Mineralys Therapeutics Inc (MLYS) 2025 Q3 法說會逐字稿

Greetings, and welcome to Mineralys third-quarter 2025 earnings conference call. (Operator Instructions) As a reminder, this conference is being recorded.

各位好，歡迎參加 Mineralys 2025 年第三季財報電話會議。（操作說明）提醒各位，本次會議正在錄音。

I would now like to turn the conference over to your host, Dan Ferry. Thank you. You may begin.

現在我將把會議交給主持人丹費裡。謝謝。你可以開始了。

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

謝謝接線生。歡迎各位參加我們2025年第三季電話會議。今天下午早些時候，我們發布了一份新聞稿，提供了我們 2025 年第三季的財務表現和業務最新進展。今天的電話會議錄音將在會議結束後約一小時後在公司網站的投資者關係版塊提供回放。在我們發言完畢後，我們將開放問答環節。

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 materially -- 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.

在會議開始之前，我想提醒大家，本次電話會議和網路直播將包含有關公司的前瞻性聲明。由於公司業務存在風險和不確定性，實際結果可能與這些前瞻性聲明中所述或暗示的結果有重大差異。這些前瞻性聲明受到今天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）中所包含的警示性聲明的限制。

Please note that these forward-looking statements reflect our opinions only as of today, November 10, 2025. 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，這些前瞻性陳述僅反映我們截至 2025 年 11 月 10 日的觀點。除法律另有規定外，我們特此聲明，不承擔因新資訊或未來事件而更新或修改這些前瞻性聲明的任何義務。

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

現在我將把電話交給 Mineralys Therapeutics 的執行長 Jon Congleton。

Thank you, Dan. Good afternoon, everyone, and welcome to our third-quarter 2025 financial results and corporate update conference call. I'm joined today by Adam Levy, our Chief Financial Officer; Dr. David Rodman, our Chief Medical Officer; and Eric Warren, our Chief Commercial Officer.

謝謝你，丹。各位下午好，歡迎參加我們2025年第三季財務業績及公司最新進展電話會議。今天與我一同出席的有：財務長亞當·利維；首席醫療官大衛·羅德曼博士；以及首席商務官埃里克·沃倫。

I'll begin with an overview of the business, our clinical programs, and recent milestones, followed by Adam to review our third quarter financial results before we open up the call for your questions.

我將首先概述公司業務、臨床項目和近期取得的里程碑，然後由 Adam 回顧我們第三季度的財務業績，之後我們將開放問答環節。

We're excited to have this opportunity today to provide an update on the progress our team has made over the past couple of months. Last month, we received pre-NDA feedback from the FDA. There were no surprises in this feedback and we're moving ahead with our NDA filing, which we expect to submit either late this quarter or in the first quarter of 2026.

今天我們很高興有機會向大家報告我們團隊在過去幾個月的進展。上個月，我們收到了 FDA 的 NDA 前回饋意見。此次回饋並無意外，我們將繼續推進 NDA 申請，預計將於本季末或 2026 年第一季提交。

In preparation for the submission, we developed a robust data package featuring results from multiple clinical trials across the spectrum of distinct and diverse participants with lorundrostat, which we believe support its potential as a best-in-class treatment for high-risk patients with uncontrolled of resistant hypertension and beyond.

為了準備提交，我們開發了一個強大的數據包，其中包含了來自多項臨床試驗的結果，這些試驗涵蓋了各種不同和多樣化的參與者，我們相信這些結果支持了 lorundrostat 作為一流療法在難治性高血壓等高風險患者中的應用潛力。

Earlier this year, we announced data from the Launch-HTN and Advance-HTN pivotal trials. The results from both trials demonstrate that lorundrostat offers a clinically meaningful and sustained reduction in systolic blood pressure. These data have generated broad interest across the medical community, underscoring the unmet need, the desire for innovation and the management of hypertension, and the commercial potential of lorundrostat.

今年早些時候，我們公佈了 Launch-HTN 和 Advance-HTN 關鍵性試驗的數據。兩項試驗的結果均表明，洛倫德司他能顯著降低收縮壓，且具有臨床意義並能持續降低收縮壓。這些數據引起了醫學界的廣泛關注，凸顯了高血壓治療領域尚未滿足的需求、對創新和治療的渴望，以及洛倫德司他（lorundrostat）的商業潛力。

These findings form the foundation of our NDA submission, which includes data demonstrating that lorundrostat maintains a durable and clinically meaningful response across diverse patient populations, a key consideration for its potential use in treating uncontrolled and resistant hypertension. This includes subgroup analysis from the Phase 3 Launch-HTN trial and data from confirmed hypertension patients in the Advance-HTN trial.

這些發現構成了我們提交新藥申請的基礎，其中包括證明洛倫德司他能夠對不同患者群體產生持久且具有臨床意義的反應的數據，這是其用於治療難治性高血壓的潛在用途的關鍵考慮因素。這包括來自 3 期 Launch-HTN 試驗的亞組分析和 Advance-HTN 試驗中確診高血壓患者的數據。

The Launch-HTN trial enrolled a diverse group of participants. Nearly one-third were Black or African-Americans, half the participants were women, the majority of participants were overweight or obese, and over half had resistant hypertension, requiring three or more background on hypertensive medications.

Launch-HTN試驗招募了不同背景的參與者。近三分之一是黑人或非裔美國人，一半的參與者是女性，大多數參與者超重或肥胖，超過一半患有難治性高血壓，需要服用三種或三種以上降血壓藥物。

Across all subgroups, lorundrostat 50 milligrams once daily, demonstrated consistent, statistically significant, and clinically meaningful reductions in blood pressure. All systolic BP reductions generated in Launch-HTN were measured at 24 hours after a dose, proving the sustained effect in true once-daily profile.

在所有亞組中，每日一次服用 50 毫克洛倫德司他均顯示持續、統計學上有意義且臨床意義顯著的血壓降低。 Launch-HTN 研究中所有收縮壓降低均在給藥後 24 小時測量，證實了每日一次給藥方案的持續療效。

The Advance-HTN trial designed and executed in conjunction with the Cleveland Clinic, enrolled a diverse group of hard-to-treat participants with confirmed uncontrolled and resistant hypertension by design with over half of the subjects being black or African Americans.

Advance-HTN 試驗由克利夫蘭診所設計並執行，該試驗招募了一組難以治療的參與者，這些參與者均被確診患有未控制的難治性高血壓，其中超過一半的受試者是黑人或非裔美國人。

Now let me pause for just a second, describe what I mean by confirmed. In any trial that allows participants to remain on their existing background medications such as Launch-HTN, patients may have apparent hypertension, meaning if they optimize their treatment with the existing medications, they may get to goal.

現在請容許我稍作停頓，解釋一下我所說的「確認」是什麼意思。在任何允許參與者繼續服用現有背景藥物（如 Launch-HTN）的試驗中，患者可能會出現明顯的高血壓，這意味著如果他們優化現有藥物的治療，他們可能會達到目標。

In Advance-HTN, participants' existing background medications were removed and they were started on an optimized background treatment aligned with the AHA guidelines, confirmed daily compliance with smartphone technology, and randomized only if they remained hypertensive after a three-week run-in, utilizing the measurement of 24-hour ABPM. In these most difficult-to-treat participants, lorundrostat again demonstrated a significant and clinically meaningful reduction in systolic blood pressure and was well tolerated.

在 Advance-HTN 研究中，參與者現有的背景藥物被移除，並開始接受符合 AHA 指南的優化背景治療，透過智慧型手機技術確認每日依從性，並且只有在經過三週的導入期後，使用 24 小時動態血壓監測測量血壓後仍患有高血壓時，才會進行隨機分組。在這些最難治療的參與者中，lorundrostat 再次表現出顯著且具有臨床意義的收縮壓降低，且耐受性良好。

I would now like to briefly touch on the other development activities we're pursuing to enhance and extend the lorundrostat profile in hypertension with comorbid conditions, which are largely driven by inadequately controlled blood pressure and disregulated aldosterone, starting with our proof-of-concept Explore-CKD trial, which evaluated the safety and efficacy of lorundrostat in subjects with hypertension and comorbid chronic kidney disease on a background of SGLT2 inhibitor.

現在我想簡要地談談我們正在進行的其他研發活動，以增強和擴展洛倫德司他治療合併症高血壓的療效，這些合併症主要是由於血壓控制不佳和醛固酮失調引起的。首先是我們的概念驗證性 Explore-CKD 試驗，該試驗評估了在 SGLT2 抑制劑背景下，洛倫德司他在高血壓合併慢性腎臟病患者中的安全性和有效性。

Last week, we were excited to have data from this trial presented during a late-breaking session at ASN's Kidney Week 2025. Lorundrostat demonstrated a clinically meaningful reduction on systolic BP in four weeks and was well tolerated.

上週，我們很高興在 ASN 2025 年腎臟週的最新進展會議上展示了這項試驗的數據。洛倫德司他能在四周顯著降低收縮壓，且耐受性良好。

The key secondary outcome measure of reduction of urinary albumin creatinine ratio, or uACR, an accepted surrogate for renal protection, was clinically meaningful and highly statistically significant. Immediately after the release of these data, first-world pharma surveyed 133 health care professionals, with 77% indicating they would consider prescribing lorundrostat to CKD patients with uncontrolled hypertension on either an ACE inhibitor or an ARB.

降低尿液白蛋白肌酸酐比值（uACR）是腎臟保護的公認替代指標，這項關鍵次要結果指標具有臨床意義和高度統計意義。在這些數據發布後，第一世界製藥公司立即對 133 名醫療保健專業人員進行了調查，其中 77% 的人表示，他們會考慮給服用 ACE 抑製劑或 ARB 後血壓仍未得到控制的 CKD 患者開具 lorundrostat 處方。

Turning to the ongoing Phase 2 Explore-OSA trial. In the third quarter, we completed enrollment in this trial, which is evaluating the safety and efficacy of lorundrostat in participants with moderate to sphere of obstructive sleep apnea and hypertension. We anticipate reporting top-line results from the trial in the first quarter of 2026. If the trial is successful, these data would complement the previously announced Explore-CKD results and further our strategy to extend lorundrostat's profile in treating patients with hypertension and comorbid conditions. Our rationale for targeting OSA is clear.

接下來我們來看看正在進行的 2 期 Explore-OSA 試驗。第三季度，我們完成了這項試驗的招募工作，該試驗旨在評估洛倫德司他治療中度至重度阻塞性睡眠呼吸中止症和高血壓患者的安全性和有效性。我們預計將於 2026 年第一季公佈該試驗的主要結果。如果試驗成功，這些數據將補充先前發表的 Explore-CKD 結果，並進一步推進我們擴大 lorundrostat 在治療高血壓和合併症患者方面的應用範圍的策略。我們選擇 OSA 作為治療目標的理由很明確。

A significant portion of patients with obesity and resistant hypertension also have OSA, which is often undiagnosed and untreated. These conditions are biologically linked, as blood pressure and the hypoxia rise during sleep due to upper airway obstruction. Both are drivers of major adverse cardiovascular events, including death. Prior small studies of MRAs or adrenalectomy have demonstrated reduction in AHI, which is the primary endpoint of the Explore-OSA trial.

相當一部分肥胖和難治性高血壓患者也患有 OSA，但這種疾病往往未被診斷和治療。這些症狀在生物學上是相關的，因為睡眠期間由於上呼吸道阻塞，血壓和缺氧都會升高。兩者都是導致重大不良心血管事件（包括死亡）的因素。先前的小型研究表明，MRA 或腎上腺切除術可以降低 AHI，而 AHI 正是 Explore-OSA 試驗的主要終點。

The trial will also test the effect of lorundrostat on nighttime blood pressure using 24-hour ABPM as well as the novel measurement of continuous blood pressure through the evening. While we have already clearly demonstrated lorundrostat's efficacy as a once-daily morning antihypertensive, this trial will explore nighttime dosing since the triggers for aldosterone production in OSA or reduction in oxygen delivery leading to increased sympathetic activation of aldosterone production that occurs in the night during sleep.

該試驗還將使用 24 小時動態血壓監測 (ABPM) 以及夜間連續血壓測量此新方法，測試洛倫德司他 (lorundrostat) 對夜間血壓的影響。雖然我們已經清楚地證明了洛倫德司他作為每日一次早晨服用的抗高血壓藥物的療效，但這項試驗將探索夜間給藥，因為 OSA 中醛固酮產生的觸發因素或氧氣輸送減少導致交感神經激活增加，從而在夜間睡眠期間發生醛固酮產生。

Uncontrolled and resistant hypertension remain major unmet needs, affecting over 20 million people in the US. and contributing significantly to cardiorenal complications. Our clinical data highlight the differentiated value of targeting aldosterone with an aldosterone synthase inhibitor like lorundrostat, especially compared to current third and fourth-line therapies.

未控制和難治性高血壓仍然是亟待解決的重大問題，影響美國超過 2,000 萬人，並導致心臟腎臟併發症。我們的臨床數據突顯了使用醛固酮合成酶抑制劑（如洛倫德司他）靶向醛固酮的差異化價值，特別是與目前的第三線和第四線療法相比。

As we advance toward commercialization, we are prioritizing market access planning and payer engagement to ensure the value of lorundrostat is well understood. We have also expanded our medical communications capabilities to support data dissemination through peer-reviewed publications, scientific meetings and our field-based medical science liaisons. These efforts are central to ensuring commercial readiness for this potentially transformative treatment and the successful launch of lorundrostat.

隨著我們向商業化邁進，我們將優先考慮市場准入計劃和支付方參與，以確保充分了解 lorundrostat 的價值。我們也擴大了醫療傳播能力，以支援透過同儕審查出版物、科學會議和我們駐外醫學聯絡員進行資料傳播。這些努力對於確保這種可能具有變革意義的療法的商業化準備以及洛倫德司他（lorundrostat）的成功上市至關重要。

As we near the end of 2025, we've seen significant advances in the ASI space, including multiple trial readouts. As we reflect on these data and their clinical relevance, we are more confident than ever in lorundrostat's best-in-class profile based on the meaningful blood pressure reduction, the demonstrated 24-hour control, its benefit across the spectrum of difficult-to-treat patients and its safety and tolerability.

隨著 2025 年接近尾聲，我們在 ASI 領域取得了重大進展，包括多項試驗結果公佈。當我們反思這些數據及其臨床意義時，我們比以往任何時候都更加確信 lorundrostat 具有同類最佳的特性，這基於其顯著的血壓降低、已證實的 24 小時血壓控制、對各種難治性患者的益處以及其安全性和耐受性。

As we move forward with our NDA submission, we do so with confidence in the strength of our data, our team and our mission to develop lorundrostat as a potential best-in-class therapy for the high-risk often difficult to treat patients living with uncontrolled or resistant hypertension. I will now turn the call over to Adam to review our financial results for the third quarter of 2025. Adam?

隨著我們推進新藥申請的提交，我們對自身的數據實力、團隊實力以及將 lorundrostat 開發為一流療法的使命充滿信心，該療法有望用於治療患有難治性或未控制高血壓的高風險患者。現在我將把電話交給亞當，讓他回顧我們2025年第三季的財務表現。亞當？

Thank you, Jon. Good afternoon, everyone. Today, I will discuss select portions of our third quarter 2025 financial results. Additional details can be found in our Form 10-Q which will be filed with the SEC later today, November 10.

謝謝你，喬恩。大家下午好。今天，我將討論我們2025年第三季財務業績的部分內容。更多詳情請參閱我們今天稍後（11 月 10 日）提交給美國證券交易委員會的 10-Q 表格。

We ended the quarter with cash, cash equivalents and investments of $593.6 million as of September 30, 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 permit operations into 2028. R&D expenses for the quarter ended September 30, 2025, were $31.5 million compared to $54 million for the quarter ended September 30, 2024.

截至 2025 年 9 月 30 日，我們本季末的現金、現金等價物和投資為 5.936 億美元，而截至 2024 年 12 月 31 日，數字為 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，並支持許可證運營到 2028 年。截至 2025 年 9 月 30 日的季度研發費用為 3,150 萬美元，截至 2024 年 9 月 30 日的季度研發費用為 5,400 萬美元。

The decrease in R&D expenses was primarily due to a decrease of $26.8 million in preclinical and clinical costs primarily impacted by the conclusion of the lorundrostat pivotal program in the second quarter of 2025, partially offset by increases of $3.2 million in higher compensation expense resulting from additions to headcount, increases in salaries and accrued bonuses and increased stock-based compensation and $1.1 million in higher clinical supply manufacturing, regulatory and other costs.

研發費用的減少主要是由於臨床前和臨床成本減少了 2,680 萬美元，這主要受到 lorundrostat 關鍵性項目於 2025 年第二季度結束的影響，但部分被以下因素抵消：由於人員增加、工資和應計獎金增加以及股票期權激勵增加，導致薪酬支出增加 320 萬美元；以及臨床供應製造、監管和其他成本增加 10 萬美元。

G&A expenses were $9.7 million for the quarter ended September 30, 2025, compared to $6.1 million for the quarter ended September 30, 2024. The increase in G&A expenses was primarily due to $2.2 million in higher compensation expense resulting from additions to headcount, increases in salaries and our crude bonuses and increased stock-based compensation, $1.3 million in higher professional fees and $0.1 million in other administrative expenses.

截至 2025 年 9 月 30 日的季度，一般及行政費用為 970 萬美元，而截至 2024 年 9 月 30 日的季度為 610 萬美元。一般及行政費用增加主要是由於以下原因：員工人數增加導致薪酬支出增加 220 萬美元，工資和粗略獎金增加，以及股票期權激勵增加；專業費用增加 130 萬美元；以及其他行政費用增加 10 萬美元。

Total other income net was $4.2 million for the quarter ended September 30, 2025, compared to $3.8 million for the quarter ended September 30, 2020. The increase was primarily attributable to increased interest earned on investments in money market funds and U.S. treasuries as a result of higher average cash balances invested during the quarter ended September 30, 2025.

截至 2025 年 9 月 30 日的季度，其他淨收入為 420 萬美元，而截至 2020 年 9 月 30 日的季度為 380 萬美元。此成長主要歸因於截至 2025 年 9 月 30 日的季度內，由於平均現金餘額增加，投資於貨幣市場基金和美國國債所獲得的利息增加。

Net loss was $36.9 million for the quarter ended September 30, 2025, compared to $56.3 million for the quarter ended September 30, 2024. The decrease was primarily attributable to the factors impacting our expenses that I described earlier.

截至 2025 年 9 月 30 日的季度淨虧損為 3,690 萬美元，而截至 2024 年 9 月 30 日的季度淨虧損為 5,630 萬美元。這一下降主要歸因於我前面提到的影響我們支出的因素。

With that, I will ask the operator to open up the call for questions. Operator?

接下來，我將請接線生開啟問答環節。操作員？

(Operator Instructions) Umer Raffat, Evercore.

（操作說明）Umer Raffat，Evercore。

I have a question on your resistant hypertension population. And my question specifically is, if you don't adjust for the discontinuations, basically, no imputations involved what would your minus 9-millimeter mercury have been presumably something in the teens, but is that a number you guys have evaluated if you were to not do any imputations and only look at completers like Astra did?

我有一個關於你們難治性高血壓族群的問題。我的具體問題是，如果不考慮停產情況，基本上不進行任何估算，那麼 -9 毫米汞柱的數值大概會在十幾毫米左右，但如果像 Astra 那樣只看完成者而不進行任何估算，你們評估過這個數字嗎？

Umer, thanks for the question. Maybe Dave can opine on this. But the -- we haven't done that analysis. It wasn't part of the plan. And from our standpoint, you have to account for all subjects enrolled that account for the execution within the study discontinuations and patient outcomes as well.

烏默，謝謝你的提問。或許戴夫可以就此發表意見。但是──我們還沒有進行那項分析。這不在計劃之內。從我們的角度來看，你必須考慮到所有入組的受試者，這包括研究執行過程中的中止情況以及患者的治療結果。

But Dave, do you want to give some comment to that?

戴夫，你對此有什麼看法嗎？

Yes. So you're right, Jon. We did exactly what we negotiated with the FDA should be done in the situation of missing data. As you probably know, numbers above 15% and certainly 20% are extremely problematic. And sometimes those trials can't be evaluated by the agency.

是的。你說得對，喬恩。我們完全按照與 FDA 協商的結果，在資料缺失的情況下採取了相應的措施。您可能知道，超過 15% 的數字，尤其是超過 20% 的數字，都是非常有問題的。有時，這些試驗無法得到該機構的評估。

So we wanted to make sure. So we really didn't do that. And I will caution you that it's complicated to do any estimates on imputation because you need the raw data. You can't take, say, the lead square means and try to figure out what it would be. But it can be a reasonably substantial reduction.

所以我們想確認一下。所以我們其實並沒有那麼做。我要提醒你，由於需要原始數據，因此對插補數據進行任何估計都很複雜。你不能拿領先方的平均數來試圖弄清楚它是什麼。但這可能是一個相當大的降幅。

So you're right, it would it can go up or down 3 to 5 millimeters of mercury depending on what imputation you do, et cetera.

所以你是對的，根據你採用的推算方法等，它可能會上下波動 3 到 5 毫米汞柱。

Rich Law, Goldman Sachs.

Rich Law，高盛。

Congrats on the progress. So one advantage that AstraZeneca has been highlighting for bags is the longer half-life. So in that '24 presentation over a weekend, I think we saw -- I mean it was interesting to see that the bags show 14-millimeter placebo-adjusted SVP reduction for both day and night. Have you guys looked at that the day and night for Advance-HTN? And was there any difference between the two?

恭喜你取得進展。阿斯特捷利康一直強調，袋裝產品的一大優勢是半衰期更長。所以在那個週末舉行的 '24 演示中，我認為我們看到——我的意思是，看到這些袋子顯示白天和晚上的安慰劑調整後的 SVP 減少了 14 毫米，這很有趣。你們有沒有日夜關注 Advance-HTN？兩者之間有什麼差別嗎？

And then I have questions later on follow-up.

之後我還有一些後續問題。

Rich, the 24-hour control, long-term acceptable tolerability profile. These are all things that physicians are looking for as they're treating the chronic condition like hypertension, with four studies completed, we're very confident in the 50-milligram and the 25-milligram once daily, providing that 24-hour control. And with the profile that's going to really aid long-term adherence compliance. I noted it in our prepared remarks, I think it's worth repeating. We have always measured blood pressure in the morning before that day's dose.

Rich，24 小時對照，長期可接受的耐受性特徵。這些都是醫生在治療高血壓等慢性疾病時所關注的面向。經過四項研究，我們對每日一次 50 毫克和 25 毫克的劑量非常有信心，它們能夠提供 24 小時的控制。而這樣的使用者畫像將真正有助於長期堅持治療。我在準備好的演講稿中提到了這一點，我認為值得重申。我們一直都是在當天早上服藥前測量血壓。

So we're measuring it at trough. Lorundrostat in Mineralys is the sponsor. We're the first to look at 24-hour ambulatory metrics with an ASI with our Target-HTN study. We're very comfortable with daytime and nighttime blood pressure reduction,

所以我們是在谷底測量的。Mineralys公司的Lorundrostat是贊助商。在我們的 Target-HTN 研究中，我們率先使用 ASI 來觀察 24 小時動態指標。我們對日間和夜間血壓下降的情況都非常滿意。

Advance-HTN, most rigorous study down in the truly confirmed population, which is distinct from any other steady population of at least temporal current ASI studies, again, validated the 24-hour control. We've yet to publish or disclose the nighttime, but we're comfortable with what we're seeing from Target-HTN, Advance and really for the entire program and providing 24-hour control for patients.

Advance-HTN 是一項在真正確診族群中進行的最嚴格的研究，該族群與任何其他穩定的族群（至少在時間上）都不同，目前的 ASI 研究再次驗證了 24 小時對照組。我們尚未公佈或披露夜間數據，但我們對 Target-HTN、Advance 以及整個計畫所取得的成果感到滿意，並為患者提供 24 小時控制。

I see. Got it. And then -- so then, I want to follow up to your previous discussion on the data, the missing data and how to handle that. Based on your understanding of FDA's requirement, are you -- can you exclude any missing data or invalid baseline measurements in the primary analysis?

我懂了。知道了。然後——所以，我想就您之前關於數據、缺失數據以及如何處理這些數據的討論做個後續討論。根據您對 FDA 要求的理解，您能否在主要分析中排除任何缺失資料或無效的基線測量值？

Do you have to consider the entire population, the ITT population and then perform imputation to it? So just curious to see how your -- what your thoughts are in terms of what the FDA require in these scenarios?

是否需要考慮整個總體、ITT總體，然後再插補？所以，我很好奇您—您對FDA在這些情況下提出的要求有什麼看法？

And as Dave noted, and I'll have him add some color to this. In the case of Advance-HTN, this was pre-discussed with the FDA and said in the SAP. But Dave, do you want to maybe add some color to Rich's question?

正如戴夫所指出的那樣，我會讓他補充一些細節。就 Advance-HTN 而言，這已事先與 FDA 討論過，並在 SAP 中說明。戴夫，你想不想給里奇的問題補充一些細節？

Yes. Thanks for the question, Rich. So one thing I'll mention is you can't go back and do it. You have -- it needs to be in the statistical analysis plan and spelled out. And depending on what the circumstances are you will probably have to do a number of different ones.

是的。謝謝你的提問，里奇。所以我要提一點，你不能回頭再做一次。你必須——它需要寫入統計分析計劃並詳細說明。根據具體情況，你可能需要做很多不同的事情。

And one is called jump to reference. That means you have to assume every single person randomized to active actually behave like placebo, that's obviously the most conservative, but it's also the one that they're going to want to look at. There are other ones that are more complex.

其中一種叫做跳到引用。這意味著你必須假設每個隨機分配到活性組的人實際上都表現得像安慰劑組一樣，這顯然是最保守的假設，但這也是他們想要研究的假設。還有一些更複雜的。

And -- but you have to negotiate all that in advance. And generally speaking, you would do that by looking ahead and seeing what you're missing these numbers are and then decide whether a conversation like that is needed.

但是——所有這些都必須事先協商好。一般來說，你會透過展望未來，看看你錯過了哪些數字，然後決定是否需要進行這樣的對話。

We did that when we had a risk of missing data and we're able to handle the problem. So it's complicated. But if you haven't already done it before database lock, you can't just do it later and try to make up for it.

我們之前遇到資料缺失的風險時就採取了這種做法，而且我們能夠解決這個問題。所以情況很複雜。但是，如果你在資料庫鎖定之前還沒有這樣做，你就不能在之後再做並試圖彌補。

Tim Anderson, Bank of America.

提姆安德森，美國銀行。

This is Alice on for Tim. So you mentioned there were no surprises in the pre-NDA feedback. But are you able to provide any more color on this feedback? And could you update us on any final steps before filing? And then I have a follow-up as well.

這裡是Alice替Tim報道。所以你提到過，在簽署保密協議之前的回饋中沒有任何意外。您能否就此回饋提供更多細節？能否告知我們提交申請前的最後步驟？然後我還有一個後續問題。

Yes, Alice. We're -- we haven't really disclosed that, but we're comfortable with the feedback. As I noted, there were no surprises. We're very confident in the data set we've put together across Advance-HTN, Launch-HTN and Explore-CKD. As I noted in the past, in public statements.

是的，愛麗絲。我們——我們還沒有真正公開這一點，但我們對回饋感到滿意。正如我之前提到的，一切都在意料之中。我們對透過 Advance-HTN、Launch-HTN 和 Explore-CKD 收集的資料集非常有信心。正如我過去在公開聲明中提到的那樣。

The other critical part is the on-label extension, having sufficient long-term safety data, including the randomized treatment withdrawal, all of that is progressing well. So we're comfortable with the guidance that we've given, and that is mentioned by the end of this year or into Q1 of next year.

另一個關鍵部分是適應症擴展，需要有足夠的長期安全性數據，包括隨機撤藥試驗，所有這些進展都很順利。因此，我們對我們給予的指導意見感到滿意，該指導意見提到將在今年年底或明年第一季實現。

And then just following the -- now that you're on track for submission, can you provide any updates on any partnering discussions you may be having?

然後，既然你們的投稿工作已經步入正軌，能否提供一下你們正在進行的任何合作洽談的最新進展？

Thanks, Alice. No, we continue, as we've said in the past, believing that partnering is going to be a key component of the Mineralys story. That is for ex US commercialization opportunity, maximization of value, but also in the United States.

謝謝你，愛麗絲。不，我們仍然像過去一樣，相信合作將是 Mineralys 發展歷程中的關鍵組成部分。這是為了抓住美國以外的商業化機會，實現價值最大化，但也是為了在美國本土實現這一目標。

We feel very confident in the best-in-class profile that exist with lorundrostat right now, we want to make sure that we give it the appropriate commercial lift in the United States as well as rest of world as well as Lincoln and co-development partnerships.

我們對 lorundrostat 目前所擁有的同類最佳特性非常有信心，我們希望確保它在美國以及世界其他地區獲得適當的商業推廣，並與林肯公司和合作開發夥伴建立合作關係。

And so I think we have a well-characterized molecule at this point on the cusp of an NDA submission. And I think that continues to support the partnering dialogues that we're having. We're at the end of the day, we're focused on how do we maximize the value of lorundrostat for patients, for physicians and certainly for investors.

因此，我認為我們目前已經得到了一個特徵明確的分子，即將提交新藥申請。我認為這將繼續支持我們正在進行的合作對話。歸根究底，我們關注的是如何最大限度地發揮洛倫德司他（lorundrostat）對病人、醫生以及投資者的價值。

Annabel Samimy, Stifel.

Annabel Samimy，Stifel。

This is Jayed, I'm on for Annabel. Just two questions. The first one is around the open-label extension trial. What are your expectations there? And when can we expect an update on the data?

我是傑伊德，我來替安娜貝爾發言。就兩個問題。第一個是關於開放標籤擴展試驗的。你對那裡有什麼期望？我們何時才能看到數據更新？

Yes. We continue to progress well with the open-label extension. There's been no surprises as we continue -- it's open label, obviously, so we can see data within that, the DSMB continues to review it. We continue to be confident with the safety profile that we're seeing. We will certainly look to publish the results of the open label as well as the randomized treatment withdrawal when the last subject has completed that aspect.

是的。開放標籤擴展研究持續取得良好進展。一切進展順利，沒有任何意外——顯然，這是一項開放標籤研究，所以我們可以看到其中的數據，數據安全監測委員會 (DSMB) 也繼續對其進行審查。我們仍然對目前所見的安全性充滿信心。我們一定會在最後一位受試者完成該階段後，公佈開放標籤和隨機治療撤藥的結果。

Got it. And then one more on the -- going Explore-OSA trial. How do you expect to leverage the data that comes out of that trial?

知道了。然後還有一項關於—參與 Explore-OSA 試驗。您打算如何利用該試驗產生的數據？

Yes. Our goal with Explore-CKD and Explore-OSA is really an acknowledgment that lorundrostat has a benefit that extends beyond just the reduction of blood pressure. And we know there are comorbid conditions that hypertension patients are dealing with chronically, whether it's proteinuria, whether it's CKD, whether it's OSA in the basically related cardiovascular risk that each carry.

是的。我們進行 Explore-CKD 和 Explore-OSA 研究的目標，實際上是為了證明洛倫德司他除了降低血壓之外，還有其他好處。我們知道高血壓患者常會罹患其他合併症，例如蛋白尿、慢性腎臟病、阻塞性睡眠呼吸中止症等，這些疾病都與心血管疾病有密切關係。

And so from our standpoint, adding further data beyond blood pressure reduction to the profile of lorundrostat is going to help its image and view within the prescribing population. It's going to help inform how they think about providing benefits to their patients that don't just deal with blood pressure but are dealing with the related comorbidities.

因此，從我們的角度來看，在洛倫德司他（lorundrostat）的功效描述中添加除降低血壓以外的更多數據，將有助於提升其在處方人群中的形象和認知。這將有助於他們思考如何為患者提供福利，這些福利不僅要針對血壓，還要針對相關的合併症。

And so I think it really fully round out the profile of lodrundrostat and shows the promise of this molecule for addressing hypertension, but again, for those related comorbidities.

因此，我認為這真正完善了洛德隆司他（lodrundrostat）的特性，並顯示了該分子在治療高血壓方面的潛力，但同樣，對於相關的合併症也是如此。

Mohit Bansal, Wells Fargo.

莫希特·班薩爾，富國銀行。

Congrats on all the progress. So I have two questions. So I wonder -- overall, Jon, based on the data we have seen so far with lorundrostat and be so far, do you see any major differences between the two at this point? Or do you think it validates like all those data when I take the class? And the related question is, that AstraZeneca has talked about this being a multibillion-dollar opportunity.

祝賀你們取得的所有進展。我有兩個問題。所以我想知道——總的來說，Jon，根據我們目前看到的lorundrostat和be的數據，你認為目前兩者之間有什麼主要區別嗎？或者你認為我上這門課之後，所有這些數據都會得到驗證嗎？相關的問題是，阿斯特捷利康曾表示這是一個價值數十億美元的機會。

Some of it is unlocked -- some of it would be unlocked with the combination and all those trials. So to help enable those trials what partnerships you as a company would be looking at? And what partners would be the better partner for you to collaborate with at this point?

部分內容已經解鎖——部分內容需要透過組合和所有嘗試才能解鎖。那麼，為了幫助進行這些試驗，貴公司會考慮哪些合作關係呢？那麼，在現階段，哪些合作夥伴會是您更適合的合作對象？

Yes. Thank you, Mohit. I would say, and going back to my remarks, we've seen a lot of data in 2025 from us with lorundrostat as well as competing ASIs in the space, we feel very comfortable with our best-in-class profile at this point.

是的。謝謝你，莫希特。我想說，回到我剛才的發言，我們已經從我們自己的 lorundrostat 以及該領域競爭的 ASI 中獲得了大量 2025 年的數據，我們目前對我們一流的性能感到非常有信心。

Clearly, the ASIs are going to be a differential class and addressing the significant unmet need, a population of 20 million just in the United States alone that could benefit from a drug that's targeting the dysregulated aldosterone that we believe is probably accounting for a significant portion of those patients not being able to get to their ideal goal and basically risking poor cardiovascular outcomes if they do not.

顯然，ASI 將成為一種差異化藥物類別，旨在解決重大的未滿足需求。光是在美國就有 2,000 萬人可以從針對醛固酮失調的藥物中受益，我們認為，醛固酮失調可能是導致相當一部分患者無法達到理想目標的原因，如果他們不這樣做，基本上會面臨不良心血管後果的風險。

At this stage, where we have a complete data set from Advance-HTN where we are truly looking at the most difficult to manage because they are confirmed hypertension to the really broad study launch as well as Explore-CKD.

現階段，我們擁有來自 Advance-HTN 的完整數據集，我們正在真正研究最難管理的病例，因為它們是確診的高血壓，這是一項非常廣泛的研究，同時還有 Explore-CKD。

We feel very confident in the consistent effect that we're seeing. The magnitude of reduction of systolic blood pressure that builds over time. We see a nice response within two weeks. That continues to grow out to the 12-week period of these studies. The safety profile, clearly, the on-target safety signals with electrolytes.

我們對目前看到的持續效果非常有信心。收縮壓隨時間推移而逐漸降低的幅度。兩週內我們就看到了良好的迴響。這種情況會持續發展到這些研究的 12 週期限。安全性概況，很明顯，電解質的靶向安全訊號。

We believe we've got best-in-class molecule as far as the really modest increase in potassium that's transient upon reducing or discontinuing the drug, and the tolerability of the profile. So again, I think this is an exciting time for us. I think it's going to be informative for our partnering dialogue. It's very easy at this point to say this molecule is being derisked as aldosterone-reducing agent so safely and effectively. We know that aldosterone plays a critical rolling conditions beyond hypertension, such as CKD such as OSA, conditions like heart failure.

我們相信，就減少或停止用藥後鉀含量的輕微升高（這種升高是短暫的）以及藥物耐受性而言，我們擁有同類最佳的分子。所以，我認為這對我們來說是一個令人興奮的時刻。我認為這將對我們的合作對話大有裨益。目前很容易說，這種分子作為醛固酮抑制劑，其風險正在被如此安全有效地降低。我們知道，醛固酮除了在高血壓之外，還在慢性腎臟病、阻塞性睡眠呼吸中止症、心臟衰竭等疾病中發揮關鍵作用。

We believe that it's that breadth of opportunity that will continue to inform those partnering dialogues, and that's why it's critical for us. We've said it early on. We've not -- we've not had a for-sale sign in front of this company. We've been developing this molecule to make sure that we maximize the value for that. I think at this stage, we've done so.

我們相信，正是這種廣泛的機會將繼續為這些合作對話提供訊息，因此它對我們至關重要。我們早就說過。我們沒有——我們沒有在公司前掛過出售的牌子。我們一直在研發這種分子，以確保最大限度地發揮其價值。我認為現階段我們已經做到了。

We think there's continued value that we can unlock on our own, but certainly a partner both in the commercial and the developmental perspective would help inform that and drive that even further.

我們認為，我們可以依靠自身力量繼續創造價值，但當然，在商業和開發方面有合作夥伴將有助於我們了解並進一步推動這一目標的實現。

Rami Katkhuda, LifeSci Capital.

Rami Katkhuda，生命科學資本。

AstraZeneca seems to have only enrolled a small number of African-American patients in Bax24 at least for the primary endpoint analysis, which doesn't seem super representative of the resistant hypertensive population. Do you think this could have affected the results?

阿斯特捷利康似乎只在 Bax24 研究中招募了少量非裔美國患者，至少在主要終點分析中是如此，這似乎並不能很好地代表難治性高血壓人群。你認為這可能會影響結果嗎？

And can you remind us how large of a difference in efficacy you see with lorundrostat in this patient population? And then secondly, have you noted what percentage of patients get to goal with lorundrostat in Advance or Launch?

您能否提醒我們一下，您認為洛倫德司他（lorundrostat）在該患者群體中的療效差異有多大？其次，您是否注意到在 Advance 或 Launch 試驗中，使用 lorundrostat 的患者達到治療目標的百分比是多少？

Yes. Rami, thanks for the question. It was with intent that we really wanted to ensure that we had a good diverse representation of patients within our clinical program. We know that Black African-American patients tend to be underrepresented in studies. We also know they carry some of the largest cardiovascular risk for uncontrolled hypertension.

是的。拉米，謝謝你的提問。我們有意確保臨床項目中的患者群體具有良好的多樣性。我們知道，非裔美國黑人患者在研究中往往代表性不足。我們也知道，他們罹患不受控制的高血壓會帶來最大的心血管風險。

So I was really proud of what the team did across the program in Advance-HTN, over 50% of those studies were Black African-American descent in the larger global study, Launch-HTN, we're nearly at 30%. And so we have a really clear understanding of the benefit that lorundrostat can provide these patients. In the case of both trials, when we look at forest plots, we see that race is not a determinant of response.

因此，我為團隊在 Advance-HTN 專案中所做的一切感到非常自豪，超過 50% 的研究對像是黑人非裔美國人；而在更大的全球研究 Launch-HTN 中，這一比例接近 30%。因此，我們對洛倫德司他能為這些病人帶來的益處有了非常清晰的了解。在這兩個試驗中，當我們觀察森林圖時，我們發現種族並不是反應的決定因素。

In other words, whether you're white or Black African-American, you're going to respond to the renders that and have a significant opportunity to get to your respective goal. And so it was important for us to have that population within our clinical program, to be able to speak to the effect of lorundrostat to that at-risk population that typically is underrepresented.

換句話說，無論你是白人還是非裔美國人，你都會對這些結果做出反應，並且有很大的機會實現各自的目標。因此，對我們來說，將這部分族群納入我們的臨床計畫中非常重要，這樣我們才能了解洛倫德司他對於通常被忽視的高風險族群的影響。

As to the percent to get to goal -- what we have shown in the past was, I believe, 44% in Launch got to goal at week six, and I believe it was 42% got to goal at week four with Advance. I want to make sure I got that right, 44% with Launch, 42% with Advance. And I believe for the placebo groups, they were about half. I do know the odds ratio of getting to goal was over three in each study within those time frames that I described. And I hope that answered your question, Rami.

至於達到目標的百分比——我相信，我們過去展示的數據顯示，Launch 在第六週達到了目標的百分比為 44%，而 Advance 在第四週達到了目標的百分比為 42%。我想確認我的計算是否正確，Launch 版本佔 44%，Advance 版本佔 42%。我相信安慰劑組的比例大約是一半。我知道在我所描述的時間範圍內，每項研究中達到目標的幾率都超過三。希望我的回答能解答你的疑問，拉米。

Definitely, yes.

當然，是的。

I'll just add -- Rami, it's Eric. I'll just add that the definition of goal was different when you're looking at that Bax24 data, where they used a [1 30], we used a more stringent [1 25]. I'll also say that it wasn't just Bax24 that didn't have a high quantity of Black or African-American patients. It was also bax HTN where they were about 8%.

我補充一下——拉米，我是艾瑞克。我還要補充一點，在查看 Bax24 數據時，目標的定義有所不同，他們使用的是 [1 30]，而我們使用了更嚴格的定義。[1 25]我還要補充一點，並非只有 Bax24 的黑人或非裔美國人患者數量不多。高血壓患者中也有約 8% 的人。

And this is Dave. As long as we're all jumping on this question because it's such an important question. As a developer, my perspective is this. There's a reason why we had a high percentage of people in the Advance-HTN trial of confirmed uncontrolled and resistant hypertension. Black African-Americans have a higher percentage of not being able to respond to the generic dogs as well as Caucasian patients.

這位是戴夫。既然大家都在討論這個問題，那肯定是因為它非常重要。身為開發者，我的觀點是這樣的。Advance-HTN 試驗中確診的難治性高血壓患者比例很高是有原因的。非裔美國人對普通犬類刺激沒有反應的比例高於白人患者。

And so we have a higher percentage there. The need is higher and yet we showed that the response once they get on our drug is just as good as the Caucasian population. I think that's important distinction because as we've said many times, doing that trial and getting established confirmed hypertension is what the experts ask us to do, and it's what the real gold standard is to know what this drug can do beyond generics. And in African Americans, it's obviously an extremely effective drug there.

因此，我們在那裡的比例更高。雖然需求更高，但我們已經證明，一旦他們開始服用我們的藥物，其療效就與白種人群一樣好。我認為這是一個重要的區別，因為正如我們多次說過的那樣，進行試驗並確診高血壓是專家要求我們做的，也是了解這種藥物比仿製藥更有效的真正黃金標準。對於非裔美國人來說，這顯然是一種非常有效的藥物。

We have reached the end of the question-and-answer session. I'd like to turn the call back over to Jon for closing comments.

問答環節到此結束。我想把電話交還給喬恩，讓他做總結發言。

Thank you operator. We believe the strength of the clinical results for lorundrostat show the potential benefit for uncontrolled and resistant hypertension and related comorbidities such as CKD. We look forward to our upcoming NDA submission and results from Explore-OSA.

謝謝接線生。我們認為，lorundrostat 的臨床結果顯示出其對未控制和難治性高血壓以及相關合併症（如 CKD）的潛在益處。我們期待即將提交的NDA申請以及Explore-OSA的評選結果。

This is an exciting time for our team. The uncontrolled and resistant hypertension patients who may benefit from treatment with lorundrostat, the physicians and researchers that have worked so hard and supported bringing lorundrostat through our clinical trial program and our shareholders.

對於我們的團隊來說，這是一個令人興奮的時刻。那些可能受益於洛倫司他治療的難治性高血壓患者，那些辛勤工作並支持洛倫司他通過我們臨床試驗計畫的醫生和研究人員，以及我們的股東。

We're excited for upcoming key milestones and look forward to sharing updates with you in the upcoming quarters. With that said, I'll thank everyone. Thank you for joining us today, and we'll close the call now. Thank you.

我們對即將到來的重要里程碑感到興奮，並期待在接下來的幾季與您分享最新進展。最後，我要感謝大家。感謝各位今天參加我們的電話會議，現在我們結束今天的通話。謝謝。

This concludes today's conference. You may disconnect your lines at this time. And we thank you for your participation.

今天的會議到此結束。您可以在此時斷開線路。感謝您的參與。