James Hamilton: Yes. Sure. So in terms of the chronic rat, or the chronic tox data for the pulmonary programs, that’s it. I mean, that’s the final, that’s from the final report. So there’s no more expectations. We won’t be getting any more data around chronic talks for MMP7 or RAGE. From MUC5AC that we’re still planning the chronic tox study. We wanted to get some biomarker data from the clinical study to better inform on the dose frequency for the chronic tox studies, since frequency of administration seems to be really important to avoid entering into dose levels where we see toxicity. We really wanted to nail down dose frequency. So we need to get a duration of effect from the clinical studies before we finalize the chronic tox study for MUC5AC.
Chris Anzalone: And regarding the subcu, I think and there was twofold. One, there could be other targets and other indications where subcu administration is just preferred to inhaled. And second, that could potentially also broaden or widen out our therapeutic index.
Operator: And our next question comes from Prakhar Agrawal from Cantor Fitzgerald.
Prakhar Agrawal: So on your ARO-XDH program that was partnered with Horizon, it seems that Amgen has decided to terminate this agreement. Was there any data generated by XDH program or was it just part of the recent strategic overhaul by Amgen after Horizon deal close? And what are your plans for this asset now develop internally or will you be looking for a partner again?
Chris Anzalone: So it’s early to say on that. We haven’t seen data. I don’t know that we will, but at least so far, we haven’t seen any of the clinical data. And we’ve not been told why that was being discontinued, whether it’s strategic or something else. We have some theories. James, do you want to talk about the [indiscernible] program for instance?
James Hamilton: Sure. Yes. I think another company had an siRNA targeting the same gene target XDH. It was also discontinued due to lack of decline in uric acid in the blood with immunity knockdown, all of the XDH in the liver, there are still dramatic sources. So liver knockdown might not have been enough.
Operator: Our next question comes from Mike Ulz from Morgan Stanley.
Mike Ulz: Maybe just the quick one on ARO-RAGE. Just in terms of timing of a potential Phase II study there. Now that the clinical the chronic tox studies are done for ARO-RAGE. Do you have enough data to now start to engage with the FDA? Or is the plan more to wait for some of the other cohort data like the asthma patients or high FeNO before you start to do that? Thanks.
Javier San Martin: We’re thinking about, starting Phase 2 to 2024 for sure, and there’s already work going into that, that we design, patient populations, selection of CROs. So we are already planning. As the data is coming in it will help us to decide the dose and the dose frequency, but we are already planning on the next stage development for the AO range.
Operator: And our next question comes from William Pickering from Bernstein.
William Pickering: I had a few follow ups on the DM1 announcement. So how is the drug designed to get your siRNA inside the nucleus where the mRNA is accumulating? And maybe can you share any more color on what endpoints you’ll be measuring that could suggest early of efficacy, for example, splicing assessment or any functional endpoints?
Chris Anzalone: Sure. Yes. So we will look at some of the same endpoints that other companies have looked at and we’ll look at total DMPK knockdown, changes in spliceopathy and we’ll also look at the video hand opening time as well as some of the other functional endpoints. And so your other question on knocking down siRNA in the nucleus. We’ve done some work in animals. We haven’t published this yet or shared it publicly via poster of presentation, but we’ve shown at doses similar to what we had plan on administering in the clinic that we are able to get a level of knockdown of nuclear RNA and that translates into improvements in spliceopathy. So that was the impetus for us moving this program into the clinic that we could get even with modest levels of nuclear RNA knockdown, we could get improvements in spliceopathy.
Operator: And I would now like to turn the call back over to Chris Anzalone for closing remarks.
Chris Anzalone: Thanks very much everyone for joining us today, and I wish you all a happy holiday season.
Operator: This concludes today’s conference call. Thank you for participating. You may now disconnect.
