Replies to post #169994 on Anavex Life Sciences Corp (AVXL)

[Investor2014]

Good questions and alternative interpretation.

Slide 14 states that only two concentration groups were considered or came out of KEM analysis e.g. Low/Med and high. My main argument is then that slide 15 very clearly seems to state that 8 patient were in the High Concentration cohort.

We did not get direct explanation of the outliers e.g. low concentration, but good response and high concentration no response. So it could be that the 8 with high concentration were not all on 50mg.

[Amatuer17]

Good sub-analysis. This is what I said was not correct. Co can be more transparent and give clear numbers of patients and will not become speculations.

[Investor2014]

On examination of the poster you linked, I'd like to highlight a few other things:

5 SAEs events: 1 event during PART A (5 week), 4 events during PART
B (26 week) period.
- Delirium Grade 2: Possibly related; Delirium in patient with previous
history of delirium; Safety Review Committee (SRC) deemed likely not
related to study drug; The participant fully recovered from the delirium
but took no further part in the study.
- Delirium Grade 3: Not related
- Fractured ankle Grade 2: Not related
- Urinary tract infection Grade 2: Not related
- Hodgkin's lymphoma Grade 2: Unlikely related; Patient has developed
Hodgkin’s lymphoma. Patient’s comorbidities include Sjogren’s
syndrome, which increases the risk of lymphoma between five-and ninefold.
1 Will stay on study while undergoing radiation therapy.
With respect to AEs causality relatedness to study drug: 21% of events
were definitely/probably related; 40% of events possibly related; 39% of
events unlikely/not related.

The traditional definition of MTD was updated in the presence of
inter-patient variability. For AD patients 50.58 mg of ANAVEX 2-73 is
the maximum tolerated dose taking into account most frail patients
(5% of total patients). In half of these patients a DLT event will occur.

This to me fully accounts for the drop-outs and reasons. It also further validates that 50mg is in fact safe and tolerable even in the most frail of patients. Thus 25% were left in the 50mg dose group all through Part B and its extensions.

This was the reply from Clayton IR to my question from 1st Match 2018 as previously posted:

o For Part B portion of study, was a 1/4 of patients assigned in 4 groups to their respective 10mg, 20mg, 30mg and 50mg oral doses that they exited on from Part A and then remained on that dose throughout Part B? A: The latter. Exited Part A and remained on that dose.

In other words those on 30mg and 50mg oral dose in the Part A crossover study stayed on that dose, each 25% of the population. Those on IV 3mg and 5mg, each 25% of the population, were assigned to 10mg and 20mg oral dose and remained on that.

So I will respectfully stick with my interpretation :-).