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BTD baby!!! This board needs to seriously wake up!
frrol, does your astute buddy think Missling will get all 3 trials started before the end of 2017 or is he not holding his breath again?
Thanks for sharing, Mike. My guess is Anavex follows this trial design path. Looks like the measures are subjective/caregiver-assessed and wondering if any trial biomarkers exist/been used in the past or gleaned from AVXL's genetic testing in AZ.
Avg. 16% progressive improvement in 6 weeks is the benchmark to keep in mind.
A future P3 of A2-73 should include an arm of A2-73+trofinetide. Neuren is pretty broke and Anavex could buy it if found useful.
While we head into the Rett trial picturing A2-73 as a cure-all knowing nothing about trial design & outcome, please read these sobering words from the Rett Syndrome website: (https://www.rettsyndrome.org/make-a-difference/summer-appeal)
"Rett syndrome is an incredibly complex brain disorder and multiple approaches will be needed in order to treat or cure all of those impacted. No two individuals with Rett syndrome are the same, even if they share the same MECP2 mutation; so it is unlikely there will be one treatment approach. In addition to the complexity of the brain disorder, we have to think about the age of those affected at the time treatment options become available."
Would also like to point out/ask for an explanation from the board on the timelines in the following graphic - P1/2 + P3 = 3-10 years
Missling -> purchase #3 right on schedule!
#1 8/11 750@3.55
#2 8/14 375@3.70
#3 8/18 375@3.81
next #4 on Monday 8/21, right hess?
Simple question: why didn't AVXL start with their cash raising exercise with LPC after announcing the start of the Rett trial. Is it because they think, with LPC, the end result would have been the same? Is it because to start any trial, they would have to release PK/PD first and they still don't want to?
When you say IR, if it's one of River East/DobsonMedia/Gotham Comm. i would have less confidence in their word (from past experience) than from someone directly at Anavex. These guys are juggling far too many companies to service Anavex with extra detailed attention and I don't see why Anavex would have communicated this specific info to them. Nothing to gain and everything to lose.
I wish AVXL could have done a private placement with new investor/s at this stage at $5.5-6.0, given that they have bigger investors like Park Place & Knoll in place already. It's always hard to get the first big fish but with ~25% insty holdings I wonder if the LPC agreement binds them to this funding channel and precludes any PP attempt.
Case in point, tiny Canadian Alz. player Promis Neurosc. currently in preclinical stage just raised 6mm through a pvt. placement. We are at a far more advanced stage and should have been able to scale up that number at a better price.
It's clear LPC manages a $2 bid/ask spread.
With Missling continuing to use an arithmetic average representation, it should be incumbent upon him to clarify any potential interpretation the chart may suggest. He's had I think, one presentation oppty showing week 57 data where, I certainly would have pointed to the blip and explained it as dropout related. I still think part of the blip could be protocol change related with the start of the new 52 week extension.
On the other hand the first 52 week average shows the line declining and then curving up and he's been showing that chart at many presentations over 6 months. Numerous opptys to clarify if this was dropout related or any other artifact of averaging. Lack of such guidance leads me to think it is entirely dose response related. If it's not, I would be very unhappy.
Jefferies takeaways- new and emphasized communication:
Right off the bat Missling brought up PK/PD imminent and kept bringing it up another 1/2 dozen times esp. expecting it as actionable correlation that kicks off 3 trials this year.
Full genomic analysis of patients' genome are being fed into Ariana's data analysis tool to draw correl with systematic responders. This is now routine in oncology which AVXL is drawing on to reduce future trial risk (and full marks to AVXL for being thorough.)
Per a recent study, BDNF Val66Met polymorphism correlates with
higher frequency & severity of seizure. Also correlates with cognitive decline & increased AB accum in AD. A 2-73 normalizes BDNF expression in the hippocampus (this may have been brought up at the Angelman/Seizure presentation in FL a couple of weeks ago- missed it)
In other news, detailed Bryostatin study results and analysis from the Phase 2a and Expanded Access (EA) studies was just published in the Journal of Alzheimer's Disease: http://bit.ly/2sdl4JY
Saw their stock jump 12% today as it was apparently well received. Board input would be useful.
Bloomberg interview: Didn't quite grasp the implications of Misslings opening sentence - AD... understanding the old and the young and the commonalities...!?
I try to parse his speeches for clues to changes in his thinking and I thought there might have something here I might have missed.
I checked and couldn't find any reference on the duration of the study.
If you mean 'how long ago', it was presented on Feb 17, 2016.
I don't know why Biogen, (at a minimum) would not be able to replicate the pre-clinical work on MS done my Prof. Lisak at Wayne State, presented at ACTRIMS, Feb. 2016.
http://www.anavex.com/sigma-1-receptor-agonists-inhibit-oligodendrocyte-cytotoxicity-induced-by-molecules-involved-in-cell-damage-in-multiple-sclerosis/
Don't know on both counts... hunch is hey could still be tapping down the 1st deal & not sure if this 2nd one would take as long to set up as the 1st. Surprised to learn the 1st one took so long to set up. Very hard to project needs 1 year out for these bios and for SEC to expect them to set up relatively complicated expensive financing so much in advance.
Zig, I thought they need EC approval first for the go-ahead to sell. Last time it took 1 year from S-3 filing to get approval.
MaMag, I believe, the extension has been described as a new trial from the start and we all missed it. I highlighted the PR in post# 105791 where I cited powerwalker. The PR is dated March 10, 2016.
Not a moment too soon. AAIC finishes a day before July'17 options expiration. Tick, tock.
Darn it, your specific info. dashes my construct completely. Why did they take the trouble to call the post 52-wk 1yr re-extension a "new trial" unlike in the 1st extension? There's got to be some meaning attached to that qualifier.
It leaves me still looking for an explanation for the inflection at 57 weeks...
BTW, where did you find this useful info? Been keeping my eye out and haven't seen a PR or anything. Not questioning your veracity.
EDIT: Aaah! I see your updated post. There's still hope for my theory to pan out!!!
Yeah, what they're saying is although the post 52 week phase is being considered a new (back2back / follow-on) trial, it's still a (2nd) P2a. It is not to be confused as a P2/3.
My guess is they will continue to call it 18 month, etc. because it's the same set of patients with some (super-6 +) continuing on the same dose perhaps. Some might call usage of "18-month" a bit misleading but I'm not complaining.
THAT'S IT!!!
I'm sorry if this has been obvious to you guys ever since the PR (below) but "NEW" trial means dosing after 52 weeks is not bound by the trial protocol established for the past year and dosing can be optimized at this juncture AND IN ALL LIKELIHOOD WAS! That explains the inflection to the upside at 57 weeks and brings back memories of the 5 week readout which led to massive euphoria and the climb to $14. The good news this time though is that there should be no reason to expect a subsequent dip right after (17 weeks) and then stabilization, like we saw in 6-mo data, as they have all received some amount of A2-73 in the past.
The big question is HOW FAR UP does the line ramp to before stabilizing? We have six measured at roughly >=24 MMSE in the past. If a dozen more join them, heck, I'm calling this a cure and throwing a party! ('Normal' MMSE is defined as 24-30.)
...adds up to 8 and not 7.
???
Yes, blu_1, the drug works remarkably well on at least some and maybe more and a foolproof design for the next trial will seal the deal. I think the 1.5yr data release likely has surprise/s in store rather than being more of the same.
I am confident that 2 to 3 years from P1/2 trial extensions will practically guarantee approval at the first 6-month interim look IF stat sig. This statinesque/beta-blocker-like (or even better) safety profile ensures that once approved the drug will rule the roost for long with immense detracting power against subsequent competition. It will stick like superglue.
Oh, about all the talk on CEO comp... IMO, with the prize getting bigger and bigger every day in the eyes of the BOD, they are scrambling to ensure CEO comp is gravy enough so he's in for the long haul and doesn't sell out to the highest bidder. Besides, the options are struck at the money and those who are quoting $8mil don;t understand stock options.
NB: I just hope Rett doesn't play spoilsport as A2-73 really has been all about AZ so far.
In the testing conducted in this adaptive trial so far, there is probably a pretty large dispersion in efficacy of A2-73 given the 6 super-responders on one hand and the 7 dropouts on another. The remaining population is probably spread in between. (This board hasn't quite addressed this likelihood squarely.)
It is the reason why all Anavex presentations have shown averages and avoided individual responses (eg. in time series data.) Fair enough thing to do by mgmt. as they can focus on subpopulations on which it can be statistically proven to be successful in advanced trials. Presenting mixed P1/2 data details would cause the market to take away benefit of doubt and chase Anavex out of business.
Hope a large part of the reason for mixed results is sub-optimal dosing and the curious upturn in data post 52 weeks is tantalizingly intriguing. If the protocol doesn't allow for dose escalation, as it isn't declared in clinical trial design then what is causing this inflection to the upside??? Is this new trend sustained??? Is it why Missling's playing cool?
Lastly this large dispersion (on limited n=32 sample) is likely the main reason why Anavex is taking every bit of time to release PK/PD data and trial design for P2/3. It is why they are using Ariana because if we had 32 super-responders (or even > ~16? or 20? for some of you) we would not need Ariana. Once PK/PD is out, there's no going back.
Some past AZ drugs like Prana's for example, probably did work to an extent but didn't have the efficacy enough to prove statistically significant in the trial that was approved by their mgmt. Missling & Co. knows it's not a slam dunk and trial design will make it or break it. Missling and his Scientific Advisory Board seem to have necessary savvy to make it a success.
Long AVXL - may the force be with you.
Bio, Did you end up having dinner with your patent attorney/biotech CEO friend? Was curious to know if you got soak up his insights on AVXL 1-on-1. Any feedback would be appreciated while we wait on data. Thanks.
Old news from the last quarterly report..."February 13, 2017 – Anavex announced the appointment of Peter Donhauser, D.O. to its Board of Directors. Mr. Donhauser has more than 20 years of expertise in clinical research followed by practicing osteopathic medicine with an integrated medical approach in private practice since 2000."
Seems like an unusually mediocre choice on the face of it. Any thoughts?
With regard to the large put position in the name of Dimension Capital, I assumed it's a long put holding as (standalone) put writing wouldn't be much of a strategy to be expressed on the part of any institutional manager.
It's quite a sizeable position (9681 contracts) and far more in # than the total # of put contracts CURRENTLY outstanding across strikes and expirations (after a quick glance.) It's possible some of their contracts had 2017 Jan through Apr expirations? Or maybe there's some detail i'm missing?
imho, i usually see 2 options strategies deployed by institutions, one which you did a great job laying out. I think it's a purely technical (long vol, direction agnostic) play on Citadel's part in response to a very long rising wedge (which xocode has been repeatedly pointing out.) ie. Citadel would do the same with any stock showing the same pattern. (To your explanation) not sure why they would write (slightly) more calls than they are long shares though. Lastly I'm guessing, the # of options in the straddle totally depend on the premium generated from the covered call. Lastly, to be accurate the trade does have a net upside bias as the long put protects the long position in the underlying to an almost complete extent but the trade is foremost a long vol view imho.
The other strategy i see institutions make is a simpler synthetic long or a 'lazy bull' where they are long a call and short a put for the same strike (or adjacent strikes.) This i'm guessing is either to be capital efficient and/or to save them time in accumulating shares while at the same time have a view on increasing implied vol (ie. options are currently cheap) The proportion of call to put can vary depending on the level the underlying stock price is at relative to the strike or even the relative upside / downside bias the manager might like to express.
Among the latest 13F filings, the most eye-catching (new) development is Dimension Capital's sizeable naked short expressed in options space. Hope they've done their research and don;t know any more than we collectively do here. Glad they are not a biotech specialist investor or it would have me worried.
Rare Pediatric Disease, Priority Review Voucher from FDA
I wonder if AVXL is taking any steps to secure one. They are very valuable and can be 'traded', a recent example being Sarepta selling theirs for $125 mil. (see 2nd link) Would solve ALL our funding problems.
https://www.fda.gov/forindustry/developingproductsforrarediseasesconditions/rarepediatricdiseasepriorityvoucherprogram/default.htm
http://www.raps.org/Regulatory-Focus/News/2015/07/02/21722/Regulatory-Explainer-Everything-You-Need-to-Know-About-FDA%E2%80%99s-Priority-Review-Vouchers/
Observations on options activity & history (from wildcard235's chart):
* Call trading volume was off the charts in Jul/Aug & Oct last year
* Call trading activity is dead lately - strange if the savvy guys, instys, heavyweights are expecting blowout news imminently
* SLB rates were crazy high in Jul/Aug & Oct last year in tandem with call trading activity
* SLB rates are dead lately - great that AVXL is not in the focus of the short cabal (strangely coincides with when Shkreli got under the cosh and we all know of his AXON leanings)
While there's an appreciable amount of open interest in the July expiration and leaps, I'm surprised to find the excitement of expectations not showing up in the form of hectic frontrunning and current volume in the options market.
So, apart from Park West and Knoll, are the movers and shakers really gearing up on AVXL?
Thanks, ziggy - makes sense. AVXL surely are serial offenders perpetually leaning on deadlines and late breakers but there's always method to Missling's apparent 'madness' - who am I to question the maestro.
I'm not one to conflate things but if Anavex is not presenting at AAIC 2017 (per neiu's post), then there's got to be an imposed quiet period from deal discussion. What other reason could there possibly be? Anyone?
18 month data will be available then and I can't think of why they would want to skip presenting it at AAIC 2017. (They aren't about to stop presenting at conferences, comments on this board notwithstanding.) They took the trouble of presenting at AD/PD 2017 the rehashed stuff from Nov.16 with nothing added.
ziggy, bio responded as well saying it's one more thing he will bounce off his patent attorney friend over dinner. Looking forward to professional opinion / responses to specific questions on this topic.
Biostockclub, thanks to you & Ziggy for good work clarifying AVXL's patent position. I just recalled an IHUB posting sometime back on a couple of International Patent Apps by AVXL. Your discussion has focused on USPTO which is what ultimately matters at the end of the day but I wanted to make sure ziggy and you saw these in case you missed them earlier.
http://bit.ly/2pkNG1e
http://bit.ly/2oNmWaY
Absorbing Alzheimers article (with informative links)
https://www.scientificamerican.com/article/north-dakota-is-a-laboratory-for-the-future-of-alzheimer-rsquo-s-in-america/?WT.mc_id=SA_TW_MB_NEWS
"vehicle/placebo showed a greater than expected effect" is a phrase everyone fears in clinical testing and can often be a dealkiller. Trials designed to test against an inert placebo may seem like easy slam dunks (vs. active SOC) until the trial design is violated in practice and the fail is uncovered only after unblinding at the fag end. Happened to ITEK when some patients in just 2 trial sites figured they got the placebo and helped themselves to alt. treatment undisclosed while on the trial. If something similar happened with the ALDX p2a trial, thankfully their 0.5% dose was strong enough to hit the ball out of the park in every instance to render the trial a success regardless of placebo 'outperformance.' If there is similar placebo activity in p2b, I'm pretty sure the 0.1% arm will not beat it. I'm not sure how the market will read this outcome and not optimistic of a favorable interpretation. I wish the comparator arm was the current SOC to avoid trial abuse.
I've quadrupled down here and will take half off the table before readout. Not expecting a rapid/robust bounce-back as ALDX has relatively few deep-pocketed/fluid sponsors but it will climb over May & June into announcement. In this unreal market, investors are the tail wagging the market dog and the trail the price traces is more their imprint than an efficient reflection of co. fundamentals.
Investor2014, Thx for your response. Still can't get my arms around what constitutes a successful outcome in this 3-arm trial. I have no doubt the 0.5% arm will succeed to demonstrate statistical significance as before. I have doubts the 0.1% arm will do the same in a statistically meaningful way. I would think the headline would then deem the p2b trial a failure.
The 3 arms are:
Drug: ADX-102 Ophthalmic Drops (0.5%)
Drug: ADX-102 Ophthalmic Drops (0.1%)
Drug: Vehicle of ADX-102 Ophthalmic Drops
Mgmt. says...