Mineralys Therapeutics Inc (MLYS) 2025 Q1 法說會逐字稿

Good afternoon, ladies and gentlemen, and welcome to the Mineralys' first-quarter 2025 earnings conference call. (Operator Instructions) This call is being recorded on Monday, May 12, 2025.

女士們、先生們，下午好，歡迎參加 Mineralys 2025 年第一季財報電話會議。（操作員指示）此通話於 2025 年 5 月 12 日星期一錄製。

I would now like to turn the conference over to Dan Ferry. Please go ahead.

現在我想將會議交給丹費裡。請繼續。

Thank you, operator. We'd like to welcome everyone joining us today for our first-quarter 2025 conference call. Earlier this afternoon, we issued a press release providing our first quarter 2025 financial results and business updates. A replay of today's call will be available on the Investors section of our website approximately 1 hour after its completion. After our prepared remarks, we will open the call for Q&A.

謝謝您，接線生。我們歡迎大家今天參加我們的 2025 年第一季電話會議。今天下午早些時候，我們發布了一份新聞稿，提供了我們 2025 年第一季的財務表現和業務更新。今天的電話會議重播將在會議結束後約 1 小時在我們網站的「投資者」部分提供。在我們準備好發言之後，我們將開始問答環節。

Before we begin, I would like to remind everyone that this conference call and webcast will contain forward-looking statements about the company. Actual results could differ materially from those stated or implied by these forward-looking statements due to risks and uncertainties associated with the company's business. These forward-looking statements are qualified by the cautionary statements contained in today's press release and our SEC filings, including our annual report on Form 10-K and subsequent filings.

在我們開始之前，我想提醒大家，本次電話會議和網路廣播將包含有關公司的前瞻性陳述。由於公司業務相關的風險和不確定性，實際結果可能與這些前瞻性陳述所明示或暗示的結果有重大差異。這些前瞻性陳述受到今天的新聞稿和我們向美國證券交易委員會提交的文件（包括我們的 10-K 表格年度報告和後續文件）中的警示性聲明的限制。

Please note that these statements reflect our opinions only as of today, May 12, 2025, and as except as required by law, we specifically disclaim any obligation to update or revise these forward-looking statements in light of new information or future events.

請注意，這些聲明僅反映我們截至 2025 年 5 月 12 日的觀點，除法律要求外，我們明確表示不承擔根據新資訊或未來事件更新或修改這些前瞻性聲明的義務。

I would now like to turn the call over to Jon Congleton, Chief Executive Officer of Mineralys Therapeutics.

現在我想將電話轉給 Mineralys Therapeutics 執行長 Jon Congleton。

Thank you, Dan. Good afternoon, everyone, and welcome to our first-quarter 2025 financial results and corporate update conference call. I'm joined today by Adam Levy, our Chief Financial Officer; and Dr. David Rodman, our Chief Medical Officer. I'll begin with an overview of the business, then Dave will discuss our clinical programs and recent milestones, followed by Adam to review our first quarter financial results before we open up the call for your questions.

謝謝你，丹。大家下午好，歡迎參加我們 2025 年第一季財務業績和公司更新電話會議。今天和我一起參加的是我們的財務長 Adam Levy；以及我們的首席醫療官 David Rodman 博士。我將首先概述業務，然後戴夫將討論我們的臨床計劃和最近的里程碑，接著亞當將回顧我們的第一季財務業績，然後我們開始回答您的問題。

This has been an exciting past few months for Mineralys as our team delivered on several clinical milestones to make significant progress across our entitlement pipeline. The most highly anticipated of these accomplishments was the simultaneous announcement of positive top-line data from the pivotal trials Launch-HTN in Advance-HTN, which is understand in uncontrolled and resistant hypertension subjects.

過去幾個月對 Mineralys 來說是令人興奮的，因為我們的團隊實現了幾個臨床里程碑，在我們的授權管道中取得了重大進展。這些成就中最受期待的是同時公佈的關鍵試驗 Launch-HTN 在 Advance-HTN 中的積極頂線數據，該試驗針對未控制和難治性高血壓患者。

We were pleased to announce in March that both trials successfully achieved statistical significance and were clinically meaningful in Emery efficacy end points and demonstrated a favorable safety and tolerability profile. Detailed results from the Advance-HTN trial were also published in the New England Journal of Medicine, and presented in a late-breaking presentation at the American Cardiology's ACC '25 meeting.

我們很高興在三月宣布，兩項試驗均成功實現了統計意義，並在 Emery 療效終點方面具有臨床意義，並表現出良好的安全性和耐受性。Advance-HTN 試驗的詳細結果也發表在《新英格蘭醫學雜誌》上，並在美國心臟病學會 ACC '25 會議的最新報告中進行了介紹。

The Launch-HTN data has been accepted for a late-breaking presentation at the European Society of Hypertension on May 24 with a planned future publication. Each of these exciting outcomes helps to underscore the strength of these clinical data and the potentially transformative nature of a to help people achieve their blood pressure goal and potentially reduce their cardiovascular risk.

Launch-HTN 數據已被接受於 5 月 24 日在歐洲高血壓學會上進行最新報告，並計劃在未來發表。每一個令人興奮的結果都有助於強調這些臨床數據的強度和潛在的變革性質，幫助人們實現他們的血壓目標，並可能降低他們的心血管風險。

The positive efficacy, safety and tolerability data from these two pivotal trials, along with the data from our Target-HTN Phase II trial of lorundrostat are key elements of our planned new drug application to the FDA. We continue to believe that this regulated aldosterone is not adequately addressed with currently available RAS directed therapeutics, including mineral corticoid receptor antagonist. These results we have seen with lorundrostat reinforce the need for a new Aldostero-directed therapeutic approach.

這兩項關鍵試驗的積極療效、安全性和耐受性數據，以及我們對 lorundrostat 的 Target-HTN II 期試驗的數據是我們計劃向 F​​DA 提交新藥申請的關鍵要素。我們仍然認為，目前可用的 RAS 導向療法（包括鹽皮質激素受體拮抗劑）不能充分解決這種受調節的醛固酮問題。我們在 lorundrostat 中看到的這些結果強化了對新的醛固酮導引治療方法的必要性。

The Transform-HTN open-label extension trial is evaluating the safety and efficacy of lorundrostat long-term use will be an important aspect of lorundrostat's profile and a critical component of our new drug application. We anticipate discussing the results from the Advance, Launch, Target and Transform HTN trials as well as the Explore-CKD trial with the FDA at a pre-NDA meeting in the fourth quarter of 2025, during which forward for an NDA submission and potential approval of lorundrostat. We look forward to providing updates on this program throughout the remainder of 2025.

Transform-HTN 開放標籤擴展試驗正在評估 lorundrostat 的安全性和有效性，長期使用將成為 lorundrostat 概況的一個重要方面，也是我們新藥申請的關鍵組成部分。我們預計將在 2025 年第四季的 NDA 前會議上與 FDA 討論 Advance、Launch、Target 和 Transform HTN 試驗以及 Explore-CKD 試驗的結果，在此期間提交 NDA 並可能獲得 lorundrostat 的批准。我們期待在 2025 年剩餘時間內提供有關該計劃的最新資訊。

We're very optimistic about the interest physicians have on lorundrostat overall clinical profile based on the pivotal data, especially given the double-digit absolute reduction in systolic blood pressure. Supporting our excitement around the market opportunity from lorundrostat are the data we collected in a survey fielded in March, which evaluated the data from the Launch-HTN and Advance-HTN trials with cardiologists and primary care physicians. The results from that survey showed if lorundrostat is approved, 95% of the physicians are likely to prescribe lorundrostat broadly for hypertension and specifically in the third and fourth line position. This intent to prescribe is based on the health care professionals interpretation of the efficacy data relative to what they currently have available for uncontrolled and resistant hypertension as well as lorundrostat safety and tolerability profile.

根據關鍵數據，我們對醫生對 lorundrostat 整體臨床概況的興趣非常樂觀，特別是考慮到收縮壓的絕對值降低了兩位數。我們在 3 月進行的一項調查中收集的數據支持了我們對 lorundrostat 帶來的市場機會的興奮，該調查對心臟病專家和初級保健醫生進行的 Launch-HTN 和 Advance-HTN 試驗的數據進行了評估。調查結果顯示，如果 lorundrostat 獲得批准，95% 的醫生可能會廣泛開立 lorundrostat 治療高血壓，特別是作為三線和四線藥物。這種處方意圖是基於醫療保健專業人員對療效數據的解讀，這些數據與他們目前掌握的針對不受控制和難治性高血壓的療效數據以及洛倫司他的安全性和耐受性概況有關。

The overall results speak to the desire for innovative solutions that physicians want in their treatment armamentarium to address uncontrolled and resistant hypertension. Our two ongoing proof of con trials address advanced chronic kidney disease, specifically those with uncontrolled hypertension as well as obstructive sleep apnea with nocturnal hypertension. These trials are designed to enhance and extend the lorundrostat profile in hypertension subjects with comorbid conditions, largely driven by inadequately controlled blood pressure in dysregulated aldosterone.

整體結果表明，醫生希望在治療設備中採用創新解決方案來解決不受控制和難治性高血壓。我們正在進行的兩項臨床試驗針對的是晚期慢性腎病，特別是那些患有無法控制的高血壓以及伴有夜間高血壓的阻塞性睡眠呼吸中止症的患者。這些試驗的目的是增強和擴展 lorundrostat 在合併症的高血壓患者中的應用，這些合併症主要是由於醛固酮失調導致血壓控制不足所致。

We've made steady progress with both trials since the beginning of 2025, and anticipate announcing top line data from Explore-CKD trial later this quarter.

自 2025 年初以來，我們在兩項試驗中都取得了穩步進展，並預計將於本季稍後公佈 Explore-CKD 試驗的頂線數據。

We're also pleased to announce the appointment of Eric Warren as Chief Commercial Officer. Eric brings approximately [30] years of experience in the pharmaceutical industry, during which he has developed a breadth of commercial and partnering expertise, focusing primarily on cardiometabolic and acute care medicine. He started his career as a pharmacist and then joined Merck & Company where we went on to hold commercial positions of increasing responsibility for almost two decades.

我們也很高興地宣布任命 Eric Warren 為首席商務官。Eric 在製藥業擁有大約 [30] 年的經驗，在此期間，他積累了廣泛的商業和合作專業知識，主要專注於心臟代謝和急性護理醫學。他的職業生涯始於一名藥劑師，隨後加入默克公司，在近二十年的時間裡，他擔任著越來越重要的商業職位。

In addition, Eric has held commercial leadership roles at Sanofi and Nabriva and was most recently the Chief Commercial Officer of the Therapeutics. As the Chief Commercial Officer of Mineralys will lead our commercial strategy as we prepare for the potential FDA approval of lorundrostat and support our partnering ambitions in the US and ex-US markets.

此外，Eric 還曾在賽諾菲和 Nabriva 擔任商業領導職務，最近擔任 Therapeutics 的首席商務官。作為 Mineralys 的首席商務官，他將領導我們的商業策略，為 FDA 批准 lorundrostat 做準備，並支持我們在美國和美國以外市場的合作願望。

In March, we completed a public equity financing that raised gross proceeds of approximately $201.2 million before deducting fees and expenses. This financing contributed meaningfully to the strength of our balance sheet.

3 月份，我們完成了公開股權融資，扣除費用和開支前籌集的總收益約為 2.012 億美元。此次融資對我們資產負債表的穩健性做出了重大貢獻。

Now to provide more color on our clinical pipeline and recent milestones, I'll turn the call over to Dave.

現在，為了提供有關我們的臨床流程和最近里程碑的更多細節，我將把電話轉給戴夫。

Thank you, Jon, and good afternoon, everybody. As Jon mentioned, our team has been had an exciting few months with the advancement of our clinical programs. I'll start by summarizing the top line results of the pivotal Phase III Launch-HTN trial, which randomized 1,083 subjects in North America and Europe who had failed to achieve the US guidelines specified blood pressure targets despite having been provided on multidrug antihypertensive regimen.

謝謝你，喬恩，大家下午好。正如喬恩所提到的，隨著臨床計畫的進展，我們的團隊度過了令人興奮的幾個月。我將首先總結關鍵的 III 期 Launch-HTN 試驗的主要結果，該試驗隨機選取了北美和歐洲的 1,083 名受試者，這些受試者儘管接受了多藥抗高血壓治療，但仍未能達到美國指南規定的血壓目標。

The trial, which tested lorundrostat in a real-world clinical context met its primary and secondary endpoints with highly statistically significant, clinically meaningful placebo-adjusted reduction, installed blood pressure as well as in the observed change in blood pressure that is conventionally used by prescribing physicians to assess response to antihypertensive therapy.

該試驗在現實世界的臨床環境中對 lorundrostat 進行了測試，達到了其主要和次要終點，具有高度統計意義和臨床意義的安慰劑調整降低、固定血壓以及處方醫生通常用來評估抗高血壓治療反應的血壓變化。

At week 6, the primary end point, the 50-milligram once daily lorundrostat arm demonstrated a 9.1-millimeter of mercury placebo-adjusted reduction in systolic blood pressure, and a 16.9 meter mercury reduction in observed systolic blood pressure. At week 12, the reduction in systolic BP was maintained with the point estimate being greater than that observed at week six. 11.7 millimeters of mercury and 19 millimeters of mercury for placebo-adjusted and observed changes, respectively.

在第 6 週，即主要終點，每天服用一次 50 毫克的 lorundrostat 組顯示，安慰劑調整後的收縮壓降低了 9.1 毫米汞柱，觀察到的收縮壓降低了 16.9 毫米汞柱。在第 12 週，收縮壓的降低得以維持，且點估計值高於第 6 週觀察到的點估計值。安慰劑調整和觀察到的變化分別為 11.7 毫米汞柱和 19 毫米汞柱。

Reductions in blood pressure and this magnitude is linked to significant reduction in overall cardiovascular risk and the incidence of major adverse cardiovascular events.

血壓降低及這種程度與整體心血管風險和重大不良心血管事件發生率的顯著降低有關。

The Launch-HTN trial confirmed expected modest on-target increase in serum potassium that accompanies the therapeutic benefit in individuals with inadequately controlled hypertension as well as an overall safe and well-tolerated profile. The incidence of any potential measurement over 6 millimole per liter in the Launch-HTN trial in (inaudible) milligram arm was 1.1% in placebo in active and 0.7% in placebo. The prespecified rate, excluding falsely elevated or factitious hyperkalemia was comparable to placebo with the demonstrated incidences being 0.6% and 0.4%, respectively.

Launch-HTN 試驗證實，對於高血壓控制不佳的患者，血清鉀水平預期會出現適度的目標增加，同時還會帶來治療益處，並且總體上具有安全性和良好的耐受性。在 Launch-HTN 試驗中，(聽不清楚) 毫克組的任何潛在測量值超過 6 毫摩爾/公升的發生率為：活性安慰劑組為 1.1%，安慰劑組為 0.7%。排除假性升高或人為高血鉀症後，預定發生率與安慰劑相當，實際發生率分別為 0.6% 及 0.4%。

While quantitative comparisons between different clinical trials are difficult, the incidence of moderate or severe hyperkalemia of approximately one-half of 1% compares quite favorably with most prior reports of mineralocoid receptor antagonist tested in a similar clinical context.

雖然不同臨床試驗之間的定量比較很困難，但中度或重度高血鉀症的發生率約為 0.5%，與在類似臨床環境下測試的大多數先前報告的鹽類受體拮抗劑相比，這一發生率相當高。

The Launch-HTN global pivotal trial is the largest aldosterone on synthase inhibitor trial reported to date and the benefit of risk profile compares quite favorably with previously reported smaller trials of the 3 other aldosterone synthase inhibitors that have been tested in hypertensive individuals.

Launch-HTN 全球關鍵試驗是迄今為止報告的最大規模的醛固酮合成酶抑制劑試驗，其風險概況的益處與先前報告的其他 3 種在高血壓患者中測試過的醛固酮合成酶抑制劑的較小規模試驗相比非常有利。

Now turning to the Advance-HTN trial. Here, we tested the effect of lorundrostat in the clinical context and hypertension intensive individuals who are the most refractory to current standard of care, and often referred to hypertension specialists. The trial used highly rigorous criteria for enrollment and randomized -- randomization designed to mirror best practice care provided in the most advanced hypertension referral centers, maximization of conventional best practice two and three drug treatment regimens along with active monitoring of compliance, we're used to document and confirm the existence of uncontrolled or resistant hypertension.

現在轉向 Advance-HTN 試驗。在這裡，我們測試了 lorundrostat 在臨床環境中的效果以及對目前治療標準最有抵抗力的高血壓重症患者的效果，這些患者通常會被轉診給高血壓專家。該試驗採用了非常嚴格的入組和隨機標準——隨機化設計旨在反映最先進的高血壓轉診中心提供的最佳實踐護理，最大限度地利用傳統的最佳實踐兩種和三種藥物治療方案以及積極監測依從性，我們用於記錄和確認不受控製或難治性高血壓的存在。

The results from the trial in the 50-milligram once-daily lorundrostat arm were highly statistically significant. The 7.9 millimeter mercury reduction in placebo-adjusted systolic blood pressure and 15.4 millimeter mercury reduction in observed systolic blood pressure measured by 24-hour ambulatory blood pressure were observed at the prespecified 12-week visit.

每日一次 50 毫克 lorundrostat 組的試驗結果具有高度的統計意義。在預定的 12 週追蹤中觀察到，安慰劑調整後的收縮壓降低了 7.9 毫米汞柱，透過 24 小時動態血壓測得的收縮壓降低了 15.4 毫米汞柱。

Lorundrostat demonstrated a favorable safety and tolerability profile with modest on-target changes in serum potassium, sodium and EGFR and a low discontinuation rate. This trial was designed and conducted in partnership with the comprehensive hypertension center at the Cleveland Clinic and their C5 research team. Results were presented by the Co-Director of the Cleveland Clinic Hypertension Clinic, Dr.

Lorundrostat 表現出良好的安全性和耐受性，血清鉀、鈉和 EGFR 的目標變化適中，停藥率低。該試驗是與克利夫蘭診所綜合高血壓中心及其 C5 研究團隊合作設計和進行的。研究結果由克利夫蘭診所高血壓診所聯合主任博士介紹。

Lu Lasan, in a late-breaking session at the American College of Cardiology's ACC '25 meeting and published in the New England Journal of Medicine on May 8.

盧拉桑在美國心臟病學會 ACC '25 會議的一次最新會議上發表了這一觀點，並於 5 月 8 日發表在《新英格蘭醫學雜誌》上。

As was reported in the New England Journal of Medicine Paper, the Advance-HTN trial per protocol confirmed incidence of hyperkalemia over 6 millimole per liter in the 50-milligram arm was 2.1%. Given the high dose of olmesartan, a potent long-acting arm, which also elevates serum potassium, we feel that this incidence of serum potassium greater than 6 millimole per liter has an acceptable benefit risk profile appropriate for the use in these patients.

根據《新英格蘭醫學雜誌》報導，Advance-HTN 試驗按照方案證實，50 毫克組中每公升超過 6 毫摩爾的高血鉀發生率為 2.1%。鑑於高劑量的奧美沙坦（強效長效藥物）也會升高血清鉀，我們認為血清鉀高於 6 毫摩爾/公升的發生率具有可接受的效益風險特徵，適合這些患者使用。

Okay. Now turning to our other programs, Explore-CKD and Explore-OSA Phase II proof-of-concept trials. Both of these trials are designed to provide data that augments the anti-type pretensive protocol of lorundrostat by profiling the an efficacy of lorundrostat in these 2 special populations of hypertensive individuals. During the first quarter, we announced the completion of enrollment in the Explore-CKD Phase II trial. This trial evaluates the safety and efficacy of lorundrostat for treatment of hypertension in subjects with an eGFR from 30 to 90 and at least 200 milligrams of UACR despite receiving stable treatment with an ACE inhibitor or an ARB as well as an SGLT2 inhibitor.

好的。現在轉向我們的其他項目，Explore-CKD 和 Explore-OSA 第二階段概念驗證試驗。這兩項試驗旨在透過分析 lorundrostat 對這兩類特殊高血壓患者的療效，提供增強 lorundrostat 抗類型預防性治療方案的數據。第一季度，我們宣布完成 Explore-CKD 第二階段試驗的招募。該試驗評估了儘管接受了 ACE 抑制劑或 ARB 以及 SGLT2 抑制劑的穩定治療，但 eGFR 為 30 至 90 毫克且 UACR 至少為 200 毫克的受試者使用 lorundrostat 治療高血壓的安全性和有效性。

Hypertension and associated hypertensive nephropathy is a leading cause of kidney damage alone and in combination with other obesity associated comorbidities.

高血壓和相關的高血壓腎病變是單獨或與其他肥胖相關合併症相結合導致腎臟損傷的主要原因。

This is another area with great unmet medical aldosterone synthase inhibition with lorundrostat has the potential for transformative benefit to patients. In this trial, the primary outcome measure is change in systolic blood pressure during a 4-week treatment period relative to that seen in a 4-week placebo treatment period in the same individuals. The key mechanism of kidney damage in hypertensive nephropathy is elevated blood pressure glomerular hyper perfusion, scarring and reduction of the number of glomeruli available to filter the blood. Changing prutinuria is being assessed in this trial as well.

這是另一個尚未充分滿足的醫學領域，使用 lorundrostat 抑制醛固酮合成酶有可能為患者帶來變革性的益處。在本次試驗中，主要結果測量是同一個體在 4 週治療期間收縮壓的變化相對於 4 週安慰劑治療期間收縮壓的變化。高血壓腎病變腎臟損害的關鍵機制是血壓升高、腎小球高灌注、疤痕形成以及可用於過濾血液的腎小球數量減少。本次試驗也正在評估尿蛋白變化。

In contrast to CKD due to diabetes and metabolic syndrome, where proteinuria is a useful surrogate endpoint. Individuals with predominant hypertensive nephropathy tend to have modest levels of proteinuria, change in blood pressure, along with acute physiological reduction in eGFR and rather than changing proteinuria may be a more useful outcome measure for a Phase II trial in this population.

與糖尿病和代謝症候群導致的 CKD 相比，蛋白尿是一個有用的替代終點。患有主要高血壓腎病的個體往往具有中等水平的蛋白尿、血壓變化以及 eGFR 的急性生理性降低，並且與蛋白尿變化相比，蛋白尿可能是針對該人群進行 II 期試驗更有用的結果測量指標。

In the first quarter of 2025, we announced initiation of the Explorer-OSA Phase II trial to evaluate the effect of lorundrostat in treatment of moderate to severe obstructive sleep apnea, blood pressure increases significantly as arterial oxygenation falls during upper airway obstruction at night. By dosing lorundostated bedtime, we believe we will suppress the majority of aldosterone produced during sleep, while maintaining 24-hour blood pressure control. Episodes of nocturnal hypertension are underdiagnosed and lack a demonstrated highly effective treatment.

2025 年第一季度，我們宣布啟動 Explorer-OSA II 期試驗，以評估 lorundrostat 治療中度至重度阻塞性睡眠呼吸中止症的效果，夜間上呼吸道阻塞時動脈氧合下降，血壓顯著升高。我們相信，透過在睡前服用洛拉多定，我們將抑制睡眠期間產生的大部分醛固酮，同時保持 24 小時血壓控制。夜間高血壓發作未被充分診斷​​，且缺乏經過證實的高效治療方法。

The current treatment armamentarium is limited to weight loss and the use of positive airway pressure. We believe that neither is sufficiently effective at minimizing the impact of OSA on major adverse clinical outcomes.

目前的治療方法僅限於減肥和使用氣道正壓通氣。我們認為，這兩種方法都不足以有效減少 OSA 對主要不良臨床結果的影響。

In summary, we have now demonstrated the clinically meaningful benefit risk profile of lorundrostat in individuals with aldosterone mediated hypertension. We are focused both on moving lorundrostat towards an NDA submission as well as exploring its use in prevalent comorbidities such as OSA hypertensive nephropathy, for which normalizing aldosterone production may result in meaningful clinical benefits.

總之，我們現在已經證明了洛倫司他對於醛固酮介導性高血壓患者的臨床意義的獲益風險概況。我們致力於推動 lorundrostat 提交 NDA，並探索其在 OSA 高血壓腎病變等常見合併症中的應用，對於這些合併症而言，正常化醛固酮生成可能帶來有意義的臨床益處。

I'll now turn the call over to Adam to review our financial results for the first quarter of 2025.

現在我將把電話交給亞當來回顧我們 2025 年第一季的財務表現。

Thank you, Dave. Good afternoon, everyone. Today, I will discuss elect portions of our first quarter 2025 financial results. Additional details can be found in our Form 10-Q which will be filed with the SEC today, May 12.

謝謝你，戴夫。大家下午好。今天，我將討論我們 2025 年第一季財務表現的精選部分。更多詳細資訊請參閱我們於 5 月 12 日向美國證券交易委員會 (SEC) 提交的 10-Q 表格。

We ended the quarter with cash, cash equivalents and investments of $343 million as of March 31, 2025, compared to $198.2 million as of December 31, 2024. We believe that our current cash, cash equivalents and investments will be sufficient to fund our planned clinical trials and regulatory activities as well as support corporate operations into 2027.

截至 2025 年 3 月 31 日，本季末我們的現金、現金等價物及投資為 3.43 億美元，而截至 2024 年 12 月 31 日為 1.982 億美元。我們相信，我們目前的現金、現金等價物和投資足以資助我們計劃的臨床試驗和監管活動，並支持到 2027 年的公司運作。

R&D expenses for the quarter ended March 31, 2025, were $37.9 million, compared to $30.8 million for the quarter ended March 31, 2024. The increase in R&D expenses was primarily due to increases of $4.8 million in preclinical and preclinical costs and $2.8 million in compensation expense resulting from additions to headcount, increases in salaries and accrued bonuses and increased stock-based compensation, partially offset by $0.5 million in lower clinical supply, manufacturing and regulatory costs.

截至 2025 年 3 月 31 日的季度的研發費用為 3,790 萬美元，而截至 2024 年 3 月 31 日的季度的研發費用為 3,080 萬美元。研發費用的增加主要是由於臨床前和臨床前成本增加 480 萬美元，以及由於員工人數增加、工資和應計獎金增加以及股票薪酬增加導致的薪酬費用增加 280 萬美元，但臨床供應、製造和監管成本降低 50 萬美元部分抵消了這一增加。

G&A expenses were $6.6 million for the quarter ended March 31, 2025, compared to $4.6 million for the quarter ended March 31, 2024. The increase in G&A expenses was primarily due to $1.2 million of compensation expense resulting from additions to headcount, increase in accrued bonuses and increased stock-based compensation and $0.7 million in higher professional fees.

截至 2025 年 3 月 31 日的季度，一般及行政費用為 660 萬美元，而截至 2024 年 3 月 31 日的季度為 460 萬美元。一般及行政費用的增加主要是由於員工人數增加、應計獎金增加、股票薪酬增加導致的 120 萬美元薪酬費用以及 70 萬美元的專業費用增加。

Total other income net was $2.2 million for the quarter ended March 31, 2025, compared to $3.9 million for the quarter ended March 31, 2024. The decrease was primarily attributable to decreased interest earned on our investments in money market funds and US treasuries. Net loss was $42.2 million for the quarter ended March 31, 2025, compared to $31.5 million for the quarter ended March 31, 2024. The increase was primarily attributable to the factors impacting the company's expenses described above.

截至 2025 年 3 月 31 日的季度，其他淨收入總額為 220 萬美元，而截至 2024 年 3 月 31 日的季度為 390 萬美元。下降的主要原因是我們在貨幣市場基金和美國國債上的投資所賺取的利息減少。截至 2025 年 3 月 31 日的季度淨虧損為 4,220 萬美元，而截至 2024 年 3 月 31 日的季度淨虧損為 3,150 萬美元。增加的主要原因是上述影響公司費用的因素。

With that, I'll ask the operator to open the call for questions. Operator?

說完這些，我將請接線生開始回答問題。操作員？

(Operator Instructions) Michael DiFiore, Evercore.

（操作員指示） Michael DiFiore，Evercore。

Congrats on all the progress. Just two for me. With regards to the CKD trial, in the past, you said that these patients are so sick that physicians will readily accept some level of hyperkalemia if it means that largesat will improve their blood pressure. So I guess the question is, will it be the max level of Grade 2 hyperkalemia that would be acceptable if lorundrostat were to yield a high single-digit placebo-adjusted SBP reduction? And then I have a follow-up.

祝賀你取得的所有進展。對我來說只要兩個。關於 CKD 試驗，過去您曾說過，這些患者的病情非常嚴重，如果這意味著 largesat 可以改善他們的血壓，醫生會欣然接受一定程度的高鉀血症。所以我想問題是，如果 lorundrostat 能夠產生高個位數的安慰劑調整收縮壓降低，那麼 2 級高血鉀的最高水平是否可以接受？然後我有一個後續問題。

Yes, Mike, just quick response. So I don't know that we categorized what would be an acceptable level. I think what's key and critical is we talk to specialists and our advisers who are treating these patients with hypertension and more advanced kidney disease. They're really looking at providing a benefit to the BP as well as relieving or improving the kidney function overall. I think these specialists tend to be predominantly nephrologists are more comfortable with higher level of capacity meetings within these patients.

是的，麥克，只是快速回應。所以我不知道我們對可接受的水平進行了分類。我認為關鍵的是我們要與治療這些患有高血壓和晚期腎病的患者的專家和顧問進行交談。他們真正希望的是為血壓帶來益處以及整體緩解或改善腎功能。我認為這些專家主要是腎臟病專家，他們更願意與這些患者進行更高程度的會談。

They have a means to manage that. They've got tools to use that -- they're also more likely to modulate other background treatments. In other words, if they're getting to be production with lorundrostat, they may reduce the dose of ACE or arm. So the take with us is within export, you get a clear sense of the safety, characterize the efficacy with this drug and knowing the full well, they're providing the benefit on both BP as well as kidney function in these subjects is what the specialists who are treating these patients predominantly are looking for.

他們有辦法解決這個問題。他們有工具可以使用它——他們也更有可能調節其他背景治療。換句話說，如果他們開始使用 lorundrostat 進行生產，他們可能會減少 ACE 或 arm 的劑量。因此，我們採取的措施是在出口範圍內，您可以清楚地了解安全性，描述這種藥物的功效，並充分了解，它們對這些受試者的血壓和腎功能都有益處，這正是治療這些患者的專家主要尋求的。

Got it. That's helpful. And my final question is like despite cadrostats, shorter half-life and lesser selectivity for aldosterone synthase inhibition relative to rent. It still showed a high single-digit percent SBP reduction over 14 weeks in their Phase II CKD trial. So I guess, should we expect similar efficacy and safety with lorundrostat?

知道了。這很有幫助。我的最後一個問題是，儘管有卡卓坦，但與租金相比，其半衰期較短，醛固酮合成酶抑制的選擇性較低。在第二階段 CKD 試驗中，它仍然顯示出 14 週內 SBP 降低的個位數百分比。所以我想，我們是否應該期待 lorundrostat 有類似的功效和安全性？

Yes, Mike, I think it's too hard to hedge what we expect to see. I think we would anticipate seeing the clinically meaningful reduction in BP. I think the profile for lorundrostat has been well characterized now with 3 successful studies from Target-HTN, Advance and Launch. But it's too early to hedge what we'd anticipate seeing, but I would anticipate certainly a clinically meaningful reduction and then we'll see how the data evolves as far for those other hemodynamic characteristics.

是的，麥克，我認為對我們期望看到的事情進行對沖太難了。我認為我們有望看到血壓在臨床上有意義的降低。我認為，Lorundrostat 的特性現在已透過 Target-HTN、Advance 和 Launch 的三項成功研究得到了很好的描述。但現在對我們預期會看到的結果進行預測還為時過早，但我預計肯定會出現具有臨床意義的減少，然後我們將看到其他血液動力學特徵的數據如何演變。

Richard Law, Goldman Sachs.

高盛的理查德·勞 (Richard Law)。

Great. And congrats on the process from me as well. So a couple of questions from me. Can you discuss how the overall, like the Explore-CKD study fit in the strategy for were submission with Launch and Advance. My understanding is that the study is important to provide clinical support for patients below EGFR 45.

偉大的。我也對這項進程表示祝賀。我有幾個問題。您能否討論一下整體情況，例如 Explore-CKD 研究如何適應 Launch 和 Advance 的提交策略。我的理解是，這項研究對於為 EGFR 45 以下的患者提供臨床支援非常重要。

And it will be great to hear your latest thinking on this and if that has evolved. And I have a follow-up.

我很高興聽到您對此的最新想法以及它是否有所進展。我還有一個後續問題。

Yes, Rich, thanks for the question. We're certainly excited about the benefit risk profile that's emerged now with lorundrostat with the successful completion of the Advance study and the Launch study, seeing double-digit reduction in BP with a really acceptable safety tolerability profile. The submission of the renters NDA will be inclusive of all three of those studies, as I noted, as well as the transform open-label extension, and Explore-CKD will be a component of that. Really, the biggest driver of Explore-CKD was related to informed blood pressure response in subjects with an EGFR down to 30 as well as going with a lower dose of 25 milligrams QD. And so it will be a component.

是的，Rich，謝謝你的提問。隨著 Advance 研究和 Launch 研究的成功完成，我們對目前 Lorundrostat 所展現出的效益風險狀況感到非常興奮，我們看到血壓實現了兩位數的降低，並且具有真正可接受的安全耐受性。正如我所指出的，租戶保密協議的提交將包括所有這三項研究以及轉換開放標籤擴展，而 Explore-CKD 將成為其中的一部分。實際上，Explore-CKD 的最大驅動力與 EGFR 低至 30 的受試者的知情血壓反應以及 25 毫克 QD 的較低劑量有關。所以它將成為一個組件。

I think it's going to be part of the totality of evidence of lorundrostat that will go into the NDA. I don't know if I could opine at this point as far as the specific language that will be included in the label from Explorer, but it's certainly a part of the total package what we have in the dialogue with the agency on.

我認為它將成為納入 NDA 的 lorundrostat 全部證據的一部分。我不知道現在我是否可以就 Explorer 標籤中的具體語言發表意見，但它肯定是我們與該機構對話時所討論的總體方案的一部分。

Great. Fantastic. And then -- so we saw in the New England Journal publication that the patients who have the potassium levels greater than six have a much lower average eGFR compared to the rest of the population. What is -- I mean, in your view, like what is the typical EGFR between like such study population in EXPLORE CKD study and dosed in a general hypertension study, like the 1 in your pivotal study program. like BI, the CKD study is that a good benchmark in terms of patient population?

偉大的。極好的。然後——我們在《新英格蘭醫學雜誌》的出版物中看到，鉀水平高於 6 的患者的平均 eGFR 與其他人群相比要低得多。什麼是 — — 我的意思是，在您看來，EXPLORE CKD 研究中的研究人群與一般高血壓研究中的劑量（例如您的關鍵研究計劃中的 1）之間的典型 EGFR 是多少。像 BI 一樣，CKD 研究在患者族群方面是一個很好的基準嗎？

Or is this a different population from that?

還是這是一個與那個不同的群體？

Rich, I'm sorry to do this. Can you rephrase your question? I just want to make sure I'm answering what you're looking for?

里奇，我很抱歉這樣做。你能重新表達一下你的問題嗎？我只是想確保我回答了您正在尋找的問題？

Yes. So in your New England Journal publication, patients who have the higher potassium levels greater than 6, they all have like lower than average eGFR compared to the rest of the population. So the question here is that how do we think about sort of the differences between the EGFR in your Explore-CKD study, compared to the Advance and Launch? And like what would be a good benchmark terms of the type of patient that would -- that -- in terms of the eGFR level, for your CKD study?

是的。因此，在《新英格蘭醫學雜誌》的出版物中，鉀水平高於 6 的患者與其他人群相比，其 eGFR 均低於平均水平。所以這裡的問題是，我們如何看待 Explore-CKD 研究中 EGFR 與 Advance 和 Launch 之間的差異？那麼，就 eGFR 水平而言，對於您的 CKD 研究來說，什麼是衡量患者類型的良好基準？

All right. Thanks, Rich. I appreciate that. Yes, I think that's why we're doing the Explore-CKD study. We know the eGFR, eGFR launch was higher than that in advance.

好的。謝謝，里奇。我很感激。是的，我認為這就是我們進行 Explore-CKD 研究的原因。我們知道 eGFR，eGFR 的推出比預先確定的要高。

Advance was a more high-risk population truly uncontrolled, truly confirmed resistant hypertension. They had a lower eGFR. I think you're alluding to what Luke shared at the ACC about the subjects above 6 had a mean of about 58. As far as how tight is the correlation between eGFR and risk and hypercare, I think we need more data and more evidence, but it's part of why we're doing the Explore-CKD trial. Looking at subjects going down to an eGFR 30.

Advance 是真正不受控制、真正確診為難治性高血壓的高風險族群。他們的 eGFR 較低。我認為您指的是 Luke 在 ACC 上分享的內容，關於 6 歲以上受試者的平均分數約為 58。至於 eGFR 與風險和過度照護之間的關聯有多緊密，我認為我們需要更多的數據和證據，但這也是我們進行 Explore-CKD 試驗的部分原因。觀察 eGFR 降至 30 的受試者。

We know they have the risk of potential more challenges in managing electrolyze that's why we're testing the 25-milligram QD that we believe is an effective dose of lorundrostat. But as far as the correlation, I think that's something that will continue to unfold Dave, if you've got some additional thoughts, please.

我們知道他們在管理電解方面可能面臨更多挑戰，這就是為什麼我們要測試 25 毫克 QD，我們認為這是有效劑量的 lorundrostat。但就相關性而言，我認為這將會繼續展開，戴夫，如果你還有其他想法，請。

Rich, good question. And how are you doing -- the -- when you talk about studies like this, the outliers are, in some ways, more important than the means, right? So the mean was above 60, say, for the people who didn't have any good incidents. It was a little bit lower and they had it. In this trial, what we're really looking for those individuals who are in that 30 to 45 range, maybe on the lower side and saying, what happens to them.

Rich，好問題。當您談論這樣的研究時，您是如何做到的？從某種程度上來說，異常值比平均值更重要，對嗎？因此，對於沒有遇到任何好事情的人來說，平均值在 60​​ 以上。價格稍微低一點，但他們有。在這次試驗中，我們真正尋找的是那些年齡在 30 到 45 歲之間、可能處於較低水平的個體，並想知道他們會發生什麼。

Not that this is an issue other than giving guidance to clinicians for who to keep an eye on and probably who to give a potassium binder, if needed? Or as Jon said, back off on the art and see if you can maintain the same blood pressure. So it's a guidance, it's what we call a special population profiling study, and we anticipate looking just as much an outer as we do about means in that trial.

這不是一個問題，而是一個指導臨床醫生需要關注誰以及在需要時需要給誰注射鉀結合劑的問題？或者就像喬恩所說的那樣，放棄藝術，看看你是否能保持相同的血壓。所以這是一個指導，這就是我們所說的特殊人群分析研究，我們期望在該試驗中觀察外部情況，就像觀察平均值一樣。

Got it. Very helpful. And then just one last question. Similar to Explore-CKD, do you expect to include data from the Explore-OSA in your found package?

知道了。非常有幫助。最後一個問題。與 Explore-CKD 類似，您是否希望在找到的套件中包含來自 Explore-OSA 的資料？

I think, Rich, it's fair question. I think it's too early to opine on that. We haven't guided on top line data. We're excited about that study to address a significant unmet need within that resistant hypertension OSA population, but it's too early to comment what or would that not be included in the discussions with the FDA.

我認為，里奇，這是一個公平的問題。我認為現在對此發表意見還為時過早。我們尚未對頂線數據提供指導。我們很高興看到這項研究能夠解決難治性高血壓 OSA 族群中一個尚未滿足的重要需求，但現在評論在與 FDA 的討論中是否會包括哪些內容還為時過早。

Seamus Fernandez, Guggenheim.

謝默斯·費爾南德斯，古根漢美術館。

Great. So Jon, I think on the last discussion call, you mentioned that as many as 47,000 physicians could actually be appropriate for promotion in the uncontrolled and resistant hypertension opportunity. And then you also at ACC emphasized that the opportunity may sit a little bit more initially in the sort of fourth line hypertension opportunity.

偉大的。所以喬恩，我想在上次討論電話中，你提到多達 47,000 名醫生實際上可能適合在未控制和難治性高血壓領域獲得晉升。然後您也在 ACC 強調，這個機會最初可能更多地存在於第四線高血壓機會中。

Can you just help us understand how does the sort of intersection of that broad physician base intersect with your view of the needs of a partner in that context? And what are you really looking for in the context of either a partner or something perhaps more strategic or an opportunity to actually start advancing the opportunity to promote on your own?

您能否幫助我們理解廣泛的醫生群體與您對合作夥伴需求的看法有何交集？那麼，在合作夥伴、更具策略性的東西或真正開始推動自主推廣的機會方面，您真正在尋找的是什麼？

Yes. The 47,000, Rich, those that maybe hadn't heard before. So we did a significant project about a year ago with IQVIA with about [1 million] prescription claims within that. And when you basically narrowed down, where does 50% of the prescribing come from for third line or later priming, there's about 47,000 doctors that account for about half of that prescribing and a significant portion of the influence on the other 50%. And from our standpoint, there's a very efficient commercial model, particularly with kind of clinical profile that runestat has now demonstrated to go out and target the 47,000 prescribers and generate significant value.

是的。47,000，Rich，那些人可能以前沒有聽說過。大約一年前，我們與 IQVIA 合作開展了一個重要項目，涉及約 [100 萬] 份處方藥索賠。當你基本上縮小範圍時，50% 的處方來自第三線或更晚的啟動，大約有 47,000 名醫生佔了其中一半的處方，並對另外 50% 產生了很大影響。從我們的角度來看，這是一個非常有效的商業模式，特別是具有臨床特徵的 Runestat，現在已經證明它可以針對 47,000 名處方者並產生巨大的價值。

But as we've talked about in the past, partnering for us is inclusive of US, but certainly global, looking for partners they can help optimize the opportunity of lorundrostat US because we have no intentions of creating Mineralys commercial entities stand-alone outside of United States. So finding a partner can help maximize that opportunity ex-US but then really fully tap into the opportunity in the United States as well. And that would basically mean some level of overall with the targeted physicians that we've talked about, but certainly coverage of those outside of those 47,000 that we target.

但正如我們過去所談到的，對我們來說，合作夥伴包括美國，但肯定是全球性的，尋找合作夥伴，他們可以幫助優化美國的機會，因為我們無意在美國以外獨立創建 Mineralys 商業實體。因此，找到合作夥伴可以幫助最大限度地利用美國以外的機會，同時也能充分利用美國境內的機會。這基本上意味著，我們所討論的目標醫生的整體覆蓋範圍達到了一定程度，但肯定涵蓋了我們所針對的 47,000 名醫生之外的醫生。

And in fact, that target may be a little bit smaller as we think about an initial launch of lorundrostat, fourth line is probably going to be the ideal place to go. That's where there's minimal benefit with existing treatments beyond aldosterone directed therapeutics. We know spironolactone is thought to be valuable there, but it's greatly underutilized. I think our clinical program to date where we've targeted those subjects failing to get to goal on to more med shows the value of an atosteron-directed treatment that physicians are going to want to work, patients are going to want to take and persist with. So we think there's significant opportunity there.

事實上，當我們考慮首次推出 lorundrostat 時，這個目標可能會小一些，第四行可能是理想的去處。這就是說，除了醛固酮導向療法之外，現有治療方法的益處微乎其微。我們知道螺內酯在那裡很有價值，但它的利用率卻很低。我認為，迄今為止，我們的臨床計畫針對的是那些未能達到目標的患者，並向他們提供了更多的藥物，這表明了阿托品導向治療的價值，醫生願意進行這種治療，患者也願意接受並堅持下去。因此我們認為這裡面存在著重大機會。

We think we could tap into a significant portion of those prescribers, but having a partner clearly is going to help us maximize the value of the asset in the United States.

我們認為我們可以利用這些處方者的很大一部分，但擁有合作夥伴顯然將幫助我們最大限度地提高美國資產的價值。

Great. And maybe just one follow-up. Can you just remind us what gating factors are to sort of finalizing and filing the NDA specifically?

偉大的。也許只需要一個後續行動。您能否提醒我們，最終確定並提交保密協議 (NDA) 的限制因素具體有哪些？

Yes, happy to do that. First and foremost, recently very pleased with the benefit risk profile that we continue to see with this molecule. Now with the 2 active portions of the pivotal program completed. As we've stated before, the unlabeled extension is a critical aspect of that. If you think about when the last subjects enrolled and launched in advance that was at the end of October last year, we would anticipate also just completing the 52-week open label by Q1 of next year.

是的，我很樂意這麼做。首先，最近我們對這種分子的效益風險狀況感到非常滿意。現在，關鍵程序的兩個活動部分已經完成。正如我們之前所說，未標記的擴展是其中一個關鍵方面。如果您想想最後一批受試者是在去年 10 月底提前入組和啟動的，那麼我們預計明年第一季也能完成 52 週的開放標籤研究。

Now we don't need to have all of those subjects to enable the filing. But we need the -- certainly, a majority of those subjects through 52 weeks before we'd be comfortable with the NDA. But that's part of what we'll have a dialogue with the FDA in Q4, as we've discussed in the pre-IND meeting. And so it will be both the pit programs for Advance and Launch will be part of the target data, the Explore-CKD data. And then a portion of that open-label extension will be informative for that pre-NDA meeting that will then have better guidance for timing of an NDA submission.

現在我們不需要擁有所有這些主題就可以進行歸檔。但我們需要——當然，大多數受試者需要經歷 52 週的時間才能對 NDA 感到滿意。但正如我們在 IND 前會議上討論的那樣，這是我們在第四季度與 FDA 進行對話的一部分。因此，Advance 和 Launch 的維修站程序都將成為目標資料即 Explore-CKD 資料的一部分。然後，此開放標籤擴展的一部分將為 NDA 前會議提供信息，從而為 NDA 提交的時間提供更好的指導。

Tim Anderson, Bank of America.

美國銀行的蒂姆·安德森。

This is Alice on for Tim. I just want to check, can you hear me okay?

這是愛麗絲為提姆表演的。我只是想確認一下，你聽得到我說話嗎？

Yes, we can.

是的，我們可以。

Okay. Perfect. Just following on from Seamus' questions on partnering. Could you talk about any early discussions you may have had so far? And what are the limiting factors that a partner may be looking for?

好的。完美的。剛才 Seamus 提出了關於合作的問題。您能談談迄今為止可能進行過的任何早期討論嗎？那麼合作夥伴可能正在尋找哪些限制因素？

So we're going to have the full data from Launch and the top line CKD study very soon. But do potential partners need to wait for the outcome of the pre-NDA meeting, for example, as well as the AstraZeneca Baxters at for data? And then I have a follow-up.

因此，我們很快就會獲得 Launch 和頂級 CKD 研究的完整數據。但是，潛在的合作夥伴是否需要等待 NDA 前會議的結果，以及阿斯特捷利康和巴克斯特的數據？然後我有一個後續問題。

Sure. So to date, we haven't given updates on our partnering discussion, but we do continue to believe that a partner or multiple partners will be a part of our story, and we'll keep you updated as appropriate.

當然。因此，到目前為止，我們還沒有提供有關合作討論的最新消息，但我們仍然相信，一個或多個合作夥伴將成為我們故事的一部分，我們會適時向您通報最新情況。

Okay. And then as to the economy references a $5 billion peak sales for baxdrostat. I'm curious how are you thinking that you can best leverage a partner in order to realize this sort of potential with lorundrostat. For example, does it involve developing fixed dose combinations or other indications and things like that?

好的。然後就經濟而言，巴克斯羅司他的峰值銷售額為 50 億美元。我很好奇，您認為如何才能最好地利用合作夥伴來實現 lorundrostat 的這種潛力。例如，它是否涉及開發固定劑量組合或其他適應症等？

Yes. Thanks, Alex. There's clearly great deal of unmet need in this space. We're focused exquisitely right now in hypertension, but we know there's utility for an ideal aldosterone-directed treatment beyond that. That's why we're looking at the adjacencies because there's such an overlap in all of these card renal metabolic syndromes that have either hypertension or diabetes kind of at the central point.

是的。謝謝，亞歷克斯。顯然，這個領域還有大量未滿足的需求。我們現在專注於高血壓，但我們知道理想的醛固酮導向治療還有更大的用途。這就是我們研究鄰接關係的原因，因為所有這些腎臟代謝症候群都有重疊，而高血壓或糖尿病都是其中心點。

And so we think there is significant unmet need. There's significant value to provide to patients to help reduce their BP, which is the leading modifiable risk factor for cardiovascular risk. But moving from hypertension into adjacencies, such substructive sleep apnea, hypertensive nephropathy. As you heard Dave speak about, we think basically generate significant value for us. As we have partnering dialogues, as I've spoken about in the past, part of that is partnering from a commercial perspective.

因此我們認為存在大量未滿足的需求。為患者提供降低血壓的幫助具有重要價值，而血壓是心血管風險的主要可改變風險因子。但從高血壓轉向鄰近疾病，例如阻塞性睡眠呼吸中止症、高血壓腎病變。正如戴夫所說的那樣，我們認為這基本上為我們創造了巨大的價值。正如我過去談到的，我們有合作對話，其中一部分是從商業角度的合作。

But -- for those that have a shared vision, it also could be development partnerships as well. Looking at some of these adjacent areas, such as heart figure or CKD. Again, we know that aldosterone plays a role across the spectrum, and having what we believe to be a leading ASI gives us significant opportunity to tap into that value.

但是，對於那些擁有共同願景的人來說，這也可能是發展夥伴關係。查看一些相鄰區域，例如心臟圖形或 CKD。再次強調，我們知道醛固酮在整個光譜中發揮作用，擁有我們認為領先的 ASI 為我們提供了挖掘這一價值的重要機會。

Annabel Samimy, Stifel.

安娜貝爾·薩米米（Annabel Samimy），Stifel。

This is Jed on for Annabel. I have two questions. First is, at what point do you think that guideline -- hypertension guidelines would in start including Launch and added HTN data? Is there any possibility that it could be updated before you guys would theoretically launch?

這是傑德為安娜貝爾表演的。我有兩個問題。首先，您認為高血壓指南什麼時候開始包括啟動和添加高血壓數據？你們理論上發布之前有可能進行更新嗎？

Yes, I appreciate the question. I don't know that we can opine on when the timing will be specifically. I think we can only look at historical precedents. And I think the various guideline committees when faced with new valued innovations have been responsive to try to guide their constituents on how they should think about and integrate these new innovations into their treatment paradigm. So it's too early to opine.

是的，我很感謝你提出這個問題。我不知道我們能否就具體時間發表意見。我認為我們只能看看歷史先例。我認為，各個指導委員會在面對新的有價值的創新時都會積極回應，試圖指導其成員如何思考這些新創新並將其融入他們的治療模式中。所以現在發表意見還太早。

But it's -- it's a fair question. That's why we went to the what we did in Advance-HTN because I think it fundamentally addresses the kind of questions that these guideline committees wish to have. And that is not only in maybe an existing background treatment, but when you get to truly high-risk patients like we tested in advance, what does the profile physicians could expect? And how would guideline committees inform their communication and their constituents.

但這是一個合理的問題。這就是我們致力於 Advance-HTN 的原因，因為我認為它從根本上解決了這些指導委員會希望提出的問題。這可能不僅僅是在現有的背景治療中，而且當你遇到像我們提前測試過的真正的高風險患者時，專科醫生可以期待什麼？指導委員會將如何告知他們的溝通對象及其選民。

Got it. And my other question is related to Explore-CKD. What do you think is the primary if you're looking for here? Are you looking for safety in the CKD population with concomitant drugs, inhibitors and ARBs? And then do you expect efficacy to generally be in the line of what you saw in -- or are there some nuances with that patient population that we should know?

知道了。我的另一個問題與 Explore-CKD 有關。如果您在這裡尋找什麼，您認為主要的是什麼？您是否希望 CKD 患者使用伴隨用藥、抑制劑和 ARB 來確保安全？那麼，您是否預期療效總體上與您看到的一致 - 或者我們應該了解該患者群體的一些細微差別？

Yes. I'll just reiterate what Dave had said with a profiling the study like the safety is a key element of the analysis and what we expect from a clinical benefit standpoint would be clinically meaningful reduction in blood pressure. I think that's been well characterized in the 3 studies to date. That's what we would anticipate to see in this population, and then providing additional information about the 25-milligram QD dose.

是的。我只是想重申戴夫在分析這項研究時所說的話，例如安全性是分析的關鍵要素，而從臨床益處的角度來看，我們所期望的是血壓在臨床上有意義的降低。我認為迄今為止的三項研究已經很好地描述了這一點。這就是我們期望在這個人群中看到的情況，然後提供有關 25 毫克 QD 劑量的更多資訊。

Mohit Bansal, Wells Fargo.

富國銀行的 Mohit Bansal。

This is Fatima on for Mohit. And congrats on all the recent progress. So on the hypertension readout, you've previously mentioned plans for subgroup Can you elaborate on those plans for which subgroups you're focused on and the time line for presentation of that data? And can you talk about how it could potentially help physicians select patients for lorundrostat? And if it could also influence placement of lorundrostat into treatment guidelines?

這是 Fatima 為 Mohit 表演的。並祝賀您最近的所有進展。因此，在高血壓讀數上，您之前提到了針對亞組的計劃，您能否詳細說明您關注的亞組的計劃以及呈現該數據的時間表？您能談談它如何幫助醫生選擇使用 lorundrostat 的患者嗎？它是否也會影響將 lorundrostat 納入治療指引？

Yes, thank you for the question. As you know, we've to prespecify analysis of populations that may be unique responders to lorundrostat. You saw some of that data within the Advance-HTN, ACC as well as Nigam presentation and publications, respectively. I would anticipate seeing something similar with Launch-HTN. I think to date, what we've seen and it's frankly beneficial for prescribers, whether failing to achieve goal on 2 meds or 3 meds on controller resistant hypertension, you're seeing a pretty profound reduction in regardless of gender, age, race, number of background medications.

是的，謝謝你的提問。如您所知，我們必須預先指定對 lorundrostat 有獨特反應的人群的分析。您分別在 Advance-HTN、ACC 以及 Nigam 簡報和出版物中看到了其中一些數據。我希望看到與 Launch-HTN 類似的東西。我認為到目前為止，我們所看到的，坦白說，這對處方者是有益的，無論是未能透過 2 種藥物還是 3 種藥物達到控制難治性高血壓的目標，你都會看到，無論性別、年齡、種族、背景藥物數量如何，都有相當顯著的減少。

And so it creates a predictable response that physicians can anticipate when using lorundrostat. We're going to continue to investigate and dive into the data. I mean what we've shared to date has been very informative about the value from a clinical reduction and safety standpoint. But there's a great deal of data we're going to continue to dig into within launch and advance and eventually Explore-CKD to really continue to further inform -- All right, what is the ideal population to respond to this drug. But to date, we've seen great responses across a multitude of subsets.

因此，它會產生可預測的反應，醫生在使用 lorundrostat 時可以預見這種反應。我們將繼續調查並深入研究數據。我的意思是，我們迄今為止所分享的內容從臨床減少和安全的角度來看非常有價值。但是，我們將在發布和推進過程中繼續挖掘大量數據，並最終在 Explore-CKD 中繼續提供進一步的資訊——好吧，對這種藥物有反應的理想人群是什麼。但到目前為止，我們已經看到大量子集的正面回應。

And then on the OSA trial, how are you thinking about this 4-week endpoint? How it aligns with expected time lines for improvements in the hypoxia index and nocturnal blood pressure? And what magnitude of action would you consider to be clinically meaningful and also competitive in the context of the data reported with GLPs, for example?

那麼在 OSA 試驗中，您如何考慮這個 4 週終點？它如何與缺氧指數和夜間血壓改善的預期時間線保持一致？例如，根據 GLP 報告的數據，您認為什麼程度的行動具有臨床意義且具有競爭力？

Really good questions. Let me try to take those one at a time. So the first question was 4 weeks. What might we see? So as far as APMEA popular index, the primary mechanism through which our drug will work is the diuretic effect and reducing the amount of salt and water overload.

確實是好問題。讓我嘗試一次解決一個問題。所以第一個問題是4週。我們可能會看到什麼？因此，就 APMEA 流行指數而言，我們的藥物發揮作用的主要機制是利尿作用和減少鹽和水的超負荷量。

Because when you lay down at night, the excess salt water, the fluid shifts up. It's called roster cattle redistribution into your upper body and neck. That benefit is accrued within a few weeks. And so by 4 weeks, we would expect to see the benefit on Apnea Hypopnea Index.

因為當你晚上躺下時，多餘的鹽水和液體就會上移。這被稱為將名冊牛重新分配到你的上半身和頸部。該福利在幾週內就會累積起來。因此，到 4 週時，我們有望看到呼吸暫停低通氣指數的改善。

As you know, around a 50% reduction has been seen with the Lilly study similar with the APMEA study of a different mechanism we're powered down to about 30%, and these are small trials. So we would ultimately be observing where we are in that range.

如你所知，禮來公司的研究顯示減少了約 50%，而 APMEA 的研究則採用了不同的機制，我們將功率降低至約 30%，而且這些都是小規模試驗。所以我們最終會觀察我們處於該範圍內的哪個位置。

So let me just say something. Treating at the FDA hypopnea index is important, but the main risk for adverse outcomes is this extreme burst of hypertension, these spikes that you see at night when those things happen, and we're going to be doing the first trial using sub-1-second measurements -- blood pressure over the course of an entire night. So we'll be able to look at how well does this drug actually reduce the risk for adverse clinical outcomes. In many ways, that's a more important endpoint. However, Apnea Hyponea Index and patient reported performance metrics are the current guidance from the agency for approval.

所以讓我說幾句。根據 FDA 低通氣指數進行治療很重要，但不良後果的主要風險是高血壓的極度爆發，即夜間發生這些情況時出現的峰值，我們將進行第一次試驗，使用亞秒測量法測量整個晚上的血壓。因此我們將能夠觀察這種藥物實際上在多大程度上降低不良臨床後果的風險。從許多方面來說，這是一個更重要的終點。然而，呼吸暫停低通氣指數和患者報告的表現指標是該機構目前批准的指導。

So we're going down both of those paths. This is on antihypertensive drug, and it's a sodium depleter. We expect to see benefits on both, but both are going to be meaningful. So I can't tell you for sure if apnea hypoxia index is 30, but we see a terrific impact on nighttime blood pressure, maybe restoration, nighttime dipping. We'll be the only ones with those data at that point will be reporting them.

所以我們會同時走這兩條路。這是一種抗高血壓藥物，它是一種鈉耗竭劑。我們希望看到兩者都有好處，而且兩者都將是有意義的。因此，我無法確定地告訴您呼吸暫停缺氧指數是否為 30，但我們可以看到它對夜間血壓產生了巨大影響，可能是恢復，也可能是夜間下降。到那時，我們將是唯一擁有這些數據並進行報告的人。

And I think that will be really an important milestone in studying this disease.

我認為這將是研究這種疾病的一個重要里程碑。

Rami Katkhuda, LifeSci Capital.

Rami Katkhuda，生命科學資本。

I guess I just wanted to confirm a statement that Dr. Robin made that patients with hypertensive nephropathy may have more modest levels of proteinuria. I guess, is the patient population in Explore-CKD similar to that of the Bohringer study? Or are there other key differences in enrollment criteria? And I guess is that 37% placebo-adjusted UACR reduction with monotherapy a fair bar here?

我想我只是想證實羅賓博士的說法，即患有高血壓腎病的患者的蛋白尿水平可能更適中。我猜想，Explore-CKD 中的患者群體與 Bohringer 研究中的患者群體相似嗎？或者入學標準是否有其他主要差異？我猜想，單一療法將 UACR 降低 37% 安慰劑調整後是一個公平的標準嗎？

Okay. Those are good questions. And if we think about this, and this has happened in other diseases, Chronic kidney disease is a syndrome, right? It can be autoimmune and you want to use an anti IGA, which has been very effective. If you -- it's in the context of obesity and diabetes, it's from metabolic syndrome, and that is the one that's associated with a fair amount of proteinuria, even nephrotic syndrome, which is an extreme of that.

好的。這些都是很好的問題。如果我們考慮一下，這種情況也發生在其他疾病中，那麼慢性腎病是一種綜合症，對嗎？它可能是自體免疫性的，您需要使用抗 IGA，它非常有效。如果您 - 這是在肥胖和糖尿病的背景下，它來自代謝綜合徵，並且與相當數量的蛋白尿有關，甚至腎病綜合徵，這是其中的極端情況。

What we're looking at -- some of these patients may have high levels of proteinuria, but we anticipate that will not be the majority in this trial. So a different subset and it's actually a different subset of CKD. These people have scarring of their external part of their -- the cortex of their kidney, loss of these glomeruli from this water hammer effect of the pounding of blood pressure. For these people, getting their blood pressure down to 125 or 130 is not all they need. They need lower blood pressures than those to truly protect the globe live at our left.

我們正在觀察的是——其中一些患者可能有高水平的蛋白尿，但我們預計這不會是本次試驗中的大多數。因此，這是一個不同的子集，實際上它是 CKD 的一個不同子集。這些人的腎臟外部——腎臟皮質——已經留下疤痕，由於血壓升高造成的水擊效應，腎小球也流失了。對於這些人來說，將血壓降至 125 或 130 並不是他們所需要的全部。他們需要的血壓比我們左邊真正保護地球的人低。

And so we're going to be looking at that and continuing to explore the possibility of differentiating on that basis as we get into this clinic kidney disease space.

因此，當我們進入臨床腎臟疾病領域時，我們將研究這一點並繼續探索在此基礎上區分的可能性。

It's not our primary objective per se because we are going after hypertension broadly. We're now since we've proven, that's a highly safe and effective drug for uncontrolled and resistant hypertension. Now we're starting to go to the very high unmet need subpopulations, which right now is we consider to be hypertensive for nephropathy and OSA.

這本身並不是我們的主要目標，因為我們要廣泛地研究高血壓。我們現在已經證明，這是一種治療無法控制和難治性高血壓的高度安全有效的藥物。現在我們開始關注那些未滿足需求程度極高的亞群，目前我們認為這些亞群患有高血壓、腎臟病和阻塞性睡眠呼吸中止症 (OSA)。

And Rami, just to add to that, the distinctions between the studies. I think the baseline is like BP in that study was low that is our inclusion criteria. So to Dave's point, we really are retreating the with GFR hypertension -- think that does create a distinct population between the two studies.

拉米，我還要補充一點，這些研究之間有差異。我認為基線就像研究中的血壓較低一樣，這是我們的納入標準。因此，正如戴夫所說，我們確實正在減少 GFR 高血壓——認為這確實在兩項研究之間產生了不同的人群。

There are no further questions at this time. I would hand over the call to Jon Congleton for closing remarks. Please go ahead.

目前沒有其他問題。我將把發言權交給喬恩·康格爾頓 (Jon Congleton) 來做結束語。請繼續。

Thank you, operator. Mineralys Therapeutics, we're committed to improving the lives of patients with cardiorenal metabolic diseases. Uncontrolled and resistant hypertension are significant unmet medical needs impacting more than 20 million patients in the US alone. Our launch in Advanced studies reinforce the differentiated clinical profile of lorundrostat versus agents that are typically used in the third and fourth-line treatment positions and the quantitative research that we've done supports the commercial potential.

謝謝您，接線生。Mineralys Therapeutics，我們致力於改善心臟腎臟代謝疾病患者的生活。不受控制和難治性高血壓是尚未滿足的重大醫療需求，光是在美國就影響 2,000 多萬名患者。我們在高級研究中的推出強化了 lorundrostat 與通常用於第三和第四線治療的藥物的差異化臨床特徵，並且我們所做的定量研究支持了商業潛力。

We're excited for key upcoming milestones and look forward to sharing updates with you in the coming quarters. Thank you all. Thank you for joining for joining us today. And with that, we'll close the call. Thank you, everyone.

我們對即將到來的關鍵里程碑感到興奮，並期待在未來幾季與您分享最新消息。謝謝大家。感謝您今天的加入我們。就這樣，我們就結束通話了。謝謝大家。

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation, and you may now disconnect.

女士們、先生們，今天的電話會議到此結束。感謝您的參與，您現在可以斷開連接。