Ann: Invex receives IND approval, page-38

Here are the responses to my email. Not a whole lot of info in here tbh but thought I would post nonetheless.

Hi Tom, just a few questions from shareholders when you have the time.

Has the EMA stipulated what percentage reduction in ICP is required for regulatory approval and is that public information? (Phase II had 10%, 16.5% and 18%-20% for the results so just wondering the ballpark there)

We have based our study design on all IIH trials and our own Phase 2. We are not disclosing the powering calcs or difference sought, but your observation is a good starting point. Suffice to say we are overpowered to show a difference in ICP over the 26 weeks (i.e. if drug shows something, we will see it).

Is it a binary percentage term or is there some leniency built in to the approval?

Per comments below – only part of the approval is going to hinge on showing a difference on ICP. It’s the clinical aspect too.

Is the percentage reduction in ICP required for approval determined by previous clinical trials, or if not, what is it determined by?

The ICP primary endpoint is based on what is generally accepted by the clinical community as a clinically significant difference, being measured by absolute drop in cm H2O or to your point, a % difference. For example, if we hit statistical significance on a smaller ICP decline that modelled, and we meet all clinical endpoints, it would be hard for a regulator to argue about whether the drug works. All hypothetical of course.

If the primary endpoint is met and none of the secondary endpoints are met will the drug be approved? (Are the secondary endpoints there for drug pricing and patient benefit more so than approval?)

Unlikely – the trial has been designed to meet the primary and those important secondaries (vision, headache). The order is somewhat irrelevant, as the EMA wanted to show a functional effect (ICP) and a clinical effect (vision, headache). To cover our bases, we have powered the trial for all three to be met. It will be an interesting discussion if we meet the primary and one secondary but not the other, but let’s cross that bridge if we come to it.

If the EMA approves Presendin, will the MHRA and TGA definitely approve it as well, or is there some discretion there?

I wouldn’t say one dictates the other, so think of them as all mutually exclusive.

What steps would need to be taken to get regulatory approval in jurisdictions other than the UK, EU and AUS (China, India, Africa) and is that something that Invex has considered, if so, why has Invex elected to not pursue approval in those jurisdictions?

Not at this stage. Noting we can add NZ and Israel to the mix, but these are small markets (but actually high for IIH on a per population basis). Rates are tied to obesity, so it’s a Western drug at the end of the day. Peptron have rights to Korea as part of our deal, so they may elect to do something there.