Paul Bolno: Yes. I mean, I’ll hand it over to Anne-Marie in a second on the clinical side, but I think it is important as we think about the application initially where we’re pursuing, which is — if you think about the homozygous ZZ patients, it’s both liver and lung. And so, as we think less about where the manifestation is, the actual driver of that disease is in the underlying genetics. And therefore, it’s about correcting those ZZ patients to MZ patients, and therefore, following the protein relative to that. So it’s much more about collecting for the genotype and demonstrating — evaluating the protein and the constitution of that protein in this initial period. Later, we can then say, look, we can just drive that to the lung and think about where protein infusions have been developed and thinking about achieving threshold levels of Alpha-1 antitrypsin protein and looking at liver demographics.
But I think initially, the proof-of-concept really is focused on demonstrating that translational potential of both for AATD with this particular medicine, but even the RNA editing deal more broadly and what the impact is, we think, through other hepatic targets and beyond. Anne-Marie, I don’t know if there’s anything else you want to add to that in terms of the clinical trial demographics?
Anne Cheung: No. I mean, I think you hit it. We’re focusing on ZZ patients, phenotype patients for now, and there’ll be more details about the study once we’re in full agreement with regulators.
Paul Bolno: I think the other piece is, if we think about the ZZ population, the ZZ population by itself is about 100,000 patients in the U.S. So as we think about that, there is a consequential patient population to study. So we’re not concerned that we’ll be able to find the patients for the study.
Operator: Our next question comes from the line of Paul Matteis from Stifel.
Julian Pino: Hi. This is Julian on for Paul. Thanks so much for taking our questions. On AATD, I know you said for 006, you’re not constrained by therapeutic area. Just curious regardless, is there anywhere else in particular that you find compelling beyond AATD to where you may be interested in establishing proof-of-concept moving forward? And then, any other color also you could just provide in the GSK collaboration. I know you mentioned that you’re currently working with them on numerous targets, but any other color you could provide on how that’s coming along? And how you plan on allocating your resources for joint programs versus your own moving forward would be super helpful.
Paul Bolno: Thank you, Julian. I’ll take it from the beginning, and I think you set up a really important context at the very beginning, which is I think you said AATD is not concerned by therapeutic area. I mean AATD, you’re right, liver-lung, but we’re treating the liver to ultimately create the protein that protects the lung. So I think it’s important in the context of AATD optimizes in a POC of GalNAc-conjugation and what it can do across functions. What we’ve done, and I think these are important data sets that we’ve previously shown. And again, as we said earlier that we plan to do the update on September 28 that our R&D Day, as we have shown data extra-hepatic, meaning absent GalNAc, the chemical modifications that we have distribute to a number of issues: CNS, lung, kidney and others.
So I think as we think about those therapeutic areas and what each of the potential within those tissues unlock, I think, what we’re seeing is an expansion of indication. On a previous call, and we’ll obviously share more on R&D Day, I think we’re also excited, as we talk about not just as we said, rare and prevalent, but really thinking about mechanism. So in AATD, here, we’re talking about the ability of a correction that actually changes a protein from a mutated form to a wild-type or healthy point. There are applications in a number of tissues in therapeutic areas where we can apply that in developing meaningful therapeutics. With this — been exciting and what we’ve shared previously from in vivo data on, and we’ll continue to share more on that is, the ability to do upregulation.
So to think about areas where you’re under expressing a protein and then rather than trying to augment that by trying to deliver an mRNA therapeutic or other technology, which could be constrained even by mechanism of delivery. The ability to actually stabilize a transcript increase its expression and therefore, increase the protein that’s produced, lets us think about other applications beyond just the base correction fixing of protein. And as we think about that area, we think that universe is really broad. And it gives us a lot of opportunities to think about multiple therapeutic areas for us. So we are excited about sharing more data on programs in those areas and data that supports the growth of the RNA editing field and what it can do beyond Alpha-1 antitrypsin.
Julian Pino: Excellent.
