Julian Pino: Hi. This is Julian on for Paul. Thanks so much for taking our question. On the AATD program, is there anything specific or out of the ordinary that may be required for the CTA? Just given it’s a first of its kind technology entering the clinic? So if there’s any specific ask from the regulatory agency or any other requirements, it would be great to hear. Thanks so much.
Anne-Marie Li-Kwai-Cheung: No. There are no specific or unusual requests for our filing CTAs. They’ll just follow the normal route for a CTA filing.
Paul Bolno: And I think stepping back, I mean, this is an important reason of our unique approach of using oligonucleotide to engage with endogenous RNA editing. So again, I think the question obviously refers to a whole bunch of other approaches predominantly based on the DNA editing space, the base editing space. But I think our approach has been to use endogenous enzymes as we’ve said very similar to what’s used against Ago2 for RNAi with acceptable for . And so we’re following a well driving path of RNA therapeutics.
Julian Pino: Great. Thanks so much.
Operator: Please stand by for our next question. The next question comes from Luca Issi with RBC. Your line is now open.
Unidentified Participant: Perfect. Thanks for taking our questions. This is Lisa on for Luca. Just on the APP program. I have a three part question here. It looks like your mouse data is Intracerebroventricular delivery. But is it fair to assume that if you were to move this program into humans, you would use (ph) delivery like (ph) is using for their program? Also on the chemistry, we know a Nylem is using C16 ligand. So just wondering if you can remind us about the chemistry that you’re using for your program for CNS delivery here? And finally, just maybe a bigger picture question. How are you planning to differentiate your siRNA platform? Is there any technological differentiation that we should be aware of? Or is it more of an indication selection type of play here? Any color would be much appreciated. Thank you.
Paul Bolno: That’s great. And look, I appreciate the question, because a lot of this is building on work that we began last year and, obviously, we’re continuing to build on. So I think to your question, starting with the first on mouse data and ICV delivery, that’s pretty standard for mice. But obviously, we have a long history of looking at CNS translation from IVB data in mice to nonhuman primates and ultimately into patient. And again, in that case, using the dose. We do recognize the translational value and we’ve seen that data from others in the space. I think what was impressive to us is, it doses better our own par, if not, more effective potentially than others have shown. We’ve seen target engagement across all regions of the brain with ICV administration.
I think that’s important because I think there’s always a question of where do these drugs distribute in CNS. I know these questions come up a lot as we think about potential target implications. But I think it’s encouraging again with the first CNS experiment to be able to see broad potent. And most importantly, I think relative to what we’ve seen with others, it’s durable. We know that’s an important function even when we think about ICV €“ sorry, IC injection is that the durability effect is critical because, obviously, it means reduce dosing administration frequency. So we’re encouraged by again the initial data, exciting to continue to see more work and it’s obviously something that we’ve has interest in from a number of parties. Additionally, to that, you asked a question about chemistry and I think that was the piece that was, I think, unique to what we’ve been developing all along around PN chemistry distribution.
