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DANMARKS STØRSTE INVESTORSITE MED DEBAT, CHAT OG NYHEDER

ANAVEX. NY TRÅD ÅRSRAPPORT 2021!!!!


98835 Tasso1 24/11 2021 13:03
Oversigt




24/11 2021 13:13 Solsen 898836



Anavex Så blev igangsætning af forsøg udskudt. Ærgerligt det går så langsomt.

ALS indikationen er til højrebenet og super interessant. Men de skal sq starte de forsøg for at få data.

Håber de melder ud at de får flere hænder til at hjælpe med den håbløse hastighed.

Jeg er stadig positiv på casen :-)



24/11 2021 13:33 Tasso1 698838



Anavex. Lover stadig vigtige resultater i år for RETT og 3-71 i FTD.

Opstart Fragil X, Parkinson image og ubenævnt indikation skubbet til 1. halv. 2021.
Resten som forventet - indtil videre!

Meget spændende med ny stor potentiel indikation ALS - præsentation 29./30. nov.

Vigtigst af alt er at vi stadig forventer resultaterne fra RETT fase 2/3 +17 år inden for den næste ca. 1 måned - tror dette er nøglen til det videre forløb i bl.a. Fragile X m.m.
Har det fint med og giver god mening, at vi afventer RETT før de andre indikationer startes op.

Vi må se om vi får lidt mere kød på i aften kl. 22.30.

https://wsw.com/webcast/cc/avxl20/1492110.




24/11 2021 15:24 Solsen 698844



Ja vi må høre hvad der bliver sagt.

Men jeg kan ikke se hvorfor vi skal afvente forsøgsdata fra 31 pts i Rett for at komme i gang med en endnu større og anden indikation. Hvis de skal analysere de 31 pts til bunds og herefter lave protokollen så skal vi ind i H222 eller senere med det tempo de fører. FragileX folkene sagde jo senest, at forsøget jo helst skulle være startet i går.

Per review artiklerne er også glemte.

Håber Missling åbner lidt for hvad de går og bruger tiden på og hvad de ser i de data de analyserer og analyserer.

Stadig positiv på casen ;-)



24/11 2021 23:20 Solsen 1098858



Anavex Missling imponerer stadig selv om jeg er træt af at vente.

PDD og PD pivotal er også på vej - taler med fda om disse forsøg. Så nye forsøg i 2022 står i kø.

Der blev også spurgt ind til Avatar og de relativt få pts. Men forsøget er med flere pts end tilsvarende US forsøg og med højere dosis så forventningen var mindst lige så gode data.

Ved stærke Avatar data vil man søges markedstilladelse. Ellers afventer man Excellence.

Excellence udvidet i antal for at sikre analyse af de yngre pts i to aldersgrupperinger.

OLE i AD udvidet til 3 år fra 2 år efter ønske fra deltagerne i forsøget (fase 2/3). Placebogruppen er konverteret til behandling for over 90% vedkommende. Der må været helt klar synlig effekt (min kommentar)

Vil partner med Big Pharma i PD og AD så sent som muligt for at få mest værdi til Anavex.

Nogen overlapning mellem rett og fragileX - hvilket nok er årsag til at afvente opstart i FragileX. Vel ok trods alt (min kommentar).

Meget overbevisende i mine øre.




24/11 2021 23:51 Tasso1 1198861



Anavex Udmærket Webcast!

Ingen negative overraskelser og gode kritiske spørgsmål fra de forskellige analytikere!

Helt tydeligt, at RETT Avatar kan blive det store vendepunkt - man vil lade resultaterne tale for sig selv og ud fra disse evt. ansøge FDA om markeds adgang, såfremt resultaterne er overbevisende.
Missling understregede, at man forventede endnu bedre data end i RETT US forsøget pga. af den højere dosis 2-73.
Han understregede også, at RETT US og Avatar ville kunne udgøre en stærk samlet pakke, som tilsammen potentielt ville opfylde kriterierne for det FDA kræver for godkendelse af en sjælden indikation - idet indikationen har en så lille patientgruppe og samtidig ikke har nogen behandlingsmulighed.

Missling gjorde det rimmeligt klart, at Anavex agter at køre/markedsføre de sjældne indikationer, som RETT, Fragile mm. alene - og dermed øge værdien af selskabet.
Han åbnede dog også samtidig lige så klart op for, at Anavex vil søge en større og nødvendig partner, for at få den nødvendige gennemslagskraft, når både Alzheimer og Parkinson skal på markedet - men først når man kan få det optimale økonomiske ud af det, til fordel for Anavex og dets aktionærer! - (det vil blive rigtig dyrt for disse BP`er til den tid - og den eller disse potentielle partneraftaler, vil komme til at hænge som en konstant trussel over shorterne!)

Vedr. Parkinson sagde Missling, at man afventer den fulde datapakke fra fase 2 forsøget, men at man er i tæt dialog med The Fundation ( må være MJFF ), for at finde den bedste struktur, når man skal diskutere protokollen for de 2 fase 3 forsøg i PD og PDD.
Man vil dog ikke afvente Image forsøget!

Tingene trækker ud, men Missling gentog flere gange på spørgsmål fra analytikerne, at man forventede resultaterne fra både Avatar og 3-71 i FTD omkring slutningen af året.

Anavex har ca. 152 mill. $ på bogen og der var ingen snak om yderligere nødvendig kapital - ingen gæld.

Nu er den lovpligtige årsrapport overstået og af vejen.
Næste punkt bliver så fremvisning af videnskabelige dokumentation for, at 2-73 også kan have en effekt i ALS. ( 29.-30. nov. )
Ellers kan vi kun vente på div. nyheder, som altid!

Alt er godt, men en langsomlig proces - casen fuldstædig intakt og positiv!

Shorterne har også reduceret en del fra 5,1 mill. til 4,4 mill. aktier.










25/11 2021 07:10 Tasso1 898867



Anavex. Udskrift Webcast

https://seekingalpha.com/amp/article/4471873-anavex-life-sciences-corp-avxl-ceo-christopher-missling-on-q4-2021-results-earnings-call


Anavex Life Sciences Corp. (AVXL) CEO Christopher Missling on Q4 2021 Results - Earnings Call Transcript
Nov. 24, 2021 9:35 PMAnavex Life Sciences Corp. (AVXL)
Summary

Anavex Life Sciences Corp. (NASDAQ:AVXL) Q4 2021 Earnings Conference Call November 24, 2021 4:30 PM ET

Company Participants

Clint Tomlinson - IR

Christopher Missling - President & CEO

Sandra Boenisch - Principal Financial Officer & Treasurer

Conference Call Participants

Raghuram Selvaraju - H.C. Wainwright

Soumit Roy - Jones Trading

Operator

Welcome to the Anavex Life Sciences Fiscal 2021 Fourth Quarter Conference Call. My name is Vage [ph] and I'll your operator for today's call.

At this time, all participants are in a listen-only mode. [Operator instructions] Please note this conference call is being recorded.

I'll now turn the call over to your host Clint Tomlinson. Sir, you may begin.

Clint Tomlinson

Thank you and good afternoon, everyone. We appreciate you joining us today for Anavex Life Sciences fourth quarter conference call to review financial results and discuss the company's business updates. The tape replay of this call will be available after the call. The call will also be available for replay on Anavex's website at www.anavex.com.

With us today is Dr. Christopher Missling, President and Chief Executive Officer; and Sandra Boenisch, Principal Financial Officer.

Following management's remarks, there will be a question and answer session. Before we begin, please note that during this conference call the company will make some projections and forward looking statements. These statements are only predictions based on current information and expectations and involve a number of risks and uncertainties. We encourage you to review the company's filings with the SEC. This includes without limitation the company's Form-10K and 10-Q, which identify the specific factors that may cause actual results or events to differ materially from those described in these forward looking statements. These factors may include without limitation risks inherent in the development and or commercialization of potential products, uncertainty in the results of clinical trials or regulatory approvals, need an ability to obtain future capital and maintenance of intellectual property rights.

And with that, I'd like to turn the call over to Dr. Missling.

Christopher Missling

Thank you, Clint. We really appreciate everyone joining us on today's conference call to review our most recent reported financial results and to provide obvious business update.

We concluded an exceptional fiscal year 2021 while continuing our momentum highlighted by the efficient execution [indiscernible] Phase 2/3 AVATAR clinical trials Rett Syndrome, the ANAVEX 2-73 clinical Phase 2/3 AVATAR Rett Syndrome as well as [indiscernible] ANAVEX 3-71. Starting with our lead drug candidate 2-73, we expect top line results from the second placebo controlled study for the treatment of outpatients with Rett Syndrome, which are expected to be announced [ph] around calendar year end 2021.

This study took place in Australia and the United Kingdom using a higher dose than the US based phase two study and enrolled 33 patients over seven week treatment period, including ANAVEX 2-73 specific precision medicine biomarkers. Top line results from the placebo controlled excellence phase two slash three study for the treatment of patriotic patients with Rett syndrome are expected in the first half of 2022.

This Phase 2/3 study in patriotic patients with Rett Syndrome, with five to 18 will evaluate the safety and efficacy of 2-73 in approximately 84 patients over a 12 week treatment period, including 2-73 specific precision medicine biomarkers. Regarding our Alzheimer disease program top line results from the placebo controlled phase 2b/3 Alzheimer [ph] study for the treatment of Alzheimer disease are confirmed and are expected in the second half of 2022.

The double blind placebo controlled 509 patient late stage Phase 2b/3 study in patients with Alzheimer disease exceeded enrollment of the targeted the number of 52 south across North America, Europe and Australia using others [ph] and ADCS ABL for activities of daily living and function is primary endpoints. This multicenter, double blind clinical trial is measuring efficacy, tolerability and safety of two different ones daily all on ANAVEX 2-73 doses or placebo.

[indiscernible] last month, the independent data safety monitoring board for the company's face 2B free study completed its most recent pre pretend review of the preliminary Phase 2B/3 study data in asthma patients. As specified in a protocol, the [indiscernible] reviewed the interim safety data for the 2-73 Phase 2B/3 disease clinical study and its open label extension attention study. Upon review of the interim safety data, the BS recommended to continue the study to modification.

We're very excited also to report that the top line data from another time compound of ANAVEX 3-71 is received often drug designation by the FDA for Frontotemporal dementia,, a placebo control Phase 1 study in ANAVEX 3-71 evaluating 371 in humans are expected around calendar 2021. During 2022, we were also moving closer to further expanding the pipeline for 273 using gene biomarkers of respond, applying precision medicine for another neurological disorder with unmet medical lead, including a plant initiation [ph] of 273 imaging focus, heart disease clinical study. A plant initiat initiation also of a Phase 2 cell three clinical trials for the treatment of a new rare disease indication and lastly, a planned initiation of a pivotal Phase 2 specialty of a new [indiscernible] the most genetic cause of [indiscernible].

In Federal [ph], most frequent announced August of this year data [indiscernible]. I would like to direct the call to Sandra Boenisch, Principal Financial Officer for a brief financial summary of the recently reported year end.

Sandra Boenisch

Thank you, Christopher and good afternoon to everybody. We continue to maintain a strong balance sheet and fiscal responsibility. Our cash position on September 30, 2021 was $152.1 million, which we believe is sufficient cash runway to fund operations and clinical programs beyond 2025. During fiscal 2021 cash utilization and operations was $30.4 million. We reported a net loss of $37.9 million for the full fiscal year, which is $0.54 per share as compared to $26.3 million or $0.45 per share in the comparable year 2020.

Research and development expenses for the year were $33 million compared to $25.2 million for the comparable fiscal year. The increase is primarily attributable to the continued advancement of our ongoing clinical trials. Most notably the full enrollment of our international Phase 2B/3 Alzheimer's disease trial and the related open label extension and the continued enrollment and advancement of the Rett Syndrome studies and expansion of these trials internationally. General and administrative expenses were $9 million for the year as compared to $5.9 million in the prior year. The increase is mostly significantly associated with an increase in personnel and associated non-cash stock option compensation charges.

Thank you. And now I'll return the call back over to you, Christopher.

Christopher Missling

Thank you, Samra. And as we look to the remainder of 2021 and into 2022, I'm very excited about the company's potential as we continue to advance and expand our position medicine to programs. As we look ahead, we will continue to focus on driving meaningful growth across our broad CMA one platform, portfolio to deliver transformational treatments for patients with both degenerative and developmental neurological disorders around the world.

So we look forward to providing further updates of advanced and continue and at this point, I like to also wish everyone a happy Thanksgiving. I would like now to open the call for questions. Operator, please go ahead.

Question-and-Answer Session

Operator

[Operator instructions] And our first question comes from Charles Duncan from Cantor Fitzgerald. Your line is open.

UnidentifiedAnalyst

This is Pete [ph] for Charles. Good afternoon Christopher and team and congratulations on the progress and appreciate all the updates. I have a couple of questions regarding Rett Syndrome. When you think about the efficacy measures that were made in the efficacy scene in the US adult study, how do you feel about the samples size or the planned effect size out of AVATAR and also the excellence study. And we saw that you upsized the sample size for excellence from 69 to 84 subjects which role that decision, if you can give us some color on that.

Christopher Missling

Appreciate it and thank you. So the efficacy effect size was really significant in the first US study, which was using a low dose, as you remember, and the effect size was in the range 1.3 to 1.1 -- 0.3, which is considered very large. And since we expect those response based on higher doses, we basically inclined to believe that the second study, the other AVATAR study might show a similar if not higher effect size, given that we are using a higher dose in the AVATAR study compared to the US study.

The extension of patient number in the excellent study from originally 69 to 84 was based on a request a regulatory request to also have an additional sub analysis of the number of patient in different age groups for example, from five to 18 to also have an additional analysis of patients from five to 12, and then from 12 or 13 to 18 in order to make sure we have enough power for this additional calculation, we thought it was prudent to just add additional number of patients with ended up to the total number of 84 as we communicated.

UnidentifiedAnalyst

Thank you. Very helpful. We also saw that you made a few changes to the primary and second very endpoint in the excellent study. Can you give us a help us understand on what drove those decisions, was a result of advice or interactions with the FDA or any other regulatory agency,

Christopher Missling

Right. So we have noticed that the RSQ is really the most rigorous, more rigorous endpoint. It is really going through 45, very dedicated questions and detailed question, which can be answered very precisely. There's also the ability which we have seen, and we have demonstrated that in our presentation of doing sub-analysis of the sub scores of the entire score of the RSPQ, however, when we look at that we noticed that there was a weaker ability to make this because it's a really a global assessment and it also has a very known and it's published weak I would say reliability, but we basically include that still, but we didn't want to overemphasize that score. So that was the background for the focus on the RSPQ.

UnidentifiedAnalyst

All right. Thank you. And my last question regards to the Parkinson's disease dementia program, can you provide any updates on that program, have you met with the agency to discuss it and or do you plan to anytime in the near future?

Christopher Missling

Yeah, we plan, Right. Thank you very much. Yes. We plan to do that. We actually are in the process of now discussing the data with the foundations and we are expecting to get a valuable feedback for input on the design of pivotal studies for Parkinson and also pivotal study for Parkinson dementia. And with that, in our package, if you like, we then feel more robustly educated and fully informed to go to do the discussion with the agency about a proper pivotal study in the respective communications.


UnidentifiedAnalyst

Do you think, by some chance you're going to wait for the imaging study results or it'll the meeting will occur beforehand.

Christopher Missling

This will be before the imaging study, but definitely we are still including which we have not yet reported the total gene analysis of the PD study. So that means we've not only looked at the Sigma one gene expression changes of the mRNA, but also the gene expression of all participants that is in the active arm, as well as in the placebo arm and believe that additional intelligence can be drawn out that to make an informed design of a study, which increases further the chances of a pivotal study down the road.

UnidentifiedAnalyst

All right. Thank you. Thank you very much for taking my questions and congratulations again on the progress and happy Thanksgiving,

Christopher Missling

Thank you.

Operator

Next question comes from Raghuram Selvaraju from H.C. Wainwright. Your line is open.

Raghuram Selvaraju

Congrats for the progress and thanks for taking our questions. So firstly, how early in 2022, do you envisage filing an NDA for [indiscernible] in Rett Syndrome, providing you positive readouts from the three trials?

Christopher Missling

It's really, I would let the data first come out and then we can talk about that, but obviously pending data as soon as possible.

Raghuram Selvaraju

Excellent and then with regards to 2-73 what learnings are you transitioning into your Fragile X syndrome development? For example, are you planning on cross analyzing data from the Rett Syndrome and the fragile X syndrome trials, given that the two syndromes sort of share over overlapping symptoms as well as underlying cellular mechanisms?

Christopher Missling

That exactly right. So two pockets here to look at one is the preclinical pocket, and we see a very strong in the animal model of a Fragile X and leading to even reversal of the pathology. And then we look also at the clinical study of the Rett Syndrome, and we see that the phenotypes are overlapping between these two indications. And there are some end points, which are included in the Rett Syndrome study for example, atoms [ph] is one of them and that had been responding very well with the drug and we believe this could be also used as a key measure for the Rett Syndrome for the Fragile X study, since that has been also even used prior in Fragile X study as our primary endpoint. The decision is not yet made exactly about how to use that endpoint, but this could be one potential venue.

Raghuram Selvaraju

Okay. Very helpful. And we read with interest your recent published paper in expert opinion on therapeutic targets where you described 273 and 371 as hand in hand targets for Alzheimer's disease. We were wondering if you've number one, benchmark these drugs together pre-clinically, and number two, test a company nation if not, do you plan to do so.

Christopher Missling

So the two compounds came from different angles and different labs but they are now moving more into what we call, we try to learn as we go. But so far we could not find parable assay other than a very early preclinical assay of target engagement. And there are differences in the affinities of the Sigma 1 receptor and also difference to the muscarinic receptor, which we believe is also important.

And ultimately we will be only able to see really the difference of the two if we run really both indication world drug and the same indication in the same trial. So we think that each drug has its own merits and it could very well be that 371 is really good at focusing more in Frontotemporal, and could also be very good at [indiscernible] but right now we have 273 more advance, so we will eventually find out,

Raghuram Selvaraju

Appreciate the color. And then just finally you've talked about 273 using in a prophylactic manner. We saw a recent science advances article, which describes a unique kind of brain protein signature in younger cohorts, mean age of 39. Are you currently working on or planning a genetic or protein test in a younger cohort to kind of help your 273 administration in the future?

Christopher Missling

Yeah, we look into that and it's a very good point because while the disease is showing up correlating with age, it's clear that early intervention is really most likely the most efficient way to incubate this disease. And our preclinical data indicates that potential, which was done very successfully in animals that who got the drug before they got injected with a toxic, a better load. And they never developed the symptoms of Alzheimer disease. So there's really high likelihood that we should or encouragement to also proceed. And we sat and we committed to eventually do that with the appropriate in the appropriate time, down the road. So we are committed to look into that what you described early on.

Raghuram Selvaraju

Okay. Excellent. That's it from us? Congrats again, and happy Thanksgiving to you and everyone on the call. Thanks.

Operator

Next question comes from Soumit Roy from Jones Trading. Your line is open.

Soumit Roy

Hello everyone. And thank you for taking the question. Could you give us a little color around the upcoming Rett study? So as I understand, there will be different dose cohorts. So is, could you give us an idea of the size and is there going to be intra cohort dose escalation? What should we expect?

Christopher Missling

Yeah. So let me explain that there is not a different dose. It's just a target dose is higher than the US study. So there's only one dose and one placebo arm, and that one dose will be a target dose. So that is just higher than the US study. So there will be not multiple doses, technically it's just one higher dose.

Soumit Roy

Okay. Got it. So, and you are not disclosing if it's going to be 10, 20 or 30,

Christopher Missling

Right. We will find out when we disclose the data and then we'll be able to learn about that.

Soumit Roy

Got it. And any color on the Alzheimer's trial, what are you planning as patients are coming out of the 48 week? Is, are they going to go into maintenance trial or what is the plan there?

Christopher Missling

Right. So we have an extension study called Attention ID, which is a two year study of following up as an open label after the 48 week, which has started, after the first patient finished the 48 weeks. And because these patients have actually, some of them finished this phase two open label extension, they had requested to continue to stay on the study drug.

And so what we did, we initiated and we're successful in expanding now this attention AB study open label extension from two years to three years. So patients who are finish the study, the placebo control study, enter into the extension study finish the two years will now continue to go into the third year. And that is because of request by the patient, the caretakers and the physician. It also, I like to add that the I like to add also that the conversion from the placebo controlled part of the study to the open label is very high it's above 94% currently, which is a good sign.

Soumit Roy

Great. It's really good to hear. And one last question on the back to the Rec program, where are you on the conversation turning whether these going to be the data [ph]

Christopher Missling

It's really a question now of the data and the data has to speak for itself. And we also said it's a potential pill study. So the word really weighs in, and the data really will determine this how this will be looked at. We have to point out that for adults, there is no treatment available. And the patient population is also harder to bring into the trial because they're more at large. They also are because of the disease early passing on, they're not many patient available to find in a trial. So the focus is really on the study for that reason, but still there's an unmet need for patients of all ages for X syndrome.

So we could expect, you could even start a rolling submission with the adult trial, if need be that could be approved first before the pediatric really gets filed. I would say it cannot be excluded and, but I cannot promise it either. So that's why I said we would have with ANAVEX [ph] study and the US two independent placebo control study in disease, which usually is beyond the request from for rare diseases usually. So this will be successful, a very powerful package.

Soumit Roy

Got it. Congratulate again for on all the progress and happy Thanksgiving.

Christopher Missling

Happy Thanksgiving. Thank you,

Operator

Next question comes from [ph] from BTIG. Your line is open.

Unidentified Analyst

Hi. Thanks very much for taking the question. So the first one is on Rett Syndrome and so the definition of a responder, is that on each efficacy endpoint, is that going to be the same in pediatric patient as two, an adult patient, and also the definition of a responder is that consistent with how clinicians are viewing as clinic meaningful improvement?

Christopher Missling

That's correct. It's consistent first study and then consistent with the assessment. That's correct.

Unidentified Analyst

Okay. Then I think I didn't see an update on the 371 program in 2020 sorry, 2022 in terms of upcoming milestone. So I just wanted to check if frontal temporal dementia is still going to be the first indication for that program. And when do you expect a study potentially to start.

Christopher Missling

Right. So we have mentioned that we would move ahead with prototype dementia, but we like to have really the solid phase one data in hand before we say we commit to this. And but we definitely will move forward with FTD or any other related dementia indication.

Unidentified Analyst

Okay. And then on the pipeline, I think well, it's very encouraged to be able to target multiple indications, but just wonder which indications do you think you would like to prioritize going for? Of course, the Rett Syndrome and is going to be the lead indication, but which indication do you think might be suited for partnerships?

Christopher Missling

So we believe that we have with the red disease franchise, which is Rett Syndrome FX and others the ability, and it's not been the first time that a company has built this into a commercial entity with the disease targeting rare diseases. So that seems to be very doable. It comes to the indication like Alzheimer disease and Parkinson disease, which requires also the involvement of a detailing practitioners, physicians of general physicians. Then it might be more powerful to penetrate the market with the support of a large pharma partner and at the right time to make sure that we retain most upside for Anavex and for our holders, this will be done at the right time and not to prematurely to give up to much of the upside, but it is no doubt that these large indications require additional support.

Unidentified Analyst

Okay, great. Thank you very much. And happy Thanksgiving.

Operator

And your next question comes from [indiscernible]. Your line is likewise. And that concludes the question and answer portion. And it also concludes the conference call. Thank you for participating. You may now disconnect.



26/11 2021 06:57 Kyed01 998890



Anavex præsenterer på ALS konference 29-30 november.

Interessant nok er det Nell Rebowe som gør det, som jeg har checket lidt på.

Hun er meget smuk og er også foto model.

Hvis nu hun havde præsenteret tidligere i stedet for den tørre Missling ville kursen nok værre over 100 allerede, ha-ha.

https://2021alsoneresearchsymposium.splashthat.com/?fbclid=IwAR0gzPM7QjhtoMiBLKCSxOKdo9SQSxygLPjQwiqMjYmY-CKTTC1ZqfiJkTA


https://www.nextmanagement.com/miami/profile/nell-rebowe



26/11 2021 20:02 Budweis 698925






26/11 2021 20:42 Solsen 698926



Hvis ikke man kigger på Ihub så følger dette svar fra MayoMobile på spørgsmål om Cohens Effect size

https://investorshub.advfn.com/boards/read_msg.aspx?message_id=166914423

Interessant at der er supergode Cohens effect size i rett og alzheimers i sigma1 varianten wildtype.



29/11 2021 13:10 Tasso1 698991



Anavex Live Webcast torsdag den 2. december

https://newsfilter.io/a/12a6afff289272725b9d50855e3bbb2d

Annual Evercore ISI HealthCONx Conference on December 2, 2021 at 12:10 p.m. ET. - 18.10 DK-tid.

https://www.anavex.com/investor-material

Nell Rebowe er jo også på i morgen tirsdag med ALS.


Der kan komme nyheder hver dag nu - spørgsmålet er om "around end of year" allerede er denne uge?
Bemærk at webcastet den 2. dec. er i åbningstiden - så der vil blive kontant markedsafregning ved gode/dårlige nyheder.




29/11 2021 15:59 Tasso1 799003



Anavex Evercore ISI HealthCONx Conference

Dette er en såkaldt "Firesite" konference, hvor man udover muligheden for at afholder et webcast, som Anavex, også kan mødes med andre biotekselskaber - alle de store BP er der også som regel.
Så måske Missling skal sidde lidt i en læderstol ved pejsen, med en god cognac i hånden og sludre lidt med potentiel kommende partner - efter han lige har præsenteret lidt gode data?

Hvem ved, men det er i hvert fald det konceptet går ud på!

Fik lige købt for 50.000 kr. til kurs 19.99 $ ved åbning - måske sidste gang aktiekursen var under 20 $??




30/11 2021 07:18 Tasso1 799017



Anavex Anavex og ALS

Nell Rebowe er på i dag med potentialet for 2-73 i ALS.

Helt tilbage i 2014 er der udgivet en Peer Review, som beskriver potentialitet for 2-73 i ALS:

Anavex Encouraged By Scientific Data Confirming Sigma-1 Receptor Agonist Extends Survival in ALS (Lou Gehrig's Disease)

https://www.globenewswire.com/news-release/2014/03/10/616981/10071871/en/Anavex-Encouraged-By-Scientific-Data-Confirming-Sigma-1-Receptor-Agonist-Extends-Survival-in-ALS-Lou-Gehrig-s-Disease.html

I 2019 fandt forsker fra Mainz ud af, at 2-73 stimulerer den vigtige autophagy process - udrensning af celleindholdet, som menes at spille en afgørende faktor i behandling af bl.a. AD, PD og ALS!
Siden har Anavex hidtil "kun" gået videre med Alzheimer og Parkinson i kliniske forsøg. Et valg man nok har gjort på baggrund af en den gang begrænset økonomi og afvejning af potentialet i markedet for de enkelte indikationer.
Nu da Anavex er relativ stærk kørende økonomisk og man har fået bekræftet effekten i både AD og PD, så er tiden måske nu moden til at starte kliniske forsøg op i ALS!

New preclinical data establishes ANAVEX®2-73 as a modulator of autophagy through Sigma-1 receptor activation, possibly needed for the prevention and treatment of neurodegenerative conditions including Alzheimer's disease, Parkinson's disease and ALS

https://www.anavex.com/press-releases/anavex-life-sciences-reports-publication-of-new-data-that-show-anavex%C2%AE2-73-induces-cellular-recycling-process-linked-to-the-prevention-and-treatment-of-age-associated-diseases


Anavex casen vil udvikle sig hurtigere nu, når både videnskaben og økonomien er mere solid.



1/12 2021 17:49 Tasso1 699064



Anavex Soumit Roy Jones Trading kursmål 50 $!!

Soumit Roy fra Jones Trading er en 5-stjernet analytiker, der var med da Anavex afgav årsrapporten den 24. november.
Han havde flere gode spørgsmål til Missling.
Efter hans mening skal Anavex stadig op i 50 $, så han har åbenbart stadig tillid til casen.

https://www.tipranks.com/analysts/soumit-roy


Ellers en relativ stor omsætning i går den 30. nov., over hele linjen - nogle mener, at dette var sidste dag i US, hvor negativ afkast skal realiseres, hvis det skal kunne modregnes i 2021.
Måske andre kan bekræfte dette?

Husk webcast i morgen kl. 18.10!
Der må komme en ny december præsentation lidt før, med lidt held også en pr. kl. 13.00 - men det vil jeg nu ikke satse på, da jeg som regel har taget fejl på dette.

Annual Evercore ISI HealthCONx Conference on December 2, 2021 at 12:10 p.m. ET. - 18.10 DK-tid.

https://www.anavex.com/investor-material



1/12 2021 23:38 Tasso1 599074



Anavex. Ser ud til at Anavex ansætter den 3. tidligere FDA ansat!

Fra IHUB:

Adebayo "Bayo" Laniyonu

https://www.linkedin.com/in/adebayo-bayo-laniyonu-3a5b27224/

Senior Vice President (Nonclinical Development)
Company NameAnavex Life Sciences Corp. Full-time
Dates Employed2021 - Present
Employment Durationless than a year
• Nonclinical Development Program
• Regulatory Writing
• Regulatory Policy


Blarcasamine--Great find--thanks for posting--things happening at Anavex Corp.----Dr. Adebayo (Bayo) Laniyonu, Senior Vice President for Nonclinical Development at Anavex Life Sciences Corp, has over 24 years' experience with the US Food and Drug Administration (FDA).

Prior to joining Anavex, Dr. Laniyonu served as Supervisory Pharmacologist/Toxicologist at the FDA Center for Drug Evaluation and Research (CDER). He has reviewed hundreds of NDAs, BLAs (including first in class), sNDAs, ANDAs and INDs and provided high impact regulatory and strategic recommendations to the sponsors of these products. He organized, chaired and presented at FDA workshops and at scientific sessions of professional societies, where he presented on FDA current thinking on regulatory issues. Additionally, Dr. Laniyonu has presented at FDA Advisory Committee meetings. His review and supervisory experience span several therapeutics areas, including Rare Diseases and Medical Genetics, Hematology, Medical Imaging, Radiation Medicine and Medical Counter Measures products. Dr. Laniyonu played pivotal roles in the development of several FDA regulatory guidance documents.


Tror ikke at der mange mindre biotek selskaber, der har så mange tidligere FDA ansatte.
Mon ikke dr. Bayo har fået lidt intern viden om udviklingen på de forskellige områder, inden han sagde ja til jobbet?

Man skulle næsten tro, at han tror på, at skidtet virker? - eller hopper han bare med på vognen for ussel mammon?

Uanset kunne Anavex godt have smidt en lille PR på dette!



2/12 2021 01:44 Kyed01 299075



Av av det var ikke så rart at vågne op til:

AVXL: -7.68%
SAVA: =8.79%
ANVS: -10.22%

I det mindste er det hele sektoren der for klø og Anavex klarer den lidt bedre end konkurrenterne.

Godt nok at de har hyret endnu en kapacitet indenfor FDA domænet det er et godt tegn, helt sikkert.

Kursmaal på 50$ fra en top analyst er helt fint på kort sigt.

Der er intet andet at gøre som vi har gjort hele tiden: Vi venter spændt på data!



2/12 2021 07:23 Tasso1 599077






2/12 2021 11:34 Solsen 899084



Anavex .. Ingen tvivl om, at Anavex har fat i rigtigt mange kompetente personer enten som rådgivere eller direkte ansatte.

Det er supervigtigt med viden på højt niveau samt en god tilgang til fda. Sidstnævnte kan virkelig spænde ben, hvis firmaet ikke kan levere det der ønskes fra fda's side.

Jeg har flere gange beklaget mig over hastigheden i firmaet og er stadig af den opfattelse.

Udskydelserne af Avartar og Excellence er der nok en forklaring på. Sidstnævnte forsøg efter fda guidance. Man kan diskutere hvorvidt de selv skulle have sørget for en afbalancering af forsøgsdeltagerne aldersmæssigt....

At man først efter ca et år med et færdigt PDD forsøg sidder med hele datasættet fra dette forsøg er mig ubegribeligt. Der må være gået noget galt i den proces. Normalt taler vi måneder før data foreligger endeligt. Jeg køber ikke at det tager tid. Kun et spørgsmål om at tildele ressourcer så kommer data hurtigere frem.

Nu har vi så datapakken. Anavex starter med at diskutere denne med en "faundation" - sandsynligvis MJ Fox.
Hvis ikke de selv kan finde ud af dem så skulle de hellere finde et BigPharma at samarbejde med omkring det videre forløb. Med den hastighed Anavex arbejder med kommer de forsøg jo ikke i gang før langt inde i 2022. Rekruttering vil tage rigtig lang tid i Anavex regi, mens et stort pharma vil relativt hurtigt få indrulleret pts i både PD og PDD.

Patienter og investorer skriger på, at det potentielt livsforbedrende stof kommer ud kommercielt.

Hastigheden er vigtig i forhold til patentudløb i sidste ende. Evt Rett approval sætter slutdatoen herfor. Så at forsinke data på PD og PDD og approval er med risiko for at miste 2-3 år i sidste ende af blarcamesines lifecycle. Det kan blive dyrt !

Så mit håb er, at man partner snarest muligt for at komme tættere på mål i de voldsomt mange indikationer der ligger åbne.

Det er muligt, at et positivt udkomme af Avartar kan bringe dem i en god forhandlingssitutation, idet de så står med første markedsføringstilladelse inden udgangen af 2022.

Men at vente meget længere med at tage nogle flere muskler ind er i min optik en fejl.

Investorerne mangler også at blive præsenteret for datapakken på PDD studiet, som lovet.

Missling virker overbevist, men han mangler at vise os hvorfor !

Lad os høre, om der er lidt optimisme i dagen CC vi kan klamre os til.

Aktiekursen er ligegyldig - data afgør fremtiden ikke dagens kurs !

Jeg sælger ikke en aktie, men så gerne lidt turbo tilsat :-)



2/12 2021 13:59 Solsen 399093



Anavex ... Ikke mindre en to partnership nyt i dag af interesse.

Novartis og GSK:

https://endpts.com/watch-out-roche-novartis-inks-1-5b-deal-to-chase-down-prominent-parkinsons-target/

https://endpts.com/glaxosmithkline-oxford-unveil-new-partnership-pitting-buzzy-rd-advances-against-neurological-disease/

GSKs partner Alector har nogle meget interessante tidlige data i frontotemporal dementia. En direkte konkurrent tl 3-71 vi afventer data fra.

Håbede lidt på Novartis som partner til Anavex....

Så gerne lidt fart på Anavex :-)



2/12 2021 19:35 Solsen 999103



Anavex ... Dagens webcast/fireside chat fra Evercore var igen en opmuntrene oplevelse. Helt forskellig fra kursudviklingen :-)

Missling er inde i sagerne og udspørgeren var ligeså. Evercores mand var synligt imponeret over de historiske data og spurgte ind til hvordan de enkelte igangværende forsøg var powered - for at forsikre sig, at der er nok pts til at sikre signifikante resultater. Missling kunne redegøre tilfredstillende for de enkelte forsøg, hvor historiske data udgjorde beslutningsgrundlaget herfor.

Doseringsstørrelsen blev der spurgt til. Missling redegjorde for, at der næppe er problemer med overdosering og at der er tolerence for stoffet pænt over den dosering der er anvendt. For høj dosering ses kun at hæmme virkningen en anelse.

Følgende blev endnu engang bekræftet:

- Pivotale PD og PDD forsøg er ved at blive planlagt
- Readout for Avatar og 3-71 bekræftet igen til omkring nytårsskiftet
- Readout Excellence H122 og AD ph2/3 H222
- AD ph2/3 er et registreringsforsøg/pivotal, hvis data er stærke - her nævnte Missling Aduhelm som "bencmark" (mon det kan kaldes benchmark)

Nogle spændende uger forude selvom kursen kører sit eget løb indtil data kommer.

Bemærk at der i ovennævnte tråd er lidt benchmark til 3-71 forsøget i frontotemporal dementia, hvis effekt måles.



2/12 2021 22:26 Tasso1 899104



Anavex Solsen - fint resume!

Det var i hovedtræk en bekræftelse af, hvad Missling tidligere har meldt ud.
Ser ud til de har helt styr på den aktiv mængde 2-73 og samtidig har et pænt vindue op til en unødvendig overdossering i alle indikationer.

FDA synes iflg. Missling begejstret for især RETT - og understregede, at hvis Avatar var overbevisende, så havde man meget sandsynligt nok til en godkendelse her, fordi det er en sjælden og alvorlig indikation.

Missling bekræftede også, at de med den 152 mill. $ på bogen kan financierer alt det de har og agter at sætte i gang de næste 3-5 år - UDEN at skulle hente nye penge.
(Tror dog, at Anavex som hidtil løbende sælger et mindre antal aktier, for at bevare vinduet på de ca. 4 år)

For os der kender casen, var der som sagt ikke meget nyt - men for nye potentielle investorer må de beskrevne resultater og fremtidsudsigterne da virke ret tiltalende.
Tror også at flere nu har en anledning til at sætte sig lidt ind i, hvad Anavex egentlig har gang i.


Husk Missling er på en RETT konference den 14. december!





4/12 2021 00:12 Tasso1 799138



Anavex. December præsentation.

https://www.anavex.com/_files/ugd/850d88_ff99cd3c1332457b8a010590bb0adec2.pdf

Top-line data AVATAR: Potentially pivotal Phase 2/3 adult RTT clinical trial - expected YE 2021

Top-line data Phase 1 ANAVEX®3-71 clinical trial - expected YE 2021

Ikke meget nyt ,men en bekræftelse af, at vi kan forvente data i december - spørgsmålet er så, hvor længe før en offentliggørelse/præsentation har Anavex kendskab til resultaterne?

Anavex udgør 0,92 % af XBI indekset, hvilket samlet faldt 4,4 % i dag - Anavex - 5,6 %.
Positive Avatar resultaterne vil forhåbentlig adskille os fra resten af div. indekser.

https://finance.yahoo.com/quote/XBI/?p=XBI



6/12 2021 14:43 Solsen 799190



Anavex ... En givende debat over weekenden på Ihub og med et indlæg fra bl.a. MayoMobile med en opsummering/analyse af Anavex:

https://investorshub.advfn.com/boards/read_msg.aspx?message_id=167009236

Grønne bjælker i hver slide med interessante kommentarer fra forfatteren.

Lidt surrealistisk at læse om kurs 6.000 :-)

Ikke jeg tror på de 6.000. Men mindre kan jo også gøre det.

Første alvorlige test nærmer sig med Avatar data !

NB Stadig GAP ned til 15,5



6/12 2021 15:15 Kyed01 799192



Jo så godt the flotte opsummering fra super dygtige MayoMobile og er enig i at kurs 6000 er nok i overkanten. Hvis den når derop vil mange mennesker blive helt vildt rige: 167 aktier = 1mill$.

Jeg vil værre ovenud lykkelig hvis vi passer kurs 100 en dag som er mugligt hvis RETT data er gode og medfører godkendelse da flere indikatorer vil følge efter.

Ser ud til at vi åbner i minus i dag, håber på nyheder i morgen men jeg giver det 30-40% chance, nok større næste uge før RETT konference den 14.



6/12 2021 19:00 poppelkongen 699203



øh hvorfor ikke kurs 6000, når Tesla er 10 gange mere vær end Toyota og Toyota laver 10-20 gange flere biler, så kan alt lade sig gøre, men jeg vil være glad for kurs 250 på et tidpunkt



6/12 2021 19:17 Solsen 399204



Det er rigtigt :-)



6/12 2021 21:16 Tasso1 1199208



Anavex Ja ham Mayo er super dygtig, mener han arbejder inden for analytiker eller bioteksektoren - han plejer også at være mere konservativ, så kurs 6000 er højt sat - mindre kan også gøre det. Tror desværre også, at Anavex er blevet opkøbt inden, hvilket jeg ikke håber sker - partneraftaler på enkelte indikationer ville dog på den korte bane give et større gennemslagskraft og større omsætning og nå ud til flere trængende patienter tidligere.

Avartar er nøglen - får vi den prop slået ud af bunden på whisky tønden, så er der ikke meget der kan stoppe casen - for ikke kun får vi sandsynligvis 2-73 på markedet i 2022, men lige så vigtig er, får vi bevist virkemåden MOA af 2-73 og derved sandsynliggøre at 2-73 også virker i de øvrige indikationer.



6/12 2021 21:46 Solsen 899209



Anavex ... Helt korrekt Tasso1.

Det bliver derfor også med høj puls, at vi skal læse meddelelsen omkring Avatar :-)

Hvis det mindre sandsynlige skulle ske, at det skuffer så har vi Excellence at falde tilbage på. Men aktien vil falde med mere end 50%

Mit klare indtryk er, at der er styr på det faglige og i Rett har der tidligere i patientgruppen været overbevisende data. Stadig lidt af en gåde for mig, at man ikke har taget dobbelt så mange pts ind i forsøget for en ekstra sikkerheds skyld. Men de har sikkert styr på det !

Bedste værn imod overtagelse er, at indgå flere partnerskaber kort efter evt gode Avatar data. Pt har de poison pill til at holde købere væk. Og den kan de vel opretholde længe....

Med muligheden for helt at ændre behandlingen indenfor CNS - i det mindste i større grupper indenfor de enkelte indikationer er potentialet til et meget høj Mcap til stede.

Tror de kan ramme 30% i royalty i de store indikationer, der udliciteres, samt pæne milestones (salg og regulatoriske).

Men ikke mindst så kan Anavex give håb i håbløse indikationer !!!

Time will show.






6/12 2021 22:55 Solsen 799212



Anavex ... Acandia med gode resultater i Rett:
https://finance.yahoo.com/news/acadia-pharmaceuticals-announces-positive-top-210500024.html

Men med over 80% diarre i pts i rullestol ....

Effect size under 0,5 på målepunkter (Blarcamesine har rundt regnet 1)

Jeg tror godt, at Anavex kan slå det resultat.

Bemærk patientgruppen med hovedsaglig unge piger. Så passer bedre til sammenligning med Excellence.



7/12 2021 04:35 Solsen 1099214



Anavex ... MayoMobiles syn på Acandias forsøg (som kopi fra Ihub):

From MayoMobile on stocktwits---Brief Acadia Rett Result Summary:

Statistically significant findings in primary endpoints. Relatively low effect sizes.

Anavex's RS-001 low dose RSBQ scores were over 4x better than Acadia

17% of doses cohort dis-enrolled due to adverse effects.
- 80% of dosed patients had diarrhea
-26% of dosed patients experienced vomiting

Altså både sideeffekt og effekt forventes altså bedre for Blarcamesine. Bl.a. diarre er ikke set med Blarcamesine.

De gode P-værdier i Acandias forsøg er opnået i et forsøg med 187 pts.

Anavex har forsøg i størrelsesordene 30-90. Men bedre effekt med Blarcamesine skulle begrunde det lavere antal pts i forsøgene.

Hope so :-)



7/12 2021 09:50 Tasso1 799223



Anavex ACAD stiger ca. 1 milliard $ i MC på nyheden.

Godt for RETT patienterne - men også for Anavex!

Er også overbevist om, at 2-73 vil overgå ACAD og vil følge op på de gode resultater fra det første RETT US og endda forbedre dem med den øget dosis i Avartar - uden bivirkninger.
Skulle ACAD få en markedsgodkendelse først, får vi dog en prissætning, som Anavex kan læne sig op af.
Så ACAD kan faktisk bane vejen for et bedre behandling med 2-73, både hos myndighederne og på markedet.
( 1 milliard $ i øget MC for Anavex svarer til ca. kurs 30 $ )
Anavex burde dog stige langt mere, da det som tidligere skrevet vil underbygge hele platformen og styrke casen, når Anavex starter f.eks. fase 3 forsøget op i Fragile X, som har en ca. 8 gange større patientgruppe.

Anavex`s og Nell`s ALS præsentation.
Hun kommer også rundt om andre resultater.
Understreger at Anavex har en hel platform til en potentiel bred CNS behandling.




7/12 2021 11:30 Tasso1 499231



Anavex Bedre ALS præsentation link.




12/12 2021 04:58 Kyed01 499386



Mens vi venter på nyheder som forhåbentlig kommer snart, måske næste uge før RETT konferencen (jeg har i øvrigt læst at det koster 2000$ for at se med?) kan man lige tygge lidt på nedenstående indlæg:

Den super dygtige Sokol på Ihub er kommet med en meget grundig analyse af Anavex og 2-73 & 3-71, ja måske ikke an analyse men hvad Sigma-1R agonists kan gøre.

https://investorshub.advfn.com/boards/read_msg.aspx?message_id=167089723




12/12 2021 04:59 Kyed01 599387



sokol Member Level Saturday, 12/11/21 12:40:15 PM
Re: None 0
Post # of 339577

Two Potentially Significant YE2021 Catalysts. One is obviously the Avatar data. The other is phase 1 AVXL 3-71 data. Why is the latter potentially significant? 3-71 is considered to be "good at, focusing more on Frontotemporal dementia(FTD)'' according to Missling, and FTD overlaps and is related to Amyotrophic lateral sclerosis (ALS). Many of damaged functions in these two diseases, as in some other neurodegenerative diseases, are regulated by signalling between the endoplasmic reticulum and mitochondria, and this has stimulated investigations into the role of endoplasmic reticulum-mitochondria signalling in FTD/ALS disease processes. Recently, Anavex made an ALS presentation as posted by TTTav66: "Exploring SIGMAR1 Modulators for the Treatment of ALS", presented by Nell Rebowe of Anavex Life Sciences at the 4th Annual ALS ONE Research Symposium:

It has been postulated for sometime that Sigma-1R agonists may improve the functions damaged in FTD and ALS.

ALS is a rare disorder that develops in 1.5 to 3 per 100,000 people every year in North American and European populations. Approximately 30,000 people are affected in the United States, with an estimated 5,000 new cases diagnosed each year. Is ALS the other rare disease indication that Anavex may announce? See slide 14 December 2021 presentation: "Initiation of potentially pivotal Phase 2/3 clinical trial for the treatment of a new, rare disease indication -expected 1H 2022". However, why would it be a Phase 2/3 clinical trial?

Once the 3-71 data is available Missling indicates that Anavex may move forward with FTD and any other related dementia indication. "So, we have mentioned that we will move ahead with frontotemporal dementia, but we'd like to have really the solid phase 1 data in hand before we say we commit to this. And -- but we'll definitely move forward with FTD or any other related dementia indication." When the phase 1 3-71 data is presented, maybe we will learn more about what other FTD related indications Anavex may explore. However, from the recent Nell Rebowe presentation, we may surmise that positive 3-71 data for FTD will indicate promise for a future Anavex clinical trial for ALS. We may also learn whether any prospective Anavex ALS trial will involve either 2-73 or 3-71 or both.

See supporting research 1-13 below.

1. Sigma-1R Agonist Improves Motor Function and Motoneuron Survival in ALS Mice

Abstract
Amyotrophic lateral sclerosis is a neurodegenerative disorder characterized by progressive weakness, muscle atrophy, and paralysis due to the loss of upper and lower motoneurons (MNs). Sigma-1 receptor (sigma-1R) activation promotes neuroprotection after ischemic and traumatic injuries to the central nervous system. We recently reported that sigma-1R agonist (PRE-084) improves the survival of MNs after root avulsion injury in rats. Moreover, a mutation of the sigma-1R leading to frontotemporal lobar degeneration/amyotrophic lateral sclerosis (ALS) was recently described in human patients. In the present study, we analyzed the potential therapeutic effect of the sigma-1R agonist (PRE-084) in the SOD1G93A mouse model of ALS. Mice were daily administered with PRE-084 (0.25 mg/kg) from 8 to 16 weeks of age. Functional outcome was assessed by electrophysiological tests and computerized analysis of locomotion. Histological, immunohistochemical analyses and Western blot of the spinal cord were performed. PRE-084 administration from 8 weeks of age improved the function of MNs, which was manifested by maintenance of the amplitude of muscle action potentials and locomotor behavior, and preserved neuromuscular connections and MNs in the spinal cord. Moreover, it extended survival in both female and male mice by more than 15 %. Delayed administration of PRE-084 from 12 weeks of age also significantly improved functional outcome and preservation of the MNs. There was an induction of protein kinase C-specific phosphorylation of the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor in SOD1G93A animals, and a reduction of the microglial reactivity compared with untreated mice. PRE-084 exerts a dual therapeutic contribution, modulating NMDA Ca2+ influx to protect MNs, and the microglial reactivity to ameliorate the MN environment. In conclusion, sigma-1R agonists, such as PRE-084, may be promising candidates for a therapeutical strategy of ALS.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3480575/

2. There's Something Wrong with my MAM; the ER-Mitochondria Axis and Neurodegenerative Diseases

Sebastien Paillusson 1 , Radu Stoica 1 , Patricia Gomez-Suaga 1 , Dawn H W Lau 1 , Sarah Mueller 1 , Tanya Miller 2 , Christopher C J Miller 3
Affiliations expand
PMID: 26899735 PMCID: PMC4780428 DOI: 10.1016/j.tins.2016.01.008
Free PMC article
Abstract

Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis with associated frontotemporal dementia (ALS/FTD) are major neurodegenerative diseases for which there are no cures. All are characterised by damage to several seemingly disparate cellular processes. The broad nature of this damage makes understanding pathogenic mechanisms and devising new treatments difficult. Can the different damaged functions be linked together in a common disease pathway and which damaged function should be targeted for therapy? Many functions damaged in neurodegenerative diseases are regulated by communications that mitochondria make with a specialised region of the endoplasmic reticulum (ER; mitochondria-associated ER membranes or 'MAM'). Moreover, several recent studies have shown that disturbances to ER-mitochondria contacts occur in neurodegenerative diseases. Here, we review these findings.

https://pubmed.ncbi.nlm.nih.gov/26899735/

3. The ALS-linked E102Q mutation in Sigma receptor-1 leads to ER stress-mediated defects in protein homeostasis and dysregulation of RNA-binding proteins

Alice Dreser 1 , Jan Tilmann Vollrath 1 , Antonio Sechi 2 , Sonja Johann 3 , Andreas Roos 1 4 5 , Alfred Yamoah 1 , Istvan Katona 1 , Saeed Bohlega 6 , Dominik Wiemuth 7 , Yuemin Tian 7 , Axel Schmidt 7 , Jörg Vervoorts 8 , Marc Dohmen 8 , Cordian Beyer 3 , Jasper Anink 9 , Eleonora Aronica 9 , Dirk Troost 9 , Joachim Weis 1 , Anand Goswami 1
Affiliations expand
PMID: 28622300 PMCID: PMC5596426 DOI: 10.1038/cdd.2017.88
Free PMC article
Abstract

Amyotrophic lateral sclerosis (ALS) is characterized by the selective degeneration of motor neurons (MNs) and their target muscles. Misfolded proteins which often form intracellular aggregates are a pathological hallmark of ALS. Disruption of the functional interplay between protein degradation (ubiquitin proteasome system and autophagy) and RNA-binding protein homeostasis has recently been suggested as an integrated model that merges several ALS-associated proteins into a common pathophysiological pathway. The E102Q mutation in one such candidate gene, the endoplasmic reticulum (ER) chaperone Sigma receptor-1 (SigR1), has been reported to cause juvenile ALS. Although loss of SigR1 protein contributes to neurodegeneration in several ways, the molecular mechanisms underlying E102Q-SigR1-mediated neurodegeneration are still unclear. In the present study, we showed that the E102Q-SigR1 protein rapidly aggregates and accumulates in the ER and associated compartments in transfected cells, leading to structural alterations of the ER, nuclear envelope and mitochondria and to subsequent defects in proteasomal degradation and calcium homeostasis. ER defects and proteotoxic stress generated by E102Q-SigR1 aggregates further induce autophagy impairment, accumulation of stress granules and cytoplasmic aggregation of the ALS-linked RNA-binding proteins (RBPs) matrin-3, FUS, and TDP-43. Similar ultrastructural abnormalities as well as altered protein degradation and misregulated RBP homeostasis were observed in primary lymphoblastoid cells (PLCs) derived from E102Q-SigR1 fALS patients. Consistent with these findings, lumbar a-MNs of both sALS as well as fALS patients showed cytoplasmic matrin-3 aggregates which were not co-localized with pTDP-43 aggregates. Taken together, our results support the notion that E102Q-SigR1-mediated ALS pathogenesis comprises a synergistic mechanism of both toxic gain and loss of function involving a vicious circle of altered ER function, impaired protein homeostasis and defective RBPs.

https://pubmed.ncbi.nlm.nih.gov/28622300/

4. Disruption of ER-mitochondria signalling in fronto-temporal dementia and related amyotrophic lateral sclerosis

Abstract
Fronto-temporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are two related and incurable neurodegenerative diseases. Features of these diseases include pathological protein inclusions in affected neurons with TAR DNA-binding protein 43 (TDP-43), dipeptide repeat proteins derived from the C9ORF72 gene, and fused in sarcoma (FUS) representing major constituent proteins in these inclusions. Mutations in C9ORF72 and the genes encoding TDP-43 and FUS cause familial forms of FTD/ALS which provides evidence to link the pathology and genetics of these diseases. A large number of seemingly disparate physiological functions are damaged in FTD/ALS. However, many of these damaged functions are regulated by signalling between the endoplasmic reticulum and mitochondria, and this has stimulated investigations into the role of endoplasmic reticulum-mitochondria signalling in FTD/ALS disease processes. Here, we review progress on this topic.

Facts
ER-mitochondria signalling is disrupted by a number of FTD/ALS-linked insults. These include TDP-43, FUS, mutant SOD1, and loss of the Sigma-1 receptor.

For TDP-43 and FUS this disruption involves breaking of the VAPB-PTPIP51 ER-mitochondria tethering proteins via activation of GSK3ß.

https://www.nature.com/articles/s41419-017-0022-7

5. Sigma-1 receptor is a key genetic modulator in amyotrophic lateral sclerosis

Abstract
Sigma-1 receptor (S1R) is an endoplasmic reticulum (ER) chaperone that not only regulates mitochondrial respiration but also controls cellular defense against ER and oxidative stress. This makes S1R a potential therapeutic target in amyotrophic lateral sclerosis (ALS). Especially, as a missense mutation E102Q in S1R has been reported in few familial ALS cases. However, the pathogenicity of S1RE102Q and the beneficial impact of S1R in the ALS context remain to be demonstrated in vivo. To address this, we generated transgenic Drosophila that expresses human wild-type S1R or S1RE102Q. Expression of mutant S1R in fly neurons induces abnormal eye morphology and locomotor defects in a dose-dependent manner. This was accompanied by abnormal mitochondrial fragmentation, reduced adenosine triphosphate (ATP) levels and a higher fatigability at the neuromuscular junction during high energy demand. Overexpressing IP3 receptor or glucose transporter mitigates the S1RE102Q-induced eye phenotype, further highlighting the role of calcium and energy metabolism in its toxicity. More importantly, we showed that wild-type S1R rescues locomotor activity and ATP levels of flies expressing the key ALS protein, TDP43. Moreover, overexpressing wild-type S1R enhances resistance of flies to oxidative stress. Therefore, our data provide the first genetic evidence that mutant S1R recapitulates ALS pathology in vivo while increasing S1R confers neuroprotection against TDP43 toxicity.

https://academic.oup.com/hmg/article/29/4/529/5614191

6. FTD and ALS: a tale of two diseases

Abstract
The first reports of disorders that in terms of cognitive and behavioral symptoms resemble frontotemporal dementia (FTD) and in terms of motor symptoms resemble amyotrophic lateral sclerosis (ALS) bring us back to the second half of the 1800s. Over the last 150 years, and especially in the last two decades, there has been growing evidence that FTD signs can be seen in patients primarily diagnosed with ALS, implying clinical overlap among these two disorders. In the last decade pathological investigations and genetic screening have contributed tremendously in elucidating the pathology and genetic variability associated with FTD and ALS. To the most important recentdiscoveries belong TAR DNA binding protein [TARDBP or TDP-43] and the fused in sarcoma gene [FUS] and their implication in these disorders. FTD and ALS are the focus of this review which aims to 1. summarize clinical features by describing the diagnostic criteria and specific symptomatology, 2. describe the morphological aspects and related pathology, 3. describe the genetic factors associated with the diseases and 4. summarize the current status of clinical trials and treatment options.

A better understanding of the clinical, pathological and genetic features characterizing FTD and ALS will shed light into overlaps among these two disorders and the underpinning mechanisms that contribute to the onset and development. Nevertheless, advancements in the knowledge of the biology of these two disorders will help developing novel and, hopefully, more effective diagnostic and treatment options.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3801195/

7. The Overlapping Genetics of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two diseases that form a broad neurodegenerative continuum. Considerable effort has been made to unravel the genetics of these disorders, and, based on this work, it is now clear that ALS and FTD have a significant genetic overlap. TARDBP, SQSTM1, VCP, FUS, TBK1, CHCHD10, and most importantly C9orf72, are the critical genetic players in these neurological disorders. Discoveries of these genes have implicated autophagy, RNA regulation, and vesicle and inclusion formation as the central pathways involved in neurodegeneration. Here we provide a summary of the significant genes identified in these two intrinsically linked neurodegenerative diseases and highlight the genetic and pathological overlaps.

https://www.frontiersin.org/articles/10.3389/fnins.2020.00042/full

8. FRONTOTEMPORAL DEMENTIA VS. ALS


Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, are two deeply related diseases - in many cases they are even found to be co-occurring.

https://www.als.net/news/frontotemporal-dementia-vs-als/

9. U.S. FDA Grants Orphan Drug Designation to ANAVEX 3-71 for the Treatment of Frontotemporal Dementia
...Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to ANAVEX 3-71 for the treatment of Frontotemporal demen

https://www.anavex.com/post/u-s-fda-grants-orphan-drug-designation-to-anavex-3-71-for-the-treatment-of-frontotemporal-dementia

10. Anavex Life Sciences Announces Initiation of First-in-Human Phase 1 Study of ANAVEX®3-71 (AF710B)

...Anavex is developing ANAVEX®3-71 initially for the treatment of Frontotemporal Dementia (FTD), for which ANAVEX®3-71 was previously granted orphan drug designation by the FDA. ANAVEX®3-71 demonstrated disease-modifying activity against the major hallmarks of Alzheimer's disease in transgenic (3xTg-AD) mice, including cognitive deficits, amyloid and tau pathologies, as well as beneficial effects on mitochondrial dysfunction and neuroinflammation.....

https://www.globenewswire.com/en/news-release/2020/05/21/2036906/29248/en/Anavex-Life-Sciences-Announces-Initiation-of-First-in-Human-Phase-1-Study-of-ANAVEX-3-71-AF710B.html


11. https://www.fool.com > call-transcripts > 2021/12/02
Dec 2, 2021 - AVXL earnings call for the period ending September 30, 2021 ...

Yun Zhong -- BTIG -- Analyst

OK. Then I think I didn't see an update on the 3-71 program in 2020 -- sorry, 2022 in terms of upcoming milestones, so I just wanted to check if frontotemporal dementia is still going to be the first indication for that program, and when do you expect a study potentially to start?

Christopher Missling -- President and Chief Executive Officer

Right. **So, we have mentioned that we will move ahead with frontotemporal dementia, but we'd like to have really the solid phase 1 data in hand before we say we commit to this. And -- but we'll definitely move forward with FTD or any other related dementia indication. **

......
Christopher Missling
So the two compounds (2-72 and 3-71) came from different angles and different labs but they are now moving more into what we call, we try to learn as we go. But so far we could not find parable assay other than a very early preclinical assay of target engagement. And there are differences in the affinities of the Sigma 1 receptor and also difference to the muscarinic receptor, which we believe is also important.

**And ultimately we will be only able to see really the difference of the two if we run really both indication world drug and the same indication in the same trial. So, we think that each drug has its own merits and it could very well be that 3-71 is really good at, focusing more on Frontotemporal dementia, which we had offered as ignition for and could also be very good at Alzheimer but right now we have 273 more advance, so we will eventually find out......**

12. Top-line data Phase 1 ANAVEX®3-71 clinical trial -expected YE2021 (slide 14 Dec. 2021 presentation)

13. ALS, Cognitive Impairment & Dementia - ALS Association

Is ALS related to dementia?
In ALS, some individuals develop dementia that most commonly presents as FTD, others develop cognitive and/or behavioral impairment without dementia, and some patients never develop any cognitive or behavioral impairment.

https://www.als.org/navigating-als/resources/fyi-als-cognitive-impairment-dementia





12/12 2021 12:26 Tasso1 799390



Anavex Ja- der er et meget højt niveau på IHUB.

Der er flere der arbejder indenfor området og kan sætte sig helt ind i videnskaben - og samtidig er gode til at formidle det videre.

Ja - der en RETT konference den 14. - 15. december 2021.
Missling er på dag 2 den 15. dec.

9:40 am Utilizing Precision Genetic Medicine to Treat Rare Neurodevelopmental Diseases: Focusing on Rett Syndrome
Chrisopher U Missling
President & CEO, Anavex Life Sciences
Synopsis
Requirement of clear understanding of target engagement
Importance of predictive biomarker of response correlating with efficacy
Relevance of appropriate efficacy endpoints

https://neurodevelopmental-drug-development.com/program/day-two/

Lidt spekulation:

Tror ikke Anavex har resultaterne klar fra Avatar til på onsdag den 15., men hvis de har, så bliver de vel offentliggjort og evt. gennemgået på et ekstraordinært PR/event.
Dvs. nu på mandag eller tirsdag.
Deltagelsen på RETT konferencen må have været planlagt nogle uger, så Misslings fremlægning kan evt. kun være basseret på RETT US.

Omvendt må Missling på dette tidspunkt have et vist kendskab til patienterne fra de forskellige åbne RETT forsøg - RETT US, Avatar og Excellence.
På den baggrund ville det være lidt forkert/misvisende, hvis Missling skulle gennemgå ovennævnte punkter på konferencen, hvis han evt. lå inde med en viden om, at man ikke så nogen effekt hos disse OLE patienter?

Så i min optik, må deltagelsen af Missling på denne konference på nuværende tidspunkt, være et udtryk for, at man har set positive ting fra OLE forsøgene ( og måske Avatar ) - ellers ville Anavex nok have undgået fokus på RETT lige nu og holdt en lav profil?






13/12 2021 16:46 Steen# 899416



Anavex optages i Nasdaq Biotechnology Index
https://www.bloomberg.com/press-releases/2021-12-11/annual-changes-to-the-nasdaq-biotechnology-index per 20/12
Så må der vel være nogle index-trackere og ETF'er der skal købe ind?



14/12 2021 13:38 Tasso1 799435



Anavex. JP Morgan konference den 13. januar 2022.

https://www.anavex.com/post/anavex-life-sciences-to-present-at-40th-annual-j-p-morgan-healthcare-conference

Live webcast kl. 17.15 - DK tid.
https://jpmorgan.metameetings.net/events/healthcare22/sessions/40488-anavex-life-sciences-corp/webcast?gpu_only=true&kiosk=true

JP Morgan Healthcare Conference, er en af de større konferencer - mon ikke Anavex nu er sikker på, at de har resultater klar fra Avatar og nok også fra 3-71 i FTD.
Anavex ville vel heller ikke udstille sig selv på en sådan vigtig konference, hvis man troede eller måske allerede nu vidste, at resultaterne var dårlige?
Ville man så ikke holde en lav profil?



14/12 2021 15:40 Tasso1 799439



Anavex JP Morgan er en af de største iflg. IHUB.

JP Morgan is the biggest and most prestigious healthcare conference of the year. Being invited to present is a big deal. Invitations are typically reserved for JPM banking clients (or wannabe banking clients), or companies that are in a therapeutic space of particular interest.

Every biotech company dreams of being invited to present. Few are. I'm not saying the presentation will or won't be a market-moving event from a content perspective but nevertheless it is not insignificant that Missling will be presenting because the cream of the crop of biotech investors as well as healthcare journalists attend. There are also all kinds of social networking events.

Så et perfekt sted og tidspunkt for Anavex, at komme i rampelyset - hvis de da har noget at skyde med!
- Igen tror simpelthen ikke Missling ville stille sig op på den scene, hvis ikke han havde noget ekstraordinært at komme med!!

Ville dog også passe mig fint aht. til beskatning på mine aktiesparekontoer, hvis Anavex trak spændingen ud til efter 31. december 2021 - så håber lidt Missling heller ikke overholder annoncerede deadline denne gang - bare skidtet virker!



14/12 2021 16:17 Kyed01 499440



Ja jeg læste godt at JP Morgan ER stedet at komme til hvis man er i healthcare, og en på Ihub som har gået til tidligere JP M konferencer skrev at mange små biotech firmaer håber på at blive inviteret men de fleste bliver ikke inviteret og endvidere at der foregår mange møder på andre hoteller på 1X1 basis (partner forhandlinger med mere).

Saa Missling burde give data mindst 1 uge i forvejen så eventuelle interesserende firmaer har tid til at tygge lidt på data og kan konkludere hvad de medfører i andre indikatorer.

Data er næsten helt sikkert gode ellers vil Missling jo ikke deltage som Tasso også skrev, det vil jo værre totalt sindssygt at stille op med tvivlsomme data, Missling vil aldrig få et job i sektoren mere og værre totalt til grin.

https://investorshub.advfn.com/boards/read_msg.aspx?message_id=167114295



14/12 2021 16:30 Solsen 499441



Anavex Jeg er naiv og tror i sagens natur ikke at Missling kender Avatar data.

Men han kender sine data på Blarcamesine nok til , at være i god tro ved at antage, at de er gode :-)

Han har tidligere omtalt, at han har set data på 3-71 forsøget og udtalt, at det så godt ud.

Af hensyn til PAL skatten må data gerne ligge til efter nytår. Men jeg overbevist om, at de bliver frigivet så snart de kommer til Anavex. Der bliver ikke spekuleret fra Anavexs side i at offentliggøre dem mest belejligt.

Håber at JP Morgan deltagelsen kan være stedet hvor der kommer gang i partnerforhandlinger.

Vi krydser fingre :-)



15/12 2021 21:25 Budweis 399460



Kurs udviklingen her til aften kunne tyde på Missling har givet positive signaler på dagens RETT konference? Alternativt er det ren lemming effekt?



15/12 2021 21:43 Thnleads 499462



Så vidt jeg lige kan se, så præsenterede Missling fra 15:40-16:10 dansk tid. Så er det i hvert fald en forsinket effekt.



16/12 2021 01:39 Kyed01 799465



Tror jeg ikke.

Det var Powells udmelding der fik Russel2000 til at stige og Anavex fulgte efter.



16/12 2021 05:56 Budweis 399466



Det har du ret i. Imponerende rekyl.



16/12 2021 20:43 Madmax26 399515



Tja men det ser godt nok ud til at den lige så hurtigt ryger ned igen. Den opfører så mere og mere som en krabbe aktie. Der næsten slavisk bevæger sig mellem 17-21.



17/12 2021 09:31 Tasso1 1299525



Anavex Kursen svinger såmænd bare med det meste af det øvrige markedet - når der ikke er nyheder!

Tror næppe der er mange robot/indeks relaterede handler, som bygger på de forventede milepæle for Anavex.

Indekserne svinger op og ned på stort set samme baggrund, som er en blanding af Covid-19 situationen, overordnede økonomiske faktorer og ofte manipulerede udsving, som ingen kan give en entydig forklaring på.
Der tjenes ufattelig mange penge på disse udsving og ikke bare på en kursudvikling, som går fra A til Å.
Sammenligner det ofte med en hønsegård, hvor alle høns løber forvildet rundt - uden egentlig at vide hvorfor!
Ofte aner såkaldte eksperter ikke hvorfor div. udsving sker - ja bruger endda nogle gange de samme forklaringer, både når kurserne stiger og falder - men de er jo eksperter, så de er jo tvungen til at komme med deres bud.

For Anavex har kun en ting en betydning -RESULTATER!!
Alt andet er bare pauseunderholdning - og mulighed for dem der tør og kan, at tjene lidt ved at trade på de udsving vi har.

Ved gode RETT data, kan vi få en stigning på 30-130 % - alt afhængig af, hvor overbevisende data er.

Ved dårlige RETT data, kan vi tilsvarende se et fald på 20-60 %.

Så de daglige udsving vi ser nu er fuldstændig underordnet!

Er selv fuldstændig afklaret med situationen og har på baggrund af ca. 6 års analysering af casen, taget mit valg ved at satse relativt stort på Anavex.
Der har hidtil udelukkende været gode og entydige resultater, som ingen andre hidtil har formået - og ingen bivirkninger i hverken sårbare børn og ældre.
Samtidig har der været kørt en stram og meget fornuftig finansiel politik, uden at stifte gæld eller være i lommen på grådige partnere.

Investering i biotek er som bekendt meget risikofyldt, men kan omvendt også give et ekstremt stort afkast - så man skal kun satse det man kan undvære!

Mit bud er, at vi får RETT data i starten af januar, men før JP Morgan konferencen den 13. januar 2022!
Er dog bange for, at de kan "risikere" at komme i indeværende år, med fremrykning af øget Pal skat og skat på aktiespare kontoerne til starten af 2022 til følge.



17/12 2021 18:14 poppelkongen 899543



husk lige på mandag indtræder anavex i
Nasdaq Biotechnology Index
om det har nogle betydning på kursen får vi nok at se i næste uge



18/12 2021 22:06 Tasso1 699564



Anvex. ICE Biotechnology Index (ICEBIO)

"Ved at inkludere virksomheder, der opfylder en minimumstærskel for markedsværdi og likviditet fra flere amerikanske børser, giver indekset en bedre måling af bioteknologiindustrien og hjælper med at forbedre investerbarheden for brugere, der benchmarker til indekset."

Inkludering i det nye indeks burde tiltrække flere og nye investorer.
En positiv udvikling af casen, burde blive set af flere seriøse aktører og måske også nye analytiker.

https://www.businesswire.com/news/home/20211216005424/en/ICE-Announces-Annual-Reconstitution-Changes-in-the-ICE-Biotechnology-Index



21/12 2021 18:39 Tasso1 699614



Anavex Svar fra IR i dag!

Med alle mulige forbehold!

Vores kære og meget aktive bigBIOboom fra Stocktwits påstår at have talt med Anavex`s IR i dag:

"I talked to IR NOW!! He said data is expected are the end of the year! Everyone is working very hard. .this is important data for Accelerated approval. .so it needs to be very accurate!! He said could be this week. .could be next. . It's even possible 1st week of January but that did not seem likely. .seems more likely in December."

Så pilen peger "desværre" på resultater inden året er omme.
Synes godt Missling kunne trække det til start januar, både pga. skattemæssige årsager, men også fordi januar plejer at være en rigtig god måned, når friske penge skal investeres i det nye år!
Tror resultaterne måske ikke ville få den fulde effekt i den stille julehandel?
Ville være fint med en start i 2022, som vi fik i år.

Nå - data kommer når de er klar, bare de er gode - alt andet er et luksus problem!

Torsdag den 23. er kun en halv handelsdag, fredag den 24. og 31. er lukket - så der resterer kun 5-6 handelsdag endnu i år.



21/12 2021 20:09 Solsen 699617



Anavex ... Man kan håbe, at han taler sandt. Men pudsigt, hvis IR udtaler sig som beskrevet. Kender du (Tasso1) mere til "bigBIOboom" end hans noget vilde alias ?

Et opslag på Ihub med henvisning til Facebook viser, at Excellence ikke rekrutterer før ultimo januar 2022 !

Mange forsøg er ikke igangsat i 2021 og nogen på pause ???

Eneste undskyldning er efter min overbevisning, at man afventer Avatar og at dette forsøg vil vise vejen for så vidt angår dosisstørrelse. Som bekendt er dosis ikke "disclosed" i Avatar. Måske afprøver man persontilpasset dosering.

Jeg håber ikke, at det er anden usikkerhed der tilbageholder den videre udvikling !

Jeg kan også godt vente til efter nytår med data - hvis de er positive ;-)





22/12 2021 13:30 Tasso1 499630



Anavex Solsen - nej kender ikke denne "bigBIOboom" - man skal derfor også tage udtalelser fra div. fora med et stort gran salt.
Er også meget skeptisk overfor, hvor meget IR ved mere, end det man allerede ved fra div. PR´s?
Ville give god mening med at afvente start på Excellence, når optimal dosering fra Avatar er kendt.
Denne Facebook oplysning om udskudt opstart af Excellence strider dog direkte mod et andet opslag fra RETT patienten Annelise ( Datter af RETT org. i Australien ), der tydeligvis er under 18 år, og nu kan hente 2-73 på det lokale apotek - efter afslutning af selve forsøget??

- en forklaring kunne måske være, at man mener udskydelsen af indrulning på et specifikt site?

Vi må bare afvente :)



23/12 2021 02:46 Kyed01 699656



God morgen og glædelig jul.

Saa er MayoMobile på banen igen med en super fin post om mave bakterier og hvordan de kan ændre hjernes stuktur.

Jeg kan ikke kopier alle de fine slides så man må følge linket for at se det.

MayoMobile Wednesday, 12/22/21 04:11:55 PM
Re: MayoMobile post# 340878 0
Post # of 340960

I re-worked a couple of these slides to make the information a bit more robust. I think this will closely resemble the final product. I hope you enjoy.


https://investorshub.advfn.com/boards/read_msg.aspx?message_id=167229444








23/12 2021 11:05 Solsen 699660



Anavex ... En ret interessant artikel om dosering af Blarcamesine af manden med det umulige navn :
https://piotrpeterblog.com/2021/12/23/transcription-or-translation-two-sides-of-blarcamesine-rett-syndrome-avxl-acad/

Missling har også nævnt dosering som vigtig. Han har bl.a. indikeret, at de pts i AD og PD der ikke responderer godt (non Wild Type) måske blot skal gives større dosis.

Ang. artiklen så har det også været lidt uforståeligt, at i Rett virker 5 mg, men i AD skal dosis være 50 mg.

Efterhånden falder brikkerne på plads.

Avatar er ikke afgørende, som han også beskriver, idet de som jeg også tror, har taget en ny tilgang til dosering.

Men vi håber stadig på de god resultater !

God jul til alle :-)



26/12 2021 16:52 digafarm 399688



Anavex. Glædelig bagjul.

Mens vi venter, kunne være interessant at høre om folk har en strategi ved et dårligt resultat fra Avatar? Der ville nok komme en heftig nedgang indledningsvis, som kunne bruges til supplere? Det er jo ikke en one-trick pony.



27/12 2021 08:09 Solsen 699690



Anavex ... Jeg er ikke helt sikker på Avatar. Dels pga et lille antal pts i studiet. 20 pts i forsøgsmiddel og 10 placebo giver en risiko for at p-værdierne ikke er gode nok til godkendelse. Dels fordi Anavex måske har benyttet anden dosering end vi kender fra de andre rett-forsøg

Men jeg håber og overordnet tror på gode data i Avatar.

Der er i øvrigt kommet nyt frem på Ihub, der tyder på, at deres pediatric vaucher ikke udløses, hvis Anavex søger godkendelse i Rett til voksne pts inden der søges til børn.

Det forhold er nok også baggrunden for, at Missling vil have stærke data i Avatar for, at han søger om godkendelse til voksne Rett pts. Vaucheren som fortabes ved ansøgning/godkendelse i rett til voksne anslås til at have en værdi på ca. $100 mln.

De sidste pts mangler, at blive rekrutteret i studiet i Rett-børn (Excellence). Jf facebook genoptages rekruttering i februar. Anavex vil sikkert gerne se Avatar resultater før dette sker så derfor kommer data meget snart og som Anavex lover omkring nytår.

Vi kan håbe, at data i Avatar er så gode, at der søges godkendelse. Er de ikke det må vi vente på Excellence og forvente, at Blarcamesine ikke bliver godkendt i 2022.

Det vil trykke kursen, men vil kunne være en suppleringsmulighed.



27/12 2021 08:18 Kyed01 599691



For mig er det ret svært at svare på.
Vi ved at RETT betragtes som en meget svær sygdom at behandle men hvad vi ved om Anavex RETT resultater indtil nu er meget lovende så for mig er dårlige resultater næsten udelukket.
Hvis de nu er dårlige og kursen rasler helt vildt ned vil jeg måske sælge det hele/det meste og gå ind ingen senere men det er noget jeg skal tænke meget over først.
Jeg er meget overvægtet her og vil helst ikke ende i minus så min strategi er baseret på det. Okay jeg kom med ret tidligt på GAK under 6$ så har en god "buffer".



27/12 2021 08:25 Kyed01 599692



Her er en af de bedste indlæg jeg har set i lang tid om Sigma 1 receptor (Anavex) og konkurrenternes medicin og hans detektiv arbejde om Almeimerz er bare helt utrolig!!

Biostockclub er en anden af de skrappe drenge(de har en del) på Ihub's tråd om Anavex.

https://investorshub.advfn.com/boards/read_msg.aspx?message_id=167262848


Biostockclub Monday, 12/27/21 12:22:39 AM
Re: tradeherpete post# 341254 0
Post # of 341262

Merry Christmas, tradherpete and all,

You already know what I think!

Alzheimer's is a mystery with 2 prominent clues for detectives wishing to solve its "crime" element:

First, there's physical evidence: the presence of amyloid beta. - That's like a hammer at the scene of the crime. It's there but we can't account for its presence...is it the cause of death, the murder suspect, the murder weapon, or the motive, or just an innocent bystander?


Second, there is this incredible pattern which science doesn't appear to be including in reasoning the solution to the puzzle/ mystery.
The first thing a detective would do when trying to determine sequence of events at multitudes of "serial kills" (in this case, AD) would be to look for a pattern used by the "killer" or "killers". Is it random or can we narrow the "suspects" down based on the victims' circumstances?

Yeah, we've been over this before. Whatever causes Alzheimer's must not only impair brain function (cause of death) but must also have a selection chauvinism for females to the tune of 2:1 when compared to males (gender calibrated at birth, sorry, no identity proclivity games here, can't fool Mother Nature).

Science/Big Pharma got this wrong for 30 years by looking at the physical finding and trying to pin the blame on it and make it the cause. Bosh!
Detectives and deductive reasoning will get closer: work backwards from the "victims" - MUCH LARGER CLUE than the high drama surrounding amyloid beta...(if Amyloid Beta is the Lee Harvey Oswald of CNS victims, then, Biogen is Jack Ruby, and the FDA and the Alz advocacy groups are the Warren Commission - it's THAT obvious).


Ask yourself the litmus question when considering cause of disease as a drug-able target for treatment/cure MOA in AD:
Would this account for the gender disparity?

P. Gingivitis and other bacteria would be candidates in my book if the sponsors of the trials testing the drugs which treat these (bacteria/viruses) can show the correlation between females carrying the bacterium/virus (plural, if there are many brain infections causing the inflammation) TWICE as often as their age correlated male counterparts. Everything I have read suggests that women, in general, practice superior dental hygiene to males as a habit. If not superior, at least equal to males, which would give this "suspect" a reasonable/plausible "alibis" for not being the culprit in these serial crimes...we can't account for them being in 2/3's of the victims' mouths/systems at the time when Alzheimer's begins to develop in brains and that predates the manifestation by decades. Really? An infection taking that long to become virulent?
Contemplate the soundness of the timing...people can have p. Gingivitis throughout life, even young adults/middle age, both genders...why do predominantly old females manifest neuronal death/impairment and dementia at twice the rate of older males after an infection which needed to be increasing plaque buildup for decades?
Get that answer and you get the prize (unless you're Biogen...in which case the "prize" for discovering the Holy Grail of CNS diseases turned out to be loss of share price, loss of employees (looking at you Sandrock, and coming layoffs), expert neurologists denouncing your drug's efficacy on the national stage, Congress and Fed govt (US) investigating your approval path, lot of bad press - scandals for FDA - Medicare, Medicaid walking away like it's a live grenade...hell, even the VA turned this down - someone in Vegas got rich betting AGAINST Biogen. Warren Buffett dumped the stock, Europe and Japan declined (not even politely) and it now looks as though Biogen will NOT be able to carry out the confirmatory ph 4 because they can't get 1600 participants willing to pay - and that's at half price.
Yes, LLY is announcing their intent to apply for approval of another plaque remover, as is Roche, but that's to increase current share price. They have no intention of filing - that's the second half of the 1-2 punch and is for suckers...it (filing and approval) drains the gains made off the announcement(!) to file)).

You can't get to dementia from gum disease, sorry CRTX, you're about to hang an Innocent Man.

As for SAVA's MOA - filamin A malfunction causing amyloid plaque build up from misfolded proteins, let's have the gender connection. What causes females to have this expressed at a staggeringly higher rate in old age when compared with males or young folks? I find nothing that can lawfully implicate, let alone convict, the filamin A.

As for the Sigma 1 receptor, we have already discussed the fact that the most potent inhibitor of the S1R, on the planet, is progesterone. Since there is a correlation between females using contraceptive pills (beginning in the 1970's widespread, so females around age 20 average in 1970's would now be women in their 70's) and the current population afflicted with Alzheimer's. Contraceptive pills contained much higher doses of the hormones when they began (orders of magnitude) versus today's BCP's.
Add the correlation between countries who approved use of "the pill" and today's Alzheimer's population and one can see a perfect map overlay of where our "killer" was at the time of the crime.
Add in the fact that countries which never approved use of "the pill" have statistically significant lower AD rates today.
Include the knowledge that countries where diets are rich in turmeric (India and Southeast Asia) have lower rates of AD today as well - significant. It's noted that turmeric inhibits progesterone.
Compounding evidence: Women who have had five or more pregnancies are at increased risk for AD. Fact. But, pregnancies happen when you are young... and progesterone is produced to thicken the uterine lining, endometrium, as a nurturing environment for the embryo to best develop into a fetus.
So, when pregnant, a woman's progesterone level rises from 1.2 ng/mL to 300+ ng/mL. During the pregnancy, a woman could have her S1r's inhibited for 9 months. Five or more of these extended periods, where S1r is substantially inhibited, appears to increase the risk of Alzheimer's later in life. So, shutting down the S1r for extended periods multiple times during childbearing ages can be the culprit at the right place and the right time to create the conditions for proteins to misfold and demonstrate increased cognitive impairment later.
That's not just a random pile of facts or coincidences and it's certainly not magic or conspiracy. But, it does help explain a correlation between the S1r and the gender difference of Alzheimer's population we see right now.

Then, turn your attention to chromatin and look for gender discrimination there. Outta time for now - you got this!

Can't promise that S1r agonists will cure AD but if so, the gender "mystery" will have been solved (to my satisfaction). With other treatments - just not seein' it.

Healthy, happy, prosperous, 2022 to all.

Wish that Benny were here to usher in a new year with us.
A 12/31 11pm toast to the AVXL demons, rascals, and merry makers - aces, all! will be offered and in memory of those we lost.
Raise a glass wherever you are in solidarity:)

And, at midnight, drink to those whose afflictions might see some relief in the coming year(s) as soon as possible

2022 - a better year for all, I hope

Cheers!
Biostock
PS: FTR, I know, it's not a crime scene nor detective series, and they are all just biotechs doing trials and trying to develop drugs which pass trials which is a tricky business (got that tattooed) and promise I will be very careful, once and F'r All!:)




27/12 2021 14:28 Tasso1 799704



Anavex Alt peger på positive resultater i Avatar.

Først ønskes I lige en rigtig god jul!!

RETT US forsøget havde endnu færre patienter end Avatar, men trods det, var der signifikant positiv respons på samtlige parameter og med meget lille p-værdi (usikkerhed).

Det er dog bemærkelsesværdig, at Anavex ikke har meldt størrelsen af dosis af 2-73 ud, kun at den er større end ved RETT US.
Denne disposition må være sket efter aftale med FDA.
Tror nærmere, at Anavex forsøger at finjusterer dosis ifht. de forskellige typer af RETT patienter - vægtmæssig, MRNA, sværhedsgraden af sygdommen i den enkelte patient mm.
De forsøger formentlig at knække koden, hvorfor forskellige patienter skal have forskellig dosis - for at opnå den optimale behandling.
Dette vil ikke kun have betydning for RETT indikationen, men formentlig også indgå i protokollen for de andre planlagte indikationer, som Anavex har annonceret snarlig opstart af nye forsøg i.

Alt er lidt gætværk, indtil vi har resultaterne fra Avatar - tror dog, at der er en velbegrundet disposition bag de valgte protokoller - med FDA på sidelinjen.

Der er rigtig mange gode skribenter på IHUB og de fleste er også meget positive på Avatar - men ingen ved reelt noget konkret før vi får data.

IGEN - Missling stiller simpelthen ikke op på JP Morgan den 13. januar med dårlige resultater fra Avatar i bagagen!!

Vi afventer forsat!






27/12 2021 14:48 Solsen 799705



Anavex ... Jeg tror også på gode date i Avatar.

Men iflg US RETT forsøget kom RBSQ endpoint i mål med en p-værdi på 0,048. Det er i min optik en meget lille margin til de 0,05, som er grænsen for signifikans under normale omstændigheder.
https://www.anavex.com/post/anavex-life-sciences-announces-anavex-2-73-meets-primary-and-secondary-endpoints-in-clinical-trial

Derfor og med tanke på noget doseringsmæssig i Avatar må vi have muligheden for ikke succes åben. Med det ikke sagt, at slaget er tabt, men blot at succesen udskydes.

Missling kender ikke data meget før vi kender topline.

Det bliver spændende.



29/12 2021 08:52 Budweis 799759



Piotr Pietrzkiewicz gør sig en del grundige overvejelser omkring effekten af Blarcamesine i RETT for voksne personer.

https://piotrpeterblog.com/2021/12/28/the-trouble-with-avatar-avxl-blarcamesine-rett-syndrome/



29/12 2021 13:29 TDT123 699771



Håber i har haft en god jul, og at i får et rigtig godt corona-nytår..
Hvis man ikke kendte ordet "vente" før man investeret i Bio så har man ihvertfald lært det nu.
Jeg tror ikke der sker mere på denne side af 2021, og hvor mange der har investeret ud fra misslings lovning af nyheder i dette herrens år, er ikke til at gætte, men jeg tænker en del. Så bliver der solgt ud, for måske at genkøbe i starte af det nye år, ja det tror jeg.

En PR i dag eller i morgen før market åbner kan jo ændre billedet total...

Men det ser noget sløjt ud....

Nåååå:

Godt nytår alle

Mvh

Torben



30/12 2021 14:57 Tasso1 699813



Anavex. Ny afhandling fra Randy Hagermann pr. 29. dec.

https://www.dovepress.com/fragile-x-premutation-medications-therapy-and-lifestyle-advice-peer-reviewed-fulltext-article-PGPM

Another new treatment which is pending FDA approval for research in FXTAS is Anavex 2-73, a sigma 1 agonist that works in the endoplasmic reticulum and mitochondrial interface. It can reduce oxidative stress, alleviate calcium dysregulation in neurons and improve mitochondrial function which is greatly needed in FXTAS and in other disorders.127,128 Anavex 2-73 also helps other cellular dysfunctions including proteostasis, autophagy and neuroinflammation that are present in neurodegenerative and neurodevelopmental disorders.129,130 It has been efficacious in animal models and human studies in Rett syndrome (unpublished), studies in Alzheimer Disease, in Parkinson's Disease Dementia (unpublished) and most recently in rescuing hyperactivity and other behaviors in the KO FXS mouse.127,131,132 Soon controlled trials of Anavex 2-73 will be studied in those with FXTAS.

Randy Hagermann er, som tidligere beskrevet, en af de førende kapaciteter indenfor FXTAS/Fragile X og er meget stor fan af 2-73.
Som ansvarlig for sites i RETT US forsøget, har hun tidligere udtalt sig om den overbevisende effekt hun så i RETT pigerne og senere også for de, der efterfølgende skiftede over i OLE studiet fra placeboarmen.
Hun udtalte ved en anden lejlighed, at det Fragile X forsøg, som omtalt i artiklen burde være startet i går.
- ja hun ville endda selv tage 2-73 mod aldersrelaterede sygdomme, når det kom på markedet!

Nå - stadig ingen data fra Avatar - håber godt nok Missling trækker den til efter 1. januar 2022, når vi er kommet så langt hen på tiden.
Vil hellere betale 17 % i afkast af aktier i kurs 17 $ - med aktier solgt i kurs 35 $ i januar 2022. ( Aktiesparekonto )
Skatten skal jo betales i sidste ende i 2023, men så kan pengene jo arbejde et år længere og samtidig minimere risikoen for ikke at have betalt afkast af en aktie, som måske bliver mindre værd i løbet af året.
- håber det giver mening!

Skulle der komme data, vil det normalt blive fulgt op af en CC - og det gør man vel ikke den 31. dec?

Godt og lykkebringende ( indbringende ) Nytår!!



30/12 2021 15:32 Kyed01 599814



Det med skatten fattede jeg ikke et pip af, da jeg ikke har den slags at bekymre mig over hvor jeg bor, ha-ha.

Ja data kommer nok før den store konference i januar.

Godt Nytår til alle her på tråden.




30/12 2021 16:15 Solsen 499815



Anavex ... vores ven Hagerman er stadig vild med Blarcamesine.

Hendes ordvalg har flere gange undret mig. Tidligere har hun udtalt, at hun ikke vidste om stoffet var godkendt eller lige var ved det. Nu siger hun "which is pending FDA approval" - hvilket jeg opfatter som afventer approval.

Mig bekendt er der ikke søgt approval endnu, idet der ikke er færdige forsøg at søge på.

Nå det kan være en tilfældighed, men alligevel mærkeligt af en professor.

Vi slap med PAL skattesmæk i stor stil i år. Jeg tager gerne tæsk til næste år :-)

Godt nytår.



30/12 2021 16:32 Tasso1 799816



Anavex Tror hun mener afventer endelig godkendelse for opstart af forsøg i Fragile X, hvilket også passer med det Anavex har udmeldt - endelig protokol for Fragile X ( og de øvrige forventede opstart i andre indikationer ) er måske afhængig af Avatar data.

"is pending FDA approval for research in FXTAS"



30/12 2021 16:35 Solsen 499817



Ok jeg var lidt for hurtig og havde ikke læst dit link, men fået en anden opfattelse på det jeg skimmede på Ihub....



31/12 2021 13:20 Kikl 799829



Anavex
Godt Nytår til alle jer dygtige skribenter i denne tråd. Så herligt at følge.
Hos mig er Anavex faktisk den af mine aktier, hvor staten kan hente mest i PAL-skat. , men selv betragter jeg aktien som en lottoseddel.
At forstå det hele har jeg opgivet. Spændende er det, om der kommer noget godt i 2022 fra Anavex, og interessant om der i det hele taget sker et større gennembrud inden for CNS forskning.



5/1 2022 15:20 Tasso1 899901



Anavex CC hos HC Wainwright den 10 januar.

https://ih.advfn.com/stock-market/NASDAQ/anavex-life-sciences-AVXL/stock-news/86946612/anavex-life-sciences-to-present-at-the-h-c-wainwr

Endnu en konference!
Ville nu hellere foretrække de lovede data.
Omvendt får vi data fra Avatar og 3-71, som vi var lovet omkring "end of year", så stillede Anavex nok ikke op til hele 2 CC´er her den 10. og senere den 13. januar på JP Morgan , hvis Anavex forventede dårlige resultater.

HC Wainright er kun tilgængelig via. on-demand nu på mandag, så de kan vel ikke komme med noget, som ikke er offentlig tilgængelig inden.
Dvs. man kan måske lidt naivt håbe på, at vi får data i morgen torsdag eller fredag?
Med de konsekvent forsinkelser og udskudte milepæle fra Missling, så ville jeg dog ikke satse hele bondegården på resultater inden weekenden.

Bare de er gode, er tidspunktet sekundært - om end lidt irriterende, at det altid går noget længere tid end udmeldt.

Hele det indeks Anavex er i (XBI), blev ramt i går - så Anavex blev trukket med ned.
vi skal have gode resultater for at blive afkoblet - bare en del af spillet!



5/1 2022 20:49 Solsen 699906



Anavex .... Gap closed in $15,5

Så er vi parate til at vende bussen ;-)

Men biotech får mega tæsk lige nu.



6/1 2022 13:57 klemmensen 599923



Mens vi alle venter på data, så rykker Anavex lidt rundt på organisationen, Walter Kaufmann bliver flyttet til Chief Scientific Officer og den nylig ansatte Edward R Hammond får så posten som Chief Medical Officer. Jf. pressemeddelelsen så skal det ses styrkelse af processerne omkring markedsgodkendelse og udvikling af deres præparater.
Dette synes jeg godt man kan se som et positivt tegn - men det er stadig data der fordrer de gode resultater.
https://finance.yahoo.com/news/anavex-life-sciences-promotes-walter-120000560.html



6/1 2022 15:29 Tasso1 799927



Anavex Ja har også svært ved at se noget negativt i forfremmelserne.

Det virker både som en styrkelse af organisationen og forberedelse til næste skridt mod en egentlig godkendelsesproces.
Det er må også skulle ses som et stort klap på skuldrene for veludført arbejde af den igangværende proces.
Omvendt ville dette skridt virke ulogisk, hvis man havde set eller troede på dårlige resultater.
Igen - selvom Anavex ikke skulle have kendskab til f.eks. Avatar data endnu, så må der løbende have været feedback fra de forskellige sites fra de forskellige indikationer - især også fra de åbne OLE forsøg.
Der må være mellem ca. 500 og 600 patienter, der faktisk får 2-73 på nuværende tidspunkt, på tværs af alle indikationer og stadie i forsøgene (inkl. OLE og over en flerårig periode) - det kan næsten ikke undgås, at lægerne og Anavex har kunnet se om patienterne har haft gavn af behandlingen i et eller andet omfang - eller ikke.



8/1 2022 19:13 Solsen 499964



Anavex ... Den nok bedste Ihub skribent MayoMobile har udarbejdet et længere skriv omkring blarcamesine på baggrund af mange timers arbejde.

Det er ikke lykkedes ham, at få Seekingalpha at udgive det endnu. Men han arbejder på at det sker her eller andets steds.

Han mener, at have fundet ud af noget interessant: https://investorshub.advfn.com/boards/read_msg.aspx?message_id=167430663

Spændende hvad den næste uge bringer dels fra ham og Anavex på de to konferencer de deltager i.

God lørdag aften.



10/1 2022 12:33 Solsen 599997



Anavex ... Topline data 3-71 i dag.

Spændende !



10/1 2022 12:46 Tasso1 699998



Anavex Ja fint med 3-71 først og måske Avatar senest torsdag.

Sandhedens time - kl. 20.30 - måske pr. kl. 13.00!!!

https://www.anavex.com/investor-material/events/

Kan se man skal installerer ZOOM for at se med.

Kunne måske være et godt tidspunkt at starte en ny tråd 2022???



10/1 2022 13:06 Solsen 599999



Anavex ... Data https://www.anavex.com/post/anavex-life-sciences-reports-positive-results-from-phase-1-clinical-trial-of-anavex-3-71

Ingen SAE i 5-200 mg. Met primary amd secondary endpoint.

God start til ny tråd.



10/1 2022 13:52 Solsen 4100000



Anavex ... Fra meddelelsen: Based on these results, and ANAVEX®3-71 pre-clinical profile, the Company intends to advance ANAVEX®3-71 into a biomarker-driven clinical development dementia program for the treatment of FTD, schizophrenias and Alzheimer's disease, evaluating longitudinal effect of treatment with ANAVEX®3-71 initiating in 2022. Anavex believes the results of this study, could serve as the basis for advancing into respective registration studies in the U.S.

Der bliver her åbnet for tre nye forsøg med 3-71 med begyndelse i 2022 - som jeg læser registreringsforsøg.

Der bliver mange nye forsøg åbnet i 2022 !



10/1 2022 14:00 Tasso1 5100002



Anavex Henviser venligst til ny tråd :)



10/1 2022 14:11 Steen# 2100003






TRÅDOVERSIGT


























99204 Det er rigtigt :-) ..
6/12 19:17 Solsen 3