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Good post. Yes, we have seen announcements that confirm that Blarcamesine does show improvement “day by day” and that stopping administration of Blarcamesine patients worsen only to begin improving again when treatment with Blarcamesine resumes.
We do have information that Missling says proves that continual dosing of Blarcamesine is important to response and that by halting intervention, patients worsen but can reverse for the better again by resuming treatment with Blarcamesine. So, it will be interesting to see if Anavex continues collecting data on patients in OLE and/or for compassionate use. It seems that Anavex is doing that. Some patients have been taking Blarcamesine for over two years. See below.
1. This is from Mayo's SOTC website. SOTC Update 5: 26 June 2023
Presentation at the H.C. Wainwright 4th Annual Neuropsychiatry Virtual Conference
- 11:15 min: Alzheimer's vs. Parkinson's
- - S1R does not discriminate based on pathology (initial cause of the disease). In Parkinson's genes, we found active arm (dosed patient) genes were up-regulated again. Functionality was improved on a molecular level. In the OLE, we proved that continual dosing is important to response and that by halting intervention, patients worsen but can reverse for the better again by resuming treatment -- beyond simple endpoint measures, this was also true at the gene level [new information]. We are now about to conduct the imaging (target engagement) study and Parkinson's disease pivotal trial which are both still being funded by MJFF.
2. Further, see ANAVEX®2-73 (Blarcamesine) Shows Clinical Benefit in Long-Term 48Week Phase 2 Extension Study in PDD - https://www.anavex.com/post/anavex-2-73-blarcamesine-shows-clinical-benefit-in-long-term-48week-phase-2-extension-study-in-pdd
Due to the COVID-19 pandemic, the start of the extension phase was delayed, on average, by approximately 41 weeks at the end of the preceding double-blind placebo-controlled study (DB). This led to a reduced enrollment rate for the extension phase. The period between the end of the double-blind phase to the start of the extension phase, where patients were not on ANAVEX®2-73 treatment, is known as a 'drug holiday'. The drug holiday period of treatment separation provided an opportunity to compare the trajectory of clinical scores between no ANAVEX®2-73 treatment (drug holiday) and ANAVEX®2-73 treatment in the extension phase.
All efficacy endpoints, which includes the MDS-UPDRS Part II + III and Clinical Global Impression -- Improvement (CGI-I) measured at the end of trial of the double-blind study (DB EOT), the OLE Baseline, OLE Week 24, and OLE Week 48, showed a worsening during the drug holiday. However, a consistent improvement was observed during the extension phase when patients resumed ANAVEX®2-73 treatment. These results are consistent with the pattern observed for all efficacy measures in the extension phase (see Chart and Table).[[6]](https://manage.wix.com/dashboard/e1cd7807-443e-425e-9433-41548681800c/blog/cb39a577-fa42-405a-a247-31bbefc78067/edit#_ftn3)
.....
"It is encouraging that the patients' clinical symptoms consistently improved longitudinally over time during the extension phase under active ANAVEX®2-73 treatment," said Christopher U Missling, PhD, President & CEO of Anavex. "This data suggests ANAVEX®2-73's potential capability to slow and potentially reverse the life altering symptoms of Parkinson's disease, an urgent unmet global need."
Moreover, at the request of the participants completing the 48-week open-label extension study, patient requested treatment with ANAVEX®2-73 is continuing beyond the open-label 48-weeks through the compassionate use Special Access Scheme. Currently, participants in the compassionate use program for ANAVEX®2-73 have been on average, for over 2 years and counting.
Yes, under the old outdated method of pharmaceutical companies hiring drug detail representatives and employees to market drugs, the information flow about new drugs was limited to representatives traveling to doctors offices and promoting big pharma drugs. Small companies could not afford to do this and do it effectively, but this new and innovative Partex approach changed all of that and can more efficiently and quickly disseminate information to more sources, including patients, care givers, advocacy groups, doctors, etc.
From AI chat:
“Partex NV has always been committed to innovation and making a positive impact on the industries it operates in. While Partex NV may not directly inform patients and caregivers about new innovative drugs, it can play a crucial role in facilitating the dissemination of information through its AI-powered drug asset management system.
Partex NV's AI platform can analyze vast amounts of data from clinical trials, research papers, and drug databases to identify potential breakthroughs and innovative drugs that are undergoing clinical trials or have recently entered the market. By leveraging machine learning algorithms and data analytics, Partex NV can rapidly identify emerging trends and advancements in drug development.
Once Partex NV's AI platform detects new drugs, the company can share this information with medical professionals, patient advocacy groups, and healthcare providers. By collaborating with these stakeholders, Partex NV can actively contribute to the flow of information to patients and caregivers, ensuring that they are informed about the availability of these innovative drugs.
To facilitate this knowledge transfer, Partex NV's AI system can generate reports, summaries, and insights on the latest drugs in clinical trials or on the market. These reports can provide details on efficacy, safety profiles, potential side effects, and access information for specific diseases. Partex NV can also work with healthcare providers and advocacy groups to host educational events, webinars, or conferences to disseminate information and enable dialogue between medical professionals, patients, and caregivers.
Furthermore, Partex NV can collaborate with pharmaceutical companies to support the development of patient-focused materials that explain the benefits, risks, and potential outcomes of new drugs. These materials may include patient information leaflets, brochures, websites, or digital applications that provide easy-to-understand information about the drugs and how they can be accessed.
Partex NV can also contribute to the development of online platforms or databases that aggregate information about innovative drugs, clinical trials, and ongoing research. These platforms can serve as comprehensive resources for patients and caregivers, empowering them to stay updated on emerging treatments and engage in informed discussions with their healthcare providers.
It is important to note that while Partex NV can support the dissemination of information, the responsibility lies with healthcare providers, patient advocacy groups, and medical professionals to communicate this information to patients and caregivers effectively. These entities play a critical role in empowering patients and caregivers, guiding them through treatment options, and ensuring that they have access to the necessary resources.
In conclusion, while Partex NV does not directly inform patients and caregivers about new innovative drugs, its AI-powered drug asset management system can contribute immensely to facilitating the flow of information. By analyzing data, generating reports, collaborating with stakeholders, and supporting the development of patient-focused materials, Partex NV aids in informing patients and caregivers about new drugs in clinical trials and on the market. Ultimately, the collaboration between Partex NV, healthcare providers, patient advocacy groups, and medical professionals can empower patients and caregivers, enabling them to make informed decisions and access new innovative treatments for better healthcare outcomes.”
Note: This Partex - Anavex partnership changes all of that and allows Anavex to market its drug platform without the traditional, old, expensive, and cumbersome drug marketing department system.
Partex website:
https://www.partex.io/
Kentucky: TD sequential on the daily chart reached a 9 perfection on Friday indicating selling exhaustion on this latest AVXL down move. Furthermore, this down move may have completed a wave 2 correction from a wave 1 high reached in May. If the share price has bottomed or is bottoming, we should see a substantial wave 3 move up. However, I have to admit that I get nervous every time Missling speaks. Unless he or the company presents new promising, believable data, the share price will likely continue to drop as it so often has each time Missling speaks.
Joseph:
Cost of a drug is not a factor in re FDA approval. However, it is a factor in the EU, Japan and Australia, which I think advances Blarcamesine’s chances of approval in those areas of the world. This ,cost, is one of several reasons why I believe Anavex should focus on early approval overseas, as I said in a post yesterday.
The U.S. - FDA is biased towards big pharma. I say this based on published research and personal experience. That may be a reason why the FDA is not concerned with costs.
In any event, Anavex, I believe has better odds of approval in Australia, the EU and Japan (assuming Anavex finds a suitable partner in Japan).
Here are a few citations to support what I say:
1. Affordability of medicines in the European Union
Abstract
Background
Medications and their prices are key issues for healthcare. Although access to medicines at affordable prices had been specified as a key objective of the European Health Policy, it seems that these goals have not been achieved. Therefore, we attempted an evaluation of affordability of selected medicines at full prices.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5328386/
2. Pharmaceutical Sales in Japan:
Balancing Innovation and Cost Control
https://ashpublications.org/ashclinicalnews/news/6030/Pharmaceutical-Sales-in-Japan-Balancing-Innovation?searchresult=1
3. The Pharmaceutical Benefits Scheme (PBS) **lets Australians use lots of prescribed medicines without paying full price**. The PBS is part of the Australian Government's National Medicines Policy. The National Medicines Policy aims to balance the need for medicines with good health results and economic limits.
[Pharmaceutical Benefits Scheme (PBS) - Healthdirect](https://www.healthdirect.gov.au/pharmaceutical-benefits-scheme-pbs#:~:text=The%20Pharmaceutical%20Benefits%20Scheme%20(PBS,health%20results%20and%20economic%20limits.)
4. New research suggests biases play a role in FDA drug approval
Innovative drugs are sometimes held up due to old-fashioned human biases.
.....
KEY TAKEAWAYS
- When new drugs are similar to popular drugs on the market, FDA approval takes up to 75 percent longer.
Agreed, Investor is correct, and this is an excellent strategy chosen by Anavex and explained by investor. This is what Missling was trying to convey in the last CC, although not so artfully. Here is some of what he said to not so artfully convey the strategy:
"...The next question is, will the AD NDA be submitted before the confirmatory trial is completed? The answer is after discussion with the agency for Accelerated Approval Pathway, this would be the path which was also given to the other accelerated approval company approvals (my insert: Lecanemab for example). So this could be the case as well. Otherwise, it would be not accelerated approval if you need a study to begin with. So that is the goal of getting the drug approved before completing a confirmatory second trial....
.....Again, a confirmatory study is needed after accelerated approval. And so that is regarding the additional study, but it's not required for accelerated approval for approval of the drug for the Alzheimer's study....."
https://www.insidermonkey.com/blog/anavex-life-sciences-corp-nasdaqavxl-q2-2023-earnings-call-transcript-1149124/
I am bullish Anavex, and I am pleased with this strategy Anavex is pursuing. It is a very wise strategy. I think some posters here are thinking that if you label the “confirmatory trial a Phase 3, Anavex is precluded from obtaining AA, which is simply not the case. So, relax and enjoy the rest of your weekend. One of these days, we will know all we need to know, but I would never bet on when that may be. Keep your expectations low on when that day will come, and you will lower your stress level (your cortisol level will drop precipitously!).
Thanks
If it were me, I would put forth a push to seek approval in Australia, the EU and Japan (after landing a partnership in Japan) first and foremost because of a bias in favor of big pharma in the US and due to surrogate biomarker issues. If approval overseas is a big hit, the US will fall in line.
Fast Track Approval Pathways in Australia. Here is an internet search and AIChat inquiry about early approval of a drug in Australia. It may be Anavex has its best chance for approval of Anavex 2-73 in Australia. Also, according to AIChat, no surrogate biomarker is necessary for early approval in Australia. See this:
# Fast track approval pathways
Last updated
16 March 2023
Before a new prescription medicine can be available for use in Australia, the TGA assesses it for safety, quality and efficacy.
There are three pathways the TGA can use to assess a prescription medicine: the standard pathway, the priority review pathway and the provisional approval pathway.
Priority review and provisional approval are pathways that fast track prescription medicines onto the market, making them available to patients sooner than they would be under the standard pathway.
Typically, a pharmaceutical company needs many years to collect evidence that confirms the safety, quality and efficacy of a medicine by running clinical trials and doing other research. It could also take up to eleven months for us to review this evidence through the standard pathway depending on the complexity of the medicine. In the meantime, some patients with serious, life-threatening conditions could need urgent access to the medicine, but not be able to access the medicine until it is approved.
For this reason, medicines for serious or life-threatening conditions are sometimes eligible to undergo a fast track process to make the medicine available to patients sooner than normal. The sponsor must apply and the medicine must meet criteria to use a fast track pathway. For example, the medicine must be a major advance over any similar medicines that are already approved for supply.
Fast track pathways can be used for both new medicines and new uses for already approved medicines.
Some medicines that have already been approved through a fast track pathway treat conditions like prostate cancer, skin cancer, and haemophilia.
On this page: [Priority review](https://www.tga.gov.au/fast-track-approval-pathways#priority) | [Provisional approval](https://www.tga.gov.au/fast-track-approval-pathways#provisional) | [It is important to report side effects](https://www.tga.gov.au/fast-track-approval-pathways#report) | [Other important information](https://www.tga.gov.au/fast-track-approval-pathways#other) | [Medicines subsidies through the PBS](https://www.tga.gov.au/fast-track-approval-pathways#pbs)
## Priority review
Under priority review we aim to finish our review of a medicine up to three months earlier.
We can complete these reviews faster because the approval process is more flexible. For example, under priority review we ask the pharmaceutical company questions about their application as they arise, rather than sending the questions as a group after we finish a round of assessment.
Priority review involves the same amount and type of evidence as the standard review process, and so has no impact on the level of safety, quality or efficacy of the medicine. Unlike provisional medicines, a medicine approved under priority review will receive ongoing approval, identical to approval under the standard pathway.
The flexible approach we take on priority applications is much more resource intensive than the standard pathway. This is not a feasible option for all medicines, so the pathway is reserved only for medicines that treat serious and life-threatening conditions.
## Provisional approval
We can give provisional approval to medicines which provide a promising treatment for a serious or life threatening condition. This makes the medicine available for a limited period while the pharmaceutical company completes final clinical trials.
Under the standard pathway, a medicine is not available until after all clinical trials have been completed, so this can make a medicine available up to two years earlier than normal.
In order to do this, the sponsor must apply and we must be satisfied that the benefit of earlier access for patients is greater than the risk of not yet having all of the supporting evidence that we usually require.
For further information, please refer to the [Provisional approval pathway: prescription medicines](https://www.tga.gov.au/provisional-approval-pathway-prescription-medicines) webpage.
## It is important to report side effects
While all medicines may have side effects, it is particularly important that you report to your doctor any issues you experience with a provisionally approved medicine.
Any issues should also be reported to us so we can build up the full picture of a new medicine's safety profile. You can ask your doctor to do that on your behalf.
One of the best ways to report is over the phone to an NPS Medicinewise pharmacist on [1300 134 237](tel:1300 134 237) as they can ask questions to get the best information and provide advice on how to manage the side effect. You can also [report any issues](https://www.tga.gov.au/node/287456) directly to the TGA.
## Other important information
Your doctor will give you information about medicines they prescribe, including if the medicine is provisionally approved. However, for more information you can also check the [Consumer Medicines Information (CMI)](https://www.tga.gov.au/node/287207).
When looking at the CMI for provisional or priority medicines, you may notice a [black triangle symbol](https://www.tga.gov.au/node/287699) (). This symbol is a reminder to report side effects. The black triangle does not mean that there are known problems with the medicine, only that the medicine is new, or being used in a new way, and the TGA is seeking as much information as possible to get the full picture of its safety profile.
If you have concerns about any medicine you are taking, always consult your doctor.
## Medicines subsidies through the PBS
Subsidies are determined and administered by a different section of the Department. For information on which medicines are subsidised by the Australian Government, consult the [Pharmaceutical Benefits Scheme website- external site](http://www.pbs.gov.au/pbs/home;jsessionid=1939lc3p78hu1lbb47c3u9zdy).
https://www.tga.gov.au/fast-track-approval-pathways
I asked AIChat if a surrogate biomarker was required for early approval of a drug in Australia. This is the response I received from AIChat:
No, the use of surrogate biomarkers is not specifically required for fast track approval of drugs in Australia. Australia does not have a formal Fast Track program similar to the FDA's Accelerated Approval Program in the United States. However, there are several routes available in Australia for expedited approvals of innovative drugs that target serious or life-threatening conditions.
In Australia, the provisional approval pathway is the closest analogue to the accelerated or conditional approval pathways in other jurisdictions. The TGA, which is responsible for drug approvals in Australia, grants provisional approval to drugs that demonstrate promise in treating serious or life-threatening medical conditions where no or only limited treatment options exist.
To qualify for provisional approval, the drug must show promise over the defined target indication, and its net clinical benefit profile is expected to outweigh its potential significant risks. Like other regulatory frameworks conditional approval, the provisional approval captures data before confirming sufficient confirmatory data comes forward through post-marketing clinical trials requested of the approval gain. This allows reinforced assessment of the drug performance against that observed with the surrogate endpoint and against placebo or established standards of care with adequate statistical analysis.
However, even without a formal Fast Track pathway, it is possible for companies to request an accelerated review or expedited assessment by the TGA. The TGA can grant these requests if they are satisfied that the drug meets the requirements for priority assessment and has the potential to provide high clinical benefits to a high need patient population for life threatening or serious diseases when treatment options cannot address the necessary clinical need.
While surrogate markers can offer a useful surrogate of depending on the context of benefit surrogates within the intended population, their use is subject to assessment against the common consensus of proofs established and practical outcomes in individual cases. Their deployment can depend on the clinical target endpoints, intended population, and other factors at the time of their use in clinical trials on which their value as a surrogate is dependent until confirmed.
Precisely, the FDA simply wants confirmation and has been concerned about companies dragging their feet on conducting confirmatory trials after accelerated approval is granted. I believe that Anavex’s parallel trial in progress increases chances of AA. Labels don't matter. However, it matters greatly that a confirmatory trial is in progress.
Investor is correct. With FDA accelerated approval, the confirmatory trial may be a phase 3 or phase 4 trial. Accelerated approval is a regulatory pathway that allows for the approval of a drug based on preliminary or surrogate endpoints, with the requirement that the drug undergo further study to confirm its clinical benefit. This follow-up study can be a phase 3 or phase 4 trial, depending on the specific circumstances of the drug and the condition it is intended to treat.
Also, “FDA strongly recommends that the confirmatory trial(s) be well underway if not fully enrolled at the time of accelerated approval. These completion deadlines are based on unique considerations related to the indication and confirmatory trial design. Confirmatory trials that are in progress at the time of accelerated approval are more likely to result in a timely verification of benefit. ‘’
https://www.fda.gov/about-fda/oncology-center-excellence/project-confirm
Sent from my iPhone
Thank you, Hoskuld. My post reflects frustration, which is one of the first steps to capitulation and failure. Your posts are encouraging. I complain, but I will not throw in the towel.
Thank you. Good post, and I like your attitude. I hope to share that attitude as well and remain long AVXL!
Yes, I agree. I too want early approval and a phase 4 trial. However, to say that a phase 4 trial is what is meant by “confirmatory” is incorrect. Both phase 3 and phase 4 are confirmatory trials.
See: Making a medicine. Step 8: Confirmatory studies
Phase III clinical studies, or confirmatory studies, are the final confirmation of the safety and efficacy of a medicine before it can be launched on the market. Phase III studies are the largest, most complicated, and most expensive part of the medicines development process, and nearly 50% of medicines that enter this phase will fail.
https://toolbox.eupati.eu/glossary/confirmatory-studies/
Unfortunately, for now, we continue with more mystery and intrigue. Note: I am long AVXL. However, I am disappointed with the continuation of muddled reports. I hope we will get to the bottom of the mystery and intrigue, but I have no “expectation” about when that will be.
Lastly, I feel the constant “expect” this and that posts are unhelpful, monotonous, and damaging. Repeatedly raising expectations have led to multiple disappointments for many. I do not think that the intentions behind the “expect” posts are bad, but let’s stop paving the road to disappointment with these frequent and failed posts, which discourage shareholders and do not advance the company or its share price.
Well said, Nidan. Understand.
I certainly hope your prediction turns out to be correct. I have been following Anavex since 2015, when I initially purchased shares. Although I have made a great deal of money from my Anavex investments, I have been disappointed because I thought that the drug would be available before now. My expectations have failed. Rather than make a lot of money that I can make do without at my age, I would rather see the drug available as I have hoped for before now. One difficulty with clinical trial results is that by the time Alzheimer’s is diagnosed, too much damage has been done. I would like to see the drug available to treat patients earlier like statin drugs do. I have had a good life, but I miss my friends and family that may have benefited from this drug but are no longer around. Therefore, I refrain from getting my hopes too high because I don’t want to be disappointed again and again.
Perhaps this (below) may be a basis for performing calculations to estimate “super” or “exceptional performers”. Based on this, it may be that 80% of treated patients (those with the wild type gene) that actually completed the phase 2b/3 Anavex AD trial likely received some benefit from AVXL 2-73, but those with an exceptional response is apparently much lower than the 80% number of fully treated patients.
Based on this (referenced below) … out of the 21 patients for which whole exome and transcriptome sequences were obtained, two patients showed exceptional therapeutic response during the longitudinal study (148-week period) - rounded to 10% of the 21 had exceptional response. This is the analysis of the phase 2a AVXL 2-73 clinical trial and may be the best we can find for a basis for calculating super responders. This article points out that 2 out of the 21 had an exceptional response - 10% (rounded).
Of course, some other patients within the 80% number of treated patients in the most recent AVXL AD trial likely benefited to some extent - some clinically meaningful, but the 76 number for super responders is likely a wild guess.
See this: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167374/
Thank you.
AVXL likely bottomed for a good move up. Looking for confirmation-SP to break $8.50 and follow through.
Investor, thank you for wading through the patent. Most interesting examples. Intermittent dosing and periods involved (6months in example 1) raise intriguing questions such as whether the SR1/muscarinic agonist Blarcamesine does in fact result in restoring the body to function in a state of homeostasis - to seek and maintain a condition of equilibrium or stability compared to its dysfunctional state brought about by aging and associated health problems?
We have a lot to learn. Hopefully, we will begin to receive more information and data.
Sab: Try this for knee pain. https://signalrelief.com/collections/main-site-collection
Actually, it may be that the synergistic effect of the two drugs may increase sales of lecanemab.
Steady is correct about the WT gene. I add this.
The FDA is inclined to grant accelerated approval of Alzheimer’s drugs. The FDA approved aducanumab because it found that the drug was reasonably likely to lead to a reduction in clinical decline of AD. It approved lecanemab because if found it is likely to slightly or moderately target and affect the underlying disease process of Alzheimer’s (slow decline), instead of only treating the symptoms of the disease.
Previous AVXL clinical trials have produced evidence that 8O% of the population that possess the SR1 WT gene are more likely to benefit from AVXL 2-73. If the latter is confirmed again with the phase 2b/3 trial data and that Anavex’s drug leads to a reduction in clinical decline, accelerated approval is likely assuming the clinical trial also demonstrates a surrogate biomarker(s) acceptable to the FDA or other regulatory agency. Anavex indicates more than one possible surrogate biomarker to present to the FDA along with other evidence, genomic and otherwise.
Dr. Jin will draw on his extensive experience, including recently as the Statistical Team Leader at the U.S. Food and Drug Administration (FDA). Dr. Jin provided statistical review coverage and expertise for neurological drug products for the Center for Drug Evaluation and Research (CDER), to lead Anavex’s attempt for accelerated approval of AVXL 2-73 in the U.S. and in various venues such as Canada, the EU, Australia, Great Britain and Asia.
Based on all of this, It seems that Anavex has a good shot to obtain accelerated approval in some parts of the world. What does Anavex have to lose in taking that shot? I believe that the least that may happen is some regulatory agencies may say do another phase 3 trial; however, I also believe that the odds are that at least one regulatory agency will grant early approval and require a phase 4 confirmation.
Anavex’s approval apparently will not eliminate lecanemab lecanemab as a “competitor” as Missling pointed out in his latest presentation. The two drugs are synergistic and may be used together. Accelerated approval now with a confirmatory trial will provide a chance to treat AD patients with both drugs. Actually, it may be that this may increase the use of lecanemab.
Sab:
I think we do have reason to believe we may be turning up for a change. It looks like a wave 2 correction that commenced in early February (daily chart) is about done if not done. The stochastic crossover was one of the early indications. MACD has followed with a crossover as well as Joseph points out. You are correct that the daily chart needs to prove itself. If we get further confirmation of a wave 2 bottom, we may see a decent move up (wave 3). The MACD crossover is an indication wave 2 may be ending. See the daily chart where MACD crossed downward in early February and has now crossed upward as Joseph mentions. The MACD on the daily chart matches what I am thinking about the wave 2 correction from early February to date. However, we need confirmation as you say. Anything can happen. But, possibly the fundamentals (see Mayo’s SOTC analysis) are there as well to support an intermediate move up in Anavex's share price. See Mayo’s timeline. Let’s see what happens, but all of this looks interesting to me.
Lastly, although not that clear, TD sequential seems to be aligned with what’s said above. All of this may support the odds for a move up, but the only thing that is certain is uncertainty. What will be will be?
It's just another “expectation” that can lead to disappointment as has been the case since I have been a member of this board. I believe Anavex has potential, but I invest without expectations. The markets (including Anavex) will do whatever it/they do, and I just try to take advantage of wherever it/they go at any point in time. Investing based on a mere belief (expectation), especially someone else’s “expectations” gets investors in trouble.
It’s best to have a probabilistic mind-set pertaining to trading consisting of five fundamental truths.
1. Anything can happen.
2. You don’t need to know what is going to happen next (noone knows what is going to happen next) in order to make money.
3. There is a random distribution between wins and losses for any given set of variables that define an edge.
4. An edge is nothing more than an indication of a higher probability of one thing happening over another.
5. Every moment in the market is unique.
Anything can happen. So, ignore “expectations”. We should know this by now from expecting good news to drive Anavex’s price up. We get the “good news” and maybe the share price takes a dive like it has sometimes done. Expectations are useless and harmful to yourself and others.
I have made a lot of money investing in Anavex and other biotechs, but I ignore useless expectations. I have made money mostly by getting an edge and reacting to whatever happens - not on these endless “expectations”. I think constant DD and research may increase probabilities - get you an edge, but “expectations” get you nowhere except most likely disappointment and failure.
Based on past presentations of this sort, it is unrealistic to expect anything new on Monday. I say this based on being an Anavex investor since 2015, and a biotech investor for many years before that.
Thank you, Cresentmotor.
Thank you, Abe. That makes Ma’s appointment even more relevant!
Exactly, Ma’s appointment as independent Chairman of the Board is great news. This is a significant event for Anavex and its shareholders. The below excerpt is from the May 2021 appointment of Ma to Anavex’s board. She has been serving as a board member of Anavex for almost two years, which adds to her other impressive background set forth below:
Anavex Life Sciences Announces Appointment of Ms Jiong Ma, PhD to Board of Directors
Published: May 26, 2021
...Ms. Ma is Senior Board executive with over 25 years of experience in investing, building, scaling of companies with focus on innovative product launches in digital health, technology and the new energy transition. Dr. Jiong Ma serves and served as a Board Director of LinkinVax, Aledia, Voxel8, Lo3 Energy, mc10, acquired by Medidata, Storiant, Fulham, Convey Computer, acquired by Micron Technology, Powervation, acquired by RHOM Semiconductor, Laser Light Engine and Carbonite, Inc., which went public via IPO in 2011 and was subsequently acquired by OpenText in 2019 for approximately $1.45 billion.
As a Partner at Braemar Energy Ventures ($600 million AUM), Ms. Ma focused on investments in digitization of industry, resource efficiency, mobility, renewable energy infrastructure, and deeptech. She was on the firm’s investment committee and has led more than 15 investments in growth stage companies with focus on innovative product launches, as well as raising funding, negotiating and structuring investments, hiring management teams, and assembling boards.
Prior, she was with the Venture Capital Group at 3i, a global private equity firm ($17 billion AUM), where she led investments across multiple stages in Digital Health, TMT and Cleantech. Among them TransMedics Group (Nasdaq: TMDX), ImpactRx/Symphony Health Solutions, which was later acquired by PRA Health Sciences (Nasdaq:PRAH).
Preceding the Venture Capital Group at 3i, Ms. Ma held several senior positions at Lucent Technologies and Bell Labs. Her responsibilities included lead roles in product portfolio strategy, new product launches for Optical and Data Networking, and research and product development. Ms. Ma was also a founding team member of Onetta, a fiber networks company.
She has a PhD in Electrical and Computer Engineering from the University Colorado at Boulder and an MS in Electrical Engineering from Worcester Polytechnic Institute. Ms. Ma is a Kauffman Fellow.
“It’s an honor to join Anavex’s Board of Directors,” said Ms. Ma. “With the focus on neurodegeneration and neurodevelopmental diseases, Anavex is tackling one of the biggest medical challenges that our society faces today. I am impressed with the breadth of Anavex’s pipeline. I look forward to applying my insights to advance Anavex towards its next stage of growth on the way to commercial success.”
https://www.biospace.com/article/releases/anavex-life-sciences-announces-appointment-of-ms-jiong-ma-phd-to-board-of-directors/
INDEPENDENT BOARD CHAIRMAN
Glass Lewis believes that shareholders are better served when the board is led by an independent chairman who we believe is better able to oversee the executives of the Company and set a pro-shareholder agenda without the management conflicts that exists when a CEO or other executive also serves as chairman. This, in turn, leads to a more proactive and effective board of directors.
Research suggests that combining the positions of chairman and CEO may hinder a board’s ability to dismiss an ineffective CEO.
https://www.glasslewis.com/wp-content/uploads/2016/03/2016-In-Depth-Report-INDEPENDENT-BOARD-CHAIRMAN.pdf (https://www.glasslewis.com/wp-content/uploads/2016/03/2016-In-Depth-Report-INDEPENDENT-BOARD-CHAIRMAN.pdf)
That is a very interesting article about the benefits of having an independent chairman for a company's board of directors. Not only does this avoid potential conflicts of interest, but it also helps to ensure that the CEO is accountable to the board and shareholders. This can lead to more effective decision-making and a focus on creating long-term shareholder value.
Agreed. AVXL share price is likely to move higher. RSI, stochastic, on balance volume turning up, and TD sequential is looking promising. Also, a wave 2 correction may have bottomed, which indicates we may get a wave 3 move-up. We could see a good move up after declining since early February. Of course, volatility moves up and down may occur, which is natural for a biotech like Anavex; however, at some point, each biotech investor must decide if the odds are favorable to accept the risk to hopefully make some real money.
So, your post that “the company falsely communicated along the way” and that “COVID did not make Missling lie” implicates Anavex in the commission of securities fraud. Are you sure about that?
Stocktwits reports this morning that both ANVS presentations have been rescheduled for tomorrow, Saturday?
Sab: TD 9 perfection today. Maybe selling has exhausted for now.
Correct!
Mayo: Great work! Thank you. Sokol
Mitochondrial Diseases
What are mitochondrial diseases?
Mitochondrial diseases are chronic (long-term), genetic, often inherited disorders that occur when mitochondria fail to produce enough energy for the body to function properly. (Inherited means the disorder was passed on from parents to children.) Mitochondrial diseases can be present at birth, but can also occur at any age.
Mitochondrial diseases can affect almost any part of the body, including the cells of the brain, nerves, muscles, kidneys, heart, liver, eyes, ears or pancreas.
Mitochondrial dysfunction occurs when the mitochondria don't work as well as they should due to another disease or condition. Many conditions can lead to secondary mitochondrial dysfunction and affect other diseases, including:
- [Alzheimer's disease](https://my.clevelandclinic.org/health/diseases/9164-alzheimers-disease-an-overview).
- [Muscular dystrophy](https://my.clevelandclinic.org/health/diseases/14128-muscular-dystrophy).
- [Lou Gehrig's disease](https://my.clevelandclinic.org/health/diseases/16729-amyotrophic-lateral-sclerosis-als).
- [Diabetes](https://my.clevelandclinic.org/health/diseases/7104-diabetes-mellitus-an-overview).
- [Cancer](https://my.clevelandclinic.org/health/diseases/12194-cancer-overview).
ShowImage.ashx
Mitochondrial Diseases: Causes, Symptoms, Diagnosis & Treatment
my.clevelandclinic.org
Blarcamesine is a novel small molecule drug compound that has shown promising results in preclinical studies as a potential treatment for mitochondrial dysfunction in various diseases. It has been shown to enhance mitochondrial energy production and protect against oxidative stress, which are key factors in mitochondrial dysfunction.
See “The Potential of Small Molecules to Modulate the Mitochondria–Endoplasmic Reticulum Interplay in Alzheimer’s Disease”
“Alzheimer’s disease (AD) is the most common neurodegenerative disease affecting a growing number of elderly individuals. No disease-modifying drugs have yet been identi?ed despite over 30 years of research on the topic, showing the need for further research on this multifactorial disease. In addition to the accumulation of amyloid ß-peptide (Aß) and hyperphosphorylated tau (p-tau), several other alterations have been associated with AD such as calcium (Ca2+) signaling, glucose-, fatty acid-, cholesterol-, and phospholipid metabolism, in?ammation, and mitochondrial dysfunction. Interestingly, all these processes have been associated with the mitochondria–endoplasmic reticulum (ER) contact site (MERCS) signaling hub. We and others have hypothesized that the dysregulated MERCS function may be one of the main pathogenic pathways driving AD pathology.…
…Concordantly, different S1R modulators such as pridopidine, N-n-propyl-3-(3-hydroxyphenyl) piperidine (3-PPP), and AF710B (ANAVEX 3–71) displayed neuroprotective properties in animal models of AD, reviewed in Ryskamp D. et al. (2019). Several ongoing trials for HD such as PROOF-HD (Phase 3) (Reilmann et al., 2021) and HEALEY ALS (Phase 2–3) (Paganoni et al., 2022) have been spurred by promising results of pridopidine in vitro and in vivo. AD pridopidine itself is not currently being tested; nonetheless, other S1R agonists including blarcamesine (phase II/III) (Hampel et al., 2020), edonerpic (phase II) (Schneider et al., 2019), dextromethorphan formulations AVP-786 (phase III) (Cummings et al., 2015), AVP-923 (phase IV) (Fralick et al., 2019), and AXS-05 (phase II-III) (Wilkinson and Sanacora, 2019) are undergoing clinical trial validation. In summary, these studies suggest that pridopidine and other S1R agonists could act as diseasemodifying and neuroprotective agents in AD by stimulating MERCS-associated functions. In the context of AD, we believe such molecules could be used in the early stages to sustain MERCS-mediated bioenergetics and ATP production.”
nlm.nih.gov
See also:
The Mitochondria–Endoplasmic Reticulum Contacts and Their Critical Role in Aging and Age-Associated Diseases
Ornella Moltedo,1 Paolo Remondelli,2,* and Giuseppina Amodio2,*
Author information Article notes Copyright and License information Disclaimer
Go to:
Abstract
The recent discovery of interconnections between the endoplasmic reticulum (ER) membrane and those of almost all the cell compartments is providing novel perspectives for the understanding of the molecular events underlying cellular mechanisms in both physiological and pathological conditions. In particular, growing evidence strongly supports the idea that the molecular interactions occurring between ER and mitochondrial membranes, referred as the mitochondria (MT)–ER contacts (MERCs), may play a crucial role in aging and in the development of age-associated diseases. As emerged in the last decade, MERCs behave as signaling hubs composed by structural components that act as critical players in different age-associated disorders, such as neurodegenerative diseases and motor disorders, cancer, metabolic syndrome, as well as cardiovascular diseases. Age-associated disorders often derive from mitochondrial or ER dysfunction as consequences of oxidative stress, mitochondrial DNA mutations, accumulation of misfolded proteins, and defective organelle turnover. In this review, we discuss the recent advances associating MERCs to aging in the context of ER–MT crosstalk regulating redox signaling, ER-to MT lipid transfer, mitochondrial dynamics, and autophagy.
nlm.nih.gov
The AAIC 2022 poster says this: Study of the Mechanism of Action of Blarcamesine (ANAVEX®2-73): Whole Blood Transcriptomics Analysis (RNAseq)
Identifies Treatment Impact on Compensatory Pathways by Restoring Key Neurodegenerative Pathways Functionality,
including Alzheimer’s and Parkinson’s Disease Pathways
https://79bcf7a1-8b8e-483b-b7cf-f5c5192a6d63.usrfiles.com/ugd/79bcf7_c5813c517d9f4ca5aacbeb719508827a.pdf
In other words, Blarcamesine restored dysregulated genes associated with Alzheimer's and Parkinson's. If so, was that restoration evident in all patients treated with Blarcamesine versus no restoration in the placebo patients? More importantly, did all treated patients show some degree of improvement or decline in the progression of the diseases? Or was it that the restoration occurred only in those patients treated with the Blarcamesine high dose?
What I am driving at is this: If the gene restoration occurred in all or most all patients treated with Blarcamesine compared to no such repair in placebo patients, this would be important. It would involve a more significant number of patients showing some positive response to the drug. If so, this would go a long way to demonstrate that the drug has a positive biological response in the body of a significant number of Blarcamesine-treated patients.
Yes, I have noticed. The chart for ANVS looks good. Volume/on-balance volume is increasing, with the share price rising above the Bollinger bands. It certainly looks like an accumulation period from October 2022 through January this year. TD sequential gave a buy signal four days ago. The share price now breaks out after several months of accumulation. It appears to have quite a bit of life to this move, with near-term catalyst-interim analysis in Q2, as clearly and plainly explained by the CEO. Sab, I wish you the best. Sokol