Okay, Jim, why don’t you take it from there?
Jim Wassil: Yeah. So, for the superiority, what I’ve seen in the past year is that sometimes the FDA wants to take into account some assay variability because if they’re going to put a statistical superiority claim in your label, they want to make sure that you’re absolutely sure that it’s superior. So, it wouldn’t be materially higher than 1.0, but it might be slightly higher to give some degree of leeway in case there’s some mass variability. So, we don’t expect it not to be 1.0, but even if it’s even higher, I think we can achieve at least four and more. And then the last thing I’ll say on that is that even if we aren’t able to get superiority play in the label, that absolute immunogenicity value will then reset the bar for others to demonstrate non-inferiority again. So, even if it’s not on the label, we’ll have raised the bar for others who want to follow to demonstrate non-inferiority.
David Risinger: That’s very helpful. Thank you very much.
Operator: Thank you. One moment while we prepare for the next question. Our next question will be coming from Seamus Fernandez of Guggenheim. Please go ahead.
Seamus Fernandez: All right. Thanks. Thanks so much for the question. So, really wanted to drill in a little bit to VAX-31. Just hoping you guys could provide us with a little bit of color on what it’s going to take to get that IND through, expand the manufacturing to the 31-valent targets? And then separately, I was just hoping you might help us understand where you see the real differentiation opportunity for VAX-31. My impression was that the team was really thinking about some unique opportunities, particularly in otitis media as an opportunity there. So, just love to touch on VAX-31. Thanks.
Grant Pickering: Yeah. Thanks for the question, Seamus. So, as it relates to the VAX-31 program, we’ve guided to an IND going into the second half of this year. And like we saw with VAX-24 last year, these adult studies accrue and readout quickly. So, we have guided to being in receipt of the data from that study, top line data next year in 2024. So, in order for us to be able to guide to an IND in the second half, it means we’re well on our way from a manufacturing perspective. We’ve said publicly that we made a surplus of the 24 drug substances that are in both VAX-24 and VAX-XP. So what we’ve been in the process of doing is manufacturing the incremental seven polysaccharides and then conjugates and then doing the drug product formulation work.
So what we’ve said in other conversations is that we’re well on our way. We’ve made all the polysaccharides under GMP. We’ve made the conjugates and now we’re heading towards the drug product formulation stage. And so far, so good. And as per today, we’re maintaining that guidance of second half IND filing. So really excited about that and we believe we’ll be able to leverage the same Lonza infrastructure for the production of VAX-31 that we’ve been budgeting for, for VAX-24. As it result — as it relates to the differentiation, maybe Jim and I can tag-team this one. But for starters, in the adult space, once you get up to 31 strains, you’re effectively covering the evidenced pathogenic serotypes for pneumococci. So, in the U.S., those 31 conjugates will cover 95% of the circulating disease.
In Europe, it gets as high as 98%. So, you really feel like you covered the gamut once you get to these 31 conjugates. And what we think we can do with the carrier-sparing technology that we possess is not only scale to cover those newly circulating strains, but not take the pressure off those strains that have historically been pathogenic, but have been brought under control with vaccination currently. And so this is the big opportunity that we have, and we don’t believe we face the same trade-off that the conventional PCV developers are facing where, to get the kind of coverage of the newly certain strains, they have to no longer include those strains that have been taken out of circulation. So, as we mentioned in the prepared remarks, there’s historical precedent where vaccination has been withdrawn for currently covered controlled strain can result in a rebound.
