Pascal Soriot: Thanks, Mark. So I think the first question was the bispecific immune checkpoint inhibitor, Susan, you could take this one. And the second one is also for you in terms of the B7-H4.
Susan Galbraith: The bispecifics PD-1 that you said T-cell engagers. We do have T cell engagers in our portfolio, but I think we’re talking about volrustomig and rilvegostomig. Volrustomig in terms of the EVOLVE02 study, you can imagine the context of first-line non-small cell lung cancer. A clinically meaningful benefit, is something where you’re looking for some months of improvement on median PFS and often an improvement of the hazard ratio with that tail. And of course, CTLA-4 inhibition is particularly potent producing that tail inhibition. So I can’t tell you what the design criteria for the study, but you’ll see the size of the study, and I’m sure you can work that out. But we’re confident based on the data that we’ve seen.
We’ve got the potential to improve on it. In the patient population where checkpoint inhibitors don’t currently work as well, which is clearly that lower end of the PD-L1 expression level. And then for B7-H4 lead ADC. This is an important molecule for us because, first of all, it’s the first molecule that’s come out of our proprietary ADC discovery platforms. We’ve got a proprietary link and topo warhead on that. You saw some data presented for other B7-H4 targeted ADCs at ESMO. So I think this is going to be an important target. It’s overexpressed in parts of ovarian cancer, endometrial cancer, breast cancer and some biliary tract cancer. We’re exploring cohorts in multiple of those cancers, and we look forward to sharing data next year on this.
But we’re excited by what we’ve seen so far. We will, obviously, because there’s a competitive landscape over there, we’re going to move at pace.
Pascal Soriot: The next one is Eric Le Berrigaud at Stifel.
Eric Le Berrigaud: Two questions, please. First, you’re presenting the CAPItello for 2024, probably you pick just a few of those. So just because SERENA-6 is not on it, just to confirm that it’s still on schedule. We’re hearing from physicians that it may come quite early and maybe as early as the turn of the year. So just to get your level of excitement and see that there is no decrease here? The second question is about V&I. We’re hearing a lot about the significant investment to come in CVRM, adding to oncology. And so you made a quick and pragmatic investment here around COVID vaccine and antibody. How much do Astra need B&I and how much is it a distraction now to oncology, CVRM and rare disease in terms of resource allocation? Thank you.
Pascal Soriot: Thank you, Eric. So maybe Susan, you could take the first one.
Susan Galbraith: So again, we don’t guide on interims, the SERENA-6 outcome is currently guided for beyond 2024. I would just say that our core instrument trials overall are going really well, and we’re pleased with the investigator feedback we’ve had from the investigators who are participating in these trials.
Pascal Soriot: Thank you, Susan. So maybe, let me just make a couple of comments, and I could ask is has to jump in. It is not a distraction. I mean our focus really has been and continues to be on antibodies, and particular antibodies for patients who are immuno-compromised and we work on 3152, and we do believe that there is an unmet need out there that is not addressed and needs to be addressed. The mortality in patients who are hematology patients, transplant patients, patients who are immunocompromised is very high, actually, 30%, 40% chance of dying if you have a blood cancer and you are infected with COVID. I’m not even talking about being hospitalized, the risk of dying if you’re hospitalized, I’m talking about the risk of dying if you are infected.
So this is very high, and there is a need for those patients. In fact, we know many countries are ready to order is 3152 if it works. So of course, as always, we cannot guarantee success in anything we do. But we believe there is an opportunity for 3152, if it does work. And we’re working on other antibodies. And for vaccines, we have a very focused strategy on new technologies that for now, we really are disclosed because we need more data. But the 1 thing I would say is that there is actually a synergy with our other activities. If you think of hematology cancer again, doctors, hematologists, they want to protect their patients against COVID, especially during periods of increasing COVID infections. So for us, it’s really a door opener if we have antibody to offer.
The door opener the team that is promoting Calquence and the same is true for immune diseases. So there is a clear commercial strategy. And from a resource viewpoint, overall, it’s limited investments in other distraction. Iskra, if you want to comment a little bit more on where we are and what we do.
Susan Galbraith: Thanks, Pascal, for the comments. So just to add, I think looking beyond the immunocompromise and I think you described unmet need very clearly. I mean, you can also see an unprecedented demand we see with the ports that we are commercializing together with our partner, Sanofi, and there is a clear unmet need RSV in the infant population. So I really believe that we can build and leverage in our in-house, know-how the building long-acting monoclonal antibody is definitely has a need across the different populations. And then also, I think, Pascal, as you mentioned, looking at the kind of what is next generation platform and how we can potentially contribute to bringing the new and differentiated vaccine is something that we are constantly focused on. And obviously, I will be very pleased to share more information with you in the due course.
Pascal Soriot: Maybe last point in [indiscernible] was really a different story. It was really to help the world deal with this terrible pandemic. But outside of this, what we focus on is products where we can actually be differentiated and address an unmet need. And of course, it’s true for these antibodies. On the vaccine side, we would actually only go into large investments if we believe we have something that is truly differentiated. So next one is Richard Parkes at BNP.
Richard Parkes: Hopefully you can hear me okay. I’ve got one for Aradhana and one for Susan. Firstly, for Aradhana. Just on R&D spend, actually as you go into that budgeting negotiation later this year, you’ve had an incredible number of new Phase III starts this year. You’re also investing in new technology platforms, you managed to keep R&D spend growth to mid-single digits, I think, in the third quarter. So I’m just wondering if you could talk about the moving parts of how that growing pipeline can be funded? How much of it can be funded through reinvestment as you — and kind of the previous Phase III trials versus need for a step-up in the R&D spend growth trajectory into next year? I ask the question partly because we’ve seen other companies with — surprising investors negatively with a step-up in R&D spend.
So that’s the first one. Then secondly, for Susan, I can see you’re starting a Phase III of the Part I selective inhibitor in prostate cancer. But obviously, there’s a huge potential for that drug if you can unlock potential for synergy with an ADC, with a DNA damaging payload. So I just wondered if you could talk about your enthusiasm and optimism of that program? And potential, more broadly, and what we might see, I guess, insight to that — your plans? Thank you.
Aradhana Sarin: In terms of R&D, we obviously go through a very detailed process that is both bottoms-up and top-down. And I think we’ve obviously said in the past that we expect R&D to be somewhere in the low 20s percentage of revenue, and what that helps us with is actually provide some discipline in terms of which projects to prioritize and so forth. Also, I would say, as we have started a number of Phase III studies. But when you look at Phase III studies, there’s also been a number of studies that we’re tapering down or we’ve read out and so forth. So it’s a constant phase and all the Phase III expense doesn’t come necessarily in 1 year, right? It’s raised over the entire study period. We start a number of Phase III studies, for example, this year, but some of that expense, a lot of that expense also goes in study starts, in the site recruitment, in the clinical study supply, et cetera.
