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Once the Rett trial starts, and as we understand it likely as the first of the planned trials, we will have 12 weeks plus enrolment time and perhaps some additional delay before readout.
The Rett readout is, as far as I can see, one of those binary biotech events. Either we meet the end points or we don't.
If we don't, is it game over or 'just' a major set back for Anavex?
Most of us, I think, presume that the SP will significantly rise once the trial is announced and subsequently when enrolling. At that point I am curious how many of us will see that as a time to buy more shares, or a time to sell enough to cover the cost of one's position?
An ATM with a known maximum amount of $100M of which we must by now be near half of.
LP is buying 5M shares at aggregate maximum of $29M. That is minimum $5.80 per share.
When LP 'off load' those shares and to whom is unknown, although one must presume only when they can get at least $5.80 a share average.
I am petty sure that when Missling says fully funded for was it 2 years, then he means including drawing on the already publicly know LPC facility - as good as cash.
Missling has also indicated several times that Anavex will partner, but for the commercialisation stage. I take that to mean that we can run all 3 announced trials with the combination of grants and LPC.
If correctly interpreted, I think that is smart and in investors best interest.
Some of the bigger ones were mine and I am no Tute . Filling up the pension fund too.
The bio sector and broadly the market sharply down with VIX up 10%.
A patent covers 20 years from the priority data, meaning when the disclosure was first filed. Not from when granted or fees paid.
Indeed and no he is not being compensated with 11m out of cashflow. He has been granted options as part of his package.
Maybe just the sentence tripping me, "for which" applying only to Rett.
“We are on track to initiate placebo-controlled efficacy and safety trials this year in Alzheimer’s and Parkinson’s disease as well as Rett syndrome, for which ANAVEX 2-73 was granted Orphan Drug Designation (ODD) by the U.S. Food and Drug Administration (FDA).”
ODD in those 3 indications, is that news or did I miss something?
I know about ODD in Rett and Infantile Spasm. Did we get ODD for PD and AD too or by implication in general for A2-73?
I have some experience with technology patents, but not specifically with bio / pharma ones. Admittedly the examples cited in that application appear very real with specific doses and responses, but this may be conjectured on sound insights without actually being the results of human tests (yet!).
In order to later file continuation claims, these must be supported by previous disclosures to benefit from the original priority date. If some or all of those disclosed examples eventually stick in an actual trial, then further claims may be granted beyond those filed as continuation of the present patent application and benefiting from it's priority date. Ref. the previous document I provided a link to.
In the technology patents that I have provided disclosures for, the description would equally include quite specific situations in which the invention could have utility. A description in principle cannot be too thorough or long and does not have to describe actual realised implementations, but rather other embodiments / methods of use of the invention that one expects could have utility. However, the actual claims must have a sufficiently detailed description and illustrations, such that someone skilled in the art can later utilise the invention (i.e. after the patents expiry).
If one discovers or think about other embodiments of the invention after the patent has been filed, which were not disclosed in the description, then a new patent and thus new priority date will be required. The priority date is important to hopefully ensure no one have filed or otherwise made similar disclosures before your own.
When later filing continuation claims based upon the example disclosures, one could use wording such as 'a dose substantially in the range of a - b within which the example dose fits etc.
Yes investors could be responding to the assumption that those examples may relate to actual clinical results. Kudos to any detective who can uncover related clinical trial information.
According to some, technical analysis is only about price volume matters not.
Indeed, hence it is conceivable that the cited examples could have been based on clinical trials outside the US. If so with some detective work one should be able to find these trials registered at some other country's regulatory authority.
I think so too. Merely having filed a patent, which is then 18 months later published, is not yet cause for exuberance - the patent may or may not be granted in some form and likely not for at least a couple of years. However, the allowance on the PLUS patent is cause for celebration.
Drafting Biotechnology and Pharmaceutical Patent Claims:
http://www.aipla.org/Test%20Document%20Library/2010/pppt/Sung_Paper.pdf
Written Description.
To obtain patent protection, an inventor must set forth an adequate written description of the invention. This statutory requirement ensures that the subject matter of a claim presented after the filing date of the patent application was sufficiently disclosed at the time of filing so that the prima facie date of invention can fairly be held to be the filing date of the application.19 This issue arises, for example, out of an assertion of entitlement to the filing date of a previously filed application under 35 U.S.C. § 120.20.
The adequacy of a written description is a question of fact that the Federal Circuit reviews for substantial evidence to support the jury’s
verdict or otherwise for clear error.
I doubt they are actual clinical examples, as this would as I understand have required a registered trial. I guess it is possible that some trials have been done outside the USA and FDA.
I lean towards the examples being conceived in the inventors minds as possible uses of the invention.
I fear everyone are over interpreting the example 'embodiments' in the seizure control patent description section. These are not claims, but examples of the kind embodiments that someone skilled in the art would conceive as a possible uses of the invention. It is about disclosing as much as possible to prevent others from navigating and protecting some use of the invention that you'd rather not see happening. Once disclosed, whether ultimately useful or not, no one can patent that method of use.
My qualified answer to both your questions would be definitely maybe.
I believe the examples are other so called embodiments of the invention that someone skilled in the art could envisage. This is done in the textual description of most patents as disclosures thus preventing others broadly from protecting similar inventions.
Correct. Usually a patent has not been reviewed by a patent examiner at the publishing stage. It could take another few years before we know if the patent will in some form be granted.
Until then it is patent pending.
Yes, the seizure control patent was only just published and this usually occur 18 months after first filing.
I am not experienced specifically with pharmaceutical patents, but in general in the text description section of a patent it is normal practice to cite various examples of possible utility of the invention even if these have not been realised in practice.
Compared to the unexpected therapeutic response across several Alz symptoms on the HAM-D scale that A2-73 have shown in P2, below PR from Lundbeck seems weak.
LUN: Otsuka and Lundbeck announce improvement of agitation symptoms related to Alzheimer’s-type dementia following treatment with brexpiprazole relative to placebo
Valby, Denmark, 2017-05-02 09:10 CEST (GLOBE NEWSWIRE) --
Valby, Denmark, 2 May 2017 - H. Lundbeck A/S (Lundbeck) and Otsuka
Pharmaceutical Co., Ltd. (Otsuka) announce top-line results from two phase III clinical trials evaluating the efficacy, safety and tolerability of brexpiprazole in the treatment of agitation in patients with dementia of the Alzheimer’s type.
The primary endpoint of both trials was change from baseline in the
Cohen-Mansfield Agitation Inventory (CMAI) total score, a 29-item scale to systematically assess the symptoms of agitation. The key secondary endpoint was the change from baseline in the Clinical Global Impression-Severity of Illness (CGI-S) score, a 7-point scale assessing overall severity of the patient’s agitation. These studies were done in multiple countries in North America and Europe, and in the Russian Federation.
In both studies, patients treated with brexpiprazole showed improvements in symptoms of agitation relative to placebo. In the first study, the improvements in the primary endpoint of CMAI for 2 mg brexpiprazole were statistically better than placebo (p<0.05) and appeared more robust than the improvements on the key secondary endpoint of CGI-S (p>0.05). In the second study, the improvements in the primary endpoint of CMAI (p>0.05) appeared less robust than the improvements on the key secondary endpoint of CGI-S (p<0.05). In both studies, there was variability in the data from different countries, perhaps associated with differing standards of care; the data from Russian sites showed especially poor separation between placebo and drug.
Regarding safety and tolerability, both studies confirmed the profile of
brexpiprazole as observed in the clinical trials for schizophrenia and for adjunctive treatment of major depressive disorder (MDD). The most common adverse events in patients receiving brexpiprazole versus placebo (incidence >3% and greater than placebo) were insomnia (4.7% vs. 3.3%), agitation (3.5% vs. 2.9%), and somnolence (3.3% vs. 2.2%). Overall mortality during the studies was low (0.86%) and none of the deaths were considered to be related to treatment.
Perhaps he was responsible for the FDA guidance that Missling has been referring to.
Have seen the unexpected strong placebo effect too. In a U.K. cat allergy trial the reduction in allergic reaction was 60% and exactly 60% too for the placebo arm in phase 3 study. In the phase 2 studies the drug had proven superior statistical significance.
I do agree that the ALDX choice of 0.1% solution is worrisome, particularly as I have seen no dose response data or explanation of this assumed minimum response dose.
As you said, nor is it clear what ALDX have agreed with the FDA. Is it confirmation of statistical significance against placebo for the 0.5% dose, while simply accepting whatever minimal dose effect we get. Or is there some set expectation from the 0.1% arm.
I don't know, but CEO Brady seems to think it is all Dandy. I guess only time will tell.
Seems little ALDX is now exposed to the 'good news push the sp down' manipulation...
Having looked again at Clinicaltrials.gov and thought about it, [ceiling] possible should have been 'healing'.
It seems vehicle, that is the placebo, had greater than expected effect, while 0.5% dose still showed superior statistical significance. I don't know how Aldeyra have arrived at 0.1% as the control arm for establishing minimum effective dose (as required by the FDA), but we must assume they have previously determined some form of dose response curve to make them confident that 0.1% is high enough to show effect against even a strong placebo effect.
Then Tom Brady is adding that, all that being correct, establishing minimum effective dose is all they are missing to potentially have the FDA agree the P2b trial and results leading directly to a P3 registration trial.
Understand your concern on how Aldeyra chose 0.1% and why they feel confident about that being a minimum effective dose. Hopefully IR will eventually provide a reply to you (let us know), but I guess we just have to decide if we trust Tom Brady and crew on the science.
I might double or quadruple down. If successful the rest of the pipeline, not least ADX-102 in SLS with Orphan Drug Designation, is awesome.
I think [ceiling] is a best guess filled in word by the conference call service due to the audio being intelligible to them.
Your interpretation is probably right.
I considering adding too. The ALDX pipeline, and possibly beyond, is attractive assuming the whole aldehyde trapping approach ultimately turns out to be right.
7thwave,
I have held a small'ish position in ALDX for about a year and keep an eye.
My (educated layman's) view on the science is positive. With regards to your question, I think the quote below from the latest investor's call sounds objectively confident.
The 0.1% arm is meant as a control against the statistically SUPERIOR 0.5% dose. Since the response was higher than anticipated with 0.5%, and presumably with a dose response curve being available, I think it is reasonable to expect to see a statistically significant response also at 0.1%.
As always only time will tell...
Todd Brady
Yes. Good morning, Adam. And thank you for the question. It's a very interesting question because there are some changes to the Phase 2b but I think they are very positive changes and they are based on discussions with the FDA. I'd say successful discussions with the FDA. The first thing I'll note is the Phase 2b for Allergic Conjunctivitis is two doses of drug. This is a standard requirement from the agency that you establish what is generally known as the minimally effective dose. So we've selected the dose we used in the last trial which was statistically superior to vehicle. And in addition a lower dose, it's 0.5% what we used prior, 0.1% is what we are using in this trial. As we said last year we did see a higher than anticipated vehicle response in the Phase 2a study that we described in February of last year. The discussions with the agency centered around what is an appropriate control and we've convinced the agency to allow us to use [ceiling] as the control such that there is no doubt that there is any interaction between the vehicle and the allergens used to stimulate the response in the eyes of the subjects. We consider this a major success we think in theory increases the odds of success in the Phase 2b. The one thing I will note, Adam, and I know you know this but if the trial, the Phase 2b trial is positive then it could emphasis on could be considered one of two pivotal trials for approval and the indication. So one possible scenario I'd say an upside scenario is an addition to the Phase 2b if positive, you would perform a Phase III subsequently and then be in a potential position to file an NDA. So I think that answers your question. There are some differences but I think they are in our favor.
The poster does not appear to contain any not previously disclosed information. As such not material and hence no need to PR.
To pretend and then not present, that is the question!
Just skimmed the Biogen Q1 2017 update PR. I saw no hints as to Anavex or in general any notes on possible acquisitions and partnerships on Biogen's radar.
I had in mind that the combination of the preferred stock and the rights plan may be important?
If the 10M preferred were issued in a 'friendly' deal, then that would be some 25+ percent dilution. At the same time the rights plan would kick in allowing longs to buy an additional share for $26 for each owned. Let's just say the PS at the time would be $40, then end result for us longs would be no dilution or even better depending on share price at the time.
Over 50% institutional ownership, I should hope not!
Orphan drug designation announced and the SP tanks. Is that small biotech manipulation or what?
Your guess is as good as mine.
I am though optimistic about the prospects of Anavex. I do my own DD and believe the science, advisors, independent research etc. is bonafide stuff.
Message boards are frequented by all sort from the rational posters on either side of the argument to those that just make no sense at all.
Time will tell.
GTLA, not least the afflicted and their loved ones.
I am long and positive towards Anavex, but it is undeniable that we have heard the same story for quite a long time now.
Hope and expect we see constructive news soon.
Very little to none, but hard to back test.
AGM statement's from Missling consistent with previously published info.
TWST interview SEC filing
TWST: What drug candidates are the farthest along in the pipeline? Where are they and when could they potentially be commercialized?
Dr. Missling: The most of advanced compound in our pipeline is ANAVEX 2-73, which is now in a Phase 2a clinical trial in 32 mild-to-moderate Alzheimer’s patients. The next most advanced compounds are ANAVEX 3-71 and ANAVEX 1-41, which are both at the pre-IND stage. The next stage of clinical trials is in preparation for ANAVEX 2-73: a larger Phase 2/3 study as well as another Phase 2 in an orphan indication, and it could be Rett syndrome.
TWST: Is this for Alzheimer's?
Dr. Missling: We will conduct the Phase 2/3 for Alzheimer’s.
TWST: Do you have the financing you need to get through the development of ANAVEX 2-73 at this current stage?
Dr. Missling: Yes, we believe that sufficient financing in place and also because we are working with several foundations on specific diseases like the Michael J. Fox Foundation that has supported us very strongly for exploring ANAVEX 2-73 in a pre-clinical study of Parkinson’s disease, for which positive data was recently reported on September 22nd. And we also received support from the Rettsyndrome.org foundation, which also supported exploring ANAVEX 2-73 in a pre-clinical study in Rett syndrome, a rare disease for which Anavex received FDA orphan designation this year. We might continue these collaborations if the data continues to be promising.
Let's say everyday we generate 10 random numbers +/-10% from previous close. I suspect one of these would match quite closely with next day's high/low and closing prices.
Would be an interesting benchmark versus TA. Maybe someone has tried it?