Amylyx Pharmaceuticals Inc (AMLX) 2023 Q2 法說會逐字稿

Good afternoon. My name is Tom, and I will be your conference operator today. At this time, I would like to welcome everyone to the Amylyx Pharmaceuticals Second Quarter 2023 Earnings Conference Call. (Operator Instructions) Please be advised that this call is being recorded at the company's request.

午安.我叫湯姆，今天我將擔任你們的會議操作員。現在，我歡迎大家參加 Amylyx Pharmaceuticals 2023 年第二季財報電話會議。 （操作員說明）請注意，本次通話是應公司要求進行錄音的。

I would now like to turn the conference over to Lindsey Allen, Head of Investor Relations and Communications. Please go ahead.

我現在想將會議交給投資者關係和傳播主管林賽艾倫 (Lindsey Allen)。請繼續。

Good afternoon and thank you for joining us today to discuss our second quarter 2023 earnings. With me on the call are Josh Cohen and Justin Klee, our Co-CEOs; Margaret Olinger, our Chief Commercial Officer; and Jim Frates, our Chief Financial Officer.

下午好，感謝您今天加入我們討論我們 2023 年第二季的收益。與我一起參加電話會議的還有我們的聯合執行長 Josh Cohen 和 Justin Klee；瑪格麗特‧奧林格 (Margaret Olinger)，我們的首席商務官；以及我們的財務長 Jim Frates。

Before we begin, I would like to remind everyone that any statements we make or information presented on this call that are not historical facts are forward-looking statements that are made based on our current beliefs, plans and expectations and are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, our expectations with respect to RELYVRIO and ALBRIOZA, statements regarding our clinical trials and regulatory developments and the expected timing thereof, our business strategy and outlook, and our expected financial performance.

在我們開始之前，我想提醒大家，我們在本次電話會議中所做的任何非歷史事實的陳述或提供的資訊都是前瞻性陳述，這些陳述是基於我們當前的信念、計劃和期望而做出的，並且是根據安全資訊做出的。遵守1995 年《私人證券訴訟改革法案》的規定。這些聲明包括但不限於我們對RELYVRIO 和ALBRIOZA 的期望、有關我們的臨床試驗和監管發展及其預期時間的聲​​明、我們的業務策略和前景，以及我們預期的財務表現。

Actual events and results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties and other factors, including those set forth in our most recent filings with the SEC and any other future filings that we may make with the SEC. You are cautioned not to place any undue reliance on these forward-looking statements, and Amylyx disclaims any obligation to update such statements unless required by law.

由於各種風險、不確定性和其他因素，包括我們最近向SEC 提交的文件以及我們可能未來提交的任何其他文件中所述的因素，實際事件和結果可能與任何前瞻性陳述中明示或暗示的內容存在重大差異。與 SEC 合作。請您注意不要過度依賴這些前瞻性陳述，除非法律要求，Amylyx 不承擔更新此類陳述的義務。

Now I will turn the call over to Justin.

現在我會把電話轉給賈斯汀。

Thank you, Lindsey, and good afternoon. In the second quarter, we made significant progress in bringing RELYVRIO and ALBRIOZA to people with ALS in the U.S. and Canada, respectively, and advancing our mission of one day ending the suffering caused by ALS and other neurodegenerative diseases.

謝謝你，林賽，下午好。第二季度，我們在分別為美國和加拿大的 ALS 患者提供 RELYVRIO 和 ALBRIOZA 方面取得了重大進展，並推進了我們終有一天結束 ALS 和其他神經退化性疾病造成的痛苦的使命。

We are incredibly proud of our entire team, who has continued to deliver on the goals that we outlined following the full FDA approval of RELYVRIO last September. These goals included raising awareness and educating people living with ALS with -- and physicians about RELYVRIO, working with insurers to provide access to our approved treatment, helping people who have been prescribed RELYVRIO through our Amylyx Care Team patient support program, and deepening our understanding of the ALS market.

我們為我們的整個團隊感到無比自豪，他們在去年 9 月 FDA 全面批准 RELYVRIO 後繼續實現我們概述的目標。這些目標包括提高 ALS 患者和醫生對 RELYVRIO 的認識和教育，與保險公司合作提供我們批准的治療方法，透過我們的 Amylyx 護理團隊患者支持計劃幫助服用 RELYVRIO 的人，以及加深我們的理解ALS 市場。

Let me walk you through our progress. Our commercial organization is off to a strong start educating and raising awareness about RELYVRIO as evidenced by the strong and steady demand we saw in the second quarter. As of June 30, 2023, there were roughly 3,800 people on RELYVRIO in the U.S., up from roughly 3,000 people on RELYVRIO as of March 31, 2023, and just over 1,300 at the end of 2022.

讓我向您介紹我們的進展。我們的商業組織在教育和提高 RELYVRIO 意識方面取得了良好的開端，第二季強勁而穩定的需求就證明了這一點。截至 2023 年 6 月 30 日，美國 RELYVRIO 約有 3,800 人，而截至 2023 年 3 月 31 日，RELYVRIO 約有 3,000 人，2022 年底略高於 1,300 人。

As for an insurance coverage, adoption has been rapid, and a vast majority of policies have been broad and supportive. Insurers covering nearly all people living with ALS have published formal policies and are covering RELYVRIO, and people living with ALS that have been prescribed RELYVRIO are now able to start therapy more quickly. The average time between the prescription being written and RELYVRIO being shipped was about 25 days in the second quarter, down from around 30 days in the first quarter of this year and a little over 45 days when we shared this metric on our fourth quarter earnings call.

至於保險範圍，採用速度很快，而且絕大多數政策都是廣泛和支持性的。涵蓋幾乎所有 ALS 患者的保險公司已經發布了正式保單，並承保 RELYVRIO，而服用 RELYVRIO 處方的 ALS 患者現在能夠更快地開始治療。第二季度，處方開立和RELYVRIO 出貨之間的平均時間約為25 天，低於今年第一季的30 天左右，而我們在第四季財報電話會議上分享這項指標時的時間略多於45 天。

Turning to Canada. We reached our 1-year anniversary of the Health Canada approval with conditions in June. As we reflect on our progress, we are pleased with what we have achieved on behalf of the Canadian ALS community. In the fourth quarter of last year, we announced that all major private insurers in Canada covered ALBRIOZA. And we are pleased to share today that by the end of August, we expect ALBRIOZA coverage to be in place for the vast majority of publicly insured lives in Canada.

轉向加拿大。六月，我們迎來了加拿大衛生部有條件批准一週年。當我們回顧我們的進步時，我們對代表加拿大 ALS 社區的成就感到高興。去年第四季度，我們宣布加拿大所有主要私人保險公司均承保 ALBRIOZA。今天我們很高興地與大家分享，到 8 月底，我們預計 ALBRIOZA 保險將涵蓋加拿大絕大多數公共保險的人。

The early success of our commercial launches has enabled us to both invest in bringing RELYVRIO to more people living with ALS globally and advance our pipeline opportunities that support our mission. We continue to expect a final opinion on our MAA from CHMP in the fall and prepare to execute a successful launch in the EU if approved.

我們商業發布的早期成功使我們能夠投資將 RELYVRIO 帶給全球更多的 ALS 患者，並推動支持我們使命的管道機會。我們繼續期待 CHMP 在秋季對我們的 MAA 提出最終意見，並準備在獲得批准後在歐盟成功啟動。

We are excited to initiate our new Phase III ORION clinical trial of AMX0035 in progressive supranuclear palsy later this year. And of course, we continue to work diligently to complete the PHOENIX trial with top line results anticipated in mid-2024. In summary, we are proud of our progress so far in 2023 and excited about what we can achieve as an organization. We have a clear mission, and we are executing on our goals.

我們很高興在今年稍後啟動 AMX0035 治療進行性核上性麻痺的新 III 期 ORION 臨床試驗。當然，我們將繼續努力完成 PHOENIX 試驗，並預計在 2024 年中期取得頂線結果。總之，我們對 2023 年迄今的進展感到自豪，並對我們作為一個組織所能取得的成就感到興奮。我們有明確的使命，並且正在努力實現我們的目標。

I'll now turn the call over to Margaret to provide an update on our commercial performance.

我現在將把電話轉給瑪格麗特，以提供我們商業表現的最新資訊。

Thank you, Justin. In the second quarter, we continued to make significant progress on our 3 key priorities. The first is our effort to drive awareness and educate about the benefits of RELYVRIO among people living with ALS and clinicians. This includes educating that RELYVRIO is the first and only approved drug for adults with ALS to demonstrate a statistically significant benefit and function in a clinical trial as well as the survival benefit and a longer-term post hoc analysis.

謝謝你，賈斯汀。第二季度，我們繼續在 3 個關鍵優先事項上取得重大進展。首先是我們努力提高 ALS 患者和臨床醫生對 RELYVRIO 益處的認識並進行教育。這包括宣傳 RELYVRIO 是第一個也是唯一一個被批准用於 ALS 成人患者的藥物，在臨床試驗以及生存獲益和長期事後分析中證明具有統計學上顯著的益處和功能。

As a reminder, clinical trial data published in the New England Journal of Medicine demonstrated that after 24 weeks, participants treated with RELYVRIO scored on average 2.32 points higher on the ALSFRS scale than the placebo group. Even a 1-point change in the ALSFRS score can indicate a significant difference in a person's ability to function independently with activities of daily living, including eating, bathing, dressing or walking. Participants treated with RELYVRIO at the start of the clinical trial, which means that they both started RELYVRIO 6 months earlier and were on it for longer than participants starting on placebo saw a greater survival benefit.

提醒一下，《新英格蘭醫學雜誌》上發表的臨床試驗數據表明，24 週後，接受 RELYVRIO 治療的參與者在 ALSFRS 量表上的得分比安慰劑組平均高出 2.32 分。即使 ALSFRS 評分發生 1 分的變化，也可能表明一個人獨立進行日常生活活動（包括吃飯、洗澡、穿衣或行走）的能力有顯著差異。參與者在臨床試驗開始時接受 RELYVRIO 治療，這意味著他們比開始使用安慰劑的參與者提前 6 個月開始使用 RELYVRIO，並且服用時間更長，看到了更大的生存獲益。

During the second quarter, interest in and demand for RELYVRIO continued to build at a steady pace from both those that are newly diagnosed and people who have been living with ALS for years. As a result of our educational efforts, as of June 30, there were roughly 3,800 people on RELYVRIO in the United States. We are very pleased that so many people have gained access to this important new treatment so quickly.

第二季度，新診斷出的患者和患有 ALS 多年的患者對 RELYVRIO 的興趣和需求持續穩定成長。由於我們的教育努力，截至 6 月 30 日，美國大約有 3,800 人使用 RELYVRIO。我們很高興這麼多人如此迅速地獲得了這種重要的新療法。

Now let me run through a few key metrics that demonstrate our progress and growth opportunities ahead of us. Prescribing remains fairly concentrated with just over 80 prescribers, mostly at major ALS centers, representing approximately half of all RELYVRIO prescriptions at the end of the quarter. We are encouraged by the level of interest among this group and believe that we have an opportunity for growth as we bring our message to more prescribers and deepen our relationships within these key ALS centers.

現在讓我回顧幾個關鍵指標，這些指標展示了我們的進步和我們面前的成長機會。處方仍然相當集中，只有 80 多名處方者，其中大多數在主要的 ALS 中心，佔本季度末所有 RELYVRIO 處方的大約一半。我們對該群體的興趣程度感到鼓舞，並相信，當我們將我們的訊息傳達給更多的處方醫生並加深我們與這些主要 ALS 中心的關係時，我們就有發展的機會。

By the end of the second quarter, approximately 75% of the top 500 U.S. prescribers and nearly all of the key ALS centers have prescribed RELYVRIO to at least 1 person since launch. We are focused on driving awareness and education and on deepening our penetration within the top prescribers and key ALS centers. In addition, we have a large untapped opportunity for growth outside of this group of top prescribers as we expand our outreach and educational efforts more broadly.

截至第二季末，自推出以來，美國前 500 名處方醫生和幾乎所有主要 ALS 中心中約有 75% 已為至少 1 人開了 RELYVRIO 處方。我們專注於提高意識和教育，並加深我們在頂級處方醫生和主要 ALS 中心的滲透。此外，隨著我們更廣泛地擴大我們的外展和教育工作，在這群頂級處方醫生之外，我們還有大量未開發的成長機會。

Our second priority is engaging with payers to work to help ensure that every eligible person who could benefit from RELYVRIO treatment has access as quickly and efficiently as possible. Consistent with the targets we previously outlined, by the end of the second quarter, our estimates suggest that U.S. insurers representing nearly all ALS covered lives had published formal coverage policies. The vast majority of these insurers provide broad access to RELYVRIO. This is a significant accomplishment just 3 quarters into our commercial launch.

我們的第二個優先事項是與付款人合作，幫助確保每個可以從 RELYVRIO 治療中受益的合格人員都能盡快、有效率地獲得治療。與我們之前概述的目標一致，到第二季末，我們的估計表明，代表幾乎所有 ALS 承保人的美國保險公司已經發布了正式的承保保單。這些保險公司中的絕大多數都提供廣泛的 RELYVRIO 服務。這是我們商業發布僅三個季度後取得的重大成就。

Our third priority is ensuring eligible people living with ALS have positive interactions through their treatment journey with RELYVRIO and ALS clinics have positive interactions with Amylyx. This includes facilitating an organized, clear process to get people who have been prescribed RELYVRIO access to therapy as quickly as possible and optimizing people's experience obtaining RELYVRIO as best we can.

我們的第三個優先事項是確保符合條件的 ALS 患者在他們的治療過程中與 RELYVRIO 進行積極的互動，並且 ALS 診所與 Amylyx 進行積極的互動。這包括促進一個有組織的、清晰的流程，讓接受 RELYVRIO 處方的人盡快獲得治療，並盡可能優化人們獲得 RELYVRIO 的體驗。

Our team has done a tremendous job of facilitating the process, increasing the speed between the prescription being written and RELYVRIO being shipped. In the second quarter, on average, this time line was shortened to about 25 days, aided by the increase in insurance coverage. Our team continues to work expeditiously to get people living with ALS who have been prescribed RELYVRIO on therapy as quickly as possible.

我們的團隊在促進這項流程、提高開立處方和 RELYVRIO 出貨之間的速度方面做了大量工作。第二季度，由於保險覆蓋範圍的增加，這條時間線平均縮短至 25 天左右。我們的團隊將繼續迅速開展工作，讓已接受 RELYVRIO 治療的 ALS 患者盡快接受治療。

Turning to our launch in Canada. Interest in ALBRIOZA remains high. We have made significant progress on our public insurance coverage efforts. We are thrilled that 5 Canadian provinces, Ontario, Quebec, British Columbia, New Brunswick and most recently, Alberta, announced public reimbursement of ALBRIOZA. By the end of August, we expect ALBRIOZA coverage to be in place for the vast majority of publicly insured lives in Canada.

談到我們在加拿大的推出。人們對 ALBRIOZA 的興趣仍然很高。我們在公共保險覆蓋方面取得了重大進展。我們很高興加拿大 5 個省（安大略省、魁北克省、不列顛哥倫比亞省、新不倫瑞克省以及最近的阿爾伯塔省）宣布對 ALBRIOZA 進行公共報銷。到 8 月底，我們預計 ALBRIOZA 保險將涵蓋加拿大絕大多數公共保險的人。

Our goal is to ultimately change the way people living with ALS are treated, and we believe RELYVRIO is becoming a foundational therapy for ALS. As we move into the third quarter, our team remains focused on driving awareness and education about RELYVRIO among people living with ALS and clinicians.

我們的目標是最終改變 ALS 患者的治療方式，我們相信 RELYVRIO 正在成為 ALS 的基礎療法。進入第三季度，我們的團隊仍然致力於提高 ALS 患者和臨床醫生對 RELYVRIO 的認識和教育。

I will now turn the call over to Jim to discuss our financial results for the second quarter.

我現在將電話轉給吉姆，討論我們第二季的財務表現。

Thanks, Margaret. We're encouraged by the strong interest and demand we continued to see from the ALS community in the second quarter. From a financial point of view, our business remains strong. Net product revenues were $98.2 million for the quarter compared to net product revenue of $71.4 million for the first quarter of 2023 with the vast majority of that revenue coming from the United States.

謝謝，瑪格麗特。我們對第二季 ALS 社區持續表現出的強烈興趣和需求感到鼓舞。從財務角度來看，我們的業務仍然強勁。本季產品淨收入為 9,820 萬美元，而 2023 年第一季產品淨收入為 7,140 萬美元，其中絕大多數收入來自美國。

Gross-to-net adjustments were approximately 10% in the quarter, which is a little lower than that what we would normally anticipate due to the favorable true-up of reserve estimates in the second quarter based on our actual experience in the past 9 months. Going forward, we anticipate gross-to-net discounts will be in the 12% to 15% range.

本季毛淨調整約為 10%，略低於我們的正常預期，因為根據我們過去 9 個月的實際經驗，第二季的準備金預測得到了有利的調整。展望未來，我們預計毛淨折扣將在 12% 至 15% 範圍內。

Inventory levels at the quarter end were as expected with approximately 2 weeks of inventory in the channel at specialty pharmacies, similar to what we've seen in previous quarters. Cost of sales were $5.6 million for the quarter, roughly 6% for net product revenues, and our expectation is that COGS will remain in the range of 6% to 10% of sales going forward.

季度末的庫存水準符合預期，專業藥房管道中的庫存約為兩週，與我們在前幾個季度看到的情況類似。本季銷售成本為 560 萬美元，約佔淨產品收入的 6%，我們預計 COGS 未來將維持在銷售額的 6% 至 10% 範圍內。

Note that we fully expensed all of our remaining royalty obligations this quarter and will not be incurring any additional royalty expenses related to sales in ALS going forward. For modeling purposes, keep in mind that roughly 10% of the people on RELYVRIO are receiving it for free through either our interim access program or patient assistance program.

請注意，我們本季已全額支出了所有剩餘的特許權使用費，並且不會產生與未來 ALS 銷售相關的任何額外特許權使用費。出於建模目的，請記住，RELYVRIO 上大約 10% 的人透過我們的臨時訪問計劃或患者援助計劃免費接收它。

Research and development expenses were $29 million for the quarter. You should expect R&D expenses to be in the $30 million to $40 million range per quarter for the remainder of the year. As we outlined in our Q1 call, our expectation is that R&D expenses will move toward the higher end of this range later this year as we start enrolling patients in our new Phase III trial in PSP.

該季度的研發費用為 2,900 萬美元。您預計今年剩餘時間內每季的研發費用將在 3,000 萬至 4,000 萬美元之間。正如我們在第一季電話會議中概述的那樣，我們預計，隨著我們開始在 PSP 新的 III 期試驗中招募患者，研發費用將在今年稍後向該範圍的高端移動。

Selling, general and administrative expenses, or SG&A, were $43.4 million for the quarter, in line with the $45 million per quarter run rate that we mentioned on our first quarter call. We continue to expect SG&A expenses in this range for the remainder of the year. These results led to an excellent bottom line. We generated $22.1 million in net income, representing our second quarter in a row of profitability.

本季銷售、一般和管理費用 (SG&A) 為 4,340 萬美元，與我們在第一季電話會議中提到的每季 4,500 萬美元的運行率一致。我們繼續預計今年剩餘時間的銷售、管理及行政費用將維持在此範圍內。這些結果帶來了出色的利潤。我們實現了 2,210 萬美元的淨利潤，這是我們連續第二季實現盈利。

Finally, we ended the quarter with cash and short-term investments of $357.3 million and 0 debt. We're pleased with our strong financial results and with the disciplined execution throughout the organization. From a capital perspective, we have the resources we need to execute on our mission. We're well positioned to grow our top line, invest in our pipeline to provide more much needed treatments for neurodegenerative diseases and deliver on our bottom line.

最後，本季結束時，我們的現金和短期投資為 3.573 億美元，債務為零。我們對強勁的財務業績和整個組織嚴格的執行力感到滿意。從資本的角度來看，我們擁有執行使命所需的資源。我們處於有利地位，可以增加我們的營收，投資我們的產品線，為神經退化性疾病提供更多急需的治療方法，並實現我們的盈利。

I'll now turn the call over to Josh to discuss our R&D programs.

我現在將電話轉給喬什，討論我們的研發計劃。

Thanks, Jim. We have demonstrated the benefit of AMX0035 in ALS and believe it could help in other neurodegenerative diseases. When we originally developed AMX0035, our goal was to target endoplasmic reticulum stress, or ER stress, and mitochondrial dysfunction, 2 connected central pathways that lead to neurodegeneration. As we announced on our last call, we intend to initiate a global pivotal Phase III study in PSP later this year called ORION. ORION is a well-powered study that will enroll approximately 600 participants, and it was designed and planned in collaboration with key global academic leaders, people living with PSP and advocacy groups.

謝謝，吉姆。我們已經證明了 AMX0035 在 ALS 中的益處，並相信它可以幫助治療其他神經退化性疾病。當我們最初開發 AMX0035 時，我們的目標是針對內質網壓力（或 ER 壓力）和粒線體功能障礙，這是導致神經退化性疾病的 2 個相互關聯的中樞通路。正如我們在上次電話會議上宣布的那樣，我們打算在今年稍後啟動一項名為 ORION 的 PSP 全球關鍵 III 期研究。 ORION 是一項強有力的研究，將招募約 600 名參與者，它是與全球主要學術領袖、PSP 患者和倡導團體合作設計和規劃的。

PSP is a rare but recognizable, progressive and fatal neurodegenerative disease with clear and well-known clinical hallmarks that include progressive disability with respect to eye movement, walking imbalance, speech and swallowing, and cognitive function. There are currently no disease-modifying treatments for PSP, and we are hopeful that AMX0035 might be able to help.

PSP 是一種罕見但可識別的進行性和致命性神經退化性疾病，具有明顯且眾所周知的臨床特徵，包括眼球運動、行走不平衡、言語和吞嚥以及認知功能方面的進行性殘疾。目前尚無針對 PSP 的疾病緩解療法，我們希望 AMX0035 能提供協助。

PSP is characterized as a tauopathy with genetic and pathological findings, supporting a primary role for tau in this disease. Given AMX0035's proposed mechanism of action that targets pathways upstream of tau aggregation and the Phase II placebo-controlled PEGASUS clinical trial data, which demonstrated that AMX0035 significantly lowered both phospho tau 181 and total tau in the cerebrospinal fluid of people with Alzheimer's disease, we are excited to pursue this indication in PSP.

PSP 被描述為一種 tau 蛋白疾病，其遺傳和病理學結果支持了 tau 蛋白在疾病中的主要作用。鑑於AMX0035 提出的針對tau 聚集上游途徑的作用機制以及II 期安慰劑對照PEGASUS 臨床試驗數據（該數據表明AMX0035 顯著降低了阿茲海默症患者腦脊髓液中的磷酸化tau 181 和總tau），我們認為很高興能在 PSP 中追求這一指示。

We recently hosted a webcast with Professor Dr. Günter Höglinger, a leading expert in PSP and the primary investigator for our Phase III ORION trial. As part of the webcast, we shared insights into the scientific rationale for studying AMX0035 in PSP and an overview of the Phase III trial design.

我們最近主持了一次由 Günter Höglinger 教授主持的網路廣播，他是 PSP 領域的領先專家，也是我們 III 期 ORION 試驗的主要研究者。作為網路廣播的一部分，我們分享了在 PSP 中研究 AMX0035 的科學原理的見解以及 III 期試驗設計的概述。

Additionally, Dr. Höglinger provided his perspectives on the PSP treatment landscape, the role of tau in this disease and the potential to use AMX0035 in people living with PSP should it be approved. The replay is available in the Events section of our IR website, and we encourage you to listen to it if you didn't have a chance to join us for the live event.

此外，Höglinger 博士還提供了他對 PSP 治療前景、tau 在這種疾病中的作用以及 AMX0035 如果獲得批准用於 PSP 患者的潛力的看法。我們的 IR 網站的「活動」部分提供重播，如果您沒有機會參加我們的現場活動，我們鼓勵您收聽。

In addition to this exciting study in PSP, we are also pursuing a program in another rare disease Wolfram syndrome called HELIOS. Wolfram syndrome is a rare disease that leads to multisystem failure, resulting in blindness, deafness, diabetes, ataxia, neurodegeneration and often death in early adulthood. Our R&D team conducted roughly 4 years of in vitro and in vivo studies of AMX0035 in Wolfram syndrome together with a leading researcher, Dr. Fumihiko Urano, at Washington University.

除了這項令人興奮的 PSP 研究之外，我們還在進行另一種罕見疾病 Wolfram 症候群（稱為 HELIOS）的計畫。沃爾夫拉姆氏症候群是一種罕見疾病，會導致多重系統衰竭，導致失明、失聰、糖尿病、共濟失調、神經退化，甚至常常在成年早期死亡。我們的研發團隊與華盛頓大學的首席研究員 Fumihiko Urano 博士一起，對 AMX0035 在 Wolfram 症候群中的作用進行了大約 4 年的體外和體內研究。

These studies have promising results, some of which were published in the Journal of Clinical Investigation Insight. Several papers characterize the disease as a prototypical disease of ER stress. And as we have discussed in the past, we believe this study, which is currently enrolling participants, will provide key data to guide future studies, and we expect top line results next year.

這些研究取得了有希望的結果，其中一些發表在《臨床研究洞察期刊》上。幾篇論文將這種疾病描述為內質網壓力的典型疾病。正如我們過去所討論的那樣，我們相信這項目前正在招募參與者的研究將為指導未來的研究提供關鍵數據，我們預計明年將獲得頂線結果。

We also continue to broaden our ALS and neurodegenerative disease pipeline. We believe that in order to ultimately find a cure for ALS, it's going to take a combination approach, targeting multiple cellular pathways implicated in disease pathogenesis. We continue to progress AMX0114, our antisense oligonucleotide targeting Calpain-2 through IND-enabling studies. We have presented data on this candidate at the NEALS, MDA and Todd's conferences. We're excited to present more data on AMX0114 and other advancements in our pipeline in the future.

我們也持續擴大 ALS 和神經退化性疾病產品線。我們相信，為了最終找到 ALS 的治療方法，需要採取組合方法，針對與疾病發病機制相關的多種細胞途徑。我們透過 IND 研究繼續推進 AMX0114，這是我們針對 Calpain-2 的反義寡核苷酸。我們已在 NEALS、MDA 和 Todd 會議上提供了有關該候選人的數據。我們很高興能夠在未來提供有關 AMX0114 的更多數據以及我們管道中的其他進展。

In closing, we are proud of our team's progress and the work that we are doing on behalf of the ALS community. We are in a very strong financial position, which allows us to continue to support our launches in ALS and invest in our pipeline to find new treatment options for people living with ALS and other relentlessly progressive neurodegenerative diseases.

最後，我們為我們團隊的進步以及我們代表 ALS 社區所做的工作感到自豪。我們的財務狀況非常強勁，這使我們能夠繼續支持我們在 ALS 領域的推出，並投資於我們的產品線，為 ALS 和其他不斷進展的神經退化性疾病患者尋找新的治療選擇。

Now we'll be happy to take your questions. Operator, please open the call up to Q&A.

現在我們很樂意回答您的問題。接線員，請打開電話問答。

(Operator Instructions) And the first question comes from Corinne Jenkins with Goldman Sachs.

（操作員說明）第一個問題來自高盛的 Corinne Jenkins。

Maybe just first, what are you seeing with respect to compliance and discontinuation rates? And I'll just go ahead with my follow-up here. Are you seeing any emerging trends with respect to the primary reasons for discontinuation? It would be helpful whatever you can share there.

也許首先，您對合規率和停藥率有何看法？我將在這裡繼續我的後續行動。您是否發現停產主要原因的新趨勢？無論您在那裡分享什麼，都會很有幫助。

Thanks very much for the question. Maybe just to start, as a reminder, we report on net patients on therapy. So this is inclusive of any discontinuation. We are really pleased with our ability to serve the roughly 3,800 net patients on RELYVRIO at the end of Q2.

非常感謝您的提問。也許只是為了提醒大家，我們報告了接受治療的網路患者。因此，這包括任何中斷。我們非常高興能夠在第二季末為 RELYVRIO 上約 3,800 名淨患者提供服務。

I would say it's really too early to see any long-term trends at this point in our launch. But maybe a reference point in the CENTAUR trial, which again as a reminder was a 6-month trial, approximately 70% of participants remained on drug. And we're tracking close to that in terms of the commercial setting. But I would say this is clearly an area where we're going to continue to keep a very close eye on as we expect the patient mix to shift over time.

我想說，在我們發布的這個階段，要看到任何長期趨勢還為時過早。但也許可以參考 CENTAUR 試驗，再次提醒大家，這是一項為期 6 個月的試驗，大約 70% 的參與者仍服用藥物。在商業環境方面，我們正在接近這一點。但我想說，這顯然是我們將繼續密切關注的領域，因為我們預期患者組合會隨著時間的推移而改變。

And maybe I'll just add...

也許我會添加...

Any one of the reasons, yes.

任何一個原因，都可以。

Yes, sure. On the compliance side, one of the reasons. So on the compliance side, we've seen most rare disease drugs, you'll find in the 75% to 80% range in terms of drug compliance. We're in that range as well. And in terms of reasons for discontinuation, they're varied. People with ALS are going through many different things. Of course, one of the more common ones certainly is death and disease progression, which is expected in ALS as well.

是的，當然。在合規方面，這是原因之一。因此，在合規性方面，我們見過大多數罕見疾病藥物，您會發現藥物合規性在 75% 到 80% 的範圍內。我們也在這個範圍內。就停止的原因而言，它們是多種多樣的。患有 ALS 的人正在經歷許多不同的事情。當然，最常見的問題之一肯定是死亡和疾病進展，這在 ALS 中也是預料之中的。

The next question comes from Geoff Meacham with Bank of America.

下一個問題來自美國銀行的傑夫‧米查姆 (Geoff Meacham)。

Congrats on the quarter. I had a couple. The first is the EU, the CHMP process. I wanted to ask kind of how you guys view that process now. And maybe just help us with kind of how you view the next steps here. I wasn't sure for reexamination what the protocol or the success rate could be there. And the second question is just related to capital deployment. I know you guys have done some deals, some BD. I want to ask maybe how that's evolved over time as you look to be sustainably profitable.

恭喜本季。我有一對。第一個是歐盟，即 CHMP 流程。我想問一下你們現在如何看待這個過程。也許只是幫助我們了解您如何看待接下來的步驟。我不確定是否需要重新檢查協議或成功率。第二個問題就跟資本配置有關。我知道你們已經做了一些交易，一些 BD。我想問的是，隨著時間的推移，當你尋求可持續盈利時，這種情況是如何演變的。

Sure. So on the EU and CHMP, so as we've shared previously, in the EU adopted initially a negative opinion. We strongly disagree with that opinion. And I think the basis for that is we are in a randomized placebo-controlled study, met our prespecified primary outcome, showing a slowing in the rate of progression on the ALSFRS-R. We've also observed a difference on overall survival. And that data, of course, led to our approval, but there are full U.S. FDA approval and our approval with conditions in Health Canada. So we believe we have a data package that should, in our view, support approval. But of course, ultimately, this is up to CHMP.

當然。因此，關於歐盟和 CHMP，正如我們之前所分享的，歐盟最初採取了負面意見。我們強烈不同意這個觀點。我認為其基礎是我們正在進行一項隨機安慰劑對照研究，達到了我們預先指定的主要結果，顯示 ALSFRS-R 的進展速度減慢。我們也觀察到整體存活率的差異。當然，這些數據導致了我們的批准，但美國 FDA 已完全批准，加拿大衛生部也有條件批准。因此，我們相信我們擁有一個資料包，在我們看來應該支持批准。但當然，最終這取決於 CHMP。

So we submitted for reexamination. That's roughly a 4-month process, under which 2 new repertories are assigned and review the application. We submitted that shortly after we got the negative opinion. So you can expect that near the end of this year, we'll hear back regarding that opinion.

於是我們提交了複審。這大約是一個為期 4 個月的過程，在此期間分配 2 個新劇目並審查申請。我們在收到負面意見後不久就提交了該意見。因此，您可以預期，在今年年底附近，我們將收到有關該意見的回應。

In terms of capital deployment and potential BD, I'll talk to -- I'll pass to Jim.

在資本部署和潛在的業務發展方面，我將與吉姆交談。

Yes. Thanks, Geoff. And clearly, profitability this early on in our launch is very gratifying. I mean, I think that ultimately is a direct result of the need in this patient -- in this area and the vast -- the dearth of options that people living with ALS have had so far. So we're very proud to be filling some of that need.

是的。謝謝，傑夫。顯然，我們推出初期的獲利能力非常令人滿意。我的意思是，我認為這最終是由於該患者的需求（在這個領域以及廣大的 ALS 患者迄今為止缺乏選擇）的直接結果。因此，我們非常自豪能夠滿足其中一些需求。

I think the other thing I would say, too, is we're really focused on what we have on our plate now, right, with obviously still in the middle of the launch in the United States and Canada, working through what's going to happen in Europe and potentially, hopefully, looking forward to a launch next year. We've started off and are interacting with the Japanese and other places around the world, too, to see where we can continue to take this drug. With our PSP program and our Wolfram program ongoing, that's what we're doing. I'd say the watch it around here right now is focus.

我想我還要說的另一件事是，我們真正專注於我們現在要做的事情，對吧，顯然仍處於在美國和加拿大推出的過程中，正在研究將要發生的事情在歐洲，並有望在明年推出。我們已經開始與日本和世界其他地方互動，看看我們可以在哪裡繼續服用這種藥物。隨著我們的 PSP 計劃和 Wolfram 計劃的持續進行，這就是我們正在做的事情。我想說現在這裡的觀看是焦點。

Now longer term, I think we have the opportunity with our launch and with the business that we're in to potentially do some business development over the longer term. But I think that, hopefully, we'll be able to grow the top line, grow our bottom line and then also invest in a robust pipeline. But we have a pretty high standard here for new programs. And as I said, I think right now the watch word is on focus.

現在從長遠來看，我認為我們有機會透過我們的推出以及我們所從事的業務來進行長期的一些業務發展。但我認為，希望我們能夠增加收入，增加我們的利潤，然後投資一個強大的管道。但我們對新項目有相當高的標準。正如我所說，我認為現在的關鍵字是焦點。

And the next question comes from Michael DiFiore with Evercore.

下一個問題來自 Evercore 的 Michael DiFiore。

Congrats on the quarter. Two for me. Now with the passage of more time, do you have any better sense of the size of the patient bolus at this point? And my follow-up is this, I want to push you a little bit on the discontinuation rates. I mean among the early patients to have received commercial drug in 4Q of last year, presumably, some of these patients are -- would have been on drug for at least 6 months now. Would you be able to provide any color as to what percent of them are still on therapy at this point, again, just among the patients who started in 4Q?

恭喜本季。給我兩個。現在，隨著時間的推移，您現在對患者推注的量有沒有更好的認識？我的後續行動是，我想向您介紹停藥率。我的意思是，在去年第四季接受商業藥物的早期患者中，大概其中一些患者現在已經服用藥物至少 6 個月了。您是否能夠提供任何顏色說明，僅在第四季度開始的患者中，目前仍在接受治療的患者百分比是多少？

Yes. Maybe I'll just start with your question regarding the bolus. We continue to be pleased that the interest in and demand for RELYVRIO continues to be as -- at a very strong pace and I think importantly, includes a mix of both newly diagnosed patients and people who have been diagnosed and living with ALS for many years.

是的。也許我會從你關於推注的問題開始。我們仍然感到高興的是，人們對 RELYVRIO 的興趣和需求繼續以非常強勁的速度增長，我認為重要的是，其中包括新診斷的患者和已診斷並患有 ALS 多年的患者。

Again, at the end of Q2, we had roughly 3,800 net patients on therapy, up from roughly 3,000 patients in Q1 and just over 1,300 in Q4. So we really believe that at this point in time, RELYVRIO is really starting to become a foundational therapy in ALS and meeting a really high unmet need for this patient community, which is obviously our mission and what we've been focused on for some time. As far as the growth opportunities, which is equally important to us, we see several different opportunities ahead of us. First, the prescribing remains really concentrated with the 80 prescribers mostly at the major ALS centers, where our focus was at the beginning of launch, representing about half of all RELYVRIO prescriptions this quarter.

同樣，在第二季末，我們有大約 3,800 名淨患者接受治療，高於第一季的約 3,000 名患者和第四季的 1,300 多名患者。因此，我們確實相信，在這個時間點，RELYVRIO 確實開始成為 ALS 的基礎療法，並滿足該患者群體未滿足的非常高的需求，這顯然是我們的使命，也是我們一段時間以來一直關注的目標。就對我們同樣重要的成長機會而言，我們看到了眼前的幾個不同的機會。首先，處方仍然非常集中於主要 ALS 中心的 80 名處方者，我們的重點是在推出之初，約佔本季度所有 RELYVRIO 處方的一半。

We're also encouraged that the level of interest among this group and believe that we have a large opportunity for growth ahead of us as we bring our messaging to more prescribers and deepen our relationships within those key centers. And I think importantly, we've seen with those prescribers be much more prolific in their prescribing, which I think is an important part.

我們也對該群體的興趣程度感到鼓舞，並相信，隨著我們將訊息傳遞給更多處方者並加深我們與這些關鍵中心的關係，我們面前有巨大的成長機會。我認為重要的是，我們已經看到這些處方者的處方更加豐富，我認為這是一個重要的部分。

And second, we have a really large untapped opportunity for growth outside of this group. As I mentioned, we were heavily focused on the key ALS centers at launch. We're continuing to expand our outreach and educational efforts more broadly because we believe it's critically important that everybody is aware that RELYVRIO is the first-and-only product to have both function and survival demonstrated in the clinical trial, and we believe we can change the paradigm for treatment moving forward.

其次，我們在這個群體之外還有巨大的未開發的成長機會。正如我所提到的，我們在推出時重點關注關鍵的 ALS 中心。我們正在繼續更廣泛地擴大我們的外展和教育工作，因為我們相信讓每個人都意識到RELYVRIO 是第一個也是唯一一個在臨床試驗中證明其功能和生存能力的產品至關重要，我們相信我們可以改變前進的治療範式。

And maybe just to answer your second question on discontinuation, again, we're only going to be reporting on net patient numbers for a quarter. But indeed, I think it's important to reflect that the first cohort of patients who started on therapy at launch, many of those who have been really fairly progressed early on. So I think we're going to see the dynamic of the patients change over time. So it's a little too early to really give any trends there.

也許只是為了回答您關於停藥的第二個問題，我們只會報告一個季度的淨患者人數。但事實上，我認為重要的是要反映出第一批在啟動時開始接受治療的患者，其中許多人在早期就取得了相當大的進展。所以我認為我們會看到患者的動態隨著時間的推移而變化。因此，現在真正給出任何趨勢還為時過早。

Yes. And one thing I'll remind that I think Margaret shared earlier as well, we -- in some of CENTAUR study, approximately 70% of people completed that study on study drug. And what we're seeing in the real world is not so different from that. But again...

是的。我要提醒的一件事是，我認為瑪格麗特之前也分享過，我們——在 CENTAUR 的一些研究中，大約 70% 的人完成了研究藥物的研究。我們在現實世界中看到的情況與此並沒有太大不同。但又...

The next question comes from Marc Goodman with Leerink Partners.

下一個問題來自 Leerink Partners 的 Marc Goodman。

First question is, are you willing to make any comment about what kind of trends you're seeing -- you saw in July? And then secondly, can you just confirm -- you mentioned 10% of the patients are getting free drug. Just to be clear, that 10% is in the numbers that you provide, right, in the 3,800 patients that you were talking about, and it's all included in your gross-to-net calculation and everything? I just want to be clear on that.

第一個問題是，您願意對 7 月看到的趨勢發表評論嗎？其次，您能否確認一下—您提到 10% 的患者正在獲得免費藥物。需要澄清的是，這 10% 是在您提供的數字中，對吧，在您所說的 3,800 名患者中，並且這一切都包含在您的總淨值計算中以及所有內容中？我只是想澄清這一點。

Yes. Marc, it's Jim. Yes, the 10% of the patients that are receiving free drug is included. So those 10% are included in the net patients. Those are all the patients on therapy at the end of June. And yes, free drug would be included in gross-to-nets -- excuse me, free drug is actually in COGS, right? You've given the drug and you're not getting any sales for it. So the free drug goes in COGS. Any patient assistance that we pay in terms of co-pay assistance or things like that, that's what goes in the gross-to-nets, just to be clear on that.

是的。馬克，是吉姆。是的，其中包括 10% 接受免費藥物的患者。所以這 10% 包含在淨患者中。這些是六月底接受治療的所有患者。是的，免費藥物將包含在總淨收入中——請問，免費藥物實際上包含在銷貨成本中，對嗎？您已經提供了該藥物，但沒有獲得任何銷售。因此，免費藥物計入銷貨成本 (COGS)。我們以共同支付援助或類似方式支付的任何患者援助，這都是毛淨額的內容，只是需要澄清這一點。

And then finally, in terms of July, I think we'll comment on the July trends when we report our quarterly results for Q3. But I think our business is -- with now 3 quarters under our belt, we're all starting to get a chance to see what our business is like moving forward. But we won't be giving specifics on July at this stage.

最後，就 7 月而言，我認為當我們報告第三季的季度業績時，我們將評論 7 月的趨勢。但我認為我們的業務已經過去了三個季度，我們都開始有機會了解我們的業務向前發展的情況。但現階段我們不會透露 7 月的具體情況。

The next question comes from Graig Suvannavejh with Mizuho.

下一個問題來自 Mizuho 的 Graig Suvannavejh。

Congrats on the quarter. Just 2 questions. One, maybe another way to ask a question that people seem to be trying to get at. Do you have any color on -- or can you provide any color on kind of new prescription trends versus refill trends? Any kind of metrics you can provide there and how that's evolved? And then my follow-up is I'm curious about the expansion efforts to go beyond the ALS centers. And if you could perhaps put into context the portion of ALS prescribers that you're targeting or that you hope to get that are outside of the ALS center setting.

恭喜本季。只有 2 個問題。一個，也許是另一種提出人們似乎試圖回答的問題的方式。您是否有任何顏色 - 或者您能否提供有關新處方趨勢與補充趨勢的任何顏色？您可以在那裡提供任何類型的指標以及它是如何演變的？我的後續行動是我對 ALS 中心以外的擴張工作感到好奇。您是否可以將您所針對的或您希望獲得的 ALS 處方者部分置於 ALS 中心設置之外的背景中。

Yes. So maybe I'll start and then have Margaret join in, too. So again, we're 3 quarters into launch. We have roughly 3,800 net people on treatment as of the end of Q2, which we're very pleased about. I mean that's 3,800 people with ALS we're helping. But that means that there's many, many more people that we'd like to help as well. But I think we all here are constantly reminded of the mission at hand.

是的。所以也許我會開始，然後讓瑪格麗特也加入。再說一次，我們距離發布還有 3 個季度了。截至第二季末，我們有大約 3,800 名淨患者正在接受治療，對此我們感到非常高興。我的意思是，我們正在幫助 3,800 名 ALS 患者。但這意味著我們還想幫助更多的人。但我認為我們所有人都在不斷地提醒自己手邊的使命。

And I think the ALS market in many ways is unique, and it's -- because it's a large rare disease, there's a huge unmet medical need. And historically, there have been few treatment options. And so I think the way that we've thought about our business, as Margaret was sharing, is to focus on the ALS specialists and then continuing to look to broaden out. And so I think as we look at our prescription numbers, where our people have focused is where we're seeing the prescriptions as well.

我認為 ALS 市場在許多方面都是獨一無二的，因為它是一種大型罕見疾病，所以存在巨大的未滿足的醫療需求。從歷史上看，治療選擇很少。因此，我認為，正如瑪格麗特分享的那樣，我們對業務的思考方式是專注於 ALS 專家，然後繼續尋求拓展。因此，我認為，當我們查看處方數量時，我們的人員關注的地方也是我們看到處方的地方。

And then Margaret, I'll invite you to share any more details on that.

然後瑪格麗特，我將邀請您分享更多相關細節。

Yes. As we've indicated, we're heavily focused at launch, which I think was the right strategic decision to focus on the key ALS centers where the majority of ALS patients are actually treated. However, there's also a number of ALS patients that are treated outside of ALS centers for multiple reasons, either they can't transport, they can't get there at a reasonable time, and it's -- they typically need to go there every quarter to see the multidisciplinary care.

是的。正如我們所指出的，我們在啟動時重點關注，我認為這是正確的策略決策，重點關注大多數 ALS 患者實際接受治療的關鍵 ALS 中心。然而，也有許多 ALS 患者由於多種原因在 ALS 中心外接受治療，要么無法運輸，要么無法在合理的時間到達那裡，而且他們通常需要每個季度去那裡看看多學科護理。

There are a number of general community neurologists that are equally important to be educated, and that's where we're expanding our focus. And we are continuing to increase our penetration and reach out to those what we call our Tier A, Tier B targets. And we're just going to continue to work on that expansion moving forward because it's really important for us that every physician who treats an ALS patient is educated about the significant RELYVRIO benefits that we can bring to be able to serve this patient community optimally.

有許多社區神經科醫生同樣需要接受教育，這就是我們正在擴大關注範圍的地方。我們正在繼續提高滲透率，並達到我們所說的 A 級、B 級目標。我們將繼續致力於這一擴展，因為對我們來說非常重要的是，每位治療ALS 患者的醫生都應該接受有關RELYVRIO 的顯著優勢的教育，這些優勢是我們可以帶來的，以便能夠為該患者社區提供最佳服務。

(Operator Instructions) And the next question comes from Ananda Ghosh with H.C. Wainwright.

（操作員說明）下一個問題來自 Ananda Ghosh 和 H.C.溫賴特。

Congrats on the quarter. So I have 2 questions on the ALS program and one for the PSP. The first question is basically some of the question which keeps coming from the industrial community, and that would be if PHOENIX is a required confirmatory study for accelerated approval of RELYVRIO and what -- if it says, then can FDA initiate a process to pull it off from the market? So any clarification on that would be great. And then I have a follow-up question on the ALS program and then a PSP.

恭喜本季。我有 2 個關於 ALS 計劃的問題，還有 1 個關於 PSP 的問題。第一個問題基本上是工業界不斷提出的一些問題，那就是 PHOENIX 是否是加速批准 RELYVRIO 所必需的驗證性研究，如果它說的話，那麼 FDA 可以啟動一個程序來取消它嗎？退出市場？所以對此的任何澄清都會很好。然後我有一個關於 ALS 計劃和 PSP 的後續問題。

Sure, and thank you for the question, Ananda. And yes, I mean, first, there is a full FDA approval. There's no condition of the PHOENIX study. In Canada, it's an NOCC, which means a Noticing Compliance with Conditions. And again, our expectation in Europe if there's an approval, is that it would also be a conditional marketing authorization, and the condition there would be PHOENIX. So we continue to run the PHOENIX study. We'll have those results mid- next year. That's a very highly powered study. And we and I think the ALS community are looking forward to those results. But from an FDA perspective, it's a full FDA approval.

當然，謝謝你的提問，阿南達。是的，我的意思是，首先，有 FDA 的全面批准。 PHOENIX 研究沒有任何條件。在加拿大，它是 NOCC，意思是「注意遵守條件」。再說一次，我們在歐洲的期望是，如果獲得批准，這也將是有條件的行銷授權，而條件是 PHOENIX。所以我們繼續進行 PHOENIX 研究。我們將在明年年中得到這些結果。這是一項非常有力的研究。我和我認為 ALS 社區都期待這些結果。但從 FDA 的角度來看，這是 FDA 的完全批准。

Great. The next question is the last quarter, you had remarked that the patient that might show signs of stability. So is it still -- is that segment still remains valid for as we think ahead in terms of the growth with RELYVRIO?

偉大的。下一個問題是上個季度，您曾說過患者可能會表現出穩定的跡象。那麼，當我們展望 RELYVRIO 的成長時，該細分市場仍然有效嗎？

Well, so I think the question you're bringing up on patient responses is a critical one in neurodegenerative disease. And it's a new area for all of us, and I think it's really, really exciting. But I'd say it's still too early to really tell. Now in the CENTAUR study, we certainly -- we saw some people who seem to progress very little and others who progress faster.

嗯，所以我認為你提出的關於患者反應的問題是神經退化性疾病中的關鍵問題。這對我們所有人來說都是一個新領域，我認為這真的非常令人興奮。但我想說，現在下結論還太早。現在，在 CENTAUR 研究中，我們確實看到了一些人似乎進步很小，而其他人則進步更快。

But whether that was due to their specifics, whether it's genetics or environmental or whether that was just due to their course of disease, those are the questions that we're still asking and we haven't been able to ask because we haven't had effective treatments. But at this time, it's just too early to know. But certainly, those sorts of real-world evidence-type approaches is something that we're very, very excited to do more of because I think you can start to ask some really, really critical questions when you have an effective treatment.

但無論這是由於他們的具體情況，無論是遺傳或環境，還是僅僅是由於他們的病程，這些都是我們仍在問的問題，但我們無法問，因為我們還沒有進行了有效的治療。但現在知道還太早。但當然，我們非常非常興奮能夠做更多這些現實世界的證據類型的方法，因為我認為當你有了有效的治療方法時，你可以開始問一些非常非常關鍵的問題。

Right. And my last question is on PSP. Based on some natural history data, so we kind of saw that the PSP studies in general has couple of disadvantages. One is a very high rate of dropouts. And some of the scales to say cognition and depression mostly fails, at least in the historical PSP trials. So what has been your thought on it? And how have you kind of incorporated these into your Phase III trial design?

正確的。我的最後一個問題是關於 PSP 的。根據一些自然史數據，我們發現 PSP 研究總體上有幾個缺點。一是輟學率非常高。一些表示認知和憂鬱的量表大多失敗，至少在歷史上的 PSP 試驗中是如此。那麼您對此有何想法？您是如何將這些納入您的 III 期試驗設計中的？

Yes. So we shared and probably even more importantly, Prof. Dr. Günter Höglinger shared on a recent call that we did that's published on our website a much more in-depth view of PSP and our upcoming clinical trial. So in our PSP trial, we are designing the study based on the PSPRF, the PSP rating scale. This is a scale that tracks primarily -- I would say, primarily kind of motor and functional rather than cognitive outcomes of PSP. The PSP rating scale studied in several past trials, what's been found quite consistently is an approximate 10-point progression over approximately a year with a pretty small error and a pretty tight kind of variance when you're in these studies.

是的。因此，我們分享了，也許更重要的是，Günter Höglinger 教授博士在最近的一次電話會議上分享了我們在我們網站上發布的對 PSP 和我們即將進行的臨床試驗的更深入的看法。因此，在我們的 PSP 試驗中，我們根據 PSPRF（PSP 評級量表）設計研究。這是一個主要追蹤 PSP 的運動和功能而不是認知結果的量表。在過去的幾次試驗中研究的 PSP 評分量表，發現在大約一年內大約有 10 分的進展，當您參與這些研究時，誤差非常小，變異數也非常小。

Dropout is not in our view and has not been in previous studies beyond what you might have in other neurodegenerative diseases. And again, as has been shown from the previous studies, this is a space actually where the power is quite good compared to most neurodegenerative diseases. So I'd say overall -- and again, I encourage people to listen to the webinar where we go into this in a lot more detail. But I'd say overall, we feel very strongly that we have a great trial design, we have a great scientific rationale, and this is a great indication to take AMX0035 into.

在我們看來，輟學並不存在，在先前的研究中也沒有出現超出其他神經退化性疾病中可能存在的情況。而且，正如先前的研究所表明的那樣，與大多數神經退化性疾病相比，這個空間實際上具有相當好的功效。所以我想說的是，總的來說，我再次鼓勵人們收聽網路研討會，我們將在其中更詳細地討論這個問題。但我想說，總的來說，我們強烈感覺到我們有一個很棒的試驗設計，我們有一個很好的科學原理，這是一個很好的跡象來考慮 AMX0035。

This will conclude our question-and-answer session. I'll turn the conference back over to Justin Klee for any closing remarks.

我們的問答環節到此結束。我將把會議轉回賈斯汀·克利（Justin Klee）發表閉幕詞。

Well, thank you, operator, and thank you all for joining us on the call today and for your support. So we hope you all have a good evening. Thanks for joining us.

好的，謝謝接線員，也謝謝大家今天加入我們的電話會議並感謝你們的支持。所以我們希望大家度過一個美好的夜晚。感謝您加入我們。

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.

會議現已結束。感謝您參加今天的演講。您現在可以斷開連線。