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.
IMO, a learning process driven by peeling back the steps/sequence (gradual/spontaneous) by which cognition is snuffed out is critical. The reverse engineering of the whole sequence will certainly get us to the root cause. If M. is correct and the restoration of CNS cellular Homeostasis suggests cognitive health and behavioral normalcy then this kind of imagery might be used to validate such a correlation and to verify restoration. We would expect any restoration would vary from pt to pt measured over time/compared with controls of course. Using reverse engineering techniques/thinking keeps the ball on the field all the time, we expect to see the cause/effect virtually real time. If AD is progressive w/time then the reverse must/might also be true. There has been anecdotal evidence that some AD pt's recover, but what about the rest? Does partial restoration count, how is it measured? RWE/PET and cognitive testing will certainly be factors in AD future trials testing.
I declare as a volunteer for the continuous frat boy control branch of the trial.
Sponsors must give the Agency adequate information to thoroughly critique the SPA and decide if it addresses the key scientific concerns. Therefore, any potentially problematic features of the study protocol should be addressed with sufficient information for the FDA to come to a consensus.
Despite the provided justification, the FDA does not always agree that the submitted protocol will satisfy all questions. Subsequently, a nonagreement letter can be issued. When a nonagreement letter is reached, the Sponsor has three general options. They can initiate the clinical trial without an agreed upon SPA, send a written response to the FDA regarding the nonagreement letter, or request a meeting to discuss the nonagreement letter. To ensure the most effective utilization of resources, reaching an agreed upon SPA is recommended before initiating the clinical trial. Depending on how many outstanding protocol issues are presented, a meeting or written response may be preferred.
The significance of the RETT trials continues to grow every day. No wonder they kept going w/the amyloid plaque trials even though a child could see they went no where. Powerful AI and strong intervention skills will be needed here.
[quoteBiogen just adapted their amyloid drug study by adding more patients ][/quote]
Thanks doc. Like the man said. "Tip of the iceberg". Very much appreciate your contribution I understand you to say that this is going to take a while and there is no, "one size fits all" solution.
At some point the science must be tested*. When that happens (* tested means under established controlled conditions ) the smoke will begin to clear. On days like today I am actually happy I do not have the level of scientific knowledge of Falconer/Doc and others. I used to tell a brilliant friend and 820 product sterilization expert that I was happy I did not know what he knew b/c I could not sleep at night if I did.(we all assume that products labeled STERILE have been correctly processed) Again longs were compelled to be civil while being attacked. I remain thankful for the 15# post limit on iHub.
Better days are ahead for certain, baseball season has begun, the Red Sox are going to kick the NYY ass all season and eventually little Rett patients will get a shot at a better life. All the best.
In fact bio investment (waiting for trials) pass/fail bungee investor reflex will be gone. IND trial agreements/starts will eventually be equivalent to strong P2/3 results if not more. B/C of the new scrutiny done by sponsors and regulatory. Will not be same ole FDA guidance. All this work will migrate to the sponsors process left where it should have been all along. IMO you are correct. If RWE IND patient comm. gets hacked then we will see SP chaos. Less (maybe no) emphasis on long term massive statistical models which accomplished nothing till now except cover some committee hacks ass.
BUT, if AVXL IS worth what clinical evidence indicates is possible then the SP will reflex faster than the hackers can anticipate. IMO. But, it WILL drive SP chaos for sure.
T-38...thx again for all you have done and for your over the horizon insights.
We must appreciate the scope of the AVXL task. We are presented with either one massive binary event (a true OMG moment) leading to effective treatments or an old school BP/WS CFIT. All the best.
Doc...thanks for grounding all of us in the reality of dealing w/regulatory bodies during times of change. Can you say ,in this context, how the new "precision Medicine" trials rules are being developed/applied. Are these guidance or are they requirements being applied to the first trials and how is RWE being treated? If new learning occurs which change the trial plans, do they stop/go back and restart or evolve as they go? TIA
How does an enterprise establish a IND protocol with these process controls in place?
Type B meetings are as follows:4
• Pre-investigational new drug application (pre-IND) meetings (21 CFR 312.82)
• Certain end-of-phase 1 meetings (21 CFR 312.82)
• End-of-phase 2 and pre-phase 3 meetings (21 CFR 312.47)
• Pre-new drug application/biologics license application meetings (21 CFR 312.47)
Type B meetings should be scheduled to occur within 60 days of FDA receipt of the written meeting request. If a sponsor or applicant requests a meeting date that is beyond 60 days from the date of request receipt, we will work with the sponsor or applicant to determine the earliest agreeable date.
To promote efficient management of formal meetings, the requestor should try to anticipate future needs and, to the extent practical, combine product development issues into the fewest possible meetings. Generally, we will not grant more than one of each of the Type B meetings
[quote“As clinical trials become more virtual, sponsors will be able to ‘dial in’ what capabilities they want virtualized,” he said. “This new Apple feature will enable new capabilities that were not possible before.”]
Can you imagine trying to do a config mgmnt validation to comply w/part 11 under on the fly/cloud based clinical system?
Are Apple iPhones a key to the progress of our future trials?
On the other hand this results path is absolutely consistent w/RWE concepts. Who will own/validate trials results? How will FDA use this trials data to do pass/fail? What could go wrong?
The reported conversation with IR on IND status is very encouraging news. Some of us have suggested a scenario similar to the one described by IR. A study of what has been published by the FDA on new IND-Precision Medicine protocols also indicates we are doing what was expected working with the FDA. We could not predict how much time would be required to do the back-forth planning/critique but months(not weeks) are to be expected. Anyone with any FDA interface experience can see what is being done. Extreme caution must be exercised at the trials expectation/RWE/PR-news interface. The work must be done well and it must be reproducible. Expense and time must be forecasted while day to day conflicts are resolved. Conflicts galore.
Go look at what the FDA has already released on the topic (we have posted the links here a while back with discussion). The FDA has established a structure/framework of the trial design with required checkpoint with emphasis on what not how and RWE-patient interface-takeaways. It all reads to me like they expect tp rely heavily on pts/RWE and being as flexible as possible in interpretation. Nothing at all like conventional FDA trials. What would be unknown at this point is what clinical/pts evaluations must be done, at what point in the protocol, what will/must be measured and when, what pass/fail acceptance criteria (if any) will be used and when applied.
We must keep in mind that these CNS diseases have NEVER been effectively treated. Even though pre trial information establishes basic expectations no one has ever been here before. Not only do we need results to be precise and meaningful but we better not make an error b/c the entire pharma world has just had it's collective ass handed to it. We can intuit that something very important will eventually come from this molecules testing. Let's hope it is soon but sadly we have no way of knowing when or what. I do believe that some very exciting science is about to demonstrated.
Varian Medical Systems has projected that by 2022, approximately 15 million patients will be affected by metastatic brain cancer. According to DeSantis CE’s cancer treatment and survivorship statistics for 2014, 20%–40% of those total cancer patients have brain metastases. These factors highlight a growing demand for stereotactic radiosurgery solutions for treating brain metastases. That, in turn, is expected to accelerate the buying of new and the replacement of older radiotherapy systems that will be fitted with the HyperArc solution. Additionally, upgradations of the company’s large TrueBeam Eclipse installed base are expected to be a key driver in increasing the adoption of the HyperArc solution. The company has projected the market opportunity for HyperArc to be $300 million by 2022.
...ever been to Singapore? YYYUUUUHHGGGE wealth and it is 80%+ Chinese. Don't look now but the Chinese ALREADY OWN just about everything. They just let us think we own anything. IMO, the "T" man get's it.
Xena..cannot do PM. Would expect Si3N4 -silicon nitride body of knowledge to be extensive (semiconductor guys have been all over the physics for decades) compared to CNS. Should be much lower risk than AVXL. Looks very solid.
Discovery of new levels of scientific knowledge that change the trial structure is not a "miss".
IMO, this point you make helps explain some/most of any back-forth between sponsor(AVXL) and FDA on Rett IND. We may never know for certain but we can speculate that the "Precision" process is doing what it should be doing, it is raising the bar. Another important consideration is no one has ever done this before. The term "Untreatable" is applied in the CNS disease space every day. The FDA and all BP have failed completely to after decades of their "best" efforts, etc.. The risks do not get any higher in investment.
References in other posts have been made here to quotes from famous martial arts leaders-poets. A favorite of mine is from Musashi, "Walk as a dead Man." As a samurai, fight as though you were already dead. The risk is so extreme you should assume your investment is already gone.
I think all the preclinical data being revealed as to sigma 1 r agonism restoring cell function and achieving homeostasis in a multitude of indications is a warning bomb and a big stick. I think the absence of data contradicting this or showing adverse effects means the big stick is made of strong wood which won’t splinter easily...when the time comes to use it
think all the preclinical data being revealed as to sigma 1 r agonism restoring cell function and achieving homeostasis in a multitude of indications is a warning bomb and a big stick. I think the absence of data contradicting this or showing adverse effects means the big stick is made of strong wood which won’t splinter easily...when the time comes to use it.
Bios...thanks for an excellent leadership post. The key points for me are as far as we know the science is real. There is still no contradictory scientific thesis. You make the point that Dr. M. cannot provide details b/c the size and strength of the opposition is too much to defeat head on. I had not considered that before and it is a legitimate point. Avoiding death in the military varies day to day but you better act like it is constant ,"act like a dead man".
He had a duty to "take his time" and get it right the first time, to assess the needs to get it right, to assess the pitfalls of the FDA, to submit a clean IND, and to get trials on the timeline HE set. He failed.
Name ANY organization that has filed IND since new FDA "precision medicine" requirements have been set.
Not an apology for M just trying to establish a meaningful context for this comment. Increased "precision" infers a more detailed factual assessment process. Looks to me like the rules/protocols are being rewritten. If any examples/facts exist it would be helpful to review them and in fact any relevant example could add credibility to your statements.
Got this from a site specific Google search use "m4 site:anavex.com":
Good effort, thanks. Still possible, still no contradictions. Can only imagine what the parents and caregivers for these little girls go through night and day. Makes one feel a little guilty for whining about lack of news/movement/progress/validation/verification/trials/test results ...anything that is not negative.
All we need is a solid-fact based set of objective evidence that the science has been validated again in some CNS context. Substantial but no need to be massive(would be great but), I'll go w/substantial and not a PR Puff piece only.
I think that the FDA will want to see data that shows changing those biomarkers affects the trajectory of AD. Doing that will take many years and a lot of subjects.
IMO, once clear and convincing evidence of biomarker-AD links exist then immediate pre trials will start on acceleration factors. Of course it will take years to refine these links but (IMO) science will find a way to speed up the process.
I’ve written my Senators but getting them up to speed will take time and many emails from investors. The shorts gained a big advantage after Hillary’s tweet in 2015 bringing all the baby bio’s under $2.00 where they became defenseless. No one wants to touch them there while they get pounded. Now the entire sector is bound and gagged which suits BP fine. No competition for their “approved” money makers.
And retail doesn’t have the funds or the coordination to compete with deep pocket professional bashers, H/F computers and cooperating MM’s. It’s fugly.
We have Dr. Gottlieb and hopefully a Rett trial to get started to see if we can overturn their apple cart. A lot of us here are betting on that.
Agree w/this thread and others stand alone observations on how the scientific facts and overall potential on AVXL do not fit with the current sp. These inconsistencies have been reviewed here many times from different points of view. We are left with only two possible explanations. Either Anavex science and supporting facts are totally wrong or there is an organized effort to collectively hold AVXL SP down. We have all seen and would witness the recently exposed massive corruption in areas we never would expect. Anything is possible.
As retailers we are not in an informed position so we rely on our analytical skills and information we can dig up. Those of us who believe there must be an explanation. We can only look to Dr.M. for tips/clues but his policy of silence (which may explain itself at some point) leaves us in a place of trust our instincts and pray a lot. Seems clear enough that the current status is not sustainable and we expect the world to come to it's senses. We are definitely fighting an uphill battle, it would help a lot if we knew why.
The disparity of Market Caps between ACAD ($2.8 Bil. and as high as $5 Bil.) and AVXL ($122 Mil) is staggering, 23X. What would a similar valuation of Anaxex do to the price of AVXL stock? One does not have to have a great imagination to see what Anavex should be valued at today. Just examine the market caps of other CNS clinical stage companies like ACAD and Sage ($7 Bil with NO APPROVALS) or like AXON ($2.4 Bil, before) in its, Wall Street sponsored pre-clinical pump stage. Why is AVXL stock priced so low? That is the $63(thousand) question and may be partly due to Anavex not being a Wall Street Sponsored/Controlled company having not IPO'd with the controlling stock interests in the hands of Wall Street. Is Wall Street getting their shares by running over and running out retail holders as best they can with manipulation?
A very wise man once to me ..."If you are expecting justice, you will always be miserable."
Agree, that is what most of it looks like. Still looking for any new/innovative AD studies or PII trail plans being started since the recent BP stand downs.
Most of these drugs are either plaque attack or re-purposed. I don't see much that is novel or apt to be competitive to 2-73 if it works as we hope it will.
Xena...very well done. thx. Surprised anyone would still be spending $$$/time on some of these considering what the past couple of decades of similar studies have accomplished.
Thanks for the efforts to clarify and evaluate what AD trials are being conducted. The research efforts are commendable of course but, really? Crickets.
We need to be aware of the time bubble which most biotech-pharma labs/development organizations live in. H/W medical device people(part 820) have H/W regression curves/methods which can be used to safely accelerate failures, for example. They are able to accelerate H/W failures. The bio clock variable is experiential, some may have clocks that run synched with the rest of us but often bio clocks are not synched. Consequently they might have 3 yrs to wait for results in the lab while the rest of us decompose in 1 year. All of this gets completely screwed up when someone stops the train and requires a restart(Precision medicine for example). AVXL may be slower than even the normal clocks due to the nature of CNS diseases. Hopefully, RETT will soon accelerate the clock somewhat. It is all very frustrating as we await evidence-results. IMO, the clocks will probably be reset/synched up when we start to see PII timelines/results. I have seen nothing that predicts how much time it will take to demonstrate efficacy or if the normal clocks will even matter much. Many of us expect quick feedback though.
Talon..thanks for the excellent observation here..
However, these examples of leadership with strong communication and persuasiveness are not a effective yard stick of leadership in Christopher Missling case. In the cases of each of your cited personalities they needed leadership to advance a mission or product to success. Dr Missling on the other hand, needs management skills in the business, financial and regulatory area to advance a drug through very controlled development. No amount of electric or eloquent pep talks will advance the FDA process faster or with any higher probability of success. The drug lives or dies on its own effectiveness. The amazing fact is, that CM has put 2-73 on stage in an astounding number of CNS "plays" and has a number private, academic and government entities as benefactors. He and Anavex have accomplished this with little fanfare much to the chagrin of a number people on this board. A possible better comparison would be to another quiet German, Warner VonBraun.
So though we agree on much, even the need for Anavex Management to communicate more often, I would not classify it as a "fatal flaw". Let success by the end of the year speak for itself. Meanwhile, there are a good number of Bio/Pharmas that have over promoted their drugs and are now having to leave the field of battle with their tails between their legs!!
After many years of international studies in regulatory operational environments I have also observed a key point touched on by Talon. Many national cultures have developed their own management/leadership rule sets. Americans tend to view every action according to American rules/laws/practices and , in this case, guidance docs. Americans project our interpretation of the RULES. For example, FDA inspectors are trained to judge leadership effectiveness based on the actions they take. I can say with certainty that German, Swedish, Japanese in country management practices are not anything like American practices, even though the rule/required outcomes are identical. Actions that might be considered unethical in daily American practice will not work and would be instantly called out in American business are common (cultural) practice in other business cultures. Anyone doing regulatory work WW could cite many examples of this fact. Dr. M. may be (I believe he is) applying his own hybrid business management culture. The one rule set that stands out is his judgement on when and what should be communicated. It's complicated.
But biomarkers are not the same as symptoms, so the risk is that costly new drugs will be approved that do not actually work.
He is right on, IMO. Translates to: We (ME&FDA staff) do not know if we are going to spend a lot of money and time and get nothing for it .(Like BP has for the last 40 years w/FDA guidance) We just cannot go through another 30 years of telling people we cannot help them. There is no treatment.
Therefore, FDA are going to use the Cancer Treatments model/methodologies and will map-follow progress very closely. We do not know what will work and what will not work but expect that RWE and clinical testing should(quickly) tell us if we are on the right path. We think this human based instinctive model will/should at least provide feedback we can use real time.
A2-73 should provide quick feedback on efficacy of treatments. It may not be a "one size fits all" molecule but the process of measuring and adjusting is known to work. Sample size and statistical rationale will still be involved as protocol but they will be used in different ways than in the past. There are a lot of moving parts and not everyone is on the same page yet. We do not expect 100% failure with A2-73 like in the past AD trials, for which many are still in denial. We have still not figured out who to fault for all of that. Wouldn't it be nice if we could just start doing our new trials and not tell anyone yet.
You are correct a suit can overwhelm a small company like AVXL. Hopefully we can move on now with full understanding of what and when to say about things material.
Now is the time to get and stay focused. Start and finish RETT trials. Yes, we all have bigger, bolder thoughts of future CNS work but right now it is just blocking and tackling. It is execution time. It is about X's and O's. Keep it simple, and communicate.
News 
Market Data 
Discover 
