Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Here is a nice overview of the publication process at one medical journal. This process can take well over the arbitrary 3-month deadline you set.
https://www.nejm.org/media-center/publication-process
Publication Process
The New England Journal of Medicine (NEJM) employs a rigorous peer review and editing process to evaluate all manuscripts for scientific accuracy, novelty, and importance. This painstaking publication process has been tested over many decades and is a major reason for the Journal’s reputation as the world’s leading medical journal.
NEJM receives over 4,500 original research submissions each year — more than a dozen each business day — with over half coming from outside the U.S.
At least five experts review and edit each Original Article or Special Article manuscript published by NEJM. Of thousands of research reports submitted each year, about 5% are eventually published by NEJM.
The peer review process works to improve research reports while preventing overstated results from reaching physicians and the public. Each published NEJM manuscript benefits from hundreds of hours of work by editors, statistical experts, manuscript editors, illustrators, proofreaders, and production personnel, who work to ensure that every paper meets exacting standards.
About the Editors
The NEJM core editorial team comprises nine physician editors and one Ph.D. geneticist.
The Path of a Research Manuscript
NEJM Executive Deputy Editor Mary Beth Hamel, M.D., M.P.H., reviews each research manuscript submission and determines whether it meets essential NEJM criteria to warrant further consideration and peer review. About 10% of submitted papers are declined at this stage without further editorial consideration.
A paper passing Dr. Hamel’s initial review moves to an appropriate associate editor, who determines whether it meets fundamental criteria for:
Quality
Novelty
Potential clinical impact
If so, the associate editor sends the manuscript to at least two peer reviewers.
Should an associate editor wish to decline a paper without peer review, it goes first to a deputy editor for a second opinion; if the deputy editor disagrees with the associate editor, the paper will be sent on for peer review.
Peer Review
NEJM maintains a database of more than 30,000 peer reviewers worldwide in all areas of medicine. In almost all cases, two peer reviewers evaluate each submission within one to two weeks and submit written reports to the NEJM editors.
During peer review, all manuscripts are considered privileged communications. Without prior approval from the NEJM editorial office, peer reviewers are expressly prohibited from:
Copying manuscripts
Sharing with others
Discussing their personal evaluations or recommendations
NEJM also instructs peer reviewers to:
Report immediately any possible personal, professional, or financial conflicts of interest with authors or related to a paper’s topic; where conflicts arise, NEJM editors find substitute reviewers.
Destroy manuscript copies once reviews are complete.
Full Editorial Team Review and Statistical Review
Using peer reviews and their own judgments, NEJM associate editors then decide whether to decline a manuscript (a decision which must be seconded by a deputy editor) or to bring it to a weekly editorial meeting attended by all NEJM deputy editors, associate editors, and statistical consultants for discussion and debate.
Following discussion at a weekly editorial meeting, a paper will be assigned one of three statuses:
Rejection: Publication is declined; reviewers’ comments are provided to authors.
Provisional Rejection: The manuscript is not suitable for publication unless the authors conduct further research or collect additional data.
Revision: NEJM has interest in the paper, but the manuscript is not acceptable in its current form and must be revised before further consideration for publication. If a manuscript is moved to Revision status, the paper will be sent on for statistical review — an additional, rigorous review step. Most research manuscripts published by NEJM undergo at least one statistical review by one of five statistical consultants prior to acceptance.
More on the Revision Process
The associate editor communicates a paper’s status to its authors in a letter detailing questions raised in the review process and, where applicable, recommending revisions needed to meet NEJM standards for publication. Authors respond to the associate editor with a revised manuscript and letter detailing their changes.
When authors resubmit a revised manuscript, the associate editor again reviews it and decides whether further peer or statistical review is needed and often brings the paper back to a weekly editorial meeting for further discussion.
If additional outside review is not needed, the manuscript will be sent to a deputy editor for additional editing and revisions in collaboration with the associate editor and its authors.
Final Review & Acceptance for Publication
The NEJM Editor-in-Chief reviews all final (revised) submissions and may raise further questions. The Editor-in-Chief is the only person who can officially accept a paper for publication. Following Dr. Drazen’s formal acceptance for publication, a paper will then move through rigorous processes for manuscript editing, production, illustration, design, and publication.
The lower the p-value the more likely the observed difference is not due to chance. A low p-value is a good thing.
Educate yourself:
https://www.dummies.com/education/math/statistics/what-a-p-value-tells-you-about-statistical-data/
Here's your answer right from the presentation that was posted several times today.
https://www.anavex.com/wp-content/uploads/2019/07/Anavex-Microbiota-Presentation-AAIC-July-2019-1.pdf
Slide 8
"Out of 21 patients in the extension study, microbiota analysis was performed on 16 patients who consented to stool sampling (1 patient withdrew from study, 4 patients did not consent."
So there are 20 patients remaining in the extension study. Considering the demographic they belong to, I'd say that's astounding.
Assuming you'll even bother to click on the link this time, while you're there, check out the p-value between the low blood concentration group and the high concentration group. The larger the sample size the easier it is to get a p-value that indicates the difference between the groups is unlikely to be due to chance. The smaller the sample size the harder it is to get a p-value that indicates the difference between the groups is unlikely to be due to chance.
Slide 8 has been disclosed before. How can anyone seeing that slide not want to be in this stock? People keep saying the results of the extension study don't count, because there is no placebo group. That's nonsense. The low blood concentration group is the placebo. It's better than placebo. It's an objective measure that the patient/care giver can know nothing about. Slide 8 shows that the blood concentration of A273 correlates positively with improved daily living scores. Out to 148 weeks!
I think it was this one. Used a strawberry flavored solution, just like the article mentioned.
https://clinicaltrials.gov/ct2/show/NCT01703533?term=birmingham&cond=rett&rank=6
That's 3.7M shares held long by index funds
3.1M shares at the close. No change in price.
30 ml liquid dose
"She would eventually calm, and we would leave with our next cooler of mystery dose, strawberry flavored, “drug” bottles. We’d stop in Huntsville and trade Papa Coach for Andi Mac before making our way back to Nashville, where we’d continue to administer 30 mg of liquid each morning, taking copious notes of anything and everything we and others noted about Blake while taking “the drug”."
"After the first dose, I knew we had something. She was calm. She was clear. She was “ON”. There was a sparkle in her eyes. It’s hard to explain, but her eyes always tell all. They were different, in a good way. She felt better. Over the coming weeks, there were fewer meltdowns, more smiles, less tension, more sleep. The renewing kind. “She just seems to feel good.” is what I wrote in our binder. She moves better, she eats better, she smiles better (nothing earth shattering, just better)."
Mother's UAB Rett trial story from June 2019. Is this Anavaex??
https://www.girlpower2cure.org/our-cause/blog/the-summer-of-hope-and-adele/
"Companies that are added to, deleted from or simply remain in one of the Russell 3000 indexes should expect to see higher than normal volumes this June 28. This is because index funds conform to new index weights that are effective after the close on that day. Most of the related trading will take place at the end of the day. For most companies, it will be a pretty "normal" day until about 4:00 p.m. EDT. Then, many issuers will see block trades in their stock at the bell and afterwards. It can seem very unusual if you are not expecting it."
https://www.nasdaq.com/article/2019-russell-reconstitution-and-potential-impact-to-your-stock-cm1167905
AVXL 90% bullish. Next target 3.76:
https://www.stockconsultant.com/consultnow/basicplus.cgi?symbol=AVXL
"Russell Rebalancing Brings Frenzy to a Summer Friday"
https://www.wsj.com/articles/russell-rebalancing-brings-frenzy-to-a-summer-friday-11561636806
Hope this is true for AVXL
What's going on with all the one share trades today?
Agree about the timing of the journal publication. After the manuscript is submitted for review, the authors have very little control over the timing of the events that follow, and the journal publishes the article as soon as all of its boxes have been checked. In my experience, this process typically takes between about 6 weeks to about 6 months. Since this is the publication of the results of a clinical trial, I doubt the peer review portion (which often takes the longest chunk of time) will take very long.
I think he's just being very, very conservative. There is a similar analysis on that same page for Neurotrope.
So he's basically saying, even with only 10% market penetration, and even using it only in mild AD, and assuming a protracted adoption by the market, it's still a $1.5B/year drug. But if it works, the market will adopt way faster than that, with way more than 10% penetration into the mild AD market, with there being no competitor molecules. And it'll be prescribed for those with more than mild AD. And that doesn't take into account PDD and other forms of dementia which will also generate scripts.
"Mr. Zhong received his Ph.D. in neuroscience and molecular biology from the Rockefeller University"
Mr. Zhong also covers:
bluebird bio, Inc. (BLUE)
Global Blood Therapeutics, Inc. (GBT)
Nightstar Therapeutics plc (NITE)
Sarepta Therapeutics, Inc. (SRPT)
Selecta Biosciences, Inc. (SELB)
Summit Therapeutics plc (SMMT)
uniQure N.V (QURE)
https://247wallst.com/healthcare-business/2019/06/18/two-very-speculative-biotechs-with-promising-alzheimers-treatment-hopefuls/
"ANAVEX 2-73 modulates muscarinic acetylcholine receptors (mAChRs) in addition to S1R. Activation of both receptors produces synergistic effects and leads to further enhanced neuroprotection. A high concentration demonstrated statistically significant separation in clinical benefit from a low concentration in a Phase IIa study after only five weeks of treatment. The treatment period was extended upon patient request and efficacy was maintained after 148 weeks of treatment… We project ANAVEX 2-73 use only in patients with mild AD and forecast peak U.S. market penetration to be below 10%. We reach U.S. sales of over $1.5 billion in 2032, which we believe should be conservative when compared to historical sales of FDA-approved treatments for AD."
Sorry, my last post was for PDD. This is the one for ALZ...
https://clinicaltrials.gov/ct2/show/NCT03790709?term=anavex&rank=5
Primary Outcome Measures :
ADAS-Cog (Alzheimer Disease Assessment Scale-Cognition) [ Time Frame: 48 weeks ]
Change from baseline to week 48 in cognition according to the Alzheimer Disease Assessment Scale-Cognition (ADAS-Cog) compared to placebo
ADCS-ADL (Activities of Daily Living) [ Time Frame: 48 weeks ]
Changes from baseline to week 48 in ability to perform daily activities according to the Activities of Daily Living Scale (ADCS-ADL) compared to placebo
Secondary Outcome Measures :
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 [ Time Frame: 48 weeks ]
Assess the safety and tolerability of ANAVEX2-73 compared to placebo
CDR-SB (Clinical Dementia Rating Scale Sum of Boxes) [ Time Frame: 48 weeks ]
Change from baseline to week 48 on Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) compared to placebo
RSCAQ sleep score [ Time Frame: Weeks 0, 4, 12, 24, 36, and 48 ]
To evaluate whether ANAVEX2-73 improves sleep continuity as assessed on a serial basis (weeks 0, 4, 12, 24, 36, and 48) with a questionnaire that assess reported sleep continuity (RSCAQ)
That was hard to find....
https://clinicaltrials.gov/ct2/show/NCT03774459?term=anavex&rank=2
Primary Outcome Measures :
Cognitive Drug Research (CDR) Computerized Assessment System Continuity of Attention [ Time Frame: 14 weeks ]
Change from Baseline to End of Treatment in Continuity of Attention as measured by Cognitive Drug Research (CDR) Computerized Assessment System Continuity of Attention test
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 14 weeks ]
Assess the safety and tolerability of ANAVEX2-73 compared to placebo
Secondary Outcome Measures :
MDS-UPDRS Part III Total Score (Motor Scores) [ Time Frame: 14 weeks ]
Change from baseline to End of Treatment as measured by MDS-UPDRS Part III Total Score (Motor Scores)
SDS-CL-25 [ Time Frame: 14 weeks ]
Incidence of sleep disorders symptoms (SDS-CL-25)
"The trial blinding must be maintained until all data sets are locked. Until then investigators, site staff, sponsors and most other participants must not be aware of the treatment patients are receiving. However, there are certain functions like clinical supply or safety that require access to unblinded data. Having detailed standard operating procedures (SOPs) in place is imperative. This ensures a standardized, documented approach on access to unblinding information is appropriately restricted to authorized individuals throughout the lifecycle of the study."
https://www.clinicalinformaticsnews.com/2018/06/08/avoid-unintentional-unblinding-in-clinical-trials.aspx
Rett is triple and Alz and PDD are quadruple.
see https://clinicaltrials.gov/ct2/results?cond=&term=anavex&cntry=&state=&city=&dist=
Rett
Masking: Triple (Participant, Care Provider, Investigator)
Alz
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
PDD
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Well their trial protocols say otherwise.
https://en.wikipedia.org/wiki/Blinded_experiment#Unblinding
Actually, all the data is 'locked away' until every patient has finished being dosed. Otherwise they'd be breaking the blinding.
From clinicaltrials.gov
Rett
Masking: Triple (Participant, Care Provider, Investigator)
Alz
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
PDD
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Not terrible. Not a surprise.
From the agreement:
"The table above assumes for illustrative purposes that an aggregate of 6,711,410 shares of our common stock are sold pursuant to this prospectus supplement and the accompanying prospectus at a price of $2.98 per share, the last reported sale price of our common stock on the Nasdaq Capital Market on June 7, 2019, for aggregate gross proceeds of $20 million"
Price is now 3.25, so even less dilution as compared to June 7th.
I don't see anything like that on my TD feed and total volume right now is 217k.
"Sigma 1 has been studied and reported on in the scientific literature for over 40 years, yet no drug targeting Sigma 1 has shown definitive clinical benefit or been approved by a regulator."
Except for these sigma 1 receptor modulators, which were each approved by a regulator:
Agonists:
Fluvoxamine
Citalopram
Amitriptyline
Dextromethorphan
Antagonists:
Sertraline
cmissling@anavexcorp.com
Found it on this abstract:
https://aanddjournal.net/article/S1552-5260(15)02833-2/pdf
And on this SEC filing:
https://www.sec.gov/Archives/edgar/data/1314052/000161577415003021/s102057_exhibit10-1.htm
And on this program:
https://www.alz.org/aaic/downloads2018/Wed-am-briefing-developing-topics.pdf
And on this employment agreement:
https://www.lawinsider.com/contracts/25xBJLNFMSewfjr8c8Yc5W/anavex-life-sciences-corp/employment-agreement/2015-12-29
Maybe he's just hiding from people who can't google.
Spanish language publication dated May 2019
Anavex on page 6.
I can't read spanish.
https://issuu.com/parkinsonmadrid/docs/revista_70_issue/1?ff
Cup and handle
From Wikipedia, the free encyclopedia
In the domain of technical analysis of market prices, a cup and handle or cup with handle formation is a chart pattern consisting of a drop in the price and a rise back up to the original value, followed a smaller drop and a rise past the previous peak.[1] It is interpreted as an indication of bullish sentiment in the market and possible further price increases.[2]
The cup part of the pattern should be fairly shallow, with a rounded or flat "bottom" (not a V-shaped one), and ideally reach to the same price at the upper end of both sides. The drop of the handle part should retrace about 30% to 50% of the rise at the end of the cup. For stock prices, the pattern may span from a few weeks to a few years; but commonly the cup lasts from 1 to 6 months, while the handle should only last for 1 to 4 weeks.[3]
cup (3/26-5/22) and handle
That's the net present value of A2-73 in Alzheimer's, not all of AVXL. The S&P article doesn't consider any other molecule or indication. The NPV's of those other molecules and indications can be added to the $750M to get to the NPV of AVXL.
https://fintel.io/so/us/avxl
Citigroup increased their position
The placebo group will get the active. It would be unethical, and not permitted, to do it any other way.
Not necessarily:
https://medlineplus.gov/ency/article/001536.htm
"Outlook (Prognosis)
The disease slowly gets worse until the teen years. Then, symptoms may improve. For example, seizures or breathing problems tend to lessen in the late teens.
...
Life expectancies are not well studied, although survival at least until the mid-20s is likely. The average life expectancy for girls may be mid-40s. Death is often related to seizure, aspiration pneumonia, malnutrition, and accidents."
I believe it means they have the goods. If they didn't, they'd have an incentive to pump up the price as much as possible right now to try to collect as much cash as they could before they're found out. Instead, they're not pumping at all, letting anyone in the know get in now while it's still incredibly affordable.
This just played on NPRs "All Things Considered"
https://www.npr.org/sections/health-shots/2019/05/03/718754791/after-a-big-failure-scientists-and-patients-hunt-for-a-new-type-of-alzheimers-dr
The only alternative they really talked about was Neurotrope, and they didn't mention sigma receptor as a target.
Anyone want to send Jon Hamilton a note about Anavex? Maybe share some of the Australian patient videos?
"Although including a placebo group in dose-response studies is desirable, it is not theoretically necessary in all cases; a positive slope, even without a placebo group, provides evidence of a drug effect."
See page 9:
https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM073115.pdf
45,000 were bought, so 45,000 were sold, right?