Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
It is really unexpected to see such variations in the answers to questions.
runncoach
Good comments. Thanks for your post.
raja48185
As you know, I spent a lot of time on the SAVA board and share a lot of their conviction in SAVA as a good investment potential.
But, I don't think many of them see its weaknesses, vunerabilities, or risk profile. I think that AVXL has weaknesses, vunerablitites and risks too, but the way I understand the S1R literature, there is nothing like that to comfort the SAVA savages and offer a level of independent research that they are on the right track.
For SAVA investors, it is all based on SAVA's test results, that are biomarker supported, but mostly, so far, in an OL format. Personally, I like the collection of test results that AVXL has developed better in most respect than what SAVA has developed.
One very signficant argument that made me choose AVXL over SAVA, and their are several, is that while both claim to provide data showing cognitive and behavioral improvements, only AVXL has a hypothetical MOA that explains how "improvements" come about. SAVA dual action to stop neurodegeneration and inflamation does not offer an explanation of why stopping that yields large improvements. It seems to be true they are getting improvements in their tests, however, and maybe that is all that matters. Some think they are doing more than fixing misfolded filamen A, and that simufilam may be triggering some of the same receptors as AVXL.
But if you get away from the merits of the drugs, it is kind of like deciding what team you want to root for. For some reason, investors build up some kind of non-scientific "faith" in their chosen investment. Once they marry it, they stop critically evaluating it, and start championing it, while attacking all competitors.
That sort of blind faith is not the way to go, IMO. You need to always keep studying, researching, and trying to understand your investment, its progress and the possibility that you don't have it right. Never be so loyal to your initial choice that you stop re-examining whether you made the wrong choice. But also don't freak yourself out at every little setback. LOL.
In the end, no one really knows the future and all these biotech plays are big gambles. GLTY
ImGettingBetter
Thanks for posting that segment of the Call.
Surely the FDA will see the merits of AVXL's endpoints, and that they are superior to what AVAD has presented. Moreover, not only are the endpoints superior methodlogically, but the data seem far superior too, with or without consideration of the side effects.
It seems quite certain that anyone that sold after the AVATAR results were announced will be kicking themselves when AVXL gains their approvals for use of A2-73 in the both the adult and adolecent Rett indications.
It seems that Missling has completely and carefully thought through his endpoint's choice, and, as so many on this board have already remarked, WE GOT THIS!! loL
runncoach
ACAD had done an earlier study that I have linked a few times in which they worked with the AUC computation, and talked about it being potentially more appropriate due to variances that resulted from the concentration of the drug in the blood which varied with the weight of the subject. Based on the earlier development of that AUC data, I am assuming they continued to develop the AUC data. If correct, they could have used it for their PH3 endpoint. It is not clear to me why they didn't other than the likely conclusion that they got better numbers with the RSBQ total score, ie. perhaps they are cherry picking?
You seem to be knowledgable about what ACAD did, so I have a question for you.
Investor2014
Can you compare what sort of effect sizes ACAD obtained in that early study vs what AVXL is getting in AVATAR?
Biotech Stocks: Are Mergers Ahead?
The environment is ripe for biotech mergers, says Brad Loncar, chief executive of Loncar Investments. Loncar provides the indexes for two exchange traded funds focused on biotech stocks.
"There are some large companies that have jaw-dropping levels of cash that they need to spend," he said in an interview.
Pfizer is profiting to the tune of billions from its Covid wares. Novartis (NVS) also sold a $20 billion position it held in Roche (RHHBY). Another pharmaceutical behemoth, Sanofi (SNY), is also spinning off its active pharmaceutical ingredients division into a Europe-based company called Euroapi.
Meanwhile, valuations in biotech stocks have fallen precipitously.
"You have really a perfect environment," Loncar said. "You have tons of great companies that have been dragged down and appear to be at attractive prices, and you have large pharmaceutical companies that are more flush with cash than ever before. It's the perfect environment for M&A matchmaking."
Collaboration Deals On The Rise
Some of that is already coming to fruition. In late January, Belgium-based UCB pledged to pay up to $1.9 billion to buy Zogenix (ZGNX), an epilepsy expert.
Zogenix biotech
Epilepsy expert Zogenix was bought by Belgium-based UCB in late January for $1.9 billion. (ZUMAPRESS.com/Newscom)
Pfizer and Bayer (BAYRY) also entered into collaboration deals to up their chances of success in CRISPR gene editing. Moderna announced a deal to work on next-generation cancer drugs.
Pfizer also snagged deals to help bolster its burgeoning messenger RNA empire.
Those deals could just be the beginning, said Reid Huber, a partner at health care-focused venture firm Third Rock Ventures.
"There's a lot of dry powder out there in companies and the innovation ecosystem continues to be centered in small-to-midsize companies," Huber told Investor's Business Daily. "It's been a relatively quiet 18-24 months in M&A, and I think most folks believe that's going to change. I tend to believe that."
https://www.investors.com/news/technology/biotech-stocks-are-down-and-out-can-these-2022-trends-save-them/
ImGettingBetter and Investor
LakeshoreLeo1953
I discovered SAVA in Sept 2020 and started studying AD, as well as SAVA's hypothesis for how their drug works. I built a list of about 40 other stocks working on CNS indications and started reading about all of them.
During that review, I looked at AVXL, and was attracted by the large amount of independent scientific literature looking at the S1R receptor, and I liked AVXLs multi-indication approach that did not have all its eggs in one basket.
I liked that AVXL reported good results in multiple indications and the potential that the S1R receptor is an evolutionary conserved repair mechanism in brain cells.
I also liked how my understanding of what it does could explain how the results of the trials were consistently positive. I also figured that at $1 to $2 Billion, and substantial cash, AVXL was not overpriced and not in immediate need to dilute.
I still like the SAVA story, but find it much more expensive and much more a binary proposition, with a larger downside risk than AVXL. To my way of looking at it, AVXL has a pie in the sky upside with a more limited downside, yielding a good risk/reward ratio.
If it turns out that Missling is right about how A-2-73 works and what it does, my position here is a keeper for life. LOL.
I also bought into AXSM as an outcome of my CNS review. Their 05 drug for PDD also relies in part on the S1R receptor.
Was just saying the "peanut gallery" to point out that, IMO, we all on the MB are outsiders without the requisite information to decide how to proceed, even if we are qualified executives. That includes you, and me both. I don't say you are wrong, because I don't know. I just say you don't know either, LOL.
blu_1
'mrplmer'
It is not a football game! Filing a premature NDA can cause large delays. They need to discuss this subject with the FDA, and your advice may not be what the FDA tells them. Be patient, and, I suggest, you are jumping to unfounded conclusions that they already have the needed data to file an NDA. Maybe they do, but consulting with the FDA is what they get as a fast track candidate. So that is what they should do, IMO.
Isn't that the job of management to decide, or is it really the job of the peanut gallery. LOL. I wonder if you would really like the AVXL team to follow your advice rather than Misslings! LOL.
Reyeton
If AVXL files an inadequate NDA, the FDA says "no approval" in a Complete Response letter (CRL). That requires a lot of time and money to continue the application with the new data requested by the FDA. It is much better to file an application that is sufficient to start with, so the issue is what they include in their NDA. Do they need EXCELLENCE or not? Do they need the 48-week OL extension data from AVATAR or not? What really is the fastest way to approval? It takes a little longer to include all the data that is coming. Should they wait for their best case, or try to push through an NDA that will only get a CRL? The answer probably requires meetings and discussions with the FDA, which is what Missling said he plans to have as soon as all the AVATAR data is sent to the FDA.
Another thing that is not clear is whether ACAD's endpoint's will be accepted by the FDA. Since they seem to be using the RSBQ score that the FDA has criticized, will they get an approval or a CRL telling them to use AUC or some other endpoint.
While I do not fully understand the math used to run a total RSBQ score vs using the RSBQ AUC scores, it is my understanding that the latter approach is more difficult, at least in part, because it requires the addition of a threshold gain of 25% before the score is deemed clinically meaningful, something not part of the total RSBQ score which simply compares scores at the baseline to those at the endpoint time.
I am not sure I have understood this correctly, so I would welcome any further explanation of the comparisons and any corrections that more knowledgeable posters may be able to offer.
Justice Department Targets ‘Spoofing’ and ‘Scalping’ in Short-Seller Investigation
Muddy Waters’s Carson Block served with a search warrant in the probe of illegal trading tactics
Feb. 16, 2022 8:45 am ET
Federal prosecutors are investigating whether short-sellers conspired to drive down stock prices by sharing damaging research reports ahead of time and engaging in illegal trading tactics, people familiar with the matter said.
The U.S. Justice Department has seized hardware, trading records and private communications in an effort to prove a wide-ranging conspiracy among investors who bet against corporate shares, the people said. One tactic under investigation is “spoofing,” an illegal ploy that involves flooding the market with fake orders in an effort to push a stock price up or down, they said. Another is “scalping,” where activist short-sellers cash out their positions without disclosing it.
Carson Block, the fiery short-seller behind Muddy Waters, was served with a search warrant by an FBI agent in October, said people familiar with the matter, one of whom added that the warrant extended to Mr. Block’s phones. Federal agents took computers belonging to Andrew Left, another prominent short-seller, according to Bloomberg News, which previously reported the existence of an investigation.
Never the most popular camp on Wall Street, short-sellers have had an especially bruising few years. Soaring stock markets, even through the pandemic, undercut their bearish bets. They were cast as villains last year by the meme-stock crowd, who delighted in forcing them into steep losses. Some have thrown in the towel altogether.
Still, they can play a crucial role in uncovering corporate frauds. One short-seller helped turn up the heat on Enron. Others were early to sound the alarm on the 2008 financial crisis and more recent scandals including at Wirecard AG . Now they may have to defend themselves against a federal investigation, which is being led in part by the U.S. Attorney’s Office in Los Angeles, an office known for prosecuting organized crime rings.
Media reports on the investigation have compelled prominent short-sellers such as Andrew Left to defend their actions.
PHOTO: BRENDAN MCDERMID/REUTERS
Spoofing is essentially high-speed bluffing, in which one trader dupes others into transacting at artificially high or low prices. A spoofer, for example, might offer to sell a big block of shares at $10 when the last sale was at $10.03. After other sellers rush to match the lower price, the spoofer quickly pivots, canceling his sell order and instead buying at the $10 price he generated with the fake bid. Repeated enough times, spoofing can produce big profits.
The tactic was outlawed in 2010. In 2016 a New Jersey commodities trader was sentenced to three years in prison, the government’s first criminal spoofing case and the beginning of a crackdown. The same year, the trader who was blamed for the 2010 “flash crash,” when the stock market lost and quickly regained almost $1 trillion in value, pleaded guilty to spoofing and was sentenced to a year’s house arrest. By 2020, the Justice Department had charged 20 people with spoofing-related crimes and collected more than $1 billion in fines from banks and other financial institutions.
Media reports on the current investigation have compelled prominent short-sellers such as Messrs. Block and Left to defend their actions and highlight their success in uncovering corporate frauds. The investors and their lawyers have said they are confused by the Justice Department’s interest in their investing tactics and suspect the government has seized on academic research they believe has unfairly portrayed activist investors as bad actors who conspire to manipulate markets.
Columbia Law School professor Joshua Mitts, who published a 2020 academic paper entitled “Short and Distort” that was critical of short-selling tactics, has been advising the Justice Department in its investigation, people familiar with the matter said. Mr. Mitts has in the past also served as an expert for companies and executives, including Farmland Partners Inc. and Banc of California’s former CEO, that have sued short-sellers, alleging they promoted false or misleading research.
MORE MARKET-MOVING NEWS
Roblox Shares Fall More Than 20% as Earnings Disappoint February 16, 2022
Can Bitcoin Be a National Currency? El Salvador Is Trying to Find Out. February 16, 2022
Blackstone to Buy Preferred Apartment in $5.8 Billion Deal February 16, 2022
Japan’s Stock Market Plans Revamp to Draw More Investors February 16, 2022
Analyses performed by Mr. Mitts on those companies—prepared in private litigation, not for the Justice Department investigation—show that in the moments around the release of a short-seller report, heavy volumes of sell orders are sent to exchanges and then canceled within fractions of a second, according to documents reviewed by The Wall Street Journal. That behavior, Mr. Mitts argues in the documents, is a telltale sign of spoofing.
“We are happy that the Justice Department is looking into this, as we have said for a long time our shareholders were the victims of an orchestrated ‘short-and-distort’ attack,” said Paul Pittman, chief executive of Farmland, whose shares fell 39% the day a Texas short-seller accused the company of financial misdeeds in 2018.
Farmland sued both an investment-research firm and a hedge fund, alleging they publicized a false and misleading report. The researcher later issued a public apology, a rare win for a company targeted in such a campaign.
Short sellers argue that, at least once, Mr. Mitts’s theories on spoofing didn’t hold up in court. In 2020, a U.K. High Court judge dismissed his findings that short-sellers had relied on spoofing to drive down the stock price of Burford Capital Ltd. , a litigation-finance firm.
It was Mr. Block’s Muddy Waters whose research report on Burford had triggered a 50% drop in the stock.
https://www.wsj.com/articles/justice-department-is-pursuing-wide-ranging-investigation-of-short-sellers-sources-say-11645019122?mod=markets_lead_pos1
Amatuer17
The way I look at it, both the A3-71 news and the Rett AVATAR news are very strong positives for AVXL.
The shorts ran a profitable for them operation, and a few weak hands exited. It does not make much sense for them to hold their short positions at this point.
At the same time, three institional players added shares opportunistically, and the PPS is recovering.
We should re- test $13.50 this week, and, this time when/if Russia chooses diplomacy, the Biotechs will rally.
If AVXL breaks resistance, I think it will continue upward.
Barring war in the Ukraine, or other surprises, I don't foresee anything holding Annevex back.
It's finally time for the market to recognize positive news; and, that AVXL is quite a good value at current MC.
IMO, It looks like things are aligning now, and I think AVXL's PPS should double from here, as we approach the EXCELLENCE readout with a pediatric population expected to out perform the great adult results.
Please be sure to do your own research and due diligence, and don't rely on posters. GLTY.
Ortiz
In a world that lets short selling happen, the institutions can own more than 100% of the stock outstanding. It is nuts, but it happens. And it does not matter if you hold your stock or not, LOL.
Jonjones325
So many arm chair quarterbacks on this MB that think they can run AVXL better than the current management. But it is preposterious to think that Missling does not understand he has good data in PDD but he is delaying trials for no good reason.
We just don't know the exact thinking on this subject because Missling is obviously deciding not to reveal it just yet. It suggests something he does not want to talk about right now, and one possibility that could make sense for the lack of discussion is that he is in discussion with the FDA.
Also, I don't think AVXL gets priority attention at the FDA and that is another matter he is not going to announce, discuss, or complain about in public.
Until you know the obstacales, you can't really say anything sensible other than you would like to see PH3 trials get started on PDD. Every shareholder and every member of AVXLs management and its BOD all want that. It is obvious. Just suggesting there is some unknown impediment.
Investor2014
Brain Guide for those worried about AD, first of its kind, it claims. Test yourself for AD.
https://mybrainguide.org/
Base Editors Modify Mitochondrial Genome in Live Mice
February 9, 2022
“This is the first time that anyone has been able to change DNA base pairs in mitochondria in a live animal,” noted Pedro Silva-Pinheiro, PhD, a postdoctoral researcher in the Minczuk lab at the MRC Mitochondrial Biology Unit at the University of Cambridge. “It shows that, in principle, we can go in and correct spelling mistakes in defective mitochondrial DNA, producing healthy mitochondria that allow the cells to function properly.”
https://www.genengnews.com/news/base-editors-modify-mitochondrial-genome-in-live-mice/?MailingID=%DEPLOYMENTID%&utm_medium=newsletter&utm_source=GEN+Daily+News+Highlights&utm_content=01&utm_campaign=GEN+Daily+News+Highlights_20220209&oly_enc_id=0906I4479178I3E
Investor2014
Thank you for that collection of Missling interviews that I have never heard. I will look forward to listening to them. One thing that struck me in the last one you posted:
A very sad event, my condolences.
OT- Powerwalker already posted, so I deleted the article.
Also, before Missling became CEO, if I recall correctly, he was one of AVXL's Scientific Advisors from 2011 to 2013. He obviously had seen potential in A2-73 at a very early time.
falconer66a
In response to your inquiry:
The way I read what he said, those in the trial will get continuation drugs for free, but no mention of FREE was specifically indicated for others, and I don't think he meant free for all as that does not really make too much cents. LOL