Christopher Anzalone: Sure. So look, that’s a little bit of a hard question to answer broadly because various drug candidates will have specific advantage. But I’ll tell you broadly the way we look at this. RNAi is not the right modality for every indication, of course, but for many indications where you really — where you need to reduce the expression of some gene product, it’s a good one. I think we’ve shown — we and others have shown time and time again that RNAi appears to be a potentially better modality than antisense oligos in terms of dosing schedule, in terms of depth of knockdown in terms of safety. We think that will continue, at least as it relates to hepatocyte targets, and we’ll see if that applies more broadly.
When you look at gene editing, look, I think that’s an interesting idea. I think that we’re not quite ready for prime time there. And I think that there is a permanence associated with gene editing that may be — that may cause some pause with at least for certain indications. What’s great about RNAi is that we get a good, long, durable effect, but yet it is ultimately reversible. After some period of time, that drug wears off and it doesn’t knock down the gene product any longer. What would concern me at least in the near to midterm with the gene editing approach is that the idea of having to unCRISPRize something is a daunting one. And so I think it’s still a bit of an early technology. But at least as it relates to the indications we’re going after, we believe that RNAi at least in our current pipeline is likely to — and from my perspective, at least the preferred modality.
Patrick Trucchio : Yes. That’s helpful. And then earlier in the call, there was commentary around increased clarity on which programs and how large the pipeline could become in the next few years with the goals outlined through 2025. So I’m wondering if you can elaborate a bit more on this commentary, particularly regarding gating factors involved in deciding which targets or disease to pursue, such as the level of genetic or clinical validation required? And how many programs either in terms of new INDs or some other metric would you be expected to announce on an annual basis going forward as you expand the pipeline?
Christopher Anzalone: Well, yes. So we’re excited about our 20 in ’25 program. We feel comfortable that we’ll get there. I think 20 clinical candidates, whether wholly owned or partnered is a lofty goal, and I think we’re going to achieve it. Regarding genetically validated targets and such, if you go down our pipeline, I think that there is pretty good consensus that these are all well-validated targets, with the possible exception of HBV just because it’s a complicated virus, of course. But everything else, I think, clearly, there is consensus among KOLs that if you can reduce the expression of these various targets, positive phenotypes will result. And our goal is to continue with that. Second, if you look down our pipeline, everything we’ve gone after, we’ve been the first RNAi player there.
I’d like to continue that at least in the near term, I think we will be continuing that. And then finally, with respect to our ability to get outside the liver, as we talked about with pulmonary, with skeletal muscle, we’ll be announcing our next cell type in the first half of next year. With all of these, it gives us the ability to run out and take land, right? We don’t see any near-term competitors in these extra-hepatic spaces at least so far. And so it gives us the ability to really be choosy and go after targets that are well validated to decrease our biology risk.
Operator: And our next question comes from Madhu Kumar from Goldman Sachs.
Madhu Kumar: Maybe following up on Ellie’s question, what do you think is the dynamic range of RAGE and MUC5AC knockdown that will be predictive of clinical benefit in these obstructive pulmonary conditions?
Christopher Anzalone: James?
