Grant Pickering: Yes. Jason, thank you for the question. So yes, as we look forward to that data, that we expect to see in the third quarter, I mean, we’re quite optimistic. The way we’re looking at this program is a combination of the empiric evidence generated to date combined with the circumstances. So from any empirical data perspective, certainly we have not only of course compelling preclinical data with VAX-31, but also the VAX-24 data that’s been generated across the Phase 2 program that’s readout already with a particular emphasis on that mix dose cohort, where we were able to already test the cumulative amount of protein carrier that we would expect to have put into the clinic with VAX-31. So for us, we’re really looking as you pointed out at a couple of different endpoints.
So this is a non-inferiority comparison to Prevnar 20 across those 20 conjugates. And then there are the incremental 11 where it said, slightly different endpoint where you’re looking at fourfold rise over baseline. So for us the data that we generated with VAX-24 cohort demonstrated even at that mix dose level, really good comparative results across the 20, that are in Prevnar 20, and then the incremental 11, you know, four have already read out, the next seven will come with this study. And so, yes, for us, I think we’re feeling good. The data is going to be here in the not-too-distant future. And as you mentioned the idea of adjusting the ratio, that is certainly something that has been at our disposal, historically. We do have a level of precision with our chemistry that permits us to adjust the ratio of sugar to protein in ways that we don’t believe anyone else can.
We’ve used that to great effect to date with greater sugar than proteins than convention, a lot of that carrier-sparing conjugates. But for the foreseeable future, we don’t think we need to go back to the drawing board on that, but that would be something we could always look at down the road. For us we’ve been able to show that adjustments in dose yield improved immune responses. So the first order, if necessary, would be more likely to come in the form of adjusted doses. But again, as you know, Jason, this is not perfection that’s required. The whole focus of this class has been to preserve coverage over historically circulating strains while looking to expand coverage to newly circulating strains. And in that trade, it’s been recognized that even with lower immune responses, that’s an okay trade-off.
Fortunately for us, at least for VAX-24, we didn’t look like that was going to be required to push coverage. We’ll see what the VAX-31 data looks like, but I guess the point is, perfection is not the requirement. We’ve seen a few missed strains being considered a good trade-off, at least in the eyes of the regulators. And I think ultimately that’s been a good decision, and we’ll see what data comes out of this study in the third quarter.
Jason Gerberry: Great. Thanks so much.
Operator: Thank you. We’ll go next now to Roger Song at Jefferies.
Roger Song: Great. Congrats for the progress. A few questions from us, I limit to two. So the first one is, with this 31 data in 3Q, you probably need another end of Phase 2 meeting with the FDA. The question is how much you can leverage from your VAX-24 end of Phase 2 meeting package for that meeting. Because your timeline is basically, you’re going to start a Phase 3 in 2025 and 2024. I think, if you move forward with the 31, particularly around the CMC because that’s something since holding you back for the 24 at this moment. Thank you.
Jim Wassil: Thanks, Roger. This is Jim Wassil. And I’ll try and answer that question for you. I think you’re very perceptive in your question. We’re hoping to leverage a lot of the study designs that we propose to put forward with our end of Phase 2 design for VAX-24 and use the very similar design for VAX-31. Obviously, we’ll look at the data from the Phase 1/2 of VAX-31. We’ll do a reanalysis from a statistical perspective. We’ll power the studies appropriately to ensure that we maximize the probability of success in our non-inferiority study and our other Phase 3 studies. But essentially the proposal that we put forward in VAX-24 will be very similar in terms of the overall study design that we’ll see for 30 months.
Roger Song: Got it. And how about the CMC portion of the 31?
Jim Wassil: Yes, the same thing as well. We’re using very similar manufacturing processes, if not exact manufacturing processes, in some cases between the 24 polysaccharides and 31, as well as the drug substance. And of course, the carrier protein is still the same carrier protein. So a lot of similarities between 24 and 31. So whatever we learn from feedback from the FDA or from a CMC perspective, from 24, we believe is applicable to 31 as well.
Roger Song: Excellent. Maybe just a follow-up question for the 31 higher dose you mentioned on the call, the mixed dose from this third 24 is mimicking the middle dose for 31. Maybe just any color you can provide related to the high dose for 31, particularly in terms of the carrier protein, how much higher and what are the key serotypes potentially can be dosed higher, if you can give us some color around that. Thank you.
Grant Pickering: Yes. Hey, Roger, Grant again. Yes, we’ve been a little bit more coy with regard to the doses we did provide a bit more detail here just for competitive purposes. But we want to make sure that we come out of this Phase 2 experiment with a clear dose to advance to Phase 3. So here go the bracketing with lower and higher doses. We haven’t gotten into explicit detail, but there is a pretty tight window of dosing that’s been historically applied in the pneumococcal conjugate vaccine space, so we wouldn’t do anything that would be radical there. But we’re not going to go into the explicit details of what those are, at least for the time being, and that will be decided at the time we review the data.
