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You may be ok. We will see. It may not go below 10. If selling exhaustion occurs the end of the week as I expect, we should see higher prices for the next week or so.
I am waiting to possibly buy lower near the end of the week. I am looking for selling exhaustion - looking for the low on Wednesday (March 3) or Thursday (March 4) to be less than or equal to the lows on Monday and Tuesday of this week for a buy setup.
Falconer, thank you. To answer your question about what organisms could be used doing a studies. Dogs and Cats I think are ideal. Studies could be done for kidney disease. Plus, what do you think a drug would be worth if it could treat pets and extend their lives for their pet owners.
“About 60% of dogs and cats with this disease either die or are humanely euthanized because of failure to respond to supportive care.”
https://bluepearlvet.com/medical-articles-for-pet-owners/acute-renal-failure-in-dogs/
Dogs and Kidney Disease
“Kidney disease is a serious health problem in dogs that require medical attention.”
https://www.thesprucepets.com/dogs-and-kidney-disease-4092948
Chromatin dynamics in kidney development and function
Wibke Bechtel-Walz 1 , Tobias B Huber
Affiliations expand
PMID: 24817101 DOI: 10.1007/s00441-014-1884-y
Abstract
“Epigenetic mechanisms are fundamental key features of developing cells connecting developmental regulatory factors to chromatin modification. Changes in the environment during renal development can have long-lasting effects on the permanent tissue structure and the level of expression of important functional genes. These changes are believed to contribute to kidney disease occurrence and progression. Although the mechanisms of early patterning and cell fate have been well described for renal development, little is known about associated epigenetic modifications and their impact on how genes interact to specify the renal epithelial cells of nephrons and how this specification is relevant to maintaining normal renal function. A better understanding of the renal cell-specific epigenetic modifications and the interaction of different cell types to form this highly complex organ will not only help to better understand developmental defects and early loss of kidney function in children, but also help to understand and improve chronic disease progression, cell regeneration and renal aging.”
https://pubmed.ncbi.nlm.nih.gov/24817101/
Thank you, RedShoulder. That’s a good supplement to my post.
Excellent! Thank you.
The new chromatin MOA of the drug further indicates that we should be on to something extraordinarily great to the point that it boggles the mind. As Dado’s recent post says: “When you have the courage of your own convictions - you gain confidence in knowing what the future holds...”. We have been mocked and punched, but we have made so much progress over the last 5 or 6 years. Based on the chromatin MOA, we have another foundation or footing of support for our drug and its potential to treat multiple diseases. Therefore, I am more confident than ever.
Anavex 2-73 activates the Sigma-1 Receptor, which restores chromatin structures. Aberrations in chromatin remodeling proteins are found to be associated with many human diseases. This appears to have enormous implications for Anavex.
This is from the February 11 report from Anavex
"Anavex Life Sciences’ 2021 Business and Clinical Outlook:
Underlying cause of Alzheimer's disease and therapeutic intervention:
-Researchers at the University of California San Diego have identified the underlying cause of Alzheimer's disease in neurons. They discovered that changes in the structure of chromatin are responsible.2 Sigma-1 Receptor (SIGMAR1), the direct target which gets activated with ANAVEX®2-73 demonstrated to restore chromatin structures.3
-ANAVEX®2-73 linked to the prevention and treatment of age-associated diseases through induction of the autophagy “cellular recycling” process and enhanced protein clearance in cells.4"
https://www.globenewswire.com/news-release/2021/02/11/2173958/0/en/Anavex-Life-Sciences-Reports-Fiscal-2021-First-Quarter-Financial-Results-And-Business-Outlook.html
The following is from Wikipedia:
"Besides actively regulating gene expression, dynamic remodeling of chromatin imparts an epigenetic regulatory role in several key biological processes, egg cells DNA replication and repair; apoptosis; chromosome segregation as well as development and pluripotency. Aberrations in chromatin remodeling proteins are found to be associated with human diseases, including cancer. Targeting chromatin remodeling pathways is currently evolving as a major therapeutic strategy in the treatment of several cancers."
Here are two additional scientific articles supportive to the path that Anavex is pursing that may lead to treatment of multiple diseases.
1. Chromatin deregulation in disease
Abstract
"The regulation of chromatin by epigenetic mechanisms plays a central role in gene expression and is essential for development and maintenance of cell identity and function. Aberrant chromatin regulation is observed in many diseases where it leads to defects in epigenetic gene regulation resulting in pathological gene expression programmes. These defects are caused by inherited or acquired mutations in genes encoding enzymes that deposit or remove DNA and histone modifications and that shape chromatin architecture. Chromatin deregulation often results in neurodevelopmental disorders and intellectual disabilities, frequently linked to physical and developmental abnormalities, but can also cause neurodegenerative diseases, immunodeficiency, or muscle wasting syndromes. Epigenetic diseases can either be of monogenic origin or manifest themselves as complex multifactorial diseases such as in congenital heart disease, autism spectrum disorders, or cancer in which mutations in chromatin regulators are contributing factors. The environment directly influences the epigenome and can induce changes that cause or predispose to diseases through risk factors such as stress, malnutrition or exposure to harmful chemicals. The plasticity of chromatin regulation makes targeting the enzymatic machinery an attractive strategy for therapeutic intervention and an increasing number of small molecule inhibitors against a variety of epigenetic regulators are in clinical use or under development. In this review, we will give an overview of the molecular lesions that underlie epigenetic diseases, and we will discuss the impact of the environment and prospects for epigenetic therapies."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761009/
2. The Sigma-1 Receptor as a Pluripotent Modulator in Living Systems
"The sigma-1 receptor (Sig-1R) is an endoplasmic reticulum (ER) protein that resides specifically in the mitochondria-associated endoplasmic reticulum (ER) membrane (MAM), an interface between ER and mitochondria. In addition to being able to translocate to the plasma membrane (PM) to interact with ion channels and other receptors, Sig-1R also occurs at the nuclear envelope, where it recruits chromatin-remodeling factors to affect the transcription of genes. Sig-1Rs have also been reported to interact with other membranous or soluble proteins at other loci, including the cytosol, and to be involved in several central nervous system (CNS) diseases. Here, we propose that Sig-1R is a pluripotent modulator with resultant multiple functional manifestations in living systems."
https://www.sciencedirect.com/science/article/abs/pii/S0166223619302243
I believe Black Rock operates various index mutual funds.
Black Rock, I see disclosed more than 5% ownership in SAVA and AVXL today.
UsAgainstAlzheimer’s organization is urging people to contact the FDA to advocate for approval of Biogen’s aducanumab, which they say would be the first disease modifying drug for Alzheimer’s.
An FDA advisory panel previously declined to recommend approval. Biogen’s drug failed at first. Later, Biogen and its partner, Eisai, obtained a different outcome with a new measure of efficacy. They came up with a new standard to measure ”success” to seek FDA approval despite the prior failure of the drug and despite side effects. Among the side effects that the companies reported were reactions at the sites of the infusion and swelling around blood vessels observed with brain imaging.
The drug is IV injected, meaning multiple trips are made to a clinic for injections.
I think it is likely that Anavex is discussing the undisclosed rare disease clinical trial with another party, which could be a foundation other organization or entity. As Investor pointed out, Missling is a member of Rare Advocacy Group (RAM). Perhaps Missling is waiting to finalize the details of this trial. Or, maybe plans have been made, but the other party has requested confidentiality for now. The point is, there is an adequate reason, and it may be a favorable one to boot.
"RAM is focused on establishing a unified rare disease community amongst the already diverse real world rare disease landscape through the development of sustainable community enhancing programs, resources and opportunities dubbed RAM Collaborations." https://www.rareadvocacymovement.com
Anavex's pursuit of rare diseases is an essential factor that I believe investors are overlooking.
There are about 362 million people living with a rare disease worldwide - 2019 Statistic
5% of the global population has a rare disease. The current world population is 7.7 billion. - 2020 Statistic
Rare diseases may be eligible for numerous programs that may accelerate drug approval.
Anavex seems to be a front runner in treating CNS related rare diseases for which there is no cure.
Perhaps dilution is not an ugly word for Anavex at this stage. In reading today's announcement, it is expanding its clinical trials with drugs based on sound science and backed by studies. Dilution is undoubtedly a factor in analyzing early biotech stocks, but I believe astute investors weigh the totality of circumstances. I am pleased to see Anavex well funded at this stage in its development. I am happy to see that Anavex is in a position to build on its successes.
Yes, I agree. Thank you.
A few observations regarding Anavex:
I have followed and invested in Anavex shares and options for something like six years. The company has made substantial progress with the share price grudgingly increasing in price from pennies per share to today, although we scratch our heads and ask why it is not higher.
I think the answer is that investors do not grasp the importance of the data and the Anavex pipeline. Anavex recently made another definite step toward its first drug approval, i.e., for Rett. Thousands of people suffer from Rett, with consequences for their families and caregivers as well, and there is no approved therapy.
Secondly, few realize or remember that ANAVEX2-73 has three designations to accelerate FDA approval for Rett syndrome: fast track, rare pediatric disease, and orphan drug designation.
Thirdly, Anavex is well funded, as I believe will be confirmed when Anavex announces earnings. Therefore, it will continue to make progress with all of its multiple clinical trials.
Short term and long term potential catalyst exist, including feedback from the FDA with Rett, two more Rett data readouts next year, PDD data, AD data, and FTD (Anavex 3-71). However, we should not forget the potential developments for all drugs within the Anavex pipeline for PD in general, infantile spasms, fragile X, Angelman's, depression, stroke, visceral pain, acute & neuropathic pain, etc.
I wish Happy Holidays, Merry Christmas, and a prosperous and healthy new year for all! Lastly, thank all of you that have made and continue to make contributions to this board. I look forward to reading your posts whether I agree, disagree like, dislike or fail to understand. Peace on Earth and Goodwill toward everyone.
Bio:
Thank you. Also, do you have any comments about the following?
Glutamate is a destructive factor in CNS disorders. For example:
"Abundant evidence points to glutamate as a destructive factor in ALS and investigators are working to find out how this can be changed.
...Researchers are working towards gene therapy approaches to deliver the glutamate transporter molecule to cells affected by ALS. Other avenues towards control of glutamate in ALS are also under active investigation."
http://web.alsa.org/site/PageServer?pagename=ALSA_Glutamate
The AVXL 2-73 Rett clinical trials demonstrate improvement in glutamate plasma levels. It appears to me that at the very least AVXL 2-73 may be an adjunct therapy for ALS and possibly other CNS diseases.
“Autologous MSC-NTF cells can effectively deliver multiple NTFs and immunomodulatory cytokines directly to the site of damage to elicit a desired biological effect and ultimately slow or stabilize disease progression.”
The biomarker information from the phase 3 clinical trial was favorable, indicating that NurOwn is eliciting a desired biological effect. This effect may “ultimately slow or stabilize disease progression.” So, what is meant or implied by “ultimately”? Is it that NurOwn may need to be administered for a more extended period to be useful for some patients? Does the data demonstrate that NurOwn is effective sooner for patients with earlier onset of the disease and that NurOwn, if effective at all, may slow or stabilize disease progression in those patients are farther along in the disease progression with more severe damage?
Lindborg Stacy, head of Global Clinical Research for Brainstorm, acquired 200 May $10 call option contracts on November 17 at a price of $11,000. Stacy is betting Brainstorm's share price will exceed $10 per share between now and May 21, 2021. Stacy has the right to purchase 20,000 shares of Brainstorm at a price of $10.00 between now and May 21, 2021. The share price of Brainstorm would have to equal $10.55 for Stacy to break even. See the Statement of Changes in Beneficial Ownership filed today, November 19th, referenced in the Recent News section above.
Conference call: Here is a link to sign in to listen to yesterday’s conference call about the NurOwn results. https://www.webcaster4.com/Webcast/Page/2354/38723
I am mystified about the placebo results; however, I am encouraged about the results amongst the specified group, which indicates that NurOwn may be effective if the drug is administered at early onset of ALS. I am also intrigued about the biomarker outcome, which was positive for the treated patients and non-existent in those receiving the placebo. Treated patients exhibited a significant increase of neurotrophic factors and reduction in neurodegenerative and neuroinflammatory biomarkers.
Will the FDA approve the drug for patients that fall in the pre-specified group? Will the FDA require further study for this group?
Fmello:
It seems to me that any additional trials, including trials for MS, would need to focus on the “pre-specified group” and involve less severe patients. Also, is it possible that NurOwn may be useful as an adjunct therapy? I am not sure about any of this (maybe Midas is better suited to speak to all of this), but here is the discussion about the pre-specified group and less severe patients:
“In an important, pre-specified subgroup with early disease based on ALSFRS-R baseline score ³ 35, NurOwn demonstrated a clinically meaningful treatment response across the primary and key secondary endpoints and remained consistent with our pre-trial, data-derived assumptions. In this subgroup, there were 34.6% responders who met the primary endpoint definition on NurOwn and 15.6% on Placebo (p=0.288), and the average change from baseline to week 28 in ALSFRS-R total score was -1.77 on NurOwn and -3.78 on Placebo (p=0.198), an improvement of 2.01 ALSFRS-R points favoring NurOwn.
Cerebrospinal fluid (CSF) biomarker analyses confirmed that treatment with NurOwn resulted in a statistically significant increase of neurotrophic factors and reduction in neurodegenerative and neuroinflammatory biomarkers that was not observed in the placebo treatment group. We also carried out pre-specified statistical modeling designed to predict clinical response with high sensitivity and specificity based on ALS biomarkers and ALS Function and confirmed that NurOwn treatment outcomes could be predicted by baseline ALS function as well as key CSF neurodegenerative and neuroinflammatory biomarkers.
Dr. Merit Cudkowicz, one of the Principal Investigators of this trial and the Julianne Dorn Professor of Neurology at Harvard Medical School and the Director of the Healey Center for ALS and Chair of Neurology at Mass General Hospital said, "We found a clinically meaningful response to NurOwn in a pre-specified group of patients (greater than or equal to 35 ALSFRS-R at baseline). A change in pre- to post- treatment slope of 1.25 or more is substantial and clinically important. Given the heterogeneity of ALS, it is not surprising that measurement of treatment effect may be influenced by disease severity including the behavior of disease progression rates at the lower end of the scale. It is important to fully explore this finding. In addition, NurOwn was observed to have its clear intended biological effects with important changes in the pre-specified disease and drug related biomarkers."
"This clinical trial included a more severely affected ALS population compared to other recent ALS clinical trials. We identified a superior treatment response in a pre-specified subgroup of patients with less advanced disease.”
Yes, it could take a couple of years or more. However, I am thinking that, if the safety issue is not a problem, access may be gained sooner through compassionate use or some accelerated approval due to the nature of the diseases involved. It may be that Brainstorm may need to establish that NurOwn is safe for each of these diseases. In other words, is there anything about these other diseases that may pose a safety issue if those patients are administered NurOwn? There is also speculation that there may be faster approvals of drugs for serious diseases as a result of the pandemic approvals of vaccines and drugs to treat the C-virus. The pandemic approvals may be considered a precedent for speeding up approval of these drugs.
It should. To add a new indication for an approved drug a supplemental drug application is filed with the FDA. Relevant information, data and findings from the clinical trails Brainstorm has conducted may be used to support the supplemental application.
Also, once a drug has been approved for one indication, it may be prescribed off label; however, I am not so sure that physicians will be willing to prescribe NurOwn infusions off label for these other diseases you mention. I think it is highly doubtful that NurOwn will be prescribed off label. That said, there is such a thing as compassionate use special access scheme that may come into play. For example, Australia has such a scheme that allows Australians access to drugs - especially drugs that have received some sort of approval elsewhere. I am not sure how compassionate use under a special access scheme would work for an infusion drug like NurOwn. Physicians have to submit a request for such a use, and the submitting physician is not relieved of any liability for prescribing a drug under the compassionate use special access scheme even if the scheme is approved by regulatory authorities.
Unfortunately, this thumb’s down vote is not binding. The FDA could still approve aducanumab:
“The nonbinding vote by an advisory panel for the Food and Drug Administration does not mean the agency won’t approve the drug, aducanumab, made by Biogen. But it signals that many experts in the field are not convinced of its effectiveness, another major setback in the long journey to find a treatment for Alzheimer’s that works.”
https://www.nytimes.com/2020/11/06/health/aducanumab-alzheimers-drug-fda-panel.html
Fmello:
There is no comparison, except that maybe that both are infusions, between Brainstorm’s NurOwn and Biogen’s infusion (aducanumab) to treat Alzheimer’s. Here is a portion of a letter that I sent to the WSJ a year or so ago about aducanumab:
The Biogen and Eisai drug, BAN240 (aducanumab), failed before. So what's new about their latest announcement?
WSJ article: ”Analysts said questions remain about the results of the BAN2401 study. For one thing, researchers used a novel measure of efficacy that was developed by Eisai’s in-house researchers, rather than standard measures in the field.”
They, Biogen and Eisai, obtained a different outcome with a new measure of efficacy. Biogen’s partner Eisai, a Japanese pharmaceutical company, came up with a new standard to measure ”success”. This ”success” measured by a new internally conflicted standard should by itself raise a red flag.
Even then this ”success” may not be so great considering their drug is an infusion and the same WSJ article points out: ”The study involved 856 subjects in the early stage of the disease. Among the side effects that the companies reported were reactions at the sites of the infusion and swelling around blood vessels observed with brain imaging.”
Making multiple trips to a clinic or medical office for infusions as opposed to taking a pill poses difficulties in addition to the risks of adverse events, and for what: BAN240 does not stop or reverse Alzheimer’s. To sum up : IV injected, only works at highest dosage at if at all, takes 6 months to kick in, and the cognitive tests we're created in house and not standard. And, what percentage of adverse events occurred at this highest dosage? It would be of interest to know what percentage of those receiving ONLY the highest dosage, the one that reportedly works, developed adverse events.
Alzheimer’s is a cruel disease. Let's not promote false hopes - especially one based on the amyloid hypothesis that has been virtually a 100% failure.
Early on reports about the benefit and length of benefit from NurOwn, although not sufficient in numbers of patients, offer some encouragement that multiple administrations possibly slow ALS down for a significant period of time.
This is from the report about the soldier an the rabbi.
Four ALS patients in an advanced stage of disease received NurOwn transplants at Hadassah starting in 2012 as “compassionate use” cases, including Omri Chotam, a former paratrooper in his 20s, and octogenarian sage Rabbi Rafael Shmuelevitz.
....All four had, at least for three to six months, a response of improvement in respiratory function or muscle power,” reports Karussis.
”The most impressive response was in the rabbi, who had a very severe and unique combination of ALS and myasthenia gravis. He improved for about six months substantially, started walking and speaking, and then the effects faded and then we did a second injection and he had even more impressive improvement. This makes it highly unlikely to be a placebo effect, which is important to note.”
Chotam also received two additional NurOwn injections through the compassionate use program, resulting in functional improvements and halting the progression of the disease for about 18 months now.
“According to the data we have, the treatment makes a beneficial change in the progression of the disease. This is the first step. Now the US study is starting, and we are collaborating and consulting with them,” says Karussis. “We probably need to improve the protocol to do multiple injections for the longer term, and find the best way of administration in each individual patient.”
https://www.israel21c.org/revolutionary-stem-cell-als-treatment-begins-advanced-trials/
In May of this year, Brainstorm leased an Israeli facility to manufacture NurOwn for the EU.
BrainStorm Leases a New Cleanroom Facility at The Tel Aviv Sourasky Medical Center to Manufacture NurOwn® for The European Union
May 7, 2020: https://www.globenewswire.com/news-release/2020/05/07/2029044/0/en/BrainStorm-Leases-a-New-Cleanroom-Facility-at-The-Tel-Aviv-Sourasky-Medical-Center-to-Manufacture-NurOwn-for-The-European-Union.html
Here is a petition for accelerated approval in the UK:
Accelerated Access for Motor Neurone Disease (MND / ALS) treatment in the UK - NurOwn
https://www.change.org/p/boris-johnson-accelerated-assessment-access-review-for-motor-neurone-disease-mnd-als-treatments-in-the-united-kingdom-nurown-stemcells
All of this reminds me of the fight for approval of Sarepta's drug for Duchenne.
Dr. Jeremy Shefner, senior vice president of Barrow Neurological Institute, believes that while it may be frustrating for patients waiting for an ALS drug to be approved, the FDA process is not for nothing.
Dr. Shefner says the trouble is that if you have a disease, which on the average, leads to death in somewhere between three and five years, a drug can’t be looked at for only a couple of months.“You need a significant amount of time,” he said. “Another issue is that ALS patients are relatively rare so you need to recruit in the hundreds of patients to definitively determine if the drug works or not.
Since there are no BIOMARKERS with ALS, the only endpoint or measure is whether the patient administered the real drug is getting worse or not. We have anecdotal evidence that several patients have improved; however, the FDA will be looking at how the patients receiving the drug compared to patients receiving the placebo. Additionally, according to Dr. Shefner, the FDA will need to be convinced that patients receiving the drug did better for a "significant amount of time."
https://yourvalley.net/stories/facing-devastating-diagnosis-als-community-remains-dedicated-to-finding-new-treatments,163938
So, it may be that Brainstorm (for some unknown reason) believes that NurOwn patients in the phase 3 trial performed better for a significant period of time than those administered the placebo, which is why it has gone to the trouble and some expense to get production facilities in place. However, what will the data demonstrate to the FDA? What does the data actually show regarding NurOwn patients? No one knows which trial participants received NurOwn versus the placebo. I suppose that if we received reports that a number of patients in the phase 3 trial did not get worse or improved, than we may speculate that those patients received NurOwn, but we do not know that.
Doc: Assuming the successful completion of AVXL 2-73 clinical trials for AD, I believe your opinion is that its NDA to the FDA for AD here in the United States is several years away. However, what about PDD and Rett? Lastly, again assuming all trials go well, what do you think a reasonable timeline may be for Anavex to file for approval for AVXL 2-73 for AD, Rett, or PDD elsewhere - outside the United States.
Could be: “Due to the complexities of manufacturing biological products, a pre-license inspection of the facility is generally required before a BLA is approved. Pre-approval inspections sometimes also take place during an NDA review, but are typically conducted based on risk assessment by the Agency.”
https://www.nuventra.com/resources/blog/regulatory-differences-between-an-nda-bla/
Yes. "Lewy bodies are also found in other brain disorders, including Alzheimer's disease and Parkinson's disease dementia. Many people with Parkinson's eventually develop problems with thinking and reasoning, and many people with Lewy body dementia experience movement symptoms, such as hunched posture, rigid muscles, a shuffling walk and trouble initiating movement.
This overlap in symptoms and other evidence suggest that Lewy body dementia, Parkinson's disease and Parkinson's disease dementia may be linked to the same underlying abnormalities in how the brain processes the protein alpha-synuclein. Many people with both Lewy body dementia and Parkinson's dementia also have plaques and tangles — hallmark brain changes linked to Alzheimer's disease."
https://www.alz.org/alzheimers-dementia/what-is-dementia/types-of-dementia/lewy-body-dementia
Yes, I think you may be correct. That may happen - at least to some extent. Also, there will be quite a number of people involved with Anavex’s clinical trials present at the conference. They, of course, will be communicating about PDD, Rett, AD, etc. with people attending and involved with the conference.
CTAD presentation: The 15 minute presentation will be limited to cognitive measures from the PDD study that are relevant to Alzheimer's. We should not expect a full discussion of the PDD data - only the data that relates to Alzheimer's, which is relevant to this Alzheimer's conference. The final program schedule/agenda for CTAD 2020 that is available and may be downloaded from the site provided below. Anavex’s presentation on November 6 at 11:00 EST will be an analysis of “Cognitive Outcome Measures Relevant in AD” of the PDD phase 2 clinical trial. So, this will be about cognitive measures from the PDD trial and how those measures apply to Alzheimer’s Disease. Do NOT expect a full blown discussion of the PDD data, which, of course, is not relevant to this conference! And, do not be disappointed with the limitations placed on this presentation! https://www.ctad-alzheimer.com/files/files/DIGITALprogram_CTAD2020_23oct.pdf
I imagine everyone has seen this final program schedule/agenda for CTAD 2020 that is available and may be downloaded from the site provided below. Anavex’s presentation on November 6 at 11:00 EST will be an analysis of “Cognitive Outcome Measures Relevant in AD” of the PDD phase 2 clinical trial. So, this will be about cognitive measures from the PDD trial and how those measures apply to Alzheimer’s Disease.
“LB25 - ANAVEX®2-73 (blarcamesine) Currently in Phase 2b/3 Early Alzheimer’s Disease (AD): Analysis of Cognitive Outcome Measures Relevant in AD of Double-blind, Multicenter, Placebo-controlled Phase 2 Clinical Trial in 132 Patients with Parkinson’s Disease Dementia Dag Aarsland (1), Jaime Kulisevsky Bojarski (2), Mohammad Afshar (3), Coralie Williams (3), Frederic Parmentier (3), Martin Kindermans (3), Tayo Fadiran (4), Andy Mattai (4), Christopher U Missling (4), Walter E Kaufmann (4) (1)King’s College - London (United Kingdom); (2)University of Barcelona - Barcelona (Spain); (3)Ariana Pharma - Paris (France); (4)Anavex Life Sciences - New York, NY (United States)”
https://www.ctad-alzheimer.com/files/files/DIGITALprogram_CTAD2020_23oct.pdf
Fmello: Thank you for posting the video. It is superb. Everyone interested in BrainStorm and in learning more about ALS in general should watch this video. It is extremely informative.
For whatever it is worth, Corey Davis is an account manager at
LifeSci Advisors, and he does have a PhD. Without any evidence or real news to the contrary, I guess we have to assume it is not bogus for now at least.
https://www.lifesciadvisors.com/team/
Midas:
Today’s drop in stock price is due, I believe, to a misleading - poorly worded news wire available to TD Ameritrade account holders and others that says this about BCLI:
“The company said it was uncertain if it would be able to raise capital to commercialize Nurown, and warned that it may not be able to continue to function as a going concern.
‘While the company has been successful in raising financing recently and in the past, there can be no assurance that it will be able to do so in the future on a timely basis on terms acceptable to the company, or at all," the firm said in a Securities and Exchange Commission filing. "This pandemic has caused substantial disruption in the financial markets and may adversely impact economies worldwide, both of which could result in adverse effects on company's business, operations and ability to raise capital.’’’
I looked up the SEC filing referred to in the news blurb. The SEC filing contains the usual canned or standardized wording provided by securities lawyers. Here it is:
“Brainstorm Cell Therapeutics 10-Q20202020 Q3 Quarterly report
......
GOING CONCERN:
Since its inception, the Company has devoted substantially all of its efforts to research and development. The Company is still in its development and clinical stage and has not yet generated revenues. The extent of the Company's future operating losses and the timing of becoming profitable are uncertain.
Additional funding will be required to begin the commercialization efforts and to achieve a level of sales adequate to support the Company's cost structure.
To meet its capital needs, the Company is considering multiple alternatives, including, but not limited to, additional public and private sales of its Common Stock and warrants, the exercise of warrants, the issuance of convertible promissory notes, sales of Common Stock via its ATM program and other funding transactions. While the Company has been successful in raising financing recently and in the past, there can be no assurance that it will be able to do so in the future on a timely basis on terms acceptable to the Company, or at all.
The COVID-19 pandemic may continue to adversely disrupt the Company's operations, including the ability to complete the ongoing clinical trials and may have other adverse effects on Company's business and operations. In addition, this pandemic has caused substantial disruption in the financial markets and may adversely impact economies worldwide, both of which could result in adverse effects on Company's business, operations and ability to raise capital.
Management expects that the Company will continue to generate losses from the clinical development and regulatory activities, which will result in a negative cash flow from operating activity. The Company currently has sufficient cash to complete its ongoing Phase 3 ALS, Phase 2 PMS and Phase 2 AD clinical trials. Over the longer term, if the Company is granted a BLA approval, additional capital raise will be needed in connection with strategic partnerships and to commercialize Nurown® for ALS, and to conduct additional trials for other indications. If the Company is not able to raise additional capital for these purposes, management may need to slow the pace of commercialization or the Company may not be able to continue to function as a going concern. The Company's consolidated financial statements do not reflect any adjustments that might result from the outcome of this uncertainty.”
"The RPD designation provides priority review by the FDA to encourage treatments for rare pediatric diseases. Under the RPD program, a sponsor who receives an approval for a drug for a “rare pediatric disease” may qualify for a voucher that can be redeemed to receive a priority review by the FDA of a subsequent marketing application for a different product."
https://www.anavex.com/anavex-life-sciences-receives-rare-pediatric-disease-designation-from-fda-for-anavex2-73-blarcamesine-for-the-treatment-of-rett-syndrome/
So glad you liked it. Thank you.
The last study I cited, I believe, was announced in March 2013, but I think you will find later studies as well.
Peroxynitrite Is a powerful oxidant that, among other things, inhibits mitochondrial respiration. Mitochondrial dysfunction is reported as a cause of Alzheimer's disease and as a factor that contributes to other CNS diseases. Mitochondrial dysfunction is a result of oxidative stress. ANAVEX 2-73 is believed to have CNS disease-modifying effects, including the ability to repair normal mitochondrial functionality.
1. Anavex 2-73 inhibits oxidative stress by inhibiting the release of intracellular calcium... Lane article. (Lane also mentions that Anavex 2-73, a tetrahydrofuran, can be an H donor, which Doc contradicts, but so far I see no other authority for this one way or another; nevertheless, inhibiting oxidative stress is key to preventing and/or relieving CNS diseases).
2. For more than half a century free radical-induced alterations at cellular and organ levels have been investigated as a probable underlying mechanism of a number of adverse health conditions. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462847/
3. Apoptosis, an essential physiological process that is required for the normal development and maintenance of tissue homeostasis, is mediated by active intrinsic mechanisms, although extrinsic factors can also contribute. Aerobic metabolism induces the production of reactive oxygen species (ROS), which are able to induce oxidative stress that promotes cellular apoptosis. The mechanisms of ROS-induced modifications in ion transport pathways involves oxidation of sulphydryl groups located in the ion transport proteins, peroxidation of membrane phospholipids, inhibition of membrane-bound regulatory enzymes and modification of the oxidative phosphorylation and ATP levels. Alterations in the ion transport mechanisms lead to changes in a second messenger system, primary Ca2+ homeostasis. Ca2+ disregulation induces mitochondrial depolarization, which further augments the abnormal electrical activity and disturbs signal transduction, causing cell dysfunction and apoptosis. Control of ROS levels in cells is important, because cellular dysfunction triggered by ROS is a major factor contributing to the development of many diseases. Available evidences show that ROS can induce increases in cytosolic free Ca2+ concentration ([Ca2+]c) by release of the divalent cation from internal stores and impairment of Ca2+ clearance systems. In fact, [Ca2+]c increase is a constant feature of pathological states associated with oxidative stress and apoptosis. https://link.springer.com/chapter/10.1007/978-1-4020-9873-4_1
4. Amyloid-beta peptide has been shown to result in mitochondrial and endoplasmic reticulum stress, intracellular calcium dysregulation leading to oxidative stress and apoptosis (cell death). The authors point to the role of ANAVEX 2-73 in prevention of oxidative stress and apoptosis and other data suggesting modulation of Bcl-2 and reactive oxygen species. See Anti-amnesic and neuroprotective potentials of the mixed muscarinic receptor/sigma 1 ligand ANAVEX 2-73, a novel aminotetrahydrofuran derivative”, is available online at http://jop.sagepub.com/cgi/content/abstract/0269881110379286v1?papetoc. See also, https://www.anavex.com/anavex-2-73-journal-of-psychopharmacology-publishes-anti-amnesic-and-neuroprotective-data-against-amyloid-toxicity-for-first-of-a-new-class-in-alzheimers-disease/
5. Peroxynitrite: Peroxynitrite is a powerful oxidant exhibiting a wide array of tissue damaging effects, including lipid peroxidation, inactivation of enzymes and ion channels via protein oxidation and nitration, and inhibition of mitochondrial respiration (Virag et al., 2003). From: Handbook of Toxicology of Chemical Warfare Agents (Second Edition), 2015
6. Mitochondrial dysfunctions significantly contribute to the pathogenesis of Alzheimer's disease (AD). https://pubmed.ncbi.nlm.nih.gov/26971932/
Lastly,
"In a scientific study conducted in France at the University of Montpellier and INSERM, ANAVEX 2-73 demonstrated disease-modifying effects, including the ability to repair normal mitochondrial functionality in the hippocampus, the part of the brain involved with learning, memory and emotions. Mitochondrial dysfunction has been consistently reported as an early cause of Alzheimer’s disease. It appears before amyloid-beta plaques can start to accumulate and memory loss begins in Alzheimer’s patients and transgenic mice. In the same study, ANAVEX 2-73 blocked apoptosis (cell death) and oxidative stress, which is believed to prevent the onset of Alzheimer’s disease.
'ANAVEX 2-73 appears to be a valuable drug for protection against mitochondrial damages relative to Alzheimer’s disease physiopathology,” said Tangui Maurice, PhD, CNRS Research Director, Head of Team 2 ‘Endogenous Neuroprotection in Neurodegenerative Diseases’, at the University of Montpellier and INSERM. “The unique target combination of the drug is responsible for its activity on mitochondrial dysfunction which is likely the triggering event of the pathology.'
The new study data was revealed in a presentation at the international conference on Alzheimer’s and Parkinson’s Diseases in Florence, Italy. .... The presentation is titled, “Mitochondrial protection in mouse hippocampus against Aß25-35 toxicity is induced by the novel tetrahydrofuran derivative ANAVEX2-73, a mixed s1 receptor and cholinergic agonist.”
https://www.anavex.com/anavex-2-73-restores-mitochondrial-functionality-blocks-cell-death-and-oxidative-stress-preventing-onset-of-alzheimers-disease/
Baltimore,
Baltimore, perhaps you should not interpret what is said too literally as I am often prone to do. "God's gift to mankind" is another way to convey a person's talent, natural ability, etc. You could apply the saying to athletes, scholars, doctors, lawyers, leaders, and yes, scientists or entrepreneurs. We may all be considered created equal under our constitution, but we are not all equal in athletic performance and other endeavors. You must also remember that Anavex needed someone to pull it out of the dregs and put it on track to pursue a CNS disease treatment that no other company was seeking. I agree with your statement that Anavex may need a different kind of CEO one-day. However, when you sit on the bottom as Anavex was a few years ago, Missling was God's gift to poor little Anavex. Missling was the best talent Anavex could obtain at that time. Anavex has come a long way since Missling came on board. It may need a new CEO one day when it can afford it, but that day is not here, YET!
Bio-
I appreciate and thank you for this post. It tells a beautiful story and provides a perspective for us to understand that seemingly impossible things, like a deaf person composing a symphony, are possible. Missling and Anavex are striving to find treatments for diseases that have no cures. ''It is not the critic who counts..." as Teddy Roosevelt said. It is those like Beethoven that repeatedly strive to accomplish great deeds despite hardships, limitations and handicaps. Anavex, compared to Biogen and other major pharmaceutical companies, is handicapped. Its resources are limited. Yet, it seeks to achieve what significant companies have tried for years and failed to execute, which shows that what Anavex is doing is not easy. Nitpickers and faultfinders, please - give Anavex a break. It's trying, and so far it has not failed. It's just running a little late.
There are many potential reasons for the delay in PDD results, but no one knows why PDD data was not available in September. Potential catalysts, however, lie very shortly, including PDD and very likely Rett. PDD is imminent, but Rett data is also due in this fourth quarter based on the early September U.S. Rett trial completion. So, until I hear otherwise, no news is good news. Everything else is mere speculation. Sooner or later, I look forward to: "The thrill of victory and (or) the agony of defeat" (ABC Sports in the old days).