Mineralys Therapeutics is a clinical-stage biopharmaceutical company developing innovative therapies for diseases driven by dysregulated aldosterone, such as hypertension and chronic kidney disease.
Jon, how did you start your career, and what has been your perspective on innovation in hypertension treatment?
I started my career in the 1980s selling drugs for hypertension and heart disease, during a time of real transformation in treatment. We saw the introduction of drug classes like calcium channel blockers, beta-blockers, ACE inhibitors, and angiotensin receptor blockers (ARBs). These advancements fundamentally changed the management of hypertension and related conditions like chronic kidney disease, heart failure, and heart disease.
Unfortunately, over the past 30 years, there has been little innovation in this space. Stroke, kidney disease, and heart disease remain among the top global burdens of disease, contributing to the highest number of days lost to illness. Despite having effective drugs, the growing influence of obesity has created shifting biological challenges, making it difficult to achieve blood pressure control—a key modifiable risk factor for these conditions.
Why is controlling blood pressure so critical, and how does innovation play into this today?
Controlling blood pressure is essential to prevent end-organ damage, which can lead to reduced kidney and cardiac function, strokes, and even dementia. For instance, reducing blood pressure by just 10 mmHg can lower cardiovascular risk by at least 20% and slow the progression of kidney disease. Yet, in the U.S., nearly half of treated patients—about 30 million people—fail to reach their blood pressure goals.
We are finally seeing a renaissance in this field, with several new mechanisms under clinical development to address these unmet needs. These innovations, coupled with an understanding of the shifting biology linked to obesity—particularly the role of hormones like aldosterone—offer hope for better outcomes in resistant hypertension cases.
Mineralys Therapeutics’ focus is on addressing aldosterone. Is that the sole driver of hypertension?
No, aldosterone is not the sole cause of hypertension. In the U.S., there are 120 million adults with hypertension, and the condition typically stems from either increased vasoconstriction or excessive volume. Think of it like a garden hose—pressure can rise if the hose is too stiff or if there is too much water flowing through it.
We estimate that about a quarter of hypertension patients have dysregulated aldosterone. This does not always mean elevated levels; some patients are simply more sensitive to it. Aldosterone drives blood pressure by increasing sodium retention, which raises blood volume, and by contributing to vascular stiffness. Targeting aldosterone can lower volume, improve vascular elasticity, and help reduce hypertension’s harmful effects.
Can you share insights into your pipeline?
We completed a proof-of-concept study in 2022, showing a robust effect on blood pressure in obese patients—a population often linked to elevated aldosterone. Based on these findings, we initiated two pivotal hypertension studies: one in the U.S. and one globally.
In the U.S. study, patients are transitioned to an American Heart Association-recommended baseline treatment before adding either our drug or a placebo if their blood pressure remains uncontrolled. This study will conclude in March 2025. The global study, which maintains patients' existing treatments and adds either our drug or a placebo, will be read out in the first half of 2025. By then, we aim to have a package ready for FDA submission and are actively discussing regulatory paths in Europe and Asia.
What is the safety profile of your drug compared to traditional treatments?
Our drug's side effects are relatively mild and comparable to those of ACE inhibitors and ARBs. Since it works by lowering aldosterone, it can influence potassium retention as the kidneys excrete sodium. This is a common concern with therapies targeting blood pressure through volume reduction.
So far, the safety profile has been consistent with existing treatments, with potassium management being the primary consideration. We continue to monitor this closely in ongoing trials to ensure safety alongside efficacy.
How has Mineralys managed to attract investment? And what can you tell us about your future commercialization strategy?
Innovation and unmet need drive financing, and we have been fortunate to secure funding since our founding four years ago. This has allowed us to complete proof-of-concept studies and launch pivotal trials. Investors recognize the novelty and promise of our therapy, not just for hypertension but also for chronic kidney disease and heart failure.
We have also attracted interest from large pharmaceutical companies. With three of the top eight global disease burdens—stroke, kidney disease, and heart disease—being linked to hypertension, there’s renewed strategic interest in this space. Partnering will likely be part of our future commercialization strategy.
What do you hope to achieve in the next year?
Following our data readouts in 2025, we hope to demonstrate that our drug, lorundrostat, offers significant benefits in safely lowering blood pressure. Beyond efficacy and safety, we aim to provide insights for physicians on identifying patients most likely to benefit from this therapy, particularly those with aldosterone-driven hypertension.
Our ultimate goal is not only to deliver an innovative solution, but also to address the broader cardio-renal-metabolic needs, affirming the drug’s value for patients and providers alike.
