Hi. Good morning, everyone. Actually, good afternoon, and welcome to the Mineralys session. It's our pleasure to have with us CEO Jon Congleton and CFO Adam Levy with us today. We're talking about the hypertension landscape that saw its first new class in aldosterone synthase inhibitors just this year. I think the market has started to turn towards these ASIs. Mineralys is obviously awaiting their PDUFA for the second to market, and presumably, hopefully more broadly applicable in lorundrostat than the first.
Maybe you can give us a quick overview, Jon, and then we can launch into Q&A. Is Jon frozen? He's coming back. There we go.
Apologies, Annabel. I don't know.
You're leaving us in suspense.
Apologies. It was right as you were giving the nice introduction. All of a sudden, everything just went gone.
It's all right. We're human. We're not AI.
I didn't touch anything, I promise.
Maybe you can give us a quick overview, and then we can launch into some Q&A.
Yeah, happy to do it, and apologies about that.
No worries.
And really appreciate Stifel hosting this, Annabel, the invite and the chance to speak. Look, we're really excited about everything that's coming forward for the company. We've spent the last five years really thoughtfully developing lorundrostat. And what I mean by that is it's been 20 years since there's been any innovation in this space, so we're really developing a data set for those patients third line and later that could benefit from lorundrostat. Build a data set that informs not only physicians, but payers, speaks to the unique needs of these patients and their efforts to try to get to goal. We were excited about the NDA late last year. I would say the dialogue with the FDA headed into our PDUFA December 22nd this year has been normal course, so very excited about that.
Our commercial pre-launch plans are very much on track. We've got a very experienced commercial leadership team. We continue to have really good dialogues with thought leaders in this space, the payers that cover the vast majority of patients' lives in the United States, and are really doing everything you would expect a big pharma to basically be doing in preparation for launch. Our goal is on track for having our sales team in place by the time of the PDUFA date. Just very excited with the progress there. From a capital standpoint, we reported at the end of Q2, we have $661 million in capital available. We believe that's sufficient to get us through the launch and support the launch of lorundrostat.
Just overall, it's exciting times. We're getting close to the point of achieving what we really set out to achieve, and that is to get this drug into the hands of patients and make a meaningful difference in their lives.
Great. Thanks for the intro. Maybe like I mentioned earlier, obviously the entry of the first ASI just happened with Baxfendy. How would you say now that there's one on the market that the medical community is receiving this novel class? Is it viewed as a welcome addition, or are they still trying to really understand its place and the population?
Yeah, I would say the early signal is very encouraging. We see the same data that you all see as far as the number of RXs, the number of patients. But I think most critically, it's very supportive of the market research we've been conducting for five years that really articulates the unmet need. Over half of the patients treated can't get to goal. Clearly there's a need for alternatives, new innovative solutions, particularly ones that target aldosterone. The demand that we saw in the market research, I think, is playing out in real time with baxdrostat.
I think there were always questions about access over the last five years. Our market research clearly said these payers understand the clinical value of getting patients to goal, and that access would be available. I think this early days of the baxdrostat launch further support that access is going to be there for innovation. I think it's encouraging from our standpoint, but I wouldn't characterize it as surprising.
Okay. So just going into your own program, you've obviously conducted a very comprehensive phase III program, probably more so than for baxdrostat. As you're approaching the PDUFA date, what is your wish list for what you want to see in the label and what would be very differentiating for you?
Yeah. I'll go back to a point I made in my opening statements. There's not been true innovation for 20+ years in this space. As we thought about the development plan, we thought about the current practices ongoing and where the true unmet needs were. Even going back to our proof of concept, we've always looked at patients that were on at least two meds and could not get to goal because we thought at the time, continue to think, that that's where the physician demand is, and that's where we think accessible choice is from a payer standpoint. Our program is progressively built to these third-line or later patients, and the fact that they're not just hypertension patients. They have a lot of comorbidities. There's a lot of diversity within this population.
We wanted to build a data set that really spoke to the distinct patients that physicians see on a daily basis. As we think about our label, which is still pending negotiation, that'll begin to happen in a month or so here now. We think Launch-HTN is clearly going to be a core part of that label. We're very excited about the data that we saw over the 12-week period, a nearly 19 mm mercury absolute drop, an 11.6 mm mercury placebo-adjusted drop, and a really low incidence of hyperkalemia or potassium above 5.5. That study was a real-world study. It speaks to not only cardiologists and nephrologists, but primary care docs. I think that's going to be a core component of the label, the approval in Section 14.
We also, again, acknowledging there are different distinct and complex hypertension patients that our Advance-HTN trial that you're very familiar with, this is in confirmed hypertension, taking patients off their meds, optimizing their background before randomization, and only randomizing those confirmed patients that cannot get to goal. That's the kind of data set the cardiologists, nephrologists, specialists will really gravitate towards because those are the kind of patients they're dealing with that are as optimally treated as can be and still can't get to goal. In that case, we saw a 15 mm absolute drop and a nearly 8 mm placebo-adjusted. Even with high dose, our background saw pretty modest impact on potassium. Our EXPLORE programs. Explore-CKD was part of the label. Explore-OSA was completed after, so it was not part of the submission.
Explore -CKD, again, looks at patients with a lower eGFR that we think could get into the label as far as experience down to 30 eGFR, and again, saw a very meaningful reduction in blood pressure, which is the number one goal that physicians have in comorbid hypertension and CKD, is to get that hypertension to goal to slow the progression of CKD. But within that, we saw a nice impact on UACR. I would not anticipate the UACR data from Explore -CKD in the label, but the blood pressure we think is informative, and we put that into our label. That will be part of the discussions with the agency.
We believe that we have got a very robust and distinct population, both in comorbidities, in race. We had 28% black African-American in LAUNCH, 53% in ADVANCE, and a higher prevalence of women in the studies than typically in hypertension trials. We are very excited about the meaningful data set that could translate into a label to really inform a lot of different physicians.
Okay, great. And just while we are on the topic of a heterogeneous population, the OSA trial that you have, are you going to be able to leverage that in any way into a label, or is it just information to have?
I think it is going to be more scientific communication. We know there is a really distinct overlap between obesity, OSA, and resistant hypertension, and that kind of trifecta has really poor cardiovascular outcomes. In Explore -OSA, we had that population there. I think their BMI was on average 37. Their AHI was 48 relative to 30 being called severe, so very severely affected. And even in that really challenging population, lorundrostat showed that benefit on blood pressure. But I would not anticipate it being part of the label, but it will certainly be part of the scientific communications and just, again, speaking to these complex patients that physicians are dealing with.
Okay, great. Just while we're talking about all these different studies, are you expecting any post-marketing requirements, or is there anything that you're planning right now that's going to further help you stand apart?
Yeah, I think it's too early to opine on what any post-marketing commitments will be. That'll be kind of timed the same time that we do the label discussions. That said, I think we've achieved what the FDA always wants. They want to be able to have a drug and subsequent label that speaks to all the different types of patients that physicians could encounter. Now, setting aside the post-marketing commitments, we're continuing to evaluate how we continue to build the profile of lorundrostat, and there are clinical studies that are under consideration right now. I'm not at liberty to discuss specifically where they're at, but in due course, we look to bring those to the market and announce those trials.
Okay, got it. Let's move maybe to what you've already been presenting at the several conferences that you've been. What's been the reception to the LAUNCH data that's captured the broad population with the different treatment backgrounds? Is there anything that stood out for lorundrostat, we need a nickname for that one, for KOL feedback, and maybe what they honed in on, just as you're approaching that broader audience?
Yeah, I think there are a lot of things. This is the largest trial done with an ASI in hypertension. We had 1,082 subjects. As I noted before, we have 20% Black or African-American and a higher-than-normal representation of females. That really enables us to do a lot of post-hoc deep dive analysis. We had recently, the European Society of Hypertension, an analysis of these patients that met the blood pressure criteria, but also had an elevated albumin. That wasn't part of the inclusion criteria, but we were able to go through their baseline measurements and look at those that had elevated albuminuria, and we saw over the 12-week period, whether they were or were not high albumin, we saw a similar reduction in BP. But for those that were high, we saw a 52% reduction in their albuminuria.
That's in line and supports what we saw on Explore-CKD just in four weeks with a 31%. That's a really interesting piece of information to provide to such as nephrologists, high-volume PCPs that are dealing with hypertension and CKD together. They're going to get both benefits. This summer, there was a subset analysis or an analysis looking at impact on heart failure biomarkers via proteomics, saw a significant benefit on NT-proBNP, which is a clear marker for benefit in heart failure patients. We're progressively going through this really robust trial that has great data in really articulating, again, information that's informative for some of these distinct patients, and that's on top of what we have already with advanced HTN and other trials.
Okay, great. You touched on this before, but one of the, I guess, concerns people have had is access and reimbursement. Can you talk about market positioning? Because AstraZeneca seems to be aiming for, I guess, a third-line population. You've positioned yourself very distinctly as fourth line being an optimal entry point. So what have you observed in the market that might change how you might approach the market, or do you intend to change how you approach the market based on the experience that you're seeing AstraZeneca have in terms of access?
Yeah, I think maybe I'd clarify. You can look at our clinical trials, and again, going back to our proof of concept. We've always viewed third line as part of the opportunity data set. It's why the proof of concept, our pivotal studies, we look at that third line later because we think there's clearly a benefit, and we see equivalent data, whether patients are on two meds or three or more meds. They're getting the same really robust, meaningful reduction in systolic BP safely with lorundrostat.
I think what we've said in the past is that fourth line is likely to be the early entry point just from an access standpoint, that there's going to be more access at that fourth line setting. It doesn't mean that we're not going to position this drug. It doesn't mean that we're not going to argue that third line, ultimately, to try to let these patients stop cycling through drugs and get to goal very quickly, is a part of the market space. We're seeing that really play out in real time right now, Annabel. If you look at the data on baxdrostat's first few months of launch, it's about an 80/20 split between fourth and third line. The third line will be there for lorundrostat.
We've got the data to support that. I just think there's a pragmatic part with payers that says the fourth line is the quicker, easier entry point, and then that will grow into third line over time.
What is that path to third line, given that demand may be just as high in that segment, and you're just as suited for that segment? Is it just a matter of time, or do you have to present more data? What do you have to do to convince payers to facilitate that for you?
Yeah, I think the data exists there. Throughout our pivotal study, the label will be indiscriminate on number of background. It'll just say on top of background meds. It won't say a specific number. Some of that's going to be demand, and that demand is going to be partially built by physician experience. I think the majority of physician experience in the first 12 months is going to be fourth line, but progressively, as they see responders, they are going to want to have that experience with somebody that is in that third-line setting.
Part of the third line will just be through time experience, but I think it is going to be a pretty short ramp to that. Like I said, we are already seeing about a fifth of the baxdrostat scripts are used at third line, and as we enter the market and convey the message that, A, aldosterone matters, B, ASIs are the way to go, and then the differential stories that we have around lorundrostat, I think you will continue to see that demand grow, and that demand is inevitably what drives the access.
Do you have any sense right now in the market, when physicians approach these resistant patients, are they making just a clinical diagnosis of you must have hyperaldosteronism, or do they have to jump through any kind of hoops to identify the patient very precisely for the payers? What are you hearing?
Yeah, it is more just the trial. The market has been conditioned to not just switch back and forth within drugs, but to add drugs, when somebody's resistant, so on three meds and still not at goal, there's not a requirement for a marker because there's just not a good marker right now. I think there is an appreciation from the literature that the further you get from uncontrolled to resistant, the prevalence of aldosterone as maybe the driving force is appreciated more and more.
And I think, this we've talked to in the past, we've efforted to try to target lorundrostat based on renin. This drug works high or low renin. Obesity, the drug seems to work whether you have BMI above 30 or below. And I think our clinical program ultimately highlighted everybody's responding to lorundrostat, which means that a lot of these people failing to get to goal on two meds, aldosterone is what's driving their condition. And so I think it's less about a marker, and it's more about trial, which is going to be driven by their enthusiasm and excitement about a new innovation like lorundrostat.
Okay, great. And so just when you think about, I know you're not dealing with many step-throughs by the time you get to third line or fourth, their third or fourth drug, but is it going to be something that's somewhat easily accessible? With electronic medical records, they have a full record, so it's not really a step through kind of dynamic. It's just an automatic population that's visible and identifiable to you?
Yeah. The market research we have done and the feedback we are getting from our national account directors that have been speaking to the payers since Q1 of this year is pretty consistent. It is going to be a step at it, so evidence that patients are failing two or three meds, and it is a basket kind of approach. In other words, it is not a specific type or class of drugs. It is just failing two or three meds. It is a look back in their Electronic Medical Record of 6- 12 months, which to me just creates this bolus of almost pre-approved patients because everybody's data is in EMR.
We know there are at least 10 million patients that are resistant, 10 million that are uncontrolled, and now it is just a matter of building that enthusiasm and excitement from the physicians, having them prescribe, and then the access is a fairly straightforward utilization management pathway.
Okay, got it. Maybe you can talk a little bit about competitive dynamics. What are the things that are in play in the PBM market that might make the launch of a second drug so close to a first? Can it help you? Does it hurt you? Is your launch more dependent on the clinical value proposition than just contracting and rebating? How should we think about these dynamics?
I think it all plays together. To your first part, is it a help or hurt? I think having baxdrostat in the market now, having our managed care team in place in Q1 is all opening up the payers to a space they have not had to think about for 20 years because of the lack of innovation. I think that opens it up from that standpoint. The latter part of your question, remind me again, Annabel.
When you are approaching these payers, are you having to push the clinical.
No. Yeah.
Are you able to talk about the clinical value proposition rather than negotiating a rebate or a contracting or just the annoying aspect of it?
I think it is very much the clinical value prop. We have seen that in the market research. We are seeing that in our dialogues now. There is a clear appreciation of the impact of somebody on two or particularly three meds and still not a goal, and the risk and the correlation to poor outcomes. There is an appreciation for that. I think there continues to be an appreciation that spironolactone, which is the leading MRA, is not the answer, that there are a lot of challenges with patients going on the drug. They do not want to be on the drug.
I think the clinical value proposition is a big piece, and then certainly contracting will be a component of that. That really boils down to utilization management, and if it is a step at it, there will be a certain level of contract. If they want to PA through some specific other drug, then that just becomes contract negotiations.
Okay, got it. I guess in the past, and I know we're not on this pricing conversation yet, but we do have one benchmark, at least in Baxfendy, and that's about $900, which seems to be a little bit higher than what we've heard in the past from you of trying to stay out of the specialty tier. What are your thoughts around that, and are you still trying to keep it below that threshold so that you don't fall into that category?
Yeah. I think to your point, it's too early for us to talk specifically about our price. We'll do that closer to the time we launch. But I think the price that AZ came out with was reasoned based on our market research. What gets you into the specialty tier is a net price above a certain level that is frankly above the list price they have right now. I think specialty tier is not going to be a constraint as it relates to baxdrostat's price. I think it fits within the window that we looked at from a market research standpoint relative to the clinical value being provided by this new class of drugs, and it's informative as we think about our price going forward.
Okay, got it. Maybe then we can talk about the infrastructure that you're building for the launch. I do not know how big it is going to be, but obviously it is to tap into not just the specialty, but the primary care could be important for you. Maybe you can talk about that, your primary target audience, and the education you need around that.
Yeah. We are staying really consistent with what we have guided in the past, that when you look at the top prescribers for third line or later, it is about 50,000 doctors that control about 40%-50% of that prescribing, and then they influence the other 50%-60%. That is how we are thinking about the market framing. That is how we are thinking about our sales force, a team sufficient to address the needs of those roughly 45,000 docs. We have been progressively building going back into 2025, the commercial infrastructure that really kind of fits into three categories, if you will.
Market access and making sure that we have got the right team in front of payers right now, patient support, so the hub to really enable and ease the burden of prescribing an innovative therapy for physicians and patients and field-based reimbursement managers. The marketing team, we have got really experienced marketing teams that are working on the campaign, the communication, the messaging around that.
Then lastly, the sales team that, as I said, we plan on having in place before the PDUFA. I have had a chance to meet many of our RSDs and some of our new incoming territory managers. Really excited about the energy, the focus. There is a distinct phenotype of an individual that comes into a biotech like this and really wants to make a significant value and impression on the patients that we are trying to serve.
Did you mention the size of the sales force yet?
We haven't yet. That's something that we've kept a little bit close to the vest.
I was wondering why I couldn't remember it.
Yeah. Nope. We've never said it. That's why you can't remember it.
Oh, okay. Great. Maybe you can talk about your educational effort. Obviously, aldosterone seems to be understood by the community, but in practice, going back, how do they make that determination? I think we know that sometimes there's other factors that are a source of hypertension that's not necessarily aldosterone, whether it's elevated cortisol or anything else. You're going to end up sticking with that rule out type of diagnosis, or is there anything else that they can lean on?
Yeah. You're exactly right. Hypertension is multifactorial, right? You need to hit a lot of different vectors. I think that's why we positioned lorundrostat for third line or later. With ACEs and ARBs, you can really affect vascular constriction, diuretic, fluids, volume. The ASIs, I think, are obviously ideally suited for those aldosterone patients, and we know there's a high prevalence. I think over the last five years I've been involved with Mineralys, we're seeing the understanding and appreciation by the medical community, independent of pharma doing education, really grow and appreciate that they've been missing something. AstraZeneca, as well as the work we've been doing progressively from an education standpoint, I think really brings that awareness, that appreciation for that extra lever.
Again, there's no marker, so I don't think there's going to be a requirement for a marker, but I think it's just an appreciation when you get to latter stages of uncontrolled and resistant hypertension, there is a high likelihood that aldosterone is that key vector that's not been addressed, that the ASIs can. I think that's the opportunity, is fundamentally for us to reinforce the role of aldosterone, the opportunity with an ASI, and then the value of lorundrostat. That differentiation is less about us to baxdrostat and more the ASIs to what's currently used third and fourth line.
I know that you said that you're going to be pushing for guidelines, and you have good contacts into the Cleveland Clinic and all the KOLs there. Have you seen any movement from AstraZeneca's sides to try to push those guidelines along?
I can't speak for what AZ is doing. I know that we're having contact with the various constituents. They have made a commitment that they want to be very rapid to respond to new innovations. Rather than just every five years, really provide their constituents guidance when new innovations like the ASIs come forward. We've been having dialogues with those groups. I think we've got an outstanding data set, not the least of which Advance-HTN to really make that argument. The timing of it is still not clear, but I would anticipate sometime early in next year as both of these drugs are available.
Okay, great. I'm just going to end this last with the most sensitive question about strategics. I imagine the stage is there, the interest from strategic might hinge on how you launch. Would you characterize that as high right now, or are they really waiting to see how this market develops?
We continue to be interested in partnerships if they can drive the value of lorundrostat. We've not really commented on the color and texture of those dialogues. But I think it's fair to say there is a clear return to cardiorenal metabolic by big pharma. I think there's an appreciation that these larger markets represent significant value. I think the clinical profile for lorundrostat is well appreciated and understood, as well as that market opportunity. We're focused on generating significant value, whether it's on our own or through a partnership.
Great. I guess I'll have to leave it at that because we're out of time.
Yeah. Apologies on the snafu up front, but really appreciate the time.
No worries.
Appreciate Stifel doing this conference.
All right. Thank you so much.
You bet. Thanks, Annabel.
Thanks.