Jay Luly: Sure. Thanks for the question, Liisa. So one of the key reads that we’ll be watching for on the viral logic side of the table is viral load. And one of the things that we know is standard risk patients and high-risk patients have very similar viral loads. What happens after that to those various patient populations differs. But this is why, if you’re looking at symptoms or outcomes, some of those things, those would be harder to measure in this so-called standard risk patient population. So — but again, when bringing it back to looking at the virus, trying to figure out which dose you’re going to use, looking at safety and tolerability, those are the kinds of things that you should be able to do quite adequately in this patient population.
And then once we’ve got our dose based on all those parameters, again, going into Phase 3, you can broaden out and look at many different outcomes, and we’ll have obviously larger-powered studies to look at those kinds of things. So, yes, so Pfizer’s shown that it’s — the viral loads are very similar standard risk or high risk and Shinobi saw viral load effects in that standard risk population.
Liisa Bayko: Thank you.
Jay Luly: You’re welcome.
Operator: Thank you. One moment while we compile our next question. And our next question comes from the line of Eric Joseph from JPMorgan. Please go ahead.
Eric Joseph: Hi, good evening and thanks for taking the questions. I was just thinking about this phenomenon of viral rebound seen with Pfizer’s paxlobid. I’m just wondering sort of what your understanding is behind that phenomenon and whether SPRINT offers the opportunity kind of looking at a similar but I’m going to at least assess for it in the post-treatment follow-up period. Are you looking at viral load beyond, let’s say, two weeks? And then as it relates to RSV and the potential for kind of thinking through potential combinations with 938 and 323. I guess, practically speaking, what would be sort of the first opportunity to really explore that potential? Is there a useful true clinical model that would kind of inform the potential for additive benefit through combinations? Thanks.
Jay Luly: Yes. So, two good questions. So, the rebound thing is interesting. I mean, it does seem to be certainly a real phenomenon, although you can get rebound even in people who don’t take paxlobid, and its just part of the natural course in patients. Some will resolve, you think you’re better and then you rebound in, but that phenomenon has definitely been observed in protease-treated patients to-date. And part of the — the thing that we’ve been wondering about is, well, why is that? And clearly, there must be some little pocket of virus that’s not fully taken care of. Ideally, you want to beat the virus down to a low enough level in whatever tissue you need to beat it down in and then get it down to sufficiently low levels that the immune system can kind of come in and mop things up and help you out.
So, our speculation is that among the possibilities there could be a little reservoir virus hiding somewhere and that you need to further extinguish it. And so do you do that by treating for longer days? I think that’s one parameter that will be sorted out over time. But the other intriguing possibility is one that potentially EDP-235 could have an advantage on. And that is higher tissue uptake in terms of uptake into key target organs such as lung tissue, where we’ve demonstrated at least pre-clinically, drug concentration out of the plasma and into the tissue at least in lung tissue of four to one concentration. So, that wasn’t observed with another protease inhibitor that’s out there. And so we’ve looked not only at lung tissue, but we’ve looked at many other tissues as well that are potential reservoirs for virus.
