'm betting yes.
GO AVXL
In the past, on this msg board, there has been much discussion and conjecture about the dose of A2-73 for an individual and the relationship to the blood concentration for the same individual.
In the latest article I noticed the following paragraphs;
------------------------------------------------------------
"Steady-state plasma levels of blarcamesine (ANAVEX2-73) and its metabolite ANAVEX19-144 were measured in Part B in blood samples collected at prespecified time points (weeks 17, 31, 41, and 53). Mean concentration values in ng/mL were averaged for each patient. Figure S1e shows mean plasma concentrations of blarcamesine (ANAVEX2-73) and its metabolite ANAVEX19-144 in the ANAVEX2-73-002 study.
The relationship between dose and plasma concentration of blarcamesine (ANAVEX2-73) was determined in a Phase 1 study,13 and can be assumed to be linear in the 1 to 60 mg range in healthy male subjects. The dose-dependent increase of plasma concentration of blarcamesine (ANAVEX2-73) and metabolite has also been confirmed in the present study, as shown in Fig. S1b."
-----------------------------------------------------------
It seems that this paper is stating the concentration of A2-73 and it's metabolite have a linear relationship with the dosage. In previous company presentations I had thought that this was not the case. A low dosage might yield a higher concentration and a high dose doesn't necessarily mean a high concentration.
I searched through this paper and didn't find any explicit information for dosage to blood concentration. Nor did I find this in previous company presentations. What I see is the company stating high, medium or low dose or high, low concentration.
I'm very interested to see what happens if the PDD trial shows a significant number of patients taking 50mg per day (and tolerating this dose).
I don't view A2-73 as being able to cure many patients, unfortunately. However, I think the bar with current treatments for PDD, AD and Rett is so low that we have a good shot of approval for these indications. Especially if the safety profile continues to look good.
GABA increase has already been measured and recorded in the first 6 Rett patients.
https://parkinsonsmi.org/managing-pd/entry/gaba-a-a-new-avenue-in-pd-research
".. Animal studies of PD suggest that one of the reasons why people with PD have difficulties with balance and gait is that GABA is excessively blocking the outgoing connections of the basal ganglia (movement centers) in the brain. Therefore, the use of medications that may slightly decrease these excessive blocking functions may help people with PD to move better."
Glutamate decrease has already been measured and reported in the first 6 Rett patients.
https://www.sciencedirect.com/science/article/abs/pii/S2210533613001196
In pathological conditions such as Parkinson's disease (PD), glutamatergic transmission is considerably affected, thereby contributing to the alterations involved in this disorder. Neurotransmitter alterations in direct and indirect nigro-striatal pathways occurring in PD are known to involve glutamatergic hyperactivity. It has been suggested that this hyperactive pattern plays a dual role: on one hand, it promotes excitotoxic events that contribute to the neurodegenerative process, while on the other hand, it contributes to the pathophysiology of dyskinesias and motor fluctuations that have been associated with the chronic use of levodopa (l-DOPA).
https://www.anavex.com/anavex-life-sciences-announces-preliminary-clinical-efficacy-data-of-its-u-s-phase-2-clinical-trial-of-anavex2-73-in-patients-with-rett-syndrome/
I believe that A2-73 will be shown to be effective in helping patients with Parkinson's Disease.
Why?
Because we already have proof, in humans, that A2-73 helps restore the correct balance of GABA and Glutamate in Rett patients.
https://www.frontiersin.org/articles/10.3389/fneur.2018.00806/full
Literally dozens of studies can be found which exam GABA and Glutamate levels in PD patients.
An imbalance of GABA and Glutamate is measurable in PD patients.
Restoration toward normal levels was measured in Rett patients, not in the lab or in mice, but in humans. I would expect a similar restoration of a normal balance between GABA and Glutamate in PD patients and a subsequent relief of some of the symptoms of PD.
GO AVXL
20 mg when we come out of lock down and start interacting in society again. More if / when I get sick. 20 mg is ~200% of daily recommended amount. Zinc is known to be fairly rapidly depleted when you are sick.
For best results they should use zinc supplementation with hydroxychloroquine. HydroxC is an ionophore for zinc which allows zinc to cross the cell membrane. Once in a cell zinc prevents C19 virus replication. All the studies using hydroxychloroquine without zinc supplementation are not resulting in the clinical benefits that are being seen by some docs because they are not supplementing with zinc. Can't these people do diligence. So frustrating that hydrox + zinc is languishing while some expensive IV treatment of marginal benefit from BP is getting fast tracked.
GO NWBO.
ps. Quercetin is also a ionophore for zinc. While I will try and avoid getting Covid-19 I do expect that eventually I will get the virus. Hard to avoid indefinitely. But I'm supplementing with VitD already and will start zinc + quercetin when we come out of lock down.
Be safe
I'll grab 8/13/20
What I've had happen is that the broker automatically executes the other side of the trade. You should check but I think that is probably pretty standard. The other thing to do is when you setup the trade consider using puts. If the price takes off the put you sold, an obligation to purchase, will never get exercised because why would someone buy stock on the market at say $25 and then exercise a put to sell at $20. Only issue with the puts is that there will not be as much volume so you may not be able to get executed as close to the midpoint as on the call side.