James Gordon: Hello. James Gordon, JPMorgan. Thanks for taking the questions. Firstly, a question on at Dato, which would be, is the plan to change anything on the back of the recent Dato update? And what might change? For instance, could you tweak any of the trials to enroll patients that you think are going to show stronger efficacy in some sort of subpopulation — and is it Trop02 or is it something more sophisticated that you’re actually looking at? Because a Trop02 expression is like a pillow on the slide is laying out the Dato program. But is this something else where you might end up stratifying — and will you kick off any more Dato Phase III trials from now? Or are you going to wait until you’ve got a bit more data from other trials to work how were the strongest efficacy is going to be generated?
And then just one other question, which was Imfinzi, so very strong growth today. But is there anything one-off here that help performance? Or actually, if we put Dato aside, is Imfinzi and a HER2 really going to be the two key growth drivers from now and to the end of decade. Can we really extrapolate the strong growth forward for Imfinzi today?
Pascal Soriot: Susan?
Susan Galbraith: Okay. All right. So in terms of Dato-DXd new trials, let me start with that one. Yes, we are continuing to planned new Phase III trials with Dato-DXd. As we had indicated at the end of last year and we continue to be excited about the potential for this molecule in multiple different settings. In terms of the biomarker, Trop02 is highly expressed across many different tumor types, including lung cancer. I think in general, about ADCs and prediction of outcome, receptor expression is one element, receptor internalization and another element and sensitivity to warhead as a third element. So the there were multiple elements to consider about predicting the patients that are most likely to respond and of course, we’re looking at those different elements in what we’re working on from a biomarker perspective.
David Fredrickson: Thanks, Susan. James, on Imfinzi. I mean I think the first thing I’d note is that we double-clicked into it into the prepared remarks because we think that the opportunity for Imfinzi going forward is an important one. We’ve made a series of investments into the life cycle plan in the clinical development plan for Imfinzi. And those now are paying off in terms of positive readouts, and we’re commercially taking advantage of that. I think that to go a little bit more specifically, somewhere between 20% and 30% of the Imfinzi growth that we’re seeing is coming from the established portfolio, so the PACIFIC and Caspian indications where we’re seeing strength in PACIFIC across the globe as we kind of get further away from some of the COVID-19 challenges.
We’re continuing to progress against Caspian in parts of the globe where we have opportunities. But really, it’s the new launches of TOPAZ, HIMALAYA and POSEIDON that are making up the balance of that. TOPAZ has rapidly gotten to a place in the markets where we’ve launched, where we have market share that’s well north of 50%. And I’d say, HIMALAYA has had a nice uptake, but still quite a bit of opportunity to continue to move with HIMALAYA. It is a competitive context. And it’s one where we are certainly coming up against therapeutic alternatives, but we like the uptake that we’ve had. Maybe the last proof point just to offer on this. While with TOPAZ and HIMALAYA, we have regulatory approvals in over 50-plus markets across the globe. We only now today have reimbursement in just around 10.
Now they’re 10 of the largest. So, it’s the US and Japan, and we have early access that exists within France. But we still have a number of countries within Europe and a lot of countries within international, which yet to come on board. So we think the outlook for Imfinzi forward is strong.
