Mineralys Therapeutics is a clinical-stage biopharmaceutical company headquartered in Radnor, Pennsylvania, developing targeted therapies for hypertension and cardio-renal diseases. Its lead candidate, lorundrostat, is designed to treat conditions driven by excess aldosterone.
Has the GLP-1 and women's-health story overshadowed the importance of hypertension for global health?
The summer of 2023 was really interesting. That is when the two GLP-1s came out to great fanfare, and the data was compelling not only on weight loss but on the concordant benefits, on cardiovascular disease, on kidney disease, and on hypertension. Hypertension took a bit of a backseat, but I have been in this industry long enough to remember when antihypertensives had their moment, in the 80s and 90s, with ACE inhibitors, calcium channel blockers, and ARBs. It has been more than 20 years since anything truly innovative arrived in that space.
That is what excites me about the focus on aldosterone. When you find a target that is foundational to disease, obesity in the case of GLP-1s, aldosterone in our case, it can potentially have an impact on multiple outcomes at once as blood pressure is a widely accepted clinical surrogate endpoint for cardiovascular risk. We have known for decades that losing weight, whether through diet, exercise, or surgery, brings benefits across the health spectrum, and GLP-1s are a means to get there. I expect aldosterone-directed treatment to do the same, because our lorundrostat development program showed results not only in uncontrolled hypertension but in uncontrolled hypertension with CKD and with obstructive sleep apnea, with consistent reductions in blood pressure and in markers of kidney dysfunction.
How significant is aldosterone as a driver of disease, and how close are we to widespread adoption of a targeted therapy?
Aldosterone plays a critical role, and its prevalence is far higher than was appreciated. A lot of that is linked to obesity. Visceral, core fat can drive aldosterone and create what is called dysregulated or elevated aldosteronism. We have known for decades that aldosterone drives volume, retaining water and raising blood pressure, but it is also deleterious to the vasculature, driving inflammation, fibrosis, and oxidative stress. There are really two levers at work.
Over the five years I have been involved with Mineralys, the medical community has independently realized a few things: that the breadth of this problem is much greater than assumed, that it has been woefully underdiagnosed, and that it is worth testing for aldosterone earlier, which several medical societies now suggest. The tests are not the most sensitive, but it is a first step. There are also limited targeted alternatives, and that is why the aldosterone synthase inhibitor class stands to be potentially transformative in hypertension and in cardio-kidney-metabolic conditions.
There is growing focus on prevention. Could you position yourselves between prevention and treatment?
Yes, though it depends on what you mean by prevention. Uncontrolled hypertension, an elevated systolic blood pressure, is one of the best markers we have for predicting longer-term outcomes, whether kidney disease, heart disease, heart failure, or vascular dementia. It is the canary in the coal mine. Substantial evidence supports the impact if you pay attention to systolic pressure and get it to goal. Countless studies show long-term benefit from getting blood pressure below 130, and in some cases below 120, with anywhere from a 13 to 30 percent reduction in stroke, heart disease, and kidney disease.
The challenge is that 40 years ago the goal was 140. Now the goal is 130, or 120 in some cases, and we have had no real innovation. With aldosterone growing in prevalence, no true aldosterone-directed treatment available, and over half of treated patients not at goal, there is a significant opportunity to introduce a new approach that targets aldosterone and potentially helps a good portion of those patients reach goal.
Guidelines have shifted blood pressure goals to 130 or 120 in some cases, yet few treatment innovations can do this. With dysregulated aldosterone on the rise and over half of patients not at goal, there is a significant opportunity for a therapeutic approach that targets aldosterone biology.
You are expecting approval by the end of 2026. What are your expectations once that happens?
The medical community is primed for this. They are more aware of the problems with aldosterone, its prevalence, and the difficulty of addressing it, and they are focused on getting patients to their blood pressure goals. If approved, the introduction of lorundrostat would represent a new treatment option for prescribers to leverage. . We are not planning to introduce it as a first-line monotherapy. Hypertension is multifactorial, and there are good drugs already in use, including ACE inhibitors, ARBs, and diuretics.
But when you reach a later line of treatment and a patient still is not at goal, a targeted aldosterone synthase inhibitor like lorundrostat could potentially benefit physicians, patients, and ultimately the healthcare system, because the cost of uncontrolled systolic blood pressure is significant. It could be the right drug at the right time. Hypertension is not the end of the journey either. We continue to explore lorundrostat in additional patient populations, including patients with comorbid CKD, with heart failure, and other conditions, and we will communicate our future clinical development plans as they advance.
What does the environment for treating hypertension and related diseases look like five to ten years from now?
The medical community is moving in the right direction, recognizing that these cardio-renal-metabolic conditions are interrelated. Ten or twenty years ago it was siloed: hypertension, diabetes, chronic kidney disease, heart failure, all treated as distinct. Now, go to a nephrology meeting and there are sessions on metabolism and the heart; go to a cardiology meeting and they are discussing the kidney and diabetes. It is all coming together.
The two core foundational drivers are vascular disease, meaning hypertension, and metabolic disease, meaning diabetes and obesity. There is not going to be a single silver bullet. It is about addressing the fundamental drivers that affect multiple outcomes.
Within the space, who else is doing important work, and how do you see the GLP-1s fitting in?
Different companies are developing aldosterone-directed treatments for hypertension, and Medtronic is working on renal denervation. To me all of that is good. It has been more than 20 years since real innovation, so the renewed focus is welcome, and the reason is obvious: the job is not done when half of treated patients cannot get to goal. Something is being missed, and I believe the data supports aldosterone could be the biggest missed node in the process.
On the metabolic side, the GLP-1s and the dual and triple agonists coming will all be foundational. But even as strong as that data is across cardio, kidney, and metabolic disease, real risk remains. Advances in these areas have demonstrated the importance of understanding biological pathways that may contribute to disease and their interconnected mechanisms. Semaglutide showed roughly a 20 percent reduction in cardiovascular risk, which is great, but 80 percent still exists. That is why the GLP-1s, as good as they are, will not be the complete story. What they proved is that there is the potential if you hit the right node you can see the downstream impact beyond a single disease area, and I expect similar principles may apply to the aldosterone pathway.
Practically, what does the FDA decision look like from inside a company this size?
What I think is remarkable about our path is that we've moved from early-stage Phase 1 clinical development to an NDA-ready asset in five years. That's uncommon at this size. If we receive FDA approval, our plan is to launch in 2027 to provide a new treatment option for people living with uncontrolled or resistant hypertension.
Where does the name Mineralys come from?
Lorundrostat was developed through phase one by Mitsubishi Tanabe, and our seed investor, Catalys Pacific, a Japanese venture capital fund, licensed the asset and started Mineralys. A number of their portfolio companies carry the same ending, and the mineral itself points to the mineralocorticoid receptor, which aldosterone interacts with so significantly. That is how Mineralys was born.
