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Market value suppression of a publicly-traded company is frowned upon, if you know what I mean.
Either provide the fact-based bad news regarding Anavex or its trials, or published contradicting evidence countering our MOA’s effectiveness, else you effectively prove my thesis correct.
Having listened to the 10/4/19 presentation again and now internalizing it with the backdrop of: knowing the Company has considerable OPEN LABEL uncontrolled data at their fingertips for 3 different CNS disease indications/patients using our 2-73 compound at varying dose levels and corresponding data on safety/efficacy/behavior over many months/years, I would characterize my current optimism level as ever-increasing.
EOM
Reminder of Dr M’s comments at the 5:31 mark of the 10/4/19 Cantor Fitzgerald investor presentation: “so we now are about to find treatments for these indications, which we call neurodevelopmental neurodegenerative diseases” (speaking of AD PDD RS). ... could be a language translation but it sounded quite confident IMO
And at 5:47 of presentation: “And pleased to share that we are expecting data on the first study soon, we have already the first 6 patients’ data which we will see in a minute” (in regard to Rett studies)
I’m inclined to believe that the 21 patients (over 18 years old) in the US RS trial are already dosing and readouts expected soon, otherwise I’m not sure why he’d say what he said at the 5:47 mark. Why say that if you were still looking for the first 21 patients? Would seem odd if so.
Just random thoughts on a slow Friday afternoon.
It would appear logical to me to
expect some news regarding either the discussions with the fda/ema mentioned 45 days ago, or applicability of the AU provisional approval new rules to our fact pattern, or enrollment figures in our 7 or 8 current trials, or the oft-referred-to 2019 peer reviewed pub regarding our Alzheimer’s participants, or possibly a 3-71 trial initiation, etc.
It does seem reasonable to assume that those projects/updates are forthcoming.
It’s gamesmanship: money, power and influence. How far will those 3 elements take the large pharmaceutical companies on the path to market.
The same large pharmas with connections and lobbyists embedded deep within Congress, decision making bodies and the media.
It’s the golden rule in financial markets. He with the gold makes the rules.
The patients’ well being and best interests come later.
Yes basparks, Acadia & neuren are targeting Rett symptoms, and only showed statistically significant improvement over placebo at the highest 200mg/day dosage subset, and there were also side effects to contend with.
https://journals.lww.com/neurotodayonline/Fulltext/2019/04040/In_a_Randomized_Trial,_Trofinetide_Ameliorates.4.aspx
“The most common side effects in all treatment groups were moderate diarrhea, mild vomiting, upper respiratory tract infection, and pyrexia. Only one participant (200 mg/kg group) was withdrawn from the study at her parents' request, due to worsening mild gastroesophageal reflux, moderate diarrhea, and mild vomiting, which later resolved uneventfully.
There was statistically significant evidence of clinical improvement (p<0.05) for the 200 mg/kg BID dose over placebo in three core measures: Rett Syndrome Behavior Questionnaire (total score, core neurobehavioral symptoms, p=0.042), Clinical Global Impression of Improvement (overall clinical status, p=0.029), and Domain Specific Concerns Visual Analog Scale (most concerning aspects identified by clinicians, p=0.025).
Some of the efficacy measures indicated improvements across a range of symptom domains and individual symptoms, such as repetitive behaviors, breathing problems, mood abnormalities/disruptive behavior, ambulation impairment, and seizures. This multiple-domain effect was in accordance with the findings of the adolescent and adult Rett-001 trial, which enrolled participants ages 16 to 45.“
We are simply applying the verbiage of the new AU provisional approval process to our current set of Anavex facts.
It does not require a phase 3 trial.
Have you read our Australian PI’s comments regarding the effects of 2-73 on our AD patients?
The company presentations and Ariana’s analysis have indicated same.
We’ve now 4 years of Australian AD open label extension and dosing/response data in our Company’s possession.
Check out the new mid-2019 AU process in the links below as well.
“For many participants of the previous trial, their results at 12 months showed their cognitive status remained largely unchanged, he said.
Professor Macfarlane said some participants also regained functions previously lost, such as the ability to paint and play the piano while a person who re-sat the driving exam successfully regained their licence.
At the end of the study, participants requested an extension to continue to have access to the drug, which was granted.”
https://www.australianageingagenda.com.au/2018/07/13/next-stage-of-national-drug-trial-underway/
https://www.dementiacentre.com/search-testing/143-meet-stephen-macfarlane-head-of-clinical-services
https://www.tga.gov.au/provisional-approval-pathway-prescription-medicines
“As part of the Government's response to the Review of Medicines and Medical Devices Regulation (MMDR review), we are implementing a pathway for the provisional registration of prescription medicines. Approval through the provisional pathway will be on the basis of preliminary clinical data where there is the potential for a substantial benefit to Australian patients.”
And
“The eligibility criteria are:
New prescription medicine or new indications medicine
For treating a serious condition
Favourable comparison against existing therapeutic goods
Major therapeutic advance
Evidence of a plan to submit comprehensive clinical data.”
https://www.tga.gov.au/first-provisional-approval
After 4 years of waiting and observing here, I think our binary moment is near.
Still have questions and doubts about how the deep & pervasive BP ties and influence within our governmental bodies and organizations will ultimately affect our path to market.
But the 2-73 advantages over current SOC appear obvious to me and would as well to a 3rd grader.
Recently diagnosed patients literally have nothing currently.
Regulators should take decisive action in the coming few months.
Allow the S1R to be agonized and let the body heal itself naturally.
Comparison of side effects:
ANAVEX 2-73 (Blarcamesine)
“Tolerability: Maximum tolerated dose (MTD) of ANAVEX 2-73 was defined as 55mg. Observed adverse events at doses above the MTD included dizziness and headache, which were moderate in severity and reversible. These side effects are often seen with drugs that target CNS conditions, including Alzheimer's disease.”
ARICEPT (Donepezil) current SOC
More common side effects:
The more common side effects that can occur with donepezil include:
nausea
diarrhea
not sleeping well
vomiting
muscle cramps
tiredness
not wanting to eat or having a poor appetite
bruising
weight loss
Serious side effects:
Slow heart rate and fainting
Stomach ulcers and bleeding, symptoms can include:
heartburn
stomach pain that won’t go away
nausea or vomiting
blood in your vomit, or dark-colored vomit that looks like coffee grounds
bowel movements that look like black tar
Worsening of lung problems in people with asthma or other lung diseases
Seizures
Trouble urinating
ADUCANUMAB
Side effects included headache, diarrhea, and dizziness. They were mild or moderate, some possibly related to the study drug but not to the dose.
“ the higher the dose of aducanumab in the trial, the more signs of brain swelling and hemorrhaging—which show up as ARIA-E, or amyloid-related imaging abnormalities-edema.
That Phase I trial started with 165 participants, 32 of which received the higher dose. Of those, 15 developed ARIA-E, and 10 patients dropped out of the study because of adverse events, a troubling sign.”
Good reminder regarding the new AU provisional approval process started in mid 2019.
If the AU regulators consult with our trial principal investigator and head of clinical services at HammondCare in Australia, Prof Stephen Macfarlane, I wonder what his recommendation might be?
“For many participants of the previous trial, their results at 12 months showed their cognitive status remained largely unchanged, he said.
Professor Macfarlane said some participants also regained functions previously lost, such as the ability to paint and play the piano while a person who re-sat the driving exam successfully regained their licence.
At the end of the study, participants requested an extension to continue to have access to the drug, which was granted.”
https://www.australianageingagenda.com.au/2018/07/13/next-stage-of-national-drug-trial-underway/
https://www.dementiacentre.com/search-testing/143-meet-stephen-macfarlane-head-of-clinical-services
https://www.tga.gov.au/provisional-approval-pathway-prescription-medicines
“As part of the Government's response to the Review of Medicines and Medical Devices Regulation (MMDR review), we are implementing a pathway for the provisional registration of prescription medicines. Approval through the provisional pathway will be on the basis of preliminary clinical data where there is the potential for a substantial benefit to Australian patients.”
And
“The eligibility criteria are:
New prescription medicine or new indications medicine
For treating a serious condition
Favourable comparison against existing therapeutic goods
Major therapeutic advance
Evidence of a plan to submit comprehensive clinical data.”
https://www.tga.gov.au/first-provisional-approval
Important point yes, xena & jwc3, the FDA’s chosen firm (Ariana) “to improve the analysis of genomic data in support of personalised medicine” had this to say about Anavex’s dose/concentration/response relationships in our ph2a Alzheimer’s Disease trial over 57 weeks:
Cited from the October 2017 PK/PD presentation
http://www.anavex.com/my_uploads/ANAVEX2-73-PKPD-Phase-2a-2017.pdf
· Slide 3: in depth analysis using Ariana technology demonstrates “relationship between Anavex2-73 measured exposure and dose (PK) are consistent across study periods”
Slide 3: in depth analysis using Ariana technology demonstrates “strong drug concentration / response relationship revealed for key Alzheimer’s disease trial endpoints cognition and function, MMSE and ADCS-ADL (PK/PD). This relationship is consistent across multiple time periods”
· Slide 3: “same applies for the brain activity biomarker ERP (PK/PD)”
· Slide 6: across the 5 weeks and the 52 weeks their slides say that the achieved (check mark) “dose-effect relationship”
Slide 12: Ariana indicates “confirmed reliable inter-individual variability (dispersion) for the Anavex2-73 phase 2a study with 32 patient cohort” and that “this is confirmation that the sample of 32 patients of the Phase 2a provides reliable information regarding dispersion and as such allows for meaningful predictions for larger populations”
· Slide 13: Ariana indicates “relation between Anavex2-73 exposure and dose (PK) are consistent across administrations”
· Slide 14: “High Dose of Anavex2-73 correlates with exposure”
Slide 19: “ERP Biomarker Shows Significant Drug Response: P3a Amplitude Increases with Anavex2-73”
· Slide 24: through Ariana’s KEM Systematic Analysis, they found 83 rules (possible relations across variables, endpoints, PK parameters and time) and “97% of them showing coherent dose-response relation”
Slide 25: entitled “Robust Dose (Concentration) / Response Effect of Anavex2-73” and their KEM analysis provided “consistency for 6 main exploratory endpoints cognition, function and biomarker (MMSE, ADCS-ADL & EEG/ERPs) demonstrated through systemic exploration of the full data matrix”
· Slide 25: “97% consistency: MMSE, ADCS-ADL and EEG/ERPs: Identified relations show that high dose (concentration) is linked to improved response and low dose (concentration) to poor response”
Slide 26: chart shows that for our participants that achieved >4ng/mL blood concentration level (9 total) during the 57 week study, that 4 improved on the MMSE tests and 1 remained at baseline (5 out of 9 is a majority)
· Slide 28: “an increase of MMSE is a rare event.” And “a patient receiving a higher concentration of Anavex2-73 has a +110% (2.1 fold) chance of improving its MMSE during 57 weeks”
Slide 29: “KEM identifies strong non linear relations linking concentration with response for both MMSE and ADCS-ADL”
· Slide 30: High Anavex2-73 concentration linked to improved response consistently across all analytes and periods” and “both Anavex2-73 and metabolite show a consistent response across the 3 different time frames”
Slide 32: “KEM analysis has identified exclusion / inclusion criteria. Each criteria has the potential to improve MMSE / ADAS-Cog for mild to moderate Alzheimer’s patients treated with Anavex2-73” and “these criteria will be incorporated into the upcoming Anavex2-73 phase 2/3 trial”
http://www.pharmatimes.com/news/fda_taps_ariana_kem_platform_for_biomarker_signature_analysis_982469
Fair points but I do believe that Dr M and Fadiran likely have powered the current ph2/3 AD trial to be more than sufficient in both numbers and endpoints, especially with the biomarker PM analysis . GLTY
Mcmag “ ..and I don’t see one of them posting about the crap science of Biogen on IHUB?
Wow .. that says a lot”
Certainly makes one wonder WHY??
Instead of questioning a back-from-the-dead drug that resembles the same MOA of all the recent symptom-based tau/beta-amyloid failures:
Roche dropping 2 AD trials in January this year, then back in 2016 Eli Lilly's solanezumab failed its phase 3 trial of 2,100 patients. Pfizer also failed with bapineuzumab in a ph 3 three years prior to Lilly. Merck’s beta-amyloid BACE inhibitor verubecestat (late-stage AD) went down in flames in 2017. Then Merck attempted early stage with the same drug and pulled the plug early in 2019. Further J&J‘s BACE inhibitor atabecestat was put out to pasture in 2018 (liver problems as well).
Many would instead rather sling mud at our promising upstream novel approach (targeting the CAUSE rather than chase symptoms) speaks volumes about motivations.
Anavex’s CEO and P/R communications and our investor/scientific presentations from 2017-2019 and quotes from global CNS disease experts including Drs George Perry and Harald Hampel etc have made it clear that 2-73 (blarcamesine) has a unique and clearly differentiated upstream MOA (should be evident by now to scientific media with open eyes).
We are NOT an anti-amyloid beta drug, and we should not be lumped in with those BP failures in recent years.
Tack on our 4-5 years of safety/results and CNS precision-medicine leadership and being championed by leading AD and RSD experts, and our S1R MOA being validated in multiple recent peer reviewed publications, and having our patients/caregivers/trial PI’s requesting to EXTEND 2-73 trials and treatment, this SHOULD grant us more quality exposure rather than online degradation.
Hmmm, who would have the most to lose with our success??
GLTY
I think you may’ve been referring to Blackrock’s recent substantially-increased position in Anavex as of 8/22/19 when you said:
“.....the regulatory agencies and non-indexed equity funds will look at the stats”
If Blackrock was simply making an indexed allocation in Anavex, then why as of 8/22/19 did they only hold a .5% position in Neurotrope valued at $482,000?
Whereas on 8/22/19 BlackRock had increased its Anavex position by 1,145% to now hold 2,812,421 shares of Anavex’s 52,650,000 outstanding common shares.
An over 5% shareholder in Anavex at this point. New position valued at $7,500,000.
I do not think that Russell “indexing” would necessitate BlackRock acquiring over 5% of Anavex.
Again this appears to be an outsized position they’re building.
Do you disagree? If so why would “indexing“ equate to over 5% ownership?
https://fintel.io/soh/us/ntrp/blackrock
https://fintel.io/soh/us/avxl/blackrock
My confusion primarily stems from understanding WHY Alzheimer’s patients & their caregivers are going to interested in IV administration of a drug that must be at its highest dosages for an extended period of time.
And then after said extended period of time, a patient may see a 23% slowdown of the eventual cognitive decline of the disease progression (according to Biogen’s figures). Plus there’s a risk of brain swelling, among other side effects.
I’m personally interested in therapies with better results than the above. Therapies that are disease-modifying, which target the root cause of the disease rather than its symptoms.
(If I’m a practitioner and my patients keep developing obesity-related illnesses from consuming too much sweet tea and frozen dinners, then do I target and address their dietary choices, or just perform liposuction each year at their annual visit?)
Anders “Did you read the stories
The data is not out yet BUT There are many hundreds of patients that have been reported to stabilize the illness.”
With due respect, what you’re describing is inconsistent with everything I’ve read to date about Biogen’s back-from-the-dead medication.
Can you cite some pubs or articles that mention stabilized patients?
Biogen said that a subset of aducanumab patients:
“showed a significant reduction of clinical decline from baseline in CDR-SB scores at 78 weeks (23% versus placebo, P=0.01). In EMERGE, patients treated with high dose aducanumab also showed a consistent reduction of clinical decline as measured by the pre-specified secondary endpoints: the Mini-Mental State Examination (MMSE; 15% versus placebo, P=0.06), the AD Assessment Scale-Cognitive Subscale 13 Items (ADAS-Cog 13; 27% versus placebo, P=0.01), and the AD Cooperative Study-Activities of Daily Living Inventory Mild Cognitive Impairment Version (ADCS-ADL-MCI; 40% versus placebo, P=0.001).”
https://investors.biogen.com/news-releases/news-release-details/biogen-plans-regulatory-filing-aducanumab-alzheimers-disease
Yes! I particularly enjoyed the “urgently hiring” part, so much that I almost applied for the position.
https://www.indeed.com/m/jobs?sameL=1&q=Anavex&l=&from=searchOnSerp
Clinical Supply Manager 2+ yrs Clinical Supply Exp Req
Anavex Life Sciences
New York, NY 10036
Urgently hiring
Job details
Job Type
Full-time
Good question, and the PDD trial is listed as a single trial with sites in both Spain and Australia and because the Australian sites did not start recruiting PDD patients until May 2019 (at the earliest), that may have slowed the process while setting up the two new Australian PDD trial sites & getting enrollment completed for the new AU participants.
Because on October 30, 2018 the 1st patient was enrolled in Spain for the trial and the 1/2 way mark for enrollment was announced mid March 2019 ( 4.5 months later), ahead of schedule.
“Estimated enrollment” is listed as 120, I suppose they could’ve exceeded that number when they announced the addition of 2 new AU sites in May 2019??
Otherwise though it seemingly would’ve already been fully enrolled by now you’re right.
You didn’t ask me, but personally I’m not concerned because:
• Earlier this month Dr M listed our PDD study results release in 2019/2020 as a “value-creating catalyst” on slide 37 of the October 2019 corporate presentation
• And during the 10/4/19 oral presentation M discussed the importance of the pdd trial and emphasized all of the support from the MJF Foundation.
• And back on August 7, 2019 it was announced that at the request of Investigators there was in preparation a pdd trial extension as well.
So if things were not progressing according to plan for PDD I think we’d have heard about it by now.
“The enrollment of the Phase 2 ANAVEX®2-73 (blarcamesine) Parkinson’s disease dementia (PDD) study[3] is proceeding well and is getting closer to reach completion. At the request of investigators in order to offer all participants of the clinical study access to ANAVEX®2-73 (blarcamesine) a voluntary extension of this study is in preparation including microbiome assessment.”
https://clinicaltrials.gov/ct2/show/NCT03774459?term=Anavex&draw=2&rank=2
https://www.hammond.com.au/about/news/melbourne-trial-of-new-drug-to-treat-parkinson-s-dementia
https://parkinsonsnewstoday.com/2019/03/13/anavex-life-sciences-reaches-50-enrollment-threshold-in-anavex2-73-parkinsons-disease-dementia-pdd-phase-2-study-ahead-of-schedule/
https://www.anavex.com/first-patient-enrolled-in-anavex-life-sciences-phase-2-clinical-trial-of-anavex2-73-for-the-treatment-of-parkinsons-disease-dementia-pdd/
As you & others have mentioned this IP was likely another contributor to M’s stealth mode in the past 12-24 months.
Along with the blank check preferreds in March to avoid an undervalued change in control.
His tone and tenor during the 10/4 corporate update was definitely more confident.
Things are coming to a head.
Nidan: “Does the fact that getting worse at a slightly slower rate suggest to anyone that this treatment is ONLY ABOUT THE SYMPTOM? and is really not very good at that. Some sick people might ask if they could, why do this? Is this just cruel? How is this even a treatment?”
Spot on and frankly the comparison and correct decision for regulators and prescribing physicians would be obvious to a 3RD GRADER.
IF our Anavex results bear fruit as we suspect they will in the coming months, then would patients prefer:
• A compound with an MOA focused on the upstream causes of their disease, a compound that assists the patient’s own body to fight the cause; increases GABA which helps with RWE to improve sleep, anxiety/agitation, has been shown to induce autophagy and shown in preclinical to help with blood pressure, has no serious side effects, is orally available and in AD has been shown in our ph2a open label study to stabilize/improve patients at the higher therapeutic dosage.
OR
• A drug that was previously declared a failure, which shares a common MOA with many prior failed symptom based amyloid drugs that other BP’s have abandoned. IV administration; serious reported side effects such as swelling of the brain, and currently limited to only a slowing by 23% of the expected dementia decline.
With the low bar of efficacy to clear and the sheer size of the worldwide patient population & their families that are STARVING for a better and safer solution to these cruel diseases, it would appear only logical that our transatlantic ship will soon come in.
AIMHO
Thanks and in the quiet of my mind l get the sense that (due to the absence of any published bad news to date or publications negating our upstream approach to multiple CNS indications) things are culminating well behind the scenes.
Dr M was “extremely pleased” on 10/2/19 after the long awaited new IP protection was p/r’d.
And back in March 2019 the Company successfully achieved its goal of passing the 10mm blank check preferred shares takeover protection (by amending the Company’s articles of incorporation to allow for the approval of up to 10,000,000 blank check preferred shares; according to Anavex thereby “discouraging, delaying or preventing an undervalued change in control of the Company”).
Then lump in the March 2019 Cells important publication that added wood to our growing MOA fire by showing 2-73 leads to prominent induction of autophagy.
The Company was understandably pleased as well with the regulators’ Independent Data Safety Monitoring Board recommending the continuation without modification of our US Rett study based on safety and efficacy in the prelim 7 week results which showed 6 out 6 participants’ positive biomarker-correlated efficacy and behavior improvements p/r’d by Anavex last month and presented in Finland by our CMO, the world’s leading RS researcher. All on a low 5mg liquid dose.
No IV’s, orally-administered, no brain swelling, no serious SAEs reported to date, ancillary QOL benefits for sleep/anxiety/agitation (per our ph2a AD caregivers....effect of GABA increases?), efficacy on a dose-correlated basis per Anavex/Ariana analysis presented at conferences (especially at a therapeutic higher dosage for AD patients).
Patients/caregivers/trial PI’s consistently asking to extend treatment or be guaranteed the drug on extension of our various CNS trials.
Lastly I believe that the heightened level of excitement and clarity and confidence that Dr Missling displayed during the 10/4 investor presentation and company update was not by accident. You don’t display that level of confidence and clarity and excitement about a historically-difficult-to-treat range of CNS diseases at this stage of our Anavex clinical trials (mere months away from confirmatory readouts) unless you’ve ample data & solid rationale for doing so, in my opinion of course.
Godspeed Anavex
“The current findings show for the first time that activation of Sig-1R with ANAVEX®2-73 leads to the prominent induction of the autophagy “cellular recycling” process and enhanced protein clearance in cells. The study, led by Christian Behl et. al. of the University Medical Center at Johannes Gutenberg University, in Mainz, Germany, has been published in the peer-reviewed journal, Cells (link).
“These results show that activating the sigma-1 receptor (Sig-1R) with ANAVEX®2-73 can selectively induce the autophagy process and increase protein homeostasis in both in vitroand in vivo models,” said Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex. “The ability to identify key molecular functions in age-related disease is central to developing new therapeutic strategies that target these mechanisms and ultimately provide clinical impact by preventing or treating disease.””
And
“We are extremely pleased with the continued development of the patent portfolio for ANAVEX®2-73 (blarcamesine). This new issuance of the U.S. patent continues to expand the breadth and depth of our intellectual property and is another step in the development of a robust patent portfolio relating to ANAVEX®2-73 (blarcamesine),” said Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex.”
Also
https://www.anavex.com/anavex-life-sciences-reports-publication-of-new-data-that-show-anavex2-73-induces-cellular-recycling-process-linked-to-the-prevention-and-treatment-of-age-associated-diseases/
Indeed, the golden rule. BP’s making the rules. And regulators are likely desperate to show they are doing something to address the growing dementia epidemic; even if it means exhuming a BP zombie medication.
Anavex and other small promising biotechs are up against this BP-lobbied/controlled machine. Question still remains whether they’ll be able to stop our CNS breakthrough.
My hunch however is that Dr M and our BOD have been acting strategically in Europe and Australia as a counter measure.
FDA medical adviser: 'Congress is owned by pharma'
Yahoo FinanceMarch 13, 2019
https://www.google.com/amp/s/finance.yahoo.com/amphtml/news/congress-big-pharma-money-123757664.html
“I’m really much more concerned because Congress is supposed to have oversight for the FDA,” Brown said. “If the FDA isn’t going to hold pharma accountable, and Congress is getting paid to not hold pharma accountable, then it really doesn’t matter who the president is because it’s really about Congress.”
“Pathetic Medicine vs Precision Medicine” sounds about right
Zombie Medication brought back from the dead!
Great thoughts as usual thank you, and let’s hope we’ve clarity and positive resolution to the battle in the coming few months.
Greetings steady, and as you already know, there’s tens of billions at stake and we are clearly one of the front runners in the race toward a materially effective CNS treatment. So many BP failures, too many to list in recent years.
We are on the verge of confirmatory readouts and thus far there’s been no Anavex failures or bad news or serious SAE’s (read: swelling of the brain), and I’m supposed to believe that the competition/establishment will roll over like scalded dogs without a fight?
The fight is all around us daily here. They are trying to shut down/suppress Anavex and they are trying hard.
BP also has ties and influence deep within the government/regulatory bodies. Suppression can come from various directions.
Even if the only result is to slow us down or make it difficult for us to raise needed funds for our clinical development; the smaller and weaker we are the better for them to either take large equity stakes from weak shareholders now, or condition retailers to bail at low sales prices in the coming months.
Point is, IN MY OPINION, these are not just random short positions by speculators, rather there are deep pocketed “interested parties” behind the 4mm short position.
No disinterested (sane minded) fund manager would learn our story and view our situation with only 150mm of market cap left and decide to try and short down that last amount of value.
Apologies for interjecting.
Very interesting mmd, thank you for the GABA deficiency links with insomnia and anxiety and mood disorders.
Naturally I find it comforting to know that our Australian AD trial PI, Dr Macfarlane, and Anavex have stated that 8 out of 8 of our AD trial participants that started with insomnia/sleep disturbances were without said symptoms at the end of one of our AD phase 2a extension dates.
And that Anavex reported to us the below feedback from our participants’ caregivers, especially as it relates to mood and anxiety and social engagement improvements.
Reminds me of the old Tesla song lyric “signs, signs, everywhere are signs...”
[Real world perspectives from our patients’ caregivers (Jefferies slide from June 2017):
"PATIENT EVENTS: THERAPEUTIC RESPONSE UNEXPECTED
101001 MORE ALERT REGARDING SURROUNDINGS
101002 FEELS MUCH HAPPIER MAKING JOKES
101003 MUCH HAPPIER WHEN ATTENDING CLINIC APPTS AND ENJOYS MAKING JOKES
AND ENGAGES WELL IN CONVERSATION
101004 BETTER HAND COORDINATION. CALMER AND MORE COMMUNICATIVE
101006 IMPROVING MOODS. READING MORE BOOKS
101007
ABILITY TO PLAY THE PIANO AND READ MUSIC NOTES AT ABOUT 9 MONTHS
INTO TRIAL. SHE USED TO PLAY THE PIANO AT AGE 5 AND LOST HER ABILITY PREALZHEIMER
TRIAL
101010 ABLE TO FOLLOW PLOT WHEN WATCHING MOVIES WHEREAS PREVIOUSLY
COULD NOT
101010 MORE COMPASSION FOR CHILDREN
101011 WIFE THINKS PATIENT IS A BIT MORE CHEERFUL
101013 ABLE TO DO MUCH MORE HOUSEWORK THAN BEFORE
101013 MORE DRIVEN AND UPBEAT LESS ANXIOUS ACCORDING TO CARER
101014
AN INTERNATIONAL ARTIST WHO RESUMED HER PAINTING ABILITIES AND NOW HAVING AN EXHIBITION IN NOV 2016. WRITTEN A 3 PAGE LETTER TO LONG LOST
BROTHER
101015 PLAYING MORE GOLF NOW BY HIMSELF. MORE CONFIDENT AT GOING OUT BY
HIMSELF
101017 ENJOYED HER TRIP TO BELGIUM - TALKS ABOUT SOME BITS OF HER TRIP
102001 IMPROVED ENGAGEMENT WITH FAMILY/FRIENDS/OUTSIDE WORLD
102008 IMPROVEMENT IN MOOD
102010 FEELING GREAT -
IMPROVEMENT IN COGNITION AND MOOD, BALANCE AND
GAIT HAS IMPROVED
103001 PATIENT REMEMBERING SOMETHING HE WOULDN'T HAVE PREVIOUSLY"
I’ve no idea what you’re attempting to communicate.
Were you writing a Haiku? I love those.
If so please stick to seventeen syllables, in three lines of five, seven, and five.
Agree completely tradherpete, IMO that’s their plan. Instill frustration/desperation/confusion and CONDITION us retail holders (over 70% retail held) to view 1-2 billion as a fair market cap and utilize market psychology to encourage us to bail out at the first big pop in price.
You’re right they can afford the initial “short loss” hit on 5-6 million shares at 15/share loss (maybe a 75mm loss). These are deep pockets we’re up against and 75mm is a cost of doing business for them in this regard.
They step into our shoes at around 20-30/share cost and have their desired large stake in the Company equity.
Either way they win. If Anavex fails they win, but if the positive binary result occurs as we hope, then they know what type of true value that entails going forward (hint it’s likely many multiples of 20/share).
We’re stuck in the middle of a financial war game.
Enjoy your day.
Bourbon here’s something to consider on a slow news day. There’s 15,000 affected Rett patients in the US and 350,000 worldwide. If the estimated treatment cost per patient is 400 per month and a SOC medication is utilized by just 50% of the worldwide RS patients, that equates to around 840 million per year in revenue.
Profit of 50% to the pharma = 420 million per year.
15 times p/e would approximate a 6.3 billion market cap for such a Company.
IF the working conclusion holds true that our RS extension participants’ results are substantially similar to (or improved upon) our initial 6 out of 6 positive from the preliminary 7 week RS trial as presented by Dr Kaufmann last month, I personally would give our Company at least a 50% chance of approval for said disorder.
3.15 billion MC approximation IF 50% chance of approval.
And even at a lower 25% chance of approval that’s over 1.5 billion today. We’re oddly trading at 10% of that conservative valuation currently.
This is just RS, not PDD or AD or any other pipeline indication for Anavex.
(Disclaimer: For discussion & analysis purposes only. Not a recommendation to buy or sell any security.)
“Prevalence
It is estimated that one in ten thousand girls will be born with Rett Syndrome. This means about 15,000 girls and women in the US and 350,000 worldwide have the disorder.”
https://reverserett.org/about-rett/more-about-rett/
BlackRock appears to only own 60,041 shares of ntrp, a position valued at $482,000 as of 8/22/19. Ntrp has 13 million outstanding shares so this is only .5% of the neurotrope stock.
Whereas it appears that as of 8/22/19 BlackRock had increased its Anavex position by 1,145% to now hold 2,812,421 shares of Anavex’s 52,650,000 outstanding common shares.
An over 5% shareholder in Anavex at this point.
I do not think that Russell indexing would necessitate BlackRock acquiring over 5% of Anavex.
Appears an outsized position they’re building here.
https://fintel.io/soh/us/ntrp/blackrock
https://fintel.io/soh/us/avxl/blackrock
Hard to say which fund(s) is to blame, and I’ve no reason to suspect any in particular; but I wonder what type of methods one might employ to help move shares from stubborn retailers’ hands??
In theory a rising share price commiserate with the positive after positive after positive Anavex news development (for the past couple of years), especially now as we inch towards 2019/early 2020 confirmatory readouts, would just embolden the stubborn retailers. Mustn’t let that happen, right?!
Perhaps set and hold the market value at 150 million? Short and distort? Create confusion/desperation/distraction online where we live; has this been the psychological weapon of choice?
Interesting thoughts and you mentioned PDD:
Dr M did list our PDD study results release in 2019/2020 as a “value-creating catalyst” recently on slide 37 of the October 2019 corporate presentation.
And during the 10/4/19 oral presentation M discussed the importance of the pdd trial and all of the support from the MJF Foundation.
And of course back on August 7, 2019 it was announced that at the request of Investigators there was in preparation a pdd trial extension as well.
“The enrollment of the Phase 2 ANAVEX®2-73 (blarcamesine) Parkinson’s disease dementia (PDD) study[3] is proceeding well and is getting closer to reach completion. At the request of investigators in order to offer all participants of the clinical study access to ANAVEX®2-73 (blarcamesine) a voluntary extension of this study is in preparation including microbiome assessment.”
So I agree that by all appearances the pdd trial is likely proving helpful to them in confirming our MOA/compound’s effectiveness.
And BTW if our working conclusion regarding Rett Syndrome continued positive efficacy in the past 4 months of extension is accurate (and I’m having a really hard time finding a break in the logic), then we likely have reason to believe scheduled discussions with fda/ema (see 9/16/19 p/r) will be productive to say the least.
Efficacy in Rett Syndrome is very nice, but the positive working conclusion also helps to illuminate the broad CNS upstream approach of our unique 2-73 S1R MOA across MULTIPLE indications IMO.
And l’est we forget, we’ve years of safety, safety, safety.
Combined with patient/PI/caregiver request after request after request to stay on the compound after trial completion.
Topped off with a healthy serving of positive reported RWE during the AD ph2a (such as improved sleep, less agitation/anxiety etc); and recent publications discussing our 2-73 compound’s promising preclinical impacts on blood pressure and autophagy (further evidence of efficacious effect on the body).
While all must do their own due diligence of course, and while anything is still possible, I’m quite encouraged and ready for 2-73 to gain approval to benefit patients.
(I’ve reached the ready room by the way.)
From the recent Deductive Logic 101 midterm exam at Precision Medicine University:
Find the break in the chain, if any:
Did Anavex begin open label uncontrolled Rett Syndrome trial extension dosing on 6/25/19?
If yes, continue
Were real-time dosing effects & efficacy results AVAILABLE to the Company and our CMO Dr Walter Kaufmann on these trial EXTENSION RS participants during the 3-4 months since 6/25/19?
If yes, continue
Similarly, have these open label extension results provided continued safety and corresponding response rates in efficacy and behavior (along with GABA and glutamate correlated biomarkers analysis) since 6/25/19?
If yes, continue
Did the Company and its CMO have access to said RS extension data/efficacy results by at least September 16, 2019?
If yes, continue
Is our CMO the leading Rett Syndrome researcher and co-author of the current diagnostic guidelines for the disorder? And does he have a long history and relationship with the afflicted families and sufferers of this RS disease?
If yes, continue
Did Anavex and our trial PI (CMO) release two (2) September 2019 significantly positive and promising p/r’s and an associated 9/27/19 European Rett conference presentation by Dr K outlining the preliminary 7 week (6 out of 6 patients) positive biomarker-correlated efficacy and behavior results for the Rett Syndrome & scientific community to read and hear?
If yes, continue
Is it therefore the working conclusion that our Rett Syndrome study participants’ extension results since 6/25/19 are similarly and significantly positive in efficacy and behavior and biomarker-correlated (similar to the 7 week results p/r’d by Anavex on 9/16/19)?
If yes, game on, right?
If no, one must either assume (a) the 3 months of extension results were not available/analyzed in real time (goes against the definition of open label and uncontrolled extension studies); or (b) that our highly-decorated CMO would present and release information in September that is inconsistent with the AVAILABLE 3 months of extension results (editorial: he doesn’t strike me as the type AT ALL).
https://www.globenewswire.com/news-release/2019/06/25/1873535/0/en/Anavex-Life-Sciences-Announces-First-Patient-Dosed-in-Extension-Study-to-its-U-S-Phase-2-Clinical-Trial-of-ANAVEX-2-73-in-Patients-for-Rett-Syndrome.html
https://www.globenewswire.com/news-release/2019/07/31/1894581/0/en/Anavex-Life-Sciences-Reports-Recent-Data-Review-by-the-Independent-Data-Safety-Monitoring-Board-for-its-U-S-Phase-2-Clinical-Trial-of-ANAVEX-2-73-in-Patients-with-Rett-Syndrome.html
http://www.globenewswire.com/news-release/2019/09/16/1915810/0/en/Anavex-Life-Sciences-Announces-Preliminary-Clinical-Efficacy-Data-of-its-U-S-Phase-2-Clinical-Trial-of-ANAVEX-2-73-in-Patients-with-Rett-Syndrome.html
https://www.globenewswire.com/news-release/2019/09/27/1921667/0/en/Anavex-Life-Sciences-Presented-at-the-6th-Annual-European-Rett-Syndrome-Conference-Preliminary-Clinical-Efficacy-Data-from-the-U-S-Rett-Syndrome-Phase-2-ANAVEX-2-73-Study.html
https://www.anavex.com/anavex-life-sciences-announces-the-appointment-of-walter-e-kaufmann-md-as-chief-medical-officer/
(Disclaimer: I’m not a scientist and just trying to make sense of our current situation)
• So the Company & our trial principal investigators & our published results TO DATE are telling us that our participants are improving (in Rett, and in AD at therapeutic dosages).
• The company & SAB have detailed our 2-73 MOA which addresses the upstream causes of these diseases (“targeting protein misfolding (when proteins fail to fold correctly, into a normal configuration, they do not work as intended), oxidative stress (which damages cells due oxygen molecules with free radicals, or unpaired electrons), mitochondrial dysfunction, inflammation, and cellular stress”), RATHER THAN the failed symptom-based approaches of Big Pharma failures over the past 30 years.
• And independent respected peer reviewed researchers are seemingly confirming our methods through publication after publication, as recently as yesterday.
https://www.genengnews.com/news/metabolic-mitochondria-dysfunction-may-be-primary-cause-of-alzheimers/
Difficult to break the logic chain, at least for me.
Awesome, thank you
Very interesting and important (for Anavex) publication released yesterday 10/18/19. Thank you georgegii.
“Metabolic Mitochondria Dysfunction May Be Primary Cause of Alzheimer’s
A team of researchers led by Yale-NUS College says it has found evidence that metabolic dysfunction is a primary cause of Alzheimer’s disease.”
https://www.genengnews.com/news/metabolic-mitochondria-dysfunction-may-be-primary-cause-of-alzheimers/
And just 5 days ago Alzheimer’s News Today has this to say about our compound:
“Anavex 2-73 is a small molecule that activates the sigma-1 receptor, which is known to modulate cellular processes relevant to neurodegeneration. Specifically, Anavex 2-73 is thought to help restore cellular balance by targeting protein misfolding (when proteins fail to fold correctly, into a normal configuration, they do not work as intended), oxidative stress (which damages cells due oxygen molecules with free radicals, or unpaired electrons), mitochondrial dysfunction, inflammation, and cellular stress.”
https://alzheimersnewstoday.com/anavex-2-73/
The picture is coming more and more into focus. At least for those willing to think clearly.
Great points jimmy, appreciate your insights as usual
That was a stream of consciousness which I decided to share. Ultimately intended to confuse you.
Sounds like mission accomplished.
For those that claim there’s no connection between Anavex and Merck:
https://www.marketwatch.com/press-release/industry-consortium-launched-to-qualify-biomarkers-for-schizophrenia-drug-development-2019-03-20
https://erpbiomarkers.org/
Post by tttav66
Friday, 03/22/19 02:50:29 PM
Re: None 0
Post # of 215103
Anavex is returning to the 2nd Annual Neuropsychiatric Drug Development Summit from July 23-25 in Boston.
On July 23, Dr. Missling will lead 1 of 3 pre-conference workshops; Reviewing the Potential for Precision Medicine in Neurological Diseases.
On July 25, he will also be featured in a 2-person panel with Sean Smith, the Executive Director of Neuroscience Discovery at Merck; Panel Discussion: The Precision Medicine Approach to Neuropsychiatry – For or Against?
Download the Full Event Guide at the website below for further details:
https://npd-summit.com/