RJ Tesi: Yeah. So I think that’s an excellent question. Let me give you the derisk, and then I will give you an educated guess on the — on whether a partner’s going to have to this specific issues. So what happened when they used the original non-selected TNF inhibitors in mouse models, in mouse models to treat DMD. There — long term, there was a decrease in cardiac output in the mice. Now remember, patients and animals with DMD actually see a decrease in cardiac function over time. It’s part of the muscular effects of the dystrophin abnormalities. But actually the TNF inhibitors made it worse. So that basically they just stopped. And what I found pretty interesting from the literature if they stopped and this literature is kind of old, let’s call it, early 2000s.
They stopped because they became contented with the results they were getting with corticosteroids, right? So the reason we’re quite confident that this is not going to be an issue because of selective nature of soluble TNF. We have one published paper that shows in a model of exercise induced atrial hypertrophy in mice that actually XPro decreases hypertrophy and decreases the fibrosis. Fibrosis as part of the pathology of DMD. And we have unpublished data in another cardiac model that shows that XPro, you should see that data probably midyear, that XPro has benefit on cardiac disease. So in fact, we have pretty good evidence in animal studies that XPro is actually beneficial to the heart. And we are soon completing a six month DMD study in the mice where the primary endpoint is cardiac output.
So at that point, I’m pretty confident we’ll completely derisk it. Now does this mean that when someone takes this and drops it into kids, are they going to have to somehow derisk it beyond the standard clinical trial perspective. I don’t think so, but because of the benefits of the drugs that are beyond just anti-inflammatory, but I would rather wait until we ask someone, hopefully a partner actually talks to the FDA. But the bottom line is, our data in cardiac with XPro is quite positive. We will have really unequivocal data based on the animal models quite soon, but everything is pointing to that should not be a problem and the fact that XPro actually improves cardiac function in most disease models.
Tom Shrader: Got it. Thank you. And maybe probably a CJ question. I understand you want to get XPro approved as a standalone therapeutic in Alzheimer’s disease. But it’s increasingly clear that ARIA is neuroinflammatory process associated with the A beta antibodies. Have you thought about trying to get a signal to reduce ARIA in an A beta model or in a small trial? Is that a reasonable way to think about getting a quick signal that I think a lot of people would be interested in?
CJ Barnum: I think we’ve said previously that’s something we think — we agree with you. And we think about all sorts of things, not just ARIA, but across the board. And we think XPro is going to be an excellent drug for combination therapy in general. So I guess the answer to your question is yes, we thought about it quite a bit, we thought about a lot of things and hopefully in the near future as we get going in our programs here we can start entertaining them a little more.
