Christopher Anzalone: I think it’s substantially de-risking. This will be the first clinical data from our lung franchise. The structure of these candidates is really quite similar between MMP7, MUC5AC, RAGE, and future ones. They are simple conjugates, as you know. It’s simple RNAi, trigger that is chemically modified linked to targeting. So, to the extent that that it is well tolerated and can get into these pulmonary epithelial cells, I think it is telling as it relates to future candidates. These cells don’t care what the sequence of the RNAi trigger is. Once you get into this cell and get loaded into the risk complex, it can be any sequence. So, I think that it is a substantial de-risking event, again, to the extent that we do show clinically relevant knockdown in a well-tolerated fashion.
Joel Beatty: Great. That’s helpful. And then for AAT, are you going to discuss the powering assumptions or otherwise, just kind of speak at a high level as to what gives you confidence in the powering for the 160-patient registrational Phase 3 of this plan?
Javier San Martin: Yes. I can give you a high-level concept, but this is Takeda’s protocol design and is already in the public domain in clinicaltrial.gov. But essentially, if you look at what Takeda has been thinking is taking a conservative approach for the active treatment group, and not as conservative for the placebo group. But with that made the assumptions and the typical standard deviations that are expected and with that in mind to power calculation, they took, we think, good and conservative approach with regard to the duration, which is 106 weeks, so 2 years essentially and the sample size and the patient population they selected. So, it’s not just the assumption, but it’s the assumption in the context of sample size of 160 patients, a 2-year observation and all patients we have at least a F2 fibrosis stage patients with NAFLD.
So, when you look at the totality of the study design, we believe this study is well set to show the benefit in fibrosis levels. And then the details for Takeda will eventually come out with more details.
Joel Beatty: Okay. Thank you.
Operator: Thank you. Our next question comes from the line of Madhu Kumar of Goldman Sachs. Your line is open, Madhu.
Madhu Kumar: Great. Thanks for taking our questions. So I guess our first one relates to the idea in the lung of which cell type matters? And how do you think about in various pulmonary indications targeting the lung epileptic cells in the lung epithelium versus, say, other cell types that are just present in the lung, particularly immune cells in the lung. How do you kind of thread that needle? And then kind of secondly, along the question of threading the needle, how do you think the phenomenon of knockdown pretty powerful inflammatory modulars where want suppress the enough so that you reduce the kind of autoimmune functions, but you don’t suppress them so much that you reduce the viral protective solutions. How do you think about kind of that balance?
James Hamilton: Sure. So well, first of all, regarding the epithelial cells that are the cells that we are trying to target those are generally the cell types where we are looking for targets. So, we are looking for targets that are expressed by lung epithelial cells. And if there is a target that is related to a disease that we could knockdown, that’s the ideal situation. I think that’s where our system performs the best is in getting into those cell types and knocking down targets expressed in pulmonary epithelial cells or some of the derivatives, something like the basaloid cells in €“ that are more specific to an IPF patient population. Right now, we are not targeting any gene targets in macrophages or other immune cells in the one.
