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Yes, which is why Kauffman (the gatekeeper to the Rett community) was hired as the CMO and not an Alz. expert, though someone from the SAB/outside could take on a spot in 2021.
Yes, may not remain 2nd class for too long after the moon landing in a couple of days.
The ground is firming under A2-73 every day.
Doc328, all excellent points. You said...
A confirmation of any error in Nature mag (or its derivative journal) can be made by simply bringing it to their attention by a simple Twitter tweet with @nature in the message. They respond quite promptly that they will look into any potential error and then confirm or deny it.
FT is nowhere near as huge as AA or BTD. Each has its own different set of qualifiers obviously.
Revealed autophagy mechanism is potential dementia target
bit.ly/2Z8BP9S
Jeffrey Cummings is on the SAB at Alkahest. I wonder what he thinks of A2-73 v/s Alkahest's GRF6019.
Quote: Christopher Missling
The expectation is that we are – that we have the study completed VERY SOON. We are almost there and it’s a great accomplishment by the team. And we know that the study has a 14 week treatment duration. So if we are able to complete the study, that will then needed to be added this 14 week in order then to have the data locked and then subsequently becoming – possibly available in a press release, the top line data.
The 3 separate ramp-ups to $4 earlier this year could have been Blackrock's algos. Now buyers will wait until after data.
Biochecker4, The likelihood of PW liquidating is just the 'what if the sky falls on our heads' argument by retail investors that's telltale of muddled confused thinking on their own part.
AVXL Oct 2019 options implied vol is elevated suggesting expectations of mkt moving event/s prior. It's not a surprise to those expecting an announcement of study completion in Rett & PDD with data soon after. (Missling's call indicated he has chosen to forego the announcements of enrollment completion.
I'm sure when Missling filed the 250mm S-3, he had AXSM in the back of his mind - a pop to 6 drifting up to 10+ and then the secondary around 10. Otherwise that size doesn't make sense. Needless to say it's contingent on strong data but all of us here have seen strong signals.
So I wouldn't focus my worries around PW's machinations.
biochecker4, i agree with your overall assessment on institutional holders but wouldn't read too negatively into Park West's trimming given AVXL's context in their overall portfolio.
Alzheimer's is a 'show me' indication and while the broad MOA is established, the outperformance of A2-73 to other S1R's is still unknown IMO.
No money mgr is expected to risk one's career and reputation by going out on a limb. If AVXL trials are successful, there will be plenty of time & oppty for mgrs to pile in and that's what they do.
Case in point AXSM: (i'm fervently praying AVXL chart follows AXSM which is currently a 10x bagger and still under 1bn mktcap.)
AXSM failed multiple trials until they struck big in MDD. Stock popped to 6+ from where we are currently and mmgrs have subsequently obliged and have come out looking like stars.
Also check out SAGE and even Avanir which got acquired. Success in neuro indications usually reaps big rewards.
Our fate hinges on trial outcome & then financing & leadership; everything else will take care of itself.
True, Investor2014. When you witness the comprehensive approach AVXL has undertaken in addressing this complex disease, NTRP's singular, narrow approach is clear to see.
AVXL has had to sink in 2 extra years for this and IMO Missling's budget management to date has been exceptional. Bio-land is replete with examples of leadership looting investors.
runcoach, I'm sure you know bryostatin has a very narrow therapeutic window (if any) which NTRP is trying to finesse with. Their trial result in Apr 2017 couldn't demonstrate a positive dose response effect. In fact, NTRP has failed to release trial data for the entire higher dose cohort (or half the original 147 patient trial.) Why do you put faith in a company that openly manipulates.
NTRP has targeted a placebo-adjusted improvement in the SIB of 2.6 points at 3 months for bryostatin, which is not clinically meaningful. By comparison, the Pfizer's Alzheimer's drug Aricept showed a placebo-adjusted change in the SIB of 5.9 points after six months. So NTRP is chasing an endpoint which will not be rewarded by investors.
Diarrhea is a very lousy side effect to have in the geriatric population. A2-73's side effect is a mild tingling in the head or mild passing dizziness in some patients. I wouldn't mind a mild tingling while the misfolded proteins in my neural mitochondria regained proper form and function - I would be encouraged by it.
I do wish for every clinical trial to demonstrate genuine statistically meaningful therapeutic effect for the benefit of all patients.
PW & Leo, with due respect there is a massive chasm between trial result showing a stat sig and DSMB stopping trial due to futility for which they always look at efficacy.
I wouldn't hang my hat on trial success based on DSMB review of efficacy data.
NTRP: a 107 day trial is useless in Alzheimers. In any case they are targeting beta-amyloid reduction which is a dead endeavor now. I will be shorting any pop from any deemed "successful" outcome media announcement. (Funding secured.)
So are you dissing A2-73 for it's inability to maintain or increase these cognitive measures. While there may be 5-10% super-responders, expecting it across the tested population an unrealistic expectation that no one on this board harbors.
The A2-73 p2b trial *WILL* show an identifiable differentiation. The question is one of magnitude of differentiation and statistical significance.
Remember, the bar for success is super low as nothing really works currently.
Yes, a lower degree of demonstrated differentiation will result in low gains in SP initially, its safety will ensure it will be the go-to solution for all globally and SP gains will follow prescription growth to our desired SP potential.
NTRP's compound is highly toxic and its use can only be justified on the very severe Alzheimers cases. AVXL is testing on mild Alz cases on which the benefit vs. toxicity tradeoff from NTRP's compound cannot even begin to be justified. Therefore, even of their current trial is successful, they won't even try. Secondly, NTRP's trial is very short (prob. because of toxicity) and therefore demonstration of a reversal in severe consition is key. In contrast, demonstration a long duration of benefit is a key requirement in mild & moderste cases.
No one on this board expects MMSE/ADCS-ADL to remain unchanged or increase over time for A2-73 patients. Period. The bar is low as no current treatment has been able to decelerate the natural rate of decline in patients. You're assertions reveal a questionable grasp of the issues related to trial outcome.
If strong efficacy/dose response to blood concentration of A2-73 (or its metabolite) has been firmly established and the big hurdle (that's making us all sweat) is metabolite gut absorption specificity for which the bulk of biomarkers are being established, has anyone asked the question...
Why don't we do a trial for an A2-73/19-144 patch (eg. on arm) and dodge the whole gut absorption issue?
19-144 is probably a nano-molecule which crosses the blood-brain barrier - surely its readily absorbed through the skin. A patch is a much better dispensation method for the geriatric population.
Is part of the treatment also happening in the gut?
Humor me through this.
Cassava anyone?
Cassava Sciences, Inc., a clinical-stage drug development company, develops drugs for nervous system disorders. The company's lead therapeutic product candidate PTI-125, a small molecule drug that is in Phase II clinical trial for the treatment of Alzheimer's disease. It is also developing PTI-125Dx, a blood-based biomarker/diagnostic to detect Alzheimer's disease. The company was formerly known as Pain Therapeutics, Inc. and changed its name to Cassava Sciences, Inc. in March 2019. Cassava Sciences, Inc. was founded in 1998 and is based in Austin, Texas.
(FYI $PTIE's Remoxy was a multi-part drama that played out over years...)
Whopping $23mm mkt. cap!
2H2019: P2a study (safety, tolerability, PK & biomarker validation) with PTI-125 in Alzheimer's Disease
$SAVA H.C. Wainwright starts Buy with $3 PT. "The analyst sees "unique" disease-modifying potential of PTI-125, the company's Phase 2 stage drug candidate for Alzheimer's disease., saying it demonstrates potential to restore dysfunctional brain cell signaling."
Not a very imaginative name for a co. pursuing Alz. Healthy short.
Why ERP/COGNISION consortium, ARIANA and practical+effective biomarker ID is an absolute must going forward
https://bit.ly/2Kn1aGh
Key quotes/info from article:
"137 Phase 2 and Phase 3 Alzheimer’s trials currently underway will require 25,000 patients per year over the next several years."
"Unfortunately, the only way to identify an accumulation of plaque in these patients is via the PET scan, which can cost between $4,000 and $6,000."
“To recruit 100 patients for a Phase 3 trial, you will test about a thousand patients, most of whom will be screened out after taking a PET scan,”
"In order to identify those 25,000 patients, between 250,000 and 500,000 individuals will need to be screened."
Observation: A blood tested biomarker ID approach that is then optionally confirmed with a PET scan will be...
1. far more economical,
2. save a great deal of time in recruitment,
3. will save potential patients the agony of being screened and rejected (9 in 10 chance) at multiple trials and
4. with the additional likelihood of a true negative diagnosis in mild cases which snowball later from a false sense of security.
BioStockClub, Thanks. SoCal dudes holding AVXL have to bank on the big A2-73/Alz hope strikes before the other one so we can all cash out and head to a destination of our choice. Otherwise for us Californians, it's high COLA added to death and taxes!
RE: ERP / COGNISION - I am surprised people here are wondering how Anavex might be involved with one comment saying, "they probably just joined in."
Cannot be further from the truth IMVHO.
Anavex CHOSE Neuronetrix for its A2-73 P2a trial for Alzh. (see Nov. 7,2014 press release). Their COGNISION system likely adapted symbiotically while working out a solution for Anavex - any lab grown AI system needs a real world application to mould itself into a commercially viable solution.
Now how on earth would obscure little Neuronetrix even start to cobble together a consortium of heavy hitters in neuro-space let alone have them sign them up for a standardization process for the future?
The key is successful VALIDATION of COGNISION in a trial to influence its outcome in an complex multifactorial indication that has seen ZERO trial success for ages. Needless to say it's required the help of influencers like Hampel, French and Anavex's other stellar SAB members, but they have all needed to sprinkle the SPICE(Dunes) of convincing trial outcomes (so far in their possession) to make heads turn.
So make no mistake - Anavex is very much driving this through its influencers in the field.
Analogy: Here in SoCal, we've had quite a few tremblers lately (as high as a shallow 7) and it's generated plenty of talk of "the big one" and also of the yellowstone caldera. A big one is always preceded by an increasing frequency and magnitude of quakes and I cannot help but remark how similar this ERP consortium formation is as one small step that heralds the big leap for mankind with AVXL's A2-73 in Alzheimers, a little more than a year away.
PS: BIIB is so 20th century.
Did anyone notice a new study involving AVXL on Clinical Trials?
"Event-Related Potential (ERP) Biomarkers in Subjects With Schizophrenia and Healthy Volunteer Subjects"
ClinicalTrials.gov Identifier: NCT04025502 (First Posted: July 19, 2019)
Sponsor:
ERP Biomarker Qualification Consortium
Collaborators:
COGNISION
Cadent Therapeutics
Alkermes, Inc.
Anavex Life Sciences Corp.
Merck Sharp & Dohme Corp.
Takeda
Sage Therapeutics
H. Lundbeck A/S
We are among the HEAVY HITTERS now!!!
PDD enrollment completion any day now - expect a pop in SP to 3+ from it.
Oct 30, 2018 - enrollment start announced
Mar 11, 2019 - 50% enrollment threshold announced (4&1/2 mo)
At the same rate, another 4&1/2 months means...
Monday, Jul 29, 2019 - Enrollment completion?
14 week trial => Primary Completion Dt: 11/4/2019?
Add 3 weeks => Study Completion Dt./Data Announce: 11/25/2019?
Not sure how Missling can justify $250mm need for 'anticipated growth' when he's been insisting that $20mm would be sufficient for 2 years of ops. Even if you double it to $40mm burn every 2yrs going out the full raise should last 12 years! (admittedly simplistic but I'm trying to spotlight the magnitude of the proposition.)
Esp. when proposed raise $ is larger than the current mktcap at the time of filing of S-3. Never seen that happen before by a long stretch. I would have anticipated a next raise to take OS from 51mm to ~70mm or so. An instant doubling of OS is quite insane. I'm aware, co's often don't draw on entire shelf all at once but haven't seen such size in context of current mktcap.
I expect the SP to crater for the next few days.
Not questioning 2-73 or 3-71 at all - that's why I'm here.
I don't think a shelf is needed to provide a share-stake to a partner. They ought to either announce an open mkt acquisition at an above-market price or start accumulating before an announcement. Dilution is not prerequisite IMO.
I'm sorry, i don't get it...
If AVXL partners with Eisai (sells Japan only rights in PDD & Rett) for upfront (& milestone) $$, then why did AVXL need to file the massive shelf?
Pre-deal posturing? Or Plan B (for backup)? I don't think so.
Potentially serious competition in Rett: Avexis (acquired by Novartis in 4/2018 for $8.7bn for their gene therapy in SMA)
Still have to do DD on this but came across the following tweet:
https://twitter.com/AveXisInc/status/1141341930598649856
New Alzheimer's competitor: Cortexyme (CRTX) just IPO'ed.
COR388, an orally-administered brain-penetrating small molecule gingipain inhibitor, which has completed Phase 1a and Phase 1b clinical trials for use in patients with mild to moderate Alzheimer's disease. The company was incorporated in 2012 and is headquartered in South San Francisco, California.
Make money on the side long AVXL, short CRTX
I'm not 100% sure but I think in blinded trials, while progress & outcome of individual trial arms may be blinded, the progress & outcome of the overall trial is privy to the CRO and by extension, the sponsor but never publicized or acknowledged outside this sphere. This overall data is enough to provide enough information in any trial where a drug provides a differentiated outcome from control.
Not to mention, the PDD trial in Spain has requested a trial extension already. This would not have been done on a whim or gut feeling.
The latest shelf may not be for a stronger hand at the poker table but to fund the Australian PDD & Rett trials which were never part of the original plan through the period Missling kept insisting they were funded for 2yrs out. That & he's made some key hires since.
PDD trial extension request, trial expansion to Australia and some of the hires are clear signals to me of a successful outcome. While study completion dates for Spanish PDD and US Rett is Dec 2019 I expect data as early as late-Oct/early-Nov as the PDD trial was recruiting ahead of schedule and a lot of pre-enrollment ID legwork was completed in Rett for quicker recruitment.
Missling could well commence with his characteristic "breadcrumb trail" purchases in the late summer. I don't think any LPC activity will depress SP too much this time around (barring an overall mkt slump) as the stealth accumulation has begun and all hell will break lose when Missling starts to nibble. Been a loooooonnng-time holder and this is home-stretch.
BIO CEO & investor Conf - video - Proactive investors Stocktube
https://bit.ly/2NlpEO3
not sure if this was posted earlier
Rett topline readout - EOY'19
PDD readout - EOY'19/Start'20
Alz readout - coming years [2021 earliest? - coming year (singular) would be 2020]
what a slog it's been already
By not being clear on (on the back of no formal public confirmation of) the nature of any purported continuing relationship, Missling is like most other CEOs probably namedropping while providing courtesy feedback to MJFF. Wasn't insinuating anything earlier - respect your posts. wouldn't care to take this up with anyone else on the board.
It's a bit of a leap to think MJFF is actively involved in P2 sponsorship or any other meaningful way, although I wish it were the case. Missling's statement could mean they gave MJFF feedback on their decision on P2 trial design because of MJFF's prior sponsorship and recognition of MJFF's influence in PDD research. Anavex's SAB clout easily outweighs any constructive input MJFF may be capable of providing.
Rett Gtx: MECP2 GTx programs are finally making it to the clinic.
https://t.co/62yhk9mYSZ
OT United Neuroscience "cautiously optimistic" about Alzheimers synthetic peptide vax candidate UB-311 after ph 2a study achieves 96% response rate w/good safety profile, suggesting early clinical findings "reproducible"; CEO Hu not looking to develop “one-shot wonder"
Needs looking into. First time I'm hearing about this & don't know MOA
Smithsonian Magazine: Your Appendix May Be Starting Point for Parkinson’s Disease
#SmithsonianMag
Re: "Dementia Australia": Recruitment notice...
How is one supposed to interpret the phrase "Occurring Dates:
05/07/2018 to 30/07/2020" ???
Is this the max. potential timespan of the recruitment window? Do these recruitment notices broadly cuff these windows and typically finish recruitment well within? I haven't come across recruitment notices before.
I'm expecting a 8-10 month recruitment period which hopefully starts soon. It would put final readout in June-Sept 2020.
***FDA opens new path for earlier-stage Alzheimer's drugs***
REUTERS
Published Feb 16, 2018, 10:26 am
U.S. regulators have proposed lowering the bar for clinical trial success for experimental Alzheimer’s drugs to better align with the current emphasis on the need to treat people when they are in the earliest stages of the brain-wasting disease.
Medicines tested to treat Alzheimer’s have had a dismal track record, and the Food and Drug Administration has recognized that goals for clinical trials need to evolve to assess drugs aimed at earlier-stage patients.
In proposed new guidelines released on Thursday, the FDA appears open to trial goals that better match early patient populations, including people who have yet to display memory loss or functional impairment, such as the ability to wash or dress themselves or cook meals.
The draft guidelines suggest that improvement in biomarkers, such as amount of beta amyloid in the brain, a protein linked to the disease, may be an acceptable goal for deeming a drug successful in patients with no symptoms.
FDA guidelines used in prior studies demanded that a drug demonstrate both cognitive and functional improvements.
“Biomarkers may actually be able to detect who’s on that Alzheimer’s path,” Maria Carrillo, chief science officer for the Alzheimer’s Association, said in an interview.
Early stage and asymptomatic patients may be identified through sensitive cognitive screening, imaging tests or biomarkers, the FDA said.
For testing a drug in patients with early signs of cognitive impairment but no functional disability, just improvement in memory and thinking ability would be an acceptable trial goal.
“If we can ... slow down overt symptoms of cognitive problems, why would we wait years for functional evidence, when we could detect it earlier and stop it at the cognitive problem?,” Carrillo added.
“What we need now is those bold and brave trials that are going to test that hypothesis to see if we can prevent the overt symptoms,” said Carrillo, adding that she did not believe past trials would have succeeded under the proposed guidelines because of the disease stage of most patients involved and available screening techniques at the time.
In the most recent major disappointment in the field, Merck & Co said on Tuesday it would halt a late-stage trial of verubecestat in early-disease patients after it was determined the drug was unlikely to work.
Biogen Inc, which has one of the few promising drugs still in late-stage development, spooked investors on Wednesday when it said it needed to add several hundred patients to its ongoing study of aducanumab in order to clearly see whether the drug is having a significant effect.
Biogen spokesman David Caouette said the company welcomes the FDA’s willingness to progress its thinking around appropriate trial goals for patients at earlier stages of Alzheimer’s disease.
There is no cure for Alzheimer‘s, a fatal brain disease that slowly robs victims of the ability to think and care for themselves. It is the sixth-leading cause of death in the United States, according to the Centers for Disease Control and Prevention.
This draft guidance “gives the field more confidence in being bold about the trials that we design and then carry out,” Carrillo said. “It’s going to be really important.”
Pfizer GIVES UP on its search in AD & PK indications
https://t.co/ttMnuoNe82
http://bit.ly/1n3Bi16