Bear..agree

None of us has all the lab/trial data/facts. We can only connect the best available dots , being rational and objective. I take some comfort (as you suggest) that I have limited funds to invest therefore I make choices on what to invest in according to what difference the company/product will make.

A2-73 is a stand out choice in making a difference for lots of reasons. We cannot do a thing about the timing, but any day now would sure work for me.

..Bio, IMO that trial discussion is being saved for the yet to be announced FDA/AVXL trial PR.

Cb...agree w/your platform belief comment.

I would also suggest that not only will we rally but I also expect (following relief/caution expression) that some results will be tough to verify in a classic trials context. Just exactly how will restored CNS cell functioning present itself? Do we expect Rett children to regain/gain CNS controls for example? Let's pray for that. These are really the least of our worries for now.

The gap between present AVXL SP reality and potential value is a mystery to me if not by design I have to admit. What explanation is there for this?

Huh? No planned dates for new guidelines implementation?? This is going to be very interesting. Thx Walker

BTW, the question is, does A2-73 restore CNS Homeostasis or not? And then what happens? If, Y then game over. Since no known patient has ever stabilized, much less recovered, form AD how is the question of statistical confidence even relevant. We miss the point if we try to debate/agree on n. That thinking is what got us the last 50 years.....zippo, nada, ziltch...It's a breakthrough. Have a great day.

OK...September 5th is your speculation. Thx, that works. As long as we get it out of the way before the 11th. Curious there are no triggers (must do dates) tied to a Gov. calendar.

Thx

Who knows the timelines for new FDA trials/planning/protocol. When will they announce the new rules? Is there an FDA requirement for publication of the rules and effective dates?

My guess is it must be before sept.11 but that is a guess.

Biogen adds $$1B in cap. based on this? kinda makes you wonder what a drug that really worked would be worth. I guess a LITTLE BRAIN BLEED is tolerable.

Tell me, if A2-73 performed like this would you be here? I would not.

Bear, excellent summary posting. thx

John, considering the dynamics of this scenario and the stakes involved why are so many holding their cards so close? One wrong move, one peep and massive moves will happen w/o limits or controls. If A2-73 performance data, trials starts, peeps on BP deals, possible FDA Wunderkint examples (non of which are controlled) no one will be able to catch it. Is the system that well wired on timing?

Lot of moving parts here. Eventually, something has to give. We think A2-73 is not vapor and so do a lot of others. New patent news,the Sept.11 conference and FDA new trial rules all running a couple of atomic layers below the surface. Pressure is building for something to be whispered.

Bear..

You are right on with this. IMO there are two basic camps. One camp is made up of the hand wringers whose personal uncertainties drive them to continuously attack anyone trying to lead. Second camp are the big guys who have controlled what gets approved, made, sold, rejected and used (almost regardless of efficacy which they define BTW). IF A 2-73 performs as expected I predict both of these camps will be buried by an effective presentation of one treated little RETT girl. I am pulling for her and the AVXL team to kick axx.

Yeah, and what about the eclipse? Then what?

If this means what I think it means it is welcome news.

T-38, what an exceptional post you have done. Thanks. Can you imagine a room full of smart researchers who see for the first time a CNS disease treatment potential the rest of us can only wonder about.

bear..IMO you are going in the right direction here...

AVXL staff/BOD have chosen to not engage a battle that they are completely outnumbered/resourced on. Very wise to avoid being pummeled daily by BP and their band.

Fear of A2-73 demonstrations of CNS restoration/regeneration has BP on the ledge. Sadly, silence cuts both ways in this case.

IMO, there is an important-subtle change in addition to WW regulatory body rethinks. They (Dr. M.) are saying (IMO)..."this is all about the process". Compared to pass fail/event driven/good bad passed trials.

In AVXL case (I pray this is true) we claim A2-73 (others to follow) is capable of restoring CNS cellular function (Homeostasis). Pre clinical trials and our studies indicate the story is true and the efficacy of the process certainly will be shown. We are developing dose models, but the basic process should be effective. The degree to which this thesis can be proven/demonstrated/studied/evolved/improved remains to be seen. IMO, Dr. M. and team are on the point demonstrating and validating the process. He acts like if we just follow the process we will get the results we are looking for. If he is right then variations of CNS restoration thesis will certainly evolve quickly.

So, the new international trial rules will rely less on sample size and statistical analysis and more on adaptive learning using new tools/methods to validate the concepts. Can we imagine a trial with no adverse events? Get ready, smaller, shorter, faster, more granular and more predictable results. Five years from now we will look back at this moment. It's time to move on but I in no way expect all WW regulatory bodies to evolve the same processes. It is all about a collaborative learning process from here on out.

Very strong facts, well presented, Thx

Rey, agree w/your thinking. Complex but possible link. If they do sign the message it sends about A2-73 is massive.

Agree this should be read as good news for AVXL holders. We really have no idea what level of systems/clinical complexity AVXL staff are dealing with. We do know this ain't your father's Oldsmobile. Like you, I think IF Biogen does link up on an MS deal then that is a MASSIVE message on the AVXL science and overall credibility.

T-38, once again thx for your insights here. IMO, you are correct to bring up how the SAUSAGE gets made, it is critical that we have both political connections and the technical/clinical wisdom of the new protocol language on our team.

I have also considered the possibility that understanding CNS Homeostasis will allow FDA&AVXL to start to work to peel the onion of medical mysteries that have destroyed so many lives. As they do(IMO) and as learning happens a new dynamic will be added to the trials process. Hopefully Dr. Woodcock and crew will be out in front b/c this next few years are going to be explosive for the FDA.

TOGA.....TOGA......TOGA

At some point soon the cloud will open and new information will begin to flow. We should not expect cut/dry perfection...BUT, when the parents of the first little girl w/Rett see progress we will know this has all been worth it.

Wink, Wink. Nudge, Nudge.

The guy has been straight with us all along. Even on the worst days his story has been consistent. All the best to longs.

Falconer. Agree largely w/your message. News voids/vacuums cannot be respun/twisted/etc. Appreciate it if you would continue to scan the horizon for any credible CNS Homeostasis technical papers/other which contradict Dr. M.'s thesis, or any that reinforce the AVXL story.

powerwalker, thanks for your post.

The facts, dates, events which you refer to are a good sample of the behind the scenes work/information being boiled. There is obviously more we know about and probably a lot more we do not know about, all of which raises the bar on the importance of every little informed peep that escapes.

Those of us who are VERY close to every word are in wonder of the privacy/security being applied. We know we don't know a lot of things on trials, patent release PR date, Biib conference details, extended trial results, impact of new FDA trial regs and so on as you have identified so well.

NO LEAKS, not even an informed whisper, that's impressive considering what is at stake here. Makes one wonder about the things we do not know, we do not know b/c of the gaps above. I am inclined to believe that if this whole thing were vapor we would know or have leaks/clues/contradictions, considering the number of informed people here analyzing every peep/gesture/expression. This is reality, retailers and self declared experts are equally clueless.

https://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/scienceboardtothefoodanddrugadministration/ucm556618.pdf

see sec3051 FDA estimate up 20% growth in BTD b/c of legislation.

Although many others will be candidates, we should have a good shot at rapid processing. It has been a puzzle to me how Dr. M. could be so certain of 3 trials in CY 2017 while he must have known the FDA holdup was expected due to new rules (September?). Hate to speculate wildly but maybe they are telling us the pieces to this puzzle are in place? After the crap we have been through lately it is good to have a positive thought at least.

RMAT designation and granted four such designations to date?
Thanks for great post.

"



T? Any way of finding out what four have already been granted? What can we learn from those?

Any thoughts-timelines to establish the statutory framework. It looks like they expedited at least four already. I guess we can fanaticize about being in the four already done.

Does anyone know or be willing to give and educated guess on what date the new FDA rules will take effect? TIA.

Well Done..thx

IMO, some trials PR is seriously needed but cannot happen until FDA discloses new guidance developments. We have been caught in a box along with others, IMO. Agree it is a serious/exhausting test. IMO, when new PR describes trials/rules then we may get insights into results till now. I'm guessing but believe the trial plans have to be put into some context (protocol/rationale) to make sense, then we will have facts. I could be wrong, it may be kept from public view.

Yep, looks to me like a little bush shaking going on.

Cullen, Is it possible we are seeing push/scare action prior to possible news from Dr. Mac F on Weds from Australia? Hope for pop in A.M. if not by EOD today.

Just a thought

Is RGIN static b/c we await new FDA guidelines for trials? New trial rules, technical, other will slow things up. Just a thought, held up like everyone else till sometime in Sept.

Is this why BP are either in denial or throwing up in their Cheerios right now? see Anavex pr April 3, 2017.

We can be assured they are not happy. New deck of cards, new dealers, new anti rules...uuuughh

Is this any kind of indicator for when the FDA releases new trial guidance? Curious, a possibility. The sooner the better.

I understood him to say that a broader set of combined trial data could be used to validate the hypothesis of CNS homeostasis as the fundamental root cause of (3 for now) identified CNS diseases. This is simply my read of his message. If proven true then of course the term breakthrough is entirely appropriate and I will probably retire .

T., nailed it.

That assumes that the trial design does NOT use the new rules on adaptive trials which are not supposed to be issued until September.



This why some of us have been convinced that the AVXL trial start delays have been at least partially attributed to links with FDA planning/new rules. A reasonable assumption considering FDA PR.

Jimmy, agreed...there is a risk of getting off in the weeds w/interpretation but it is low risk to say ...and they know EXACTLY what they are looking for. Yes, of course there is learning still going on but this ain't your father's Oldsmobile any more. Maybe not to late to save FDA which explains their motivation. It's a win-win.