Anavex Life Sciences Corp (AVXL)

[Doc328]

....but why are some posting 7-10x/day saying the same thing over and over?
It would be most helpful if a short (Doc or someone) would share a response to one question.... "What have you seen from all the results published to date that strongly suggests Blarcamesine is not effective even among the ABCLEASR3 cohort?"

I am not sure why you singled me out as a short. I have never once shorted AVXL or bought a put (have owned many shares in the past and a kept a small number of shares until last week, have sold thousands of puts (which is a neutral to positive trade) and sold many covered calls) . I have been appropriately skeptical of blarcamesine's strength and Missling's leadership ability. Quick questions: Was my skepticism right or wrong? Were people trashing me right or wrong? You can read posts I have written over the last 8 years to learn how to approach biotech trading. Alternatively you can just join the bagholder club and take Missling at his word. Are you investing to make money or to be in a clique.

"What have you seen from all the results published to date that strongly suggests Blarcamesine is not effective even among the ABCLEASR3 cohort?

back when the Col24A1 data first came out, I posted about the difference between hypothesis generating and hypothesis testing. I also posted about WES and GWAS and how low p values need to be to be truly significant. You are asking me what I have seen that suggests Blarcamesine is not effective (even in ABC3) when the real questions should be , have I seen enough evidence to strongly believe that Blarc is effective in ABC3 patients. The answer is that there is a suggestion of benefit not proof of benefit --- now prove the benefit. Try to understand the Bayesian math,or at least the concept, that go into my last statements. Repeat WITH NEW DATA until you get significance or futility. P(H | D)=P(D | H)*P(H) ? / P(D)

Other questions you might want to ask:
Why does Missling refuse to spend 100 MM to do what is necessary to persuade regulatory agencies to allow them to make 20+ billion over the next decade. Instead he wants them to listen to Advocates over data. Why is he not confident enough - this makes me wonder if the company need a to pivot.

Some say that a proper P3 could not have been designed in 2023 after the data was presented in Dec 2022 (in a now known to be false highlighting of 'primary endpoint'). That's rubbish of course. The trial ended 6/2022 (nearly 4 years ago). The first patient was in 2018 so first OLE patient rolled over in 2019. They knew tolerability issues were a problem --- start low and go slow in the elderly was a slogan way back when I was a medical student. Nighttime dosing of drugs with CNS side effects is also not novel. The OLE protocol could have been changed in 2019 or 2020. One did not need patients to complete 3 years of OLE to prove better tolerability - by 2022 this was the standard for the OLE. How about subsets: ABC1 was hypothesized after the 2a. ABC2 and 3 was post-hoc with p values .00001 - this is suggestive in WES and minimally suggestive in GWAS - do you really think this is proof? Post-hoc correlation is not causation. The ABC data would all have been available by mid 2023 - they just chose to emphasize at different times. Regardless, by the end of 2023, the trial could have been designed with first patient early 2024. This would not be completely enrolled and done by the end of 2026.

I have also posted about an appropriate P3 design. Recalculating sample size from the assumptions of the JPAD paper with reasonable variance (not the small variance in the JPAD paper) I get around 800 patients, 400 control and 400 at 30 mg (perhaps higher if unpublished data from OLE tolerability allows), 72-78 weeks, MCI only or MCI/Mild AD mix (they have the complete data set, not us to let Dr. Jin decide between these options), CDR-SB as primary with secondary clinical endpoints of ADAS-Cog14 and either ADCS-iADL or ADCS-MCI-ADL depending on MCI/MIld or MCI only. How to handle genetic ABCs - I would limit the study to S1R-WT only (this is ABC1 and 70% of population), this will be the primary cohort for primary analysis, ABC2 (and hence ABC3) will be in the primary endpoint analysis hierarchy. Putting ABC 2/3 at the top, above ABC1, would be risky. Tertiary endpoints: Would also check AB 42/40 ratio, pTau217 (or 181) and NfL and MRI regions INCLUDING HIPPOCAMPUS (that still has never been reported despite being part of QyScore report)