Business Overview
−Removed: We are a clinical-stage biopharmaceutical company focused on developing medicines to target diseases driven by dysregulated aldosterone.
−Removed: Our clinical-stage product candidate, lorundrostat, is a proprietary, orally administered, highly selective aldosterone synthase inhibitor (ASI) that we are developing for the treatment of cardiorenal conditions affected by dysregulated aldosterone, including hypertension, chronic kidney disease (CKD), and obstructive sleep apnea (OSA).
−Removed: In the United States, approximately 120 million patients have sustained elevated blood pressure (BP), or hypertension, and more than half of this population fails to achieve their BP goals, defined as BP below 130/80 mmHg, with currently available medications.
−Removed: There are over 30 million treated patients who do not achieve their BP goal, of whom approximately 20 million have systolic BP levels greater than 140 mmHg.
+Added: We are a biopharmaceutical company focused on developing medicines to target diseases driven by dysregulated aldosterone.
+Added: Our product candidate, lorundrostat, is a proprietary, orally administered, highly selective aldosterone synthase inhibitor (ASI) that we are developing for the treatment of cardiorenal conditions affected by dysregulated aldosterone, including hypertension and related comorbidities such as chronic kidney disease (CKD) and obstructive sleep apnea (OSA).
+Added: In the United States, there are approximately 120 million patients with sustained elevated blood pressure (BP), or hypertension.
+Added: Approximately 60 million patients are treated and over 30 million do not achieve their BP goal, with approximately 20 million having systolic BP levels greater than 140 mmHg.
Patients with hypertension that persists despite taking two or more medications have 1.8 and 2.5 times greater mortality risk due to either cardiovascular disease or stroke, respectively.
−Removed: In a Phase 2 proof-of-concept clinical trial evaluating 200 subjects (Target-HTN) with uncontrolled hypertension (uHTN), defined as individuals who are unable to achieve BP of below 130/80 mmHg despite taking two to five lines of antihypertensive medication, or resistant hypertension (rHTN), defined as individuals who are unable to achieve BP of below 130/80 mmHg despite taking three or more antihypertensive medications typically including a diuretic, lorundrostat demonstrated a clinically meaningful and statistically significant reduction in BP with once-daily (QD) dosing and was well tolerated.
−Removed: Dysregulated aldosterone levels are a key factor in driving hypertension in approximately 30% of hypertensive patients.
−Removed: In addition to hypertension, we are investigating the benefits of lorundrostat in subjects with hypertension and CKD and in subjects with hypertension and OSA.
−Removed: We believe that our product candidate holds promise to be an innovative solution for the rapidly growing unmet need in multiple cardiorenal metabolic disorders.
−Removed: Hypertension is one of the most common medical conditions globally, afflicting approximately 1.3 billion people.
−Removed: In the United States, hypertension was associated with $219 billion in health care expenditures.
−Removed: Despite the availability of multiple treatment options, including thiazide diuretics, angiotensin-converting enzyme (ACE)-inhibitors, angiotensin II receptor blockers (ARBs), calcium channel blockers, beta blockers, and mineralocorticoid receptor antagonists (MRAs), the prevalence of uHTN continues to grow, further exacerbated by the rapidly rising rate of obesity.
−Removed: Over 30 million hypertensive patients in the United States are unable to achieve their BP goal despite treatment.
−Removed: Within this population, there are approximately 10.3 million patients suffering from rHTN.
−Removed: Multiple large-scale studies have demonstrated that patients who fail to achieve their BP goal have a significantly elevated risk of developing heart disease, stroke, and kidney disease (Wright JT Jr, et al.
−Removed: A randomized trial of intensive versus standard blood-pressure control.
−Removed: N Engl J Med.
−Removed: 2015;373(22):2103-2116;
−Removed: and Zhou, et al., Uncontrolled Hypertension Increases Risk of All-Cause and Cardiovascular Disease Mortality in US Adults:
−Removed: the NHANES III Linked Mortality Study.
−Removed: Scientific Reports, 2018;8(1):1-7).
−Removed: Patients with rHTN have a 1.5 and 2.3 times higher risk than normotensive patients for composite cardiovascular events and end-stage renal disease, respectively.
−Removed: Notwithstanding this significant and growing unmet need, there has been a lack of U.S.
−Removed: Food and Drug Administration (FDA)-approved novel therapies targeting hypertension, with no new class of antihypertensive treatment approved within the last fifteen years.
+Added: Dysregulated aldosterone levels are a key factor in uncontrolled hypertension (uHTN) or resistant hypertension (rHTN) in approximately 30% of patients.
+Added: Ahead of the NDA submission in December 2025, we completed five successful clinical trials of lorundrostat supporting the efficacy and safety profile while also validating aldosterone as an integral therapeutic target in uHTN or rHTN.
+Added: This includes two pivotal, registrational trials, the Phase 3 Launch-HTN trial and Phase 2 Advance-HTN trial, which support the robust, durable, and clinically meaningful reductions in systolic BP by lorundrostat.
+Added: Lorundrostat was well tolerated in both trials with a favorable safety profile.
+Added: Based on the positive results from our pivotal program, we submitted an NDA in December 2025 for lorundrostat for the treatment of hypertension in combination with other antihypertensive drugs.
+Added: The FDA accepted the NDA submission and provided us with a Prescription Drug User Fee Act (PDUFA) target action date of December 22, 2026.
+Added: We believe, based on available clinical data, that our product candidate holds promise to be an innovative solution for the rapidly growing unmet need in multiple cardiorenal metabolic disorders.
+Added: In addition to hypertension, we have been investigating the potential benefits of lorundrostat in participants with hypertension and CKD and in participants with hypertension and OSA.
+Added: In June 2025, we announced that the result of our Phase 2 Explore-CKD trial, which evaluated the safety and efficacy of lorundrostat in participants with hypertension and comorbid CKD, was highly statistically significant and clinically meaningful in reducing systolic BP and in reducing urinary albumin creatinine ratio (UACR), a marker of kidney disease progression, as well as demonstrating a favorable safety and tolerability profile.
+Added: On March 9, 2026, we announced topline data from our Phase 2 Explore-OSA trial that evaluated the effect of lorundrostat in the treatment of overweight and obese participants with moderate-to-severe OSA and hypertension.
+Added: While the Explore-OSA trial did not demonstrate a reduction in apnea-hypopnea index (AHI), the BP reductions were clinically meaningful and the safety profile was favorable, especially for this population with difficult to control hypertension.
Our Product Candidate, Lorundrostat
Our product candidate, lorundrostat, is a proprietary, orally administered, highly selective ASI that is designed to reduce aldosterone levels by inhibiting CYP11B2, the enzyme responsible for producing the hormone.
−Removed: We licensed lorundrostat from Mitsubishi Tanabe Pharmaceutical Company (Mitsubishi Tanabe), who discovered the compound and provided the early foundational work, including demonstrating the selectivity of lorundrostat, and progressing the asset through Phase 1 clinical development.
−Removed: We completed the Target-HTN trial, a Phase 2 proof-of-concept trial for lorundrostat in the treatment of uHTN and rHTN in 2022.
−Removed: Given that hypertension and abnormal aldosterone biology can lead to cardiorenal disease, we are further investigating the benefits of lorundrostat in hypertensive subjects with comorbidities such as CKD or OSA.
+Added: We licensed lorundrostat from Tanabe Pharma Corporation (Tanabe), which discovered the compound and provided the early foundational work, including demonstrating the selectivity of lorundrostat, and progressing the asset through Phase 1 clinical development.
+Added: We have completed six clinical trials of lorundrostat in uHTN or rHTN as well as hypertension in uHTN or rHTN with comorbidities such as CKD or OSA.
+Added: A summary of our clinical development is outlined below.
Summary of Historical and Current Clinical Trials of Lorundrostat
−Removed: The first-in-human Phase 1 clinical trial of lorundrostat was conducted by Mitsubishi Tanabe.
−Removed: See “ Phase 1 Clinical Trial Results ” beginning on page 15 for additional details regarding this trial.
−Removed: We conducted the Target-HTN Phase 2 trial of 200 subjects with uHTN and rHTN to evaluate the efficacy of lorundrostat at various doses either once or twice a day.
−Removed: The results of Target-HTN led to the advancement of our pivotal program of lorundrostat outlined below.
−Removed: See “ Target-HTN Phase 2 Clinical Trial ” beginning on page 8 for additional details regarding this trial.
+Added: The first-in-human Phase 1 clinical trial of lorundrostat was conducted by Tanabe and showed that lorundrostat was well tolerated and did not inhibit cortisol following single dose and once-daily dosing over multiple days.
+Added: We conducted the Target-HTN Phase 2 proof-of-concept trial in participants with uHTN and rHTN to evaluate the efficacy of lorundrostat at various doses either once or twice a day.
+Added: The results of Target-HTN led to the advancement of our pivotal program of lorundrostat.
Pivotal Program:
−Removed: In 2023 we initiated our pivotal program of lorundrostat.
−Removed: See “ Lorundrostat as a Potential Treatment for Hypertension ” beginning on page 6 for additional details regarding these clinical trials.
−Removed: • Advance-HTN is our Phase 2 clinical trial to evaluate the efficacy and safety of lorundrostat for the treatment of uHTN or rHTN, when used as an add-on therapy to a standardized background treatment of two or three antihypertensive medications.
−Removed: Randomization of 285 subjects was completed in the fourth quarter of 2024, and topline data from this trial is anticipated in March 2025.
−Removed: • Launch-HTN is our Phase 3 clinical trial to evaluate the efficacy and safety of lorundrostat for the treatment of uHTN or rHTN, when used as an add-on therapy to their existing, prescribed background treatment of two to five antihypertensive medications.
−Removed: Randomization of 1,083 subjects was completed in the fourth quarter of 2024, and topline data from this trial is anticipated in mid first half of 2025.
−Removed: • Explore-CKD is our crossover trial designed to evaluate the safety and efficacy of 25 mg QD lorundrostat in addition to an SGLT2 inhibitor for the treatment of hypertension in subjects with Stage 2 to 3b CKD and albuminuria despite receiving stable treatment with an ACE inhibitor or ARB.
−Removed: Randomization of 60 subjects was completed in the first quarter of 2025, and topline data from this trial is anticipated in the second quarter of 2025.
−Removed: • Transform-HTN is an open-label extension trial allowing subjects to continue to receive lorundrostat and to obtain long-term efficacy and safety data.
−Removed: This trial is ongoing.
−Removed: Other indications:
−Removed: We anticipate initiating our Phase 2 clinical trial (Explore-OSA) in the first quarter of 2025, which is planned to evaluate the safety and efficacy of lorundrostat 50 mg QD in approximately 40 subjects with moderate-to-severe OSA.
−Removed: See “ Lorundrostat as a Potential Treatment for Hypertension ” beginning on page 6 for additional details regarding this clinical trial.
+Added: In 2023, we initiated our pivotal program of lorundrostat, and we reported the results of Launch-HTN and Advance-HTN in March 2025.
+Added: See “ Pivotal Program Clinical Trial Results ” beginning on page 7 for additional details regarding the results of these clinical trials.
+Added: • Launch-HTN evaluated the efficacy and safety of lorundrostat for the treatment of uHTN or rHTN when used as an add-on therapy to participants’ existing, prescribed background treatment of two to five antihypertensive medications.
+Added: • Advance-HTN evaluated the efficacy and safety of lorundrostat for the treatment of confirmed uHTN or rHTN when used as add-on therapy to a standardized, optimized, and adherent background treatment of two or three antihypertensive medications.
+Added: • Transform-HTN is an ongoing open-label extension trial enabling participants to continue to receive lorundrostat and allows us to obtain long-term efficacy and safety data.
+Added: All participants in the pivotal hypertension program, including the Advance-HTN and Launch-HTN trials, as well as the Explore-CKD trial, were given the opportunity to participate in the extension trial.
+Added: • Explore-CKD evaluated the safety and efficacy of 25 mg once daily (QD) lorundrostat in addition to a sodium-glucose cotransporter 2 (SGLT2) inhibitor for the treatment of hypertension in participants with Stage 2 to 3b CKD and albuminuria despite receiving stable treatment with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB).
+Added: We reported the results of this trial in June 2025.
+Added: See “ Explore-CKD Clinical Trial Results ” beginning on page 9 for additional details regarding the results of this clinical trial.
+Added: • Explore-OSA evaluated the safety and efficacy of lorundrostat 50 mg QD with moderate-to-severe OSA.
+Added: See “ Explore-OSA Clinical Trial Results ” beginning on page 10 for additional details regarding this clinical trial.
Background of Hypertension
−Removed: In healthy individuals, normal BP, also known as peripheral blood pressure, is below 130 over 80, meaning the pressure measurement is lower than 130 mmHg when the heart is contracting (systolic BP) and at or below 80 mmHg when the heart is relaxed (diastolic BP).
+Added: In healthy individuals, normal BP, also known as peripheral blood pressure, is below 130 over 80, meaning the pressure measurement is lower than or at 130 mmHg when the heart is contracting (systolic BP) and at or below 80 mmHg when the heart is relaxed (diastolic BP).
Sustained, elevated BP, or hypertension, can result in increased chances of life-threatening complications such as heart disease, stroke, or kidney disease, among others.
2 unchanged sentences
Furthermore, obesity, especially when associated with increased visceral adiposity, is a major cause of hypertension, accounting for 65% to 75% of the risk for developing human primary (essential) hypertension.
−Removed: Despite hypertension being one of the most common preventable risk factors for premature death, approximately 1.3 billion people worldwide have hypertension, with hypertension as a primary or contributing cause of 685,875 deaths in the United States in 2022 alone.
+Added: Despite hypertension being one of the most common preventable risk factors for premature death, approximately 1.3 billion people worldwide have hypertension, with hypertension as a primary or contributing cause of more than 685,000 deaths in the United States in 2022 alone.
The costs of hypertension and related health issues are a major burden on already strained healthcare systems, with an estimated cost of $219 billion in the United States in 2019.
1 unchanged sentence
Dysregulated aldosterone levels are a key factor in driving hypertension in approximately 30% of hypertensive patients.
−Removed: The current standard-of-care for patients newly diagnosed with hypertension is based on a set of guidelines set forth by the American College of Cardiology and the American Heart Association.
+Added: The current standard-of-care for patients newly diagnosed with hypertension is based on a set of guidelines set forth by the American College of Cardiology (ACC) and the American Heart Association (AHA).
A hypertensive patient’s target BP is defined as below 130/80 mmHg.
−Removed: Depending on baseline BP levels, these guidelines recommend the patient typically begin with lifestyle modifications and then, assuming BP does not achieve the desired target, initiate treatment with antihypertensive agents selected primarily from the following five drug classes, which may later be combined with each other if the patient’s target BP is not successfully achieved with the initial therapy:
+Added: Depending on baseline BP levels, these guidelines recommend that the patient typically begin with lifestyle modifications and then, assuming BP does not achieve the desired target, initiate treatment with antihypertensive agents selected primarily from the following five drug classes, which may later be combined with each other if the patient’s target BP is not successfully achieved with the initial therapy:
• Thiazide diuretics, which increase fluid excretion from the kidney by blocking reabsorption of sodium and chloride in the nephron;
2 unchanged sentences
• Calcium channel blockers, which slow cardiac contractions and relax arteries by preventing calcium from entering the cells of the heart and arteries;
−Removed: • Beta blockers, which cause the heart to beat more slowly and with less force, which lowers BP.
+Added: • Beta blockers, which cause the heart to beat more slowly and with less force, which lower BP.
Despite numerous available treatment options, the majority of hypertensive patients require multiple therapies to achieve their target BP.
1 unchanged sentence
However, the incremental reduction in systolic BP provided by successive lines of treatment does not always adequately enable patients to reach their BP goal.
−Removed: Therefore, many patients require three, four, or more antihypertensive agents in an attempt
−Removed: to achieve their target BP.
−Removed: In addition, while hypertension is an asymptomatic disease, many of the currently available treatments have side effects and tolerability issues, which may limit their use.
+Added: Therefore, many patients require three, four, or more antihypertensive agents in an attempt to achieve their target BP.
+Added: ACE inhibitors and ARBs are standard-of-care in the majority of all treated patients.
+Added: Approximately 30-40% of patients receiving long-term ACE inhibitor or ARB therapy experience aldosterone breakthrough, which is associated with volume expansion and adverse cardiorenal effects that can undermine BP control.
+Added: In addition, while hypertension is an asymptomatic disease, many of the currently available
+Added: treatments have side effects and tolerability issues, which may limit their use.
For example, patients taking ACE inhibitors often develop a chronic cough, and those taking beta blockers often experience lethargy.
5 unchanged sentences
Over 30 million hypertensive patients in the United States are unable to achieve their BP goal despite treatment, and within this population, 10 million suffer from rHTN.
−Removed: Treatment options are limited for rHTN patients, and the current standard-of-care is to introduce an MRA agent, which blocks the effect of aldosterone, to their existing antihypertensive regimen.
+Added: Treatment options are limited for rHTN patients, and the current ACC and AHA guidelines recommend introducing a mineralocorticoid receptor antagonist (MRA) agent, which blocks the effect of aldosterone, to the patient’s existing antihypertensive regimen.
Background of Chronic Kidney Disease (CKD)
1 unchanged sentence
According to the U.S.
−Removed: Centers for Disease Control and Prevention, an estimated 1-in-7 (15%) of U.S.
−Removed: adults have CKD.
−Removed: Diabetes and hypertension are responsible for approximately two-thirds of CKD cases.
−Removed: Early detection and treatment can often keep CKD from getting worse.
−Removed: When CKD progresses, it may eventually lead to kidney failure, which requires dialysis or a kidney transplant to maintain life.
+Added: Centers for Disease Control and Prevention, an estimated 1-in-7 (approximately 37 million) U.S.
+Added: adults have CKD, and approximately 22 million people in the United States are living with both hypertension and CKD.
+Added: The relationship between these conditions is tightly linked:
+Added: sustained hypertension may contribute to impaired kidney function, and progressive decrease in kidney function may lead to worsening BP control.
+Added: Achieving BP control in these complex patients is the number one goal in slowing the progression of CKD.
+Added: When CKD is present in patients with hypertension, the risk of cardiovascular disease and mortality rises significantly.
+Added: Emerging evidence points to dysregulated aldosterone as a key driver of both diseases.
+Added: Excess aldosterone promotes sodium retention, vascular inflammation, and fibrosis, contributing to both uncontrolled BP and kidney injury.
+Added: Despite the availability of existing therapies, a significant proportion of patients remain uncontrolled or undertreated.
+Added: Early detection and targeted interventions that address underlying mechanisms, such as aldosterone dysregulation, may offer the potential to slow CKD progression, reduce cardiovascular risk, and improve long-term outcomes.
+Added: Without effective management, CKD can advance to kidney failure, requiring dialysis or transplantation.
Background of Obstructive Sleep Apnea (OSA)
−Removed: OSA is characterized by repetitive overnight hypoxic episodes and subsequent sleep fragmentation due to a complete or partial collapse of the upper airway.
−Removed: Moderate OSA is defined as having between 15 and 30 breathing pauses (apnea or hypopnea events) per hour of sleep, while severe OSA indicates more than 30 breathing pauses per hour.
−Removed: OSA impacts over 54 million people in the United States, including 24 million moderate-to-severe cases.
+Added: OSA is characterized by repetitive overnight hypoxic episodes and subsequent sleep fragmentation related to many factors, including volume overload and a complete or partial collapse of the upper airway.
+Added: Moderate to severe OSA is associated with increased production of aldosterone and increased nighttime BP;
+Added: standard treatment with positive airway pressure is not sufficient for BP reduction.
+Added: OSA impacts almost one billion people globally, including 425 million moderate-to-severe cases.
Around 80% of adults with OSA are undiagnosed.
−Removed: As of 2015, undiagnosed OSA is estimated to cost the United States approximately $149.6 billion annually from comorbid disease, workplace accidents, motor vehicle accidents, and loss of workplace productivity.
−Removed: Between 30-50% of adults with hypertension have OSA, and this number increases to between 70-80% in adults with resistant hypertension.
−Removed: Additionally, untreated moderate-to-severe OSA increases the risk of resistant hypertension.
+Added: As of 2025, untreated OSA is estimated to cost the United States more than $150 billion annually when considering direct medical expenses, productivity losses, and accident-related costs.
+Added: Between 30-50% of adults with hypertension have OSA, and this number increases to between 70-80% in adults with rHTN.
+Added: Additionally, untreated moderate-to-severe OSA increases the risk of rHTN.
Along with hypertension, OSA is a major risk factor for cardiovascular disease, type-2 diabetes mellitus, and stroke.
Background of Aldosterone and its Role in Hypertension
−Removed: Aldosterone is a mineralocorticoid steroid hormone primarily made in the outer layer of the adrenal gland called the adrenal cortex, which plays an important role in controlling the balance of water and salts by keeping sodium in and releasing potassium from the body.
−Removed: This maintenance of homeostasis ensures the body can maintain normal BP.
+Added: Aldosterone is a mineralocorticoid steroid hormone primarily made in the outer layer of the adrenal gland called the adrenal cortex, which plays an important role in controlling the balance of water and salts by regulating the exchange of sodium and potassium in the body.
+Added: This maintenance of fluid homeostasis ensures the body can maintain normal BP.
In a healthy person, homeostatic balance is maintained via a feedback loop called the RAAS.
24 unchanged sentences
The task of creating a safe and effective ASI can be technically challenging because the major enzymes in the synthesis of aldosterone and cortisol share a high degree of amino acid sequence similarity.
−Removed: While challenging to develop, there are currently four ASIs (including lorundrostat) in advanced clinical development in conditions including hypertension, OSA, primary aldosteronism, heart failure, and CKD.
−Removed: Lorundrostat as a Potential Treatment for Hypertension
+Added: While challenging to develop, there are currently three ASIs (including lorundrostat) in advanced clinical development and one in early clinical development in conditions including hypertension, OSA, primary aldosteronism, heart failure, and CKD.
+Added: Clinical Development of Lorundrostat
Our product candidate, lorundrostat, is a proprietary, orally administered, highly selective ASI designed to reduce aldosterone levels by inhibiting CYP11B2, the enzyme responsible for producing the hormone.
−Removed: We are initially developing lorundrostat for the treatment of hypertension and have completed Target-HTN, our initial Phase 2 proof-of-concept clinical trial.
−Removed: In this trial, lorundrostat was well tolerated and demonstrated compelling clinical results, and once-daily dosing flexibility.
+Added: We are initially developing lorundrostat for the treatment of hypertension and have completed six clinical trials.
+Added: In our trials, lorundrostat was well tolerated and demonstrated compelling clinical results, and once-daily dosing flexibility.
The observed 10 to 12 hour pharmacokinetic half-life of lorundrostat has the potential to normalize aldosterone levels to provide a clinically meaningful reduction in BP and to flexibly manage the challenges of elevated serum potassium.
We believe that lorundrostat’s profile may be compelling based on the following attributes:
−Removed: • Compelling Clinical Results:
−Removed: Target-HTN demonstrated a statistically significant 9.6 mmHg and 7.8 mmHg reduction in systolic BP in the 50 mg and 100 mg QD cohorts, respectively, which we believe to be clinically meaningful.
−Removed: The reduction in systolic BP was validated and confirmed by
−Removed: 24-hour mean ambulatory blood pressure monitoring (ABPM), which further demonstrated that lorundrostat provides both central and nighttime BP reduction;
+Added: • Compelling Clinical Results in Hypertension:
+Added: The Launch-HTN global Phase 3 trial demonstrated a statistically significant and clinically meaningful 11.6 mmHg placebo-adjusted
+Added: reduction in systolic BP in the 50 mg 12-week cohort.
+Added: This clinical benefit was consistent across patient subtypes and specifically in high-risk populations such as women and Black or African Americans.
+Added: Furthermore, a low rate of hyperkalemia was observed, with 0.6% of participants exceeding 6.0 mmol/L potassium.
+Added: • Distinct Benefit in Hypertension and Related Comorbidities:
+Added: Explore-CKD demonstrated a statistically significant and clinically meaningful reduction in systolic BP and UACR in participants with hypertension and comorbid CKD.
+Added: In Explore-OSA, lorundrostat demonstrated a clinically meaningful reduction in systolic BP in participants with hypertension and comorbid OSA.
• High Selectivity:
−Removed: Phase 1 and Phase 2 clinical data demonstrated high aldosterone selectivity with no cortisol suppression and no incidence of adrenal insufficiency, as anticipated by the 374 to 1 inhibitory effect on the CYP11B2 enzyme compared to the CYP11B1 enzyme, which is responsible for synthesizing cortisol;
+Added: Lorundrostat is highly selective for aldosterone and shows no cortisol suppression and no incidence of adrenal insufficiency, as anticipated by the 374-to-1 inhibitory effect on the CYP11B2 enzyme compared to the CYP11B1 enzyme, which is responsible for synthesizing cortisol.
• Optimal Half-Life:
−Removed: A majority of our clinical trial subjects maintained a serum potassium in the normal range.
−Removed: There were modest incidences of hyperkalemia requiring dose adjustment or discontinuation.
−Removed: Six subjects experienced transient elevated serum potassium greater than 6.0 mmol/L, none of which were considered a serious adverse effect (SAE) and all rapidly resolved after discontinuation or dose adjustment.
−Removed: One of the events was assessed as erroneous due to sample misprocessing.
−Removed: Lorundrostat’s observed 10 to 12 hour half-life may be viewed more favorably by physicians compared to compounds with longer half-lives, which may have greater risk of sustained potassium elevation;
+Added: The half-life of lorundrostat (10-12 hours) is ideally suited for once-daily dosing.
+Added: Our clinical trials validated the 24-hour efficacy achieved with once-daily dosing.
+Added: A majority of our clinical trial participants maintained a serum potassium in the normal range.
+Added: There have been modest incidences of hyperkalemia requiring dose adjustment or discontinuation.
+Added: Lorundrostat’s observed 10 to 12 hour half-life may be viewed more favorably by physicians compared to compounds with longer half-lives, which may have a greater risk of sustained potassium elevation.
• Convenient Dosing and Well Tolerated:
−Removed: Target-HTN demonstrated clinically meaningful results on a once-daily dosing regimen.
+Added: Our clinical trials demonstrated clinically meaningful results on a once-daily dosing regimen.
Furthermore, lorundrostat was well-tolerated.
−Removed: Based on the results of the Phase 1 and Target-HTN clinical trials, we initiated our pivotal program in 2023 for lorundrostat in the following trials:
−Removed: Advance-HTN is a randomized, double-blind, placebo-controlled Phase 2 clinical trial to evaluate the efficacy and safety of lorundrostat for the treatment of uHTN or rHTN, when used as an add-on therapy to a standardized background treatment of two or three antihypertensive medications.
−Removed: Subjects who met screening criteria discontinued their existing hypertension medications and started on a standard regimen of an ARB and a diuretic, if previously on two medications, or a standard regimen of ARB, diuretic and calcium channel blocker if previously on three to five medications.
−Removed: Subjects who remained hypertensive despite the standardized regimen were then randomized into three cohorts for twelve weeks receiving one of the following treatments:
−Removed: lorundrostat 50 mg QD, lorundrostat 50 mg QD and an option to titrate to 100 mg QD at week four based on defined criteria or placebo.
−Removed: The primary endpoint of Advance-HTN is change in 24-hour ambulatory systolic BP at week twelve from baseline for each active cohort versus placebo.
−Removed: Randomization of 285 subjects was completed in the fourth quarter of 2024, and topline data from this trial is anticipated in March 2025.
−Removed: Launch-HTN is a global, randomized, double-blind, placebo-controlled Phase 3 clinical trial to evaluate the efficacy and safety of lorundrostat for the treatment of uHTN or rHTN, when used as an add-on therapy to their existing, prescribed background treatment of two to five antihypertensive medications.
−Removed: Subjects were randomized into three cohorts for twelve weeks receiving one of the following treatments:
+Added: In Launch-HTN, serious adverse events (SAEs) were reported in 2.4% of participants receiving 50 mg lorundrostat and in 3.3% of participants receiving placebo.
+Added: Pivotal Program Clinical Trial Results
+Added: Efficacy Results
+Added: Launch-HTN was a large, global, randomized, double-blinded, placebo-controlled Phase 3 clinical trial, which enrolled eligible adult participants who failed to achieve their BP goal despite being on two to five antihypertensive medications.
+Added: Launch-HTN reflects the real-world setting for clinicians by utilizing automated office blood pressure measurement (AOBP) and allowing participants to stay on their existing medications.
+Added: Participants were randomized into three cohorts for twelve weeks, receiving one of the following treatments:
lorundrostat 50 mg QD, lorundrostat 50 mg QD and an option to titrate to 100 mg QD at week six based on defined criteria or placebo.
−Removed: The primary endpoint of the trial is the assessment of automated office measured systolic BP from baseline for active cohorts versus placebo at six weeks, with the results pooled for all subjects on 50 mg QD.
−Removed: Randomization of 1,083 subjects was completed in the fourth quarter of 2024, and topline data from this trial is anticipated in mid first half of 2025.
−Removed: Explore-CKD is a randomized, double-blind, placebo-controlled, two-period, two-sequence (2x2) crossover trial designed to evaluate the safety and efficacy of 25 mg QD lorundrostat in addition to an SGLT2 inhibitor for the treatment of hypertension in subjects with Stage 2 to 3b CKD and albuminuria despite receiving stable treatment with an ACE inhibitor or ARB.
−Removed: The primary endpoint is placebo-adjusted change from baseline in systolic BP at week four and an exploratory endpoint is placebo-adjusted percent change from baseline in urine albumin-to-creatinine ratio at week four.
−Removed: Randomization of 60 subjects was completed in the first quarter of 2025, and topline data from this trial is anticipated in the second quarter of 2025.
−Removed: Transform-HTN is an open-label extension trial allowing subjects to continue to receive lorundrostat and to obtain long-term efficacy and safety data.
−Removed: All subjects in the pivotal hypertension program, including the Advance-HTN and Launch-HTN trials, as well as the Explore-CKD trial, will be given the opportunity to participate in the extension trial.
−Removed: Lorundrostat has been developed to address dysregulated aldosterone, and we believe this mechanism may be applicable to other indications where dysregulated aldosterone biology plays a role.
−Removed: Most recently, we have begun to explore lorundrostat for patients with OSA and hypertension.
−Removed: In January 2025, we announced that the FDA cleared our investigational new drug application (IND) for Explore-OSA to evaluate the effect of lorundrostat in the treatment of subjects with moderate-to-severe OSA and hypertension.
−Removed: We anticipate initiating Explore-OSA in the first quarter of 2025.
−Removed: Explore-OSA is planned to be a placebo-controlled, crossover trial to evaluate the safety and efficacy of lorundrostat 50 mg QD in the evening in approximately 40 subjects with moderate-to-severe OSA.
−Removed: Subjects will be at least 18 years old, with a BMI ≥27 kg/m 2 , and the trial will be conducted across approximately 40 sites.
−Removed: The key objective of this trial is to evaluate the hypothesis that lorundrostat both alleviates the severity of upper airway obstruction and reduces nocturnal hypertension.
−Removed: The primary outcome measure is absolute change in the frequency of apnea-hypopnea episodes compared to placebo.
−Removed: The key secondary objective is to quantify BP throughout the night using continuous BP monitoring during performance of a standard sleep study without the use of CPAP.
−Removed: Standard patient reported outcomes specific to OSA will also be assessed.
−Removed: Target-HTN Phase 2 Clinical Trial
−Removed: Target-HTN was a two-part Phase 2 randomized, double-blind, placebo-controlled, dose-ranging, multi-center trial designed to evaluate the safety, efficacy, and tolerability of orally administered lorundrostat for the treatment of uHTN and rHTN when used as an add-on therapy to stable background treatment of two or more antihypertensive medications in 200 males and females.
−Removed: The trial was conducted in the United States.
−Removed: The following table illustrates the key clinical results of Target-HTN:
−Removed: *Mixed effects model with repeated measures (MMRM) results for 100mg QD Part1 and 50mg QD were -7.8 mmHg and -9.6 mmHg, respectively.
−Removed: The observed means include only those subjects with observations at visit eight with no imputation for missing values, while MMRM imputes missing values.
−Removed: The values for observed and MMRM means may differ slightly.
−Removed: **Results from post-hoc sensitivity analysis reflecting subjects who passed Quality Control criteria and in whom both baseline AOBP and ABPM > 130mmHg.
−Removed: The results of the Target-HTN trial demonstrated a clinically meaningful and statistically significant placebo-adjusted reduction in systolic BP, as measured by automated office blood pressure (AOBP), of 9.6 mmHg (p<0.01) and 7.8 mmHg (p<0.04) in the 50 mg and 100 mg QD cohorts, respectively.
−Removed: A p-value is the
−Removed: probability that the reported result was achieved purely by chance, such that a p-value of less than or equal to 0.05 means that there is a less than or equal to 5% probability that the difference between the control group and the treatment group is purely due to chance.
−Removed: A p-value of 0.05 or less typically represents a statistically significant result.
−Removed: The FDA’s evidentiary standard when evaluating the results of a clinical trial generally relies on a p-value of less than or equal to 0.05.
−Removed: In a meta-analysis of 147 randomized trials, a 10 mmHg reduction of systolic BP or a 5 mmHg reduction in diastolic BP has been shown to reduce the risk of stroke by 41% and coronary heart disease by 22%.
−Removed: The reduction in systolic BP in Target-HTN, as measured by AOBP, was validated and confirmed by comparable reductions in systolic BP with lorundrostat, as measured by 24-hour mean ABPM.
−Removed: The ABPM data further demonstrated the benefits of lorundrostat on both central and nighttime BP reduction, which have been strongly linked to cardiovascular health risk.
−Removed: In the trial, patients with a body mass index (BMI) greater than 30, or obese patients, who are at an elevated risk of cardiorenal diseases, exhibited a 12.3 or 16.7 mmHg placebo-adjusted reduction in systolic BP with a 100 mg QD or 50 mg QD dose, respectively.
−Removed: Treatment-emergent SAEs were reported in three subjects, one of which was deemed to be possibly related to lorundrostat in a subject with worsening of preexisting hyponatremia, which reversed after discontinuation.
−Removed: The two active, once-daily doses saw modest increases in potassium levels across the cohorts of 0.25 mmol/L with the 50 mg QD and 0.29 mmol/L with the 100 mg QD dose.
−Removed: Six subjects experienced transient elevated serum potassium greater than 6.0 mmol/L, none of which were considered an SAE, and all rapidly resolved after discontinuation or dose adjustment, which is consistent with the half-life of lorundrostat.
−Removed: One of the events was assessed as erroneous due to sample misprocessing.
−Removed: As anticipated, and in a manner similar to ACE inhibitors and ARBs, the BP lowering effect of lorundrostat led to a beneficial, reversible dose-dependent reduction in estimated glomerular filtration rate (eGFR), a measure of kidney function.
−Removed: Finally, the selectivity of lorundrostat for aldosterone inhibition was confirmed as cortisol levels were not observed to be inhibited across the range of doses.
−Removed: The trial was conducted in two parts.
−Removed: In Part 1, subjects were initially pre-screened for a period of up to two weeks with a requirement for their systolic/diastolic BP to be over 130/80 mmHg with the use of two or more background medications indicated for hypertension such as ACE inhibitors, ARBs, calcium channel blockers, or diuretics.
−Removed: Subjects in Part 1 were also required to have low-renin hypertension defined as hypertension with a plasma renin activity level of 1.0 ng/mL/h or less.
−Removed: Subjects were excluded if they were taking an MRA or sodium channel blocker.
−Removed: Once subjects met the prescreening criteria, they were followed for two weeks during a blinded, placebo run-in period where their elevated BP was reconfirmed while compliant on background medication and placebo.
−Removed: If patients were compliant on their background medication and continued to have BP above 130/80 mmHg, subjects were randomized into five active cohorts and one placebo cohort.
−Removed: Subjects were dosed for eight weeks, then, upon withdrawal of study medication, followed for another four weeks.
−Removed: Baseline Demographics of the Patients Enrolled in Target-HTN Part 1 — Full Analysis Set (FAS)
−Removed: We conducted a pre-planned interim analysis for Part 1 of the trial when approximately one-third (65 subjects) of the planned enrollment had completed a minimum of four weeks of treatment, representing approximately 10-12 subjects per cohort.
−Removed: To preserve the blinding of the trial, the interim analysis was conducted by a small team that was not involved in operational aspects of the trial and no results of the analysis were shared with the operational team at clinical trial sites.
−Removed: The primary purpose of the interim analysis was to assess whether the chosen dose range appeared to adequately span the range from sub-therapeutic to maximum therapeutic response determined by change in systolic BP at week four relative to baseline.
−Removed: As a result of the interim analysis, we discontinued further enrollment in two of the lower dose cohorts (12.5 mg QD and 12.5 mg BID) due to the modest efficacy and projected benefit/risk ratio and initiated Part 2 of the trial.
−Removed: Part 2 was designed to study the effect of lorundrostat in subjects with normal-to-high renin levels, and we selected 100 mg QD as the dose to study based on its efficacy and safety as demonstrated in the interim analysis.
−Removed: Subjects enrolled in Part 2 were randomized to either 100 mg of lorundrostat once-daily (n=31) or placebo (n=6) to preserve the blinded randomization of the trial.
−Removed: The Part 2 subjects followed the same study conduct as Part 1 subjects, with the exception of the follow-up period, which was shortened from four weeks to two weeks.
−Removed: The primary endpoint of Target-HTN was change in seated, pre-dose morning systolic BP at week 8 versus baseline reading as measured by AOBP.
−Removed: The pre-planned analysis of the primary endpoint was an MMRM.
−Removed: Between Part 1 and Part 2, 100 mg QD, the pre-planned comparison of the primary endpoint was an unpaired, two-tailed T-test, using the observed change from baseline to week 8.
−Removed: Secondary endpoints included
−Removed: 24-hour ABPM change at week 8 versus baseline, diastolic BP change at week 8 versus baseline, and proportion of subjects achieving BP goal at week 8.
−Removed: For the purpose of evaluating safety, findings from the 100 mg QD cohorts from Parts 1 and 2 were pooled.
−Removed: Phase 2 Target-HTN Clinical Trial Design
−Removed: BID = twice-daily;
−Removed: EOT = end of treatment;
−Removed: FU = follow up;
−Removed: PRA = plasma renin activity;
−Removed: QD = once-daily
−Removed: The outcomes of the Phase 2 proof-of-concept study of lorundrostat, as shown in the chart below, demonstrated efficacy across defined endpoints and was well tolerated in once-daily dosing.
−Removed: The primary endpoint for Part 1 of Target-HTN was the change in systolic BP at week 8 relative to baseline.
−Removed: As indicated in the table below, in an intent-to-treat analysis, lorundrostat showed a statistically significant reduction in systolic BP, which we believe to be clinically meaningful, in a dose-dependent manner.
−Removed: The once-daily doses of 50 mg and 100 mg of lorundrostat demonstrated comparable reduction in systolic BP, as compared to the twice-daily dosing of lorundrostat with either 12.5 mg or 25 mg of lorundrostat.
−Removed: The higher doses of both once-daily and twice-daily lorundrostat also generated a reduction in diastolic BP over the course of the trial, which we believe to be clinically meaningful.
−Removed: Target-HTN Efficacy Data, as Measured by AOBP
−Removed: In Part 2, 31 subjects with normal or elevated renin were treated with once-daily lorundrostat at 100 mg QD and assessed similarly to those in Part 1.
−Removed: The reduction in systolic BP in Part 2 of this trial was not
−Removed: statistically different from the reduction seen in Part 1 (see figure below).
−Removed: As a result, we believe that lorundrostat has the potential to be effective across the entire range of renin levels.
−Removed: Individual Change in BP at Week 8
−Removed: *N = subjects with baseline and week 8 data, modeled mean using FAS.
−Removed: A further predefined objective of this trial was to evaluate potential predictors of clinical response to lorundrostat.
−Removed: There was no consistent difference in clinical response to lorundrostat observed based on gender, race, age, or number of baseline antihypertensive medicines.
−Removed: Our analysis of the clinical results demonstrated the following determinants to be positively correlated to clinical response:
−Removed: Hypertensive subjects with a BMI ≥30 kg/m2 demonstrated a significant reduction of systolic BP with a placebo-adjusted reduction of 16.7 mmHg with 50 mg QD and a reduction of 12.3 mmHg with 100 mg QD in Part 1 of the study.
−Removed: The obesity finding, in particular, lends support to our hypothesis of the linkage between obesity-leptin-aldosterone axis and hypertension;
−Removed: • Use of diuretics.
−Removed: Subjects taking a diuretic as a part of their background regimen demonstrated a significant reduction of systolic BP with a placebo-adjusted reduction of 12.9 mmHg with 50 mg QD and 10.0 mmHg with 100 mg QD in Part 1 of the study.
−Removed: Placebo-Adjusted Improvement in Systolic BP by Responder Determinant
−Removed: During two periods of time in the study, the week prior to randomization and the last week of study drug treatment, subjects were required to wear a device that captures BP readings multiple times per hour over a 24-hour period.
−Removed: This measurement provides a more complete picture of the patient’s hypertension status than in-office measurements and eliminates the impact of the phenomenon known as “white coat” hypertension, which occurs when BP readings at a healthcare provider’s office are higher than in other settings such as at home.
−Removed: The change in 24-hour systolic ABPM from baseline to week 7 or 8 for the Part 1 100 mg QD cohort, demonstrated an 8.1 mmHg observed mean placebo-adjusted reduction in systolic BP.
−Removed: The ABPM response in the 50 mg QD was complicated by evidence of “white coat” hypertension, but after eliminating data from individuals who were not hypertensive, as measured by ABPM, there was evidence of a 10.5 mmHg observed mean placebo-adjusted reduction in systolic BP in individuals who were hypertensive as measured by ABPM (the 50mg QD hypertensive ABPM set).
−Removed: The average overnight BP reduction in the 100 mg QD cohort was an observed mean placebo-adjusted reduction of 8.0 mmHg and in the 50 mg QD hypertensive ABPM set there was an observed mean placebo-adjusted reduction of 4.1 mmHg.
−Removed: The reduction in overnight BP and restoration of dipping that was also observed are of potential importance to the objective of reducing morbidity and mortality from uHTN, as the link between elevated nighttime BP and cardiovascular risk has been long established in the medical literature.
−Removed: The eGFR measures how well an individual’s kidneys are filtering waste and extra water from the body via the urine.
−Removed: In hypertensive patients, the eGFR will progressively decline and individuals may begin to exhibit signs and symptoms of CKD at eGFR levels below 45mL/min/1.73m 2 .
−Removed: As demonstrated in previous studies with antihypertensives, such as ACE inhibitors and ARBs, an initial reduction of eGFR in treated hypertensive patients may represent a positive benefit as it indicates an alleviation of pressure on the glomerulus and potentially slows or arrests the progression to CKD.
−Removed: In this trial, a dose-dependent reduction in eGFR was demonstrated, which we believe is clinically meaningful and has the potential to provide a renal protection benefit that we intend to further assess in future clinical trials.
−Removed: Lorundrostat has been observed to be well-tolerated, specifically in four key measures that we believe to be of special interest when evaluating the safety of lorundrostat:
−Removed: • Cortisol Inhibition:
−Removed: There was no clinically relevant suppression of cortisol production in serum cortisol testing as well as adrenocorticotropic hormone (ACTH)-stimulation testing.
−Removed: A slight increase in cortisol was observed in all cohorts, including placebo, but did not demonstrate a trend above normal physiological levels;
−Removed: • Hypotension (sitting systolic BP < 100 mmHg):
−Removed: Each of hypotension and orthostatic hypotension was seen in three subjects and was reversible, likely related to study medication and expected based on lorundrostat’s mechanism of action;
−Removed: • Hyponatremia (serum sodium < 135 mmol/L):
−Removed: Severe hyponatremia, possibly related to study medication, was seen in one subject with preexisting hyponatremia, and was reversible after drug discontinuation;
−Removed: • Hyperkalemia (serum potassium > 5.1 mmol/L):
−Removed: There was an expected, dose-dependent increase in serum potassium, though the majority of subjects maintained a serum potassium in the normal range.
−Removed: The two active, once-daily doses saw modest increases in potassium levels across the cohorts of 0.25 mmol/L with the 50 mg QD and 0.29 mmol/L with the 100 mg QD dose.
−Removed: Six subjects across the five active dose cohorts experienced an isolated instance of elevated potassium above 6 mmol/L (two were deemed to be a factitious reading, three worsening of pre-existing hyperkalemia and one was a confirmed de-novo episode of hyperkalemia).
−Removed: Consistent with the short terminal elimination half-life of lorundrostat, all episodes were rapidly reversible after per protocol dose reduction, temporarily holding study medication, or treatment discontinuation.
−Removed: An independent data safety monitoring board expressed no concerns about the effect of lorundrostat on serum potassium in the Target-HTN trial.
−Removed: Based on the totality of available data, there were no safety concerns that prompted changes to the Investigator’s Brochure or protocol.
−Removed: Three SAEs, including one event of chest pain, one event of metastases to peritoneum, and one event of hyponatremia, were reported and treatment was discontinued.
−Removed: Hyponatremia was assessed as possibly related to the study drug.
−Removed: The other two events were assessed as unrelated to the study drug.
−Removed: The most frequent non-serious AEs reported, defined as events with five or more affected subjects, including the placebo group, were related to hyperkalemia – all determinations above the upper limit of normal of 5.1 mmol/L (23.3%), decreased glomerular filtration (6.8%), urinary tract infections (5.3%) and hypertension (3.8%).
−Removed: In some of the hyperkalemia events, study treatment was dose adjusted temporarily or permanently discontinued according to safety guidelines in the protocol.
−Removed: Pharmacokinetics
−Removed: The 24-hour exposure/response relationship for systolic BP at week 8 across treatment groups suggests QD dosing up to 100 mg.
−Removed: The trial results suggest a minimal effective dose between 12.5 mg/24 hours and 25 mg/24 hours (12.5mg BID) and a maximum efficacious dose of 50 mg to 100 mg QD for lorundrostat.
−Removed: All doses in excess of 12.5 mg QD are active doses, which is to be expected.
−Removed: Given the relatively short half-life of lorundrostat, the group mean exposure in the 25 mg BID and 50 mg QD cohorts was similar, suggesting little
−Removed: drug accumulation.
−Removed: The comparable efficacy of the 25 mg BID and 50 mg QD cohorts suggests that once-daily dosing is sufficient to achieve maximum BP reduction.
−Removed: Exposure Versus Change in Systolic BP
−Removed: Phase 1 Clinical Trial Results
−Removed: The Phase 1 program of lorundrostat consisted of a randomized, double-blind, placebo-controlled, first-in-human trial to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple ascending doses (MAD) of lorundrostat in healthy subjects, including the effect of gender and age on the pharmacokinetics of a single dose of lorundrostat in healthy subjects.
−Removed: This trial was conducted by Mitsubishi Tanabe in the Netherlands and the trial data was used to support our open IND, under which our current lorundrostat development program is being conducted.
−Removed: We submitted the IND in February 2021, which was allowed to proceed by the FDA in March 2021.
−Removed: Lorundrostat was well-tolerated at single and multiple doses in the first-in-human trial.
−Removed: No deaths or other SAEs were observed.
−Removed: One subject in the Part 2 MAD trial, 360 mg dose group discontinued treatment due to a treatment-emergent AE of sinus tachycardia.
−Removed: Across all cohorts, dizziness/dizziness postural was reported by 9 out of 87 (10.3%) lorundrostat-treated subjects compared to 1 out of 29 (3.4%) placebo subjects.
−Removed: The high selectivity of lorundrostat was demonstrated in both the single ascending dose (SAD) and MAD parts of this trial.
−Removed: It was shown that lorundrostat decreased plasma aldosterone concentration in a dose-dependent manner in the SAD portion of the trial with a 36-77% reduction in 24-hour serum aldosterone at doses ranging from 5 mg to 800 mg.
−Removed: This finding was further validated in the MAD part of the trial with 40 mg, 120 mg, and 360 mg reducing 24-hour serum aldosterone in a dose-dependent manner.
−Removed: In the SAD trial, lorundrostat did not inhibit cortisol production across the range of doses and in the MAD study cortisol was not inhibited even with ACTH cortisol stimulation challenge on day six.
−Removed: The results of this trial demonstrated the selectivity for aldosterone synthase with lorundrostat.
−Removed: This study also assessed the effect of single and multiple doses of lorundrostat on QT prolongation and lorundrostat did not have a clinically relevant, dose-dependent effect.
−Removed: The FDA has accepted this data and granted a thorough QT study waiver.
−Removed: The impact on age and gender was also evaluated in the Phase 1 program for lorundrostat.
−Removed: It was demonstrated that neither of these sub-groups exhibited differentiated exposure levels to lorundrostat.
−Removed: A Phase 1, open-label, randomized, 2-sequence study to evaluate the effect of food on the pharmacokinetics of lorundrostat in healthy subjects has been completed.
−Removed: Based on the results of this trial, lorundrostat can be administered without regard to meals in all ongoing and future clinical trials as well as upon approval in hypertensive patients.
−Removed: We have also completed drug interaction studies with lorundrostat with metformin, esomeprazole, itraconazole, carbamazepine, digoxin, and rosuvastatin.
−Removed: The metformin study was completed based on the possible inhibition of the MATE1 transporter by lorundrostat.
−Removed: This trial demonstrated that lorundrostat has little effect on plasma exposure of metformin.
−Removed: The DDI study with esomeprazole was conducted to evaluate the effect of varying gastric pH levels on the absorption and availability of lorundrostat.
−Removed: As anticipated for lorundrostat, which is a weak base, there was reduced absorption in the alkaline gastric environment produced by the proton pump inhibitor (PPI).
−Removed: The DDI study with itraconazole was conducted to evaluate the effect of strong cytochrome P450 (CYP450) 3A4 inhibition on the exposure of lorundrostat.
−Removed: As anticipated, there was a minimal increase in lorundrostat exposure when co-administered with a strong CYP3A4 inhibitor.
−Removed: The DDI study with carbamazepine was conducted to evaluate the effect of strong CYP3A4 induction on the exposure of lorundrostat.
−Removed: As anticipated, the plasma exposure of lorundrostat was decreased when co-administered with a strong CYP3A4 inducer.
−Removed: A DDI study was conducted to evaluate the effects of lorundrostat on the p-glycoprotein substrate digoxin.
−Removed: This study revealed that in the presence of lorundrostat, digoxin exposure was increased by 67%.
−Removed: A DDI study was conducted to evaluate the effects of lorundrostat on the breast cancer resistant protein rosuvastatin.
−Removed: This study revealed that in the presence of lorundrostat, rosuvastatin exposure was increased by 23%.
−Removed: A Phase 1, open-label, parallel design study to evaluate the pharmacokinetics of lorundrostat in subjects with normal renal function (eGFR ≥ 90 mL/min/1.73 m2) and subjects with severe renal impairment (eGFR < 30 mL/min/1.73 m2) has been completed.
−Removed: Based on the results of this trial, there was no statistically significant effect of severe renal impairment on the pharmacokinetics of lorundrostat.
−Removed: A Phase 1, open-label, parallel design study to evaluate the pharmacokinetics of lorundrostat in subjects with normal liver function and subjects with mild, moderate, and severe hepatic impairment has been completed.
−Removed: The results from this indicate that lorundrostat exposure was minimally increased in subjects with mild and moderate, and larger increases were seen in subjects with severe hepatic impairment compared to subjects with normal liver function.
−Removed: Preclinical Data
−Removed: The pharmacological profile for lorundrostat was assessed via in vitro pharmacology studies that demonstrated a selectivity ratio of 374 times more selective for aldosterone inhibition over cortisol inhibition.
−Removed: Lorundrostat inhibited hCYP11B2, the synthetic pathway for aldosterone, and hCYP11B1, the synthetic pathway of cortisol with inhibition constant values of 1.27 nmol/L and 475 nmol/L, respectively.
−Removed: Single-dose oral administration of lorundrostat significantly decreased plasma aldosterone concentration (PAC) in a sodium-depleted non-human primate model.
−Removed: However, single-dose oral administration of lorundrostat did not affect cortisol in ACTH-loaded non-human primates even at a dose 100-fold higher than those required to reduce PAC.
−Removed: These results indicate that lorundrostat inhibits CYP11B2 with higher selectivity over CYP11B1, an enzyme responsible for cortisol production.
+Added: The primary endpoint of the trial was the assessment of automated office measured systolic BP from baseline for active cohorts versus placebo at six weeks, with the results pooled for all participants on 50 mg QD.
+Added: The trial met its endpoints, demonstrating clinically meaningful, statistically significant mean reduction from baseline in placebo-adjusted systolic BP at week six, and the benefit was sustained with further reduction through week 12.
+Added: Launch-HTN Phase 3 Trial
+Added: (automated office systolic BP measure, n=1,083 randomized)
+Added: Week 6 (50 mg pooled)
+Added: Placebo-Adjusted
+Added: Placebo-Adjusted
+Added: 50 mg -16.9 mmHg -9.1 mmHg
+Added: (p<0.0001)* -19.0 mmHg
+Added: 50 to100 mg -15.7 mmHg
+Added: * Primary endpoint
+Added: Key characteristics of participants enrolled in the Launch-HTN trial include:
+Added: approximately 63% had a BMI greater than or equal to 30kg/m 2 , approximately 47% were women, and approximately 29% were Black or African American.
+Added: The Advance-HTN trial was a randomized, double-blind, placebo-controlled Phase 2 pivotal trial that evaluated the efficacy and safety of lorundrostat for the treatment of confirmed uHTN or rHTN, when used as add-on therapy to a standardized, optimized, and adherent background treatment of two or three antihypertensive medications in adult participants.
+Added: Participants who met screening criteria discontinued their existing hypertension medications and started on a standard regimen of an ARB and a diuretic, if previously on two medications, or a standard regimen of ARB, diuretic, and calcium channel blocker if previously on three to five medications.
+Added: Participants who remained hypertensive despite the standardized regimen were then randomized into three cohorts for twelve weeks, receiving one of the following treatments:
+Added: lorundrostat 50 mg QD, lorundrostat 50 mg QD and an option to titrate to 100 mg QD at week four based on defined criteria or placebo.
+Added: The primary endpoint of Advance-HTN was change in 24-hour ambulatory systolic BP at week twelve from baseline for each active cohort versus placebo.
+Added: The trial was designed to evaluate lorundrostat in a uHTN or rHTN population at the highest risk, which would normally be treated by a specialist, given the severity of their condition.
+Added: The trial met its primary endpoint as well as additional prespecified outcome measures, including safety, and tolerability, and were consistent with those observed in the Launch-HTN trial.
+Added: Advance-HTN Phase 2 Trial
+Added: (24-hour ambulatory systolic BP, n=285 randomized)
+Added: Week 4 (50 mg pooled)
+Added: Placebo-Adjusted
+Added: Placebo-Adjusted
+Added: 50 mg -11.5 mmHg
+Added: 50 to100 mg -13.9 mmHg
+Added: * Primary endpoint
+Added: Key characteristics of participants enrolled in the Advance-HTN trial include:
+Added: approximately 66% had a BMI greater than or equal to 30kg/m 2 , approximately 40% were women, and approximately 53% were Black or African American.
+Added: Safety and Tolerability Results
+Added: We believe clinical safety findings in the two pivotal trials, including adrenocorticotropic hormone-stimulated and serum cortisol, change in serum potassium, serum sodium, and estimated glomerular filtration rate (eGFR), as well as incidence of hypotension, support a favorable benefit-risk profile.
+Added: In the two active treatment arms of the Launch-HTN trial, 50 mg and 50 mg with optional dose escalation to 100 mg, the incidence of treatment-emergent SAEs was twelve participants (2.2%) and two participants (0.7%), respectively, compared with eight participants (3.0%) in the placebo arm.
+Added: There was only one participant (0.2%) in the trial with a treatment-related SAE that occurred in the 50 mg arm.
+Added: The incidence of hyperkalemia (serum potassium >6.0 mmol/L) at the scheduled study visit was 1.1% and 1.5% in the 50 mg and 50 to 100 mg arms, respectively.
+Added: The per-protocol procedure for validation of suspected factitious hyperkalemia (most often due to phlebotomy-related hemolysis and release of potassium from red blood cells) specified a repeat potassium measurement within 72 hours while still taking study medication to confirm validity and provide an accurate determination of the true incidence of hyperkalemia.
+Added: After exclusion of the spurious results, the incidence of confirmed hyperkalemia was 0.6% and 1.1% in the 50 mg and 50 to 100 mg arms, respectively.
+Added: In the Advance-HTN trial, there were six participants (6.4%) and eight participants (8.4%) with treatment-emergent SAEs in the lorundrostat 50 mg and lorundrostat 50 to 100 mg arms, respectively, compared to two participants (2.1%) in the placebo arm.
+Added: Treatment-related SAEs occurred in 2%, 1%, and 0% of participants in the lorundrostat 50 mg, lorundrostat 50 to 100 mg, and placebo arms, respectively.
+Added: The incidence of hyperkalemia (serum potassium >6.0 mmol/L) at the scheduled study visit was 5.3% and 7.4% in the 50 mg and 50 to 100 mg arms, respectively.
+Added: The per-protocol procedure for validation of suspected factitious hyperkalemia (most often due to phlebotomy-related hemolysis and release of potassium from red blood cells) specified a repeat potassium measurement within 72 hours while still taking study medication to confirm validity and provide an accurate determination of the true incidence of hyperkalemia.
+Added: After exclusion of the spurious results, the incidence of confirmed hyperkalemia was 2.1% and 3.2% in the 50 mg and 50 to 100 mg arms, respectively.
+Added: Explore-CKD Clinical Trial Results
+Added: Efficacy, Safety, and Tolerability Results
+Added: The Explore-CKD trial was a randomized, double-blind, placebo-controlled, two-period, two-sequence (2x2) crossover trial.
+Added: This phase 2 trial was designed to evaluate efficacy in terms of systolic BP and UACR reduction, and safety of 25 mg QD lorundrostat added to a background treatment that included an SGLT2 inhibitor and an ACE inhibitor or an ARB in participants with uHTN or rHTN and CKD with an eGFR ≥ 30 mL/min/1.73m 2 and albuminuria (UACR of 200-5,000 mg/g) during a four-week treatment period.
+Added: The primary endpoint was placebo-adjusted change from baseline in systolic BP at week four, and an exploratory endpoint was placebo-adjusted percent change from baseline in UACR at week four.
+Added: The trial was highly statistically significant and was clinically meaningful in both of these endpoints and demonstrated a favorable safety and tolerability profile.
+Added: Explore-CKD Phase 2 Trial (N=59)
+Added: Placebo Lorundrostat 25 mg
+Added: Placebo-Adjusted
+Added: Change in systolic BP (mmHg)* -1.76 -9.25 -7.5 (p=0.0024)
+Added: Change in spot UACR (mg/g) -6.60% -30.51% -25.60% (p=0.0015)
+Added: Change in eGFR** (mL/min/1.73m 2 )
+Added: -2.20% -6.78% -4.58% (p=0.0362)
+Added: Treatment Emergent Adverse Events (TEAEs) leading to discontinuation of study drug
+Added: Confirmed hyperkalemia (K + >6.0 mmol/L)
+Added: BP, blood pressure;
+Added: UACR, Urine albumin-to-creatinine ratio;
+Added: TEAE, Treatment-emergent adverse event
+Added: * Primary endpoint.
+Added: ** Cystatin-C formula, a surrogate biomarker of renal function not subject to MATE1 transport and elimination in the glomeruli of the kidney.
+Added: Per protocol Systolic BP, UACR, and eGFR estimates and p values from Mixed Effects Model for a crossover trial with multiple baselines.
+Added: SAEs were reported in two participants (3%) during the lorundrostat treatment period and none during the placebo treatment period.
+Added: TEAEs leading to discontinuation occurred in one participant (2%) during the placebo treatment period and in two participants (3%) during the lorundrostat treatment period.
+Added: During lorundrostat treatment, one participant discontinued treatment due to elevation of potassium associated with reduced eGFR, and one participant discontinued treatment due to reduction in eGFR alone.
+Added: During the lorundrostat treatment period, an anticipated, modest decrease in mean eGFR was observed (-6.8% lorundrostat, -4.6% mL/min/1.73m 2 placebo-adjusted).
+Added: Reduction in eGFR is also seen with other renin-angiotensin-aldosterone pathway inhibitors, including ACE inhibitors, ARBs, and MRAs.
+Added: This is the result of a reduction in the deleterious over-perfusion of glomeruli due, in part, to reduced BP.
+Added: These findings add to a growing body of evidence supporting the efficacy and safety of ASIs in addressing the underlying mechanisms of hypertension, including in individuals with reduced kidney function and albuminuria.
+Added: The reduction in UACR observed in this trial is consistent with the potential of lorundrostat to have renal protective effects.
+Added: Explore-OSA Clinical Trial Results
+Added: Efficacy, Safety, and Tolerability Results
+Added: The Explore-OSA trial was a Phase 2, randomized, double-blind, placebo-controlled, two-period, two-sequence (2x2) crossover, exploratory trial that evaluated the safety and efficacy of lorundrostat 50 mg QD administered in the evening in 48 participants with hypertension and moderate-to-severe OSA.
+Added: Participants were at least 18 years old, with a systolic BP ≥ 130 mmHg and ≤ 180 mmHg, with a body mass index (BMI) ≥27 kg/m 2 .
+Added: The primary endpoint of the trial was absolute change from baseline in AHI after four weeks of active treatment compared to placebo.
+Added: After four weeks of treatment, lorundrostat 50 mg dosed in the evening did not demonstrate a clinically meaningful difference relative to placebo on the AHI, the primary endpoint.
+Added: The trial demonstrated a clinically meaningful reduction in BP at week four, with an 11.1 mmHg (p < 0.0001) and a 1.0 mmHg (p = NS) BP reduction with lorundrostat and placebo, respectively, in the pre-planned parallel arm analysis of the first period.
+Added: There was a 6.2 mmHg placebo-adjusted reduction (p < 0.0003) in BP in the crossover analysis.
+Added: Lorundrostat demonstrated a favorable safety profile and was well tolerated, with no serum potassium excursions above 5.5 mmol/L.
+Added: Analysis is ongoing for other endpoints in the trial and may be reported in future publications or medical meetings.
Our Team and Investors
Founded by Catalys Pacific in 2019, we are led by an experienced management team with diverse backgrounds and significant experience in drug discovery, development, and company building.
−Removed: Our management team consists of industry veterans with extensive experience at pharmaceutical companies such as
−Removed: Amgen, Novartis, ProQR, Sanifit, Teva, and Vertex.
+Added: Our management team consists of industry veterans with extensive experience at pharmaceutical companies such as Merck, Novartis, ProQR, Sanifit, Teva, and Vertex.
Together, our team has a proven track record in the discovery, development, and commercialization of numerous approved therapeutics.
−Removed: Since inception, we have raised approximately $498.8 million of capital from various investors, which includes $220.8 million raised in our initial public offering that occurred on February 14, 2023 from the sale of 13,800,000 shares of our common stock at $16.00 per share initial public offering (IPO) and $120.0 million raised in a private offering in February 2024 from the sale of 8,888,924 aggregate shares of our common stock and pre-funded warrants at an aggregate price of $13.50 per share.
−Removed: License Agreement with Mitsubishi Tanabe
−Removed: In July 2020, we entered into the Mitsubishi License with Mitsubishi Tanabe, pursuant to which Mitsubishi Tanabe granted us an exclusive, worldwide, royalty-bearing, sublicensable license under Mitsubishi Tanabe’s patent and other intellectual property rights to exploit products incorporating lorundrostat (formerly MT-4129) (Lorundrostat Products) for the prevention, treatment, diagnosis, detection, monitoring or predisposition testing with respect to indications, diseases and conditions in humans (the Field).
−Removed: Pursuant to the Mitsubishi License, we paid Mitsubishi Tanabe a $1.0 million upfront fee and development milestone payments of $9.0 million in the aggregate.
−Removed: We have remaining obligations to pay Mitsubishi Tanabe commercial milestone payments of up to $155.0 million in the aggregate upon first commercial sale and upon meeting certain annual sales targets, as well as additional commercial milestone payments of up to $10.0 million for a second indication.
−Removed: Additionally, we are obligated to pay Mitsubishi Tanabe tiered royalties at percentages ranging from the mid-single digits to ten percent (10%) of aggregate net sales of each Lorundrostat Product on a Lorundrostat Product-by-Lorundrostat Product and country-by-country basis, until the later of (i) the expiration of the last-to-expire valid Mitsubishi Tanabe patent claim covering a Lorundrostat Product, (ii) ten years from the first commercial sale of a Lorundrostat Product, or (iii) the expiration of regulatory exclusivity in such country.
+Added: Since inception, we have raised aggregate gross proceeds of approximately $1.1 billion from the sale of the Company’s common stock, convertible preferred stock, pre-funded warrants, and convertible notes.
+Added: License Agreement with Tanabe
+Added: In July 2020, we entered into the Tanabe License with Tanabe, pursuant to which Tanabe granted us an exclusive, worldwide, royalty-bearing, sublicensable license under Tanabe’s patent and other intellectual
+Added: property rights to exploit products incorporating lorundrostat (formerly MT-4129) (Lorundrostat Products) for the prevention, treatment, diagnosis, detection, monitoring, or predisposition testing with respect to indications, diseases, and conditions in humans (the Field).
+Added: Pursuant to the Tanabe License, we paid Tanabe a $1.0 million upfront fee and development milestone payments of $9.0 million in the aggregate.
+Added: We have remaining obligations to pay Tanabe commercial milestone payments of up to $155.0 million in the aggregate upon first commercial sale and upon meeting certain annual sales targets, as well as additional commercial milestone payments of up to $10.0 million for a second indication.
+Added: Additionally, we are obligated to pay Tanabe tiered royalties at percentages ranging from the mid-single-digits to ten percent (10%) of aggregate net sales of each Lorundrostat Product on a Lorundrostat Product-by-Lorundrostat Product and country-by-country basis, until the later of (i) the expiration of the last-to-expire valid Tanabe patent claim covering a Lorundrostat Product, (ii) ten years from the first commercial sale of a Lorundrostat Product, or (iii) the expiration of regulatory exclusivity in such country.
Such royalties are subject to reduction under specified conditions, including lack of patent coverage and generic competition.
−Removed: We are obligated to use commercially reasonable efforts to conduct and complete the development activities and to file for regulatory approval for at least one Lorundrostat Product in a major market country and consider in good faith to develop at least one Lorundrostat Product in a non-major market country.
−Removed: If we elect to sublicense our rights under the Mitsubishi License to a third party with respect to exploitation of lorundrostat or any Lorundrostat Product in certain countries in Asia, Mitsubishi Tanabe has a right of first negotiation, for a specified period of time.
−Removed: We also agreed not to commercialize any competing product prior to three years following the first commercial sale of the first Lorundrostat Product in any country without Mitsubishi Tanabe’s prior consent.
−Removed: Unless terminated earlier, the Mitsubishi License will continue until the expiration of all of our royalty obligations to Mitsubishi Tanabe.
−Removed: We may terminate the Mitsubishi License for any or no reason upon 90 or 180 days’ prior written notice to Mitsubishi Tanabe depending on whether the Lorundrostat Product has received regulatory approval.
−Removed: Mitsubishi Tanabe may terminate the Mitsubishi License if we have not initiated regulatory consultation for the first global clinical trials of lorundrostat in at least one major market country within a specified amount of time or if we or our affiliates or sublicensees initiate a challenge to the patent rights licensed to us by Mitsubishi Tanabe.
−Removed: In addition, either party may terminate the Mitsubishi License in the event of an uncured material breach by or bankruptcy of the other party, subject to certain notice and cure periods, or upon the other party’s bankruptcy or insolvency.
+Added: We are obligated to use commercially reasonable efforts to conduct and complete the development activities and to file for regulatory approval for at least one Lorundrostat Product in a major market country and consider in good faith developing at least one Lorundrostat Product in a non-major market country.
+Added: If we elect to sublicense our rights under the Tanabe License to a third party with respect to exploitation of lorundrostat or any Lorundrostat Product in certain countries in Asia, we have agreed to negotiate such a sublicense first, for a specified period of time, with Tanabe, if Tanabe notifies us that it would like to obtain such a sublicense.
+Added: We also agreed not to commercialize any competing product prior to three years following the first commercial sale of the first Lorundrostat Product in any country without Tanabe’s prior consent.
+Added: Unless terminated earlier, the Tanabe License will continue until the expiration of all of our royalty obligations to Tanabe.
+Added: We may terminate the Tanabe License for any or no reason upon 90 or 180 days’ prior written notice to Tanabe, depending on whether the Lorundrostat Product has received regulatory approval.
+Added: Tanabe may terminate the Tanabe License if we or our affiliates or sublicensees initiate a challenge to the patent rights licensed to us by Tanabe.
+Added: In addition, either party may terminate the Tanabe License in the event of an uncured material breach by or bankruptcy of the other party, subject to certain notice and cure periods, or upon the other party’s bankruptcy or insolvency.
Manufacturing
3 unchanged sentences
Sales and Marketing
−Removed: We have not yet defined our sales, marketing, or product distribution strategy for lorundrostat because it is still in clinical development.
+Added: We have not yet defined our sales, marketing, or product distribution strategy for lorundrostat because it is still in clinical development and pending regulatory approval.
Our commercial strategy may include the use of strategic partners, distributors, a contract sales force, or the establishment of our own commercial sales force.
5 unchanged sentences
Lorundrostat, if approved, will have to compete with existing therapies and new therapies that may become available in the future.
−Removed: We face potential competition from many different sources, including larger and better-funded pharmaceutical, biopharmaceutical, biotechnological, and therapeutics companies.
+Added: potential competition from many different sources, including larger and better-funded pharmaceutical, biopharmaceutical, biotechnological, and therapeutics companies.
In many cases, the companies with competing programs will have access to greater financial, technical, manufacturing, marketing, sales, and supply resources, will have more expertise and experience than us, and may be more advanced in those programs.
9 unchanged sentences
Intellectual property, including patents, trade secrets, know-how, trademarks, and copyrights, is important to our business.
−Removed: Our commercial success depends in part on our ability to obtain and maintain proprietary intellectual property protection for our clinical-stage product candidate, lorundrostat, as well as for future product candidates and novel discoveries, product development technologies, and know-how.
+Added: Our commercial success depends in part on our ability to obtain and maintain proprietary intellectual property protection for our product candidate, lorundrostat, as well as for future product candidates and novel discoveries, product development technologies, and know-how.
Our commercial success also depends in part on our ability to operate without infringing on the proprietary rights of others and to prevent others from infringing our proprietary rights.
3 unchanged sentences
We are seeking and maintaining patent protection in the United States and key foreign jurisdictions where we intend to market lorundrostat.
−Removed: Our patent portfolio includes a combination of patents and pending patent applications solely owned by us, patents and pending patent applications licensed from Mitsubishi Tanabe, and pending patent applications jointly owned with Mitsubishi Tanabe.
+Added: Our patent portfolio includes a combination of patents and pending patent applications solely owned by us, patents and pending patent applications licensed from Tanabe, and pending patent applications jointly owned with Tanabe.
As of February 26, 2026, our patent portfolio comprises 16 distinct patent families protecting our technology relating to lorundrostat and its synthetic intermediates, methods of synthesizing lorundrostat and related compounds, various formulations of lorundrostat products, as well as methods of treating diseases with lorundrostat and related compounds.
−Removed: As of January 16, 2025, our portfolio of exclusively licensed patents and pending patent applications consists of four granted U.S.
+Added: As of February 26, 2026, our portfolio of exclusively licensed patents and pending patent applications consists of four granted U.S.
one pending U.S.
−Removed: patent application;
+Added: reissue application;
+Added: two pending U.S.
+Added: patent applications;
one granted European patent that has been validated in Austria, Belgium, Czechia, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Liechtenstein, Netherlands, Norway, Poland, Portugal, Spain, Sweden, Turkey, and the United Kingdom;
−Removed: one granted European patent that has been validated in France, Germany, Italy, Spain, and the United Kingdom;
−Removed: two pending European patent applications;
+Added: one granted European patent that has been validated in France, Germany, Italy, Spain,
+Added: and the United Kingdom;
+Added: three pending European patent applications;
four granted Japanese patents;
−Removed: one pending Japanese patent application;
+Added: two pending Japanese patent applications;
one granted Canadian patent;
4 unchanged sentences
one granted Chinese patent;
−Removed: one pending Chinese patent application;
+Added: two pending Chinese patent applications;
one pending Israeli patent application;
5 unchanged sentences
one granted Mexican patent;
+Added: one pending Philippines patent application;
two granted Russian patents;
3 unchanged sentences
and one granted Vietnamese patent.
−Removed: Our portfolio of wholly owned pending patent applications consists of one pending European patent application;
−Removed: one pending Japanese patent application, one pending U.S.
−Removed: patent application;
+Added: Our portfolio of wholly owned pending patent applications consists of two pending Australian patent applications;
+Added: one pending Brazilian patent application;
+Added: four pending Canadian patent applications;
+Added: one pending Chinese patent application;
+Added: five pending European patent applications;
+Added: five pending Japanese patent applications;
+Added: three pending Korean patent applications;
+Added: three pending Malaysian patent applications;
+Added: two pending New Zealand patent applications;
+Added: three pending Singaporean patent applications;
+Added: six pending U.S.
+Added: patent applications;
+Added: one pending Vietnamese patent application;
four pending PCT International Applications;
−Removed: four pending Taiwanese patent applications;
−Removed: and four pending U.S.
+Added: five pending Taiwanese patent applications;
+Added: three pending Thai patent applications;
+Added: and five pending U.S.
provisional patent applications.
−Removed: Our portfolio of jointly owned pending patent applications consists of one pending Chinese patent application;
+Added: Our portfolio of jointly owned pending patent applications consists of one pending Canadian patent application;
+Added: one pending Chinese patent application;
two pending European patent applications;
2 unchanged sentences
two pending Malaysian patent applications;
−Removed: one pending Chinese patent application;
two pending Korean patent applications;
1 unchanged sentence
two pending Singaporean patent applications;
+Added: one pending Taiwanese patent application;
+Added: two pending Thai patent applications;
two pending U.S.
10 unchanged sentences
In addition, for patents that cover an FDA-approved drug, the Drug Price Competition and Patent Term Restoration Act of 1984, or the Hatch-Waxman Act, permits a patent term extension of up to five years beyond the expiration of the patent.
−Removed: While the length of the patent term extension is related to the length of time the drug is under regulatory review, patent term extension cannot extend the remaining term of a patent beyond a
−Removed: total of 14 years from the date of product approval, and only one patent per approved drug may be extended under the Hatch-Waxman Act.
+Added: While the length of the patent term extension is related to the length of time the drug is under regulatory review, patent term extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval, and only one patent per approved drug may be extended under the Hatch-Waxman Act.
Similar provisions are available in Europe and other foreign jurisdictions to extend the term of a patent that covers an approved drug.
24 unchanged sentences
Government authorities in the United States, at the federal, state, and local level, and in other countries extensively regulate, among other things, the research, development, testing, manufacture, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, marketing and export and import of products such as those we are developing.
−Removed: A new drug must be approved by the FDA through the new drug application (NDA) process before it may be legally marketed in the United States.
+Added: A new drug must be approved by the FDA through the NDA process before it may be legally marketed in the United States.
Drug Development Process
18 unchanged sentences
In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin.
−Removed: Clinical holds also may be imposed by the FDA at any time before or during clinical trials due to safety concerns about ongoing or proposed clinical trials or non-compliance with specific
−Removed: FDA requirements, and the trials may not begin or continue until the FDA notifies the sponsor that the hold has been lifted.
−Removed: All clinical trials must be conducted under the supervision of one or more qualified investigators in accordance with GCPs, which include the requirement that all research subjects provide their informed consent in writing for their participation in any clinical trial.
+Added: Clinical holds also may be imposed by the FDA at any time before or during clinical trials due to safety concerns about ongoing or proposed clinical trials or non-compliance with specific FDA requirements, and the trials may not begin or continue until the FDA notifies the sponsor that the hold has been lifted.
+Added: All clinical trials must be conducted under the supervision of one or more qualified investigators in accordance with GCPs, which include the requirement that all research participants provide their informed consent in writing for their participation in any clinical trial.
Clinical trials must be conducted under protocols detailing the objectives of the trial, dosing procedures, subject selection and exclusion criteria and the safety and effectiveness criteria to be evaluated.
−Removed: Each protocol must be submitted to the FDA as part of the IND, and a separate submission to the existing IND must be made for each successive clinical trial conducted during product development and for any subsequent protocol amendments.
+Added: Each protocol must be submitted to the FDA as part of the IND, and a separate submission to the existing IND must be made for each successive clinical trial conducted during
+Added: product development and for any subsequent protocol amendments.
While the IND is active, progress reports summarizing the results of the clinical trials and nonclinical studies performed since the last progress report, among other information, must be submitted at least annually to the FDA, and written IND safety reports must be submitted to the FDA and investigators for serious and unexpected suspected adverse events, findings from other studies suggesting a significant risk to humans exposed to the same or similar drugs, findings from animal or in vitro testing suggesting a significant risk to humans, and any clinically important increased incidence of a serious suspected adverse reaction compared to that listed in the protocol or investigator brochure.
Furthermore, an independent IRB at each institution participating in the clinical trial must review and approve each protocol before a clinical trial commences at that institution and must also approve the information regarding the trial and the consent form that must be provided to each trial subject or his or her legal representative, monitor the study until completed and otherwise comply with IRB regulations.
−Removed: The FDA or the sponsor may suspend a clinical trial at any time on various grounds, including a finding that the research subjects or patients are being exposed to an unacceptable health risk.
−Removed: Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the drug has been associated with unexpected serious harm to patients.
+Added: The FDA or the sponsor may suspend a clinical trial at any time on various grounds, including a finding that the research participants or patients are being exposed to an unacceptable health risk.
+Added: Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the drug has been associated with unexpected serious harm to participants.
In addition, some clinical trials are overseen by an independent group of qualified experts organized by the sponsor, known as a data safety monitoring board or committee.
2 unchanged sentences
Human clinical trials are typically conducted in three sequential phases that may overlap or be combined:
−Removed: The product candidate is initially introduced into healthy human subjects and tested for safety, dosage tolerance, absorption, metabolism, distribution, and excretion and, if possible, to gain an early indication of its effectiveness.
+Added: The product candidate is initially introduced into healthy human participants and tested for safety, dosage tolerance, absorption, metabolism, distribution, and excretion and, if possible, to gain an early indication of its effectiveness.
The product candidate is administered to a limited patient population with a specified disease or condition to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product candidate for specific targeted diseases, and to determine dosage tolerance and appropriate dosage.
9 unchanged sentences
Concurrent with clinical trials, companies usually complete additional animal studies and must also develop additional information about the chemistry and physical characteristics of the drug and finalize a process for manufacturing the product in commercial quantities in accordance with cGMPs.
−Removed: The manufacturing process must be capable of consistently producing quality batches of the product candidate and, among other things, the manufacturer must develop methods for testing the identity, strength, quality, and purity of the final drug.
+Added: The manufacturing
+Added: process must be capable of consistently producing quality batches of the product candidate and, among other things, the manufacturer must develop methods for testing the identity, strength, quality, and purity of the final drug.
In addition, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.
Review and Approval Process
−Removed: The results of product development, preclinical and other nonclinical studies, and clinical trials, along with descriptions of the manufacturing process, analytical tests conducted on the chemistry, strength and purity of the drug, proposed labeling, and other relevant information are submitted to the FDA as part of an NDA requesting approval to market the product.
−Removed: The submission of an NDA is subject to the payment of substantial user fees;
−Removed: a waiver of such fees may be obtained under certain limited circumstances.
+Added: The results of product development, preclinical and other nonclinical studies, and clinical trials, along with descriptions of the manufacturing process, analytical testing performed on the chemistry, strength and purity of the drug, proposed labeling, and other relevant information, are submitted to the FDA as part of an NDA requesting approval to market the product.
+Added: The submission of an NDA is subject to the payment of substantial user fees, although waivers or reductions may be available in certain limited circumstances.
The FDA conducts a preliminary review of all NDAs within the first 60 days after submission, before accepting them for filing, to determine whether they are sufficiently complete to permit substantive review.
+Added: In certain cases, such as when additional administrative components or user‑fee‑related materials are included, the FDA may operate under an extended timeline and issue its filing decision and related communication within 74 days of submission.
The FDA may request additional information rather than accept an NDA for filing.
In this event, the NDA must be resubmitted with the additional information.
−Removed: The resubmitted application also is subject to review before the FDA accepts it for filing.
+Added: The resubmitted application is also subject to review before the FDA accepts it for filing.
Once filed, the FDA reviews an NDA to determine, among other things, safety and efficacy for its intended use and whether its manufacturing is cGMP-compliant to assure and preserve the product’s quality and purity.
−Removed: Under the Prescription Drug User Fee Act, or PDUFA, guidelines that are currently in effect, the FDA has a goal of ten months from the date of “filing” of a standard NDA for a new molecular entity to review and act on the submission.
+Added: Under the PDUFA guidelines that are currently in effect, the FDA has a goal of ten months from the date of “filing” of a standard NDA for a new molecular entity to review and act on the submission.
This review typically takes twelve months from the date the NDA is submitted to the FDA because the FDA has approximately two months to make a “filing” decision after the application is submitted.
15 unchanged sentences
The FDA will not approve the marketing application without an approved REMS, if required.
−Removed: A REMS could include medication guides, physician communication plans, or elements to assure safe use, such as restricted distribution methods, patient registries, and other risk minimization tools.
+Added: A REMS could include medication guides, physician communication plans, or
+Added: elements to assure safe use, such as restricted distribution methods, patient registries, and other risk minimization tools.
Any of these limitations on approval or marketing could restrict the commercial promotion, distribution, prescription, or dispensing of products.
20 unchanged sentences
The sponsor of a fast-track product candidate has opportunities for more frequent interactions with the applicable FDA review team during product development and, once an NDA is submitted, the product candidate may be eligible for priority review.
−Removed: With regard to a fast track product candidate, the FDA may review sections of a marketing application on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission of the sections of the application, the FDA agrees to accept sections of the application and determines that the schedule is acceptable, and the sponsor pays any required user fees upon first submission of the section(s) of the NDA.
+Added: With regard to a fast-track product candidate, the FDA may review sections of a marketing application on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission of the sections of the application, the FDA agrees to accept
+Added: sections of the application and determines that the schedule is acceptable, and the sponsor pays any required user fees upon first submission of the section(s) of the NDA.
A product candidate intended to treat a serious or life-threatening disease or condition may also be eligible for breakthrough therapy designation to expedite its development and review.
16 unchanged sentences
Drug manufacturers and other entities involved in the manufacture and distribution of approved drugs are required to register their establishments with the FDA and certain state agencies and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with cGMPs and other laws and regulations.
−Removed: Changes to the manufacturing process are strictly regulated, and, depending on the significance of the change, may require prior FDA approval before being implemented.
+Added: Changes to the manufacturing process are strictly regulated, and, depending on the significance of the change,
+Added: may require prior FDA approval before being implemented.
Accordingly, manufacturers must continue to expend time, money, and effort in the area of production and quality control to maintain compliance with cGMPs and other aspects of regulatory compliance.
19 unchanged sentences
Such off-label uses are common across medical specialties.
−Removed: Physicians may believe that such off-label uses are the best treatment for
−Removed: many patients in varied circumstances.
+Added: Physicians may believe that such off-label uses are the best treatment for many patients in varied circumstances.
The FDA does not regulate the behavior of physicians in their choice of treatments.
4 unchanged sentences
A drug is a new chemical entity if the FDA has not previously approved any other new drug containing the same active moiety, which is the molecule or ion responsible for the action of the drug substance.
−Removed: During the exclusivity period, the FDA may not accept for review an abbreviated new drug application (ANDA), or an NDA submitted under Section 505(b)(2) (505(b)(2) NDA) submitted by another company for another drug based on the same active moiety, regardless of whether the drug is intended for the same indication as the original innovative drug or for another indication, where the applicant does not own or have a legal right of reference to all the data required for approval.
+Added: During the exclusivity period, the FDA may not accept for review an abbreviated new drug
+Added: application (ANDA), or an NDA submitted under Section 505(b)(2) (505(b)(2) NDA) submitted by another company for another drug based on the same active moiety, regardless of whether the drug is intended for the same indication as the original innovative drug or for another indication, where the applicant does not own or have a legal right of reference to all the data required for approval.
However, an application may be submitted after four years if it contains a certification of patent invalidity or non-infringement to one of the patents listed with the FDA by the innovator NDA holder.
12 unchanged sentences
Sales of any product depend, in part, on the extent to which such product will be covered by third-party payors, such as federal, state, and foreign government healthcare programs, commercial insurance, and managed healthcare organizations, and the level of reimbursement for such product by third-party payors.
−Removed: regarding the extent of coverage and amount of reimbursement to be provided are made on a plan-by-plan basis.
+Added: Decisions regarding the extent of coverage and amount of reimbursement to be provided are made on a plan-by-plan basis.
The coverage determination process is often a time-consuming and costly process that will require us to provide scientific and clinical support for the use of our products to each payor separately, with no assurance that coverage and adequate reimbursement will be obtained.
19 unchanged sentences
The IRA permits the Secretary of the Department of Health and Human Services (HHS) to implement many of these provisions through guidance, as opposed to regulation, for the initial years.
−Removed: For that and other reasons, it is currently unclear how the IRA will be effectuated.
+Added: While HHS has released guidance on a number of key provisions of the IRA (including Medicare drug rebates, Medicare drug pricing negotiation, and Part B and Part D prescription drug plans), it remains unclear how agencies will choose to implement the IRA and whether more formal rulemaking is forthcoming.
Moreover, there has recently been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several Congressional inquiries, proposed and enacted legislation, and executive orders issued by the President designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient assistance programs, and reform government program reimbursement methodologies for drug products.
−Removed: Individual states in the United States have also become increasingly active in implementing regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints,
−Removed: discounts, restrictions on certain product access, and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.
+Added: Individual states in the United States have also become increasingly active in implementing regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access, and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.
As of December 31, 2025, we had 76 full-time employees, of whom 39 were primarily engaged in research and development.
None of our employees are represented by a labor union, and we consider our employee relations to be good.
−Removed: Legal Proceedings
−Removed: We are not currently a party to any material proceeding.
−Removed: From time to time, we may become involved in legal proceedings arising in the ordinary course of our business.
−Removed: Regardless of outcome, litigation can have an adverse impact on us due to defense and settlement costs, diversion of management resources, negative publicity, reputational harm, and other factors.
Corporate Information
5 unchanged sentences
Our website address is www.mineralystx.com.
−Removed: Our investor relations website is located at https://ir.mineralystx.com.
+Added: Our investor relations website is located at https://www.ir.mineralystx.com.
We make available free of charge on our investor relations website under “SEC Filings” our annual reports on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K, our directors’ and officers’ Section 16 reports, and any amendments to those reports as soon as reasonably practicable after filing or furnishing such materials to the SEC.
7 unchanged sentences
Name Age Position
−Removed: Jon Congleton 61 Chief Executive Officer and Director
+Added: Jon Congleton 62 President, Chief Executive Officer, and Director
Adam Levy 47 Chief Financial Officer and Secretary
1 unchanged sentence
70 Chief Medical Officer
−Removed: Jon Congleton has served as our Chief Executive Officer and as a member of our board of directors since November 2020.
−Removed: Prior to joining us, Mr.
+Added: Eric Warren, R.Ph.
+Added: 53 Chief Commercial Officer
+Added: Jon Congleton has served as our President and Chief Executive Officer and as a member of our board of directors since November 2020.
+Added: Previously, Mr.
Congleton was the Chief Executive Officer of Impel NeuroPharma, Inc.
3 unchanged sentences
Congleton was previously at Teva Pharmaceutical Industries, Ltd.
−Removed: (Teva) where over 18 years he held positions in general management and global strategic marketing, including Senior Vice President of Teva’s Global Central Nervous System Disorders from April 2013 to December 2014, Senior Vice President of the Global Medicine Group from November 2011 to April 2013, and General Manager of Teva Neuroscience, Inc.
+Added: (Teva) from November 1996 to December 2014, where over 18 years he held positions in general management and global strategic marketing, including Senior Vice President of Teva’s Global Central Nervous System Disorders from April 2013 to December 2014, Senior Vice President of the Global Medicine Group from November 2011 to April 2013, and General Manager of Teva Neuroscience, Inc.
in the United States.
3 unchanged sentences
in marketing from Kansas State University.
−Removed: knowledge of our business and his extensive executive experience at multiple biopharmaceutical companies contributed to our board of directors’ conclusion that he should serve as a director of our company.
+Added: Congleton’s knowledge of our business and his extensive executive experience at multiple biopharmaceutical companies contributed to our board of directors’ conclusion that he should serve as a director of our company.
Adam Levy has served as our Chief Financial Officer since March 2022 and as our Chief Business Officer from March 2022 through January 4, 2024.
Levy also serves as a member of the board of directors of Praxis Bioresearch.
−Removed: Prior to joining Mineralys, he was the Chief Financial Officer at Sanifit Therapeutics until the company was acquired by Vifor Pharma in 2022.
+Added: Previously, he was the Chief Financial Officer at Sanifit Therapeutics until the company was acquired by Vifor Pharma in 2022.
Previously, Adam served as the Chief Business Officer at Brickell Biotech from 2019 to 2020 and led the organization’s financial operations transition as it became a publicly listed company on Nasdaq.
−Removed: Prior to that, he served as the Chief Business Officer at miRagen Therapeutics from 2016 to 2019, where he was responsible for a variety of functions including financial strategy, investor relations, business development, legal affairs, intellectual property, project and program management, and human resources.
+Added: Prior to that, he served as the Chief Business Officer at miRagen Therapeutics from 2016 to 2019, where he was responsible for a variety of functions including financial strategy, investor relations, business development, legal affairs, intellectual property, project and program management, and
+Added: human resources.
Between 2000 and 2016, Mr.
8 unchanged sentences
Rodman received his medical degree from the University of Pennsylvania and was subsequently Board Certified in Internal Medicine, Pulmonary Medicine, and Critical Care Medicine at the University of Colorado.
+Added: Eric Warren, R.Ph.
+Added: has served as our Chief Commercial Officer since April 2025.
+Added: Previously, Mr.
+Added: Warren was at Esperion Therapeutics, Inc., a commercial-stage biopharmaceutical company, where he most recently served as its Chief Commercial Officer from March 2022 to April 2025, and previously in roles as Vice President, US Sales and Marketing from January 2021 to March 2022.
+Added: From August 2020 to January 2021, Mr.
+Added: Warren was Vice President, Head of Sales and Marketing at Nabriva Therapeutics plc, a commercial-stage biopharmaceutical company.
+Added: From April 2018 to August 2020, Mr.
+Added: Warren held Vice President roles in marketing at Sanofi S.A., a pharmaceutical and healthcare company, in their cardiovascular franchise.
+Added: Additionally, from May 2006 to April 2018, Mr.
+Added: Warren held roles of increasing responsibility at Merck & Co., a pharmaceutical company.
+Added: Warren holds a Bachelor of Science in Pharmacy and is a licensed pharmacist in New York State.
Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.