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tschussmann, depending if and how you use leverage in that brokerage account, you should be able to restrict your broker from lending those AVXL shares out. Back in the day, my institutional clients loved to do that with heavily shorted stocks, making it known to their fellow institutional shareholders when they were doing that. The resulting squeeze could not only cause some short term levitation in the price but create outright panic when positive news hit the tape.
"13. Defendant Christopher U.Missling is and was at all material times Board Chair, CEO, President and Secretary of Anavex."
It would suggest better due diligence from the shysters at Levi & Korsinsky if they weren't wrong about Missling being the Board Chair currently and at all material times.
I would imagine, sage, that there was some dialogue with the FDA in the second half of 2023 when he could have brought up that idea you alluded to, AA with the OLE serving as a confirmatory trial. Again if I were guessing, he got some push back on that, so we have the more recent statement from him (in a conference call Q&A?) that the OLE would be part of the NDA package.
By "claimed," frrol, I meant that Missling said those things. As I suggested, I have no idea if they were statistically significant.
So, what can be said about the FDA's move to call in an advisory committee to review Lilly's drug application for Donanemab? First of all, a similar move was made during the Biogen/Eisai application for Lecanemab (LEQEMBI). However, at this late stage it was totally unanticipated by Lilly and the stock market. Predictably, LLY is down sharply today (shedding over $15 billion in market cap) on a day when Big Pharma stocks are up (despite Biden railing against prescription prices in the US last night) and BIIB is outperforming the group. The BIIB move is logical on the theory that it will have quite a few more months to establish LEQEMBI in the market before Donanemab is approved, assuming it actually is.
Beyond that, however, the publicity around this review (as well as the one currently being conducted on LEQEMBI by a Scientific Advisory Group for the EMA) is not helping the cause of monoclonal antibody treatment in the eyes of physicians and caregivers. LEQEMBI is already underperforming the initial targets set by Biogen/Eisai in the marketplace, and in recent special edition I noticed a poll taken by publisher "BioSpace" in which response to the question "Do you believe the current data show a benefit worthy of LEQEMBI's $26,500 price tag?" was 32% Yes, and 68% No.
In answer to sage4's question as to whether this is good timing (for Anavex) I would say it surely is. Both agencies, EMA and FDA, clearly have factions that are skeptical of the benefit to cost ratio - cost including safety, convenience of administration, and expense. Whether they approve LEQEMBI or Donanemab, respectively, or whether they don't, it seems that the outcomes will have been contentious. The physicians who prescribe for Alzheimer's patients by now fully recognize that there are significant limitations to what mAb therapy has offered up so far. The appearance of a drug application for Blarcamesine with a different solution (in a pill) that matches or exceeds the efficacy of mAb's in a shorter period of time, eliminates the risk of serious side effect, and slows brain shrinkage instead of accelerating it, will be taken very seriously at both agencies. (I didn't even mentioned the claimed benefits of better sleep, reduced blood pressure, improved tau levels and reduced inflammation, where we haven't seen the data yet.) So, yes, I think the timing of these calls for advisory groups, which is sparking renewed controversy over the mAb's in the press, coupled with apparently lackluster LEQEMBI sales, is very beneficial for Anavex's cause.
If you hadn't called the presentation a non event, I wouldn't be disagreeing with you, Investor. Whether there is any material information that is new to you or me is irrelevant. What is important is that this, to my knowledge, is the first presentation of the summary information from the Phase 2b/3 trial to an audience in Europe. It is not targeted to institutional investors, as was the TD Cowen presentation on Monday. It is targeted to opinion leaders - researchers and health care providers in the field of degenerative neurological diseases. It is being delivered not by a CEO but by a scientist, Timo Grimmer, well known in his field internationally and particularly in Europe. It is part of the first salvo by Anavex to get approval for Blarcamesine on the continent, and it comes at a time when there is little enthusiasm for LEQEMBI, whether or not that drug gets approved there over the next month or so. In my view it is a real event, not one that should be measured by whether it moves the stock at all on Monday.
Yes, plexrec, you can register for the online version of the conference. If you are not a nurse, student, or citizen of a third world country, you will pay 450 Euros for the privilege (last I checked), or E30 for every minute that Grimmer speaks. If you are good with that, you have to stay up very late tomorrow or get up very early early on Saturday to hear it. Go for it!
He doesn't have to read through the Safe Harbor.
Enquiring minds want to know!
Joseph, as to your question regarding submission announcements by the company and/or the EMA, I can recall on at least one occasion Missling saying that the company would announce the filing of a formal drug application. (I don't know if he meant after acceptance or prior or both.) As to the EMA, my correspondence earlier in the year with a Greek woman in the Regulatory Affairs department yielded the following response: "There is usually an announcement at the start of the marketing authorization assessment when the dossiers are received which you will find out by following the announcements that EMA is doing periodically." Vague enough for bureaucratic purposes?
Excellent succinct summary, boi, of what I too believed were the newer and most salient elements of emphasis in yesterday's presentation.
In recent weeks I have read a couple of reviews of Donanemab and/or Lecanemab (LEQEMBI) in which the commentator expresses his/her concern over the accelerated brain shrinkage caused by treatment with these monoclonal antibodies. The fact that Blarcamesine actually slows the shrinkage vs. placebo is a stunning contrast.
Indeed, Slide 21 (at about 14:30 of the presentation) was the juicy new bone that Missling threw out from the data pile. Larger and faster improvement in the plasma AB 42/40 ratio vs. placebo for the blarcamesine patients than those treated with LEQEMBI was impressive and unexpected. Nice to see this biomarker show an mAb beaten at its own game, even if it isn't the one blarcamesine professes to play. I suspect the EMA will enjoy that slide.
You are also spot on with your observation that Anavex looks set to push the restorative effects found in its genomic study, and I also fully agree that this was a superior presentation from what Missling has often delivered in the past.
Was she not the TD Cowen analyst/moderator?
Why didn't the small group of 5%-15% make the cut? Well, if LEQEMBI fails at the EMA in the next couple of months after a review by an SAG called in to render an opinion, we can say that one of the applicants (or about 1% of total, as I recall) did not pass in terms of the efficacy/safety ratio and/or an efficacy/cost ratio.
Yes, plexrec, the timing is actually quite good with impending donanemab approval turning some attention back to Alzheimer's. Furthermore the forum is excellent, Missling not having presented at TD Cowen recently (if ever?), and offering a solid institutional audience, the majority of whom have never heard the story before. The time slot in the afternoon of first day is a good one as well. The presentation by Grimmer at the end of the week, albeit to the wholly different audience of his colleagues, is no less important and no less timely in my view.
Thanks for recommending me for a slot in the marketing department. I was in media before the investment business, and once upon a time worked in the building which was the previous HQ for Anavex. Rockefeller Center would be fine. I could walk to work and eat the delicious "Bison au Poivre" at Le Rock downstairs. I will give it some thought...
Yes, Besao, I saw part of Cramer's pitch on Lilly, and he attributed part of the recent strong movement in LLY to the anticipation of FDA approval for its new Alzheimer's drug, donanedab. I believe the company suggested that approved was expected in the next week or two. Like the Biogen/Eisai drug, lecanemab (LEQEMBI), as well as its now defunct predecessor, aducanemab (ADUHELM), donanemab is a monoclonal antibody (mAb) treatment that reduces the quantity of amyloid plaque in the brain and therefore hopefully retards the development of Alzheimer's. After decades of work in pursuit of that theory, the results from the mAb's have been disappointing to put it mildly. Donanemab might be somewhat better than LEQEMBI, but it certainly seems a huge stretch to call it a game changer. Like the others it requires infusions at a medical facility. The side effects can be quite serious, particularly cerebral edema potentially leading to life threatening brain bleeds. The latter possibility requires patients to receive regular brain scans. In addition, like its mAb predecessors, it accelerates brain shrinkage. Also a significant number of patients in the trials apparently dropped out because of nausea.
If you indeed read this board regularly, you know that blarcamesine, Anavex' current entry in the Alzheimer's field, does not have the serious safety issues common to the mAb's. There is no cerebral edema and therefore no need for ongoing brain scans. As I recall, there was no issue with nausea, as seemed to plague the donanemab trials. Some patients reported mild to moderate dizziness, and the company now recommending an evening dosing protocol. As you mentioned, it is a small molecule oral drug, in contrast to the mAb infusions (which may evolve into injections). As to efficacy, I would refer you to page 19 of the new (2024) Anavex Corporate Presentation on the company website. No longer does Anavex need to compare itself to ADUHELM, so now we see a chart of ADAS-COG showing that blarcamesine slows the cognitive decline vs. placebo by 28% over 48 weeks. That is a faster and stronger response than donanemab, which slows the cognitive decline vs. placebo by 19% over 76 weeks, as noted in the sidebar. I am sure that Missling won't fail to highlight this at the TD Cowen presentation on Monday.
So, of the two which is more likely to be the game changer? The stock price of AVXL should take care of itself after an MAA is filed and accepted at the EMA and and/or after the peer reviewed article is published.
Pretty spiffy, that VKTX. An incremental $5 billion in market cap today on a Phase 2 in an increasingly crowded field. Total market cap = $9 billion; total revenue = 0. Bodes well for other pre-revenue companies that might succeed in gaining drug approval for a large market indication.
I agree with you on that, plexrec, particularly if that one presentation is all that someone is registering for. Since it is only 15 minutes in total (with little if any time for questions, I imagine) and since you have access to most of the likely content in the company's latest presentation piece, it is not really a question of new information for you and me. I think the significance of this is that it appears to be the first presentation on the data and biometrics from the 2b/3 trial to a European audience, and that it is being done by Timo Grimmer. It comes at a time when an SAG for the EMA is being called to give its opinion on Lecanemab to the Agency, which appears to be deadlocked on the issue (or at least looking for cover). It is also being delivered by an extremely respected Alzheimer's expert on the continent, who seems to me to be taking a more aggressive stance on the advisability of near term approval for Blarcamesine than might have appeared to us a year ago in the company conference call or the MayoMobile interview. Aside from being naturally cautious at the outset, I might speculate that he was quite impressed by the biometrics available since then, in particular the slowing of brain shrinkage. The key here will be the reception he gets with his colleagues in Europe. I think it will be quite positive.
Plexrec, I looked at the PD/AD site a week or two ago, and as I recall, you could sign up as an offsite participant and have access to any presentation that you wished, either live or previously recorded, up until the end of the conference (March 9th) for a fee of 300 Euros. A somewhat higher ("Gold Track"?) payment allowed for access after the conclusion of the conference. The time difference between Portugal and EST here is five hours, I believe, so you would have to get up early (or if on PST, go to bed late the night before) to hear it live.
Gute Frage, Missing. Rereading the FQ4 conference call transcript gives a strong hint about your speculation.
In regard to waiting to following up with the FDA, I would reverse it a bit. I think Missling was waiting for the EMA application process to be set in motion and also to (diplomatically) confront the FDA with the results/projections for Leqembi, the most recent mAb to come out of Biogen (following Aduhelm), be approved by the FDA, and come a cropper in the market.
Langostino, it is hard for anyone to disagree with your comment that "only the FDA and EMA matter." Furthermore, I won't in a general sense take issue with your observation that "we have to hope that the bar is set so low that approval won't be an issue even with mediocre-to-good data with excellent data for a small population." However, it is worthwhile to recall the height of the bar that Leqembi crawled over. It excluded 80% of the mild/moderate AD patients, and was thereby culled down to a group which achieved mediocre-to-good data. Anavex accepted 80%-90% of the patients who were available. Put another way, there is no data on 80% of relevant AD patients for Leqembi and the remainder are good-to-moderate, while blarcamesine scored good-to-moderate data for 80%-90% of the total relevant mild/moderate AD patients and excellent data for a subset thereof (in a significantly shorter period of time). This only covers the efficacy bar. Safety as well as the relevant incremental cost and convenience for patients didn't turn out to be a bar for Leqembi (at least in the US), and clearly blarcamesine scores far more favorably on those issues. (Boi has already pointed out that blarcamesine reduces brain shrinkage, and, unless I am mistaken, mAb's tend to accelerate that process.)
So, this is a long winded way of saying that I agree with you, but that I would note that if the bars are set fairly and equitably to what leqembi faced (and what donanamab likely faces), then they are clearly not insurmountable.
If you listened to the JPM presentation, kspar1, you might also recall that Missling put in a big plug for Dr. Jin as having had a significant positive impact.
Note also, boi, from the recent presentation that blarcamesine also compares favorably on ADAS-Cog (on a shorter period of time) with Lilly's donanemab, the latest and supposedly greatest(?) mAb for AD.
FWIW, and I hope I am not repeating what someone else has posted, I noticed today that UBS has just downgraded Biogen (BIIB) from BUY to NEUTRAL and reduced the price target. The analyst says that "inflection" for Leqembi will take longer than anticipated. Substantial sales increase in 2024 is not anticipated.
Crescent, it seems to me that what Missling said in the FQ4 conference call was a bit more than "is allowed to submit": "And we were from this meeting recommended to procede with this application, full approval application. And that's what we proceeded with last week accordingly."
How did you come up with end of March, bas? Isn't there a 7 month minimum set by the EMA between the initial ""letter of intent" and the earliest MAA filing? How early do you believe that the clock started last year?
Joseph, I think Missling gave us the answer on the last quarterly earnings call. Soumit Roy (after asking about the EMA) inquired: “And what are the plans for US approval?” Missling answers: “We have the ongoing ATTENTION-AD study ongoing and that’s part of the package of the application with the Phase 2b/3 study.”
He doesn’t say that it has to be completed to be part of the package, but I would understand that to be the case. Do you read it differently?
Funny how the EMA didn't pick up on that...
Yes, I read what boi said. I am not challenging what Investor said about not selling the skin until the bear is shot. However, he seemed a bit skeptical that the trigger would be pulled and that a real bullet would come out. (Beyond that, I do believe that the odds of success are very good.)
Are you suggesting that Dr. Kun Jin and his team are incapable of filing a complete MAA?
Excellent post, boi. Although the phrasing was a bit stilted, almost as if it were a direct translation from the German, Missling didn't mince words on the Q4 conference call regarding the reaction of the EMA to the data and the meetings. It didn't sound as if the EMA officials were passively indifferent to whether Anavex filed or not, as some on this board would suggest. After noting that the yet to be published data had been shared with the Agency, he said, "And we were from this meeting recommended to proceed with this application, full approval application. And that's what we proceeded with last week accordingly."
This is probably true, Pazzo, and some have pointed to that and criticized him for that perceived impropriety. On the other hand, what no one has mentioned is that if Missling had released that PR in the waning days of 2023, those same people would have excoriated him for trying to hide the disappointing results in the holiday period where it would escape attention. He couldn't win on this, and I think, deliberate or not, it was appropriate to release it in the full light of the New Year.
Steady, Missling said the EMA had seen "the data which has not been published." He did not say "data that has not been published," implying that it could have been only some of the data. I read that sentence from him as meaning the full data.
Your instincts are correct, north. Individual investors, whether they are "professional biotech investors" or not, are not required to report their holdings to the SEC unless the number of shares equals at least 5% of the company's total shares outstanding. Therefore, unless one holds something over 4.1 million shares there is no requirement to file. I know of a number of individual investors - at least one of whom by background would qualify as a professional biotech investor - who each own hundreds of thousands of shares of AVXL, holdings which never get reported. For those funds (private or not) that manage over $100 million in assets quarterly filing of holdings is required. No doubt a number of smaller pools of capital below that $100 million limit also own hundreds of thousands of shares of the stock. With the exception of index funds, more sizable institutions are not comfortable owning pre revenue (or at least pre drug approval) companies and/or ones that have a market cap below $1 billion and trade less than $10 million in volume on a daily average, like AVXL. They are too speculative, too volatile, and too illiquid for their tastes. These managers also require more sell side coverage than small companies typically get so they can dig into their files and wave those brokerage reports at their bosses if a stock heads south. With filings at the EMA and the FDA this coming year and perhaps even an approval or two by yearend, I believe that AVXL will gain the publicity and traction necessary to induce sell side coverage and real institutional appetite. In my view, the slog from single digits to $30 will prove to have been a lot more difficult than the run from $30 to $100.
At this point in my life I have read about and experienced enough strategic planning as well as M&A, and I can certainly count shares. If Biogen ever really agrees to an offer like 2 BIIB shares for each AVXL, it would be because the Biogen management has gotten itself into deep trouble.
mrplmer, you keep repeating this hypothetical offer of 2 shares of BIIB for each share of AVXL. Given your antipathy to the Anavex CEO, you might want to rethink that construct. You cite the "weakness of our leadership," but if a deal is agreed to at that exchange ratio, there will have been a recognition of the weakness of their leadership, as evidenced by the failure of Aduhelm and Leqembi. Don't know whether you calculated it or not, but the majority of shares in NewCo (BioVex?) subsequent to the closing of your hypothesized deal would be held by former AVXL shareholders. Most of the latter will be institutional shareholders by that time, very few of whom will be at all dissatisfied with Anavex leadership. Far more likely than not, the CEO of the combined company will be none other than your nemesis, Herr Doktor Missling, should he choose to remain. The idea of sheltering money from the immediate tax hit sounds great, but you will be condemned to an ongoing state of agita. You can't have your fig pudding and eat it too. For the moment, however, relax and enjoy Christmas!
So, Langostino, given this new IP protection for Blarcamesine on not just Rett but a wide range of neurodevelopmental diseases, would you say we are in a happier place for dotted dominoes to fall?
Let's put it to you this way, Jimbo, if I had a spare $2.3 billion to invest or could put together an investment group, I would be willing buy out AVXL at $28 in a heart beat. You could run hard with that bird in hand and I would heartily wish you all the best with your going forward reinvestment strategy.
Power, you are absolutely correct. Cerevel (CERE) is a pre revenue company in the neurosciences sector. If you look at their pipeline, it is no more advanced than Anavex' (in fact less so), is not currently targeting any indication as large as (full) Alzheimer's, and has not commenced a drug application process as has AVXL with the EMA. Nonetheless, AbbVie is paying $8.7 billion for the company. At that price tag AVXL would be over $100 per share.
Cerevel has been humped and pumped by Goldman and Morgan Stanley. Anavex, while having taken a less dilutive path to financing, labors in relative obscurity without significant Street coverage. I firmly believe that this valuation issue will be redressed in the coming months, as the review of the AD 2b/3 trial is published, the TLD from the EXCELLENCE (Rett) trial is released, and the Phase 3 Parkinson's trial commences.
No, we know the answer right now. The statistics tell us that the EMA would not have given them the green light to proceed if they didn't believe the odds of approval weren't very considerably more than 25% out of the current trials.