Annovis Bio Inc (ANVS)

[MZlu]

I got a reply from Maria about what she thinks of the dosage response in terms of efficacy.
She pointed out this is what was seen in animal models for AD and PD.

For PD mouse model: positive response was seen at 3mg/kg, optimal dose was 10mg and the mice did worse at 25mg/kg.
For AD mouse model: positive response was seen at 10mg/kg, optimal dose was 25mg/kg and mice did worse at 50mg/kg.

On the biomarker and dosage, she said some of them was down to 50% at almost toxic dose of Posiphen (based on previous human trials, I assume the dosage is around 180mg/kg). So far, we are seeing 5% to 20% in optimal doses (Maria mentioned she is considering 10mg to 30mg for future trials), we are actually no that far off in terms of dose dependent response for biomarkers. Maria said that for PD, a 5% decrease in alpha-synucleins is "absolutely adequate". When you think about Posiphen's MOA, it is sensible as you don't want to inhibit APP 100% since this protein precursor is still needed.

My take on all the data we have so far:
- It is not incommon for drugs to demonstrate a non-linear relationship and that's why you have phase 2 trials.
- All the results on humans are consistent with animal models so far.
- Given the short duration of the trial, we have seen consistent improvement in anything related to short-term and working memory, which is what deteriorates first at the onset of the disease (We have seen improvement in WAIS coding test, ADAS-cog3, 6 &11).
- The design of the trial just did what Maria intended to do: determining the optimal dosage to demonstrate efficacy.