Stephen Hoge: All very good questions and I think the short answer is we are looking into that data right now. And we will provide an update I am not exactly sure when we will have that, but we do have the Vaccines Day Investor Meeting coming up in April of the spring and then obviously, we will be looking to publish that data and share as it comes in and is it available. You have highlighted one of the key challenges in active comparator studies in influenza in particular, which is that you can see high titers, but actually because you are looking at a ratio, say for whatever reason, your active comparator does really well against one of the strains, that can impact your ability to non-inferiority statistically. And at the end of the day, the challenge is even more complicated as you look at older adults where, for instance, the influenza B strains are not a big driver of efficacy or disease.
And so we will look at all of that as will regulators. I would note that it is well precedented. In fact, many of the currently approved influenza vaccines have, in the past, missed on non-inferiority for €“ and influenza B strain end point here or there and still have received full approval or accelerated approvals. And the reason for that is, as we have said sort throughout, that at the end of the day, influenza B is not a primary driver of concern and it is known to be among the different strains of influenza in the virus in the vaccines of lower import for disease in older adults. In fact, one of the four strains, there have been active debate about the B/Yamagata strain as to whether or not it’s gone extinct, and even should be removed from quadrivalent vaccines in many of the recent WHO and other debates.
And so influenza B is a well-trodden path for many of these vaccines as well as now for mRNA-1010, where there is differential performance, and ultimately, there is precedent for moving forward where you do not technically need non-inferiority on immunity your sales conversion endpoints and still moving forward because of the lower concern about that disease in older adults. So, we will look at that data. We will develop our strategy. We will obviously engage with regulators with that data, and ultimately determine a path forward. The most important thing for us, though, in the near terms continuing with the efficacy study trying to establish whether or not we have non-inferior or even superior efficacy for mRNA-1010 in its current form against influenza A, which is really where we think payers and public health officials will have the most attention because it is prevention of that disease, not the immunogenicity endpoint, prevention of influenza-like illness, hospitalizations, that is the primary objective of the vaccine and that’s where we are focusing our attention right now.
Ellie Merle: Great. Thanks for the color.
Operator: Our next question comes from Joseph Stringer with Needham. Your line is open.
Joseph Stringer: Hi. Good morning. Thanks for taking my questions. Two from us, the first one on 4157-KEYTRUDA combo program. Just curious, if you could give us a little bit more color on how we should think about the cadence of the additional trial starts? Is it something that will be a more stepwise and measured approach, or should we expect sort of a full force kind of multiple trial starts approach? And then secondly, on rare disease, outside of your MMA, GSD and PA program, what is the next rare disease program that we can expect to enter the clinic? Thank you.
