Brendan Smith: Just a couple of quick ones, if I could. I also want to have a follow-up just on the timing to pulmonary data. Is it fair to say we’ll see the high dose RAGE data in asthma patients by Q2 of next year, with the high FeNO data in Q3? And then really just any color you can give us on MUC5AC, MMP7, maybe when we might see some of that data next year would be great. And then quickly, I just wanted to see if there’s any updates on the ARO-C3 program and if there’s any plans to put out any data from that next year either? Thanks.
Chris Anzalone: Sure. James?
James Hamilton: Sure. Yes, the intention would be to release the sRAGE data from the asthma cohorts When it becomes available to us, so probably, middle of the first half of next year, I think for the asthma, the high dose asthma sRAGE data. And then in terms of FeNO in the high FeNO cohorts, we’re looking at Q3 for FeNO data in those patients. And then, MUC5AC has been a little more challenging to enroll some protocol requirements in there and then the requirement of those patients being severe asthmatics, but likely towards the middle of the year for ARO-MUC5AC data we still need to enroll the highest dose cohort of those patients. And in terms of C3, we are in the process of enrolling the patient cohorts, the IgA nephropathy patients as well as the C3G patients. So probably the second half of 2024 for proteinuria data.
Operator: And our next question comes from Mayank Mamtani from B. Riley Securities.
Mayank Mamtani: So maybe James, if you could dive a bit deeper on the safety margin difference that you’ve seen between MUC5 versus RAGE in the recent preclinical data that you received? And if you’re able to comment on how the NOAEL doses for MUC5 correlate the top dose that’s being tested in the clinic? And maybe a high-level question on like what, for MUC5 would be, human proof of concept like investors think about for outer age in terms of the higher asthma patients? Like you just commented, it’s severe asthmatic patients, but what sort of biological signal would be relevant here given, obviously, this is more downstream physiology to IL-4 efficacy?
James Hamilton: Yes, I think on the last question, it’s a bit tough to pin down what’s clinically relevant in terms of MUC5AC knockdown since there’s not a great correlate out there from other drugs. So I can’t give you an exact number on that. In terms of the safety margins comparing MMP7 or RAGE with ENaC, I guess it depends on the dose level, we used a low, mid and high dose level for all of those chronic tox studies in the rats. If you compare the cumulative dose given over a 6-month rat study at the high dose level for RAGE, we had there’s a sevenfold difference between the high dose level used in ENaC and in RAGE and the 4 to 5 full difference for MMP7 in the rat, so it’s significant difference between the total cumulative doses that were administered in those 2, with those 2 different molecules.
Mayank Mamtani: And then just on the muscle targeting programs that’s for DM1, could you just remind us the targeting receptor ligand approach here? And as obviously you guys know, it’s an active field, there are alternative antibody ASO approaches. Maybe how does sort of your preclinical data inform, what you’ve seen? And maybe related to that, is there a plan to secure non-dilutive capital for that no longer a near-term event, Chris, or, you’re just going to be opportunistic, recognizing that there might be some more clinical data coming from these targets from any of your peers?
Chris Anzalone: I’m sorry. I misunderstood the — what kind of capital and say that again?
Mayank Mamtani: Yes. I think I think you had plans for non-dilutive capital, at some point, which delayed the DUX4 program. So I’m just curious if you’re no longer, going to do anything strategically there for the muscle in the near-term?
Chris Anzalone: Yes. That ran its course for now. We are happy to run the DUX4 as well as DM1 clinical programs and then and which did not mean that we will never partner them, but we were exploring as you know, we are exploring potentially partnering DUX4, and it just made sense to us to stop those discussions and we’re moving ourselves for right now. James, do you want to?
James Hamilton: Sure. And then on the comparison with the other muscle targeting platforms that are out there. For DM1, we’ve looked at knockdown in the [siRNA] and have achieved — it’s a comparative — similar knockdown or similar duration of effect with what’s been published, for example, the transfer and targeted platforms. We use the peptide targeting the alpha-v beta-6. So it’s a different way of getting the sRNA into the cell. I think in terms of total drug dosage or dosages should be much lower compared to the transferring conjugates, which of course conjugating sRNA to a monoclonal antibody. And then I’d also anticipate that we would not expect to see some of the transferring related safety issues that have been out there. Of course, the time will tell and the data will tell us, but something we did not anticipate.
Operator: And our next question comes from Patrick Trucchio from H.C. Wainwright & Company.
Patrick Trucchio: Just regarding the 2025 targeting goals, can you give us a sense of from which platforms the 20 drug candidates are expected emerge from understanding several have been announced this year and if along with CNS pulmonary liver, adipose and muscle, additional tissues may be targeted with TRIM?
Chris Anzalone: I don’t have any guidance to tell you on additional cell types other than the fact that we will be in new cell types. We’ve said publicly that we think we can be into a new cell type every 18 to 24 months. I think that continues. Look, I expect by the year 2025, we will have new or additional candidates in every one of those verticals.
Patrick Trucchio: And then just a few follow-ups on the pulmonary compounds. Just first regarding Initial chronic tox results for the ARO-RAGE and ARO-MMP7. I’m wondering if you can tell us if or when further chronic tox data is expected and the level of confidence that data should continue to support advancement of those programs and when you might have similar data for ARO-MUC5AC in 2024? And just to follow-up on ARO-RAGE, if you can discuss the targeting mechanism of the subcu administration and advantages that would be expected for this route relative to the inhaled route.
