Replies to post #508358 on Anavex Life Sciences Corp (AVXL)

[oldmystic]

Some MDs are amazing CEOs like Steve Paul of Karuna (P2 start to Market and buyout in 5 years) or Dr. Levenson (Genentech), but most KOLs do not have broad enough knowledge to get to the finish line

Thank you for that clarification

[oldmystic]

Doc, what do you make of this?

fibonacci on ST-
“ I think EMA has told the management that Blarcamesine will be approved upon submission of the biomarker data. Here is why:
1. See the word choices across the PR
yesterday, in particular "based on feedback and continued guidance". CHMP wants to see the SIGMAR1 biomarker data from Sept 9.
The LOls were adopted on Sept 18. It seems
AVXL couldn't provide the SIGMAR1 data as part of LOls because LOls didn't specifically ask for the SIGMAR1 data, and submitting this data in LOls would have constituted
"unsolicited data" which is against CHMP rules.
2. The entire PR is about "CHMP this, CHMP that, shared commitment, and precision medicine." It seems the only way the CHMP can move this application forward is through a re-examination, during which the CHMP will review the SIGMAR1 data and approve blarcamesine for 70% of the AD population.

3. Usually, CHMP just gives its final opinion, and lets the company decide whether to appeal. But here, CHMP wants to "continue guidance".do you make of this?

[12x]

PDD ain't happening

Doc, could you help us understand why you think PDD/PD P3 is less likely to succeed compared with AD/Schizo/Rett? I get that a PD/PDD P3 is probably in the ~$70M range and that they need to cut the ~$160M burn, but I’m trying to frame the relative chances across the programs rather than just write PD off entirely.

On the MAA side, the PR says they’ll be “providing relevant biomarker data” for the re-exam. Does that imply biomarkers were one of CHMP’s main concerns?
If we line up Blarcamesine vs the mAbs on A/T/N:

Donanemab: Strong A/T; mixed N (ARIA-confounded); ~29% CDR-SB effect at 76 wks; high ARIA + infusion risk.
Lecanemab: Strong A/T; supportive N; ~28% at 18 mo; significant ARIA + boxed warning.
Blarcamesine: Modest A, basically no T yet; strong N signal (MRI neuroprotection, no ARIA); ~28% CDR-SB at 48 wks; oral + clean safety.

But on the A/T/N biomarker spectrum (Aß42/40, p-tau181, p-tau231, NfL), Blarcamesine still has no reported p-tau181, p-tau231, or NfL data.

So:
Can they really claim “disease-modifying” or “upstream to amyloid and tau” if the tau markers don’t show any convincing correlation?
If CHMP is benchmarking against donanemab/lecanemab on A/T/N, how big a hole is that for Blar?

There are still folks hoping the post-hoc ABCLEAR3 genetics can rescue the re-exam. I’m curious how you view that in light of how rare post-hoc biomarkers actually move the needle at EMA.

The one clean precedent I can find is panitumumab (Vectibix) in mCRC:

Panitumumab (Vectibix) – KRAS (later RAS) wild-type in metastatic colorectal cancer
– Phase 3 trials were initially all-comer.
– Only after the trials were done did they run post-hoc KRAS analyses.
– Retrospective genetics showed benefit only in KRAS wild-type and possible harm in KRAS-mutant.
– EMA’s assessment called the KRAS work “post-hoc exploratory” that needed confirmation, but they still tied authorization to KRAS wild-type tumors.
– Pignatti later described this as a case where a post-hoc genetic subgroup essentially formed the basis of conditional EU approval.
– The final EU label requires proof of wild-type KRAS before starting Vectibix.

Do you think ABCLEAR3 has any realistic chance of playing a similar role here, or is that kind of oncology-style post-hoc genetic rescue basically off the table for an AD MAA that already has a negative CHMP opinion?

[kevindenver]

Interesting info...but your insider sales comment is a bit ridiculous.

"He also sold vested options that had not yet expired in Sept/Oct which he would not have done if he had great confidence in a much higher SP."

https://www.sec.gov/Archives/edgar/data/1314052/000173112225001246/xslF345X05/ownership.xml

The cashless exercise and hold transaction by the CEO was done on 09/11/2025 with and option expiration date of 09/18/2025, one week before before expiration and IMO had zero bearing on his confidence.