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Logically, wouldn’t the 3-4 months of UNCONTROLLED and OPEN-LABEL Rett extension data since 6/25/19 have to be significantly positive (and biomarker and dose correlated) in efficacy & behavior for Drs Missling and Kaufmann to be comfortable enough to:
(1) broadcast in September through 3 different press releases the significantly positive and very encouraging Rett Syndrome results from
our 2-73 trial, and
(2) to present same in Finland at the European Rett Syndrome Conference for all in the worldwide Rett community to see and have their hopes raised?
They had months of open label data in their hands at that point.
I suppose it comes down to trust in the Company leadership/ethics and in Dr Kaufmann’s relationship with and expertise in this RS community and disease.
Do we really think they’d raise the hopes of this RS community carelessly or without just cause and without continuing strong open label data? I personally don’t think they would do that.
AIMHO
On 6/25/19 the first Rett patient was announced in the Anavex 2-73 open label Rett Syndrome extension study.
“The open label, 12 week extension study is designed to evaluate long term safety, tolerability, and the effect of ANAVEX®2-73 on Rett syndrome patients following the completion of the Phase 2 study.”
So almost 4 months of open label Rett data & results for Anavex to study thus far.
As the extension is uncontrolled, they can evaluate the extension patients’ progress and liquid dosage titrations and effects throughout.
Correlations with the established biomarkers and increases in dosages.
Data is continuing to pile up in this extension and my opinion is that it is continuing to confirm our 7 week preliminary significantly positive efficacy & behavior results.
Why? Because while only the Company has that open label extension data at this point, IMO said extension data must be pointing to similar positive biomarker-correlated efficacy and behavior improvements, logically-speaking; otherwise I think that Dr M and Dr K would have had serious reservations about presenting and putting out 3 p/r’s announcing these significant improvements in the preliminary 7 week Rett Syndrome trial (6 out of 6) positive participant results in September.
Just my opinion & intuition.
https://www.anavex.com/anavex-life-sciences-announces-first-patient-dosed-in-extension-study-to-its-u-s-phase-2-clinical-trial-of-anavex2-73-in-patients-for-rett-syndrome/
Great points tradherpete and do you have the transcript to that April 2019 H.C. wainwright presentation regarding pdd? I’ve looked and can’t find it thanks
Posted 8 days ago by Anavex H/R. “Urgently hiring”
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
“Full Job Description
Young NASDAQ-listed biotech company in CNS based in NYC is looking to recruit a Clinical Supply Manager (CSM) who will manage the Contract Research/Manufacturing Organization vendors in the areas of drug product manufacturing, packaging, labelling, and distribution for all clinical studies. This position assists with representing Chemistry, Manufacturing, and Control (CMC)/Clinical Supplies in project and study level teams involving Regulatory, Quality, Clinical Operations, Pharmacology, Pharmacovigilance, and Project Management functions.
Responsibilities include but not limited to:
Forecasts and plans IP requirements and strategies for clinical studies.
Manages the Integrated Response Technology system (IRT), clinical supply inventories, and the global. inventory/resupply strategies.
Oversees the Clinical Supply section of the eTMF, including but not limited to the investigational product’s distribution, return, and destruction areas.
Manages CMC’s and Clinical Supply’s project financial tracking and budgeting process.
Prepares invoices for payment by verifying that the work billed for was actually done.
Prepares proposals for clinical supply/CMC related projects.
Assist in forecasting project budget process and forecasting of CMC Team annual project budgets.
Collaborates with project and study level teams comprised of all functional areas.
Assists and manages vendors in the areas of drug product manufacturing, packaging, labelling, distribution, and IRT services.
Monitor and review of on-going Drug Substance and Drug Product release and stability test results for accuracy and regulatory compliance.
Assist in writing and preparation of regulatory submission documents: drug product and drug substance sections in IND, Annual reports, and Information amendments.
Review manufacturing, packaging, and labeling Master Batch Records.
Monitor batch manufacture, packaging and labeling at vendors.”
- 8 days ago report job
https://www.indeed.com/m/viewjob?jk=9b48eba783cabc0e&from=serp&prevUrl=https%3A%2F%2Fwww.indeed.com%2Fm%2Fjobs%3FsameL%3D1%26q%3DAnavex%26l%3D%26from%3DsearchOnSerp
Any relation to recent regulatory discussions?:
“This is a remarkable first strong signal for patients with Rett syndrome especially given that the strong effects were seen in adult patients, and we look forward to discussing these results with the FDA and the European regulatory agency as we continue our Rett Syndrome Program including pediatric patients,” said Walter E Kaufmann, MD, Principal Investigator of the study and Chief Medical Officer of Anavex. “Importantly, we've now observed that the ANAVEX®2-73 (blarcamesine) effect is correlated with changes of Glutamate and GABA levels, objective measures and biomarkers in several neurodevelopmental disorders.”
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
From August 7, 2019
https://www.anavex.com/anavex-life-sciences-reports-fiscal-2019-third-quarter-financial-results-and-provides-clinical-study-updates/
“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.”
Online misinformation and distraction campaign in full force. Working in conjunction with dark pool (likely overseas) funds selling short and purposely depressing the market cap of a promising small cap biotech which aims to provide life changing positive compounds to those crippled with devastating diseases.
If that’s not illicit activity then I do not know what is.
EOM
It is a conundrum for the shorts/BP agents. With a small daily volume to purchase and a large position to cover.
Cover now and the price undoubtedly spikes. That would instill confidence for current retailers and embolden us in our beliefs & DD that we indeed have something very valuable.
I think they’d rather maintain the short position and beat us down so that we’ll sell ASAP at the first decent opportunity.
And if I was corporate counsel I’d be seeking the derivation of the large short positions if at all possible.
Agreed and this adds credence to the concept that they cannot cover a large quantity at these levels. The large % of retail shareholders are apparently not selling enough down here.
In which case Xena’s theory is correct that often the daily volume is prearranged exchanging of shares between hedge funds and the market maker, many times putting pressure on the price.
Meanwhile we’ve the distinct pleasure of the daily online misinformation and consternation campaign.
Frustrate us & condition us to bail out at the first opportunity.
Good luck to you Mauismart; naturally you should invest at your own risk.
I’m here to try and make sense of our current situation, primarily through deductive logic. None of my posts are to be construed as an offer or a recommendation to buy or sell any security.
But of course you already knew that. Enjoy your lunch today.
I’m obviously not alone in thinking the goal of the HFs & dark pool funds and online agents (hired by.....) is and has been to suppress our market cap and wear down shareholders and free up the large % of retail-held shares.
Condition us to welcome and accept a 1-2B market cap buyout or sales price for our shares.
Then, on a potential morning spike to $20, a 6.5mm short shares times $20 = 130mm loss. But we’re up against very deep pockets. That’s chump change to those behind it IMO.
Lose 130mm to gain a huge position; buying from beaten down retailers conditioned to sell at a $20 stock price.
Meanwhile the new stockholders have their large long position from $20 to the moon.
Cost of doing business.
Again just my 2 cents. There are no guarantees of success of course.
(BTW there’s little chance IMO that these are just retail short positions at this stage of the game)
This could possibly explain the sheer volume and regularity of the misinformation campaign we get to experience here daily.
And I suspect that our CEO and BOD have moved the ball much farther down the field than the competition (and their online agents) may realize.
Just based on my own imperfect DD.
Well put, xena, you’ve done an excellent job compiling the years of fact-based & relevant Anavex DD in the compiled due diligence sticky.
And in my mind’s eye, the whole will be even greater than the sum of its parts.
https://www.prnewswire.com/news-releases/noble-capital-markets-initiates-research-coverage-on-anavex-life-sciences-corp-avxl-300403268.html
In Feb 2017 coverage started at Noble Capital with analyst Kumar Raja PhD.
Then sometime later in 2017 Kumar left Noble and joined Brookline Capital Markets as a Director & senior biotech analyst.
Often when the covering analyst leaves, so does the coverage.
https://rettsyndromenews.com/2019/10/15/rett-cells-have-defects-in-energy-production-greater-oxidative-stress-study-suggests/
Excerpt
“Several lines of research have suggested problems in the metabolism of cells, in particular exposure to oxidative stress and deficiencies in mitochondria, in both diseases.
Oxidative stress is an imbalance between the production of free radicals and the ability of cells to detoxify them. These free radicals, or reactive oxygen species (ROS), are harmful to the cells and are associated with a number of diseases.
Importantly, nerve cells — those mainly affected in Rett — may be particularly susceptible to oxidative stress, as the brain has few active defense pathways against ROS (antioxidative activity).
To uncover how these alterations are linked to Rett and CDD, researchers at Boston’s Massachusetts General Hospital and Harvard Medical School investigated mitochondrial function in cells from RTT and CDD patients.”
Thanks JWC3 and Xena for posting this new 2019 AU provisional early approval process. Will be interesting to see how this develops after our CEO’s visit to Australia this week.
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
Excellent point, thank you. Just what the Doctor ordered.
Isn’t the writing on the proverbial wall?
Hmmmm, indication after indication of (thus far) positive CNS preclinical and clinical results and numerous supportive peer reviewed scientific publications and quotes from excited trial PI’s and from global leading researchers over past few years. No known or published contradictions to MOA. Solid safety for years. Patients consistently requesting to extend treatment. Positive/important additional RWE reported.
On the flip side, there’s a consistent flow of online denigration & misinformation and purposeful attempts to suppress the market cap of a public company aiming to serve the unserved and seriously afflicted.
Will the monied/lobbied-machine win out, or will common sense and the greater good prevail?
I’m here for the latter.
Is the BP-lobbied/controlled machine powerful enough to stop our breakthrough? IMO they’re here and they’re trying. Trying very hard.
Thank you to Anavex for pushing ahead to help patients and their families.
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.”
A friendly reminder for the regulators & decision makers?
“Alzheimer's disease is a progressive, irreversible neurological disease and the most common cause of dementia. In the U.S., there are over five million individuals living with Alzheimer's disease and an estimated 50 million people live with dementia worldwide. Today, there are no commercially available therapies to address the underlying cause of Alzheimer's. According to the World Alzheimer Report 2019, the current annual cost of dementia is estimated at $1 trillion, a figure set to double by 2030.1”
https://www.globenewswire.com/news-release/2019/10/09/1927217/0/en/Anavex-Life-Sciences-Announces-ATTENTION-AD-ANAVEX-2-73-Extension-Clinical-Study-in-Early-Alzheimer-s-Disease.html
“This is an important development as the patients who have completed the main study, ANAVEX2-73-AD-004, are consistently expressing the wish to gain ongoing access to this investigational therapy” says A/Professor Stephen Macfarlane, FRANZCP, Head of Clinical Services at the Dementia Centre, HammondCare and Principal Investigator for both studies.
“People living with Alzheimer’s disease desperately need new therapies and ATTENTION-AD reflects our commitment to the patients who participated in the Phase 2b/3 ANAVEX®2-73-AD-004 study and who have contributed enormously to the development of a potential new medicine for patients with Early Alzheimer’s disease,” said Christopher U Missling, PhD, Chief Executive Officer of Anavex. “This study will provide supplemental data on ANAVEX®2-73 (blarcamesine).”
Flash, this must be welcome news, as previously you were communicating doubts about our AD emphasis.
GLTY
I’m wondering the same thing.
Right there with you on the 10/4 conference yesterday; but I don’t know exactly the differences between the two 18 and older Rett trials.
Nidan: “In fact I heard Dr.M. during yesterday's conference say..., "WE KNOW EXACTLY WHAT THE A2-73 molecule works as it does and WHY..."”
Yes you’re right I heard that distinctly as well. While we’ve gotten that sense from him for awhile now, it was very nice to hear him state it in such a confident and emboldened manner.
For those of us paying close attention and anticipating our (one or zero) binary moment, I found that statement illustrative.
Anders, if you’re referring to the preferreds, yes as Jonjones importantly points out, earlier this year Anavex undertook a time-intensive and legally-burdensome process to seek approval to amend the Company’s articles of incorporation to allow for the approval of up to 10,000,000 blank check preferred shares.
Glossy full page mailers were mailed to all shareholders with an “important message” in bold print to encourage voting to approve the amendment thereby “discouraging, delaying or preventing an undervalued change in control of the Company”.
Now one has to ask themselves if Anavex took this step for valid & time sensitive business reasons, or if they simply ran out of things to do around the office and decided to needlessly throw a bunch of money at attorneys, accountants & consultants?
I’m going with the former and taking them at their word. The Anavex BOD took quick action to discourage, delay, or prevent an undervalued takeover attempt.
Great point Talon, and I’m now fairly convinced that Dr M and the BOD envision Anavex becoming a BP of their own making. Yes there are puzzle pieces that must still fall into place and results still to be published from our current controlled trials.
However didn’t he just say that AD readouts could be in 2020? At least we know that PDD and RS placebo controlled results will be released in the next 3-4 months.
Gold standard MOA proof of concept for the regulators and scientific community potentially within 90-120 days?
I’m just not sure why we’d need big pharma at this stage; maybe just a marketing/sales/ distribution partner.
A buyout prior to RSD or PDD binary events would seem premature. And why sell out if they (seem) to know we’ve effective life changing compounds for the previously untreatable CNS disease(s)?
But I do concur that we need publicly-recognized “buy-in” at some point from the regulators and large scale scientific media and clinicians to propel us forward so as to raise capital at non-punitive stock price levels.
The competition/HFs have IMO been fighting a stock price suppression/FUD battle against Anavex for years now for that very reason.
Stop us from funding our progress.
As well to strong arm and brow-beat the Company to accept low-value license or buyout deals and to convince retail stockholders to throw in the towel (or condition us to view a 1 or 2 billion market cap as a fair buyout price).
It’s psychological and financial warfare. IMO
Either provide the fact-based bad news or published contradicting evidence countering our MOA’s effectiveness, else you’ll prove my thesis correct.
Agreed and in light of our being one of the last oral presentations and the late breaking presentations at the AAIC and CTAD in the past couple of years, and with the BIO panels and bold presentations such as yesterday’s, you’re right Merck and other BP are aware.
Rightly many have been concerned for a few years I’m sure.
Anavex has basically put the scientific/investing world on notice that our compounds, and 2-73 in particular, SEEM to be illustrating (through results and publications) that they may very well be efficacious for AD, Epilepsy, PDD, RSD, MS?, FTD, autism, among other benefits/indications.
AND that they can illustrate how/why, correlated to established biomarkers (something the FDA has encouraged, on paper at least, for new PM initiatives).
And that we aren’t interested in or pursuing BP’s failed symptoms-based approach, but rather we are targeting/solving the root causes of these diseases.
To think that the BP masters of the universe, and those in control of the system, haven’t heard about us at this point would be unfathomable.
Their goal is to marginalize, block & tackle, use online agents to create uncertainty and doubt. And likely lobby/influence Washington & regulators behind the scenes to slow down threats from small promising companies such as ours.
Dr M appears to be steps ahead of those tactics now however.
That’s a public link and you just click on the tab for Posts and should be able to see their posts during the year. Almost all have been about 2-73.
Good find inv14 and the below is an excerpt from that Nov 2015 HSP paper you linked for falconer that discusses S1R:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681538/#!po=66.0920
“Support for this result comes from the knock down study of either of the two proteins essential for MAM tethering, sigma-1 receptor and phosphofurin acidic cluster sorting protein-2 (PACS-2), which resulted in neuronal degeneration.25,26,39,60–62 In healthy cells, the ER-mitochondria tethering ensures the propagation of inositol 1,4,5-triphosphate receptor (IP3R)-linked Ca2+ signals to the mitochondria to coordinate ATP production and to enable mitochondrial Ca2+ buffering. In the situation where the ER-mitochondria coupling is reduced, such as in cells with sigma-1 receptor or PACS-2 knocked down, or cells expressing Reep1 disease mutations, the Ca2+ signal propagation to the mitochondria is suppressed and the Ca2+-dependent control of mitochondrial metabolism likely becomes at risk. Consistent with this, cells obtained from HSP patients with REEP1 mutations showed reduced mitochondrial respiratory rate and oxygen consumption.13,14,55,63,64 In contrast, when the coupling is enhanced, as in the cells with mutations in PS2, a-synuclein, parkin and DJ-1, mitochondria are susceptible to Ca2+ overloading and may undergo mPTP permeabilization, thus committing the cells to a cell death pathway. Thus, maintaining proper ER-mitochondria interactions seems to be pivotal for maintaining normal mitochondrial function and ultimately neuronal integrity.”
Cites:
13. Goizet C, Depienne C, Benard G, et al. REEP1 mutations in SPG31: Frequency, mutational spectrum, and potential association with mitochondrial morpho-functional dysfunction. Hum. Mutat. 2011;32(10):1118–1127. [PubMed] [Google Scholar]
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25. Guardia-Laguarta C, Area-Gomez E, Rub C, et al. a-Synuclein Is Localized to Mitochondria-Associated ER Membranes. J Neurosci. 2013;34(1):249–259. [PMC free article] [PubMed] [Google Scholar]
26. Ottolini D, Cali T, Negro A, Brini M. The Parkinson disease-related protein DJ-1 counteracts mitochondrial impairment induced by the tumour suppressor protein p53 by enhancing endoplasmic reticulum-mitochondria tethering. Hum Mol Genet. 2013;22(11):2152–2168. [PubMed] [Google Scholar]
39. Hedskog L, Pinho CM, Filadi R, et al. Modulation of the endoplasmic reticulum–mitochondria interface in Alzheimer’s disease and related models. Proc Natl Acad Sci USA. 2013;110(19):7916–7921. [PMC free article] [PubMed] [Google Scholar]
55. Villegas R, Martinez NW, Lillo J, et al. Calcium Release from Intra-Axonal Endoplasmic Reticulum Leads to Axon Degeneration through Mitochondrial Dysfunction. J Neurosci. 2014;34(21):7179–7189. [PMC free article] [PubMed] [Google Scholar]
60. Lim Y, Kehm VM, Lee EB, et al. a-Syn Suppression Reverses Synaptic and Memory Defects in a Mouse Model of Dementia with Lewy Bodies. J Neurosci. 2011;31(27):10076–10087. [PMC free article] [PubMed] [Google Scholar]
61. Stoica R, De Vos KJ, Paillusson SEB, et al. ER–mitochondria associations are regulated by the VAPB–PTPIP51 interaction and are disrupted by ALS/FTD-associated TDP-43. Nature Commun. 2014;5:3996. [PMC free article] [PubMed] [Google Scholar]
62. Calì T, Ottolini D, Negro A, Brini M. Biochimica et Biophysica Acta. BBA - Molecular Basis of Disease. 2013;1832(4):495–508. [PubMed] [Google Scholar]
63. Barrientos SA, Martinez NW, Yoo S, et al. Axonal Degeneration Is Mediated by the Mitochondrial Permeability Transition Pore. J Neurosci. 2011;31(3):966–978. [PMC free article] [PubMed] [Google Scholar]
64. Court FA, Coleman MP. Mitochondria as a central sensor for axonal degenerative stimuli. Trends Neurosci. 2012;35(6):364–372. [PubMed] [Google Scholar]
Here you go flash. See Xena’s compilation of IP. I would like very much for you to spend your Saturday and Sunday searching for any and all wormholes that could help you achieve your goals and objectives.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=151418888
Enjoyed the story. And today’s presentation and its clear and confident tone & tenor and rapid fire representations to the investing public of 2-73 positive results that the Company knows to be occurring (and why.... across multiple indications) had the hallmarks of another Dr Missling clarion call (to those willing to listen) that it’s time to either get on board or prepare to be run the &$@# over.
Just my opinion of course.
PW I’ve not checked much this week but you can see on the RSAA’s fb that it’s largely posts about Anavex and 2-73 in 2019
https://m.facebook.com/rettaustralia/posts/?ref=page_internal&mt_nav=0
Thanks for that; amazing that it was only 2/10 of a tspn per day.
Off topic I believe I heard him emphasize that enrollment details and updates are forthcoming. Why not give them today? Not sure. Maybe a p/r next week.
But along with enrollment details, let’s hope he’ll tell us if the PDD participants are on a participant/caregiver/PI-requested open label extension already or not. (For Jonjones)
Indeed that’s what I heard also. Very large effects. Very low dose. Administered in oral liquid. Behavior improved, sleep improved, correlated with biomarkers (gaba and glutamate), 6 out of 6 improved, significant improvement per Dr Kaufmann, one in particular was a “super responder”, leading worldwide Rett Syndrome researcher presented as such last Friday in Finland as well.
What type of action might I take if my daughter was suffering with this devastating disease and I followed the developments of today and last Friday?
Knocking down the door comes to mind.
The presentation was excellent. Anyone saying otherwise needs to have their head examined.
I understand the CEO was speaking quickly and you may’ve had difficulty comprehending. I’m glad to work on a written transcript if that would help you?
Chances are we’ll find out the answer in about 68 hours.
Exactly! It’s intriguing since I’ve personally found that that there’s yet to be any Anavex released bad news or trial failures reported or serious adverse 2-73 safety issues or publications released that would invalidate our MOA, and that the number of peer-reviewed validating scientific publications supporting Anavex and our MOA continues to grow by the month, and highly respected CNS/epilepsy/RS scientists and researchers continue to join our Anavex SAB/team in recent years and patients/caregivers/trial PI’s continue to request to extend 2-73 treatment after completion of trials (in multiple indications).
Yet after reading a particular post today (which they clearly worked very hard on during their Sunday, which was much appreciated), I just couldn’t help but wonder if I should set aside all of the above (and all of the other charts on slides 6-8 showing each patient improving in various efficacy/behavior measures) and rely instead on a statistical-nomenclature-contortion-argument and thereby jump to the conclusion that our SAB/BOD/CEO/CMO all have it wrong and that they were collectively-unqualified to properly analyze these first 6 Rett Syndrome patients.
And confusingly as well, that the world’s most experienced Rett Syndrome researcher should not be the one that we trust to tell us what really happened during the course of that 7 week trial.
https://www.anavex.com/wp-content/uploads/2019/09/ANAVEX2-73-RS-001-Finland-Conference-Sept-2019-Final.pdf
Wait, so the world’s foremost Rett Syndrome researcher should not be the one we trust to tell us what really happened during the course of that 7 week trial?