Dr. Susan Galbraith

The next question is, do patients' tumours become resistant to the mechanism of action of the payload, or do they upregulate drug exporters so they become relatively less sensitive to that?

And I think we're going to have to look at that with translational science data sets over time to help answer that question.

This is one of the reasons why I think very pragmatically physicians will look at that disease-free interval and then you can retest and see whether or not patients have become responsive to the disease.

Well, one thing that has been seen, I think, and is an area of interest is the expression of juggy flux pumps.

So in some of the preclinical models, high expression of juggy flux pumps makes them relatively less sensitive to the treatment with the payload.

Exactly how frequently that's seen as a clinical mechanism of resistance is to be determined yet.

But of course, there's more data gathered

we'll have greater clarity on that point.

Well I think we'll all work that out over time.

I mean I think from a patient perspective just to go back

The idea that we can reduce the incidence of metastatic disease by treating people more effectively in the neoadjuvant setting, I think is a goal that we all should have.

There are, of course, patients that still get diagnosed with de novo metastatic disease.

And so again, this is one of the reasons why the advent of screening in disease is so important.

so that we can pick up as many patients as possible where there's still this higher potential for cure in the early stage setting and ultimately over time reduce the incidence of metastatic disease.

I'd be very happy to see the reduction in the rate of metastatic disease.

Of course, in the context of the overall opportunity with an aging population across the world,

Actually, the incidence of cancers is still going up, even if we're more effective at diagnosing those at an early stage.

So, you know, I think there's two separate things that are going to happen here that will counter one another in terms of a commercial opportunity.

And we'll see how that evolves over time.

Yeah, we do have those questions.