Albuminuria

– On track to initiate planned Phase 3 pivotal Launch-HTN trial of lorundrostat to treat patients with uncontrolled or resistant hypertension in 2H 2023 – – Expect to initiate planned Phase 2 Explore-CKD trial of lorundrostat alone and in combination with SGLT2 inhibitor to treat hypertensive patients with chronic kidney disease (CKD) in 2H 2023 – – Conference call today at 4:30 p.m. ET – RADNOR, Pa., Nov. 07, 2023 (GLOBE NEWSWIRE) -- Mineralys Therapeutics, Inc. (Nasdaq: MLYS), a clinical-stage biopharmaceutical company focused on developing medicines to target hypertension, chronic kidney disease (CKD) and other diseases driven by abnormally elevated aldosterone, today announced financial results for the quarter ending September 30, 2023, and provided a corporate update. “The third quarter was productive for Mineralys with ongoing progress in our clinical development of lorundrostat, the publication of our proof-of-concept study, Target-HTN, in the Journal of the American Medical Association and the addition of two new Board members. We have finalized the designs of Launch-HTN and Explore-CKD, which we believe strengthens our ability to generate data that will support patients’ real-world needs. We continue to anticipate that the Phase 3 Launch-HTN and the Phase 2 Explore-CKD trials will be initiated by the end of 2023,” stated Jon Congleton, Chief Executive Officer of Mineralys Therapeutics. Recent Corporate and Clinical Highlights Pivotal Advance-HTN trial – The ongoing trial is evaluating the safety and efficacy of lorundrostat for the treatment of uncontrolled hypertension (uHTN) or resistant hypertension (rHTN), when used as an add-on therapy to standardized background treatment of two or three antihypertensive medications. For subjects in the Advance-HTN trial, the treatment withdrawal component of the program has been moved forward from week 48 of treatment in the open-label extension trial to week 12 of Advance-HTN. This amendment was implemented to characterize the durability of changes in blood pressure and other pharmacodynamic measures of efficacy following the double-blind treatment period. Due to this protocol amendment and the Company’s current visibility into the enrollment curve, the Company’s expectations for topline data have been revised from the first half of 2024 to the second half of 2024. Open-Label Extension Trial – In mid-2023, the Company initiated an open-label extension trial to allow subjects to continue to receive lorundrostat and obtain long-term safety and efficacy data. 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.Late-Breaking Poster Presented at ASN’s Kidney Week 2023 – The late-breaking poster presented at the American Society of Nephrology’s (ASN) Kidney Week 2023 by David Rodman, Chief Medical Officer of Mineralys, highlighted lorundrostat’s potential as the first precision targeted treatment for hypertension. This poster concluded that obesity, and other obesity-associated physiological changes, contribute to an enhanced response to lorundrostat. The poster is titled, “Identification of a hypertensive endotype with a median treatment effect of -32mmHg in response to the novel aldosterone synthase inhibitor lorundrostat”.JAMA Published Full Data from Target-HTN Trial – In September 2023, The Journal of the American Medical Association (JAMA) published the results of Target-HTN, the first in patient trial of lorundrostat in individuals with uHTN and rHTN. This paper, authored by doctors Laffin and Nissen at the Cleveland Clinic, reported the robust blood pressure lowering potential of lorundrostat as well as a favorable tolerability profile.Expanded Board of Directors – Appointed Daphne Karydas and Glenn Sblendorio to the Company’s Board of Directors, effective September 13, 2023. Ms. Karydas and Mr. Sblendorio bring executive, financial and operational leadership experience in biotechnology and biopharmaceuticals markets. Ms. Karydas was appointed chairperson of the audit committee and Mr. Sblendorio was appointed chairperson of the compensation committee. Key Upcoming Milestones Upcoming Poster Presentation at AHA Scientific Sessions 2023 - The Company has been selected to present a poster at the American Heart Association (AHA) Scientific Sessions 2023, which is being held from November 10 – 13, 2023, in Philadelphia, PA. The poster is titled, “Lorundrostat for Treatment of Obesity-Related, Aldosterone-Dependent Hypertension - An Endotype-Specific, Targeted Approach to the Treatment of Uncontrolled Hypertension”.Phase 3 pivotal Launch-HTN trial – In the second half of 2023, the Company remains on track to initiate a randomized, double-blind, placebo-controlled Phase 3 trial to evaluate the safety and efficacy of lorundrostat for the treatment of uHTN or rHTN. Lorundrostat will be studied when used as an add-on therapy to prescribed background treatment of two to five antihypertensive medications in up to approximately 1,000 adult subjects. In keeping with the objective of the trial, to model real world treatment of uHTN and rHTN in the primary care setting, the trial’s primary endpoint will be in-office blood pressure measurement rather than 24-hour ambulatory blood pressure measurement. Based on current projections, the topline data from this trial is now expected in the second half of 2025.Explore-CKD Phase 2 trial – The Company expects to initiate a two-part Phase 2 clinical trial for lorundrostat in hypertensive patients with stage 2-3b CKD in the second half of 2023, with topline data expected in the fourth quarter of 2024 to the first quarter of 2025. In consultation with its advisors and based on the significant unmet need, the Company has made the strategic decision to study subjects with systolic blood pressure (BP) greater than or equal to 135mmHg, as well as CKD with albuminuria. The objective in Part A is to assess the effect of lorundrostat, alone or in combination with dapagliflozin in subjects with uncontrolled hypertension and stage 2-3a CKD, on systolic BP, as well as albuminuria, a surrogate endpoint that supports long-term benefit in CKD. The Company plans to study 25mg once daily (QD) in this trial.The objective in Part B is to characterize the safety and tolerability of lorundrostat in subjects with uncontrolled hypertension and stage 3b CKD with albuminuria. This open-label safety study will evaluate 12.5mg QD lorundrostat with titration to 25mg QD based on pre-specified criteria. A new key exploratory objective for Part B is to assess the effect of lorundrostat on systolic BP. Third Quarter 2023 Financial HighlightsCash, cash equivalents and investments were $265.9 million as of September 30, 2023, compared to $110.1 million as of December 31, 2022. The Company believes that its cash, cash equivalents and investments as of September 30, 2023 will be sufficient to allow the Company to fund its planned clinical studies, as well as support corporate operations, through mid-2025. Research and Development (R&D) expenses were $22.5 million for the quarter ended September 30, 2023, compared to $6.1 million for the quarter ended September 30, 2022. The increase in R&D expenses was primarily due to increases of $12.4 million in preclinical and clinical costs, driven by the initiation of the lorundrostat pivotal program in 2023, $2.3 million in clinical supply, manufacturing and regulatory costs and $1.7 million in higher compensation expense resulting from additions to headcount. General and Administrative (G&A) expenses were $3.8 million for the quarter ended September 30, 2023, compared to $1.4 million for the quarter ended September 30, 2022. The increase in G&A expenses was primarily due to $1.2 million in higher professional fees associated with operating as a public company, $0.8 million in higher compensation expense resulting from additions to headcount, $0.3 million of higher insurance expense associated with new director and officer insurance policies and $0.1 million in higher other administrative expenses. Total other income, net was $3.5 million for the quarter ended September 30, 2023, compared to $0.7 million for the quarter ended September 30, 2022, which was primarily attributable to increased interest earned on the Company’s investments in money market funds and U.S. treasuries. Net loss was $22.8 million for the quarter ended September 30, 2023, compared to $6.7 million for the quarter ended September 30, 2022. The increase was primarily attributable to the factors impacting the Company’s expenses described above. Conference Call The Company’s management team will host a conference call at 4:30 p.m. ET on Tuesday, November 7, 2023. To access the call, please dial 1-888-886-7786 in the U.S. or 1-416-764-8658 outside the U.S., followed by the conference ID: 27015887. A live webcast of the conference call may be found here https://viavid.webcasts.com/starthere.jsp?ei=1632661&tp_key=eecbf184d5. A replay of the call will be available on the “News & Events” page in the Investor Relations section of the Mineralys Therapeutics website. About HypertensionHaving sustained, elevated blood pressure (or hypertension) increases the risk of heart disease, heart attack and stroke, which are leading causes of death in the U.S. In 2020, more than 670,000 deaths in the U.S. included hypertension as a primary or contributing cause. Hypertension and related health issues resulted in an average annual economic burden of about $130 billion each year in the U.S., averaged over 12 years from 2003 to 2014. Less than 50 percent of hypertension patients achieve their blood pressure goal with currently available medications. Abnormally elevated aldosterone levels are a key factor in driving hypertension in approximately 25 percent of all hypertensive patients. About Chronic Kidney Disease (CKD)CKD, which is characterized by the gradual loss of kidney function, is estimated to affect more than 10% of the global population and is one of the leading causes of mortality worldwide. According to the U.S. Centers for Disease Control and Prevention (CDC), an estimated 1-in-7 (15%) of U.S. adults have CKD. Diabetes and hypertension are responsible for approximately two-thirds of CKD cases. Early detection and treatment can often keep CKD from getting worse. When CKD progresses, it may eventually lead to kidney failure, which requires dialysis or a kidney transplant to maintain life. About LorundrostatLorundrostat is a proprietary, orally administered, highly selective aldosterone synthase inhibitor being developed for the treatment of uncontrolled hypertension and CKD. Lorundrostat was designed to reduce aldosterone levels by inhibiting CYP11B2, the enzyme responsible for its production. Lorundrostat has 374-fold selectivity for aldosterone-synthase inhibition versus cortisol-synthase inhibition in vitro, an observed half-life of 10-12 hours and demonstrated approximately a 70% reduction in plasma aldosterone concentration in hypertensive subjects. In a Phase 2, proof-of-concept trial (Target-HTN) in uncontrolled or resistant hypertensive subjects, once-daily lorundrostat demonstrated clinically meaningful blood pressure reduction in individuals with uncontrolled hypertension, in both automated office blood pressure measurement and 24-hour ambulatory blood pressure monitoring. Adverse events observed were a modest increase in serum potassium, decrease in estimated glomerular filtration rate, urinary tract infection and hypertension with one serious adverse event possibly related to study drug being hyponatremia. About Mineralys TherapeuticsMineralys Therapeutics is a clinical-stage biopharmaceutical company focused on developing medicines to target hypertension, CKD and other diseases driven by abnormally elevated aldosterone. Its initial product candidate, lorundrostat, is a proprietary, orally administered, highly selective aldosterone synthase inhibitor that Mineralys Therapeutics is developing for cardiorenal conditions affected by abnormally elevated aldosterone, including hypertension and CKD. Mineralys is based in Radnor, Pennsylvania, and was founded by Catalys Pacific. For more information, please visit https://mineralystx.com. Follow Mineralys on LinkedIn and Twitter. Forward-Looking StatementsMineralys Therapeutics cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. The forward-looking statements are based on our current beliefs and expectations and include, but are not limited to, statements regarding: the potential therapeutic benefits of lorundrostat; the Company’s expectation that aldosterone synthase inhibitors with an SGLT2 inhibitor may provide additive clinical benefits to patients; the Company’s expectation that the Advance-HTN and the planned Phase 3 clinical trial of lorundrostat may serve as pivotal trials in any submission of a new drug application (NDA) to the United States Food and Drug Administration (FDA); the Company’s ability to evaluate lorundrostat as a potential treatment for CKD or uncontrolled hypertension; the planned future clinical development of lorundrostat and the timing thereof; and the expected timing of commencement and enrollment of patients in clinical trials and topline results from clinical trials. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in our business, including, without limitation: our future performance is dependent entirely on the success of lorundrostat; potential delays in the commencement, enrollment and completion of clinical trials and nonclinical studies; later developments with the FDA may be inconsistent with the feedback from the completed end of Phase 2 meeting, including whether the proposed pivotal program will support registration of lorundrostat which is a review issue with the FDA upon submission of an NDA; our dependence on third parties in connection with manufacturing, research and clinical and nonclinical testing; unexpected adverse side effects or inadequate efficacy of lorundrostat that may limit its development, regulatory approval and/or commercialization; unfavorable results from clinical trials and nonclinical studies; results of prior clinical trials and studies of lorundrostat are not necessarily predictive of future results; our ability to maintain undisrupted business operations due to any pandemic or future public health concerns; regulatory developments in the United States and foreign countries; our reliance on our exclusive license with Mitsubishi Tanabe Pharma to provide us with intellectual property rights to develop and commercialize lorundrostat; and other risks described in our filings with the Securities and Exchange Commission (SEC), including under the heading “Risk Factors” in our annual report on Form 10-K, and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and we undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Contact:Investor Relationsinvestorrelations@mineralystx.com Media RelationsTom WeibleElixir Health Public RelationsPhone: (1) 515-707-9678Email: tweible@elixirhealthpr.com Mineralys Therapeutics, Inc.Condensed Statements of Operations(in thousands, except share and per share data)(unaudited) Three Months Ended Nine Months Ended September 30, September 30, 2023 2022 2023 2022 Operating expenses: Research and development$22,499 $6,059 $46,676 $18,432 General and administrative 3,774 1,364 10,270 3,039 Total operating expenses 26,273 7,423 56,946 21,471 Loss from operations (26,273) (7,423) (56,946) (21,471)Interest income, net 3,513 741 9,435 741 Other income — 4 2 4 Total other income, net 3,513 745 9,437 745 Net loss$(22,760) $(6,678) $(47,509) $(20,726)Net loss per share attributable to common stockholders, basic and diluted$(0.57) $(1.29) $(1.36) $(4.02)Weighted-average shares used to compute net loss per share attributable to common stockholders, basic and diluted 39,930,748 5,181,410 34,872,287 5,152,752 Mineralys Therapeutics, Inc.Selected Financial InformationCondensed Balance Sheet Data(amounts in thousands)(unaudited) September 30, December 31, 2023 2022 Cash, cash equivalents and investments$265,890 $110,110 Total assets$277,555 $114,442 Total liabilities$13,543 $8,067 Total stockholders’ equity (deficit)$264,012 $(52,269)

Idorsia Ltd (SIX: IDIA) announced today that further data for aprocitentan, Idorsia’s investigational dual endothelin receptor antagonist for the treatment of patients with resistant hypertension, were presented as an oral presentation entitled “Effects of aprocitentan on blood pressure lowering and proteinuria in patients with chronic kidney disease and resistant hypertension” by George Bakris, MD, at the American Society of Nephrology (ASN) Kidney Week 2023. Patients with hypertension can often successfully control their blood pressure by combining a healthier lifestyle with effective medication. However, approximately 10% of patients have resistant hypertension where the blood pressure remains high despite receiving at least three antihypertensive medications of different pharmacological classes, including a diuretic, at optimal doses. The Phase 3 PRECISION study demonstrated both the safety and the efficacy of aprocitentan to significantly lower blood pressure (BP) in patients with resitant hypertension on top of at least three antihypertensive medications of different classes, including a diuretic. Detailed results were published in The Lancet and presented as a Late-Breaking Science presentation during the American Heart Association (AHA) Scientific Sessions in November 2022. More details and commentary can be found in the dedicated press release and an investor webcast featuring Prof. Markus Schlaich, an investigator in PRECISION. The presentation at ASN Kidney Week 2023 focused on the effect of aprocitentan on BP in a subgroup of 162 patients with stage 3 or 4 chronic kidney disease (CKD), defined by an estimated glomerular filtration rate (eGFR) of 15 to <60mL/min/1.73m2. The presentation included pre-specified exploratory analysis (not adjusted for multiplicity) of aprocitentan on BP measured by an automated Office BP measurement (AOBPM), and post-hoc analysis of ambulatory BP monitoring (ABPM) and urinary albumin-to-creatinine ratio (UACR) – a marker of kidney damage – in this patient population. Both the 12.5 mg and 25 mg doses of aprocitentan resulted in a pronounced BP reduction from baseline to week 4 compared to placebo in patients with CKD stage 3 or 4. The mean change in office systolic BP at 4 weeks (for patients with both baseline and week 4 values) was –13.7 mmHg for aprocitentan 12.5 mg, –18.4 mmHg for 25 mg, and –6.5 mmHg for placebo, for a difference versus placebo of –7.2 mmHg and –11.9 mmHg, respectively. The results from ambulatory BP monitoring confirmed those derived from office measurements. The UACR at week 4, was reduced by 28% for aprocitentan 12.5 mg, 44% for aprocitentan 25 mg, and remained stable (reduction of 4%) in the placebo group. Aprocitentan was generally well tolerated; with the most common adverse events being edema/fluid retention (18% and 24% of patients receiving aprocitentan 12.5mg and 25mg, respectively, versus 2% with placebo, at week 4). Adverse events of fluid retention and edema were primarily peripheral edema of mild intensity, mostly occurring during the first 4 to 8 weeks of treatment and were effectively managed with additional diuretic therapy. Discontinuation due to edema/fluid retention was reported for 3 out of 162 patients. George Bakris, MD, Professor of Medicine and Director, Comprehensive Hypertension Center, University of Chicago School of Medicine and an investigator in the PRECISION study commented: “It is great that the PRECISION study with aprocitentan included such a large cohort of patients with resistant hypertension and CKD stage 3 or 4, as CKD is a frequent cause – and consequence of – resistant hypertension. Very often these high-risk patients are under-represented in clinical studies of hypertension, but it is very important to include these patients in order to translate the clinical data into a real-world situation. We found that aprocitentan, when added to at least three other antihypertensive medications, resulted in a substantial and clinically meaningful reduction of both office and ambulatory blood pressure, as well as a reduction in albuminuria. It is also important that the mechanism is not associated to an increased risk of hyperkalemia, which often limits the use of anti-hypertensive medications in patients with CKD.” Alberto Gimona, Head of Global Clinical Development of Idorsia, concluded: “While this prespecified subgroup analysis is exploratory in nature, I was very glad to see the marked efficacy of aprocitentan in reducing blood pressure and proteinuria in patients with CKD who are already heavily medicated. I was also glad to see the safety results, while we did see an increased incidence of edema and fluid retention in the first 4 to 8 weeks, this was mostly peripheral edema, the incidence decreased rapidly, and was effectively managed with additional diuretic therapy. In this frail population with a lot of comorbidities, on top of other vasodilators, cases of edema were not unexpected.” In May 2022, Idorsia announced positive top-line results of the Phase 3 PRECISION study with aprocitentan for the treatment of patients with resistant hypertension. Detailed results were published in The Lancet and presented as a Late-Breaking Science presentation during the American Heart Association (AHA) Scientific Sessions in November 2022. More details and commentary can be found in the dedicated press release and an investor webcast featuring Prof. Markus Schlaich, an investigator in PRECISION. A new drug application (NDA) for aprocitentan was accepted for review by the US FDA. Following the provision of additional Risk Evaluation and Mitigation Strategy (REMS) materials to support a streamlined REMS designed specifically for aprocitentan, the company is working towards a PDUFA date of March 19, 2024. A market authorisation application (MAA) was submitted to the EMA at the end January 2023. Hypertension (high blood pressure) is one of the most common cardiovascular risk factors, and its prevalence continues to rise. According to a recent study, there are more than 1.3 billion people living with hypertension worldwide4 – a startling number, which has almost doubled in the past 40 years. Left uncontrolled, people have a greater risk of life-threatening conditions such as heart attack, stroke, and chronic kidney disease.5 Patients with hypertension can often successfully control their blood pressure by combining a healthier lifestyle with effective medication. However, approximately 10% of patients have difficult-to-control hypertension where the blood pressure remains high despite receiving at least three antihypertensive medications of different pharmacological classes, including a diuretic, at optimal doses,1,6 (also categorized in hypertension guidelines and the medical community as having resistant hypertension). The endothelin pathway has been implicated in the pathogenesis of hypertension, especially in volume- and salt-dependent forms, which are a common feature in patients with resistant hypertension. The endothelin pathway has not been targeted by existing anti-hypertensive therapies until now, thereby leaving this relevant pathophysiologic pathway unopposed with currently available medications.1,7,8 The endothelin system is also activated in patients prone to developing resistant hypertension, such as Black or African American patients, patients with obesity or obstructive sleep apnea,9-11 and in comorbid conditions frequently associated with resistant hypertension such as diabetes and chronic kidney disease.12-15 Aprocitentan is an investigational, novel, oral, dual endothelin receptor antagonist (ERA), which potently inhibits the binding of ET-1 to ETA and ETB receptors. Aprocitentan has a low potential for drug-drug interaction and a mechanism of action that is ideally suited for the pathophysiology of resistant hypertension. PRECISION was a multicenter, blinded, randomized, parallel-group, Phase 3 study, which was performed in hospitals or research centers in Europe, North America, Asia, and Australia. Patients were eligible for randomization if their sitting systolic blood pressure was 140 mm Hg or higher despite taking standardized background therapy consisting of three antihypertensive drugs, including a diuretic. The study consisted of three sequential parts: Part 1 was the 4-week double-blind, randomized, and placebo-controlled part, in which 730 patients were randomized to aprocitentan 12.5 mg (n=243), aprocitentan 25 mg (n=243), or placebo (n=244) in a 1:1:1 ratio; Part 2 was a 32-week single (patient)-blind part, in which all patients received aprocitentan 25 mg (n=704); and Part 3 was a 12-week double-blind, randomized, and placebo-controlled withdrawal part, in which patients were re-randomized to aprocitentan 25 mg (n=307) or placebo (n=307) in a 1:1 ratio. The primary and key secondary endpoints were changes in unattended office systolic blood pressure from baseline to week 4 and from withdrawal baseline to week 40, respectively. Secondary endpoints included 24-h ambulatory blood pressure changes. At baseline, 69.2% of patients were obese or severely obese, 54.1% had diabetes, 22.2% had stage 3-4 chronic kidney disease and 19.6% had congestive heart failure. 63% of randomized patients were receiving at least 4 anti-hypertensive therapies at screening. Dr Bakris is a Nephrologist/Certified Hypertension Specialist trained at the Mayo Clinic and the University of Chicago Medicine. He is a Professor of Medicine and Director of the Am. Heart Assoc. Comprehensive Hypertension Center at the University of Chicago Medicine. He has published over 1000 peer-reviewed articles and book chapters in the areas of diabetic kidney disease, hypertension, and nephropathy progression. He is the Editor or Co-Editor of 24 books in the areas of Diabetic Kidney Disease Progression and Hypertension. Additionally, he is the Co-Editor of the 3rd and new 4 edition of Hypertension: A Companion to Braunwald’s: The Heart. Dr Bakris has served on the Cardiorenal Advisory Board of the FDA and consultant to CMS. He has also served on many national guideline committees, including The Joint National Committee JNC 7 executive committee and writing group, the American Diabetes Association (ADA) Clinical Practice Guideline Committee (2002-2004 and 2020-2022), and the National Kidney Foundation (K-DOQI), Blood Pressure and Diabetes Guideline committees. He Chaired the ADA Blood Pressure Consensus Report (2017) and served on the ACC/AHA writing committee on the Resistant Hypertension Consensus report (2018). He is also the senior author on the recent ADA/KDIGO Consensus Report for approaches to diabetic kidney disease (2022). Dr Bakris is the past president of the American College of Clinical Pharmacology and the American Society of Hypertension (ASH). He is the recipient of the Irvine Page-Alva Bradley Lifetime Achievement Award-Am Heart Assoc. BP Council (2019). He serves on numerous editorial boards and is the current Editor-in-Chief of Am J Nephrology, and Editor, UpToDate, Nephrology section, Hypertension Section, and Assoc. Ed of Diabetes Care and Am. Heart J. Plus. Dr. Bakris serves as a consultant to Idorsia. Key Literature Williams B, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J 2018; 39: 3021–104. Kedzierski RM, et al. Endothelin system: the double-edged sword in health and disease. Annu Rev Pharmacol Toxicol. 2001; 41:851-76. Iglarz M, et al. At the heart of tissue: endothelin system and end-organ damage. Clin Sci 2010; 119:453-63. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants. Lancet 2021; 398:957-80. Daugherty SL, et al. Incidence and prognosis of resistant hypertension in hypertensive patients. Circulation. 2012 Apr 3;125(13):1635-42. Noubiap JJ, et al. Global prevalence of resistant hypertension: a meta-analysis of data from 3·2 million patients. Heart 2019; 105: 98–105. Dhaun N, et al. Role of endothelin-1 in clinical hypertension: 20 years on. Hypertension 2008; 52:452-9. Clozel M. Aprocitentan and the endothelin system in resistant hypertension. Can J Physiol Pharmacol 2022; 100:573-83. Grubbs AL, et al. Saphenous vein endothelin system expression and activity in African American patients. Arterioscler Thromb Vasc Biol 2002; 22: 1122–7. Parrinello G, et al. Central obesity and hypertension: the role of plasma endothelin. Am J Hypertens 1996; 9: 1186–91. Phillips BG, et al. Effects of obstructive sleep apnea on endothelin-1 and blood pressure. J Hypertens 1999; 17: 61–6. Takahashi K, et al. Elevated plasma endothelin in patients with diabetes mellitus. Diabetologia 1990; 33: 306–10. Solini A, et al. Resistant hypertension in patients with type 2 diabetes: clinical correlates and association with complications. J Hypertens 2014; 32: 2401–10; discussion 10. Dhaun N, Webb DJ, Kluth DC. Endothelin-1 and the kidney--beyond BP. Br J Pharmacol 2012; 167: 720–31. Rossignol P, et al. The double challenge of resistant hypertension and chronic kidney disease. Lancet 2015; 386: 1588–98. Danaietash P et al. Identifying and treating resistant hypertension in PRECISION: A randomized long-term clinical trial with aprocitentan. J Clin Hypertension 2022 Jul;24(7):804-813. Schlaich MP, et al. A randomized controlled trial of the dual endothelin antagonist aprocitentan for resistant hypertension. The Lancet, 2022; Dec 3;400(10367):1927-1937. Dolan E, et al. Superiority of ambulatory over clinic blood pressure measurement in predicting mortality: the Dublin outcome study. Hypertension 2005; 46:156–61. Staplin N, et al. Relationship between clinic and ambulatory blood pressure and mortality: an observational cohort study in 59 124 patients. Lancet. 2023;S0140-6736(23)00733-X. Idorsia Ltd is reaching out for more – We have more ideas, we see more opportunities and we want to help more patients. In order to achieve this, we will develop Idorsia into a leading biopharmaceutical company, with a strong scientific core. Headquartered near Basel, Switzerland – a European biotech-hub – Idorsia is specialized in the discovery, development and commercialization of small molecules to transform the horizon of therapeutic options. Idorsia has a 20-year heritage of drug discovery, a broad portfolio of innovative drugs in the pipeline, an experienced team of professionals covering all disciplines from bench to bedside, and commercial operations in Europe, Japan, and the US – the ideal constellation for bringing innovative medicines to patients. Idorsia was listed on the SIX Swiss Exchange (ticker symbol: IDIA) in June 2017 and has over 1,300 highly qualified specialists dedicated to realizing our ambitious targets. The content above comes from the network. if any infringement, please contact us to modify.

INGELHEIM, Germany I November 03, 2023 I Boehringer Ingelheim today announced promising 14-week Phase II data for BI 690517, a novel selective aldosterone synthase inhibitor (ASi). The results showed a significant reduction of albuminuria, a marker of kidney damage, 2 by up to 39.5% when BI 690517 was given on top of empagliflozin, a sodium glucose cotransporter (SGLT2) inhibitor, vs. placebo. 1 This is the first clinical trial testing this novel treatment class on top of standard of care including empagliflozin in people with chronic kidney disease (CKD), 1 which affects more than 850 million people worldwide. 3 The findings were presented as a high-impact clinical trial at the American Society of Nephrology (ASN)’s Kidney Week 2023. 1 BI 690517 has a novel mode of action that effectively and sustainably inhibits aldosterone synthase, an enzyme that controls the final rate-limiting steps in aldosterone synthesis. 1,4 Excessive aldosterone levels cause organ damage and promote cardio-renal-metabolic conditions such as hypertension, chronic kidney disease or heart failure. 5 “This unique trial testing a selective aldosterone synthase inhibitor on top of standard of care including SGLT2 inhibition, showed positive and clinically relevant efficacy. Using BI 690517 along with SGLT2 inhibition may offer the potential for additive kidney benefits while possibly mitigating hyperkalemia risk,” said Dr Katherine Tuttle, Principal Study Investigator and Professor of Medicine in the Nephrology Division and Kidney Research Institute at the University of Washington, U.S. “Additional CKD treatments are urgently needed to reduce residual risks of disease progression and serious complications.” While aldosterone synthase inhibition can lead to moderate elevation of serum potassium, 6 this study suggests there is potential that empaglifozin’s mechanism of action can mitigate the risk of hyperkalemia when given as a background therapy. 7,8 This effect is of high clinical importance since severe hyperkalemia may lead to changes in medical therapy or hospitalization. 9 As a novel drug class, BI 690517, on top of empagliflozin, may address this critical unmet medical need. 1 A key secondary endpoint in the Phase II trial was a clinically meaningful reduction in UACR (≥30%) which was achieved by up to 70% of patients treated with BI 690517 on top of empagliflozin. 1 Based on analyses assessing albuminuria change as a predictive indicator, these changes may translate into risk reductions for clinical kidney disease events by at least 30%. 1 “These encouraging Phase II data not only demonstrate our commitment to developing innovative and transformational treatments for people living with cardio-renal-metabolic conditions but also have the potential to decrease the global burden of these interconnected diseases,” said Carinne Brouillon, Head of Human Pharma, Boehringer Ingelheim. “With over 1 billion people worldwide affected by these conditions, the potential to help reduce the pressure on healthcare systems and patients is immense. We are proud to be leading the way in this field and are excited to move forward with the upcoming Phase III trial to further investigate the potential of this novel compound on top of standard of care including empagliflozin." In 2024, Oxford Population Health and Boehringer Ingelheim’s new, international Phase III EASi-KIDNEY TM trial will begin recruitment. 1 The trial aims to definitively test the efficacy and safety of BI 690517 given on top of standard of care, including empagliflozin. 1 EASi-KIDNEY TM will recruit and follow about 11,000 participants with established CKD, at risk of kidney disease progression, using Oxford Population Health’s streamlined model. 1 BI 690517 was generally well tolerated without unexpected safety signals. 1 Dose-dependent modest increases in serum potassium levels were observed with BI 690517, which were slightly ameliorated in the presence of empagliflozin. Hyperkalemia occurred at a rate typical for a CKD population, 1 and most episodes did not require medical treatment or BI 690517 discontinuation. 1 About the trial (NCT05182840) This Phase II, placebo-controlled, double-blind trial assessed the efficacy and safety of multiple oral doses of BI 690517 alone or on top of an SGLT2 inhibitor in people with CKD, with or without type 2 diabetes, receiving stable background therapy with an angiotensin receptor blocker (ARB) or angiotensin-converting enzyme (ACE) inhibitor. 1 Participants were first randomized (N=714) to receive either empagliflozin 10 mg or placebo for 8 weeks, then randomized a second time (N=586) to receive one of three doses of BI 690517 (3 mg, 10 mg or 20 mg) or placebo for 14 weeks. 1 The primary endpoint of the trial was to assess the efficacy of BI 690517 by measuring the percentage change in urine albumin creatinine ratio (UACR, a measure of albuminuria, which reflects kidney damage) 2 from the second randomization to end of treatment. 1 The greatest placebo-corrected UACR reduction was among the participant group receiving BI 690517 10mg on top of empagliflozin. 1 There was a placebo-corrected flattening of the dose response at 10 mg among both treatment groups. 1 Participants who received both BI 690517 on top of empagliflozin experienced the following placebo-corrected changes in UACR: 1 These findings suggest additive efficacy when the therapies are combined. 1 Participants who received BI 690517 without empagliflozin background therapy experienced the following placebo-corrected changes in UACR: 1 Secondary endpoints were the proportion of patients with absolute decreases of ≥15% and ≥30% in UACRat week 14. 1 Additional endpoints included: safety and pharmacokinetic findings, change from baseline in serum potassium at week 14, change from baseline in estimated glomerular filtration rate at week 14 and changes from baseline in the plasma levels of aldosterone and its precursors. 1 About BI 690517 BI 690517 is a novel, potent, highly selective aldosterone synthase inhibitor (ASi), which is intended to slow the progression of kidney damage and to reduce cardiovascular events in people with CKD. The compound was discovered and developed by Boehringer Ingelheim and is part of its research and development portfolio in cardiovascular-renal-metabolic conditions. About chronic kidney disease More than 850 million people worldwide live with CKD, 10 a relentless disease with no cure, which often leads to kidney failure, dialysis, or transplantation, and increases the risk of cardiovascular events and death. 10 CKD is projected to progressively increase in parallel with interconnected conditions like diabetes, hypertension and obesity. 11,12 About Boehringer Ingelheim Boehringer Ingelheim is working on breakthrough therapies that transform lives, today and for generations to come. As a leading research-driven biopharmaceutical company, the company creates value through innovation in areas of high unmet medical need. Founded in 1885 and family-owned ever since, Boehringer Ingelheim takes a long-term, sustainable perspective. More than 53,000 employees serve over 130 markets in the two business units Human Pharma and Animal Health. Learn more at www.boehringer-ingelheim.com References 1 Tuttle KR, Hauske SJ, Canziani ME, et al. Aldosterone synthase inhibition with or without background sodium-glucose cotransporter-2 inhibition in CKD: a Phase II clinical trial. Oral presentation at: Ann Mtg of the American Society of Nephrology 2023. Abstract number FR-OR111. 2 Jongs N, et al. Lancet Diabetes Endocrinol 2021;9:755-66 3 Li P, et al. Braz J Med Biol Res. 2020; 53(3): e9614. 4 Xing Y, et al. Endocrinology. 2011;152(3):751-63. 5 Otsuka, H. et al. Int J Mol Sci. 2023; 24(6): 5370 6 Rodan, Aylin R. Pediatric Nephrology. 2017;32(7):1109-1121 7 Ferreira JP, et al . J Am Coll Cardiol. 2021;77:1397–1407. 8 Wanner C, et al. N Engl J Med. 2016;375:323–334. 9 Larivée, NL et al . Cardiol Ther. 2023;12:35–63 10 Li P, et al. Braz J Med Biol Res. 2020; 53(3): e9614. 11 Evans M, et al. Adv Ther 2022;39:33-43 12 Braun, L. et al. Int J Nephrol Renovasc. Dis 2012;5:151-63 SOURCE: Boehringer Ingelheim