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So there are several pieces to the puzzle of valuation and how it compares to REGNs early valuation and subsequent rise. I believe in 2006 Bayer and Regeneron signed their partnership agreement for the trials and commercialization of Eylea. In this respect this means that AVXL is still pre 2006 relative to REGN. However, I believe AVXL pps rise will be much quicker with good data from a trial. A2-73 targets a much much larger market than REGNs Eylea. Eylea sales continue to expand but the growth rate is not sufficient to drive the premium pps for REGN any longer. Once revenues start one metric I like to keep my eye on is the yearly growth rate in sales. If the per year growth rate is like 100% then is is actually not unusual to see a PE of 100. I believe that A2-73 sales growth will be like what GILD saw with their HCV med. The difference of course is that A2-73 will be taken for the rest of a patients life while Sovaldi or Harvoni are only take for 8 to 12 weeks.
I really hope Dr. Missling prices A2-73 to allow access for at least some patients even before insurance companies will pay reimbursement. A successful treatment for Rhett would allow AVXL to charge $100K or more per year... orphan disease. But this will put A2-73 out of reach of the vast majority of people. Imagine instead that AVXL charges say $6K per year. $500 per month. While not all families could afford this price there would be a sigificant number of extended families that could come up with $500 per month to help a family member with AZ or Epilepsy or Parkinson or any number of CNS issues. Would there be perhaps 100K families who could afford this before the trials necessary for approval and insurance reimbursement. 100K x $6K = $600M per year. This is a drop in the bucket vs. the eventual revenue stream with full approval but this would allow early access and lots of interesting data from variety of treated conditions.
I'm modeling the timeline along REGNs approximate price rise. There are so many variables though and the target market for A2-73 is much larger than REGNs Eylea that we could see an acceleration of the pps rise vs. what REGN experienced. With a successful P2/3 study that would lead to approval (think Rhett) I would expect a ~$50 - $70 pps. A successful AZ trial would yield a market cap of ~$4-6B... Then as approvals come and revenues accelerate we will follow the same path that REGN experienced.
NWDR
Thanks for the thoughts. I'm doing great.
Okay. Now I have to step away from my desk lest someone see the boss cry...
Have a great weekend.
NWDR
Agree re. depression. My wife and son have both suffered with depression in the past.
The benefit to society is staggering as is the revenue.
Anavex will eventually trade for ~$800 to $1000 per share, within the next 5 years. This statement is conditioned by A2-73 continuing to alter the course of AZ and be proven effective at treating a myriad of other CNS diseases.
Calculations
millions
AZ Epilepsy Parkinsons
US 5.3 2.2 1.0
EU 5.3 2.6 1.0
Japan 1.8 1.0 0.5
Total 20.7
Assume 25% treated, 5.2M
Assume $6k per year rev, $31.05B per year
Assume 50% rev share with BP partnership, $15.53 revenue to Anavex
Assume 55M shares outstanding
Some dilution but I'm assuming that the share count remains
relatively low as costs are covered by BP partnership milestone
payments and grants.
Assume 25% profit margin
EPS ($15.53B * .25)/55M = $70.57 per share.
PE of 10, pps of $70
PE of 15, pps of $1058
add in dementia, insomnia, pain management, cancer and the numbers are
staggering.
GILD bought their primary HCV drug for $11B. That's my first market cap target for AVXL at which I will sell half and let the rest ride.
Cheers... and a reminder... these calculations are meaningless if A2-73
doesn't prove effective and never comes to market.
Falconer,
Thank you for the time you spend on the board. Your expertise is noted and appreciated.
NWDR
Yes. I agree if the effigacy is as great as some are advocating then it seems the trial should have been stopped quite a while ago. In an earlier post someone asked had the second IA been done?
What if the second IA has already occurred and the DMC recommended a halt due to the effigacy seen in PFS events. But LP wanted to get the OS secondary endpoint before unblinding the trial. But the FDA steps in and says it is not ethical to keep recruiting patients into a trial where a halt due to effigacy has been recommended. So no more screening of patients, trial continues, but much longer than anyone thought due to the placebo patients getting DCVAX after eventing.
Hmmmm
RK,
Thank you for the write ups today. Clarified possibilities.
NWDR
Mapman,
Thanks for posting the info on the company timeline that 3-71 was ahead of 2-73 in Parkinson's disease. I had missed that and was wondering what the plan was for 3-71. 2-73 may be the first weapon to actually change the course of AZ and other CNS diseases. I'm cautiously hopeful that 3-71 will be a complete game changer... very very low doses required for efficacy signals. I'm hoping that in 2017 we see a first in human study with 3-71.
Cheers.
ps. History... cool, love history
pps. I'm old enough to have a gone to Woodstock but I was on a different coast. I should have still gone.
ppps. While not the original hippy I'm looking forward to reverting once I retire from my respectable trade.
Go AVXL.
pppps. When I first saw a picture of Dr. Missling I thought, "Can he get away with that hair?" Now I'm thinking, if he can, why can't I go back to my roots... so to speak.
Be well.
Actually I was hoping that they would not do an R/S. I'm going to hold, wait for financing news which I expect would dilute and then buy a s#$#% more. I'm feeling good that they are not doing a reverse split. I've seen that game before and it is not pretty. OTC is not ideal but I'm willing to get an lot of cheap shares and wait 4-5 years.
Cheers.
ps. Prayers for Kat and her family that this is only the first of many more Christmas' together. Death to cancer.
I've been watching and waiting during this past year as AVXL continues to work to bring an effective AZ treatment to center stage. I'm bringing forward a post I did in Nov. of last year. I believe the market valuations are still appropriate. I'm also suspect that BIIB will be looking at (testing in their lab) for efficacy signals in AZ in addition to the MS testing.
If A2-73 mono-therapy halts the decline of (or recovers) cognitive function a valuation of $1-$2B is really much too low. The bidding should begin at $4B and a more appropriate value would be ~$10B.
#####################################################################
Very wet outside so I've spent a little time doing some DD. Basic question; "How much does the market value an effective Alzheimer's treatment?"
There have been previous posts about the potential revenue, EPS and resulting market cap. In particular, I've looked at GILD acquisition of Pharmasset for their HCV drug. The acquisition price was $11B. At the time many analysts felt that GILD had paid too much for Pharmasset. Well GILDs HCV revenue is running at about ~$12B per year and looks to continue for at least another 5-10 years. In the US, EU and Japan there are ~12.4M AZ cases. If 25% are treated at a price of $500 per month that is revenue of $18.6B. Even if AVXL partners with BP and gives up (in exchange for $$ of course) 50% of the revenue from the AZ indication this would leave $9.3B in revenue per year for AVXL. Based on the GILD acquisition of Pharmasset the value of the AZ revenue stream to AVXL should be in the $10B range. With 50M shares outstanding this would be a pps of $200.
I decided to take another look around to see if I can find some other way the market may value AVXL (if the data is good).
This past year BIIB came out with some positive PH1 data from a trial of a potential drug for AZ treatment. However, the full data set released later in the year, 7/22/15 to be exact, raised some concerns. Due to these concerns which I'll highlight below BIIB sold off some 100 points, from ~$400 to a current price of ~$290. The lowest price during the sell off was down to around $256 pps. There were some other concerns about slowing revenue growth in the MS drug line so I'm not going to use this lowest price as a factor in what the market took away from BIIBs market cap due to the AZ trial data. If we look at the chart right after 7/22/15 there is a clear drop to the $300 area and then some rebound and then some drop, etc... So I'm going to use a rough estimate of 100 points lost to the less than stellar AZ trial data. Note that the AZ trial data was not terrible. It just wasn't what everyone was hoping for.
BIIB has ~222M shares outstanding. At 100 points this yields a market cap loss of $22.2B. For the rough estimates I'm using this compares pretty closely with the GILD / Pharmasset valuation of AVXL.
An effective and safe AZ treatment can expect revenues in the $18.6B range. BIIB lost roughly ~$22B in market cap due to less than stellar data.
GILD paid $11B for ~$12B in yearly revenue
BIIB lost ~$22B in MC for a potential loss of ~$19B AZ revenue
Note the roughly 1:1 relationship of revenue stream to MC.
I think if the data is good next week and through out 2016 AVXL is looking at a pps in the $200 to $275 area, (MC of $10B to $11B). This corresponds to the market expecting a revenue stream of $9.3B to AVXL for AZ. Nothing for any other indication.
When we hit $50 I'm going to sell enough to get back my original investment and maybe purchase some long term put protection for some of the profits I'm leaving in the game.
Regarding BIIBs AZ trial data;
MMSE scores at one year;
placebo, worse by avg. of 2.81, n=40
1mg/kg arm, worse by 2.18, n=31
3mg/kg arm, worse by 0.70, n=33
6mg/kg arm, worse by 1.96, n=30
10mg/kg arm, worse by 0.59, n=32
The 3 and 10 mg/kg arms achieved statistical significance. The 1 and 6 mg/kg arms did not. Note that this was one of the most disturbing issues to the market. An effective drug should show a clear dose dependent trend. That dose dependent effectiveness is not really clear from these results. There were also some issue of brain swelling in the trial. And so the sell off. However, the need for effective treatments in AZ is so great that BIIB is continuing to move their drug into PH3 trials. They are skipping PH2.
If AVXLs data continues to be good I would not be surprised to see BIIB partner up or try to purchase AVXL. BIIB is involved in MS and attends the AZ conferences. They will be very aware of AVXL.
Have a great weekend. Looking forward to next week.
Reg,
Very sad to hear of your diagnosis.
In Feb of this year I had a high PSA reading... 9.1
This eventually led to a prostate biopsy and cancer diagnosis. Eight of the twelve biopsies were positive for cancer. All six on the right side and two on the left. Several samples were Gleason 7. I investigated my options... radiation, surgery, cryo-surgery, just hormone therapy, and irreversible electroporation (IR). My boss's brother-in-law had gone to Florida to see Dr. Gary Onik for his prostate cancer treatment. After talking with my boss's brother in law I contacted Dr. Onik and spoke with him about treatment. I read Dr. Onik's paper submitted to the National Cancer Institute on the first treatment, (submitted 2010, 16 patients) using IR to kill prostate cancer. Dr. Onik had published several other papers on the experimental treatment of using IR on animals. Purpose of these studies was to determine electrical pulse duration and magnitude and the resulting soft tissue kill zone prior to the first use of IR in humans.
I went to Florida for treatment the week before Memorial Day this past May.
Sat - Arrived
Sun - Exam by Dr. Onik
Mon - 3D prostate mapping biopsy (~50 samples) determines exact extant of prostate cancer in the prostate. Done under general anesthesia as an out patient.
Tue-Thur - My wife and I went to Key Largo for some R&R. During this time a 3D map of the prostate cancer is generated by a lab.
Fri - Back under general. Dr. Onik used cryo surgery on a small portion of my prostate cancer. The rest and larger portion (with margin) was treated and killed using IR. Dr. Onik still likes to use cryo on a small portion of the cancer because of the documented immune response that sometimes occurs. Something about the freeze-thaw cycles and dendritic cells recognizing the tumor as foreign as your body cleans up the dead cancer cells. :) This was also an out patient procedure.
Sat - Hung out at a hotel close to the hospital. I even went for a walk at the mall across the street.
Sun - Fly home.
The 3D mapping biopsy identified a small area of Gleason 8 cancer. For this reason I'm doing 6 months of hormone therapy just to possibly prevent any micro metastasized tumors from gaining a foothold. Before I started the hormone therapy I had regained sexual function and I am now completely continent... even with the nerve bundle on the right side being included in the IR treatment zone. IR can be tuned to only kill the soft tissues but spare the nerves, blood vessels, urethra, etc..
I chose not to do full cryo because cryo will kill the nerve bundles if the generated ice ball is close to them. Cryo can also damage the urethra, bladder or rectum if not done carefully.
I've seen more cancer centers start advertising IR treatment. The marketing name I've seen is "Nano Knife".
None of the doctors I visited in my home state mentioned IR as a possible treatment. IR is still just starting to be advertised. I would not have known about IR as a possible treatment option if not for my boss's brother in law.
I wish you all the best and will keep you in my prayers.
NWDR
ps. Go NWBO
reg2015,
Earlier this year I learned I had prostate cancer. ~70% of my prostate. I went to Dr. Gary Onik in Florida. Did a 3D mapping biopsy and followed by irreversible electroporation to kill the cancer. This treatment is gaining traction and is marketed under the name of NanoKnife. I don't know what kind of cancer you have but it can't hurt to investigate this option.
Praying for you.
NWDR
I'm sure many of us are thinking the same thing. What will the MMSE and ADCS-ADL scores of the seven patients on A2-73 mono-therapy look like at longer time frames; 32, 52 weeks etc. The 7 patient pool is too small of a sample size to positively state what the effects of mono-therapy will be on a large sampling of the population. However, IF the trend continues and the mono therapy patients continue to be stable or improve this will provide Dr. Missling with a great negotiating point at the table with BP.
IF the difference between the mono and combo therapy group continues to grow the significance will become more apparent and more interesting to any investigator or scientist in the AZ field. Especially as the TauRx PH3 trial found the same thing; patients in the mono-therapy did better than those in the combo arm of the trial. Donepezil may be blocking or hindering the benefit from other AZ drugs.
Looking forward to the future.
NWDR
For me the most disappointing chart on the poster is the EEG / ERP results at baseline, 5 week, 17 week and 31 week. Last year AVXL touted the improvement in the P300 tests for the patients. In the poster today the 5 week data shows an 80% improvement over baseline, 17 weeks shows a 29% improvement and the 31 week data shows a decline of -4% compared to the baseline. The other tests; Task Accuracy, False Alarms, Reaction Time all show similar trends. I believe this means that the stabilization in MMSE and ADCS-ADL will probably not be maintained at the 52 week mark. I do not believe that the anecdotal reports of improvement we have heard about are due to a placebo effect. I believe the improvements are due to the low level EEG / ERG early improvements and also due to the HAM-D improvements. It is not possible for a P300 test to have a placebo effect. This test directly measures brain activity due to an external stimulus. You can not improve the test result by trying harder. I believe that the A2-73 improves the low level functioning of the brain for a period of time but then AZ overwhelms the improvement. A2-73 is still way better than SOC but it is not a cure. A2-73 appears to stabilize AZ for many patients up to 31 weeks. I would really like to see the data for the individuals. I wonder if there are any super responders in the pop. Especially for those individuals who regained lost functionality.
Its just going to take longer and more dollars than I had hoped to bring A2-73 to market.
Based on these results I would expect Dr. Missling to partner with BP and do a blinded PH3 study comparing 2-73 to SOC donepezil. After 6 months on trial there should be a clear difference between the patient groups with the 2-73 group stabilized and the donepezil group showing a significant decline. I would expect that we are looking at another 1.5 years before we would see results from a PH3 trial... maybe sooner if the trial can start before the end of the year and at 6 months the trial is halted. But I would now not expect anything sooner as it would just set expectations too high, which is what has happened with this current PH2 data. There are still many indications where A2-73 may be effective and useful but its going to take some time and dollars to bring about the approval of A2-73 by the FDA.
I believe the data shows that A2-73 stabilizes higher level cognitive functions for 31 weeks. However, note on the poster the EEG/ERP results over time. These tests are a lower level cellular level of brain function. There is dramatic improvement at 5 weeks which is almost all maintained at 17 weeks. But there is a significant decrease in the positive effects at 31 weeks. I believe A2-73 is much better than the SOC and will eventually be approved. But I also believe, based on the low level EEG/ERP results, that cognitive decline (higher level functions) will resume post 31 weeks. A2-73 definitely stabilizies cognitive decline. But based on the low level EEG/ERP results I do not expect that cognitive decline will be halted for more than a year or so.
A2-73 is still much better than SOC but it is not what I hoped for... especially based on the antedotal reports from Australia. It could be there are some super responders in the patient pop and some who have not really responded at all and declined. This could leave the mean relatively unchanged. To understand this better we would need to see the responses of each patient and the median numbers.
The Facebook group has anecdotal evidence of improvement for 8 of the 32 patients in the current trial. I believe the cognitive and functional improvements will be picked up by the MMSE and ADCS-ADL tests and the results will be unprecedented improvement for the patients currently in the trial.
While we are waiting for data...
Estimated dates for approval from the FDA to market and sell A2-73 as a treatment for AZ
6/30/2018 NWDR
9/17/2018 ipulator_man
_________ XenaLives
10/18/2017 mapman1010
********************************************************************
Bringing an old post forward about cost of large PH2 / PH3 trial
*********************************************************************
I was doing a little digging on the cost of trials per patient and came across this report;
http://www.phrma.org/sites/default/files/pdf/biopharmaceutical-industry-sponsored-clinical-trials-impact-on-state-economies.pdf
Page 7 of this report has the average cost per patient for a clinical trial in a CNS disease is $36K.
So using this number and ball parking how many patients would be necessary for PH2B/3 we get the following ranges;
Patients Cost
300 $10.8M
1000 $36M
2000 $73M
These numbers are relatively significant for AVXL but not for someone like MERCK, Sanofi, GILD, BIIB, etc..
Dr. Missling has stated that they will look to partner the AZ indication. I really hope so. A BP partner will bring not only $$ but sales force, marketing, a whole department dedicated to dealing with the regulatory agencies, support structures already in place for M.D.s, etc.. REGN is a great example of what a good partnership can do for both parties. Look at REGN stock chart. That's AVXL in 3 years.
*********************************************************
And, I was looking for data on how quickly the FDA has approved a drug and came up with this;
Opdivo (nivolumab)
Late Dec. 2014 - data available and early submission to the FDA
Jan 11, 2015 - trial stopped due to efficacy of drug
Mar 4, 2015 - drug approved... 3 months early
early - most (not all) FDA takes full time to PDUFA date
Now Opdivo had previously been approved by the FDA for the treatment of melanoma. So this was not a 'new' drug that the FDA had never reviewed before. On the other hand, even with the sometimes severe side effects the FDA rapidly approved Opdivo in this indication due to the strong clinical data supporting efficacy.
Like everyone else here I just want to see the 12 and 26 week clinical data. I believe this data will be good. But what I really want to know is how long does it take for the patients to respond. This will be key to getting the PH3 trial stopped early. If we show a small response that occurs over a long time then the PH3 trial will take a long time. Conversely, if we have strong positive efficacy that occurs relatively quickly (12 weeks?) then I very much believe the DMC (Data Monitoring Committee) will halt the trial early (everyone in the trial gets A2-73 on ethical grounds) and we have a case for accelerated approval with the FDA and other regulatory agencies.
My Hopeful most ideal timeline
Summer 2016 - Anavex announces BP partner in AZ indication
9/1/2016 - Sometime in 2016, A2-73 is granted accelerated approval
4Q2016 - PH3 trial recruitment begins
Hopefully with a big pharma partner... In my mind not so much due to money issues, although that is certainly a consideration, but big pharma brings a huge number of scientists, researchers and clinicians to the table. Critical for moving quickly in my opinion.
6/1/2017 - hundreds of patients in trial and taking A2-73
how many sites, how many patients can each site enroll in a month
probably 15 or more sites eventually... but not immediately
Jan. 2017 3 sites, 5 patients per site per month, 15 patients
Feb. 2017 6 sites, 8 patients per site per month, 48 patients
Mar. 2017 8 sites, 10 patients per site per month, 80 patients
Apr. 2017 9 sites, 10 patients per site per month, 90 patients
May. 2017 10 sites, 10 patients per site per month, 100 patients
lets assume that enrollment plateaus at 100 per month. There could be close to 1000 patients in the trial by the end of 2017.
BP will have the people to support many sites. If the coming data is really good all of the top AZ research hospitals will wish to join. Patients and families will be breaking down the doors.
6/1/2017 - Anavex starts submitted data for rolling review of A2-73. More data will be submitted as it comes in.
This is where is gets interesting. If there is very strong efficacy in as little as 12 weeks the trial could be halted even a 2-5 months earlier than what I have outlined.
1/1/2018 - Data from hundreds of patients over the 2017 timeframe is so compelling that the DMC recommends that the trial be halted and all patients in placebo arm be switched to A2-73.
4/1/2018 - Anavex submits full data set requesting license to market and sell A2-73
7/1/2018 - FDA provides early approval of A2-73. This approval may be conditional on Anavex continuing the PH3 study for several more years to monitor patient progress and safety. The FDA may also request another PH3 study for confirmation. Of course Anavex agrees.
That's my best guess. Maybe we should have a pool on target date for A2-73 approval. 6/30/2018 is my spot although it could be earlier in a best guess, "Gee, everyone is so much better (golfing, painting, playing music) scenario."
Cheers.
Date?
6/30/2018 NWDR
9/17/2018 ipulator_man
_________ XenaLives
_________ mapman1010
Bringing an old post forward about cost of large PH2 / PH3 trial
*********************************************************************
I was doing a little digging on the cost of trials per patient and came across this report;
http://www.phrma.org/sites/default/files/pdf/biopharmaceutical-industry-sponsored-clinical-trials-impact-on-state-economies.pdf
Page 7 of this report has the average cost per patient for a clinical trial in a CNS disease is $36K.
So using this number and ball parking how many patients would be necessary for PH2B/3 we get the following ranges;
Patients Cost
300 $10.8M
1000 $36M
2000 $73M
These numbers are relatively significant for AVXL but not for someone like MERCK, Sanofi, GILD, BIIB, etc..
Dr. Missling has stated that they will look to partner the AZ indication. I really hope so. A BP partner will bring not only $$ but sales force, marketing, a whole department dedicated to dealing with the regulatory agencies, support structures already in place for M.D.s, etc.. REGN is a great example of what a good partnership can do for both parties. Look at REGN stock chart. That's AVXL in 3 years.
*********************************************************
And, I was looking for data on how quickly the FDA has approved a drug and came up with this;
Opdivo (nivolumab)
Late Dec. 2014 - data available and early submission to the FDA
Jan 11, 2015 - trial stopped due to efficacy of drug
Mar 4, 2015 - drug approved... 3 months early
early - most (not all) FDA takes full time to PDUFA date
Now Opdivo had previously been approved by the FDA for the treatment of melanoma. So this was not a 'new' drug that the FDA had never reviewed before. On the other side, even with the sometimes severe side effects the FDA rapidly approved Opdivo in this indication due to the strong clinical data supporting efficacy.
Like everyone else here I just want to see the 12 and 26 week clinical data. I believe this data will be good. But what I really want to know is how long does it take for the patients to respond. This will be key to getting the PH3 trial stopped early. If we show a small response that occurs over a long time then the PH3 trial will take a long time. Conversely, if we have strong positive efficacy that occurs relatively quickly (12 weeks?) then I very much believe the DMC (Data Monitoring Committee) will halt the trial early (everyone in the trial gets A2-73 on ethical grounds) and we have a case for accelerated approval with the FDA and other regulatory agencies.
My Hopeful most ideal timeline
Summer 2016 - Anavex announces BP partner in AZ indication
9/1/2016 - Sometime in 2016, A2-73 is granted accelerated approval
4Q2016 - PH3 trial recruitment begins
Hopefully with a big pharma partner... In my mind not so much due to money issues, although that is certainly a consideration, but big pharma brings a huge number of scientists, researchers and clinicians to the table. Critical for moving quickly in my opinion.
6/1/2017 - hundreds of patients in trial and taking A2-73
how many sites, how many patients can each site enroll in a month
probably 15 or more sites eventually... but not immediately
Jan. 2017 3 sites, 5 patients per site per month, 15 patients
Feb. 2017 6 sites, 8 patients per site per month, 48 patients
Mar. 2017 8 sites, 10 patients per site per month, 80 patients
Apr. 2017 9 sites, 10 patients per site per month, 90 patients
May. 2017 10 sites, 10 patients per site per month, 100 patients
lets assume that enrollment plateaus at 100 per month. There could be close to 1000 patients in the trial by the end of 2017.
BP will have the people to support many sites. If the coming data is really good all of the top AZ research hospitals will wish to join. Patients and families will be breaking down the doors.
6/1/2017 - Anavex starts submitted data for rolling review of A2-73. More data will be submitted as it comes in.
This is where is gets interesting. If there is very strong efficacy in as little as 12 weeks the trial could be halted even a little earlier than what I have outlined.
1/1/2018 - Data from hundreds of patients over the 2017 timeframe is so compelling that the DMC recommends that the trial be halted and all patients in placebo arm be switched to A2-73.
4/1/2018 - Anavex submits full data set requesting license to market and sell A2-73
7/1/2018 - FDA provides early approval of A2-73. This approval may be conditional on Anavex continuing the PH3 study for several more years to monitor patient progress and safety. The FDA may also request another PH3 study for confirmation. Of course Anavex agrees.
That's my best guess. Maybe we should have a pool on target date for A2-73 approval. 6/30/2018 is my spot although it could be earlier in a best guess, "Gee, everyone is so much better (golfing, painting, playing music) scenario."
Cheers.
Yep.
I'm not going to hang around to find out what happens. Staged at T1C. Treatment within the month.
Thanks.
So life is very interesting at times. I'm posting this because I believe it shows some physicians are trying to expand treatment options for those with cancer... as NWBO is. Also of interest is some of the similarities with DCVAX.
In Feb. of this year I had a high PSA reading... 9.1. Not good. A follow up PSA test 2 weeks later confirmed the high result... 9.3. Many of you know where this is going now... A biopsy at the end of March showed 8 of 12 prostate samples were positive for cancer. Gleason score 7 (3+4).
I started doing the investigation of therapy paths. I had pretty much settled on prostate removal by an excellent and experienced (over 1000 of these operations) surgeon in my area.
However, several weeks ago my boss decided to move on. His replacement had formally been a peer of mine. I would never have told this former peer about my situation except he was now my new boss and I would be at home for a week or so following treatment. When I explained my situation he told me his brother in law, Luke, had also had prostate cancer and went to a doctor in Florida for cryosurgery. I had investigated cryosurgery but ended up deprecating it due to some side effects and the lower published cure rates. I debated briefly with myself if I should investigate this doctor in Florida. The debate ended quickly, how can I just walk away from a potential option? I spoke with Luke regarding his cancer and treatments. Luke was very open and explained his dealing with cancer for a decade before it progressed to the point where he needed to take a more aggressive path of treatment. Luke went for focal cryosurgery to Dr. Gary Onik in Florida. Dr. Onik froze and killed half of Luke's prostate. Luke stated his PSA is under 1.0 for over several years and he is experiencing no side effects.
I investigated (internet) Dr. Gary Onik. I was encouraged to see that Dr. Onik had presented a study paper that was peer reviewed and accepted by the National Cancer Institute. This paper followed 70 men for an average of 10 years (8.8 to 18) that Dr. Onik had treated. 90% of the men are cancer free at 10 years follow up. The 90% cure rate is across low, medium and high risk prostate cancer populations. This cure rate compares favorably with cure rates for robotic radical prostatectomy or radiation therapy. Dr. Onik also uses some techniques that significantly improve the treatment and reduce potential side effects from cryosurgery.
Now before this post is deleted as off topic... here is the interesting part. I spoke with Dr. Onik last week. One of the points he emphatically made is as follows;
He uses three freeze (-20C) and thaw cycles to destroy the cancer cells. He stated that they know this sometimes triggers a systemic immune response. How do they know this? He pointed to two patients that he treated, posted about and followed. One with metastatic prostate cancer and one with metastatic liver cancer. When Dr. Onik treats these progressed cancer patients he does the freeze and thaw cycles at one tumor site, waits a couple of days and then does a follow up procedure of injecting the frozen and thawed tissue area with recently approved immune drugs in an attempt to boost the immune response. Drugs he has used are Yervoy and Nivolumab and I believe there is another which I can't remember at the moment but will be asking about next week.
During my discussion with Dr. Onik I expressed concern about preserving the nerves that run very close to the sides of the prostate. These nerves are very delicate and would not survive any type of freezing. Dr. Onik stated that for me, he would suggest a combined therapy. The cyro approach for the majority of my tumor and irreversible electroporation (IRE) for those areas close to the nerves. IRE has the advantage that the damage to cells is primarily between the electrodes and not in a circular radius around the needle point where freezing is induced. I asked why not just use the IRE for the whole tumor. Dr. Onik stated that the IRE will destroy the tumor cells structure such that there would be no possibility of a systemic immune response. Hmmm... destroy the structures of the tumor cells... destroy the antigen sites and maybe the dendritic cells in the body can't pick these up and transfer the information to the T cells.
I've spent some time this weekend reading about what happens in the body in response to trauma. Suffice it to say there is a massive amount of recent literature about the immune system response to trauma. Of interest to me is the data around the local release of pro- and anti-inflammatory cytokines. This can be summed up by this statement from a 2005 study paper on "The importance of cytokines in the post traumatic inflammatory reaction." The statement," The local release of pro- and anti-inflammatory cytokines after severe trauma indicates their potential to induce systemic immunological alterations." The 3 freeze and thaw cycles certainly constitute trauma to tissues. With this trauma comes the cytokine release that begins the immune response and with luck and maybe the right booster(s) a systemic immune response to the cancer cells.
Where have I heard about the release of cytokines and the attempt to create a systemic whole body immune response before? Why with DCVax Direct. In Dr. Bosch's own words the properly matured and then injected dendritic cells release a massive amount of cytokines. I believe that Dr. Gary Onik is sometimes able to trigger the systemic immune response that NWBO (and others) are trying to consistently achieve. Dr. Gary Onik was emphatic when I spoke with him. He stated that the trigger of a complete whole body immune response was a fact. It does not happen all the time but it does happen. My view of the situation is that NWBO, other companies, doctors and researchers are trying to understand how to ensure that the whole body immune response can be triggered in a significant majority of patients without the severe side effects of an out of control immune response.
I found the discussion with Dr. Onik interesting. I will probably be taking a trip to Florida within the next month although I have not unequivocally decided on the cryosurgery option.
I remain a frustrated long in NWBO. I believe in the science. I believe that in the next decade doctors will have the tools, drugs and protocols they need to cause a systemic immune response in cancer patients.
I am very fortunate that my own situation is not that dire. I have access to high quality medical care and also have the ability to chip in some $$ if the insurance companies will not cover the immunotherapy drugs. I have a very high probability of being cancer free 10 years down the road.
For those less fortunate I hope and pray that the doctors and researchers and companies break through the remaining barriers to comprehensive and successful immune therapy for all cancer patients.
Cheers.
ps. I will not be on line the rest of the weekend. I will try to answer any questions but I don't plan to get involved in a big debate about the science, etc..
pps. Luke is not the name of the brother in law
ppps. link to Dr. Onik's study paper on the follow up over 10 years on 70 of his patients
http://prostatecancer2.com/attachments/File/Long-Term_Results_of_Optimized_Focal_Therapy_for_Prostate_Cancer.pdf
pppps. Some things that Dr. Onik does that separates his cryosurgery approach from others:
_Saturation biopsy (3D-PMD) to map the tumor
_Saline solution injected between the prostate and rectum to protect the rectum from any freezing temperatures.
_Temperature probes placed to monitor temperatures during freezing. Both to ensure death to cancer cells and also to monitor local healthy tissue and reduce damage if possible.
_IRE near nerve structures to reduce damage and side effects.
_Three freeze thaw cycles down to -20C vs. standard of two freeze thaw cycles down to -40C. -20C vs. -40C results in more focal damage and less spread of freeze effect.
Awesome. Thank you for the information.
Regards
Just for those of us keeping track... and I know you are out there...
Anecdotal evidence of improvement
Miss Australia's relative;
_Back to playing golf, remembering how Miss A. takes her tea and I believe remembering Miss A. roommates name
_painter in news story
_piano player in news story
_younger patient who was met out and about after using public transportation
_comment on facebook regarding "much improved" father from son. Son stated that father was in the trial.
That's 5 out of 32, 15.6% If we include Lawson from the news clip last fall that would be 6 out of 32, 18.75%
Drugs are approved that show effectiveness in only 20% of the patients. Additionally, we know that 11 of 14 had measurable improvement in their MMSE scores after 5 weeks. There were also statistically significant improvements in the 5 of 6 Cogstate scores. There were also improvements in the ADCS-ADL scores.
How often do we see this early glimpse into a PH2 trial?
Besides praying that the initial improvement continues and is sustained there is a potentially interesting trade on the May options. But be warned this is a binary trade... you lose all or probably make a nice return of 2x-10x or more.
Options expire on the third Friday of the strike month. For May, the third Friday is May 20. The conference where Dr. M will talk, with the abstract not yet released, is on May 17. If good data is PRed just prior to this conference and then presented at the conference AVXL could experience a nice spike in price. Since there will be very little time value left on the May options on May 15 the $7.5 option will probably be trading at or less than $.10 per share if the AVXL pps stays between $5-$6 per share. ($10 per contract, where a contract is for 100 shares).
Purchasing 10 contracts @ $10 per contract would put at risk $100 plus commissions. This would be the maximum loss. If data is good and AVXL spikes and you are quick to sell before the options expire you could end up with $1 proceeds per share for each dollar over the strike of $7.5.
Be very cautious with this trade though... All or nothing... You essentially should be okay with burning the cash of whatever amount you put at risk.
Not trading advice. This is a public anonymous message board.
Cheers.
Prayers for all caregivers and AZ patients.
I definitely agree that it seems having a control group get something you know is only go to slow down (at best) Alzheimer's for a small length of time seems unethical.
However, the regulatory agencies may still require a control arm in a PH3 trial for it to be considered sufficient for drug approval.
What might happen, conjecture on my part, is that the PH3 trial design is such that it allows a crossover from patients in the control group who progress a certain amount to the arm of the trial getting A2-73.
Perhaps something like a measurement of MMSE at baseline and then when a measured reduction (so many points) occurs then the patient can cross over and start receiving A2-73.
I would rather just give 100 patients with mild to moderate AZ and see how they do for 6 months. But the regulatory agencies might insist on the control arm. If they do, then the cross over may help with the ethical concerns.
If the complete data set is even one quarter as good as the glimpses we are seeing then I would expect the PH3 trial to be stopped some 6 months after it has enrolled a significant number of patients. It will not take very long for the treatment group to show an overwhelming advantage in function vs. the control group.
Cheers.
I agree that GOOD 12/26 week data is absolutely necessary in order for
A2-73 to proceed to the next phase.
However, I disagree that this article means little.
We now know of 3 patients in this 32 patient trial who have regained complex functional skills;
Painting
Piano Playing
Playing Golf <-- I believe that this is Miss Australia's relative or an earlier release of a patient profile.
Two points to ponder;
(1) Up to this point in human history, AZ patients do not get better.
(2) We have an early look / hint at A2-73 results. How often does this happen for us small retail investors?
Everyone do your own DD. This is a public anonymous message board.
Thanks for filling in the names of the patients. Very positive article and functional improvements in patients are really without precedent.
This is the article and video that was noted earlier.
Actually includes a video interview with Dr. Macfarlane.
http://www.heraldsun.com.au/news/alzheimers-disease-breakthrough-melbourne-drug-trial-achieves-amazing-results/news-story/d96671bc643b16d2694e85e0639fea3d
EDIT:: Following this link brings me to a subscription page. When I did the google search for
"HEROLD SUN Melbourne drug trail achieves AMAZING results"
And then clicked on the first link I was actually brought to the article.
Now that doesn't seem to work... but
Two patients were shown with a picture of each
One patient has regained the ability to paint pictures... looked like oil painting. Not grade school quality. Nice stuff.
Another patient has regained the ability to play a piano. In the video she was shown playing. She was not banging it out but was playing almost cautiously... However, anyone looking at her playing would state she can play the piano... She had sheet music out and was playing as she read the music. Not trivial. Big smile on her face when she finished with a flourish.
Dr. Macfarlane comments... paraphrasing
"Alzheimer's drug trials littered with failure"
"need to do a larger study"
"measured cognitive improvements in this early small trial are great to see but what is really powerful is the functional improvements in these patients. That is what makes the results so compelling."
The interviewer asked Dr. Macfarlane roughly about how a doctor might view and feel about the results being seen. Is this a once in a lifetime event/achievement? This is when Dr. Macfarlane commented on the Alzheimer drug trial failures and that for AZ patients this is certainly different than what has been seen before.
I didn't get the exact transcription but this is an accurate sense of the article and interview.
Regarding the Anavex Plus patent and why I believe an approval (or not) for this patent is a non-issue for Anavex.
Anavex Plus is a combination of A2-73 and donepezil (brand name Aricept).
Donepezil is a generic drug. Meaning it no longer has patent protection and can be manufactured by any pharma company that chooses to do so (assuming they have an FDA approved lab, etc..).
Here is why I believe this patent is a non-issue.
(1) No other pharma company can manufacture, distribute and sell A2-73 without Anavex's approval.
(2) If a doctor wishes a patient to take both A2-73 and donepezil prescriptions can be written for both and a patient would need to take two pills to obtain both A2-73 and donepezil.
(3) Donepezil has many more unpleasant side effects than A2-73. Human clinical trial data is now starting to indicate that donepezil plus A2-73 is no more effective than A2-73 alone. So why prescribe something that increases side effects with no additional treatment advantage?
(4) If during larger human trials donepezil and A2-73 are shown to be more efficacious than A2-73 alone and IF it is highly desirable to reduce the number of pills a patient needs to take then Anavex could go the following route to bring a compound capsule to market with both A2-73 and donepezel.
Everyone remember Martin Shkreli. Poster bad boy for unfettered capitalism (and I'm a conservative) without any moral compass.
Here's a link if you are unaware of his activities;
http://heavy.com/news/2015/09/martin-shkreli-hedge-fund-ceo-aids-drug-price-increase-turing-pharmaceuticals-daraprim/
His actions include purchasing the only company making Daraprim and hiking the price from $13.50 per pill to $750 per pill. Daraprim is used by some AIDs and cancer patients to treat a certain type of infection. Daraprim has been on the market for over 60 years. Talk about price gouging...
However, several months after Shkreli announced this price increase there was this announcement.
http://imprimispharma.investorroom.com/2015-10-22-Imprimis-Pharmaceuticals-to-Make-Compounded-and-Customizable-Formulation-of-Pyrimethamine-and-Leucovorin-Available-for-Physicians-to-Prescribe-for-their-Patients-as-an-Alternative-to-Daraprim
and
http://money.cnn.com/2015/12/01/news/daraprim-drug-express-scripts-imprimis/
Imprimis would manufacture a capsule that contained the same ingredients as the Daraprim pill. Express Scripts announced that they would offer the Imprimis capsule instead of the high cost Daraprim pill. Imprimis can manufacture this capsule because all of the medications in the capsule are generic and have been approved by the FDA.
If Anavex Plus is never patented but A2-73 is approved I believe Anavex could have a pharma lab manufacture a capsule that contained both A2-73 and donepezil. No other company could do this because A2-73 would be patented by Anavex which would prevent any other company from combining A2-73 with donepezil in any form and marketing it.
So I believe Anavex Plus was a good idea but is not necessary for the success of Anavex.
Long AVXL.
Cheers
ps. This in no way should be construed as investment advice. This is just an anonymous message board...
Sherwood, OR
Jeneva Rose
Today I volunteered at Sherwood Oregon's annual Egg Hunt For Hope which involves an egg hunt for children of various age groups, a Raffle and a Silent Auction. This event has been going on for 10 years. Leslie and Todd McCabe, of the McCabe Reality Group, started this event and continue to pour countless hours into organizing this event.
Each year the proceeds from this event are donated to a person and family in Sherwood Oregon that are dealing with cancer. This year the recipient of the proceeds was the Jeneva Rose family; Jeneva, husband Jim Rose, daughters Jenessa, 9, and Jazlyn, 6.
When she was 29, Jeneva was diagnosed with grade-three anaplastic astrocytoma, a brain cancer. After surgery, chemo and radiation her cancer went into remission for a decade. During this time Jeneva worked as a counselor at Sherwood High School and had two beautiful daughters. In 2014 the brain cancer returned and Jeneva underwent another round of surgery, chemo and radiation. The community rallied around her and her family supporting them as best they could.
Jeneva passed away on Thursday, two days before the event this morning. Jeneva's husband, two daughter's, parents, extended family and over 1000 community members were in attendance. The event, high school student fund raising and private donations will raise close to $40,000 to help offset some of the expenses the family has incurred over the past two years.
I'm sure we all have our stories of how cancer has intruded into our lives. Brain cancer was much more "in my face" this morning. Much more than an investment.
I can only reflect on Dr. Linda Liau's presentations and marvel at the decades of hard work that the researchers and neurosurgeons have put forth to understand, treat and eventually defeat this terrible disease.
I thank the doctors and researchers for their commitment, I pray for the patients and I hope that in some way my investment in NWBO helps us move closer to a cure.
http://koin.com/2016/03/11/cancer-takes-sherwood-high-counselor-jeneva-rose/
Yes. I do agree that options and NWBO do not do well due to the expiry. I've had shorter 1 year out options on NWBO time out on me. I'm fortunate that earlier in my investing and trading career I make the mistake of being greedy and got burned by not taking some $$ off the table. So when NWBO was up at 10+ I took some off. I wish I had taken all off but I've learned about greed and fear the hard way. So I'm comfortable with this risk. Thanks.
Yeah me too.
Jan 2018 calls, @ $7 strike, filled at $.42 per contract
50 contracts * 100 * .42 = $2100.00
If (I know, I know) If NWBO does get some kind a regulatory approval and the pps hits $20, profit would be (50 * (20-7)) = $65,000. Maybe a little more if the time value in the Jan 2018 LEAPS brings in a dollar or two or maybe a little less depending on dilution.
But,
I couldn't pass up the potential risk : reward ratio. And I feel that this will all be over one way or another by Jan 2018.
And,
I believe in the science. I'm not sure if NWBO (LP) has screwed up the trial in some way but Linda Liau is a believer.
Cheers
I believe Anavex acquired the patent for 2-73 when the patent was assigned by Dr. Alexandre Vamvakides to Anavex in return for compensation.
This press release;
http://www.anavex.com/?news=anavex-life-sciences-corp-acquires-a-portfolio-of-patents-and-appoints-dr-alexandre-vamvakides-as-cso-and-director
Anavex also announced an additional notice of allowance for a patent on 2-73 here;
http://www.anavex.com/?news=anavex-receives-notice-of-allowance-for-u-s-patent-application-related-to-anavex-2-73
Anavex announced patent issued for 3-71 here;
http://www.anavex.com/?news=anavex-awarded-new-u-s-patent
Cheers
Hmmm....
Alz and now MS...
Partner.. .the name that immediately comes to mind is Biogen, BIIB.
Large revenue already in MS and they have a drug in development for Alz that had so so data in a PH1 trial. In spite of the so so data they are moving it to a PH3 trial. BIIB could partner with AVXL just to ensure they stay on the cutting edge with any new CNS drug. A partnership with milestone payments would take us to a market cap of $1B or $25 per share with 40M shares outstanding, IMHO.
MS drug revenue, 2013
Top ten;
Extavia $159M NVS
Aubagio $226M Sanofi
Ampyra $302M Acorda and BIIB
Rebif $622M Pfizer
Tecfidera $876M BIIB
Betaseron $1.05B Bayer
Tysabri $1.67B BIIB
Gilenya $1.9B NVS
Avonex $3B BIIB
Copaxone $4.33B TEVA
Huge market, some shifting of revenue will have occurred since 2013 but each of the big players will certainly be interested in preserving their revenue streams.
I'm holding at least for another 2 years and probably longer as the story unfolds. This will be fun.
LONG AVXL
Cheers
I've pondered the Direct PH2 trial design for some time. In particular, the need (or not) for a control group. I do not believe you should be injecting anything into a tumor unless you strongly believe there will be a therapeutic effect. There have been numerous instances of aggressive tumors growing along the pathway left by a biopsy needle. Injecting saline, H2O or "grapefruit juice" as a placebo could be detrimental to the patient. What I would really prefer to see is several smaller PH2 trials;
Like 2 or 3 different cancers but with only 20 or so patients each. Work on injection schedule, adjuncts, combo therapies etc.. monitor immune response, PFS, OS, etc.. get to a point in the next two years where you would the accumulated data shows that Direct could be a game changer for the treatment of cancer. If the smaller trials demonstrate the strong positive outcomes talk to the FDA about a PH2B/3 where there is no control, enroll ~60-100 patients, go for PFS / OS improvement impossible to ignore based on historical information.
I know that not having a control is probably like a duck on opening day with the FDA.
The normal course would be to do a trial with a control but allow a crossover on disease progression. Without the crossover why would you enroll in the trial. I would go for a trial where I knew I would have a chance to receive the latest therapy.
Anyway... just pondering. What would happen if for Pancreatic Cancer, NWBO enrolled 20 patients in a PH2 trial. Inject every tumor that shows up... not all at once... careful with sepsis. Goal is to kill (necrosis) all the tumors and turn on the immune system. Maybe combo with checkpoint inhibitors if the can get another company to agree. Small trials like these would go a long way to answering the questions about Direct's effectiveness without spending another $100M or more for large trials.
Maokin or should I say napkin,
I've corrected an error in my original post. The holding period for capital gains calculations starts with the exercise date.
Cheers
Hi,
I wanted to comment briefly on some possible outcomes with options that could have a significant impact on your taxes.
You mentioned in a previous post about "... taking profits and use the money to buy more whenever I choose to" As below.
<Gab, You mention "upon sale or exercise", and I presume that if the price of the stock is significantly higher than $5.00, I would choose to take the profits and use that money to buy more whenever I choose to.>
At expiration your option will either be worth nothing or basically the difference between the strike and the current market price. You could certainly choose to sell all the options the day before expiry and then use the profits to purchase AVXL or other stock. However, you will incur short term capital gains which could be substantial. A viable solution is to sell enough of the options to allow you to 'exercise' the remaining and pay the strike price as your purchase price. The date you originally purchased the options you exercised becomes your purchase date for the stock. This allows you to roll the gains into a long term capital gain which could result in a reduction in overall taxes;
Example;
On Jan 15 2016 purchase 10 contracts AVXL, July 15 2016 expiry, strike @ $5.
On July 14 2016 assume AVXL is at $15. The 10 contracts are worth;
10 * 100 *($15-$5) = $10000
Assume you purchased the 10 contracts for $1 each, total cost;
10 * 100 * $1 = $1000
Scenario 1
If you sell you will have a short term capital gain of ~$9000. Taxes could be Fed, 28% or more + state taxes of 0-11% depending on where you live. Assuming a combined Fed and state tax rate of 30% you would owe;
$9000 * .3 = $2700 in taxes. That would leave (9000-2700)~ $6300 of capital. If you immediately purchase AVXL at $15 you can get $6300/$15 = 420 shares. Your purchase date of July 14 would be the start of your holding period for tax purposes.
Scenario 2
How about you think that AVXL at $15 is still a bargain. You want to be in for the big dollars (that's me) and you would prefer to not spend some of your capital to pay taxes. So think about this instead;
Sell 4 contracts; 4 * 100 * $10 = $4000 of capital
Taxes at 30%, $4000 * .3 = $1200 taxes, $2800 of capital to re-invest
Exercise 6 contracts @ $5; cost 6 * 100 * $5 = $3000 cost
If you can come up with $200 to exercise all 6 contracts ($2800+$200) you will now be holding 600 shares that have a 'holding' start date of Jan 15 2016. When you first purchased the options you just exercised. You've also reduced your taxes for the year. And you end up with more AVXL shares.
CORRECTION: You will need to hold the shares for one year for them to be treated as a long term capital gain/loss at the sale time. My original message stated that the holding period started at the purchase date of the options. The stock holding period starts at the exercise date of the options.
If you hold the 600 shares for another year any gains will be taxed at long term capital gains rate by the Feds... currently 15% for most of us... unless you are in the 1% group then it's 20%. But at 15% you cut your capital gains tax rate in half. When you do decide to sell the 600 shares of AVXL (north of $100 I'm sure) your cost basis will be the option premium, $1 per share + the exercise price $5 per share, for a cost basis of $6 per share.
Obviously not advice. After all this is a message board. But maybe something to think about.
Regards
Yes. Agree. Each patient can contribute a primary event, PFS, and a secondary event, OS.
But the primary trial outcome and the trigger for data analysis is PFS.... not OS. The crossover will modify OS depending on how effective DCVAX is. But PFS for the placebo group should not be effected by DCVAX. So what I do not understand is the statements "..that the trial is taking longer because everyone is living longer..." or "... we are now comparing early DCVAX vs. late DCVAX..."
It seems we should have already reached the first interim number of events with the associated data analysis. UNLESS DCVAX is so effective there are very few patients in the trial arm that have progressed and can be counted as an event for the 149 events needed to reach the first interim. Which is what I hope for but I'm frustrated like everyone else. I would just like to know one thing;
Have we reached the first interim point or not?
Seems like this is material information that the company would need to tell investors but then they might hide behind, working with FDA, trial integrity, etc..
Anyway, I still believe in the science. Just wish the fog would clear soon.