Amylyx Pharmaceuticals, Inc. (AMLX) 2026 Q1 法說會逐字稿

Good morning. My name is Kate, and I will be your conference operator today. At this time, I would like to welcome everyone to the Amylyx Pharmaceuticals first quarter 2026 earnings conference call. (Operator Instructions) Please be advised that this call is being recorded at the company's request.

早安。我叫 Kate，今天將擔任各位的電話會議接線員。此刻，我謹代表公司歡迎各位參加 Amylyx Pharmaceuticals 2026 年第一季財報電話會議。(接線員指示) 請注意，應公司要求，本次通話將被錄音。

I would now like to turn the call over to Lindsey Allen, Vice President, Investor Relations and Communications. Please proceed.

現在我想把電話交給投資人關係與傳播副總裁 Lindsey Allen。請開始。

Good morning, and thank you all for joining us today to discuss our first quarter 2026 financial results and business update. With me on the call today are Josh Cohen and Justin Klee, our Co-CEOs; Dr. Camille Bedrosian, our Chief Medical Officer; Jim Frates, our Chief Financial Officer; and Dan Monahan, our Chief Commercial Officer.

早安，感謝各位今天加入我們，一同討論 2026 年第一季財務結果與業務更新。今天與我一同出席電話會議的有：共同執行長 Josh Cohen 與 Justin Klee；首席醫療長 Camille Bedrosian 醫師；首席財務長 Jim Frates；以及首席商務長 Dan Monahan。

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 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.

在開始之前，我想提醒各位：我們在本次電話會議中所作的任何陳述或所呈現、且非歷史事實的資訊，均屬前瞻性陳述，係基於我們目前的信念、計畫與預期，並依據 1995 年《私人證券訴訟改革法案》的安全港條款作出。

These statements include, but are not limited to, our expectations with respect to avexitide, AMX0035, AMX0114 and AMX0318, statements regarding regulatory and clinical developments and the impact thereof and the expected timing thereof and statements regarding our cash runway. Actual events and results could differ materially from those expressed or implied by any forward-looking statements. 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.

這些陳述包括但不限於：我們對 avexitide、AMX0035、AMX0114 與 AMX0318 的預期；有關法規與臨床進展及其影響與預期時程的陳述；以及有關我們現金可支撐期間的陳述。實際事件與結果可能與任何前瞻性陳述所明示或暗示者存在重大差異。敬請各位勿過度依賴這些前瞻性陳述；除非法律要求，Amylyx 不承擔更新此等陳述之任何義務。

Now I will turn the call over to Justin.

現在我將把電話交給 Justin。

Good morning, everyone, and thank you for joining us. The first quarter of 2026 was marked by execution across our pipeline. Most notably, we continue to progress the pivotal Phase 3 LUCIDITY trial of avexitide, our investigational first-in-class GLP-1 receptor antagonist with FDA breakthrough therapy designation in post-bariatric hypoglycemia or PBH. We are executing on the three strategic imperatives for avexitide that we outlined earlier this year.

各位早安，感謝加入我們。2026 年第一季，我們在研發管線各項工作上持續落實執行。最值得一提的是，我們持續推進 avexitide 的關鍵性第三期 LUCIDITY 試驗；avexitide 是我們正在研發的同類首創（first-in-class）GLP-1 受體拮抗劑，並已在減重手術後低血糖（post-bariatric hypoglycemia，PBH）適應症獲得 FDA 突破性療法認定。我們正依照今年稍早所提出的 avexitide 三項策略重點推進。

First, we are advancing the pivotal Phase 3 LUCIDITY trial toward top line data. Randomizing and dosing the last participant in late March was a significant milestone. We have a clear line of sight toward the completion of the 16-week trial, and we remain on track for a top line readout next quarter.

第一，我們正推動關鍵性第三期 LUCIDITY 試驗邁向主要（top line）數據。在三月下旬完成最後一位受試者的隨機分派與給藥，是一項重要里程碑。我們對於完成這項為期 16 週的試驗有清晰的可視性，並仍按計畫於下個季度公布主要結果。

Second, we are advancing NDA readiness and regulatory preparations. We are already drafting NDA sections to support a potential submission.

第二，我們正推進 NDA 申請準備與法規相關籌備工作。我們已開始撰寫 NDA 的各個章節，以支援潛在的送件。

And third, we continue to strengthen our launch readiness. We are executing against a comprehensive commercial readiness road map to help ensure we are fully prepared for commercialization of avexitide, if approved, in 2027.

第三，我們持續強化上市準備。我們正依據一套全面的商業化準備路線圖執行，以協助確保若 avexitide 獲核准，我們能在 2027 年做好全面商業化準備。

In addition to avexitide, we continue to make progress across our broader pipeline. For AMX0318, our long-acting GLP-1 receptor antagonist, IND-enabling studies are underway. We are targeting a 2027 IND filing.

除 avexitide 之外，我們也持續在更廣泛的研發管線上取得進展。就 AMX0318（我們的長效型 GLP-1 受體拮抗劑）而言，IND 申請前的支持性研究正在進行中。我們目標是在 2027 年提交 IND 申請。

For AMX0035 in Wolfram syndrome, we anticipate presenting longer-term week 96 data from the Phase 2 open-label HELIOS clinical trial at an upcoming scientific meeting.

就 Wolfram 症候群的 AMX0035 而言，我們預期將在即將到來的科學會議上發表第二期開放標籤 HELIOS 臨床試驗較長期的第 96 週數據。

And for AMX0114 in ALS, we fully enrolled Cohort two of the Phase 1 LUMINA trial in March. At the ENCALS Annual Meeting this June, we expect to present early biomarker data from Cohort one, the first and lowest of four doses being evaluated in the trial. We expect these data will provide initial information about the levels of the ALS biomarkers being assessed in the LUMINA trial from the first cohort.

就 ALS 的 AMX0114 而言，我們已於三月完成第一期 LUMINA 試驗第二隊列（Cohort two）的全數收案。在今年六月的 ENCALS 年會上，我們預期將發表第一隊列（Cohort one）的早期生物標記數據；該隊列為本試驗評估的四個劑量中第一個、也是最低劑量。我們預期這些數據將就 LUMINA 試驗第一隊列所評估的 ALS 生物標記水準提供初步資訊。

As we continue to advance our pipeline, we are simultaneously preparing for the potential commercial launch of avexitide. To discuss our launch readiness efforts, Dan Monahan, our Chief Commercial Officer, is with us on the call today.

在我們持續推進研發管線的同時，我們也同步為 avexitide 的潛在商業上市做準備。為了說明我們的上市準備工作，首席商務長 Dan Monahan 今天也與我們一同參與電話會議。

Dan joined Amylyx in January 2024, bringing more than two decades of experience. He was instrumental in the commercialization of Otsuka's Rexulti, Novartis' Cosentyx and Sanofi's Lantus and Actonel, among others.

Dan 於 2024 年 1 月加入 Amylyx，擁有超過二十年的經驗。他曾在多項產品的商業化中扮演關鍵角色，包括大塚製藥的 Rexulti、諾華的 Cosentyx，以及賽諾菲的 Lantus 與 Actonel 等。

With that, Dan, I'll turn the call over to you.

接下來，Dan，我把電話交給你。

Thank you, Justin, and good morning, everyone. I'm pleased to be on the call today to discuss how we have been refining our launch strategies as we prepare for the potential commercialization of avexitide next year. The more we engage with the PBH community, the more we understand the profound unmet need that exists. We are operating with a deep sense of urgency.

謝謝你，Justin，各位早安。很高興今天能在電話會議上與各位討論：在我們為明年 avexitide 的潛在商業化做準備之際，我們如何持續精進上市策略。我們與 PBH 社群互動越多，就越能理解其中存在的重大未被滿足醫療需求。我們以高度的急迫感在推進相關工作。

To date, our commercial efforts have been focused on gaining key insights into the PBH market. This includes gathering direct insights from people living with PBH and the health care professionals who are managing their condition.

截至目前，我們的商業化工作重點在於取得對 PBH 市場的關鍵洞察。這包括直接蒐集 PBH 患者，以及負責管理其病況的醫療專業人員所提供的第一手見解。

In addition, we are developing a deep understanding of the patient journey and continuing ongoing claims work to help us determine where patients are being treated. To enable our commercial preparations, we've made key hires across marketing, market access and commercial operations.

此外，我們也在建立對患者就醫旅程的深入理解，並持續進行理賠（claims）資料分析，以協助我們判斷患者在哪些場域接受治療。為了支援商業化準備，我們已在行銷、市場准入與商業營運等領域完成關鍵人才招募。

Ahead of the potential approval and commercial launch of avexitide, our immediate focus is on disease state education. This includes raising stakeholder awareness of PBH with an emphasis on the pathophysiology, the importance of accurate and timely diagnosis and the profound unmet need and burden of the condition. We plan to launch this disease state education campaign this summer.

在 avexitide 潛在獲批與商業上市之前，我們眼前的重點是疾病狀態教育。這包括提升利害關係人對 PBH 的認知，並著重於其病理生理機轉、準確且及時診斷的重要性，以及此疾病所帶來的重大未被滿足需求與負擔。我們計畫在今年夏天啟動這項疾病狀態教育活動。

Looking at the market opportunity, our independent claims analysis and ongoing field engagements continue to support our estimate of approximately 160,000 people living with PBH in the US who have undergone the two most common types of bariatric surgery: sleeve gastrectomy and Roux-en-Y gastric bypass.

就市場機會而言，我們的獨立理賠資料分析與持續的第一線互動，持續支持我們的估計：在美國，約有 160,000 名 PBH 患者曾接受最常見的兩種減重手術：袖狀胃切除術（sleeve gastrectomy）與 Roux-en-Y 胃繞道手術（Roux-en-Y gastric bypass）。

Our estimates are firmly rooted in the growing body of prospective and retrospective published literature, including large long-term cohort studies evaluating hypoglycemia in people who have undergone bariatric surgery. Importantly, our ongoing market research indicates that endocrinologists have a high intent to treat PBH if there were to be an approved medicine.

我們的估計建立在日益增加的前瞻性與回溯性已發表文獻之上，包括評估接受減重手術者低血糖情形的大型長期隊列研究。重要的是，我們持續進行的市場研究顯示：若有獲核准的藥物可用，內分泌科醫師對於治療 PBH 具有高度意願。

To reach appropriate patients, we have initiated our marketplace sizing efforts and continue to identify key centers and endocrinologists that manage this condition. Building up to the potential launch, we will refine these efforts as more insights are generated.

為了觸及合適的患者，我們已啟動市場規模估算工作，並持續辨識管理此病況的關鍵醫療中心與內分泌科醫師。隨著取得更多洞察、逐步接近潛在上市，我們將進一步精進這些工作。

Our commercial preparations are advancing in lockstep with our clinical progress, and we look forward to sharing additional details as we move closer to the commercialization of avexitide, if approved.

我們的商業化準備與臨床進展同步推進；若 avexitide 獲核准，隨著我們更接近其商業化，我們也期待分享更多細節。

With that, I'll turn the call over to Camille to provide an update on our clinical and medical affairs progress this quarter.

接下來，我把電話交給 Camille，請她就本季度臨床與醫療事務的進展提供更新。

Thank you, Dan. To start, PBH is a chronic metabolic condition driven by an exaggerated GLP-1 response, primarily after food intake, resulting in persistent recurrent and often debilitating hypoglycemia. These events cause an inadequate supply of glucose to the brain known as neuroglycopenia with potential clinical consequences such as cognitive dysfunction, seizures and loss of consciousness.

謝謝你，Dan。首先，PBH 是一種慢性代謝性疾病，其驅動因素為誇大的 GLP-1 反應，主要發生在進食後，導致持續、反覆且往往使人衰弱的低血糖。這些事件會造成大腦葡萄糖供應不足，稱為神經性低血糖（neuroglycopenia），並可能帶來臨床後果，例如認知功能障礙、癲癇發作與意識喪失。

For people living with PBH, this can create a life of perpetual vigilance where a meal with friends or a drive to work carries the risk of debilitating hypoglycemia and its ramification. This fear can disrupt independence and compromise safety, nutrition and overall quality of life. Currently, there are no FDA-approved therapies.

對於與 PBH 共存的人而言，這可能造成一種長期處於高度警覺的生活狀態：與朋友共進一餐或開車上班，都可能伴隨發生使人衰弱的低血糖及其後果的風險。這種恐懼可能擾亂自主性，並損及安全、營養與整體生活品質。目前，尚無 FDA 核准的治療方法。

Our pivotal Phase 3 LUCIDITY trial is evaluating avexitide, 90 milligrams once daily, in individuals with PBH following Roux-en-Y gastric bypass surgery using the FDA agreed-upon primary outcome of reduction in the composite of Level 2 and Level 3 hypoglycemic events through week 16.

我們的關鍵性第 3 期 LUCIDITY 試驗正在評估 avexitide（每日一次 90 毫克）用於接受 Roux-en-Y 胃繞道手術後的 PBH 患者，並採用 FDA 同意的主要終點：至第 16 週時，第 2 級與第 3 級低血糖事件複合指標的降低。

LUCIDITY was designed with the goal of replication. Five prior avexitide trials in PBH, which demonstrated statistically significant results, including reductions in hypoglycemic events directly informed the dose, the primary endpoint, inclusion criteria and surgical subtype for LUCIDITY.

LUCIDITY 的設計目標是可重複驗證。先前五項 avexitide 用於 PBH 的試驗已顯示具統計顯著性的結果，包括低血糖事件的降低，並直接為 LUCIDITY 的劑量、主要終點、納入標準及手術亞型提供依據。

Echoing Justin's earlier remarks, our clinical team remains deeply focused on the execution of the LUCIDITY trial, and we continue to work closely with our investigators as we approach our anticipated data readout next quarter. In parallel with our clinical trial execution, we are actively ramping up our field medical affairs team to facilitate on-the-ground engagement with KOLs.

呼應 Justin 先前的評論，我們的臨床團隊仍高度專注於 LUCIDITY 試驗的執行，並在接近預期於下季公布數據讀出之際，持續與研究者密切合作。在推進臨床試驗執行的同時，我們也正積極擴編醫學事務外勤團隊，以促進與關鍵意見領袖（KOL）的第一線互動。

I also am pleased to share that we recently launched a US expanded access program to provide avexitide for up to 250 adults with PBH following Roux-en-Y gastric bypass. This program is a direct response to the urgent need we are hearing from individuals who are struggling with the devastating daily realities of PBH and the physicians who treat them.

我也很高興分享，我們近期在美國啟動了擴大使用計畫（expanded access program, EAP），為最多 250 名接受 Roux-en-Y 胃繞道手術後的 PBH 成人提供 avexitide。此計畫是對我們從正面臨 PBH 毀滅性日常現實的患者，以及治療他們的醫師所聽到之迫切需求的直接回應。

Initial eligible patients include individuals who have either completed LUCIDITY or participated in previous clinical trials of avexitide in PBH. As a reminder, avexitide is an investigational drug and has not been approved by the FDA for any indication.

初期符合資格的患者包括已完成 LUCIDITY 的個體，或曾參與先前 avexitide 用於 PBH 的臨床試驗者。提醒一下，avexitide 為研究用藥物，尚未獲 FDA 核准用於任何適應症。

Working directly with the PBH community and seeing the everyday impact of this devastating condition drives our continued commitment to our clinical and medical efforts.

直接與 PBH 社群合作並看見此毀滅性疾病對日常生活的影響，驅動我們持續投入臨床與醫學相關工作。

And with that, I will now turn over the call to Jim to review our financials. Jim?

接下來，我將把電話會議交給 Jim，請他回顧我們的財務狀況。Jim？

Thanks, Camille. Our financial results for the first quarter were in line with our plans and reflect our focus on the Phase 3 LUCIDITY trial and targeted investments in advancing our broader pipeline.

謝謝你，Camille。我們第一季的財務結果符合我們的規劃，並反映我們聚焦於第 3 期 LUCIDITY 試驗，以及在推進更廣泛產品線方面進行有針對性的投資。

We ended the fourth quarter with $279.8 million in cash and marketable securities compared to $317 million at the end of the fourth quarter of last year. This capital funds our anticipated cash runway into 2028, including our key expected milestones: the LUCIDITY top line readout expected in Q3 2026, potential FDA approval and potential commercial launch of avexitide in 2027.

我們在第四季末的現金及有價證券為 2.798 億美元，相較於去年第四季末的 3.17 億美元。這些資金可支應我們預期的現金使用期至 2028 年，並涵蓋我們預期的關鍵里程碑：LUCIDITY 預計於 2026 年第 3 季公布主要（top line）結果、avexitide 於 2027 年可能獲 FDA 核准，以及可能的商業上市。

Turning now to our results for the quarter. Total operating expenses for the quarter were $43.8 million, up 16% from the same period in 2025. Research and development expenses were $27.6 million compared to $22.1 million in Q1 2025. The increase was primarily due to an increase in spending related to the clinical development of avexitide in PBH.

接著看本季的營運結果。本季總營運費用為 4,380 萬美元，較 2025 年同期增加 16%。研發費用為 2,760 萬美元，相較於 2025 年第一季的 2,210 萬美元。增加主要來自與 avexitide 用於 PBH 的臨床開發相關支出上升。

This quarter, we also recognized a milestone payment of $4 million to Gubra following the identification of AMX0318 as a development candidate for PBH and other rare diseases. The increase was offset by decreased spending related to the clinical development of AMX0035 for progressive supranuclear palsy.

本季，我們亦在將 AMX0318 確認為 PBH 及其他罕見疾病的開發候選藥物後，向 Gubra 認列 400 萬美元的里程碑付款。此增加部分被 AMX0035 用於進行性核上性麻痺（progressive supranuclear palsy）的臨床開發支出下降所抵銷。

Selling, general and administrative expenses were $16.2 million compared to $15.7 million in Q1 2025. This increase was primarily due to an increase in consulting and professional services as we prepare for the potential commercial launch of avexitide.

銷售、一般及行政費用為 1,620 萬美元，相較於 2025 年第一季的 1,570 萬美元。此增加主要由於在我們為 avexitide 可能的商業上市做準備之際，顧問與專業服務費用上升。

We recognized $6.1 million of noncash stock-based compensation expense for the quarter compared to $6.8 million of noncash stock-based compensation expense in Q1 2025. Turning to our balance sheet. Our cash usage was slightly higher in Q1 compared to Q4 because of our Gubra milestone payments and the payment of our annual corporate bonus during the quarter.

本季我們認列 610 萬美元的非現金股份基礎給付費用，相較於 2025 年第一季的 680 萬美元。接著看資產負債表。由於本季支付了 Gubra 的里程碑款項，以及於本季支付年度公司獎金，我們第一季的現金使用量較第四季略高。

We're in the midst of a pivotal year for Amylyx with the top line data readout for LUCIDITY expected in Q3. The team will continue to focus on scaling our business with discipline, and we're actively laying the groundwork for a potential commercial launch. This focus positions us well, particularly for our work with avexitide. We continue to believe Avexitide has the potential to be a breakthrough treatment for PBH.

Amylyx 正處於關鍵的一年，LUCIDITY 的主要數據讀出預計於第 3 季公布。團隊將持續以紀律性方式專注於擴大業務規模，並正積極為可能的商業上市奠定基礎。這樣的聚焦使我們處於有利位置，特別是在 avexitide 的推進上。我們仍相信 avexitide 具有成為 PBH 突破性治療的潛力。

With that, I'll turn the call over to Josh.

接下來，我把電話會議交給 Josh。

Thanks, Jim. To close, we are focused on the execution of the LUCIDITY trial as we track toward our anticipated top line readout next quarter.

謝謝你，Jim。最後，我們正專注於 LUCIDITY 試驗的執行，並朝向預期於下季公布主要結果的目標前進。

PBH is a chronic lifelong condition with symptoms that often emerge one to three years following bariatric surgery. Many people who receive bariatric surgery are in their 40s, suggesting that if they develop PBH, they may have decades of life impacted by this condition. The broader medical community continues to recognize this critical need in PBH.

PBH 是一種慢性且終身的疾病，其症狀常在減重手術後一至三年出現。許多接受減重手術的人在 40 多歲，這表示若他們發展為 PBH，可能有數十年的生活會受到此疾病影響。更廣泛的醫療社群持續認知到 PBH 這項關鍵未被滿足的需求。

In March, Dr. Colleen Craig and her colleagues at Stanford published the first US prevalence model for PBH in surgery for obesity and related diseases, the official peer-reviewed journal of the ASMBS. And in April, CMS published their annual list of ICD-10 codes to be potentially effective October 1, 2026, which includes an ICD-10 code specific to PBH. The planned adoption of an ICD-10 code shows the growing recognition of this condition by the medical community.

3 月，史丹佛大學的 Colleen Craig 醫師及其同事在《Surgery for Obesity and Related Diseases》（ASMBS 的官方同儕審查期刊）發表了美國首個 PBH 盛行率模型。而在 4 月，CMS 公布其年度 ICD-10 代碼清單，可能於 2026 年 10 月 1 日生效，其中包含一個 PBH 專用的 ICD-10 代碼。計畫採用 PBH 的 ICD-10 代碼，顯示醫療社群對此疾病的認知正在提升。

We believe that avexitide, if approved, could play a meaningful role in addressing this highly underserved patient population. In parallel with LUCIDITY, we are actively preparing for a regulatory submission following top line results while simultaneously scaling our commercial and medical teams to support a strong commercial launch of avexitide in 2027, if approved.

我們相信，若獲核准，avexitide 可在解決這個高度未被充分服務的患者族群需求方面扮演重要角色。在推進 LUCIDITY 的同時，我們也正積極為主要結果公布後的法規申請做準備，並同步擴編商業與醫學團隊，以支持 avexitide 於 2027 年（若獲核准）強勁的商業上市。

With that, I would like to now open the call up for questions.

接下來，我想開放電話會議進入提問。

(Operator Instructions)

（接線員指示）

Seamus Fernandez, Guggenheim.

Seamus Fernandez，Guggenheim。

I hope you'll bear two for me quickly. The first question is really on the initiation of the EAP. Typically, we see companies sort of waiting for the completion of their Phase 3 and then the announcement of an EAP in the wake of a positive Phase 3. Just wanted to get a better sense of, obviously, how you were able to execute this and get it approved, and then also how you are really responding to the community with the implementation and announcement of the EAP.

希望你們能讓我快速問兩個問題。第一個問題是關於啟動 EAP。通常我們看到公司會等到第 3 期完成，並在第 3 期結果正面後才宣布 EAP。我想更了解的是，顯然你們是如何能夠執行並取得核准的，以及你們在 EAP 的落地與對外宣布上，實際上是如何回應社群需求的。

And then just a quick follow-up question. I wanted to get a sense of just sort of that relative impact that working on the NDA now could actually have from a filing perspective. Typically, when we see biotech companies with positive Phase 3 data, it will take as much as six to nine months to see that file. So just wanted to get a sense of how working on the NDA now might advance that ahead of those types of time lines.

接著是一個簡短的追問。我想了解目前就開始準備 NDA，從申報角度可能帶來的相對影響。通常我們看到生技公司在第 3 期數據正面後，可能需要 6 到 9 個月才會完成送件。所以想請教，現在就著手 NDA 的工作，可能如何讓申報時程較這類時間表提前。

Thank you very much, Seamus. This is Camille. So for the EAP, indeed, we are responding to the community where there is currently no approved therapies for PBH, and we recognize and have received several requests and demands. Importantly, we're starting the EAP now because we want to be sure there's continuity of treatment for people in the LUCIDITY study who are completing the OLED portion of the LUCIDITY trial. So that drives the timing for the EAP.

非常感謝你，Seamus。我是Camille。因此，關於EAP，確實，我們是在回應目前針對PBH尚無任何核准療法的社群需求，我們也理解並已收到多項請求與需求。重要的是，我們現在啟動EAP，是因為我們希望確保在LUCIDITY研究中、正在完成LUCIDITY試驗OLED部分的受試者，其治療能夠延續不中斷。因此，這也決定了EAP的時程。

Now with regard to your question about NDA preparation, Yes, we're sort of not typical for sure. And we are working, as noted, on NDA preparations. And we do hope that, that will allow us to be most efficient as we reach top line data next quarter. And because there is a great sense of urgency, there are no treatments for people with PBH. And if positive, we want to be sure that we're providing the opportunity for access as promptly as possible.

至於你關於NDA準備工作的問題，是的，我們的做法確實有點不太典型。而且如先前所提，我們正在進行NDA的準備工作。我們也希望這能讓我們在下個季度取得主要（top line）數據時，能以最高效率推進。由於情況非常緊迫，PBH患者目前沒有任何治療選項。如果結果為正向，我們希望確保能盡可能迅速提供取得治療的機會。

Yes. And maybe just -- maybe underscore from Camille as well. I think both of these activities both underscore too, the unmet need in PBH. We know that patients urgently need a new therapy and also our excitement about avexitide. We've had five prior trials of avexitide, all which showed very strong results.

是的。也許再補充一下——也呼應Camille的說法。我認為這兩項工作也同時凸顯了PBH領域未被滿足的醫療需求。我們知道患者迫切需要新的療法，同時我們也對avexitide感到非常振奮。我們先前已完成五項avexitide試驗，結果都非常強勁。

We have breakthrough therapy from FDA. So we want both to get patients access as quickly as possible, which, of course, is reflected with the EAP, but also, pending positive results, to be able to submit as soon as we possibly can, which is reflected by our ongoing work on the NDA.

我們已獲得FDA的突破性療法認定。因此，我們一方面希望讓患者能盡快取得治療，這當然也反映在EAP上；另一方面，在結果正向的前提下，我們也希望能在可行的最短時間內提交申請，這反映在我們目前持續進行的NDA準備工作上。

And just one more thing to add, thank you, Seamus, is we also have a very experienced team here. Our team has experience with global regulatory approval, certainly a lot of experience with FDA as well. And so that allows us to start working on the NDA documents now. Again, everything is driven by the urgent unmet need for people with PBH, but I think coupled with the strong experience we have here, both for regulatory submissions and process as well as commercialization.

另外再補充一點，謝謝你，Seamus：我們也有一支非常有經驗的團隊。我們的團隊具備全球法規核准的經驗，當然也有大量與FDA合作的經驗。因此，我們得以現在就開始著手NDA文件的準備。同樣地，一切都是由PBH患者迫切且未被滿足的需求所驅動；但我認為也要結合我們在法規申請與流程，以及商業化方面的深厚經驗。

Joseph Thome, TD Cowen.

Joseph Thome，TD Cowen。

This is Jacob on for Joe. We were wondering how the baseline for the enrolled Phase 3 population compare to the patients in the Phase 2 studies, and then what the expected placebo response in Phase 3 might be versus what we know about the patients in Phase 2 and the differences in the run-in periods.

我是Jacob，代Joe提問。我們想了解第三期已入組人群的基線特徵，與第二期研究中的患者相比如何；另外，第三期預期的安慰劑反應可能會是什麼樣子，相較於我們對第二期患者的了解，以及導入期（run-in period）差異所帶來的影響。

Sure. So the study is ongoing and blinded. And so we will not really comment on the details of this ongoing study. Having said that, we are very much looking forward to top line data next quarter where we'll share the top line data with you and hope you're sharing our excitement as well for this possibility.

好的。目前研究仍在進行且為盲態。因此，我們不會就這項進行中的研究細節做太多評論。不過，我們非常期待下個季度的主要（top line）數據，屆時會與各位分享，也希望各位能與我們一樣對這個可能性感到振奮。

With regard to the placebo, remind as well, we've had five prior highly successful trials. The Phase 2 trial showed statistical significance and clinically meaningful reductions in the composite as we presented at ENDO. In the PREVENT study, 55% reduction with a highly statistically significant value, and with -- in the Phase 2b with a 90-milligram dose, the dose in LUCIDITY, 64% reduction with a p-value of 0.0031. Those p-values do take into account all aspects of the trial, including the possibility of any placebo effect.

至於安慰劑方面，也提醒一下，我們先前已有五項非常成功的試驗。第二期試驗如我們在ENDO所呈現，顯示在複合指標上達到統計顯著且具臨床意義的下降。在PREVENT研究中，下降55%，且具高度統計顯著性；而在第二期b試驗中，使用90毫克劑量（也就是LUCIDITY的劑量），下降64%，p值為0.0031。這些p值已將試驗的各個面向納入考量，包括任何可能的安慰劑效應。

We designed LUCIDITY with the goal of replicating these prior successful trials. So -- and we powered -- we're highly powered, 90%, to detect a clinically meaningful reduction in events even under the most conservative circumstances.

我們設計LUCIDITY的目標，是重現先前成功試驗的結果。因此——而且我們的統計檢定力很高，達90%，即使在最保守的情境下，也能偵測到在事件數上具臨床意義的下降。

[Corinne] Johnson, Goldman Sachs.

[Corinne] Johnson，高盛。

This is Kevin on for Corinne. Could you just talk about the steps that you've taken beyond the event rate quota to ensure patient quality in the study for LUCIDITY and then also to ensure, sort of as much as possible, adherence to study protocols for the full 16-week treatment period?

我是Kevin，代Corinne提問。能否談談除了事件率門檻（quota）之外，你們為了確保LUCIDITY研究中的受試者品質所採取的措施；以及在完整16週治療期間，如何盡可能確保對研究方案的遵循（adherence）？

Sure. So we -- again, we're replicating as much as possible the way LUCIDITY is being conducted, mirroring what was done in the successful Phase 2 and Phase 2b studies. We have training -- extensive training at the clinical sites at the onset of the clinical trial. That training is reinforced throughout the conduct.

好的。我們——再次強調——盡可能以相同方式執行LUCIDITY，並比照先前成功的第二期與第二期b研究做法。我們在臨床試驗開始時，對各臨床中心進行訓練——而且是廣泛且深入的訓練。在試驗執行過程中，也會持續強化這些訓練。

And we also have materials for the participants to guide them on the study procedures throughout the study as well. And we also do have quality checks on the data overall to be sure that things are moving along well.

此外，我們也提供受試者相關資料，指引他們在整個研究期間遵循研究流程。我們也會對整體資料進行品質檢查，以確保各項工作進展順利。

Yes. And I'd just add too, we have a very experienced team at Amylyx and quality starts from selecting great sites, having strong oversight. And I think throughout the whole course of the study, I've been quite proud of the team's efforts, just kind of continually keeping close and making sure that quality is kind of built in from the start and continues through the whole study.

是的。我也想補充，我們Amylyx有一支非常有經驗的團隊，而品質管理從選擇優質的研究中心、以及強而有力的監督開始。我認為在整個研究期間，我對團隊的努力感到相當自豪；我們持續密切追蹤，確保品質從一開始就被納入設計，並貫穿整個研究。

Michael DiFiore, Evercore ISI.

Michael DiFiore，Evercore ISI。

Congrats on all the continued progress. First one for me is, now that LUCIDITY is fully enrolled, can you help us think through what the top line disclosure will actually look like, what it will contain, beyond whether the primary endpoint is met? What do you think will be the most important aspect of the data for people to understand, again, beyond the primary endpoint in that initial release?

恭喜你們持續取得進展。我第一個問題是，既然LUCIDITY已完成全數入組，你們能否協助我們理解主要（top line）揭露實際會是什麼樣子、會包含哪些內容，除了是否達成主要終點之外？在初次發布中，除了主要終點之外，你認為對外界理解數據最重要的面向會是什麼？

And secondly, since you're already preparing for NDA, since the last update, can you share more light on what work remains to be done between top line and potential submission, maybe in terms of QC, any additional studies, et cetera?

第二個問題是，既然你們已在準備NDA，從上次更新以來，能否再多分享一些在主要數據與可能提交之間，還有哪些工作需要完成，例如品質控管（QC）、任何額外研究等等？

Yes. Thank you, Mike. So I think first, in terms of top line disclosure, you know us well. We're a transparent company. So our goal is always to present things as they are. I think what's important in this study is probably two things to remind.

是的。謝謝你，Mike。我想先談主要（top line）揭露，你很了解我們。我們是一家透明的公司。因此，我們的目標一向是如實呈現。我認為這項研究中重要的部分，大概有兩點需要提醒。

The first is that the primary outcome, which is Level 2, Level 3 hypoglycemic events, not only is it the primary outcome, it's in FDA guidance, but it's also very well known by endocrinologists and it's inherently clinically meaningful. Level 2 events being less than 54 milligrams per deciliter blood glucose, which is the blood value at which neuroglycopenia occurs. Level 3, of course, means that the clinical manifestations of hypoglycemia have already occurred. So those are inherently clinically meaningful.

第一點是主要結果指標，也就是第2級、第3級低血糖事件；它不僅是主要結果指標，也符合FDA指引，同時也為內分泌科醫師所熟知，且本質上具有臨床意義。第2級事件指血糖低於每分升54毫克，這是發生神經性低血糖（neuroglycopenia）的血糖值。第3級當然表示低血糖的臨床表現已經發生。因此，這些本質上都具有臨床意義。

And then I think a second important point is that there are currently no treatments for PBH. And so what we have heard consistently, not just from people with PBH, but from physicians as well is that any reduction in hypoglycemic events is meaningful. Each one of these events is a medical emergency. And so what we hear from physicians often is that they are worried for their patients, and they have really very few tools to help prevent these medical emergencies. So any reduction in these hypoglycemic events is meaningful.

第二點是，目前PBH沒有任何治療。因此，我們一再聽到的不只是PBH患者，醫師也同樣表示，任何低血糖事件的降低都是有意義的。每一次這類事件都是醫療急症。因此，我們常聽到醫師說他們很擔心自己的患者，但能用來預防這些醫療急症的工具其實非常有限。所以，任何低血糖事件的降低都是有意義的。

In terms of the NDA, we're working hard on everything we can now. I think the goal would be that the last really substantial piece of work would be everything associated with the Phase 3 trial. So we're trying to write everything in advance that we can. As I said, we have a very experienced team who's been through many regulatory submissions before. So they're hard at work as we speak.

就 NDA 而言，我們目前正全力推進所有能做的工作。我認為目標是，最後一個真正重大的工作項目會是所有與第 3 期試驗相關的事項。因此，我們正嘗試把所有能事先撰寫的內容都提前完成。如我所說，我們有一支非常有經驗的團隊，過去已經歷過多次法規申報。所以他們此刻也正在全力投入。

Marc Goodman with Leerink Partners.

Leerink Partners 的 Marc Goodman。

This process of adjudicating the claims data, can you give us an example or two of just some of these efforts and just so we understand what you have done so far and how confident you are that you're finding these patients in the places that you think they are based on the claims data? And are you only counting, like, the moderate to severe ones, you're not counting the benign ones, right?

關於裁定（adjudicating）理賠資料的這個流程，你能否舉一兩個例子說明你們做了哪些工作，好讓我們理解你們目前為止做了什麼，以及你們對於根據理賠資料在你們認為的地方找到這些病患有多大信心？另外，你們只計入中度到重度的病例，沒有把良性（benign）的算進去，對吧？

Thanks, Marc. Appreciate the question. Just to talk a little bit about the claims analysis, so within the claims databases, we start with identifying patients that have a presence of bariatric surgery. And then, we look at patients who also have documented hypoglycemia, so nondiabetic hypoglycemia. And then, after that, we'll then apply and we have applied additional signs and symptoms associated with PBH such as fatigue, dizziness, seizures, even blood glucose tests or even ER visits.

謝謝你，Marc。感謝這個問題。先稍微談一下理賠分析：在理賠資料庫中，我們先從辨識曾接受減重手術（bariatric surgery）的病患開始。接著，我們會找同時有低血糖紀錄的病患，也就是非糖尿病性低血糖。然後在此之後，我們會再套用、且也已套用與 PBH 相關的其他徵象與症狀，例如疲倦、頭暈、癲癇發作，甚至血糖檢測或急診就醫（ER visits）。

And then, to add to that, we can look at it from how many of those type of events they've also had within the claims databases. So that's really how we've continued to look at the databases. I'll say we've done it several times. And each time we do it, we are confident in the 160,000 patient population that we've mentioned a few times.

此外，我們也可以從理賠資料庫中去看他們發生這類事件的次數。這就是我們持續檢視資料庫的方式。我想說的是，我們已經做過好幾次。而每次做完，我們都對我們多次提到的 16 萬名病患族群很有信心。

Yes. And I might just add, too, some added work the team has done, too, is both speaking to many of the sites and doing kind of market research with many of the sites to validate what we're finding in claims. For example, if the claims are saying a site has 50 patients, actually checking with the site and seeing if they do have 50 patients.

是的。我也補充一下，團隊還做了額外的工作，包括與許多研究中心（sites）交流，並對許多中心做一些市場調研，以驗證我們在理賠資料中看到的結果。例如，如果理賠資料顯示某個中心有 50 位病患，我們會實際向該中心確認，看看他們是否真的有 50 位病患。

And so far, those have been quite confirmatory as well. And I'll also just add from the call today, we also received notification kind of through the CMS manual list that there's likely to be an ICD-10 code for PBH going live in October, which will provide an additional tool kind of to track the claims data as well.

到目前為止，這些結果也相當具有確認性。我也再補充一點：從今天的電話會議中，我們也透過 CMS 手冊清單收到通知，PBH 很可能會有一個 ICD-10 代碼在 10 月正式啟用，這將提供另一個工具來追蹤理賠資料。

Yes. And directly to your point, too, on excluding benign, based on the coding, both on hypoglycemia, as well as the signs and symptoms, these are people who have severe hypoglycemia.

是的。也直接回應你關於排除良性病例的問題：基於低血糖的編碼，以及相關徵象與症狀的編碼，這些人都是有嚴重低血糖的患者。

Geoff Meacham, Citibank.

Citibank 的 Geoff Meacham。

I have two quick ones. So ahead of LUCIDITY top line, I know the primary outcome measure is Level 2 or 3 events as a composite. But is there a thought of looking at each one of those separately, in particular, Level 3, just to have a cleaner look at the profile from maybe a more commercial context?

我有兩個簡短問題。在 LUCIDITY 的主要結果（top line）出來之前，我知道主要結局指標是第 2 級或第 3 級事件的複合指標。但是否有考慮把兩者分開來看，特別是第 3 級，以便從可能更偏商業的角度更清楚地看其特徵？

And then, the second question. As you guys begin to focus on commercial and further evaluate the PBH prescriber base, how has your thinking evolved in terms of size and scope of sales force and MSL teams?

然後第二個問題。當你們開始聚焦商業化並進一步評估 PBH 的處方醫師基礎時，你們對於銷售團隊與 MSL 團隊的規模與範圍的想法有何演變？

Geoff, I'll take your first question and then pass to Dan for your second. So, as you say, our primary endpoint, which is FDA agreed upon, we were looking at the reduction in the composite of Level 2 and Level 3 events, and that is well established in the ADA, Diabetes Association, literature and community as well. We do intend as well -- our secondary endpoints are looking separately at Level 2, which is by fingerstick blood glucose level of less than 54 grams per deciliter, and separately Level 3.

Geoff，我先回答你的第一個問題，然後把第二個問題交給 Dan。如你所說，我們的主要終點（primary endpoint）已與 FDA 達成一致，是觀察第 2 級與第 3 級事件複合指標的降低幅度；這在 ADA（美國糖尿病學會）相關文獻與社群中也已相當成熟。我們也確實打算這麼做——我們的次要終點（secondary endpoints）會分別觀察第 2 級（以指尖採血血糖值低於 54 毫克/分升為定義），以及分別觀察第 3 級。

Which is independent of glucose level, signs and symptoms that require individuals to have another individual help or signs and symptoms that would have required someone else to help them if no one else is around. And that is adjudicated by an independent group of experienced endocrinologists who are blinded to the data as well, and they do that adjudication on an ongoing basis.

第 3 級的定義與血糖值無關，而是指需要他人協助的徵象與症狀；或是在周遭沒有人時，若有人在場本會需要他人協助的徵象與症狀。這些事件由一個獨立、具經驗的內分泌科醫師團隊進行裁定（adjudication），他們同樣對資料採盲態，並且持續進行裁定作業。

And I'll just add, too, from the sort of commercial point of view, so you're right, absolutely, Level 3 means the person has had the manifestation of hypoglycemia. And so, of course, that's important. But Level 2 being less than 54 is very well established, too. So I think endocrinologists will be interested in both. And if you think about the outcome, it's really a nice mix.

我也補充一下，從商業角度來看，你說得沒錯，第 3 級代表患者已出現低血糖的臨床表現。因此，這當然很重要。但第 2 級（低於 54）也同樣是非常成熟、被廣泛採用的定義。所以我認為內分泌科醫師會對兩者都感興趣。而且如果你從結局指標來看，這其實是一個很好的組合。

You have a blood value which indicates severe hypoglycemia, so you kind of know what's happening in the body. And then, you have a clinical outcome in Level 3, where you know the person has had the impact of severe hypoglycemia. And then, for your question on prescriber base, I'll turn it to Dan.

你有一個血液數值，顯示嚴重低血糖，因此你大致知道身體內發生了什麼。同時你也有第 3 級的臨床結局，能確認患者已受到嚴重低血糖的影響。至於你關於處方醫師基礎的問題，我把它交給 Dan。

Geoff, thanks for the commercial question. So, on the sales force sizing, we are initiating the go-to-market efforts at this moment. I would say, this is a rare endocrine launch. So from an expectation -- you can expect that the sales force would reflect this particular size of the sales force. I'd also add that on Camille's team and the medical affairs function, we have initiated hiring our regional Scientific Director team, also known as an MSL team, but those hires are in place.

Geoff，謝謝你的商業化問題。關於銷售團隊規模，我們此刻正在啟動上市（go-to-market）相關工作。我會說，這是一個罕見的內分泌領域上市案。因此就預期而言——你可以預期銷售團隊會反映這類產品上市所需的特定規模。我也補充，在 Camille 的團隊與醫藥事務（medical affairs）職能方面，我們已開始招募區域科學總監（regional Scientific Director）團隊，也就是所謂的 MSL 團隊，而這些人選已到位。

Rami Katkhuda, LifeSci Capital.

LifeSci Capital 的 Rami Katkhuda。

I guess, can you touch on the degree of natural variability there is in Level 2 and Level 3 hypoglycemic events for PBH patients? Do you expect a massive difference from one week to another? And then, secondly, from a commercial perspective, are these PBH patients generally managed at centers of excellence? Or would you need to target endocrinologists more broadly?

我想請你談談 PBH 病患在第 2 級與第 3 級低血糖事件上，自然變異（natural variability）的程度有多大？你們是否預期不同週之間會有很大的差異？另外，從商業角度來看，這些 PBH 病患通常是在卓越中心（centers of excellence）接受管理嗎？還是你們需要更廣泛地鎖定內分泌科醫師？

Sure. Maybe starting with the variability. So all of that's taken into account in our powering analysis, and I think we were quite conservative in our powering, both on the effect size and on the placebo effect, whereas we saw a 50% and 64% effect size at the 60 and 90 mg doses, we powered to a 35% effect, and then, of course, retaining power up to a 50% placebo effect, even though I don't think we expect that in this condition. You can certainly look at the variability kind of from previous studies. But again, that's all kind of accounted for in our powering analysis.

好的。也許先從變異性談起。這些都已納入我們的樣本數估算（powering analysis）考量之中；我認為我們在估算上相當保守，無論是效果量（effect size）或安慰劑效應（placebo effect）。雖然我們在 60 與 90 mg 劑量下看到 50% 與 64% 的效果量，我們在設計時是以 35% 的效果來估算，並且當然也保留在安慰劑效應高達 50% 時仍具統計力，儘管我不認為在這個適應症中會出現那樣的情況。你當然也可以從先前研究來看變異性。但再次強調，這些都已在我們的樣本數估算中加以考量。

And generally, it's a chronic condition. Generally, people are not able to prevent these events from occurring. So often, if people are having events, that will be a continuous thing. They don't kind of come in fits and starts, so to speak, all that often.

而且一般來說，這是一種慢性病況。通常，人們無法預防這些事件發生。因此，很多時候，如果人們正在發生這些事件，那會是持續性的。可以說，它們並不常以忽發忽止的方式出現。

In terms of the question of how we'll target centers of excellence versus the broader endo community, I'll pass it over to Dan.

關於我們將如何鎖定卓越中心（centers of excellence）相較於更廣泛的內分泌社群這個問題，我把問題交給 Dan。

Sure. Thanks, Josh. And I appreciate the question on the potential [indiscernible]. On the -- where the patients are potentially treated, so we have initiated that work, and we are aware, and Josh mentioned this earlier, but there are centers of excellence. There are also key opinion leaders, and that's likely where we'll start from a launch perspective.

好的。謝謝你，Josh。也感謝這個關於潛在[聽不清] 的問題。關於——病患可能在哪裡接受治療，我們已經啟動相關工作，也有所掌握；Josh 先前也提到，確實有卓越中心。另外也有關鍵意見領袖（KOL），從上市推動的角度來看，我們很可能會先從那裡開始。

We know that there's potentially 50 to 60 patients at certain centers, and some centers have even mentioned even more. But we'll start there. We know there's a concentration. And then, as our disease state education efforts take a foothold, we'll expand into the broader endocrinology community.

我們知道某些中心可能有 50 到 60 位病患，有些中心甚至提到更多。但我們會先從那裡開始。我們知道病患是集中分布的。接著，隨著我們的疾病狀態教育（disease state education）工作逐步站穩腳步，我們會擴展到更廣泛的內分泌科社群。

James Condulis, Stifel.

James Condulis，Stifel。

This is Mark on for James. One for me on Recordati. I believe we should be getting some data this quarter. And just curious your thoughts here as it relates to potential placebo effect and what the implications are for LUCIDITY and whether really this is something that can actually be sort of read through on your trial.

我是代 James 發問的 Mark。我有一題關於 Recordati。我相信我們這一季應該會拿到一些數據。想請教你們對於潛在安慰劑效應的看法，以及這對 LUCIDITY 的意涵是什麼；以及這是否真的能在你們的試驗中作為某種參照或推論。

Yes. Thank you, Mark. So I would say, no, I wouldn't think there should be any read-through. They're very different studies. And of course, we're conducting our study and Recordati is conducting their study.

是的。謝謝你，Mark。我會說，不，我不認為應該有任何可直接推論的關聯（read-through）。它們是非常不同的研究。當然，我們在進行我們的研究，而 Recordati 在進行他們的研究。

As I understand it, I think their study is a Phase 2, looking at mixed meal tolerance test. And ours is based on the prior Phase 2s, which is a much more real-world type approach, looking at Level 2, Level 3 hypoglycemic events, which, of course, is within FDA guidance, to support a potential registration. So, no, I don't think there should be any read-through between the studies.

據我了解，我想他們的研究是第二期（Phase 2），觀察混合餐耐受試驗（mixed meal tolerance test）。而我們的研究是基於先前的第二期研究，採取更貼近真實世界的方式，觀察第 2 級、第 3 級低血糖事件；這當然符合 FDA 指引，可用來支持潛在的註冊申請。所以，不，我不認為兩個研究之間應該有任何可直接推論的關聯。

Plus the mechanisms of the drugs are very different as well.

此外，藥物的作用機轉也非常不同。

Graig Suvannavejh, Mizuho.

Graig Suvannavejh，Mizuho。

This is Sam on for Graig. Maybe switching over to 0114 with the ALS data coming up shortly, can you just remind us of the specific biomarkers potential. I know there was some prior analysis done by you guys highlighting certain biomarkers. But maybe just a reminder, and then also some of the expectations you guys have or we should be thinking about going ahead into the data.

我是代 Graig 發問的 Sam。也許把話題轉到 0114，ALS 的數據很快就會出來；你們能否提醒我們具體可能會看的生物標記（biomarkers）有哪些？我知道你們之前做過一些分析，強調某些生物標記。但想請你們再提醒一下，另外也談談你們的期待，或我們在數據公布前應該如何思考。

Sure. Thanks very much. So just to remind, our ALS study with AMX0114, which is an ASO against calpain-2, is ongoing. We announced that we completed enrollment of Cohort 1 in March and that we are recruiting Cohort 2 at the moment. And earlier this year, we reported on the safety data for Cohort 1.

好的。非常感謝。先提醒一下，我們以 AMX0114（一種針對 calpain-2 的 ASO）進行的 ALS 研究仍在進行中。我們在 3 月宣布已完成第 1 隊列（Cohort 1）收案，目前正在招募第 2 隊列（Cohort 2）。而在今年稍早，我們也報告了第 1 隊列的安全性數據。

And we do anticipate, as you point out, reporting on the biomarker data. Actually, it will be this June at ENCALS in Madrid, Spain. So the biomarkers that we're studying are related to the mechanism of the calpain-2 ASO, blocking this protease, as well as biomarkers that are related also to the ALS disease process. And we look forward very much to sharing those data with you.

而且如你所說，我們確實預期會報告生物標記數據。實際上會在今年 6 月於西班牙馬德里的 ENCALS 會議上公布。我們研究的生物標記與 calpain-2 ASO 的作用機轉相關，也就是阻斷這種蛋白酶（protease）；同時也包含與 ALS 疾病進程相關的生物標記。我們非常期待與各位分享這些數據。

And just to add as well, as Camille said, the study is proceeding incredibly well. So I think as Camille was mentioning, we've completed enrollment in Cohort 2, and we're now recruiting for Cohort 3 as well.

另外補充一下，如 Camille 所說，研究進展非常順利。所以我想如 Camille 提到的，我們已完成第 2 隊列收案，現在也正在招募第 3 隊列。

Jason Gerberry, Bank of America.

Jason Gerberry，美國銀行（Bank of America）。

This is --on for Jason. Maybe just a couple of commercial questions on avexitide. I think you've mentioned before that the ICD-10 code was not necessary for successful commercialization. But just curious how ultimately having an ICD-10 code kind of alters your confidence in identifying and capturing patients at scale. I know you've outlined the centers you're targeting and what your commercial strategy is, but just curious if it impacts how you're approaching your commercial plan.

我是代 Jason 發問的。有幾個關於 avexitide 的商業化問題。我記得你們之前提過，成功商業化不一定需要 ICD-10 代碼。但想請教，最終若有 ICD-10 代碼，會如何改變你們在大規模識別並觸及病患方面的信心。我知道你們已說明鎖定的中心以及商業策略，但想了解這是否會影響你們推進商業計畫的方式。

And then, just a second quick follow-up. I believe you plan to position avexitide as a chronic therapy. I'm just curious what your -- what assumptions you're making around expectations for persistence and adherence in the real world.

然後第二個很快的追問。我相信你們計畫把 avexitide 定位為慢性治療。想請教你們對於真實世界中治療持續性（persistence）與依從性（adherence）的預期，做了哪些假設。

Great. Thanks, Tina. So, on the ICD-10 question, so in April, CMS, they published a list of ICD-10 codes to be effective October 1. These codes demonstrate a recognition of PBH in the broader medical community. The ICD-10 code, yes, it is helpful for diagnosis and tracking of patients.

好的。謝謝你，Tina。關於 ICD-10 的問題，4 月時 CMS 公布了一份 ICD-10 代碼清單，將於 10 月 1 日生效。這些代碼顯示在更廣泛的醫療社群中，PBH 已獲得認可。ICD-10 代碼確實有助於診斷與追蹤病患。

However, it's not necessarily -- it's not a necessity. ICD-10 codes are often used for epidemiology. So, in implementation of the code, this will enable patients to be tracked across the various electronic medical record systems. It's also important to note that patients, today, they still can be identified via the claims analysis, and that's how we validated the 160,000 patient population.

不過，它不一定——並非必需。ICD-10 代碼常用於流行病學（epidemiology）。因此，隨著代碼的導入，將能讓病患在各種電子病歷系統之間被追蹤。另外也要注意的是，即使在今天，病患仍可透過理賠資料（claims）分析被識別，而我們就是用這種方式驗證了 16 萬名病患族群。

And then, to your other question, too, about kind of chronic therapy and persistence, it's probably early to comment there. We're quite excited about avexitide. And PBH is a chronic condition where the needs do not go away over time. So certainly, we do think that patients will have an ongoing need for therapy.

至於你另一個問題，關於慢性治療與持續性，目前可能還太早評論。我們對 avexitide 感到非常振奮。而 PBH 是一種慢性病況，其需求不會隨時間消失。因此，我們確實認為病患會有持續的治療需求。

Chris Chen, Baird.

Chris Chen，Baird。

Congrats on the progress. Just a quick one on the OLE. Can you just remind us what the setup is specifically for that? And are you able to kind of share high level how enrollment in that is going?

恭喜進展。我有一個關於 OLE 的簡短問題。你能否提醒我們那部分的具體設計是什麼？另外，你是否能在高層次上分享一下那部分的收案進度如何？

Sure. So, are you speaking of the OLE or the EAP, just so I'm clear, please?

好的。我想確認一下，你指的是 OLE 還是 EAP？請讓我確認清楚。

The OLE for LUCIDITY, the

LUCIDITY 的 OLE，那個

Open-label extension?

開放標籤延伸？

Open-label extension, yes.

是的，開放標籤延伸。

Yes. So while I will not comment on details of our ongoing blinded trial, I am pleased to share that LUCIDITY is proceeding well, including participants transitioning from the double-blind period to the OLE portion of the study. We're confident that we're running the right study, and we're very pleased on how the team has been executing on the trial. We have such an experienced team, and they're overseeing the trial with great focus and care.

是的。雖然我不會評論我們正在進行的盲態試驗的細節，但我很高興分享 LUCIDITY 進展順利，包括受試者從雙盲期轉入研究的 OLE 部分。我們有信心正在執行正確的研究，也對團隊在試驗執行上的表現感到非常滿意。我們有一支非常有經驗的團隊，他們以高度專注與謹慎來監督這項試驗。

Yes. And you asked the OLE setup. So just to add there as well, so we expect the randomized double-blind study is the study that will -- we expect to use in our NDA to support potential commercialization. The OLE itself, though, also has a Part A and a Part B. During the Part A, we keep the study very similar to how it's conducted during the double blind.

是的。而您問到 OLE 的設計。所以也補充一下，我們預期這項隨機、雙盲研究將會——我們預期會用於我們的 NDA，以支持潛在的商業化。不過，OLE 本身也分為 A 部分與 B 部分。在 A 部分期間，我們讓研究設計與雙盲期間的執行方式非常相似。

That allows to look at kind of data in a similar way to we look at as the double blind. And then later, they enroll in the OLE B after eight weeks in the OLE, at which point, it's a little more -- there's less -- it's a less burdensome kind of trial participation at that point. But overall, just to kind of reiterate what Camille said as well, we're very pleased with the conduct of the study. There's a lot of excitement from sites and otherwise as well, and we'll look forward to reporting our data in Q3.

這使我們能以與雙盲相近的方式來檢視資料。之後，在 OLE 進行八週後，受試者會納入 OLE 的 B 部分；此時會稍微——負擔更少——在那個階段試驗參與的負擔會比較低。但整體而言，也再次呼應 Camille 所說的，我們對研究的執行非常滿意。各研究中心等也都非常振奮、充滿期待，我們也期待在第三季（Q3）公布我們的數據。

And I think it's obvious, but just to say also, for the open-label extension, I think it's very important when you work in rare debilitating conditions like post-bariatric hypoglycemia that you always try to think about the people we are trying to help. And so, for an open-label extension, if you're on treatment and you believe that you're benefiting in open-label extension, allows you to continue. And if you are randomized to placebo, then allows you to take active medication. So that's something that we always really try to think about in our programs.

我想這很明顯，但也補充說明一下，對於開放標籤延伸試驗（open-label extension），我認為在像減重手術後低血糖（post-bariatric hypoglycemia）這類罕見且致殘的疾病領域工作時，始終要把我們想要幫助的人放在心上，這非常重要。因此，在開放標籤延伸中，如果你正在接受治療且你相信自己在開放標籤延伸中受益，就能夠繼續用藥。而如果你被隨機分派到安慰劑組，則可以改為使用有效藥物。所以這是我們在各項計畫中一直努力思考的事情。

Ananda Ghosh, H.C. Wainwright.

Ananda Ghosh，H.C. Wainwright。

Maybe one question. People have been focusing on US opportunities. So one question would be, have you done work with respect to avexitide on ex-US opportunities?

也許一個問題。大家一直把焦點放在美國的機會上。所以有個問題是，你們是否已就 avexitide 在美國以外（ex-US）的機會做過相關工作？

What are you hearing from the KOLs or stakeholders? And then, I have one follow-up question on LUMINA.

你們從 KOL 或利害關係人那邊聽到什麼回饋？另外，我還有一個關於 LUMINA 的追問。

Absolutely. Thank you, Ananda. So there's a tremendous unmet need globally for post-bariatric hypoglycemia. Now, our focus is very much on the US right now with 160,000 people in the US.

當然。謝謝你，Ananda。減重手術後低血糖在全球都有極大的未被滿足醫療需求。目前我們的重點非常放在美國，因為美國有 16 萬名患者。

with PBH today. That's a substantial unmet need and people to help and address. But our -- first of all, bariatric surgeries occur globally. And also, as we mentioned before, virtually any gastric surgery has the potential to cause the same debilitating hypoglycemia.

目前有 PBH。這是相當大的未被滿足需求，也有很多人需要幫助與介入。但我們——首先，減重手術在全球各地都在進行。而且如我們先前提到，幾乎任何胃部手術都有可能造成同樣致殘的低血糖。

So, for example, in major Asian countries, gastric cancer rates, esophageal cancer rates are very high. And so, gastrectomy or esophagectomy is often indicated. And so, for people with those surgeries, they also have the potential of developing the same debilitating hypoglycemia, and we have data from the Phase 2b study of avexitide that avexitide may be beneficial for people who had those surgeries leading to this debilitating hypoglycemia as well. The pathophysiology is the same regardless of the surgical intervention. So, our focus is really on the US really on the US.

例如，在亞洲主要國家，胃癌、食道癌的發生率非常高。因此常常需要進行胃切除術或食道切除術。而接受這些手術的人，也可能發展出同樣致殘的低血糖；我們在 avexitide 的第 2b 期研究中也有數據顯示，avexitide 可能也能讓因這些手術而導致此致殘性低血糖的人受益。不論採取何種手術介入，其病理生理機制都是相同的。所以，我們的重點確實是在美國，確實是在美國。

population of post-bariatric hypoglycemia. But absolutely, there's a huge unmet need internationally. We get compassionate use requests from people around the world constantly.

減重手術後低血糖的人口。但毫無疑問，國際上也存在巨大的未被滿足需求。我們不斷收到來自世界各地的同情用藥（compassionate use）申請。

Got it. One question on LUMINA. I know there was a question on biomarkers. So given that it's the lowest dose, do we -- are we -- can we expect the preliminary NfL data or target engagement data with respect to calpain-2 levels or other downstream markers like SBDP-145 in the data readout, or that is for later...

了解。有一個關於 LUMINA 的問題。我知道之前有人問到生物標誌物。所以鑑於這是最低劑量，我們——我們是否——可以期待在數據讀出時看到初步的 NfL 數據或標的結合（target engagement）數據，例如與 calpain-2 水平相關，或其他下游標誌物如 SBDP-145，還是那要等到之後……

Yes. I mean, it's hard to know -- sorry to interrupt. It's hard to know until we have the data. I'd say, we do preclinically believe we have a potent ASO. As you look at past ASOs that have been in clinic, usually, they've been studied between the range of generally about 10 mgs to 100 mgs for CSF injection.

是的。我的意思是，很難知道——抱歉打斷一下。在我們拿到數據之前很難判斷。我會說，我們在臨床前確實相信我們有一個效力很強的 ASO。回顧過去進入臨床的 ASO，通常在腦脊髓液（CSF）注射的研究劑量範圍大致約為 10 mg 到 100 mg。

And we're at the very low end of that range. So we may see signals, but it also may require us to go to a higher dose before we start significantly moving the biomarkers.

而我們位於該範圍的非常低端。所以我們可能會看到一些訊號，但也可能需要提高劑量，才會開始顯著改變生物標誌物。

But I'll add, too, Ananda, to your point, we really are -- our goal is to have a picture of, first, are we replicating the biology that we saw in the preclinic to the clinic? Are we seeing the implications of calpain-2 knockdown? And then, are we seeing effects on biomarkers that we believe to be prognostic for ALS as well? So that is indeed the goal of the biomarkers in all of these cohorts is to try to get a picture of are we seeing the impacts of calpain-2 and are we seeing potential impacts on ALS as well?

但我也補充一下，Ananda，呼應你的觀點，我們的目標確實是——首先，建立一個整體圖像：我們是否在臨床中重現了臨床前所看到的生物學效應？我們是否看到 calpain-2 降低表達（knockdown）的影響？接著，我們是否也看到我們認為對 ALS 具有預後意義的生物標誌物出現變化？因此，所有這些隊列中生物標誌物的目標，確實就是要描繪：我們是否看到 calpain-2 的影響，以及是否也看到對 ALS 的潛在影響？

Thank you. There are no further questions at this time. I'll turn the call back to Mr. Klee.

謝謝。目前沒有其他問題。我把電話交回給 Klee 先生。

Thank you, operator, and thank you all for your time. If you have any follow-up questions, please reach out to Lindsey. And we hope you have a great rest of your day.

謝謝接線員，也謝謝各位撥冗參與。如果您有任何後續問題，請聯絡 Lindsey。也祝各位今天接下來一切順利。

Thank you, everyone.

謝謝各位。