Dr. Susan Galbraith

And I think we can look at that time until brain metastases recurrence, but it will take time for those to come through.

You know, I think obviously the trials have been run with specific patient populations.

They're not directly answering the question of if you've had, for example, four cycles of INHER2 in the BB11, but you haven't quite achieved a pathologic complete response, you know, what's the optimal treatment then in the post-neuroadjuvant setting?

So there will be medical affairs trials that we will look at that will help to address those care gaps, if you like.

But in terms of what the discussions are with investigators that we've heard so far, I think it depends a little bit on the extent of residual disease.

If you've seen patients having a very good response to INHER2 and then some stabilization on the THP part of that new regimen, it doesn't necessarily mean that they have become resistant to that treatment mechanism.

by the time you get to the post neoadjuvant setting.

And similarly, I think is in line with general principles of how drugs are used in oncology.

If there's a longer disease-free interval between treatment in the early stage setting and then a recurrence in the metastatic setting,

you know, it doesn't necessarily mean you're going to be resistant to the opportunity for treatment in the metastatic setting.

So I think over time, we will gather data from real world evidence and from some medical first studies that will help to address those important questions that remain that we haven't actually addressed yet in the design of the trials that we've run so far.

Well, I mean, you know, there are multiple mechanisms of resistance to any drug.

I think we're going to have to, again, work out over time what the reasons are why a particular patient does well or doesn't do well on particular regimen.

But I don't think that we're seeing...

significant downregulation of the target, for example, of HER2.

Remember, of course, that HER2 is an oncogene, so the tumours are relatively... They have a growth advantage by having HER2 highly expressed.

That's part of the reason.

So if they then downregulate that receptor, they're losing that growth advantage.

So there's a...

you know, just a clonal selection disadvantage from downregulation, which means that I think it's unlikely that you're going to get a substantial downregulation of the HER2 target.