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I continue to like the risk/reward ratio.
As I heard Missling, in Part B patients had continued on the dose they where on in Part A. The strong correlation coherently across all measures were that those on the higher doses continued to improved and those on too low doses did not.
The way Missling replied would imply no LPC tapping, so where is the funding coming from, Australia?
Anavex will host a conference call at 8:30 a.m. ET today, October 12, 2017. The call will be webcast live at http://www.wsw.com/webcast/cc/avxl2 and slides are accessible through the investor relations section of the Company's website at www.anavex.com. To join the call live via telephone dial 1-866-866-1333 within the United States or 1-404-260-1421 from outside the United States. A replay of the call will also be available for a period of three months through the Company's website shortly after the call.
Just been through the slides. I think we have a winner folks!
The PR says more data at CTAD.
"The stock market is a device for transferring money from the impatient to the patient." -- Warren Buffett.
BAM!!!
Press Release: Anavex Life Sciences Reports PK and PD Data from Phase 2a Trial of ANAVEX(R)2-73 in Mild-to-Moderate Alzheimer's Disease Patients; Conference call today at 8:30am ET
Anavex Life Sciences Reports PK and PD Data from Phase 2a Trial of ANAVEX(R)2-73 in Mild-to-Moderate Alzheimer's Disease Patients; Conference call today at 8:30am ET
ANAVEX2-73 demonstrates desirable PK/PD properties, describing the relationship between drug concentration and the effect observed
Anavex is incorporating advanced Artificial Intelligence platform for the analysis of Phase 2a results with the aim to increase the chances of success in forthcoming Phase 2/3 study
NEW YORK, Oct. 12, 2017 (GLOBE NEWSWIRE) -- Anavex Life Sciences Corp. (Nasdaq:AVXL) today announced pharmacokinetic (PK) and pharmacodynamic (PD) data for ANAVEX2-73 from its positive Phase 2a study in mild-to-moderate Alzheimer's disease patients. ANAVEX2-73 targets the sigma-1 receptor, which regulates neuroplasticity and cellular homeostasis. Anavex previously reported the Phase 2a trial successfully achieved both primary and secondary endpoints at the pre-specified 57-week analysis.
Data announced today establishes a clear concentration-effect relationship between ANAVEX2-73 and study measurements. These measures obtained from all patients during 57 weeks include cognitive and functional scores as well as a biomarker signal of brain activity. Additionally, ANAVEX2-73 activity appears to be enhanced by its active metabolite (ANAVEX19-144), which also targets the sigma-1 receptor with a half-life approximately twice as long as the parent molecule.
"I welcome such a thorough analysis of data before moving into a Phase 2/3. The intriguing ANAVEX2-73 data shown thus far exemplifies a precision medicine approach, to my knowledge, the first of its kind to broaden the scope of drug development in Alzheimer's disease and other central nervous system diseases," said George Perry, PhD, Dean of the College of Sciences at The University of Texas at San Antonio and editor-in-chief of the Journal of Alzheimer's Disease.
The Company is identifying the best responders to ANAVEX2-73 by using Ariana Pharma's KEM(R) advanced Artificial Intelligence technology. This cutting edge trial analysis will be used to more effectively design the upcoming Phase 2/3 clinical study, raising the odds of late stage trial success.
"We continue to be encouraged by the data from our Phase 2a clinical trial for ANAVEX2-73," said Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex. "We believe that through a systematic analysis of ANAVEX2-73 we might be able to increase the potential impact ANAVEX2-73 may have on this devastating condition."
On the conference call scheduled for this morning, Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex will be joined by Professor George Perry, PhD and Mohammad Afshar, MD, PhD, President and CEO of Ariana Pharma to discuss new findings from the ANAVEX2-73 Phase 2a trial. Further data will be presented at the Clinical Trials on Alzheimer's Disease (CTAD) meeting in November 2017.
Conference call and webcast information
Anavex will host a conference call at 8:30 a.m. ET today, October 12, 2017. The call will be webcast live at http://www.wsw.com/webcast/cc/avxl2 and slides are accessible through the investor relations section of the Company's website at www.anavex.com. To join the call live via telephone dial 1-866-866-1333 within the United States or 1-404-260-1421 from outside the United States. A replay of the call will also be available for a period of three months through the Company's website shortly after the call.
Absolutely right.
But but but, we still haven't seen an OLS fit! We are all doomed.
I think that is fair analysis of the situation.
While we await the trials to start and in turn yield hopefully positive outcomes, share price might move back up in $6 - 8 range once trials are underway.
In between, a potential licensing/partnership deal would move the share price higher. Will there be any such deal in the near term, that is the question...
If they can hold the share price above $2 for a while, then they might finally up-list to, I guess, Nasdaq.
Also the beer and sauerkraut is good.
Presumably there is a purpose to the Anavex Munich office.
Well the conference takes place in New York, and that's the truth!
I can't seem to find the post containing the petition link.
Maybe a sticky for it?
Yes, think about it!
Once AVXL has been revealed to desperately having mined meaningless data and using questionable statistical methods for a glimmer of efficacy, it would look silly to have your name on that petition.
Can I as none US citizen sign the partition?
I see that now yes.
Still curious if the PK/PD from the P2 in humans, that we have been waiting on so long, is complicated by being a brain-blood barrier penetrating drug?
As the abstract explains not only must the drug penetrate into the brain, but therapeutic concentrations of the drug must also reach the target compartments of the brain.
Perhaps this is one part of the explanation as to why it takes time.
I suppose it was a slightly leading question, so I found this:
In summary, the complex structure of the CNS makes brain penetration a very complex feature which cannot be rationalised on the basis of any single parameter. Although total brain concentrations are still the most common measure of CNS exposure, it is now emerging that they are more of an indication of high non-specific binding to brain tissue rather than being pharmacologically relevant. Neither total brain levels nor BBB permeability can be taken without considering the binding capacity of the brain tissue when a link between exposure and efficacy is needed. The current paradigm of brain penetration therefore is changing towards a more compartmentalised view which allows to better rationalise the distribution of compounds within the brain and makes use of brain compartments which are more relevant pharmacological effects. The holistic concept of CNS penetration considers rate of permeation across the BBB, extent of brain penetration and the intra-brain distribution of a CNS drug as distinct but interrelated properties of a CNS drug which have to be determined by different in vitro and in vivo methods (Reichel 2009). Therefore, the integration of data from various assays and studies is becoming a central part of the evolving paradigm in order to develop quantitative relationships between dose, exposure and efficacy. By integrating these data and technologies into PK/PD modeling and simulations it will be possible to generate a working understanding of the pharmacokinetics and pharmacodynamics of potential drug candidates in the human CNS. Such an understanding will be paramount to define PK parameters which are favourable for the desired indication, to guide the preclinical development of the compound (e.g. dose selection for toxicity testing in higher species as well as first-in-man and therapeutic doses) and ultimately to increase the chances for a successful phase II study in human patients.
Question: Is PK/PD analysis different or more complex for a drug capable of crossing the blood-brain barrier?
Very few drugs do cross into the brain and we need to understand the amounts of A2-73 crossing into the brain, how long it stays there and how it metabolises while in the brain.
Anybody able to explain, much appreciated!
One trade of 375 today.
What symbol does Ariana Pharma trade under?
In people for sure, just appeared you were referring to mice.
Ariana is NOT being used in a desperate attempt to dig out efficacy from the existence P2 data. The purpose with Ariana is to stratify patients into trial arms in a manner most likely to give positive results in the confirmatory P2/3 trial.
The PK/PD, genetics etc. described in the June and September Corp. Presentations establishes that fact.
It could well be that some of the patients in the current P2 trial turns out not to respond all that much to A2-73, perhaps based on some genetic make up, whereas others respond very well. The P2/3 trial will accordingly have the appropriate exclusion/inclusion pre-screening criteria insuring maximum chance of a successful trial.
Who knows, Alfred Health may already have completed the pre-screening and we will hear more on that by CTAD 2017.
Yes we could just say that what Anavex is doing belongs to 'data analysis'. Every AD trial result set has been subject to data analysis and look what good it did for them. Ergo Anavex is more than likely to fail too.
And there you have it, sell and forget about it.
Yes correlations are part of statistics. However, the difference with KEM is the rule base hierarchy that guides how and where to look for correlations including those that may be uni-directional.
Probably a subject that is not easily dealt with in message board posts.
So far P2/3 trials seems to have been applied primarily, if not only, in oncology. Here is a current example https://www.mgmc.org/medical-services/cancer-care/clinical-trials/details/?id=287.
I suspect the Anavex AD P2/3 trial may be the first CNS trial with a modern adaptive design. That does sound good to me, yes!
I said "Missling isn't repeatedly saying that the AD trial will be a P2/3 trial design in a Precision Medicine setting just because he thinks it sounds good.", because I perceive that several posts made on this board is ignoring the significance of P2/3 adaptive trial design versus a conventional trial regimen with distinctly separate phases. Current AD trials typically enrol considerably more that 300 patients, which is the number Missling and MacFarlane have mentioned for the upcoming Anavex P2/3 trial.
I cannot estimate the final cost of the Anavex P2/3 trial. But, it seems to me reasonable to assume it will be less than a conventional trial design. There is no basis in fact to assume cost will be equivalent to a conventional P3 trial.
The references I have provided in this and other posts about modern confirmatory adaptive trial design may be worth a read, at least before comparing their cost to conventional trials.
Wrong!
In comparison with statistical approaches, KEM® can identify all relevant relationships between variables, even if only weakly correlated.
I think it is important to appreciate that a P2/3 trial is a specific way of designing a trial to be adaptive, seamlessly transitioning from P2 to the confirmatory P3 registration stage, while reducing risk of failure, time and the number patients to enrol and thereby cost.
Missling isn't repeatedly saying that the AD trial will be a P2/3 trial design in a Precision Medicine setting just because he thinks it sounds good.
You cannot compare such a modern trial design with the conventional linear trial phases with downtime in between phases and a large number patients spilt into treatment and conventional placebo arms.
Some opinion based arguments and factual counter argument are continuously regurgitated here. Regurgitation doesn't make baseless argument more weighty.
A combined Phase 2/3 or 'seamless' design can help to save time and patient resources, by removing the white space between stages and supporting the selection of the optimal dose. A population enrichment design can mitigate risks in cases where there is heterogeneity of response between sub-populations, allowing the trial to adapt to focus on entirely responder subgroup should the drug not show efficacy in the whole population.
I would think because very few, even healthy, mice can be interviewed on the HAM-D scale.
Depends a lot on what data and other announcements we may be presented with 1st week of November.
Let's say the PK/PD data is accompanied with longitudinal data, even for a sub group of the n=25, that continues to halt progression of Alzheimer's or better along with the P2/3 trial start announcement. If so the stock will rocket probably to around the $15 analyst target.
If the data continues to look encouraging, but for whatever reason perceived as inconclusive, then assuming trial design and start announcement based on the Ariana analysis, a guess between $5 - $6 sounds about right.
A bird in the hand...
I could be persuaded.
Great to read this up to date validation, thanks!
Must be a sign, I'm sure of it.
Another solution to the $375 riddle???
Hot Research: Get Back Into Biogen -- Barrons.com
(The companies mentioned in Hot Research are subjects of research reports issued recently by investment firms. Their opinions do not represent those of Barrons.com or Dow Jones & Company, Inc. Some of the reports' issuers have provided, or hope to provide, investment-banking or other services to the companies being analyzed. Share prices at the time the report was issued and the date of the report are in parentheses.)
Biogen (BIIB: Nasdaq) By Morgan Stanley ($314.92, Oct. 5, 2017)
We are upgrading Biogen to Overweight from Equal-weight and raising the price target to $375 from $311, as we believe the base business is proving more durable than expected with Ocrevus share loss slower than expected.
Further, we see Spinraza as a $4 billion potential asset that remains underappreciated. Business development provides upside optionality while Alzheimer's remains the key, must-own catalyst.
Biogen (ticker: BIIB) has been a complicated story with uncertainty about its base business, which is facing potential market share and pricing pressure offset by a Phase 3 Alzheimer's catalyst that could make all its potential issues disappear. Few will argue that Biogen is unlikely to move higher into the 2019/2020 Alzheimer's catalyst, but the debate has been about how the business will perform into that catalyst and when to own Biogen. We believe base-business upside coupled with stability into 2018 make this a good time to get back into Biogen.
Spinraza doesn't get a multiple on gene-therapy fears; we think sustained upside will be hard to ignore: While everyone is concerned about the potential for the base business to face pressure, consensus also overlooks the key asset that tempers the issue. Spinal muscular atrophy (SMA) drug Spinraza has had the best launch of any orphan asset with about $300 million in sales in its initial two quarters. We see $4 billion in peak potential sales even with gene-therapy competition. Spinraza inflects Biogen's growth rate by about 3%-4% on the top line (over 40% of overall Biogen growth) and makes Biogen a mid-single-digit percent grower into Alzheimer's Phase 3 data.
Business development is an upside driver while Alzheimer's remains the key catalyst: Management has discussed using its strong balance sheet (about $12 billion of capacity) to fund more mergers and acquisitions (M&A). At our recent conference Chief Executive Vounatsos indicated that management is "evaluating many prospects [and] engaging with the board as business development] will be a key part of the [upcoming] agenda [and] we're going to share some of those targets [with the board]." We see business development as a potential way to supercharge growth, but it is not core to our thesis. Importantly, we remain positive on aducanumab's potential in Alzheimer's and await Phase 3 results in late 2019 or early 2020. The next key Alzheimer's catalyst is 24 months Phase 1b follow-up at linical Trials on Alzheimer's Disease (CTAD) in November.
We see a nice beat in the third quarter and 2018 stability providing opportunity: In the near term, we believe Biogen can beat by about 2% in the third quarter, driven by its multiple sclerosis (MS) business which continues to perform above expectations. Our above-consensus 2018 sales, driven by an underappreciated Ocrevus royalty from faster uptake in primary-progressive MS (PPMS), stable Tysabriand Tecfidera, increases our conviction in a stable MS franchise. That stable base business makes this story easier to own into late 2018 as investors turn their focus to Alzheimer's disease.
-- Matthew Harrison -- David N Lebowitz -- Cyrus Amoozegar -- Vikram Purohit -- Ishmael I Asante
Comments: E-mail online.editors@barrons.com
The fact that Anavex continues to firmly state that the trials in PD and Rett will be P2 and AD a P2/3 trial, probably is a good indication that each of these will be separate and independent trials.
Not convinced we depend on or are awaiting new trial regimen announcements from the FDA.
The AD trial IMO will be an open-label adaptive seamless P2/3 trial, likely with several arms as stratified by the Ariana analysis. One of these arms will be a SOC/Natural History arm in place of a traditional placebo arm.
P2/3 means that the trial starts as a P2 trial, which then depending on data at check points transition smoothly into a P3 confirmatory/registration trial. Hence Missling's 300 patient 6 - 12 months statements.
The below reference is a little old (2007) and looking into the future in which we now find ourselves:
Calls for “New tools to get
* fundamentally better answers about how the safety and effectiveness of new products can be demonstrated,
* in faster time frames,
* with more certainty,
* and at lower costs”
Seamless Phase II/III designs offer great potential for achieving these objectives
More likely this:
Press Release: Biogen's SPINRAZA(R) (nusinersen) Data Show Earlier Treatment Initiation May Lead to Improved Motor Function Across a Broad Population of People Living with Spinal Muscular Atrophy
Biogen's SPINRAZA(R) (nusinersen) Data Show Earlier Treatment Initiation May Lead to Improved Motor Function Across a Broad Population of People Living with Spinal Muscular Atrophy
-- New data from Phase 3 ENDEAR study demonstrated earlier initiation of
treatment with SPINRAZA may improve motor function outcomes in infants
with Spinal Muscular Atrophy (SMA)
-- Phase 2 EMBRACE interim analysis showed greater motor milestone
achievement in infants and children treated with SPINRAZA, compared to
those untreated, in patient populations not studied in the pivotal trials
-- Interim analysis of EMBRACE also supported the dosing regimen of four
loading doses in the first two months, followed by the administration of
SPINRAZA every four months thereafter for infantile- and later-onset SMA
CAMBRIDGE, Mass.--(BUSINESS WIRE)--October 05, 2017--
Biogen (NASDAQ: BIIB) presented new data demonstrating that earlier initiation of treatment with SPINRAZA(R) (nusinersen) may improve motor function outcomes in infants and children with spinal muscular atrophy (SMA). Results continued to reinforce the favorable efficacy and safety profile of SPINRAZA. The data were shared at the 22(nd) International Annual Congress of the World Muscle Society in Saint Malo, France (October 3-7, 2017).
A new analysis from the Phase 3 ENDEAR study showed infants with SMA who initiated treatment earlier in the disease (shorter disease duration) demonstrated greater benefit and improvement in motor function outcomes.
As measured by the Hammersmith Infant Neurological Examination (HINE), significant differences in motor milestone responders were observed between infants treated with SPINRAZA compared to untreated infants with disease duration less than or equal to 12 weeks (75% vs. 0%; P<.0001) and those with disease duration greater than 12 weeks (32% vs. 0%; P=.0026). There was also a significant benefit in event-free survival in infants treated with SPINRAZA with disease duration less than or equal to 12 weeks (P=.0004).
"These studies contribute to a growing body of evidence that SPINRAZA can make a meaningful difference in the lives of people with SMA regardless of their age or stage of the disease," said Alfred Sandrock, M.D., Ph.D., executive vice president and chief medical officer at Biogen. "Across studies, we continue to see evidence that earlier initiation of treatment with SPINRAZA can lead to improved clinical and functional outcomes."
Interim analyses were also presented from the Phase 2 EMBRACE study which was designed to assess the efficacy and safety of SPINRAZA in individuals with infantile- and later-onset SMA who were ineligible for the two earlier pivotal studies.
The EMBRACE interim analysis showed a larger proportion of infants and children treated with SPINRAZA were HINE motor milestone responders compared to those who were untreated. Results from the interim analysis also supported the dosing regimen of four loading doses in the first two months, followed by the administration of SPINRAZA every four months thereafter, for individuals with infantile- and later-onset SMA.
In the ENDEAR and EMBRACE studies SPINRAZA demonstrated a favorable benefit-risk profile. Safety data involving the intrathecal administration of SPINRAZA showed the incidence and nature of the most common lumbar puncture-related adverse events in the clinical studies were similar in children with later-onset SMA with or without scoliosis.
For more information about SPINRAZA and prescribing information in the United States, please visit www.SPINRAZA.com. Prescribing information in the European Union is available at http://www.ema.europa.eu/ema/.
Biogen's Stock Surges After Morgan Stanley Boosts Rating, Price Target -- MarketWatch
Shares of Biogen Inc. (BIIB) ran up 3.4% in morning trade Thursday, enough to make it the third-biggest gainer within the S&P 500 , after the biotechnology company was upgraded at Morgan Stanley, which cited the belief that the base business was proving "more durable" than expected. Analyst Matthew Harrison raised his rating to overweight, after being at equal weight since March, and boosted his stock price target to $375 from $311. Harrison said the market share loss of Biogen's hepatitis B treatment Ocrevus has been slower than expected, and he believes its spinal muscular atrophy treatment Spinraza has potential to become a $4 billion asset. He believes Alzheimer's therapies are a "must-own" catalyst, and Biogen has several therapies in development. The stock has surged 17% over the past three months, while the iShares Nasdaq Biotechnology ETF (IBB) has climbed 8.0% and the S&P 500 has gained 4.5%.
That I agree is the simplest and most likely explanation too.
I have no background to lecture on genetics and gene editing, but just read a lot about too many things.
As I understand it base pair gene editing, as opposed to CRISPR, has the ability to alter the instructions for how an embryo develops. That would imply, that edited just right, the gene or genes causing an inborn disease could be corrected to allow the baby to grown into a healthy adult, who in turn would pass on the corrected healthy genetic make up.
'Chemical surgery' used to mend harmful mutations in human embryos
Researchers in China have used a procedure described as “chemical surgery” to mend harmful mutations in human embryos for the first time.
The scientists found that it was possible to repair a faulty gene that gives rise to a serious blood disorder called beta thalassemia which can be caused by one misspelling in the DNA code.
None of the embryos treated in the experiments were used to produce babies, and doing so would be illegal in the UK and many other countries. But the work proves that the method, known in genetics as “base editing”, could be an effective way to prevent inherited diseases. Base editing was dubbed “chemical surgery” by its inventor, David Liu at Harvard University.
In the past decade, scientists have developed a range of powerful tools to edit the genetic code, the most popular of which is called Crispr-Cas9. The method uses enzymes to make precision cuts in faulty genes which the body can then repair with the correct DNA.