Grant Pickering: Well, from a FDA licensure perspective, the adult label is usually extended at age 18 and up. So we’ll be looking for the same sort of broad label that’s been obtained with other pneumococcal conjugate vaccines. So the next look then is at the ACIP as to how they grant the universal recommendation. But from a licensure perspective, we’ll be looking to have an across-the-spectrum sort of indication, but then it’s a question of usage. And as Jim said, when it’s universally recommended, the uptake is much greater than when it’s restricted to at-risk populations.
Jim Wassil: Yes. And I’d only add that given the interest in these at-risk groups in 50 to 65-year-olds, we’ll make sure to have adequate enrolled at-risk groups in our clinical studies so that we can support FDA — ACIP does want to move down to 50 years of age on clinical data to help with their decision.
David Risinger: That’s super helpful. Thanks so much.
Grant Pickering: Thanks, David.
Operator: Thank you. We go next now to Umer Raffat at Evercore.
Umer Raffat: Hi guys, thanks for taking my question. Among the new serotypes you’re adding to VAX-31, there is one in particular, which has a bunch of literature on it suggesting it’s very unique and perhaps difficult to manufacture. I’m referring to 35B. Can you speak to your confidence in the manufacturing as well as early immunogenicity data you saw in preclinical models of 35B in particular? And secondly, is it your expectation that Pfizer’s broader spectrum program 24, 25-valent is using a second carrier protein beyond CREM-197? Thank you.
Grant Pickering: Yes, maybe I’ll answer the second one first and then Jim will address the 35B question, Umer. Thank you for both of those. So…
Umer Raffat: Pfizer?
Grant Pickering: Oh, yes, as it relates to the fourth generation program. Yes, Umer, it’s hard to know exactly what they’re doing. So from what they’ve been willing to disclose, they’ve been considering all number of potential changes to try to extend beyond a 20-valent vaccine. But at the most recent earnings results, they seem to indicate that whatever incremental strains would be layered on top of what would presumably be the 20 strains that are in Prevnar 20. And there it then comes down to — is it a unique protein carrier, is it different chemistry, is it different linkers or some sort of other formulation? But it’s hard to know beyond that. I don’t think they’ve gotten detailed with regard to that. That said, this idea of the notion of using an additional protein carrier, that’s something other sponsors have tried, going back to GSK’s first foray in pneumococcal conjugate vaccines.
And then more recently with Sanofi’s approach intermingling diphtheria toxin and tetanus toxoid. And those have turned out to be a bit problematic, as Sanofi has not decided to proceed in the adult indication, so it’s unclear at the moment, but other attempts in a similar vein haven’t worked out particularly well. But we couldn’t say for sure if that’s the approach they’re trying as of yet. And as to 35B, Jim, do you want to comment?
Jim Wassil: Yes. Traditionally, we limit our comments on some of this due to proprietary issues, but I’ll say 35B is an important serotype. It’s one of the more common circulating strains in adults and it’s probably the most significant contributor to otitis media in the U.S. today. So we are very keen on making sure that it is manufactured appropriately and that it works well in VAX-31.
Umer Raffat: Thank you.
Grant Pickering: Thank you, Umer.
Operator: Thank you. We go next now to Seamus Fernandez at Guggenheim.
Seamus Fernandez: Great. Thanks for the question. So wanted to just talk a little bit about pediatric and what expectations, how you’d like to kind of set expectations for the three dose data. I know that is something that Merck has sort of pitched as part of the vaccine advanced story. Just interested to know, I know that breadth is likely to dominate. But a three-dose regimen has been quite successful overseas. So interested to just know how you guys are thinking about the opportunity for actually perhaps a superior profile at your third dose versus the Prevnar 20, 23rd dose, just because a number of those serotypes appeared to miss at three doses and then really required the fourth dose to catch up. So just interested to know how you’re thinking about that and its importance from a market perspective longer term.
And then just the second question is on whether you choose VAX-24 or VAX-31 in the adult vaccination program. Are you confident that you won’t be required to study versus V116 or is that something that could be decided after the ACIP recommendation in June? Thanks.
Grant Pickering: Yes. Thanks for the question, Seamus. So yes, as it relates to the infant indication, obviously a critical part of the market, three-quarters of the sales consistently in that space. And as you referred to a three dose series, I wasn’t sure exactly which direction you warranty you were until you expanded a bit. But, yes, to be clear, in the U.S., we have a three-plus-one approach. So three vaccinations within the first six months of life, that’s called the primary series, and then the fourth dose comes in the form of a boost the next year. In Europe, they restrict that primary series to only two vaccinations and then the third dose the next year. So it’s really a three in Europe versus a four-dose approach. And as you say, less doses create more pressure on lower immune responses.
And so when Pfizer studied Prevnar 20 in infants in U.S. and Europe, the impact of the one less dose was quite profound. So in the U.S., there were six of the serotypes that missed the non-inferiority comparison to Prevnar 13 after the primary series. And one can imagine that when you only give two vaccinations with a vaccine that’s providing lower immune responses, the impact of that will be felt in a fewer-vaccination approach. And sure enough, the results of their Phase 3 study in Europe had 11 of the common serotypes miss the non-inferiority comparison at the primary series. So that has been a big question mark. Nonetheless, the CHMP in Europe did recently recommend that Prevnar 20 ought to be approved. So that will be interesting to see how that plays out with that many missed non-inferiority comparisons.
