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We are a clinical-stage biopharmaceutical company focused on developing medicines to target diseases driven by abnormally elevated aldosterone.
−Removed: Our product candidate, lorundrostat, is a proprietary, orally administered, highly selective aldosterone synthase inhibitor (ASI) that we are initially developing for the treatment of patients with uncontrolled hypertension (uHTN), defined as individuals who are unable to achieve BP of below 130/80 mmHg despite taking two or more 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.
−Removed: In the United States, there are over 115 million patients who have sustained elevated blood pressure (BP), or hypertension and more than half of this population fails to achieve their BP goals, defined as BP of 130/80 mmHg with currently available medications.
+Added: Our clinical-stage product candidate, lorundrostat, is a proprietary, orally administered, highly selective aldosterone synthase inhibitor (ASI) that we are initially developing for the treatment of cardiorenal conditions affected by abnormally elevated aldosterone, including hypertension and chronic kidney disease (CKD).
+Added: In the United States, there are over 115 million patients who have sustained elevated blood pressure (BP), or hypertension, and more than half of this population fails to achieve their BP goals, defined as BP of below 130/80 mmHg, with currently available medications.
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.
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 clinical trial evaluating 200 subjects with uHTN and rHTN (Target-HTN), lorundrostat demonstrated a clinically meaningful and statistically significant reduction in BP with once-daily dosing and was well tolerated.
−Removed: In addition to hypertension, we intend to develop lorundrostat for the treatment of chronic kidney disease (CKD) and believe that our product candidate holds promise to be an innovative solution for the rapidly growing unmet need in multiple cardiorenal disorders.
+Added: 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 or more 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 dosing and was well tolerated.
+Added: Abnormally elevated aldosterone levels are a key factor in driving hypertension in approximately 25% of hypertensive patients.
+Added: In addition to hypertension, we intend to investigate the benefits of lorundrostat in subjects with hypertension and CKD.
+Added: We believe that our product candidate holds promise to be an innovative solution for the rapidly growing unmet need in multiple cardiorenal metabolic disorders.
Hypertension is one of the most common medical conditions globally, afflicting approximately 1.3 billion people and resulting in an estimated average of $130 billion annual economic burden in the United States alone between 2003 and 2014.
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Food and Drug Administration (FDA)-approved novel therapies targeting hypertension, with no new class of antihypertensive treatment approved within the last fifteen years.
−Removed: Abnormally elevated aldosterone levels are a key factor in driving hypertension in approximately 25% of hypertensive patients.
−Removed: Developing an effective hypertension therapy that targets aldosterone synthase remains a significant challenge, given the tight homology between the enzymes that regulate aldosterone and cortisol synthesis, as well as aldosterone’s role in regulating potassium.
−Removed: Several large pharmaceutical companies have tried to develop ASIs, but their efforts have been hampered due to insufficient selectivity for aldosterone, resulting in off-target toxicities associated with cortisol inhibition.
−Removed: These challenges have led to the discontinuation of many ASIs in development to date.
Our Product Candidate, Lorundrostat
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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
−Removed: lorundrostat in the treatment of uHTN and rHTN in 2022.
−Removed: Given that hypertension and abnormal aldosterone biology can lead to cardiorenal disease, we intend to further develop lorundrostat across other indications such as the treatment of CKD.
+Added: We completed the Target-HTN trial, a Phase 2 proof-of-concept trial for lorundrostat in the treatment of uHTN and rHTN in 2022.
+Added: Given that hypertension and abnormal aldosterone biology can lead to cardiorenal disease, we intend to further investigate the benefits of lorundrostat across other indications such as the treatment of hypertension and CKD.
The first-in-human Phase 1 clinical trial of lorundrostat was conducted by Mitsubishi Tanabe.
See “Phase 1 Clinical Trial Results” beginning on page 15 for additional details regarding this trial.
−Removed: We may rely on the data from lorundrostat’s completed Phase 1 trial in healthy volunteers and intend to use the observations from that trial and the Phase 2 trial in uHTN and rHTN to inform the development of lorundrostat for the treatment of CKD.
Target-HTN was a randomized, double-blind, placebo-controlled trial conducted in the United States across 200 subjects with uHTN and rHTN to evaluate the efficacy of lorundrostat at various doses either once or twice a day.
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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
−Removed: the risk of stroke by 41% and coronary heart disease by 22%.
+Added: 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%.
The reduction in systolic BP, as measured by AOBP, was validated and confirmed by comparable reductions in systolic BP with lorundrostat, as measured by 24-hour mean ambulatory blood pressure monitoring (ABPM).
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In November 2022, we held an end of Phase 2 meeting with the FDA (i) to review the results of the Target-HTN trial, and (ii) to discuss our plans for a pivotal program in hypertension.
−Removed: Based on the Phase 2 results and feedback from the FDA, we intend to initiate the pivotal program noted below for lorundrostat beginning in 2023.
−Removed: We plan to initiate our ADVANCE-HTN trial, a randomized, double-blind, placebo-controlled Phase 2 clinical trial in the first half of 2023 to evaluate the safety and efficacy of lorundrostat for the treatment of uHTN and rHTN, when used as an add-on therapy to standardized background treatment of two or three antihypertensive medications in up to approximately 300 adult subjects.
−Removed: Patients will be randomized to three cohorts and treated for twelve weeks:
−Removed: lorundrostat 50 mg QD, lorundrostat 50mg QD and then titrated to 100 mg QD at week four or placebo.
−Removed: The primary endpoint of the trial will be change in systolic BP versus placebo.
−Removed: The topline data from this trial is expected in the first half of 2024.
−Removed: We also plan to initiate a randomized, double-blind, placebo-controlled Phase 3 trial in the second half of 2023 to evaluate the safety and efficacy of lorundrostat for the treatment of uHTN and rHTN, when used as an add-on therapy to background treatment of two or more antihypertensive medications in up to approximately 1,000 adults.
−Removed: The trial is expected to have a similar design as the above-described planned Phase 2 trial.
−Removed: The topline data from this trial is expected in mid-2025.
−Removed: We also plan to initiate a randomized, double-blind, placebo-controlled Phase 2 trial in mid-2023 to evaluate the safety and efficacy of lorundrostat for the treatment of uHTN and rHTN in a CKD population with topline data from this trial expected in the first half of 2024.
−Removed: The pivotal program will include an open label extension trial in which all subjects in the aforementioned trials will be given the opportunity to participate.
−Removed: Our strategy is to develop and commercialize lorundrostat for the treatment of diseases driven by abnormally elevated aldosterone, initially focused on hypertension, with the goal of eventually expanding to other cardiorenal diseases.
−Removed: Key elements of our strategy include:
−Removed: • Advance lorundrostat, our ASI product candidate, through clinical development for the treatment of uHTN and rHTN.
−Removed: uHTN and rHTN represent a significant unmet need within the 115 million patients in the United States who have hypertension.
−Removed: More than half of hypertensive patients fail to achieve their BP goals despite treatment, and approximately 20 million treated patients have systolic BP greater than 140 mmHg.
−Removed: Data from our Target-HTN Phase 2 trial demonstrated that lorundrostat lowered the systolic BP of patients with uHTN and rHTN at a clinically meaningful and statistically significant level, with a mean placebo-adjusted reduction in systolic BP of 9.6 or 7.8 mmHg with a 50 or 100 mg QD dose, respectively.
−Removed: Additionally, treatment with lorundrostat demonstrated a robust effect in obese patients, who, studies show, tend to have abnormal aldosterone biology.
−Removed: We believe our approach of normalizing aldosterone levels can provide an effective and more targeted approach for the control of hypertension.
−Removed: We plan to continue to advance the development of lorundrostat in hypertension and anticipate initiating two clinical trials to evaluate the safety and efficacy of lorundrostat for the treatment of uHTN and rHTN in 2023, as well as an open label extension trial.
−Removed: • Expand the development of lorundrostat into additional indications where abnormally elevated aldosterone is a driver in the disease pathology, including CKD and potentially other cardiorenal indications.
−Removed: Lorundrostat has been developed to normalize the production of aldosterone, and we believe this mechanism can be applied to other indications where abnormal aldosterone biology plays a role.
−Removed: We intend to initiate a
−Removed: Phase 2 uHTN and rHTN trial in a CKD population in mid-2023.
−Removed: Uninhibited aldosterone is known to play a critical role in the progression of CKD, which affects over 23 million people in the United States.
−Removed: Furthermore, we may expand the development of lorundrostat into additional cardiorenal indications.
−Removed: • Opportunistically evaluate strategic partnerships to maximize the value of lorundrostat.
−Removed: We have worldwide development and commercialization rights to lorundrostat.
−Removed: Given the potential of aldosterone inhibition to treat multiple cardiorenal conditions, we may opportunistically explore partnerships with other biopharmaceutical companies that could provide expertise and resources to expand the development and commercialization of lorundrostat.
−Removed: • Continue to evaluate opportunities to selectively expand our pipeline beyond lorundrostat.
−Removed: Our team has experience in various aspects of drug discovery, clinical development, business development and commercialization.
−Removed: We will continue to leverage our team’s expertise to selectively evaluate potential strategic partnerships, collaborations, licenses and acquisitions to expand our pipeline, particularly in cardiorenal indications.
+Added: Based on the Phase 2 results and feedback from the FDA, we decided to initiate the pivotal program noted below for lorundrostat beginning in 2023.
+Added: In April 2023, we initiated our first pivotal trial, Advance-HTN, a randomized, double-blind, placebo-controlled Phase 2 clinical trial to evaluate the safety and efficacy 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 in 261 adult subjects.
+Added: Subjects who meet screening criteria, will have their existing hypertension medications discontinued and start 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: Subjects who remain hypertensive, despite the standardized regimen are then randomized into three cohorts and treated for twelve weeks:
+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 the trial will be change in 24-hour ambulatory systolic BP at week twelve from baseline for active cohorts versus placebo.
+Added: Topline data from this trial is anticipated in the fourth quarter of 2024.
+Added: In December 2023, we also initiated our second pivotal trial, Launch-HTN, a randomized, double-blind, placebo-controlled Phase 3 clinical trial to evaluate the safety and efficacy 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 in up to approximately 1,000 adult subjects.
+Added: Subjects are then randomized into three cohorts and treated for twelve weeks:
+Added: 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.
+Added: The primary endpoint of the trial will be change in office measured systolic BP at week twelve from baseline for active cohorts versus placebo.
+Added: Topline data from this trial is expected in the second half of 2025.
+Added: In mid-2023, we initiated an open-label extension trial to allow subjects to continue to receive lorundrostat and obtain long-term safety and efficacy data.
+Added: 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.
+Added: The Explore-CKD trial is designed to evaluate lorundrostat in hypertensive subjects with Stage 2 to 3b CKD.
+Added: The Phase 2 clinical trial is being modified from its original design to enroll both naïve to and patients on SGLT2 inhibitors.
+Added: This change reflects how SGLT2 inhibitors have quickly become standard of care for patients with CKD.
+Added: We will also have all study participants stay on an SGLT2 inhibitor throughout the course of the trial.
+Added: We have also decided to lower the eGFR criteria for the proof-of-concept study from 45ml/min/1.73m2 to 30ml/min/1.73m2 and have eliminated the original Part B profiling portion of the study.
+Added: Lastly, the study periods will be reduced from eight weeks to four weeks which we believe will provide ample time to demonstrate clinical benefit on BP reduction and kidney benefit.
+Added: The primary endpoint remains change in systolic BP and an exploratory endpoint is percent change from baseline in 24-hour urinary albumin creatinine ratio at week four.
+Added: As this is an exploratory trial, interim data analyses may be conducted at one or more points in time.
+Added: Topline data from this trial continues to be anticipated between the fourth quarter of 2024 and the first quarter of 2025.
Background of Hypertension
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While there are multiple therapeutic options available, most of which are generic and accessible, more than half of all treated hypertensive patients fail to achieve their BP goal.
+Added: Abnormally elevated aldosterone levels are a key factor in driving hypertension in approximately 25% of hypertensive patients.
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.
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• Thiazide diuretics, which increase fluid excretion from the kidney by blocking reabsorption of sodium and chloride in the nephron;
−Removed: • ACE inhibitors, which inhibit the renin-angiotensin aldosterone system axis by blocking the action of ACE in the lungs, which converts angiotensin I to angiotensin II;
+Added: • ACE inhibitors, which inhibit the renin-angiotensin aldosterone system (RAAS) axis by blocking the action of ACE in the lungs, which converts angiotensin I to angiotensin II;
• ARBs, which block the effects of angiotensin II at the level of the angiotensin receptor;
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Therefore, many patients require three, four, or more antihypertensive agents in an attempt 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
−Removed: limit their use.
+Added: 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.
For example, patients taking ACE inhibitors often develop a chronic cough and those taking beta blockers often experience lethargy.
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This maintenance of homeostasis ensures the body can maintain normal BP.
−Removed: In a healthy person, homeostatic balance is maintained via a feedback loop called the renin-angiotensin aldosterone system (RAAS).
+Added: In a healthy person, homeostatic balance is maintained via a feedback loop called the RAAS.
Renin is a key enzyme that is released by the kidneys when they sense changes in BP to control the production of aldosterone, in order to help the kidneys regulate water and salt levels in the body.
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In addition to the self-regulated RAAS, there are other pathways that drive aldosterone production.
−Removed: Evolving information about hormone regulation of visceral adipocytes and the adrenal gland support the hypothesis that adipokines, specifically elevated leptin and reduced adiponectin, can affect aldosterone and renin, respectively.
+Added: Evolving information about hormone regulation of visceral adipocytes and the adrenal gland supports the hypothesis that adipokines, specifically elevated leptin and reduced adiponectin, can affect aldosterone and renin, respectively.
The net result is an increase in aldosterone and prevention of the normal feedback inhibition of renin.
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Many of these symptoms are often comorbidities in an obese population.
−Removed: Many of the therapies designed to address hypertension, such as ACE inhibitors, ARBs, beta blockers, calcium channel blockers and diuretics, were developed and introduced several decades ago, when the incidence of obesity was
−Removed: below 20% and abnormal aldosterone production affected less than 10% of the U.S.
+Added: Many of the therapies designed to address hypertension, such as ACE inhibitors, ARBs, beta blockers, calcium channel blockers, and diuretics, were developed and introduced several decades ago when the incidence of obesity was below 20% and abnormal aldosterone production affected less than 10% of the U.S.
The increasing prevalence of obesity and hypertension, driven by the renin-independent axis, has resulted in higher incidences of uHTN and rHTN.
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Additionally, when aldosterone is blocked from binding to the MR, circulating aldosterone levels increase two- to three-fold and may cause other harmful non-MR-related effects in the body.
−Removed: More recently, several pharmaceutical companies have tried to develop ASIs.
The approach of blocking the synthesis of aldosterone and reducing plasma aldosterone levels is thought to be a preferable approach versus the use of MRAs that block the action of aldosterone at the MR.
−Removed: However, the task of creating a safe and effective ASI proved to be technically challenging.
−Removed: The major enzymes in the synthesis of aldosterone and cortisol share a high degree of amino acid sequence similarity.
−Removed: Therefore, an ASI needs to be very selective in inhibiting the synthesis of aldosterone without impacting the synthesis of cortisol.
−Removed: Initial attempts to develop ASIs failed in either preclinical or clinical development due to their inability to selectively inhibit aldosterone, which resulted in such ASIs inhibiting cortisol levels and leading to related harmful effects.
+Added: 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.
+Added: While challenging to develop, there are currently four ASIs (including lorundrostat) in advanced clinical development in conditions including hypertension, primary aldosteronism, and CKD.
Our Product Candidate, 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 recently completed Target-HTN, our initial Phase 2 proof-of-concept clinical trial.
+Added: We are initially developing lorundrostat for the treatment of hypertension and have completed Target-HTN, our initial Phase 2 proof-of-concept clinical trial.
In this trial, lorundrostat was well tolerated and demonstrated compelling clinical results, and once-daily dosing flexibility.
−Removed: The observed 10 to 12 hour 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
−Removed: Some of the key differentiators that we have observed to date for lorundrostat, relative to initially developed ASIs, include:
+Added: The observed 10 to 12 hour 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.
+Added: We believe that lorundrostat’s profile may be compelling based on the following attributes:
• Compelling Clinical Results:
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 24-hour mean ABPM, which further demonstrated that lorundrostat provides both central and nighttime BP reduction;
+Added: The reduction in systolic BP was validated and confirmed by
+Added: 24-hour mean ABPM, which further demonstrated that lorundrostat provides both central and nighttime BP reduction;
• High Selectivity:
−Removed: Phase 1 and Phase 2 clinical data demonstrated high aldosterone selectivity with no cortisol suppression, 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: 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;
• Optimal Half-Life:
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Furthermore, lorundrostat was well-tolerated.
−Removed: We plan to initiate our ADVANCE-HTN trial, a randomized, double-blind, placebo-controlled Phase 2 clinical trial in the first half of 2023 to evaluate the safety and efficacy of lorundrostat for the treatment of uHTN and rHTN, when used as an add-on therapy to standardized background treatment of two or three antihypertensive medications in up to approximately 300 adult subjects.
−Removed: Patients will be randomized to three cohorts and treated for twelve weeks:
−Removed: lorundrostat 50 mg QD, lorundrostat 50mg QD and then titrated to 100 mg QD at week four or placebo.
−Removed: The primary endpoint of the trial will be change in systolic BP versus placebo.
−Removed: The topline data from this trial is expected in the first half of 2024.
−Removed: We also plan to initiate a randomized, double-blind, placebo-controlled Phase 3 trial in the second half of 2023 to evaluate the safety and efficacy of lorundrostat for the treatment of uHTN and rHTN, when used as an add-on therapy to background treatment of two or more antihypertensive medications in up to approximately 1,000 adults.
−Removed: The trial is expected to have a similar design as the above-described planned Phase 2 trial.
−Removed: The topline data from this trial is expected in mid-2025.
−Removed: We also plan to initiate a randomized, double-blind, placebo-controlled Phase 2 trial in mid-2023 to evaluate the safety and efficacy of lorundrostat for the treatment of uHTN and rHTN in a CKD population with topline data from this trial expected in the first half of 2024.
−Removed: The pivotal program will include an open label extension in which all subjects in the aforementioned trials will be given the opportunity to participate.
+Added: In April 2023, we initiated our first pivotal trial, Advance-HTN, a randomized, double-blind, placebo-controlled Phase 2 clinical trial to evaluate the safety and efficacy 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 in 261 adult subjects.
+Added: Subjects who meet screening criteria have their existing hypertension medications discontinued and start 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: Subjects who remain hypertensive, despite the standardized regimen are then randomized into three cohorts and treated for twelve weeks:
+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 the trial will be change in 24-hour ambulatory systolic BP at week twelve from baseline for active cohorts versus placebo.
+Added: Topline data from this trial is anticipated in the fourth quarter of 2024.
+Added: In December 2023, we also initiated our second pivotal trial, Launch-HTN, a randomized, double-blind, placebo-controlled Phase 3 clinical trial to evaluate the safety and efficacy 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 in up to approximately 1,000 adult subjects.
+Added: Subjects are then randomized into three cohorts and treated for twelve weeks:
+Added: 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.
+Added: The primary endpoint of the trial will be change in office measured systolic BP at week twelve from baseline for active cohorts versus placebo.
+Added: Topline data from this trial is expected in the second half of 2025.
+Added: In mid-2023, we initiated an open-label extension trial to allow subjects to continue to receive lorundrostat and obtain long-term safety and efficacy data.
+Added: 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.
+Added: The Explore-CKD trial is designed to evaluate lorundrostat in hypertensive subjects with Stage 2 to 3b CKD.
+Added: The Phase 2 clinical trial is being modified from its original design to enroll both naïve to and patients on SGLT2 inhibitors.
+Added: This change reflects how SGLT2 inhibitors have quickly become standard of care for patients with CKD.
+Added: We will also have all study participants stay on an SGLT2 inhibitor throughout the course of the trial.
+Added: We have also decided to lower the eGFR criteria for the proof-of-concept study from 45ml/min/1.73m2 to 30ml/min/1.73m2 and have eliminated the original Part B profiling portion of the study.
+Added: Lastly, the study periods will be reduced from eight weeks to four weeks which we believe will provide ample time to demonstrate clinical benefit on BP reduction and kidney benefit.
+Added: The primary endpoint remains change in systolic BP and an exploratory endpoint is percent change from baseline in 24-hour urinary albumin creatinine ratio at week four.
+Added: As this is an exploratory trial, interim data analyses may be conducted at one or more points
+Added: Topline data from this trial continues to be anticipated between the fourth quarter of 2024 and the first quarter of 2025.
Target-HTN Phase 2 Clinical Trial
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The trial was conducted in the United States.
−Removed: The objectives of the Target-HTN trial were the following:
−Removed: • Proof-of-concept for the use of lorundrostat in patients with uHTN and rHTN;
−Removed: • Establishing the dose range and regimen for late-stage development;
−Removed: • Determining whether clinical results support a once-a-day dosing regimen;
−Removed: • Evaluating hypothesized predictors of clinical response, specifically obesity and plasma renin activity, as potentially useful strategies for prioritizing the use of lorundrostat as a targeted therapy for hypertension;
−Removed: • Characterizing safety and establishing an initial estimate of the benefit/risk profile;
−Removed: • Evaluating exploratory endpoints that may be predictive of future utility of lorundrostat in associated cardiorenal indications such as congestive heart failure and CKD.
The trial was conducted in two parts.
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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 in five active cohorts and one placebo cohort.
+Added: 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.
Subjects were dosed for eight weeks, then, upon withdrawal of study medication, followed for another four weeks.
5 unchanged sentences
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: 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.
+Added: 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.
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.
17 unchanged sentences
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 statistically different from
−Removed: the reduction seen in Part 1 (see figure below).
+Added: The reduction in systolic BP in Part 2 of this trial was not statistically different from the reduction seen in Part 1 (see figure below).
As a result, we believe that lorundrostat has the potential to be effective across the entire range of renin levels.
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• 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, 10.0 mmHg with 100 mg QD in Part 1 of the study.
+Added: 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.
Placebo-Adjusted Improvement in Systolic BP by Responder Determinant
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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: Single Subject in Part 1 of Target-HTN Demonstrated Reduction in Average 24-Hour BP
−Removed: The above reflects a treatment-responsive subject in Part 1 receiving lorundrostat 100 mg QD (purple tracing) versus baseline (light blue tracing) showing average 24-hour BP reduction and restoration of normal nocturnal dipping pattern.
−Removed: Gaps in tracings represent missing measurements due to technical reasons, such as cuff slipping off.
−Removed: Although not every patient will experience similar results, we believe the above data is indicative of a patient who has responded favorably to lorundrostat.
−Removed: Central BP is the pressure in the aorta, the large artery that sends blood from the heart throughout the body.
−Removed: Many experts believe that central BP is a useful measurement because central BP may be a more accurate way of predicting if a person will have heart disease or stroke.
−Removed: The central BP reading in this trial was captured using the 24-hour ABPM via an integrated software package that measures the pulse waveform and thus obtains central BP measurements.
−Removed: As indicated below, lorundrostat at doses of 100 mg and 50 mg once-daily demonstrated relevant reductions in central BP, which we believe to be clinically meaningful, with placebo-adjusted reductions in central systolic BP of 10.0 mmHg for 100 mg QD and 10.4 mmHg for the 50 mg QD hypertensive ABPM set.
−Removed: The placebo-adjusted reductions in central diastolic BP were 5.9 mmHg for 100 mg QD and 4.2 mmHg for the 50 mg QD hypertensive ABPM set.
−Removed: Lorundrostat Effect on Systolic and Central Systolic BP
−Removed: *Results from post-hoc sensitivity analysis reflecting subjects who passed Quality Control criteria and in whom both baseline AOBP and ABPM > 130mmHg.
The eGFR measures how well an individual’s kidneys are filtering waste and extra water from the body via the urine.
4 unchanged sentences
• Cortisol Inhibition:
−Removed: As shown in the chart below, there was no clinically relevant suppression of cortisol production in serum cortisol testing as well as ACTH-stimulation testing.
+Added: There was no clinically relevant suppression of cortisol production in serum cortisol testing as well as ACTH-stimulation testing.
A slight increase in cortisol was observed in all cohorts, including placebo, but did not demonstrate a trend above normal physiological levels;
−Removed: No Meaningful Inhibition of Cortisol Observed in Target-HTN
−Removed: Serum Cortisol
• Hypotension (sitting systolic BP < 100 mmHg):
8 unchanged sentences
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 have been no safety concerns that prompted changes to the IB 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 discontinued.
+Added: Based on the totality of available data, there have been no safety concerns that prompted changes to the Investigator's Brochure or protocol.
+Added: 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.
Hyponatremia was assessed as possibly related to the study drug.
The other two events were assessed as unrelated to the study drug.
−Removed: To date, 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 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%).
+Added: To date, 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%).
In some of the hyperkalemia events, study treatment was dose adjusted temporarily or permanently discontinued according to safety guidelines in the protocol.
3 unchanged sentences
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
−Removed: mg BID and 50 mg QD cohorts was similar, suggesting little 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 blood pressure reduction.
+Added: 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
+Added: drug accumulation.
+Added: 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.
Exposure Versus Change in Systolic BP
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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.
+Added: This trial was conducted by Mitsubishi Tanabe in the Netherlands and the trial data was used to support our open investigational new drug application (IND), under which our current lorundrostat development program is being conducted.
We submitted the IND in February 2021, which was allowed to proceed by the FDA in March 2021.
8 unchanged sentences
The results of this trial demonstrated the selectivity for aldosterone synthase with lorundrostat.
+Added: 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.
+Added: The FDA has accepted this data and granted a thorough QT study waiver.
The impact on age and gender was also evaluated in the Phase 1 program for lorundrostat.
2 unchanged sentences
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 and esomeprazole.
−Removed: The metformin study was completed based on the possible inhibition of the MATE1 metabolic pathway by lorundrostat.
−Removed: MATE1 is one of four pathways for metformin metabolism.
−Removed: This trial demonstrated that lorundrostat has little effect on metformin and based on the minimal increases in metformin concentrations, lorundrostat is not expected to be viewed as even a weak inhibitor of metformin based on FDA definitions.
−Removed: The DDI study with esomeprazole was to evaluate the effect
−Removed: 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 inhibitors (PPI).
+Added: We have also completed drug interaction studies with lorundrostat with metformin, esomeprazole, itraconazole, and carbamazepine.
+Added: The metformin study was completed based on the possible inhibition of the MATE1 transporter by lorundrostat.
+Added: This trial demonstrated that lorundrostat has little effect on plasma exposure of metformin.
+Added: The DDI study with esomeprazole was conducted to evaluate the effect of varying gastric pH levels on the absorption and availability of lorundrostat.
+Added: 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).
+Added: The DDI study with itraconazole was conducted to evaluate the effect of strong cytochrome P450 (CYP450) 3A4 inhibition on the exposure of lorundrostat.
+Added: As anticipated, there was a minimal increase in lorundrostat exposure when co-administered with a strong CYP3A4 inhibitor.
+Added: The DDI study with carbamazepine was conducted to evaluate the effect of strong CYP3A4 induction on the exposure of lorundrostat.
+Added: As anticipated, the plasma exposure of lorundrostat was decreased when co-administered with a strong CYP3A4 inducer.
Further studies will be performed to provide labeling guidelines for timing vis-à-vis meals or dose-adjustment of lorundrostat for individuals using a PPI.
+Added: Additional studies will be performed with using digoxin and rosuvastatin to assess potential transporter interactions with lorundrostat.
+Added: 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.
+Added: Based on the results of this trial, there was no statistically significant effect of severe renal impairment on the pharmacokinetics of lorundrostat.
Preclinical Data
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These results indicate that lorundrostat inhibits CYP11B2 with higher selectivity over CYP11B1, an enzyme responsible for cortisol production.
−Removed: Future Clinical Development Plans
−Removed: In November 2022, we held an end of Phase 2 meeting with the FDA (i) to review the results of the Target-HTN trial, and (ii) to discuss our plans for a pivotal program in hypertension.
−Removed: The FDA agreed that the preclinical and clinical pharmacology plan supports an NDA, that the Target-HTN data supports the pivotal study program, and the proposed doses and clinical trial designs would support an indication for hypertension.
−Removed: Based on the Phase 2 results and feedback from the FDA, we intend to initiate the pivotal program noted below for lorundrostat beginning in 2023.
−Removed: We plan to initiate our ADVANCE-HTN trial, a randomized, double-blind, placebo-controlled Phase 2 clinical trial in the first half of 2023 to evaluate the safety and efficacy of lorundrostat for the treatment of uHTN and rHTN, when used as an add-on therapy to standardized background treatment of two or three antihypertensive medications in up to approximately 300 adult subjects.
−Removed: Patients will be randomized to three cohorts and treated for twelve weeks:
−Removed: lorundrostat 50 mg QD, lorundrostat 50mg QD and then titrated to 100 mg QD at week four or placebo.
−Removed: The primary endpoint of the trial will be change in systolic BP versus placebo.
−Removed: The topline data from this trial is expected in the first half of 2024.
−Removed: We also plan to initiate a randomized, double-blind, placebo-controlled Phase 3 trial in the second half of 2023 to evaluate the safety and efficacy of lorundrostat for the treatment of uHTN and rHTN, when used as an add-on therapy to background treatment of two or more antihypertensive medications in up to approximately 1,000 adults.
−Removed: The trial is expected to have a similar design as the above-described planned Phase 2 trial.
−Removed: The topline data from this trial is expected in mid-2025.
−Removed: We also plan to initiate a randomized, double-blind, placebo-controlled Phase 2 trial in mid-2023 to evaluate the safety and efficacy of lorundrostat for the treatment of uHTN and rHTN in a CKD population with topline data from this trial expected in the first half of 2024.
−Removed: The pivotal program will include an open label extension trial in which all subjects in the aforementioned trials will be given the opportunity to participate.
−Removed: Additional Indications
−Removed: We also plan to expand the development of lorundrostat into additional indications where abnormally elevated aldosterone is a driver in the disease pathology, including CKD.
−Removed: Uninhibited aldosterone is known to play a critical role in the progression of CKD, which affects over 23 million people in the United States.
−Removed: We plan to initiate a Phase 2 trial in mid-2023 to evaluate the safety and efficacy of lorundrostat for the treatment of uHTN and rHTN in a CKD population with topline data from this trial expected in the first half of 2024.
−Removed: In the future, we may expand into other cardiorenal indications driven by abnormally elevated aldosterone.
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 Amgen, Aventis, Cephalon, Novartis, ProQR, Sanifit, Teva and Vertex.
+Added: Our management team consists of industry veterans with extensive experience at pharmaceutical companies such as Amgen, Aventis, Cephalon, Novartis, ProQR, Sanifit, Teva, Vertex, Roche, Jounce, and Affamed.
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 $378.8 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 (IPO).
−Removed: Mineralys’ License Agreement with Mitsubishi Tanabe Pharma Corporation
−Removed: In July 2020, we entered into a license agreement (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: We paid Mitsubishi Tanabe a $1.0 million upfront fee, and we are obligated to pay Mitsubishi Tanabe development milestone payments of up to $9.0 million in the aggregate and 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: 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
+Added: 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.
+Added: License Agreement with Mitsubishi Tanabe
+Added: 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).
+Added: 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.
+Added: 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.
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.
14 unchanged sentences
We have not yet defined our sales, marketing, or product distribution strategy for lorundrostat because it is still in clinical development.
−Removed: Our commercial strategy may include the use of strategic partners, distributors, a contract sales force, or the establishment of our own commercial sales force.
+Added: Our commercial strategy may include the use of strategic partners, distributors,
+Added: a contract sales force, or the establishment of our own commercial sales force.
We plan to further evaluate these alternatives as we approach approval for lorundrostat, if any.
−Removed: The biopharmaceutical industry is characterized by rapid advancing technologies, intense competition and a strong emphasis on proprietary and novel products and product candidates.
+Added: The biopharmaceutical industry is characterized by rapidly advancing technologies, intense competition, and a strong emphasis on proprietary and novel products and product candidates.
Lorundrostat, if approved, may address multiple markets.
4 unchanged sentences
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.
−Removed: may also compete with universities and other research institutions that may be active in research in our target indications and could be in direct competition with us.
+Added: Moreover, we may also compete with universities and other research institutions that may be active in research in our target indications and could be in direct competition with us.
Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.
We believe our current and future competition can be grouped into three broad categories:
−Removed: • Companies working to develop ASIs, including AstraZeneca, Boehringer Ingelheim, Damian Pharma and PhaseBio;
−Removed: • Companies with product candidates with other mechanisms of action, including Alnylam, Idorsia, Ionis, KBP BioSciences, Quantum Genomics and Sihuan Pharmaceutical Holdings Group;
−Removed: • Companies commercializing standard-of-care antihypertensive agents, such as ACE inhibitors, ARBs, thiazide diuretics and calcium channel blockers, many of which are available as generic medicines at very low prices including AstraZeneca, Johnson & Johnson, Merck, Novartis and Pfizer.
+Added: • companies working to develop ASIs, including AstraZeneca, Boehringer Ingelheim, Damian Pharma and JIXING;
+Added: • companies with product candidates with other mechanisms of action, such as non-steroidal MRAs and angiotensinogen directed therapies, including Alnylam, Idorsia, Ionis, Novo Nordisk, Quantum Genomics, and Sihuan Pharmaceutical Holdings Group, Roche;
+Added: • companies commercializing standard-of-care antihypertensive agents, such as ACE inhibitors, ARBs, thiazide diuretics, calcium channel blockers, and MRAs, many of which are available as generic medicines at very low prices including AstraZeneca, Bayer, Johnson & Johnson, Merck, Novartis, and Pfizer.
If we successfully obtain approval for lorundrostat or any future product candidate, we believe that the key competitive factors that will affect the success of lorundrostat will be efficacy, safety, tolerability, convenience, price, and the availability of reimbursement from government and other third-party payors relative to such competing products.
1 unchanged sentence
Intellectual Property
−Removed: Intellectual property, including patents, trade secrets, trademarks and copyrights, is important to our business.
+Added: Intellectual property, including patents, trade secrets, know-how, trademarks, and copyrights, is important to our business.
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.
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and foreign patents and applications relating to our product candidates, technology, inventions, and improvements that are important to the development and implementation of our business.
−Removed: Our patent portfolio is built with a goal of establishing broad protection that generally includes, for the product candidate compound, claims directed to composition of matter, pharmaceutical compositions or formulations, methods of synthesis, and methods of treatment using such pharmaceutical compositions or formulations.
−Removed: 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 patent applications solely owned by us, patents and pending patent applications licensed from Mitsubishi Tanabe Pharma Corporation, or Mitsubishi Tanabe, and pending patent applications jointly owned with Mitsubishi Tanabe.
+Added: Our patent portfolio is built with the goal of establishing broad protection that generally includes, for the product candidate compound, claims directed to composition of matter, pharmaceutical compositions or formulations, methods of synthesis, and methods of treatment using such pharmaceutical compositions or formulations.
+Added: We are seeking and maintaining patent protection in the United States and key foreign
+Added: jurisdictions where we intend to market lorundrostat.
+Added: 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.
As of February 16, 2023, our patent portfolio comprises 11 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.
As of February 16, 2023, our portfolio of exclusively licensed patents and pending patent applications consists of four granted U.S.
+Added: one pending U.S.
+Added: patent application;
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;
one granted European patent that has been validated in France, Germany, Italy, Spain, and the United Kingdom;
−Removed: one pending European application;
+Added: two pending European patent applications;
four granted Japanese patents;
+Added: one pending Japanese patent application;
one granted Canadian patent;
+Added: one pending Canadian patent application;
one granted Australian patent;
−Removed: one pending Brazilian application;
+Added: three pending Brazilian applications;
one granted Chinese patent;
+Added: one pending Chinese patent application;
+Added: one pending Israeli patent application;
one granted Indian patent;
1 unchanged sentence
one granted Korean patent;
+Added: one pending Korean patent application;
one granted Malaysian patent;
4 unchanged sentences
one pending Thai application;
−Removed: one granted Vietnamese patent;
−Removed: and one pending PCT International Application.
−Removed: Our portfolio of wholly owned pending patent applications consists of one pending PCT International Application and three pending U.S.
+Added: and one granted Vietnamese patent.
+Added: Our portfolio of wholly owned pending patent applications consists of one pending European patent application;
+Added: one pending Japanese patent application, one pending U.S.
+Added: patent application;
+Added: two pending PCT International Applications;
+Added: two pending Taiwanese patent applications;
+Added: and four pending U.S.
provisional patent applications.
−Removed: Our portfolio of jointly owned pending patent applications consists of two pending PCT International Applications and one pending U.S.
−Removed: provisional patent application.
−Removed: Granted patents and pending applications in our portfolio of exclusively licensed patents and pending patent applications, if granted, have nominal expiration dates ranging from 2035 to about 2042, without accounting for any
−Removed: available patent term adjustments or extensions.
+Added: Our portfolio of jointly owned pending patent applications consists of one pending Chinese patent application;
+Added: one pending European patent application;
+Added: one pending Indonesian patent application;
+Added: one pending Japanese patent application;
+Added: one pending Malaysian patent application;
+Added: one pending Chinese patent application;
+Added: one pending Korean patent application;
+Added: one pending Philippines patent application;
+Added: one pending Singaporean patent application;
+Added: one pending U.S.
+Added: patent application;
+Added: one pending Vietnamese patent application;
+Added: and one pending PCT International Application.
+Added: Granted patents and pending applications in our portfolio of exclusively licensed patents and pending patent applications, if granted, have nominal expiration dates ranging from 2035 to about 2042, without accounting for any available patent term adjustments or extensions.
Pending applications in our portfolio of wholly and jointly owned pending patent applications have nominal expiration dates ranging from 2041 to about 2042, without accounting for any available patent term adjustments or extensions.
If filed and subsequently granted, patent applications claiming priority to pending U.S.
−Removed: Provisional Applications in our portfolio of wholly and jointly owned pending patent applications will have expiration dates ranging from 2042 to 2043, without accounting for any available patent term adjustments or extensions.
+Added: Provisional Applications in our portfolio of wholly and jointly owned pending patent applications will have expiration dates ranging from 2042 to about 2044, without accounting for any available patent term adjustments or extensions.
The term of individual patents in our portfolio depends upon the legal term of patents in the countries in which they are obtained.
In most countries in which we file, including the United States, the patent term is 20 years from the earliest date of filing a non-provisional patent application.
−Removed: In the United States, the term of a patent may be eligible for patent term adjustment, which permits patent term restoration as compensation for delays incurred at the USPTO during the patent prosecution process.
+Added: In the United States, the term of a patent may be eligible for patent term adjustment, which permits patent term restoration as compensation for delays incurred at the United States Patent and Trademark Office (USPTO) during the patent prosecution process.
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.
2 unchanged sentences
In the future, if and when our products receive FDA approval, we expect to apply for patent term extensions on patents covering those products.
−Removed: We plan to seek any available patent term extension to any granted patents we may be granted in any jurisdiction where such extensions are available;
+Added: We plan to seek any
+Added: available patent term extension to any granted patents we may be granted in any jurisdiction where such extensions are available;
however, there is no guarantee that the applicable authorities, including the FDA in the United States, will agree with our assessment of whether such extensions should be granted, and if granted, the length of such extensions.
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Government Regulation
−Removed: Government authorities in the United States, at the federal, state and local level, and 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: 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,
+Added: approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, marketing and export and import of products such as those we are developing.
+Added: A new drug must be approved by the FDA through the new drug application (NDA) or biologics license application (BLA) process before it may be legally marketed in the United States.
Drug Development Process
−Removed: In the United States, the FDA regulates drugs under the federal Food, Drug, and Cosmetic Act (FDCA) and its implementing regulations.
+Added: In the United States, the FDA regulates drugs under the federal Food, Drug, and Cosmetic Act (FDCA), the Public Health Service (PHS) Act, and implementing regulations.
The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, and local statutes and regulations require the expenditure of substantial time and financial resources.
4 unchanged sentences
• performance of adequate and well-controlled human clinical trials in accordance with Good Clinical Practice regulations (GCPs) to evaluate the safety and efficacy of the product candidate for its intended use;
−Removed: • submission to the FDA of an NDA after completion of all pivotal trials;
+Added: • submission to the FDA of an NDA or BLA after completion of all pivotal trials;
• satisfactory completion of an FDA advisory committee review, if applicable;
−Removed: • satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the drug is produced to assess compliance with current Good Manufacturing Practices (cGMPs) requirements to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity, and of potential inspection of selected clinical investigation sites to assess compliance with GCPs;
−Removed: • FDA review and approval of the NDA to permit commercial marketing of the product for particular indications for use in the United States.
+Added: • satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the drug is produced to assess compliance with current Good Manufacturing Practice (cGMP) requirements to assure that the facilities, methods, and controls are adequate to preserve the drug’s identity, strength, quality, and purity, and of potential inspection of selected clinical investigation sites to assess compliance with GCPs;
+Added: • FDA review and approval of the NDA or BLA to permit commercial marketing of the product for particular indications for use in the United States.
Once a product candidate is identified for development, it enters the preclinical testing stage.
1 unchanged sentence
An IND sponsor must submit the results of the preclinical tests, together with manufacturing information and analytical data, to the FDA as part of an IND.
−Removed: An IND is a request for authorization from the FDA to administer an investigational drug product to humans.
+Added: An IND is a request for authorization from the FDA to administer an investigational drug product (including biological products) to humans.
An IND will also include a protocol detailing, among other things, the objectives of the clinical trial, the parameters to be used in monitoring safety, and the effectiveness criteria to be evaluated, if the trial includes an efficacy evaluation.
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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.
−Removed: While the IND is active, progress reports summarizing the results of the clinical trials and nonclinical studies performed since the
−Removed: 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.
+Added: 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.
2 unchanged sentences
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.
−Removed: Depending on its charter, this group may determine whether a trial may move forward at designated check points based on access to certain data from the trial.
+Added: Depending on its charter, this group may determine whether a trial may move forward at designated checkpoints based on access to certain data from the trial.
There are also requirements governing the reporting of ongoing clinical studies and clinical study results to public registries, including clinicaltrials.gov.
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These trials are used to gain additional experience from the treatment of patients in the intended therapeutic indication.
−Removed: In certain instances, the FDA may mandate the performance of Phase 4 clinical trials as a condition of approval of an NDA.
−Removed: During the development of a new drug, sponsors are given opportunities to meet with the FDA at certain points.
−Removed: These points may be prior to submission of an IND, at the end of Phase 2, and before an NDA is submitted.
+Added: In certain instances, the FDA may mandate the performance of Phase 4 clinical trials as a condition of approval of an NDA/BLA.
+Added: During the development of a new drug or biologic, sponsors are given opportunities to meet with the FDA at certain points.
+Added: Generally, these points may be prior to submission of an IND, at the end of Phase 2, and before an NDA/BLA is submitted.
Meetings at other times may be requested.
−Removed: These meetings can provide an opportunity for the sponsor to share information about the data gathered to date, for the FDA to provide advice, and for the sponsor and the FDA to reach agreement on the next phase of development.
+Added: These meetings can provide an
+Added: opportunity for the sponsor to share information about the data gathered to date, for the FDA to provide advice, and for the sponsor and the FDA to reach agreement on the next phase of development.
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.
2 unchanged sentences
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 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;
+Added: 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/BLA requesting approval to market the product.
+Added: The submission of an NDA/BLA is subject to the payment of substantial user fees;
a waiver of such fees may be obtained under 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.
−Removed: The FDA may request additional information rather than accept an NDA for filing.
−Removed: In this event, the NDA must be resubmitted with the additional information.
+Added: The FDA may request additional information rather than accept an NDA/BLA for filing.
+Added: In this event, the NDA/BLA must be resubmitted with the additional information.
The resubmitted application also is subject to review before the FDA accepts it for filing.
−Removed: Once filed, the FDA reviews an NDA to determine, among other things, whether a product is safe and effective for its intended use and whether its manufacturing is cGMP-compliant to assure and preserve the product’s identity, strength, quality and purity.
+Added: Once filed, the FDA reviews an NDA to determine, among other things, safety and efficacy (NDA)/safety, purity, and potency (BLA) for its intended use and whether its manufacturing is cGMP-compliant to assure and preserve the product’s identity, strength/potency, quality, and purity.
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.
−Removed: This review typically takes twelve months from the date the NDA is submitted to FDA because the FDA has approximately two months to make a “filing” decision after it the application is submitted.
−Removed: The FDA may refer an application for a novel drug to an advisory committee.
+Added: This review typically takes twelve months from the date the NDA/BLA is submitted to the FDA because the FDA has approximately two months to make a “filing” decision after the application is submitted.
+Added: The FDA may refer an application for a novel drug or therapeutic biological product to an advisory committee.
An advisory committee is a panel of independent experts, including clinicians and other scientific experts, that reviews, evaluates, and provides a recommendation as to whether the application should be approved and under what conditions.
The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.
−Removed: Before approving an NDA, the FDA will typically inspect the facility or facilities where the product is manufactured.
−Removed: Additionally, before approving an NDA, the FDA may inspect one or more clinical trial sites to assure compliance with GCPs.
−Removed: After the FDA evaluates an NDA and conducts inspections of manufacturing facilities where the investigational product and/or its drug substance will be produced, the FDA may issue an approval letter or a Complete Response Letter (CRL).
+Added: Before approving an NDA/BLA, the FDA will typically inspect the facility or facilities where the product is manufactured.
+Added: Additionally, before approving an NDA/BLA, the FDA may inspect one or more clinical trial sites to assure compliance with GCPs.
+Added: After the FDA evaluates a marketing application and conducts inspections of manufacturing facilities where the investigational product and/or its drug substance will be produced, the FDA may issue an approval letter or a Complete Response Letter (CRL).
An approval letter authorizes commercial marketing of the drug with prescribing information for specific indications.
A CRL indicates that the review cycle of the application is complete, and the application will not be approved in its present form.
−Removed: A CRL usually describes the specific deficiencies in the NDA identified by the FDA and may require additional clinical data, such as an additional clinical trial or other significant and time-consuming requirements related to clinical trials, nonclinical studies or manufacturing.
−Removed: If a CRL is issued, the sponsor must resubmit the NDA to address all of the deficiencies identified in the letter or withdraw the application.
−Removed: Even if such data and information are submitted, the FDA may decide that the NDA does not satisfy the criteria for approval.
+Added: A CRL usually describes the specific deficiencies in the NDA/BLA identified by the FDA and may require additional clinical data, such as an additional clinical trial or other significant and time-consuming requirements related to clinical trials, nonclinical studies, or manufacturing.
+Added: If a CRL is issued, the applicant must resubmit the NDA/BLA to address all of the deficiencies identified in the letter or withdraw the application.
+Added: Even if such data and information are submitted, the FDA may decide that the NDA/BLA does not satisfy the criteria for approval.
If a product receives regulatory approval, the approval may be significantly limited to specific diseases and dosages or the indications for use may otherwise be limited, which could restrict the commercial value of the product.
−Removed: In addition, the FDA may require a sponsor to conduct Phase 4 testing, which involves clinical trials designed to further assess a drug’s safety and effectiveness after NDA approval, and may require testing and surveillance programs to monitor the safety of approved products that have been commercialized.
+Added: In addition, the FDA may require a sponsor to conduct Phase 4 testing, which involves clinical trials designed to further assess a drug’s safety and effectiveness after NDA/BLA approval, and may require
+Added: testing and surveillance programs to monitor the safety of approved products that have been commercialized.
The FDA may also place other conditions on approval including the requirement for a risk evaluation and mitigation strategy (REMS), to assure the safe use of the drug.
−Removed: If the FDA concludes a REMS is needed, the sponsor of the NDA must submit a proposed REMS.
−Removed: The FDA will not approve the NDA without an approved REMS, if required.
+Added: If the FDA concludes a REMS is needed, the applicant of the NDA/BLA must submit a proposed REMS.
+Added: The FDA will not approve the marketing application without an approved REMS, if required.
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.
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In addition, the Pediatric Research Equity Act (PREA) requires a sponsor to conduct pediatric clinical trials for most drugs, for a new active ingredient, new indication, new dosage form, new dosing regimen, or new route of administration.
−Removed: Under PREA, original NDAs and supplements must contain a pediatric assessment unless the sponsor has received a deferral or waiver.
+Added: Under PREA, original NDAs and BLAs, and supplements to them, must contain a pediatric assessment unless the sponsor has received a deferral or waiver.
The required assessment must evaluate the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations and support dosing and administration for each pediatric subpopulation for which the product is safe and effective.
1 unchanged sentence
A deferral may be granted for several reasons, including a finding that the drug is ready for approval for use in adults before pediatric clinical trials are complete or that additional safety or effectiveness data needs to be collected before the pediatric clinical trials begin.
−Removed: The FDA must send a non-compliance letter to any sponsor that fails to submit the required assessment, keep a deferral current or fails to submit a request for approval of a pediatric formulation.
+Added: The FDA must send a non-compliance letter to any sponsor that fails to submit the required assessment, keep a deferral current, or submit a request for approval of a pediatric formulation.
Orphan Drug Designation
Under the Orphan Drug Act, the FDA may grant orphan designation to a drug intended to treat a rare disease or condition, which is a disease or condition that affects fewer than 200,000 individuals in the United States or, if it affects more than 200,000 individuals in the United States, there is no reasonable expectation that the cost of developing and making a drug product available in the United States for this type of disease or condition will be recovered from sales of the product.
−Removed: Orphan designation must be requested before submitting an NDA.
−Removed: After the FDA grants orphan designation,
−Removed: the identity of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA.
+Added: Orphan designation must be requested before submitting an NDA or BLA.
+Added: After the FDA grants orphan designation, the identity of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA.
Orphan designation does not convey any advantage in or shorten the duration of the regulatory review and approval process.
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For example, the fast track designation program is intended to expedite or facilitate the process of developing and reviewing product candidates that meet certain criteria.
−Removed: Specifically, investigational drugs are eligible for fast track designation if they are intended to treat a serious or life-threatening disease or condition and demonstrate the potential to address unmet medical needs for the disease or condition.
−Removed: 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 consider for review sections of the NDA on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission of the sections of the NDA, the FDA agrees to accept sections of the NDA and determines that the schedule is acceptable, and the sponsor pays any required user fees upon submission of the first section of the NDA.
+Added: Specifically, investigational drugs are eligible for fast track designation if they are intended to treat a serious or life-threatening disease or condition and demonstrate the potential to address unmet medical needs for the disease or
+Added: 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 or BLA is submitted, the product candidate may be eligible for priority review.
+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 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/BLA.
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.
2 unchanged sentences
Any product candidate submitted to the FDA for approval, including a product candidate with a fast track designation or breakthrough designation, may also be eligible for other types of FDA programs intended to expedite development and review, such as priority review and accelerated approval.
−Removed: An NDA is eligible for priority review if the product candidate is designed to treat a serious condition, and if approved, would provide a significant improvement in safety or efficacy compared to marketed products.
−Removed: The FDA will attempt to direct additional resources to the evaluation of an application for a new drug designated for priority review in an effort to facilitate the review.
−Removed: The FDA endeavors to review applications with priority review designations within six months of the filing date as compared to ten months for review of new molecular entity NDAs under its current PDUFA review goals.
+Added: An NDA/BLA is eligible for priority review if the product candidate is designed to treat a serious condition, and if approved, would provide a significant improvement in safety or efficacy compared to marketed products.
+Added: The FDA will attempt to direct additional resources to the evaluation of an application for a new drug or biologic designated for priority review in an effort to facilitate the review.
+Added: The FDA endeavors to review applications with priority review designations within six months of the filing date as compared to ten months for standard review under its current PDUFA review goals.
In addition, a product candidate may be eligible for accelerated approval.
−Removed: Drug products intended to treat serious or life-threatening diseases or conditions may be eligible for accelerated approval upon a determination that the product candidate has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments.
+Added: Drug products (including biologics) intended to treat serious or life-threatening diseases or conditions may be eligible for accelerated approval upon a determination that the product candidate has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments.
As a condition of approval, the FDA may require that a sponsor of a drug receiving accelerated approval perform adequate and well-controlled confirmatory clinical trials.
4 unchanged sentences
Post-Approval Requirements
−Removed: Any products manufactured or distributed pursuant to FDA approvals are subject to pervasive and continuing regulation by the FDA, including, among other things, requirements relating to record-keeping, reporting of adverse experiences, periodic reporting, product sampling and distribution, and advertising and promotion of the product.
−Removed: After approval, most changes to the approved product, such as adding new indications, certain manufacturing changes and additional labeling claims, are subject to further FDA review and approval.
+Added: Any products manufactured or distributed pursuant to FDA approvals are subject to pervasive and continuing regulation by the FDA, including, among other things, requirements relating to record-keeping, reporting of adverse experiences, supply chain security, reporting of permanent discontinuance or interruptions in supply, other periodic reporting, product sampling and distribution, and advertising and promotion of the product.
+Added: After approval, most changes to the approved product, such as adding new indications, certain
+Added: manufacturing changes, and additional labeling claims, are subject to further FDA review and approval.
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.
26 unchanged sentences
Market exclusivity provisions under the FDCA can delay the submission or the approval of certain marketing applications.
−Removed: The FDCA provides a five-year period of non-patent data exclusivity within the United States to the first
−Removed: applicant to obtain approval of an NDA for a new chemical entity.
+Added: In the context of smaller molecule new drugs, the FDCA provides a five-year period of non-patent data exclusivity within the United States to the first applicant to obtain approval of an NDA for a new chemical entity.
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.
5 unchanged sentences
However, an applicant submitting a full NDA would be required to conduct, or obtain a right of reference to, all of the preclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and effectiveness.
+Added: In the context of biological products, Section 351 of the PHS Act provides 12 years of market exclusivity from the date of first licensure of a reference product.
+Added: During the first four years of the period of exclusivity, the FDA may not accept for review an application for license to market a biosimilar product.
+Added: Any approved biosimilar licenses may not be made effective until expiration of the 12-year marketing exclusivity period of the reference product.
+Added: The approvability of an abbreviated BLA for biosimilar products is presently delinked from the various processes for resolving patent disputes.
Pediatric exclusivity is another type of marketing exclusivity available in the United States.
2 unchanged sentences
Other Healthcare Laws
−Removed: Pharmaceutical companies are subject to additional healthcare regulation and enforcement by the federal government and by authorities in the states and foreign jurisdictions in which they conduct their business and may constrain the financial arrangements and relationships through which we research as well as sell, market and distribute any products for which we obtain marketing approval.
+Added: Pharmaceutical companies and developers and manufacturers of therapeutic biological products are subject to additional healthcare regulation and enforcement by the federal government and by authorities in the states and foreign jurisdictions in which they conduct their business and may constrain the financial arrangements and relationships through which we research as well as sell, market, and distribute any products for which we obtain marketing approval.
Such laws include, without limitation, federal and state anti-kickback, fraud and abuse, false claims, data privacy and security, and physician and other healthcare provider transparency laws and regulations.
25 unchanged sentences
For that and other reasons, it is currently unclear how the IRA will be effectuated.
−Removed: 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 programs, and reform government program reimbursement methodologies for drug products.
−Removed: It is also possible that additional governmental action is taken in response to the COVID-19 pandemic.
+Added: 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,
+Added: 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.
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.
−Removed: As of December 31, 2022, we had 12 full-time employees, of whom eight were primarily engaged in research and development.
+Added: As of December 31, 2023, we had 28 full-time employees, of whom 22 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.
11 unchanged sentences
Our investor relations website is located at https://ir.mineralystx.com.
−Removed: 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.
+Added: 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 U.S.
+Added: Securities and Exchange Commission (the SEC).
They are also available for free on the SEC’s website at www.sec.gov.
1 unchanged sentence
Investors should monitor such website, in addition to following our press releases, SEC filings, and public conference calls and webcasts.
−Removed: Information relating to our corporate governance is also included on our investor relations website The information in or accessible through the SEC and our website are not incorporated into, and are not considered part of, this filing.
+Added: Information relating to our corporate governance is also included on our investor relations website.
+Added: The information in or accessible through the SEC and our website are not incorporated into, and are not considered part of, this filing.
+Added: Information about our Executive Officers
+Added: The following table sets forth information concerning our executive officers.
+Added: Name Age Position
+Added: Jon Congleton 60 Chief Executive Officer and Director
+Added: Adam Levy 46 Chief Financial Officer and Secretary
+Added: David Rodman, M.D.
+Added: 68 Chief Medical Officer
+Added: Jon Congleton has served as our Chief Executive Officer and as a member of our board of directors since November 2020.
+Added: Prior to joining us, Mr.
+Added: Congleton was the Chief Executive Officer of Impel NeuroPharma, Inc.
+Added: from September 2017 to May 2020.
+Added: Prior to that, he served as the Chief Executive Officer and as a director of Nivalis Therapeutics, Inc.
+Added: from January 2015 to February 2017.
+Added: Congleton was previously at Teva Pharmaceutical Industries, Ltd.
+Added: (Teva) where over 18 years he held positions in general
+Added: 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: in the United States.
+Added: Prior to joining Teva, Mr.
+Added: Congleton spent ten years in a variety of commercial roles with predecessor companies of Sanofi.
+Added: Congleton earned a B.S.
+Added: in marketing from Kansas State University.
+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.
+Added: Adam Levy has served as our Chief Financial Officer since March 2022 and as our and Chief Business Officer from March 2022 through January 4, 2024.
+Added: Levy also serves as a member of the board of directors of Praxis Bioresearch.
+Added: 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, 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.
+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 human resources.
+Added: Between 2000 and 2016, Mr.
+Added: Levy held multiple investment banking positions at Merrill Lynch, Jefferies Group, and Wedbush Securities.
+Added: Levy received a B.S.
+Added: in Business Management and Marketing from Cornell University.
+Added: David Rodman, M.D.
+Added: has served as our Chief Medical Officer since January 2021.
+Added: Previously, Dr.
+Added: Rodman served in various roles at miRagen, Vertex Pharmaceuticals Inc., and Novartis Institutes for BioMedical Research.
+Added: Rodman was elected to the American Society for Clinical Investigation and named an Established Investigator and Fellow of the American Heart Association.
+Added: 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.
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.