Stephen Hoge: Thank you for the question. So I’ll take the rare disease portion of that on PA first. And so, as we shared last September, we did a data cutoff from the PA study last September after a couple of dose levels. And we were seeing slightly more than 50% reduction in the rate of metabolic decompensation. These are the severe events that really, we believe, will ultimately be the endpoint that we’re measuring for this drug in terms of benefit. And what we are going to be sharing at ASGCT is the further update to that. And so this will be a March data cutoff. It’s about six more months and that will also include at least six months at the third dose level, 0.5 MPK and some other emerging data at the next dose level. Again, I don’t want to get ahead of sharing what that data is.
But of course, we will be looking the strength of that benefit, as we go up in dose, we would hope that we would improve from that 50% reduction in the rates of MDs, approximately 50% reduction in MDs. And we’d also want to obviously see that the drug continues to be very well tolerated with no safety concerns in that patient population. We’ll also see much more follow-up time in terms of total time on drug across the entire study, which will help to build that case moving forward. Now on the point of relationship to other programs, propionic acidemia, PA is a sister disease to methylmalonic acidemia, MMA. And as we get more and more confident, hopefully, about the dose level in which we’re expanding the PA program and the data we’re seeing there.
We do believe that reads through very directly into the data that we expect to see shortly in MMA. We have started see some of that data from that Phase 1/2 study in populations. I’ll remind you that MMA is also chronically dosing in patients and escalating through dose levels. And at the right moment, we will obviously want to provide an update on that data as well in terms of MMA. But we do believe that the PA did really positively through that. And generally I’d say that’s true for our liver metabolic rare disease programs including OTC and the others that you referenced.
Jamey Mock: And Salveen, maybe I’ll take the COGS question. So to reiterate, this year is 35% to 40% of sales. And as you mentioned, we’ll go to 20% to 25% by 2027. So I’m not sure it’s a perfectly straight line, but let me just give you the factors that will improve that over time. First is volume. So increasing volume over time as we add new products, our overall manufacturing footprint should give us better leverage. I think predictability helps that so this is a highly unknown season this year. It will be the first time we’re transitioning to an endemic. So that will become more predictable over time. ASP, I think, will continue to go up as well. What might offset that a little bit is a greater single-dose file or PFS presentation over time, and we’ve got some of that budgeted for 2023.
So overall, we feel confident inverting our inventory levels down and overall decreasing our cost as a percent of sales. As it pertains to the 2027 P&L and what does that mean for overall company profitability, we haven’t issued any guidance on that. I would say to reiterate for those that heard my prepared remarks, the respiratory vaccine business should generate $4 billion to $9 billion, which we laid out on the page there. And then we’ll just have to see, to be honest. We’ve got an exciting pipeline. We have to understand what’s happening with INT. We’re quite excited by that, rare diseases, latent diseases as well, and we’ll do what’s best for all of our stakeholders. So if it makes sense to continue to reinvest some of those profits back into the business, we’ll do that.
And we’re just going to have to wait and see where the pipeline looks like at that time.
Operator: Thank you one moment for our next question. Our next question comes from Tyler Van Buren with TD Cowen. Your line is open.
