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Beats sitting on the bid! §
I am most curious as to how 19-144 can be protected apart from the 2-73 pro drug. I found this document, and I swear I will get to reading it(uhg!). This sentence is intriguing:
"Given the
unique pharmacological value that active metabolites may possess,
patent protection for those purified or synthesized in vitro should be
preserved, but for those produced by metabolism should be declined."]
https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&cad=rja&uact=8&ved=0ahUKEwiQjtza6uLNAhWo64MKHXL7B7sQFgghMAA&url=http%3A%2F%2Fdigitalcommons.law.scu.edu%2Fcgi%2Fviewcontent.cgi%3Farticle%3D1565%26context%3Dchtlj&usg=AFQjCNEGUY9HTqvw6ZFHuZ1XlqiBd7Ugkg&sig2=iU6wRRk_vj9cwvJeC4cIDQ
I think the literature shows a definite superiority of the metabolite vs pro drug, but there are aspects such as bio-availability, metabolic necessities, manufacturing considerations, etc that I am sure weigh in, and I know little about.
"ANAVEX19-144: The mean plasma Cmax values of the metabolite
AV19-144 were lower than that of the parent compound and showed a
dose proportional linear increase over the dosage range from 10 to 60
mg.
The mean values of AUClast and AUCinf over the dosage range from 30
to 60 mg were significantly higher than that of AV2-73 and showed a
dose proportional linear increase.
The tmax values of AV19-144 across all dose groups ranged from 2.5 to
3.9 h, with no tendency of dose dependence.
Half-life (T1/2) Pharmacokinetics: T1/2 of AV 19-144 was 28.74 h and
the half-life of AV2-73 was 8.56 h.
Urine-Pharmacokinetics: The absolute cumulative amount excreted in the urine (Ae(0-48)) of the metabolite AV19-144 (sum) was about 15 to
40 times higher than the corresponding values for AV2-73 across all
dose groups tested. A similar ratio was found for AV19-144 vs. AV2-73
with regard to the percentage of the dose administered excreted in
urine (%Ae(0-48))."
http://www.anavex.com/wp-content/uploads/2014-11-14_Poster_Anavex_2-73_Phase_1_Study_CNS_Summit_2014.pdf
Someone said just 5 years of 2-73 AD exclusivity could gross $10B. That could be. Coupled with ODD indications and advanced compound development, as you suggest, and there could be plenty of R&D budget for the rest of the plentiful pipeline. M receptors in cancers is coming up quickly behind the neuro developments. And then, there is that 'CNS-penetrable mono therapy'!
Exciting times aboard the Anavex Express!!!
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Yeah! Coach signs on for another stint. (whew) The compensation is muy generoso...confidence must be high. No milestone hints in the options or the ≤$100K annual cash bonus, based "upon the achievement of certain performance goals". Looking at ~$4M vesting on 2019/07/05...not even a ripple by then.
Very well Dr. I will send another shrubbery Let's get on with those performance goals!
Go team AVXL!!!
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ed- The stock options being cash based is not particularly commoner-friendly and does not help dispel dilutive funding fears.
Anavex has rights to A2-73 so I believe we will foster any of Dr V's IP protections. The 14/395581 app which was a 'side patent' has recently been assigned to Anavex, looking like Anavex is picking up where Vamvakides left off.
I did not get a response from IR about Dr V's well being. I made a small attempt to search GR death records, but did not find a match. All indications lead me to believe he is either diseased or at least not tending personally to his legal affairs.
It is prudent to assume the company will absolutely not pursue commercialization of A2-73 without protection, but it may be a bit of a sacrificial lamb.
I think the PLUS patent will be granted. Just a matter of time.
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I am following the same line of thinking regarding A19-144 and the newer apps. I wonder if/how A19-144 may be patented apart from A2-71. Can the composition and MOU as a mono therapy still be patented? I am guessing no way. My opinion has always been that ever-greening A2-71 via combo was the only way to protect it.
I suspect PCT apps with an officer and attorney listed as inventors, such as WO2016064711, will become the norm now that Anavex is a fully patent law-aware firm.
And then there's A3-71...
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No, you are thinking clearly!
Check out this guy's work:
"Dr. Castellani, Ms. Gupta, Ms. Siedlak, Ms. Harris, Dr. Coller, and Dr. Tabaton report no conflict of interests. Dr. Perry is a consultant for Takeda Pharmaceuticals and Neurotez and owns stock options in Neurotez and Voyager. Dr. Zhu was a consultant for and received grant support from Medivation. Dr. Smith was a consultant for Anavex Life Sciences Corporation, Eisai, Medivation, Neurotez, and Takeda Pharmaceuticals; owned stock options in Aria Neurosciences, Neurotez, Panancea, and Voyager, and had received lecture fees from GSK, Medivation, and Pfizer."
He had just joined the team when he died in 2010.
http://www.case.edu/med/pathology/faculty/smith.html
The MOA of Anavex' compounds tie in with his theories precisely. He would have been a powerful ally.
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Has anyone realized that if a P2/3 were to start in early 2017 following the 6/12 month plan, it could finish before the 104 week P2a extension which states completion in Nov 2018. We could have results from the P2/3 before final P2a data.
What do you think about that?
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ANAVEX 3-71. Don't we have our own conference next year for that...or somethin'?
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Picked back up some .32s but must say they went quick @ .40
Going to come back in next week @ .36 and see how this rolls. Something's up...hopefully Medtronic!
Good for $570K on the catalyst.
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Anavex Presents Data on Neuroprotective Evidence for ANAVEX 2-73, Lead Compound for Alzheimer’s Disease
Hoboken, NJ — July 26, 2011 — Anavex Life Sciences Corp. (“Anavex”) (OTCBB: AVXL) is pleased to provide a summary of its second poster presentation at the Alzheimer’s Association International Conference (AAIC) held in Paris, entitled “Preclinical development of new tetrahydrofuran derivatives targeting the sigma-1 chaperone protein as neuroprotectants in Alzheimer’s disease.”
Neuroprotective, anti-amnesic, anti-depressive and anti-convulsive effects have previously been described with a new class of a wholly owned family of compounds, the aminotetrahydrofurans.
In this study, two of the leads from this family, ANAVEX 2-73 and ANAVEX 1-41, were studied for their anti-amnesic and neuroprotective effects. These compounds are mixed sigma-1 agonists and also have cholinergic effects.
In some respects, the authors claim, these compounds could be compared to donepezil, which is the market leader in Alzheimer’s disease (AD) medication. Donepezil also happens to be a partial sigma-1 agonist as well as exerting its well-known cholinergic effects. In addition, the metabolites for both ANAVEX 2-73 and 1-41 were identified and also studied for any effect.
Utilizing a well-known model that mimics AD by injecting oligomeric amyloid 25-35 fragments into the brain of rodents, the researchers found that:
ANAVEX 2-73 showed prevention and reversal biochemically, histologically and behaviorally.
ANAVEX 2-73 reverses amyloid 25-35-induced amnesia in mice.
ANAVEX 2-73, when administered prior to amyloid 25-35, protects against amyloid 25-35-induced amnesia in mice.
ANAVEX 2-73 protects against amyloid 25-35-induced oxidative stress, measured by lipid peroxidation in hippocampal cells, a key area of the brain associated with learning and memory.
ANAVEX 2-73 protects against amyloid 15-35-induced hippocampal cell loss.
ANAVEX 1-41 also demonstrates similar effects, but is not as selective for sigma receptors as ANAVEX 2-73.
ANAVEX 2-73 is not only active in and of itself, but is also a pro-drug. Its only metabolite, ANAVEX 19-144, is also active in these animal models. The metabolite of ANAVEX 1-41, ANAVEX 2-140, does not display such activity.
ANAVEX 19-144, when administered prior to amyloid 25-35, protects against amyloid 25-35-induced amnesia in mice.
ANAVEX 19-144 protects against amyloid 25-35-induced oxidative stress, measured by lipid peroxidation in hippocampal cells.
“It is hypothesized that cholinomimetic-only compounds would not have as much benefit as the mixed mechanism of the aminotetrahydrofurans, which may be potentiating. Interestingly, the pro drug and active drug effect of ANAVEX 2-73, which has ANAVEX 19-144 ‘embedded’ in it, may offer a longer duration of action,” said Dr. Tangui Maurice, PhD, CNRS Research Director, Team II Endogenous Neuroprotection in Neurodegenerative Diseases INSERM, University of Montpellier, one of the poster authors and a member of the Anavex Scientific Advisory Board. “Histological evidence is powerful visible evidence of neuroprotection and this study also reinforces the anti-amnesic effects already described in this animal model of amyloid toxicity benefit with aminotetrahydrofurans.”
“We are excited to have had this, as well as a poster on ANAVEX 2-73 and a potential dual role in amyloid and tau, accepted at such a prestigious event as AAIC,” said Dr. Cameron Durrant, Executive Chairman of Anavex. “These neuroprotection data may translate into clinical studies as we continue to explore disease-modifying approaches with our novel family of compounds and the lead small molecule, ANAVEX 2-73. It may be potentially beneficial to have a further positive effect on top of ANAVEX 2-73 in the form of its active metabolite ANAVEX 19-144. We eagerly await results from the ANAVEX 2-73 Phase I clinical trial, which is scheduled for completion soon.”
The posters are available on the Anavex web site:
http://www.anavex.com/files/AAIC_Poster_Tangui_July_2011.pdf and
http://www.anavex.com/files/AAIC_Poster_Tangui_tau_July_2011.pdf.
About the Alzheimer’s Association International Conference (AAIC)
AAIC (formerly ICAD, the International Conference on Alzheimer’s Disease) is the largest gathering of researchers, clinicians and other stakeholders in Alzheimer’s disease. This year, the conference drew a record-breaking number of dementia scientists to Paristo share the latest ideas, thoughts and theories in the field. Breaking studies captured global media attention as the world’s leading experts explored innovative ways to further Alzheimer’s research. For more information, please visit www.alz.org/aaic.
About the ANAVEX 2-73 Phase I Clinical Trial
This Phase I clinical trial is a randomized, placebo-controlled study to initially test ANAVEX 2-73 as a single, ascending oral dose in healthy male volunteers between the ages of 18 and 55. The trial seeks to determine the maximum tolerated single dose, safety and pharmacokinetics. The primary objective of this trial is to evaluate the safety and tolerability of ANAVEX 2-73 in humans for the first time. The secondary objective is to determine the pharmacokinetic profile of single oral ascending doses of ANAVEX 2-73.
The Phase I clinical trial is being conducted inGermanyin collaboration with ABX-CRO, a clinical research organization that has conducted several Alzheimer’s disease studies, and the Technical University of Dresden.
About Alzheimer’s Disease
While Alzheimer’s disease is most common in people over the age of 65, it can strike adults of any age irrespective of their gender, background or socioeconomic status. According to the Alzheimer’s Association, an estimated 5.4 million Americans are currently living with Alzheimer’s disease. The number of Americans aged 65 and over with Alzheimer’s is estimated to reach 7.7 million in 2030. This represents a 50 percent increase from the 5.2 million Americans aged 65 and older who are currently affected. The Alzheimer’s Association further projects that the number of Americans aged 65 and older who are affected by Alzheimer’s disease may double or triple to between 11 and 16 million by 2050 unless there are developments to prevent or more effectively treat the disease.
About ANAVEX 2-73
ANAVEX 2-73 is the first of a new class of oral drugs being studied to potentially treat Alzheimer’s through disease modification versus only treating its symptoms.
About Anavex Life Sciences Corp.
Anavex Life Sciences Corp. (www.anavex.com) is a specialty pharmaceutical company engaged in the discovery and development of novel drug candidates for the treatment of neurological diseases and cancer. The Anavex proprietary SIGMACEPTOR™ Discovery Platform involves the rational design of drug compounds targeted to specific receptors involved in the modulation of multiple cellular biochemical signaling pathways.
The SIGMACEPTOR™-N program involves the development of novel drug candidates that target neurological and neurodegenerative diseases (Alzheimer’s disease, epilepsy, depression, pain). The company’s lead drug candidates exhibit high affinity for sigma receptors, which have been extensively documented as potentially valuable drug targets and have demonstrated anti-amnesic and neuroprotective properties. A portfolio of back-up compounds to ANAVEX 2-73 are also in development.
Only if they hit those sweet offers. If they do someone is desperate for shares.
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Getting ready to wipe it out to 6.15...sweet offers §
Excellent! That will do better than a response. Publication should reveal Dr Thomas's fingerprint. Can't wait!
Thank you, as always.
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Must be 2-3 years already. §
IR depts can be like that. They get lots of questions every day that they cannot answer. I suppose it is not really the company's duty to educate on the details. They provide the meat of the matter in PRs:
http://www.anavex.com/?news=anavex-receives-notice-of-allowance-for-u-s-patent-application-related-to-anavex-2-73
All the answers are available at the site http://www.uspto.gov/.
All I know for sure is Anavex will not persue commercialization without IP protection in place.
Here is my list.
Anavex IP Portfolio:
GRANTED PATENT:
U.S. Pat. No. 8,673,931
“Bicyclic Heterocyclic Spiro Compounds” (ANAVEX 3-71, previously AF710B, composition)
U.S. Pat. No. 9,180,106
"Sigma receptors ligands with anti-apoptotic and/or pro-apoptotic properties, over cellular mechanisms, exhibiting prototypical cytoprotective and also anti-cancer activity" (ANAVEX 2-73 Method of use, cancer)
PATENT PENDING:
U.S. Pat. App. No. 14/395581
"OPTIMIZATION AND THERAPEUTIC VALORIZATION OF THE SYMPTOMATIC TREATMENT OF ALZHEIMER'S DISEASE WITH RIVASTIGMINE, GALANTAMINE OR DONEPEZIL, BY SELECTED AMINOTETRAHYDROFURANS ACTING AS MIXED SIGMA-1 / MUSCARINIC LIGANDS"
U.S. Pat. App. No.13/940,352
“Anavex2-73 and Certain Anticholinesterase Inhibitors Composition and Method for Neuroprotection”
U.S. Pub. No. 20140296211 (ANAVEX 2-73 Method of use, Alzheimer's Disease)
WIPO Pat App No.WO2016064711
U.S. Prov. Pat. App. No.62/065,833
International Application No.: PCT/US2015/056172
“A19-144, A2-73 and Certain Anticholinesterase Inhibitor Compositions and Method for Anti-Seizure Therapy”
Provisional (ANAVEX 2-73 Method of use, epilepsy)
UNPUBLISHED:
U.S. Pat. App. No. 13/777,471
“Sigma-Receptor Ligands with Anti-Apoptotic and/or Pro-Apoptotic Properties Over Cellular Biochemical Mechanisms, with Neuroprotective, Anti-Cancer, Anti-Metastatic and Anti-(Chronic) Inflammatory Action”
Not yet published
Identical to parent U.S. Pat App. No. 12/522,761 / U.S. Pub. No. 20100069484 (ANAVEX 2-73 Composition & Method of use, cancer?)
Dr V's apps"
14/865862 - PROTOTYPICAL BRAIN PROTECTIVE ACTIVITY OF TETRAHYDRO-N-METHYL-2,2-DIPHENYL-3-FURANOMETHANAMINE (AE37MET)
14/406271 - 3,3-DIPHENYL-N-(1-PHENYLETHYL) PROPAN-1-AMINE: AS A NEW SELECTIVE LIGAND OF THE SIGMA-1 RECEPTORS, WITH ANTI-APOPTOTIC (CYTOPROTECTIVE) PROPERTIES AND PROTOTYPICAL ANTICANCER ACTIVITY
The 13/777,471 (it won't come up in search) may be the clincher, IMO. Fear not! Patent discussions are sure to continue here, so stay tuned.
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That is why we have patent attorneys and they have law degrees. Learning it all does not end up giving you any advantage, anyway.
The more you understand, the harder it is to explain. I would say orveko_inc has the most informative posts on the subject.
Be careful in speculating on patent matters, though, if not an expert.
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I'll bet we do. Listed at the last possible minute, of course! §
A patented invention can include patented parts. Commercial use would require gaining rights to use the patented parts.
Generally, it is safe to assume the company will secure the necessary IP protection before attempting to commercialize. Some of us just like to follow the process. Official PR by the company will be the best source of info.
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Anavex AAIC 2016 Presentations Schedule:
Go to:
https://ep70.eventpilotadmin.com/web/planner.php?id=AAIC16lite
Enter Anavex in the search box. The Sun presentation will come up in the List column. Notice at the top of the List column are dates. Click the Wed 27 and you will see the other presentation. Click either to make it come up in the Details column and then click on Missling's name. Both will appear in the details column.
I'll sticky this.
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I think you pegged it! The oral title will give it all away, so that will unveil last.
NO! It is a different entity, MediSynergics, LLC. They are trying to patent a broader-type PLUS invention. 2-73 is listed among compounds that, when combined with a cholinesterase inhibitor (ie donepezil) could be used to treat AD. It got a double patenting rejection, meaning they are essentially trying to patent two inventions with one app. Others might elucidate more.
Big news! We are getting full 26 week data at AAIC. WOOOPIE!
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I have also been following this patent, 14/854928 as a possible endangerment to the IP. Today it received a NFR.
Very interesting day!
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OK, that makes sense.
New entry on patent app 14/395,581
06-29-2016 CTMS Miscellaneous Action with SSP PROSECUTION 2
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Nice! Some long-awaited validation for 'ol Cbd? Notice it's the THC they say does the job. No wonder Grandma never forgets where she put the pipe!
TomP1: That comment "cellular removal of amyloid beta" is misleading. The info could indicate a reduction in the production of AB via sigma 1 interaction, just as well:
"The researchers found that high levels of amyloid beta were associated with cellular inflammation and higher rates of neuron death. They demonstrated that exposing the cells to THC reduced amyloid beta protein levels and eliminated the inflammatory response from the nerve cells caused by the protein, thereby allowing the nerve cells to survive."
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Maybe the posters will do all the talking, and he gets to just chill and answer questions.
BSN: It's in the convention hall and both are listed as poster sessions. Oral presentations are in the numbered meeting rooms, ie Room:106.
Both sessions are 1 hour:
Main Session - [Posters Sun]
Presentation
Therapeutics: Clinical
New Exploratory Alzheimer’s Drug Anavex 2-73: Dose Dependent Clinical Cognitive Improvement Observed in Mini Mental State Examination (MMSE) and Other Cognitive Markers in a Phase 2a Study in Mild-to-Moderate Alzheimer’s Patients
Metro Toronto Convention Centre Room: Hall D/E
P1-046(space designation)
9:30am - 10:30am
Sun, Jul 24
Main Session - Developing Topics: Poster Presentation
Presentation
Dementia Care Practice
Safety and Efficacy 31 Week Data of Anavex 2-73 in a Phase 2a Study in Mild-Moderate Alzheimer’s Disease Patients
Metro Toronto Convention Centre Room: Hall D/E
1:00pm - 2:00pm
Wed, Jul 27
Week 26 is the last blood test for PK. Could that mean full PK/PD results?
Both presentations are poster and in same Room: Hall D/E. Sun is short overview of A2-73, then Wed a full hour in same space for update?
31 week data....hmmmm. There moving on this trial...gonna 'get'er done'! It's going to be completed, with results by Christmas!
Smells like partner itching to get a P3 going, to me!
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Click Missling's name and both sessions will come up. But wasn't Macfarlane listed for the Sun session???
Re: "1 hour session" Also starts 4:00ET
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Safety and Efficacy 31 Week Data of Anavex 2-73 in a Phase 2a Study in Mild-Moderate Alzheimer’s Disease Patients
Metro Toronto Convention Centre Room: Hall D/E
1:00pm - 2:00pm
Wed, Jul 27
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Did you guys ever figure out the dosing protocol? Are the PART B participants randomized/assigned to either 30 or 50mg? Are they going to report dose-dependent findings based on a difference between 30 and 50mg arms? We know there were 27/32 participants stabilized on donepezil, but do not know who is getting 30 vs 50mg, correct?
IV doses were 3 & 5mg, oral 30 & 50mg
2 fluffy news. 4 milly hits the bid. Sure now? §
Market cap is only $170M. Results will likely support further development, once again, at the least. If, once again, there is no miracle cure the stock may fall back. Probably not to the <$1 level, as AVXL is not a one hit wonder and this is not a pivotal stage (barring complete failure).
Results could be announced at market close on Friday, giving the weekend for digestion. If the results presented do show strong signs of disease modification the stock could open on Monday at...?
Might be better to hold through the weekend. Or, have boatloads of cash ready
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If bapineuzumab turned into 'bad-news-zumab', solanezumab will be known as 'so-long-zumab'!
http://cen.acs.org/articles/93/i22/Next-Chapter-Treating-Alzheimers.html
Anvex has the MOA, the safety profile and the trial design. Thanks for the reads...nice work 12s
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^^^BUMP^^^ and attach: What is Miscellaneous Action with SSP? Re: 14/395,581
(I think, essentially, yes gburgin)
We also have an advisory action on 13/940,352. I will leave it up to the experts to explain.
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Jun 27, 2016 at 6:05PM - "Later this month, Anavex will present data at a scientific conference showing 2-73's potential in anxiety, epilepsy, infantile spasms, Rett syndrome, Fragile X syndrome, and autism-related disorders."
Staler than last weeks bananna bread...
6¢ spread on a 35MM float with 140 market makers sitting. Unreal!
Still plenty of good gross manipulation basparks!
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20K @ 4.76 to open. Interesting. §
Marinus Fragile X (FXS) study results:
Marinus Pharma (MRNS) Says Primary Endpoint Not Met in Ganaxolone Phase 2 Exploratory Study
Ganaxolone is a CNS-selective GABAA modulator. Like other anti-epileptics it's MOA is to inhibit neurotransmission of electrical impulses?
How does Anavex's MOA, offering 'protection from tonic seizures', differ?
"In PTZ-induced convulsions it was further observed that ANAVEX 19-144 is able to significantly prolong life during a seizure. Control-group animals died after three minutes and two seconds, while animals that received ANAVEX 19-144 were still alive after 50 minutes."
"The neuroprotective properties of ANAVEX 2-73 and ANAVEX 19-144 have been observed at very low doses (0.1-0.3 mg/kg). These doses are far below the levels that induce cholinergic- or sigma 1 receptor-related side effects, verifying the anticipated enhanced safety profile of the ANAVEX epilepsy drug candidates."
http://www.anavex.com/?news=anavex-advances-drug-candidates-for-treatment-of-epilepsy
Anavex knows the drug will work in a low-dose daily chronic formula. Getting into patients for an extended period of time is all that is required to show efficacy. We are less than five months from having 32 AD patients at one year.
Dr Jacqueline French sits on the SAB.
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@adamfeuerstein Got a good beer to go with crow pie?
"it's going to take a medical miracle -- a drug or technology that's a true scientific game changer -- to convince investors biotech stocks are the place to park new money."
https://www.thestreet.com/story/13621468/1/a-biotech-stock-turnaround-requires-an-alzheimer-s-drug-miracle.html
Go AVXL!
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The science appears so...
http://www.nature.com/articles/srep15390
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