Unidentified Analyst: Great. Thank you.
Operator: Thank you. Our next question comes from the line of Seamus Fernandez at Guggenheim Securities. Please go ahead. Your line is open.
Seamus Fernandez: Great. Thanks for the question. So and congrats on all the progress. Just one of the questions that we’re getting from investors is the importance and impact of GLP-1s specifically on the 2 things. Number one, the Flow trial is going to be presented at ACC and I think there’s some enthusiasm within the, I guess, cardiology and endocrinology community for those results and its impact of 1 milligram of Semaglutide, on the outcomes in patients with limitations in disease there. Just wanted to know what your thoughts are on the impact of GLP-1s on both weight loss and in a CKD patient population. And then second question is really on the baseline patient characteristics in Advance-HTN, I assume that you’ve got a pretty good feel for what the baseline patient characteristics are kind of shaping up to.
But just hoping that you’ll reveal the baseline patient characteristics prior to the publication? And maybe you could just share with us what you think are the most important measures that you’ll be looking at in exploratory analyses. Thanks.
Jon Congleton: Yes, Seamus, thanks for the question. The GLP-1s and the GLP-1, GIP and the GGGs are all obviously presenting really interesting data as it relates to weight loss. And then as it relates to the corollary benefits to comorbidities, we, like others are interested to see the full data set. I don’t think it’s overly surprising that if you see weight loss reduction, you see improvement in overall cardio renal metabolic health. I think that’s been known for a long time through diet, exercise and everything else. I think the — and I’ll maybe have Dave add at a point to this from what we’ve seen of some of the data presented, I think it was with tirzepatide in some of the prior data over the last 3 to 6 months, there still remains significant residual risk that needs to be addressed.
We think that addressing that broader cardiovascular and renal risk is going to be multifactorial. We know from frankly, decades of research that aldosterone is a significant driver of hypertension, of CKD, of heart failure and heart disease. And that’s what we think in ASI like lorundrostat becomes a really interesting component of that broader treatment to get as much of the residual risk reduce as possible. But Dave, do you have any additional thoughts you want to add to that?
David Rodman: Well, thanks, Jon. I’m going to add a little bit to that, and then I’ll answer your second part of your question following that. So we get this question a lot. It’s a really interesting question, right, that weight loss is going to be important in reducing risk. But what Jon referred to as this, the trial that he spoke about reported a 20% reduction in cardiovascular events, major cardiovascular events. But that really translated going from 8% incidents to 6.5%. So 8 per 100 versus 6.5 per hundred, that’s 20%. But in the real world, it’s 1.5%, and there’s still more than 6% of that rate to improve upon. Weight loss is only part of it. Jon mentioned, healthy lifestyle, exercise, all of these things, avoiding tobacco, alcohol.
These things all add together and just having a drug that allows you to lose weight is not by itself a replacement for that. And so what we’ll see over time is that people will look at this as a multifactorial treatment. The idea would be these lifestyle changes. But in reality, there’s a room for other medications to be combined. And that’s what we’re seeing in everything in cardiovascular, renal metabolic. 3 and 4 drugs together making the difference. We believe our drug is going to be an important component of that. We will, regardless of weight loss, have the potential to lower all cardiovascular risk. There’s a reason why aldosterone-targeted therapies are useful in things like heart failure. Our drug is a next-generation approach to that.
So I hope that just gives you some color for where we think it’s not an either/or and we’re going to be obviously very interested in discussing this with companies that are focused on GLP-1s going forward. Now your second question was characteristics. What I — I’m not going to go into that in deeply, but what I’ll tell you is this that we had a really nice demographic profile in the Target-HTN trial, 40% African-American, about 50-50 male, female, we had about 50% on 2 drugs, 50% on 3 drugs. So our aspiration is to be in that range. And so far, we see no reason to think we won’t be in that range using the inclusion/exclusion criteria we have.
Seamus Fernandez: Great. And then if I could ask one follow-up. As the reduction in the baseline eGFR from 45 down to 30, can you maybe just talk a little bit more about the importance of that inclusion criteria?
David Rodman: Sure, I can. So from a practical standpoint, the trial sites where we go to for trials like this are referral sites that have primary care doctors referring the patients to more specialized centers with chronic kidney disease. And so they tend to see enrichment with people with GFRs below 45. So Stage 3b. And so it will be a much more efficient to include those in 1 arm instead of 2 different arms of the trial. Now one might ask the question, though, since Part B also had a dose range discussion, are we — is it important for us to be looking at dose ranging. One of the advantages of making sure everybody is on an SGLT2 is SGLT2 lower your potassium. And that’s why that our 2 competitors in the space, let’s say, AstraZeneca and Boehringer Ingelheim, who are both committed to CKD trials now are looking at the combination.
And so we’ll be doing the same thing. So it’s just a practical thing. Those 2 practical changes. Everybody on an SGLT2 inhibitor in the trial and allowing the eGFRs down to 30 is going to be a much broader population, a much more efficient way to recruit the trial and will give us the same information we were looking for in terms of safety, efficacy of the combination.
