Mineralys at BofA Securities 2025: Lorundrostat’s Hypertension Promise

On Wednesday, 14 May 2025, Mineralys Therapeutics (NASDAQ:MLYS) participated in the BofA Securities 2025 Healthcare Conference, presenting promising developments in its aldosterone synthase inhibitor, lorundrostat. The company highlighted positive trial results and strategic plans, while acknowledging the challenges in hypertension treatment.

Key Takeaways

• Mineralys announced positive results from the LAUNCH-HTN and ADVANCE-HTN studies, showing significant blood pressure reductions.
• The company is advancing its pipeline with the EXPLORER-CKD data expected soon and an OSA study initiated in early 2025.
• A pre-NDA meeting with the FDA is planned for the fourth quarter.
• Eric Warren has been appointed as Chief Commercial Officer to enhance strategic partnerships.
• Mineralys maintains a strong financial position with a cash balance of $343 million.

Financial Results

• Mineralys reported a cash balance of $343 million as of their Q1 reporting, indicating robust financial health to support ongoing and future projects.

Operational Updates

• Pipeline Progress:

- LAUNCH-HTN and ADVANCE-HTN pivotal studies completed with positive outcomes.

- EXPLORER-CKD data readout expected later this quarter.

- Initiated OSA study in Q1 2025.

- Pre-NDA meeting with the FDA planned for Q4.

• Commercial Team Expansion:

- Eric Warren joined as Chief Commercial Officer to drive strategic partnerships and commercial opportunities.

Future Outlook

• Mineralys aims to position lorundrostat as a key treatment for hypertension, addressing the unmet needs of approximately 20 million at-risk patients.
• The company emphasizes the potential of lorundrostat to transform the treatment landscape for hypertension and cardiorenal metabolic conditions.

Q&A Highlights

• No Q&A section was included in the conference call.

Readers are encouraged to refer to the full transcript for a detailed account of the conference call.

Full transcript - BofA Securities 2025 Healthcare Conference:

Alice Nettleton, Associate, Bank of America: To now. So thank you so much for joining us, today at this presentation. I’m Alice Nettleton, one of the associates from Tim Anderson’s US large cap biopharma team here at Bank of America. We are excited to host Mineralis today for a fifteen minute presentation, specifically John Congleton, CEO, and they recently presented their first quarter results on Monday. So looking forward to hearing about some of the exciting updates from your data recently as well as your first quarter updates.

So over to you, John.

John Congleton, CEO, Mineralis: Thank you. Very good. Thank you, Alyssa. Appreciate the invite. Appreciate being part of the the Bank of America conference.

My name is John Congleton, the CEO of Mineralis, where we’re focused exquisitely on targeting aldosterone and cardiorenal metabolic conditions. I’ll be making forward looking statements. There we go. So when I say targeting aldosterone, why does that matter? It matters because about twenty five to thirty percent of all hypertension patients have dysregulated aldosterone that based on research and literature would say is linked to visceral adiposity.

It’s a shift from forty years ago when I was a young sales rep with less gray hair. It’s probably about five to ten percent. So there’s some really interesting underlying biology that’s driving this condition. And the reason it’s needed to be targeted is because there are not a lot of viable and highly utilized therapeutics right now addressing aldosterone. We’re really pleased with in the first quarter, the two pivotal studies that read out with really positive data that I think not only supports the thesis that aldosterone needs to be targeted but the lorundarstat as an ASI and aldosterone synthase inhibitor is an ideal way to do that.

We saw a 19 millimeter absolute reduction in our launch HTN the real world study that I’ll get into in more detail in a moment and a 15 millimeter mercury reduction in the advanced HTN study, which is probably the most rigorous hypertension study ever done. We also have two proof of concept studies. We know that hypertension has significant overlap with a great many cardiorenal metabolic comorbidities. CKD is one that data we’ll be reading out later this quarter and then our OSA study we initiated in the first quarter of twenty twenty five. Cardio renal metabolic syndrome is and has been evolving as a thesis over the last five, ten years.

I think historically it was viewed as you treat hypertension, you treat diabetes, you treat CKD, you treat heart failure almost as independent entities. It is just as likely to go to a cardiology meeting and hear a talk about the kidney as you’ll go to a nephrology meeting and hear a talk about the heart. There’s so much interplay between these systems and hypertension and diabetes are really the the genesis and nexus points that link all of these cardio renal metabolic syndromes together. Aldosterone, we have known for decades is in a dysregulated state, a driver of pathology. What I think has grown in appreciation over the last several years is the right side of this slide.

So the left side is the mineralocorticoid receptor interaction with aldosterone. That drives your, sodium potassium electrolyte balance. It basically controls, water volume in the system and blood volume. The right side really drives fibrosis, oxidative stress, and inflammation. And the issue is the only therapeutic you have available right now to aldosterone is a mineralocorticoid receptor.

It blocks that left hand mechanism but in a compensatory response drives aldosterone higher and perturbs the right side. The aldosterone synthase inhibitor class, one of which we think we’re best in class, but there are three that are in clinical stage development, affect both sides because you’re reducing the actual ligand that can drive those pathways. ASI’s aldosterone synthase inhibitors have been a target of interest for big pharma for about fifteen years. Merck, Novartis, Lilly had what I would call first generation ASIs. They struggled with one really key point and that’s selectivity.

The selectivity relates to being able to inhibit aldosterone versus not inhibiting cortisol and there’s about 93% homology between these two synthetic pathways. And so you’ve got to be very selective just for aldosterone and not affect or inhibit cortisol. Lorundestat has best in class selectivity for that. We think it has an ideal half life as well, ten to twelve hours. What that translates to is within an hour of taking the drug you pretty much reduce aldosterone below the lower limit of detection and that lasts from a PD standpoint for about fourteen to sixteen hours.

In the remainder of time, it actually comes back to about 30% of baseline which we think helps mechanistically to clear potassium. You see, reasonable selectivity from Bactristat and Vicodirstat, I think the half lives are gonna be what’s gonna be really informative as these, programs read out clinical data. How does a longer half life or a shorter half life translate into efficacy and safety. But I can tell you based on our clinical programs such as LAUNCH that that ten to twelve hour half life and that selectivity is translated into a really, really, nice and transformative clinical profile. So LAUNCH10 is the largest hypertension study completed with an aldosterone synthase inhibitor.

We tested two doses, 50 milligrams through a twelve week course and fifty milligrams with the option to titrate up. The titration point is important here because I’ll be sharing some subset analysis, where we can pool both arms because everybody’s on 50 and haven’t had an option to titrate up. But this is looking at lorandestat’s benefit on existing background treatment. This study was really built for the primary care physician. This is the kind of practice they have.

They may not be optimizing background meds, but this is how lorundrostat would be used broadly within primary care. About forty percent of these patients in the trial were uncontrolled on two meds, about sixty percent were resistant to hypertension, had a good representation of African American about thirty percent and about two thirds were obese within this study and about ninety percent were either overweight or obese. The absolute change was significant. Great statistical significance but really clinically meaningful. At six weeks you’re seeing about a 17 millimeter mercury reduction absolute which is what physicians fundamentally look at.

You know scientifically you want look at the placebo adjusted which was nine, great statistical significance but a physician basically could take an existing patient who’s not at goal, put them on this drug and within six weeks see about a 17 mmHg reduction. That is meaningful. It validates the need to target aldosterone. It certainly shows the value of lorondestat. The nice thing is is the effect’s not only durable, but potentially improving over time.

And if you link it back to mechanistically, that may be that dual mechanism. And the early reduction is likely related to diuresis. This continued durable effect may be some level of vascular remodeling. That’s something we’re going to continue to look at over time. We’ll be reporting data at the European Society of Hypertension a week from this coming Saturday with more detail.

We do have looked at multiple different subsets, race, gender, age, eGFR level. That’ll be reported, on the May 24. We have previously shared that whether someone’s on two meds, so uncontrolled, or on three or more meds resistant, you see a similar response. Very robust. This is at week six and again sixteen and seventeen millimeter mercury absolute reduction.

There’s also, significant favoring as far as an odds ratio of getting to goal within six weeks. Forty four percent of the patients versus twenty four on placebo were able to achieve goal. That’s getting to below 130 millimeters of mercury, in office measurement. And so a significant benefit for patients that prior to this had not been a goal. Probably the biggest on target safety profile you wanna look at or safety marker, really there’s four, potassium is probably one of the key ones.

We know these drugs are going to increase potassium. ACE inhibitors do, ARBs do, MRAs do, ASIs do. If you affect the RAS system and create diuresis to lower BP, you’re going to shift that sodium potassium profile. So you wanna be really mindful of what’s the mean change. It was about 0.3 millimole per liter in this study, but also what are the incidental incursions above 5.5 and above six.

We see here two, two tables. One is the observed and then the other is confirmed. It’s really important to confirm potassium measures because you have what’s called factitious hyperkalemia. It’s just an error in the draw. If you break red blood cells, release potassium and you get a false read.

And so the confirmed number is where you really wanna focus. You’re seeing an incidence of zero point six percent or three out of five hundred and eighty three five hundred and thirty eight subjects, had a confirmed reading above six. In that case, you would just wanna either dose reduce lorundrostat or the background meds, but a really, really mild potassium profile. As anticipated, we saw this in the proof of concept. This has been seen with ACEs and ARBs.

You lower blood pressure. You relieve the pressure on the kidney, that water hammer as it’s called, and you see the eGFR come down, but that’s a good thing. Because absent reducing that blood pressure, kidney function is just gonna progressively go down. When you relieve pressure, it goes down slightly, and then it stabilizes over time. And that is what confers a benefit to the kidney.

From a safety standpoint, really clean profile, very well tolerated, two point four percent, incidents of serious adverse events, two point six percent discontinuation rate. So really pleased with what LaunchHDN speaks to the primary care provider. ADVANCE is part of this comprehensive program that we wanted to build out a data set that enables lorunderset to be part of the hypertension guidelines, but also speaks to the cardiologist. And what we do here is we take patients off their background med and we absolutely optimize to hypertension guidelines, take high dose medications, use smartphone technology to confirm compliance, and use twenty four hour ambulatory to measure. In this point, we did the titration at week four.

So when I show you the pool data, that will be at week four. You’ll see the mix of baseline characteristics here. Very proud of how the team really efforted to ensure that we had proper representation of black or African American. That is a very high risk population for uncontrolled blood pressure. Again, a couple of things I’ll point you to.

We saw a very rapid pronounced reduction in BP. In this case, it’s twenty four hour ambulatory, 15 millimeters of mercury sorry, 11 millimeters mercury at week four, 15 by week 12. Again, you’re seeing that rapid reduction, but then a pronounced durability and potential improvement over time. Similar to what we saw with launch, you’re seeing an odds ratio above three of getting the goal. Again, this is within four weeks.

And these are patients that are literally maxed out on what is currently available. So when the question is, well, do you really need another drug? You have all these generics. You got a lot of different modes of action. When you max out the best of what is available and you still can’t get patients to goal, this drug is helping those patients get there.

And we know if you get to goal, you’re significantly reducing your cardiovascular risk long term. The potassium profile here again, really modest change. We’re seeing about two percent incidence above a potassium of six. So again, it’s a non signal effect that you wanna see to show that the drug is working, but you wanna make sure that you’re not having excursions that are too high above six and, again, a very mild profile as it relates to that. As seen with launch, again, we’re seeing a change in eGFR.

Again, this confers, a benefit to kidney function. Safety profile, very compelling. I’ll point out one thing here. The discontinuation rate of twelve percent, we had an interesting finding, early on in this study. This study started before launch did.

We know that there’s an interaction, at mate one with lorandostat where there’s an inhibition of that pathway. Creatinine shares that pathway. And so there’s this competitive transport. Creatinine gets falsely elevated. EGFR typically gets measured with creatinine.

And so this interaction basically, had some subjects with a more pronounced reduction in the eGFR, and we had sites stopping patients because they were concerned. We went out and communicated the sites. This is a bit of a false read because of the competitive interaction with the transporter with creatinine. Said use cystatin c, and you see a quick course correction. But of those 12 subjects that stopped, six were due to the eGFR that we just had to convey the interaction with creatinine.

And I would take you back, I won’t do it due to time, but if you look at the same number for launch it was about two point six percent. So it was just a matter of education. We do have, because of this, overlapping comorbidities, we do have a, two proof concept studies underway. The EXPLORER CKD is gonna be reading out, later this quarter. This is a 60 subject study, exceptionally well powered because it’s crossover design.

Primary endpoint we’re gonna be looking at is change in BP. It is powered to show a clinically meaningful reduction. We will be looking at other markers of kidney function, most specifically change in eGFR, which at this point is very well characterized. We would anticipate a slight reduction in eGFR as we’ve seen previously. We’re gonna see how that translates into albuminuria, proteinuria.

We’ll look at twenty four hour UA as well as UACR and we’ll also be looking at safety signals like potassium and sodium. Really interesting study. We initiated this in q one. We’re still accruing enrollment in this trial, so we’re not guiding to, top line data just at this point. There’s a huge overlap between overweight, obese, resistant hypertension, OSA.

This population probably has the highest cardiovascular risk profile of anyone. There’s a lot of interesting data linking aldosterone to AAHI, but more specifically that during those apnea hypopnea events, see massive spikes in blood pressure. So we’re actually gonna be doing beat to beat, blood pressure measurements and correlating those to those apnea hypopnea events. And this study, I think, will be really informative for not only the hypertension profile, but potentially for other indications like AHI as well as some cardiovascular benefits. So here is the pipeline that we have right now.

We’ve now checked two boxes very positively with ADVANCE and with LAUNCH. The EXPLORER studies are forthcoming. The open label extension is really the final big piece that will enable the pre NDA meeting that we announced, during our earnings call Monday that will occur sometime in the fourth quarter. Stepping back, this is a highly genericized market. I started my career in this when it was a branded space.

Sixty million treated patients, thirty million still cannot get the goal. Some of that is due to compliance. Some of that is due to are are you on the right drugs? Some of that is due to are you on the right dose. But fundamentally, our two studies have shown when you weed out some of those yeah buts, there’s about twenty million patients that probably are at risk of stroke, heart disease, or kidney disease.

Those three are in the top eight of global burden of disease. We have not solved these problems, and that’s why I’m excited to be here driving this forward. Just very quickly, we put the profile of lorunderstand in front of cardiologists and primary care, ninety five percent intend to prescribe. It speaks to the interest in this space, the need in this space, and the response to the profile of lorunderstat. Lastly, thrilled to be working with the team that we have.

We did announce, Monday, Eric Warren has joined us as CCO to help us really crystallize the commercial opportunity here as well as help with strategic partnering discussions. And then lastly, cash balance, 343,000,000 as of our q one reporting. So I think I went over time a little bit. Hopefully, not too bad. Happy to address any questions.

Otherwise, I’ll let you go to the pool.

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