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NFLX’s PE ratio is something like 133, and its revenue is going to get wacked very soon. Paying the currently inflated price for NFLX stock - betting that it will be able to continue as it has done to reach an extreme — betting that it has a great future — is insane. As some DiscoverGold articles and the below sited Forbes article point out, NFLX’s glory days are over. Its days are numbered. Doing the same thing over and over - bidding the stock price up - is insanity. However, there will be investors that believe that this time this situation is different when it should be apprent that it is not. However, history will repeat itself, and there will be investors that continue to buy even at the top, which will come after the last overly enthustiac investor buys at these extremely high levels. Here is the Forbes article:
Netflix Has 175 Days Left To Pull Off A Miracle... Or It's All Over
https://www.forbes.com/sites/stephenmcbride1/2019/05/21/netflix-has-175-days-left-to-pull-off-a-miracle-or-its-all-over/?utm_source=newsletter&utm_medium=email&utm_campaign=investing%22&mkt_tok=eyJpIjoiTW1ZM01EY3hZek16WlRrMyIsInQiOiJKb1Ixbk1Oc1NaZ2w1aDVJWXoyaFhnRkErTFJqck9Rblh3aVNENkl5K29RUjJNckRzcU5OXC8waDJRZU5QN1FBNlc2aHVXYm5FR0k2dnREUk1YQWRSOXRmQU84MVZGbDFSb2F5Skl1U0xxUmtjYTVqSVwvMHJXdWRmeTdKSVwvVGxJciJ9#74ba364f75c4
AAIC July 14-18. We’ll see if something emerges that will help AVXL share price to bottom by Thursday 18th.
My opinion is that very little, if anything, is known about this chemical in this study in terms of sigma 1 activation. The chemical used in this study is endonerpic maleate also referred to as T-817MA.
Edonerpic maleate is described as "A neural plasticity enhancer"
https://www.biovision.com/edonerpic-maleate.html
The article you site concludes:
“The clinical outcomes of three Phase 2 trials do not provide evidence of clinical proof of concept for edonerpic maleate for patients with mild to moderate Alzheimer disease,” wrote the authors.—Gwyneth Dickey Zakaib
I am not sure that it has been established that edonerpic maleate is a sigma 1 agonist or how it may activate sigma 1?The article you site does say that edonerpic maleate is a sigma 1 activator although other articles mention that "T-817MA reportedly activates sigma receptors." https://www.alzforum.org/therapeutics/edonerpic
"Chemical Name: 1-{3-[2-(1-benzothiophen-5-yl)ethoxy] propyl}-3-azetidinol maleate". https://www.alzforum.org/therapeutics/edonerpic
I have not found anything that discusses edonerpic maleate in terms of sigma 1 activation or how it may do that.
AVXL 2-73 is a completey different chemical. "Chemical Name: Tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmethanamine hydrochloride". https://www.alzforum.org/therapeutics/anavex-2-73
"Anavex 2-73 is a small molecule that activates the sigma-1 receptor, which is known to modulate cellular processes relevant to neurodegeneration. "
https://alzheimersnewstoday.com/anavex-2-73/
AVXL 2-73 is also a mixed ligand. "This compound is an agonist of the intracellular sigma-1 chaperone protein. Specifically, it is a mixed ligand for sigma1/muscarinic receptors. Expressed in most tissues and located at focal contacts between mitochondria and the endoplasmic reticulum, the sigma-1 receptor forms heterodimers with many other membrane receptors, and as such influences multiple cellular pathways and physiological processes. Anavex 2-73 reportedly binds the sigma-1 receptor in the high nanomolar and the muscarinic receptor in the low micromolar range." https://www.alzforum.org/therapeutics/anavex-2-73
Additionally, Australia may consider any results from the PDD study in Spain because of mutual recognition agreements.
Mutual recognition agreements (MRA)
https://www.ema.europa.eu/en/human-regulatory/research-development/compliance/good-manufacturing-practice/mutual-recognition-agreements-mra
Clinical trials in human medicines
https://www.ema.europa.eu/en/human-regulatory/research-development/clinical-trials-human-medicines
https://www.ema.europa.eu/en/partners-networks/international-activities/bilateral-interactions-non-eu-regulators/australia
Multiple Endpoints in Clinical Trials
Guidance for Industry
DRAFT GUIDANCE
''Because most diseases have more than one consequence, many trials are designed to examine the effect of a drug on more than one endpoint. In some cases, efficacy cannot be adequately
established on the basis of a single endpoint. In other cases, an effect on any of several
endpoints could be sufficient to support approval of a marketing application. ''
https://www.fda.gov/media/102657/download
The Regulatory Strategist Toolbox: Clinical Endpoint Analysis Tools
"Secondary endpoints also may provide evidence that a particular mechanism underlies a demonstrated clinical effect (e.g., a drug for osteoporosis with fractures as the primary endpoint, and improved bone density as a secondary endpoint).17
Positive results on the secondary endpoints can be interpreted only if there is first a demonstration of a treatment effect on the primary endpoint."
https://www.raps.org/news-and-articles/news-articles/2018/9/the-regulatory-strategist-https://www.raps.org/news-and-articles/news-articles/2018/9/the-regulatory-strategist-toolbox-clinical-endpoi
In other words, if any treatment effect is shown for the primary endpoint, a secondary endpoint may be considered to establish efficacy of the drug. Therefore, if AVXL demonstrates some treatment effect for AD the evidence for the secondary endpoint, sleep, may be considered to approve the drug.
Yes. I think the regulatory authority will look for what it considers adequate proof the drug is effective for the particular indication or indications and for safety of the dosage required for that indication.
FDA Helps Streamline Approval Process for Supplemental Drug Indications
'More and more approved drugs are being used in multiple indications, and increasingly, supplemental new drug applications are being submitted using an intermediate endpoint as clinical benefit because the need is so critical.
“A supplemental new drug application can entail either a regular or accelerated approval,” said Amy McKee, MD, Supervisory Associate Director, FDA Office of Hematology and Oncology Products. “The agency may now grant full approval to a supplemental new drug application using an intermediate endpoint on a case-by-case basis. One reason is because we weigh the urgency of an unmet clinical need.”'
https://www.ascopost.com/issues/december-25-2017/fda-helps-streamline-approval-process-for-supplemental-drug-indications/
Biotech Stocks Brace for Another Election Cycle
https://www.barrons.com/articles/biotech-stocks-politicians-election-cycle-51555682769?emailToken=b92c05b24a3cf813a507910ca99674d9FFtuDRG1U9IU8QZBPQFg3CEVmCjjxbi46zoTUb/JhGG8XfJPdmXMbXVQyX5qkN1+CgZKtxntM5OinIoOHsZ+PbPurLznoThn6YIy06R0BDE=
Anavex is smart in planning ahead for contingencies and how it may have capital to continue its future drug development. Anavex has several options to raise funds and adding the most recent shelf offering is a very wise move for a number of reasons including the upcoming political cycle so that it will not be starved during this presidential campaign. See the above cited article, which says:
“Of course, companies with innovative products can demand more pricing power, and longer term, he still sees reason to be bullish on biotech in general. Yet nearer term the road could get tougher, and if investors flee the sector, it “can starve the capital burning small- and mid-cap companies (arguably the ones delivering the most productive innovation, paradoxically)—leading to a disproportionate valuation ‘hit.’”
The irony of a politician bashing biotech is that they may be discouraging the development of drugs to treat diseases, like AD, that cost the government and society huge amounts of money and grief.
Another observation is that we are in one of the longest economic expansions in history. It is long in the tooth, and it may end at any time in the next few years. I see that as yet another reason for plans to raise capital. Do it now while we can.
I believe Anavex anticipates growth, and it desires to be in a position to act quickly to raise capital as needed. Anavex has created many options to raise capital, which is good, but this is a quick, efficient and low cost way to do it. Why not file a shelf offering is a better question? And why not file only one, but make it large enough for the future - next 3 years. A shelf offering is good for 3 years. Personally, I believe, as Bio, that Anavex has high odds (80%) for a drug approval in the next few years. Before approval, the odds are high we will see positive clinical trial results. That will drive share price up and allow some shelf shares to be quickly issued to expand and accelerate further development.
80% odds and the high market potential for its drugs is a risk I am willing to take based on my DD done over the last four years. However, I advise everyone to do the extensive research and form their own opinions.
.... The filing, in no way, means that the company is planning on selling all of the securities mentioned in the filing immediately.' https://www.davemanuel.com/investor-dictionary/automatic-shelf-registration/
Anders, Investor and others explained it very well. See their posts and replies to their posts.
Anders and Investor: Excellent! Anavex too may be facing a lawsuit if it hauled off and issued an unreasonable number of shares. Anavex has good legal counsel that wouldn’t standby and let Missling go overboard with this. Besides, Anavex is gun shy after being sued a few years back although it won the securities lawsuit. Thank you.
Logical, sensible and obvious-now that you pointed it out. Thank you, Anders!
Most great investments begin in discomfort. The things most people feel good about – investments where the underlying premise is widely accepted are unlikely to be available at bargain prices. Rather, bargains are usually found among things that are controversial, that people are pessimistic about, and that have maybe have performed badly for a long while (look at the long term chart for AVXL - AVXL's stock performed badly for a long time). Sometimes it is uncomfortable owing AVXL stock. It is NEVER easy to do things that entail discomfort, but being uncomfortable comes with the territory when investing in new ideas.
Most people do not like change of any sort, but you need to invest in something different to make real money.
Bob Farrell said something that not only applies to the stock market generally to everything that goes on in life. The stock market reflects sentiments of how particpates, people, react. As Bob Farrell observed:
“Change of a long term or secular nature is usually gradual enough that it is obscured by the noise caused by short-term volatility. By the time secular trends are even acknowledged by the majority, they are generally obvious and mature. In the early stages of a new secular paradigm, therefore, most are conditioned to hear only the short-term noise they have been conditioned to respond to by the prior existing secular condition. Moreover, in a shift of secular or long term significance, the markets will be adapting to a new set of rules while most market participants will be still playing by the old rules.”
Do you dare to look wrong. Any new, innovative, revolutionary idea has to go through the stage of looking wrong because you are doing something that no one else is doing. Real money is not made by doing what everyone else is doing as Howard Marks, one of the most successful investors known, knows.
As Theodore Roosevelt said: “It is not the critic who counts...never be with those cold and timid souls who neither know victory nor defeat.” If you are of the opinion you have the goods when it comes to treating multiple CNS diseases that combined may be "priceless" - too valuable to imagine - load up the wagon and go for it. In the meantime, do not worry about the short term or those that are so short sighted they are incaplable of envisioning the transformation that may result from a drug or drugs that may have major monmumental positive conseques. Anavex should go to war on CNS diseases, take all of its weapons, load up the wagon, raise as much money as it can, and go for it! Think long and think big or go home. Damn the torpedoes!
Shelf announcement. Good/bad news? Short term/long term thinking. To those that think short term, the shelf announcement may be bad news, but let's see what the SP does in the next few days. It may not even be bad news short term depending on how larger investors that move the share price analyze it. To those of us that think long term, the shelf announcement is likely good news. I realized a long time ago that I could never make real money reacting short term, and my long term endeavors since have exceeded my expectations. To me, the shelf proclamation, yet to be determined whether it will ever be implimented wholly, partially or at all, is NOT bad news.
Yes, I agree with Investor and others that Missling is sending a message, raising funds “for anticipated growth”, that we are bold enough to step out there and pull the wagon forward all by ourselves. We are willing to attempt/risk raising up to $250,000,000.00, which is conceivably more than enough to get AVXL 2-73 through the trials and drug approval. Therefore, any pharma company interested, get serious or risk losing an early deal. That is exactly what I think I would do given the opportunity.
Purpose of the shelf offering “for general corporate and operations purposes and to fund our anticipated growth.” Anticipated growth?
More details are to be furnished with each specific offering.
Nidan:
I think about Anavex every day. Strangely, the night before this shelf offering announcement, I dreamed that Anavex raised $100,000,000.00 in an offering. It was a good dream - not a nightmare, and good for Anavex. I think I have had the $100,000,000 in mind all along to complete the AVXL 2-73 stage 3 clinicial trial, and that may be what prompted my dream.
Thanks, from the article you furnished:
“Lastly, @colinmagowan asked, “Did you track lead asset stage and disease, or say # of therapies in clinical trials when S-3 filed?”
I can see where the questioner is coming from; drug development costs vary by therapeutic areas. Thus, companies working in these areas may need to file larger shelves for more money. Further, the capital markets tend to value later stage assets more highly, as they are presumably closer to market. Late stage clinical trials cost more, too, so perhaps shelf filers and shelf size are related to stage of development.”
My additional comment is that the number of clinicial trials being conducted should be a factor, and I wonder how markets value a large shelf offering of a company with three clinical trials for a CNS drug to treat three CNS diseases.
In any event, see this additional article that points out:
“CNS and anti-infective treatments are the most expensive to develop.......
Clinical development times were highest for CNS and cardiovascular treatments, but clinical costs were lowest (see figure). The reverse was true for anti-infectives and analgesics/anaesthetics....
The difference in returns from each therapeutic area hints at how companies are forming strategy decisions. The ratio of life-cycle worldwide sales for new drugs approved during 1990–1994 to the development costs calculated in the study was greatest for CNS and cardiovascular drugs (see figure), which included big-sellers such as SSRIs and ACE inhibitors. Anti-infectives and analgesics/ anaesthetics fared less well. This difference in profitability could explain companies' decisions on allocation of R&D resources, says Ken Kaitin, Director of the Tufts Center. “Our findings are consistent with a model that suggests R&D efforts have generally shifted towards high net return, and away from low-return therapeutic areas.”
https://www.nature.com/articles/nrd1436
I believe the capital markets will ultimately weigh this shelf offering primarily based on the high return potential of AVXL 2-73 for treating CNS diseases and the stage or stages of development of its trials as well as the fact that Anavex is the most advanced in exploring a promising alternative for treating AD, for example, now that the amyloid plaque removal theory has faded. Anyway, right or wrong, that is how I view the situation.
Whatever the reason (we can only guess), take a look at on balance volume, which has increased sharply. This indicates institutional buying, which I believe is moving the share price higher with lower lows and higher highs in the last few days at least. To have big share price moves one way or another institutional buying or selling is needed to accomplish that. Us lesser mortals cannot achieve big moves. We can think of a lot of good and very positive reasons why institutions may be buying though as many of us on this board have done, but we are all guessing at this point. I think the only thing we may safely conclude is that institutions are definitely buying and that is good as long as it continues.
Anavex share price has been consolidating since the end of March of this year. It has, during that period, approached $4.00 twice before now, but it did not have the volume buying to punch through $4.00. Based on the last two days the volume has been much higher indicating institutional buying, which is what is needed to move share price. If the share price is to break out of this consolidation phase that has been building over the last three months, now is the time for it to do so and punch through the $4.00 pivot. The timing is right for a potential break out that may be maintained. We are leading up to AAIC 2019, which begins July 14, and our trials moving along. It is news time.
Eisai Co., Ltd. is a Japanese pharmaceutical company headquartered in Tokyo, Japan. It has some 10,000 employees, among them about 1,500 in research. It is true Eisai has failed in its AD drug development. Therefore, is it logical that it would be looking for a new horse to ride if it has not given up on an AD drug, and why would it do that - give up?
Is it logical to assume Eiasi has abandoned any interest in AD? Eisai is listed on the Tokyo Stock Exchange among others. It is a prominent company in search of new drugs. As Xena has said Japan is ideal for approval of a drug as long as Anavex can approve the drug is safe. What’s more, Japan has an aging population - consider that and more. AD is a disease of the aging populations. Therefore, if Eisai is interested in Anavex (and I am always cautious about the interest of a competitor), that is an avenue to early approval of AVXL 2-73 in Japan at least, and it may be that investors that moved the market today may be inclined to agree.
However, let’s see what the next few days of trading bring although I think that it is very likely a lot of interest in Anavex stock will continue to develop between now and the middle of July. The big conference is coming up later this month. Companies will be interested in attracting attention for their AD drugs that are in development. AVXL 2-73 seems to me to be the new horse to ride for this year’s conference at least.
Yes, today’s volume is indicitive of institutional buying, which is good. Institutions move markets as opposed to lesser mortals like ourselves, but that’s what we lesser mortal longs desire, right? The great majority of us here are long, and we need the institutions to move the market up for us as well as themselves. Besides, if we are correct about institutional buying, they will wipe out a proclaimed short or two although I do not wish anyone any harm. Therefore, I hope our professed shorts cover.
What’s more, who knows - some positive news may emerge at any point with three clinical trials ongoing, and it is getting close to Alzheimer’s conference time. It’s that time of the year for potentially hopeful news to emerge, and those attending the Alzheimer’s Association annual meeting need to find a new horse to ride. Amyloid plaque removal is either dead, or it needs to be put out of its misery. Everyone should be looking for a new horse to ride.
Yes, I agree that it is very likely the price will punch through the $4.00 pivot. The share price has been in a consolidation phase since March 26, almost 3 months. Late Friday was an indication of buying interest with pretty good volume, which should continue and increase next week. Additionally, we have strong possibilites of multiple catalysts that may kick in at any time. Institutions move share price, and I think the positive Russell surmise will attract institutional buying furnishing the fuel to boost the share price. Assuming that the present value of the drug, AVXL 2-73, for AD alone is anywhere near worth $750,000,000.00 as some posts here recently conjectured, the share price may be viewed as undervalued. Anavex is not a one trick pony. It has other value in the pipeline besides AVXL 2-73 and its potential use for treating AD.
Personally, I feel strongly that it is an excellent biotech speculation, and that biotech is one of the few places to make “real money”. Over time, I have accumulated as many shares as I can stomach to own. However, as Howard Marks says in his “Dare to be Great” memo to make real money you have to be different and you will feel uncomfortable at times with your investments that will accomplish that. You cannot make “real money” by attempting to follow what everyone else is doing. Those that are long Anavex are being different (Anavex is different) and have at times been very uncomfortable, but I, for one, believe this company is worth my sizeable speculation, but do you own DD and form your own opinions about Anavex.
“...close to a cure...” If not a complete cure, may AVXL 2-73 be an add on therapy?
Bio:
I live in a neighborhood where most residents are elderly. I have personally observed the problems that constant sleep interruption causes families of AD patients. In three instances within the last 10 years the spouses of 3 neighborhood patients living at home suffered from lack of sleep because their spouse with AD would wake up repeatedly during the night requiring the attention of the care giver spouse. AD patients wake up, sometimes hallucinate, wonder around including walking out of their home during the night, etc., interrupting the spouse care giver’s sleep and causing stress that results in problems that over time that are highly detrimental to the care giver’s health and ability to function.
The decrease or elimination of what I describe above is huge. It may also mean that the AD patient continues to remain at home versus an institution resulting in the reduction of healthcare costs. Therefore, treating sleep of the patient results in a benefit to the patient, the patient’s family, and governments that share in the burden of health care costs.
Additionally, I agree that the ability of AVXL 2-73 to improve sleep of AD patients is another indication that the drug is working to treat AD in general.
It is too difficult to qualify under the so called right to try law.
To be eligible for Right to Try, a patient must meet the following conditions:
Be diagnosed with a life-threatening disease or condition;
Have exhausted approved treatment options;
Be unable to participate in a clinical trial involving the eligible investigational drug, as certified by a doctor, who is in good standing with her licensing organization and will not be compensated directly by the manufacturer for so certifying;
and
Give written informed consentregarding the risks associated with taking the investigational treatment.
Note: By the time all available treatment options are exhausted for AD (none of which work for treatment) for example, the patient is done ... too far gone.
Here’s a theory about why Anavex may be raising more capital now that we are all speculating. Things have and are changing. What makes sense to me is that more researchers, etc., have recently become interested in therapeutic opportunities that may work for CNS diseases after finally recognizing the amyloid removal drugs failure to deliver. Therefore, the corporate plan that Anavex had in place has changed to meet new research and development situations. For example, I was surprised by the announcement of the addition of the Rett study in Australia. Perhaps there are others interested in conducting studies of the some of the many therapeutic opportunities that we know about for AVXL 2-73 and other Anavex drugs. I am not aware of any bad news for the trials Anavex has and continues to conduct. I agree with Fireman and others that we do not know what Missling and other insiders do know. We also do not know what researchers or potential researchers know that may be collaborating with Anavex. As a result, Anavex may need more capital to move more research and development forward. Here is one sentence from one of the newly discovered publications discussed on this board that supports my supposition that "no news is good news".
"Utilization of Sig-1R agents early in AD and similar other diseases has remained an overlooked therapeutic opportunity."
The Role of Sigma-1 Receptor, an Intracellular Chaperone in Neurodegenerative Diseases
Botond Penkea, * , Lívia Fülöpa , Mária Szucsa and Ede Frecskab
http://www.eurekaselect.com/node/152746/viewhtml/
We have learned many good things about potential for Anavex's drugs? What, if anything, have we learned that is negative? No one knows for sure why Anavex may be raising more funds now, but I am willing to bet that this captial will be put to good use. And there are many opportunities to put Anavex's capital to good use now that the time has come for no longer overlooking the science that supports Anavex's drugs. Anavex is "the only game in town" for the researchers that are developing interest in the utilization of Sig-1R (and muscarinic agonists). If we are correct in surmising that interest in our drugs is increasing, it makes sense that Anavex plans are changing or evolving, which means that Anavex needs to raise more capital. Doesn't it also make more sense to raise more capital to discover the full extent of what it is we have (to understand the full potential of our drugs) before we make a partnership agreement?
How may AVXL 2-73 benefit patients with Parkinson's dementia? Perphaps some understanding of autophagy or the cellular recycling process helps to answer this question. See the six references below.
1. Regulation and Function of Autophagy during Cell Survival and Cell Death
https://cshperspectives.cshlp.org/content/4/6/a008813.full
''Autophagy is an important catabolic process that delivers cytoplasmic material to the lysosome for degradation. Autophagy promotes cell survival by elimination of damaged organelles and proteins aggregates, as well as by facilitating bioenergetic homeostasis. Although autophagy has been considered a cell survival mechanism, recent studies have shown that autophagy can promote cell death. The core mechanisms that control autophagy are conserved between yeast and humans, but animals also possess genes that regulate autophagy that are not present in yeast. These regulatory differences may be explained by the need to control autophagy in a cell context-specific manner in multicellular animals, such as during cell survival and cell death. Autophagy was thought to be a bulk cytoplasmic degradation mechanism, but recent studies have shown that specific cargo is recruited for degradation. This suggests the possibility that either cell survival or death may be regulated by selective autophagic clearance of cytoplasmic material. Here we summarize the mechanisms that regulate autophagy and how they may contribute to cell survival and death.
....Autophagy is involved in maintaining cellular homeostasis......
The complex roles of autophagy in survival and death should also be considered when designing therapies for other disorders. Autophagy promotes the clearance of protein aggregates (Hara et al. 2006; Komatsu et al. 2006) and has an important neuroprotective role in several neurodegenerative disease models, including Alzheimer's and Huntington's (Menzies et al. 2011). In addition, recent evidence suggests that mitochondrial autophagy plays an important role in the pathogenesis of Parkinson's disease (Nixon and Yang 2012). Although the promotion of autophagy in neurodegenerative disease models results in healthier individuals, it is also possible that too much autophagy could have deleterious effects, including problems with bioenergetics or even worse killing the cells while trying to protect them. Future work should not only consider how autophagy may promote cell survival or death, but what the impact of modulating autophagy may have on the health of the test subject and patient......''
2. Anavex Life Sciences Reports Publication of New Data that Show ANAVEX®2-73 Induces Cellular Recycling Process Linked to the Prevention and Treatment of Age-Associated Diseases
https://www.globenewswire.com/news-release/2019/03/04/1745838/0/en/Anavex-Life-Sciences-Reports-Publication-of-New-Data-that-Show-ANAVEX-2-73-Induces-Cellular-Recycling-Process-Linked-to-the-Prevention-and-Treatment-of-Age-Associated-Diseases.html
'..... activation of Sig-1R with ANAVEX®2-73 leads to the prominent induction of the autophagy “cellular recycling” process and enhanced protein clearance in cells. The study, led by Christian Behl et. al. of the University Medical Center at Johannes Gutenberg University, in Mainz, Germany, has been published in the peer-reviewed journal, Cells (link).
There is a great amount of data linking dysfunction and malfunction of autophagy to neurodegenerative disease and, consistent with its role in proteostasis, to the accumulation of protein aggregates. Thus, the modulation of autophagy has become one key pharmacological target in neurodegeneration,” the researchers reported. “In fact, there are multiple overlaps of autophagy and pathogenesis pathways in Alzheimer’s disease, Parkinson’s disease, and ALS. Recently different alternative views and new pharmacological targets towards Alzheimer’s prevention and treatment are evolving and include a strong focus on the autophagy process.”
The Cells paper also noted that this is the ?rst report to show that Sig-1R activation enhances the autophagic ?ux in human cells and in C. elegans with positive effects on proteostasis in vitro and in vivo, an important concept towards the stabilization of neuronal survival and function that may help to prevent age-associated neurodegeneration.
The paper entitled, “Sigma-1 Receptor Activation Induces Autophagy and Increases Proteostasis Capacity In Vitro and In Vivo,” can be found online on the Cells website.'
3. Role of Autophagy in Parkinson's Disease.
https://www.ncbi.nlm.nih.gov/pubmed/29484979
"Autophagy is an essential catabolic mechanism that delivers misfolded proteins and damaged organelles to the lysosome for degradation. Autophagy pathways include macroautophagy, chaperone-mediated autophagy and microautophagy, each involving different mechanisms of substrate delivery to lysosome. Defects of these pathways and the resulting accumulation of protein aggregates represent a common pathobiological feature of neurodegenerative disorders such as Alzheimer, Parkinson and Huntington disease.
....pharmacological targets and therapeutic strategies that, by boosting autophagy, may be theoretically beneficial for PD.''
4. About Parkinson's disease dementia
https://www.arthritisusa.net/Neuro-Degenerative-Diseases
''The brain changes caused by Parkinson's disease begin in a region that plays a key role in movement. As Parkinson's brain changes gradually spread, they often begin to affect mental functions, including memory and the ability to pay attention, make sound judgments and plan the steps needed to complete a task.
The key brain changes linked to Parkinson's disease and Parkinson's disease dementia are abnormal microscopic deposits composed chiefly of alpha-synuclein, a protein that's found widely in the brain but whose normal function isn't yet known. The deposits are called "Lewy bodies".
Lewy bodies are also found in several other brain disorders, including dementia with Lewy bodies (DLB). Evidence suggests that dementia with Lewy bodies, Parkinson's disease and Parkinson's disease dementia may be linked to the same underlying abnormalities in brain processing of alpha-synuclein.
Another complicating factor is that many people with both dementia with Lewy bodies and Parkinson's disease dementia also have plaques and tangles — hallmark brain changes linked to Alzheimer's disease.''
5. Phase 2 Study of Potential Oral Therapy for Parkinson’s Dementia, Anavex 2-73, Planned
https://parkinsonsnewstoday.com/2018/04/20/anavex-planning-phase-2-trial-of-potential-parkinsons-dementia-oral-therapy/
'According to the Parkinson’s Foundation, around 50 to 80 percent of Parkinson’s patients will develop disease-related dementia. Parkinson’s is characterized by the loss of neurons in a crucial brain area that controls movement, the substantia nigra. This loss, in turn, lowers brain levels of dopamine, a key player in nerve cell or neuronal communication.
With disease progression, these changes spread to other areas of a patient’s brain, affecting memory, attention, and thinking and reasoning.
“As many as 80 percent of people with Parkinson’s will experience Parkinson’s disease dementia and treatment options are limited,” Christopher Missling, president and CEO at Anavex, said in a press release.
Results of preclinical work, fully funded by the The Michael J. Fox Foundation for Parkinson’s Research, show that treatment with Anavex 2-73 was able to restore function to damaged nerve cells in mouse models of Parkinson’s disease. Data also demonstrated that it targets misfolded proteins and poorly working mitochondria — a cell’s energy source — to prevent oxidative stress, inflammation, and cellular stress.'
6. New way to stimulate cellular recycling process
https://www.sciencedaily.com/releases/2018/05/180515162807.htm
"Brown University researchers studying the biology of aging have demonstrated a new strategy for stimulating autophagy, the process by which cells rebuild themselves by recycling their own worn-out parts."
Comment: AVXL 2-73 may be a drug that treats aging in general as well as various diseases that are associated with aging. The FDA does not recognize aging as a disease, but if this drug ever gains approval for any use, it will be demanded by aging patients (baby boomers) and prescribed off label by physcians.
Yes. During this Memorial Day weekend, I remember my friends that perished in Vietnam in the late 1960s. It is the least I can do. I am here, and they are not. Since Vietnam, I have witnessed many developments that they have missed, and it is because of the past sacrifices of those, like my friends, that we continue to advance in a free and open society based on the rule of law.
I am thankful to be here and witness progress as we move forward. I believe we are on the cusp of a transformation that, in the next 5 to 10 years, will dramatically improve the quality and extension of lives for those of us that are fortunate enough to be on this earth. Anavex will be a small but for us a significant part of this metamorphosis.
I believe we are in stage 1 Anavex share price consolidation phase commencing around March 26 that will eventually result in a move that punches through the $4.00 mark. The share price may move lower in the short term. We are in between news about our three clinical trials. However, we have had some meaningful buying from March 26 to date, and that is because we are attacking more attention based on the progress that Anavex has made.
Anavex has made smart moves in conducting its clinical trials in Australia and Spain. Enrollment for the phase 2 study for the treatment of Parkinson’s disease dementia is now 70% of target. Topline results are expected before the end of the year. Patient enrollment for the phase 2 study to treat Rett syndrome is at 40%. We will be receiving news from the Rett trial this year as well.
Anavex will also be launching the AVATAR (Rett) study in Australia where approximately 30 patients will be enrolled in a phase 2 double-blind, randomized, placebo-controlled study of ANAVEX2-73 for the treatment of Rett syndrome. The Australian government will pay around 40% of the cost of the AVATAR trial.
Enrollment for the phase 2b/3 study to treat Alzheimer’s disease has reached 20%. I know some are disappointed that the Alzheimer's trial is lagging behind the Parkinson's and Rett trials, but I believe that what we learn and gain from the Parkinson's and Rett trials will be beneficial and helpful for the advancement and eventual success of our Alzheimer's drug.
Our science is sound. Our animal and human studies have been positive, Anavex is not a one trick pony, and we have multiple chances of success. We have cash on hand for the time being and the means to raise more cash. However, we may not have to raise additional cash if we obtain results from the Parkinson's and/or Rett trials that may culminate in a partnership arrangement, which we need to help with efforts to obtain approval and marketing of AVXL 2-73 for Alzheimer's. Bio says the odds of regulatory approval for AVXL 2-73 is very high (near 90%), and I believe him.
Lastly, we all need to have faith and courage like Billy.
What about the cup formation that I see on your chart from about March 26 through yesterday, May 21?
Bio, superb! As someone highly respected might say: “We got this.”Thank you.
Yes, screening and selecting the patients for the AD trial is critical. However, over 20% of the 450 patients — around 100 patients — have been enrolled. Remember too that the PDD trial is a dementia trial. 70% enrollment in the PDD trial is achieved. If we receive positive news from the PDD trial, we should be attracting partners for Alzheimer’s and Parkinson's.
If we receive negative dementia results in the PDD trial, that will be a set back indeed, but I suppose it is possible that Anavex may still redeem itself with the larger number and more carefully selected patients in the AD trial.
You maybe correct. The PDD Australia announcement I read said this:
“Parkinson’s disease patients aged 50 years or older who have been diagnosed with dementia will be recruited for the trial which is also being conducted in other international sites and has received the support of the Michael J Fox Foundation for Parkinson’s Research and León Research.”
https://www.hammond.com.au/about/news/melbourne-trial-of-new-drug-to-treat-parkinson-s-dementia
Yes, absolutely. I agree. I think that is in the interest of both countries.
The Spanish healthcare system is one of the best in the world.
https://www.expatica.com/new/es/healthcare/general-healthcare/healthcare-system-101467/
Spain has national healthcare and is interested in continuing to deliver excellent healthcare and avoid high cost in treating its citizens. Australia's health system is also one of the best in the world. It provides quality, safe and affordable health care its citizens.
https://beta.health.gov.au/about-us/the-australian-health-system
Spain encourages transparency in clinical trials and Australia has announced an initiative to prevent and treat dementia in its country.
Life expectancy in Spain ranks number 3 in the world
http://www.worldlifeexpectancy.com/spain-life-expectancy
The Spanish have highest healthy life expectancy in Europe
https://www.theguardian.com/world/2013/mar/05/spanish-highest-life-expectancy-europe
Australia is an ideal country for Alzheimer’s and other dementia clinical trials because it offers more support for the trials, including funds for our trials. It has also launched the world-first dementia network to fast-track treatment and research.
https://www.9news.com.au/national/2018/07/02/20/06/australian-dementia-network-launched-to-track-diagnosis-and-care-of-patients
PDD/AD trials in Australia/Spain. Members of the European Union share in the exchange of information about clinical trials through mutual recognition agreements, and Australia also is involved in the exchange of scientific information with members of the European Union. It makes sense that Australia and Spain would share in the exchange of information about clinical trials and developments that occur within the European Union and Australia. Why not? After all, it is in the best interest of Spain and Australia, assuming those countries are sincere about curing their citizens diagnosed with these dreaded diseases, PDD and AD. See this about mutual recognition agreements regarding EU members and Australia.
Mutual recognition agreements (MRA)
https://www.ema.europa.eu/en/human-regulatory/research-development/compliance/good-manufacturing-practice/mutual-recognition-agreements-mra
Clinical trials in human medicines
https://www.ema.europa.eu/en/human-regulatory/research-development/clinical-trials-human-medicines
“Clinical trials in human medicines Share
The European Medicines Agency relies on the results of clinical trials carried out by pharmaceutical companies to reach its opinions on the authorisation of medicines. Although the of clinical trials occurs at Member State level, the Agency plays a key role in ensuring that the standards of good clinical practice (GCP) are applied across the European Economic Area (EEA) in cooperation with the Member States. It also manages a database of clinical trials carried out in the European Union.
Clinical trials are studies that are intended to discover or verify the effects of one or more investigational medicines. The regulation of clinical trials aims to ensure that the rights, safety and well-being of trial subjects are protected and the results of clinical trials are credible.
Regardless of where they are conducted, all clinical trials included in applications for marketing authorisation for human medicines in the European Economic Area must have been carried out in accordance with the requirements set out in Annex 1 of Directive 2001/83/EC. This means that:
clinical trials conducted in the EEA have to comply with European Union (EU) clinical-trial legislation (Directive 2001/20/EC);
clinical trials conducted outside the EEA have to comply with ethical principles equivalent to those set out in the EEA, including adhering to international good clinical practice and the Declaration of Helsinki.
In the EEA, approximately 4,000 clinical trials are authorised each year. This equals approximately 8,000 clinical-trial applications, with each trial involving two Member States on average. Approximately 61% of clinical trials are sponsored by the pharmaceutical industry and 39% by non-commercial sponsors, mainly academia.’’
https://www.ema.europa.eu/en/partners-networks/international-activities/bilateral-interactions-non-eu-regulators/australia
“Australia
The European Medicines Agency and the European Commission have had confidentiality arrangements with the Therapeutic Goods Administration (TGA) of the Australian Government Department of Heath and Ageing since 2012, to allow the exchange of information between the parties as part of their regulatory and scientific processes. The European Union (EU) and Australia also have a mutual recognition agreement (MRA) in place on good manufacturing practice (GMP) compliance.’’
Share price resilience.
I have not been able to post messages on this board in recent months. However, I would like to say that everyone on this board is privileged, myself included, by sharing in beneficial information posted by many sincere and informed posters. Even though I have been absent from posting, I have continued to follow most of the messages.
Recently, there have been several developments that are particularly encouraging in confirming that Anavex is pursuing what we have believed for years to be the most promising approach to treat CNS diseases that otherwise have no effective treatment. It is significant that doctors and patients have requested trial extensions, most of the Alzheimer’s trial patients are still on the drug, Anavex has meaningfully increased the inventory of its drug (suggests commercialization of its product), has added a CMC regulatory compliance person (suggests gearing up for an approval), Missling likes the idea of accelerated approval of PDD (Biostockclub, I believe, predicted that the PDD trail may lead to accelerated approval overseas), and that Anavex has the support of organizations, foundations and governments (Australia/Spain) vested and interested in seeking cures or treatments that work rather than preserving the status quo.
Anavex 2-73 will be the subject of a major publication. This came from the horse's mouth. If true, it will add credibility and fuel publicity about Anavex, which heretofore has been lacking.
Today's news, that the preferred offering has been approved is more good news that insures that our company will be around to continue its efforts. Anavex has demonstrated courage, determination and persistence in making progress that will soon force the drug industry and regulators to take notice. And the company is now in a position that it must be dealt with rather than ignored like a flea on an elephant that may be swatted into oblivion at the flick of big pharma’s tail – the passing of the preferred proposal helps send that message.
All promising news - keep up the good work. Continue to spread the word. Help for CNS disease is on the way. Anavex is coming!
If you want to make real money investing, you will have to do it by picking stocks in disruptive technology and biotechnology with emphasis on the latter. You cannot make a great deal of money doing what everyone else is doing, and investing in companies that are doing what every other company is doing.
However, people are uncomfortable with anything that is new and they are resistant to change. Most people do not like change of any sort.
Most great investments begin in discomfort. The things most people feel good about – investments where the underlying premise is widely accepted are unlikely to be available at bargain prices. Rather, bargains are usually found among things that are controversial, that people are pessimistic about, and that maybe have performed badly for a long while (look at the long term chart for AVXL - AVXL's stock performed badly for a long time). Buying AVXL stock has at times been uncomfortable. Sometimes it is uncomfortable owing AVXL stock. It is NEVER easy to do things that entail discomfort, but being uncomfortable comes with the territory when investing in new ideas.
The above said, you must devote large amounts of time and work in attempting to select investments that are fundamentally sound and have a good possibility of success. You must take risks, but you must take what I refer to as the right risks.
This was my approach when I begin owing AVXL some four years ago. I also own a number of other investments - “right risks” to spread the risk. I may lose on a few and still make a great deal of money. However, OFP's approach is indeed a rational and prudent approach.
I think Lima described CM as upbeat, confident, which would likely not be the case if the drug was failing or if the doctors were attempting to drain money from Anavex. Additionally, CM made other positive statements, which are inconsistent with drug failure/doctor shenanigans.