Good explanation

Jun end last patient visit
Then all the data will be collected, collated, entered, verified and database will be locked.

After all the steps the data will be unblinded and then the tabulation and analysis will be done to get TopLine data

If TLD is not as good they will do a lot of analysis to give some good news.

At this point - they possibly have unblinded the data as it is 3 1/2 months after last patient visit - so it is fair to assume that they have seen the unblinded data

If results were really great - they would issue PR in a hurry and get entry into CTAD as breaking presentation

Seems nothing of that sort has happened - so we have more chance of not so great results

Genius word is used like birthday balloons - everyone gets one for his/her birthday.

However Missling has not even shown G of Genius. He has made more bad decisions than good - he may have some business acumen but calling him Genius is stretching imagination too far

Researchers discover major new contributor to Alzheimer's disease

https://flip.it/dglcke

The novel features of this newly described pathological pathway are threefold. The AD-stimulating pathway begins inside of us – in our GI-tract microbiome - and therefore is very “locally sourced” and active throughout our lives. The highly potent neurotoxin BF-LPS is a natural by-product of GI-tract-based microbial metabolism. Bacteroides fragilis abundance in the microbiome, which is the source of the neurotoxin BF-LPS, can be regulated by dietary fiber intake.

If the results are good and sustainable - market will react positively - does not matter when they are released

https://flip.it/qt29PY

Alzheimer's: Study suggests alternative to amyloid plaque theory

So much authoritative statements - on FDA granting BTD - with no knowledge of any details more than what everyone knows.

Pure speculation and wishlist - so good luck

You are in target here
One more confirmatory P3 will be required unless the results show significant improvement.

With 1st BIIB debacle, FDA will be reluctant to take any chances

Show me the results that are good enough to take it to FDA or start a pivotal P3 trial - everything else is old - stale and does not mean anything anymore.

AV1066

Example 1
Bone Fracture Pain
An 18 year old male patient or subject (the terms are used interchangeably) presents with a fractured collar bone arising from a bicycling accident. He is complaining of significant shoulder pain. The patients' pain is classified according to the International Association for the Study of Pain as nociceptive. He is orally administered AV1066 5 mg/kg daily. He is examined at day 3,7, 16, and 28. At each visit the patients is assessed for pain control compared with the previous visit. The patient reports the pain to be both tolerable and improved at each visit.

EXAMPLE 2
Burn Pain
A 38 year old female patient presents with a second degree to her left thigh. She is complaining of significant pain. The patients' pain is classified according to the International Association for the Study of Pain as nociceptive. She is orally administered the phosphate salt of AV1066 10 mg/kg daily in two doses. She is examined at 12 hours, and daily thereafter for 4 days. At each visit the patients is assessed for pain control compared with the previous visit. The patient reports the pain to be both tolerable and improved at each visit.

EXAMPLE 3
Obstruction Pain
A 68 year old female patient presents with a benign tumor mass compressing her left shoulder causing movement pain. The patients' pain is classified according to the International Association for the Study of Pain as nociceptive. She is orally administered the sodium salt of AV1066 30 mg/kg daily in two doses. She is examined daily thereafter at 3,7 and 28 days. At each visit the patients is assessed for pain control compared with the previous visit. The patient reports the pain to be both tolerable and improved at each visit.

EXAMPLE 4
Postherpetic Pain
A 70 year old male patient presents with postherpetic neuralgia arising from a shingles outbreak. He is experiencing lingering pain in the skin of his left shoulder extending over his left shoulder blade. The patients' pain is classified according to the International Association for the Study of Pain as neuropathic. He is orally administered (+) AV1066 10 mg/kg daily on days when the pain becomes significant. The patient reports the pain reduced and the outbreaks lessened din severity and duration.

EXAMPLE 5
Trigeminal Pain
A 52 year old female patient presents with trigeminal neuralgia. She is experiencing extreme, sporadic, sudden burning or shock-like facial pain in the areas of the face where the branches of the trigeminal nerve are distributed—lips, eyes, nose, scalp, forehead, upper jaw, and lower jaw. The pain episodes last from a few seconds to as long as two minutes. These attacks can occur in quick succession, in volleys lasting as long as two hours.
She is orally administered 350 mg of (-) AV1066. She takes one to three doses in a 12 hour period depending on the result. In most instances, one or two doses significantly reduce the frequency and severity of pain.

New Discovery Means Parkinson's Could Be Diagnosed With a Swab in Just 3 Minutes

The test can be run in as little as 3 minutes after a skin swab has been taken. The swab is analyzed for changes in the chemical mix of sebum, a natural waxy oil produced by the skin that has previously been linked to Parkinson's.

https://flip.it/BvJ9wa

Yes it is proven so much that very few believe in it and the market cap is less than $1 Billion.

It is from 2016 - does not matter
We are near actual results of that drug and it can be - Yes it works good enough for approval. Or NO it does not work as good for approval

We will know in next 2 months

Agree - all these Conf organizations want such results to be presented in their org

They can always accommodate such request - they will accept such presentation even 2 weeks before the Conf

Good analysis and good point to show the difference in starting mean MMSE

Question is - how many people understand this?
Will FDA care about it during approval?

If AVXL trial starts with mean MMSE of say 23 - which means these patients are beyond initial stage - the chance of decline stabilization may not be as impressive and the trial may be called as failure

You are a great investor (kind of Warren Buffet of this board) so congratulations to you.

I am kind of Cathy wood of this stock and have picked up AVXL at different levels and my average is much higher.

My point is - company product is no where near approval after 6 years

And after 6 years - the share price is just around $10

So the naysayers have been right till now

The trial did not start as P2b/3 - the phase 3 was added much later

AD drug pricing and revenue target - there has been a lot of discussions on revenue potential

Here is a seeking Alpha article. While total AD patient population in US is 5.8 million - the author has used 750,000 patients to cover in 3 years - pricing is $30,000 per patient per year -
THIS will bankrupt Medicare but that is a different story
—————

https://seekingalpha.com/article/4543674-biogen-lecanemab-data-blows-alzheimers-race-open-again


When modeling for sales of Aduhelm shortly after approval in a post for Seeking Alpha last year, after factoring in pricing discounts, a reduction in list price from $56k to $41k after the first year, royalties paid to Eisai and Neurimmune of >50% of revenues, and infusion sites available, I calculated that by 2026, Biogen could drive net revenue of ~$11.5bn, based on 750k patients treated.

BIIB phase 3 trial had 1795 patients and it went for 18 months - quite a robust trial

AVXL trial has 509 patients only -52 week and it started as P2 trial which now designated as P2b/3

Based on this and the fact that another trial has shown good results, FDA is likely to ask for a full phase 3 trial of A2-73

Also looking at BIIB trial timeline - we can assume AVXL trial will also take similar timeline which is 3+ years after it starts (even with 2 big partners with lot of money)

There will be time gap as AVXL probably try to find a partner for P3 trial

So we are looking at 4 years for final results if P2/3 shows good results

BIIB results - any comments?



——

In absolute terms, the difference in scores between study participants who received treatment and those given a placebo was 0.45 on the main symptom rating scale, known as CDR-SB. That difference is near what some analysts had previously said would represent a clinically meaningful benefit.

The imaging abnormality, known as ARIA, occurred in 21% of patients treated with lecanemab and 9% of those on placebo. About 3% of patients on lecanemab patients had symptomatic ARIA with swelling in the brain, and 0.7% had symptomatic ARIA with micro-bleeding.
——-

You said -“Say $1B upfront and partner handles the P3 PM trial execution across PD, PDD and AD with global rights and perhaps a 50:50 profit share.”

Good luck with these numbers - with such uncertainty on AD results - no one will give $1 B upfront and then share 50% profit - a co might as well just pay $4 - 5B (which will be 6-7 times current market can) and do outright buy out.

This will turn out to be share price of around $55 to $60 - while not the best long term outcome, I would take that price now that wait for another 3 years for another P3 results

https://flip.it/EIdARS
Alzheimer’s might not be primarily a brain disease. A new theory suggests it’s an autoimmune condition.

Yes and no

Your logic is good but this is insulin - not normal medicine so it will be seen with skepticism

It was phase I - small trial - market still does not believe it - need to go with medium size trial to prove it works

There is a side issue - the drug is diabetes drug and insulin - will FDA appprove insulin for NASH as it can have adverse impact if the patient does not have diabetes

Yes - they have real good results - also Pfizer invested $25 million at $9.90 per share

There goes the Rett advantage - AVXL is at least 1 year behind

The Rett approval may still come ahead of AD as AD will need another P3 confirmatory pivotal trial

Market thinks that it is bad - they are giving away some markets to individual companies - this is not good for buyout

Everyone know China market is not reachable for these companies so out licensing is good

But South Korea market pays well - the BP like to retain rights for US - Eurozone - JPY - Korea as this is where they generate revenue.

IRMP selling rights for $2 M upfront payment and small royalty is not good. They might as well say No to them

Thanks for this

Interestingly in 8 years, M has not made much progress on 3-71

Has potential means not certain - that uncertainty also means need for additional trials

Believe what you want to - check transcripts of quarterly call and Q&A

Check one of his quarterly calls

We know for sure - M has indicated as such

Also, unless the current trial result is incredible - FDA will not approve an AD drug based on one trial of 500 patients

In my view, even if results are good - this stock can spike and give sell the news opportunity

AVXL will need another large P3 trial/s which will take years (min 2 1/2 years) so after the spike - the stock will go down and stay there for long time.

In that sense, I agree with your approach

In 2020-21, I had bought SAVA for around 10 and sold at around $78 and was cursing myself when it crossed $100 but sale the news strategy worked. I made more money in that short period than I can make after holding AVXL for 5+ years

CTAD is biggest conference to present such data - any CEO of struggling biotech will try to grab such opportunity

The timing is really lining up - from last patient last visit in last week of Jun to CTAD - 4 1/2 months - sufficient time to present Top line data if it is good

I read these exchanges with amusement - debating all the things that do not have much impact on SP or results

We are coming close to ‘show me the results’ time

Last patient visit was end of Jun - the DB and unblinding can happen anytime or would have happened by now (2 months from last visit)

Thanks giving - Nov 24th
CTAD - Nov 29th

These 2 are very good dates to announce the results and they have 2 1/2 months to generate the topline

If they find the results to be very compelling - they will ask for last minute entry as breaking presentation and they will accept

So these topline results will make all these discussions totally redundant

Thanks

Seems RECAF is following the pattern

Recaf typically does not go up so fast - it comes down next day

The video is long - can you tell at what time he mentions it?