Morning. Welcome to day one of the Jefferies Healthcare Conference. My name is Dennis Ding, Biotech Analyst here at Jefferies. I have the pleasure of having CEO, Jon Congleton, and also CFO, Adam Levy, here with us from Mineralys Therapeutics, and I'm going to turn it over to you, Adam, to give a brief overview around what happened this morning, and then the rest of the presentation.
Thank you, Dennis. I'll go through a recap of the news from this morning and then turn it over to Jon to talk about the business. We'll be making some forward-looking statements today. There were three transactions that we announced this morning. We had the opportunity to repurchase our royalties from Tanabe. We paid $200 million upfront, and there's $100 million in additional potential commercial milestones. The royalties, if people remember, were mid-single digits escalating up to 10%. Pro forma for the purchase, we'll have $100 million in new commercial milestones and $165 million from the existing commercial milestones, of which $10 million were related to a potential second indication, and the royalties are completely extinguished.
In parallel with that, we raised $150 million in equity, and we secured a $500 million debt facility with Pharmakon, of which $100 million was funded at closing, and we have an additional $400 million available to us in certain tranches. The next available tranche will be at FDA approval for $150 million. There will be $250 million in committed capital that we have the ability to draw at our discretion over the next several years, triggered by the achievement of certain sales milestones. The interest rate is floating at SOFR + 5.5%. The credit facility can be prepaid at any time, at our discretion, subject to prepayment fees. With that, I will turn it over to Jon.
Thanks, Adam. Obviously very excited about the news. I'll add one point to what Adam made. Based on the cash equivalents from the financing and what we had on hand, plus the debt facility with all tranches pulled in with our current plan, we're fully funded for the commercialization. Obviously very excited about that, enabling what we've been focused on. Here we go. Targeted aldosterone as it relates to cardiorenal and metabolic disorders. lorundrostat, for those of you that don't know the story, is a highly selective aldosterone synthase inhibitor. That's relevant because, in the U.S. and globally, we think that about 30% of all uncontrolled and resistant hypertension patients have some form of dysregulated or elevated aldosterone.
Over the last five years, we have demonstrated that lorundrostat once daily provides 24-hour control of that blood pressure, extends benefit to subjects with CKD, which I'll talk about in a moment, and has shown a benefit in reducing blood pressure in patients that are both obese and have OSA. That reduction in BP, we think, is one of the biggest drivers of potential CV risk benefit. There are 20 million patients in the United States, I'll break that down in a moment, with uncontrolled and resistant hypertension, and there's significant overlap of comorbidities such as CKD and OSA, which we think will create opportunities for lorundrostat. We filed the NDA late last year. We notified the market in March that the file was accepted and we had received a PDUFA date of December 22nd, 2026.
The role of aldosterone has been fairly well established as far as the genomic effects. This is what controls fluid volume in the system, electrolyte shift, sodium and potassium. What I think is growing to be appreciated are the non-genomic effects of aldosterone and how it can drive fibrosis, oxidative stress, and inflammation. Aldosterone in a dysregulated state can be a driver of not only uncontrolled and resistant hypertension, but also chronic kidney disease, heart failure, and vascular inflammation. Why this is relevant is we have demonstrated at this point clearly that lorundrostat has a significant benefit on uncontrolled and resistant hypertension. We've shown signals of benefit as it relates to CKD. Given the fact that aldosterone sits at the nexus of all of these cardiorenal metabolic disorders, we believe that lorundrostat has the utility to provide benefit across a host of disease indications.
For those of you that haven't met me, I started my career in 1986 selling Cardizem in the hypertension space. At that time, hypertension, uncontrolled hypertension, was one of the leading drivers of cardiorenal disease, mortality, loss of quality of life. Unfortunately, 40 years later, that has not changed. Uncontrolled and resistant hypertension continue to be one of the leading global modifiable risk factors that leads to morbidity and mortality. In fact, there's been significant evidence that demonstrates just a 10 mm mercury reduction in systolic BP can lead to significant reduction in CV risk, in stroke, in heart failure, to the tune of anywhere from 13%-28%.
As you'll see with lorundrostat, we're looking at absolute changes in the neighborhood of 15-19 mm of mercury, and thus, we think will translate significantly into benefit for patients. To kind of recap that, if you think about the opportunity for lorundrostat, anywhere from 20%-40% of patients who are treated fail to get to their prescribed goal. Part of that challenge is the goal is progressively coming down. 30, 40 years ago, it was 140 mm of mercury systolic. Now it's 130, and in some cases with comorbidities, it's 120 mm of mercury. That is part of the challenge in patients actually getting to goal because we haven't had true innovation in this space, and yet the goal continues to come down. There's needs for new alternatives to help patients achieve those goals.
Aldosterone, we do believe, is a culprit, and there's different drivers of that. We've known for, I think, decades that ACE inhibitors and ARBs can get patients to goal, but about 30%-40% of them after 6-12 months have what's called aldosterone breakthrough. They begin to lose control of their blood pressure with the ACE and the ARB because aldosterone breaks through that inhibition further upstream in the RAS system. The other element of research that has become evident is the linkage between visceral adiposity and aldosterone production. We're all very much aware of the obesity epidemic. What's, I think, less appreciated is the hidden epidemic of dysregulated aldosterone that we believe, based on literature, is linked to the obesity epidemic. Let's talk a little bit about lorundrostat clinical efficacy and safety.
We've spent the last five years executing five studies really demonstrating the best-in-class potential of this molecule. Let's start with lorundrostat itself. There are two elements that we believe are critical for an aldosterone synthase inhibitor to provide once-daily efficacy and safety appropriately. One is the half-life. lorundrostat has a half-life of 10- 12 hours. In our proof of concept trial, we looked at both BID and QD and found that once daily dosing provides the proper balance of efficacy and safety, provides 24-hour control. It matches very nicely the diurnal pattern of aldosterone, which tends to begin to surge in the pre-wake hours, peak late morning, taper in the afternoon. Selectivity is another key element. There were first-generation aldosterone synthase inhibitors that lacked selectivity for aldosterone relative to cortisol and inhibited both of those hormones.
This is obviously something you don't want to achieve with an aldosterone synthase inhibitor. With lorundrostat, relative to baxdrostat and osilodrostat, we see best-in-class selectivity by about a factor of two to one or four to one, with a 374 to 1 ratio of selectivity. On the basis of that, we moved into a very robust clinical program. What you're seeing here are four studies that I think speak very eloquently to the distinct populations of uncontrolled and resistant hypertension. The table on the left is LAUNCH-HTN. This is a real-world study. It's the largest trial ever done with an ASI in hypertension. We saw very robust, meaningful reductions as early as six weeks of about 16 mm, almost 17 mm of mercury, 9.1 placebo-adjusted. At week 12, we saw a 19 mm absolute reduction, 11.6 mm of mercury placebo-adjusted.
I think it's important to point out that within this study, 44% of these patients got to goal versus 24% at week six. This is a critical point. If you think back to the number of patients that are failing to get to their goal, the benefits of seeing these kind of reductions, this will translate into significant cardiorenal risk reduction for these patients. Additionally, within this trial, there were about 28% of this population that were Black or African American. We know that's a high-risk population, and we saw a similar benefit across all racial and ethnic groups. ADVANCE-HTN is a study that we did in partnership with the Cleveland Clinic. This is likely the most rigorous hypertension study ever completed. We did a three-week run-in period where we took patients off their existing background treatments, put them on an optimized AHA-prescribed treatment regimen.
We used smartphone technology to confirm adherence on a daily basis. Only subjects after three weeks that had failed to achieve their goal were randomized. Over that 12-week period, we saw a 15.4 mm mercury absolute reduction and a 7.9 mm mercury placebo-adjusted reduction. In this study, again, we used 24-hour ambulatory to confirm the 24-hour control for this population. 41% of the patients achieved goal in this rigorous confirmed population versus 18% on placebo at week four. I'm very proud of, again, how we ensured that we had diverse representation within this trial. 53% of the study participants were Black or African American in this study. Again, providing evidence for prescribers in a very difficult-to-control and high-risk population. In support of these two pivotal trials, we also conducted two proof of concept studies. We call these the EXPLORE programs.
EXPLORE-CKD looked at subjects with an eGFR down to 30. The prior two studies went down to an eGFR of 45. In this study population crossover design, we saw about a 7.5 mm mercury placebo-adjusted reduction just at four weeks. We also saw a concurrent reduction of 31% in UACR, which is a surrogate or a marker for renal protection. Feel very confident that for nephrologists specifically who are treating hypertensive nephropathy, they're not only going to be able to get control of the patient's blood pressure, but also see a benefit on their kidney function. EXPLORE-OSA was a study where we were exploring the benefit of reducing aldosterone with lorundrostat, to see if there's a benefit on the apnea-hypopnea index, as well as looking at blood pressure reduction. We did not see a demonstrated benefit on AHI in this population. It was a very severe population.
I think the average BMI was 37- 38. The average AHI was 48, and severe cutoff is 30. This was a very affected population. Happy to see, yet again, and as anticipated, a robust reduction and clinically meaningful reduction in systolic BP at just four weeks. Again, frankly, this is the biggest driver of cardiovascular risk for these patients. I say that because we know with CPAP you can reduce AHI, but you do not see an alteration in that patient's cardiovascular risk profile. From a safety standpoint, the ASIs are kind of a prototypical RAS inhibitor pathway, you want to look at electrolytes, you want to look at things like change in eGFR. Very pleased with what we've seen to date with the potassium profile specifically. In the largest trial, LAUNCH-HTN, we only saw 0.6% of the patients have a confirmed hyperkalemia event.
In ADVANCE-HTN, it was a little bit higher, 2.1%, but again, very low. This is an important finding for prescribers, specifically cardiologists. These patients were on nearly the highest dose of olmesartan, a very potent ARB. In ADVANCE-HTN with lorundrostat, we've demonstrated that you can achieve dual RAS inhibition with two different mechanisms and do so safely. EXPLORE-CKD, again, we went to a lower eGFR. We used a 25-mg dose once daily. We know that these patients are renally impaired. They can have more difficulty in controlling their electrolytes, and again, saw a very modest change in hyperkalemia of 5%. Then in EXPLORE-OSA, we saw no patients with a potassium noted above 6.0 mml/L . Very well tolerated.
To give you some context for these numbers, I think it's important to look at the predominant class of drugs that are used right now in treating hypertension, and that is ACE inhibitors and ARBs. About 85% of all treated patients are on one or the other. These affect the RAS pathway further upstream. This is data from a meta-analysis, and what you would typically see in large populations is hyperkalemia rates in the 1%-3% with ACEs and ARBs. Again, looking at both our real-world study, LAUNCH, and in our very confirmed, rigorously ran trial, ADVANCE, right within the goalposts of what's currently being prescribed. We feel very confident that the efficacy is well-matched with the safety with lorundrostat that will help with adoption for physicians.
I will add from a workflow standpoint, I think that's the beauty of the aldosterone synthase inhibitors, they fit very well into the current practice of treating hypertension. What I mean by that is if a physician chooses to use lorundrostat, they'll get a blood panel. They'll check potassium, sodium. They'll get an eGFR measurement as well as blood pressure. Start the patient on that, then in two to four weeks bring them back, check their blood pressure, then within that short period of time, you'll see the shift in electrolytes they can comfortably modify and periodically check on those patients going forward, presuming all are within safe zones. That brings me to where our pipeline is right now. We've completed ADVANCE-HTN, LAUNCH-HTN. TARGET-HTN was our proof of concept study that I referred to earlier.
Both ADVANCE and LAUNCH were key components of our NDA that we submitted last year, as well as the EXPLORE-CKD. The EXPLORE-OSA study was completed post the submission of the NDA, so it was not included. Some of the safety data may be in the 120-day update. We do have our TRANSFORM-HTN study continuing to progress. It's our open label extension trial. That's an omnibus open label extension that includes patients from ADVANCE, LAUNCH, and EXPLORE-CKD. That's an important data set. We anticipate publishing information from that omnibus open label extension later this year or into next year. So there's a significant commercial opportunity here. Again, as I said, I started my career in this space and saw the transformation of cardiorenal conditions because of calcium channel blockers, selective beta blockers, ACE inhibitors, and eventually ARBs.
Unfortunately, we have not seen innovation in this space for quite some time. Yes, it's a completely genericized market. I have the gray here to show that I saw the brands when they launched, but they're all generic now. The problem is we have not solved this problem. Whether it's the 20%, 40% that we try to triangulate on for those patients on two or more meds that are not a goal, fundamentally, the prescriber base feels they're missing something. I think fundamentally what it is is an effective, safe, and easy to tolerate aldosterone-directed treatment. The only thing at physicians' disposal right now is spironolactone, a mineralocorticoid receptor antagonist that was launched in 1959, has significant off-target effects, and is limited by its safety profile if you push the dose. From my standpoint, this market opportunity is immense. It's needed.
Clearly, we will see a benefit to patients on their cardiorenal risk profiles as we progress. In the U.S. alone, there are 120 million patients with hypertension. About 60 million of them are treated. About half, roughly, are at goal. The other half that are not goal, about 20 million, are on two or more meds. We believe that's the addressable market. We believe that's where the opportunity is. It's not just a belief, it's what we've seen in the market data that we've done. We've spoken to physicians, whether they're primary care, cardiology, nephrology, endocrinology. We've obviously had a lot of interactions with payers. Payers are open to creating access for innovation within that third-line or later space. They know the cost. They know the implications of uncontrolled blood pressure. That 20 million is an ideal target for us, and there's significant overlap.
These are patients that have had uncontrolled and resistant hypertension, potentially for decades. They're now beginning to see the implications of that, whether that's CKD, whether it's OSA, whether it's cardiovascular implications. That's why we continue to use our EXPLORE programs to not only show the benefit on controlling blood pressure, but also on those related comorbidities. This is a little bit of a complicated slide, but I think it gives a really good picture of the market dynamics, or what's actually going on in the treatment of hypertension right now. This is an IQVIA data set. It's from 2024. It is the total movement of scripts for that year for the ICD-10 code of treating hypertension. Said another way, there are 65 million patients that either got a new or an existing treatment or prescription filled in 2024. 26% of those were new to line.
That means a patient, either it was the first time, so a first-line treatment, or it was the third treatment added, or fourth, and so on. If we go to that middle bar, about 52% of the patients were either getting, for the first time, a third-line treatment or a fourth-line or later treatment. I will remind you, in 2024, we had no innovation in this space, and yet you see a highly activated market and a highly dissatisfied market. Physicians have not given up. They've not become nihilistic. Neither have patients. They're continuing to try new things, and it fits the empiric approach that has been the path for hypertension for 40 years. Adding new agents, trying to incrementally move the patient closer to their goal.
For me, as I look at these 65 million patients, fully a quarter of those getting new to line, half of those being third line or later, that's about 8.8 million patients just in 2024 that were trying new but old treatments. The introduction of a truly innovative approach such as lorundrostat, I think, has a grand opportunity to really tap into that churn that exists within this market and hopefully pull some of these patients out of that continued trial pathway and get to their goal effectively. The intent and interest is there. We did this Sermo survey last spring after we had the LAUNCH-HTN and ADVANCE-HTN data, we just asked, "What is your intent to prescribe?" Show them the profile of lorundrostat, 95% of the physicians said likely to very likely to try lorundrostat.
Again, I think that speaks to their interest in having innovation, having new approaches to treating these patients. For the EXPLORE-CKD, we did the same thing. 75% intent to prescribe. When the BaxHTN data came out, we basically put the BaxHTN data blinded as to what the drug was. We put our LAUNCH-HTN data blinded to what it was, put it in front of physicians, and did a forced selection. There was no middle ground. You couldn't say, "I like them both." Said, "Pick one." There was two-to-one preference for lorundrostat. I think that's based on the efficacy and safety that we see within LAUNCH-HTN in those real-world uncontrolled and resistant hypertension patients. As we think about the market opportunity and how you could enter this space, fourth line is the beachhead, low-hanging fruit, whatever you want to call it.
I didn't share it in the IQVIA data because it gets too complicated, but if you look at the fourth line and what's actually prescribed, there is no mechanism that has more than about 12% share. I envision the Wheel of Fortune wheel that just spins, the docs are just spinning and just picking something, trying something. It's not directed. It's not targeting what fundamentally these patients on three or more meds probably are dealing with, and that's dysregulated aldosterone. That fourth line is an optimized space, again, based on the payer research that we've done with a non-specialty tier price point. We believe access is going to be completely enabled for these patients. Again, they are high cost to the healthcare system, and thus, innovation is going to be accepted in this space. We've built a data set that speaks very exquisitely to this population.
ADVANCE-HTN is the confirmed uncontrolled and resistant hypertension population. This is the group that cardiologists are dealing with. They are the ones that most likely are optimizing treatment of existing antihypertensives, and yet still cannot get patients to goal. The hypertensive nephropathy for those patients with below one gram of protein as a marker of their nephropathy. EXPLORE-CKD will be very informative for those physicians. The uncontrolled patients that are complicated by OSA and obesity. Clearly, a lot of our studies cover that because I think on average, our BMI is above 30, but EXPLORE-OSA spoke very eloquently to those patients that have comorbid OSA and the kind of benefit you could expect on blood pressure control. Now, that does not mean that we're not going to effort to third line utilization as well.
I think those patients that are on two meds, not a goal, with complications and comorbidities, we'll be building the use case for, but I think this is very much a market where you build from the fourth line and then move earlier into treatment, and tap into what is collectively about 20 million subjects overall. Bringing that to conclusion, this is our financial summary as of Q1. Obviously, we'll be updating this with our Q2, based on the announcement today. As of Q1, we had $646 million in cash and 83 million shares of common stock outstanding.
I am grateful and benefit from working with some outstanding leaders that have helped us move lorundrostat from a phase I asset about five years ago to an asset under review that holds the potential to address the needs of 20 million subjects, hypertension patients here in the U.S. We're obviously also looking at pathways to get lorundrostat to subjects outside of the U.S. as well. Certainly am pleased with how we've advanced the program to date and on the cusp of introducing what we believe is a drug that can create more better days for patients going forward. I thank you for your time and your attention.
Perfect. Thank you so much, Jon.