Uniqure NV (QURE) 2025 Q3 法說會逐字稿

Good morning, and welcome to Uniqure's third-quarter 2025 earnings call. (Operator Instructions) As a reminder, this conference call is being recorded.

早安，歡迎參加Uniqure公司2025年第三季財報電話會議。 （操作說明）提醒您，本次電話會議正在錄音。

I would now like to turn the call over to Chiara Russo, Senior Director of Investor Relations. Thank you. Please go ahead.

現在我將把電話交給投資者關係高級總監基亞拉·魯索女士。謝謝。請開始。

Good morning, and thank you for joining us for Uniqure's third-quarter of 2025 earnings call. Earlier this morning, Uniqure released its financial results for the third-quarter of 2025, and our press release is available on the Investors & Media section of our website at uniqure.com. Our 10-Q was also filed with the SEC earlier today.

早安，感謝您參加Uniqure 2025年第三季財報電話會議。今天早些時候，Uniqure發布了2025年第三季財務業績，您可以在我們網站uniqure.com的「投資者與媒體」版塊查看新聞稿。我們的10-Q報告也於今天稍早提交給了美國證券交易委員會（SEC）。

Joining me on the call this morning are Matt Kapusta, Chief Executive Officer; Dr. Walid Abi-Saab, Chief Medical Officer; Kylie O'Keefe, Chief Customer and Strategy Officer; and Christian Klemt, Chief Financial Officer. After our formal remarks, we'll open the call up for Q&A.

今天早上與我一同參加電話會議的有：首席執行官馬特·卡普斯塔 (Matt Kapusta)；首席醫療官瓦利德·阿比-薩博 (Walid Abi-Saab) 博士；首席客戶與戰略官凱莉·奧基夫 (Kylie O'Keefe)；以及首席財務官克里斯蒂安·克萊姆特 (Christian Klemt)。正式致詞結束後，我們將進入問答環節。

Before we begin, please note that we will be making forward-looking statements during this investor call. All statements other than statements of historical fact are forward-looking statements. They are based on management's beliefs and assumptions and information available to management only as of the date of this conference call.

在會議開始之前，請注意，本次投資者電話會議中我們將做出一些前瞻性陳述。除歷史事實陳述外，所有其他陳述均為前瞻性陳述。這些陳述是基於管理階層截至本次電話會議當天的信念、假設以及管理階層可取得的資訊。

Our actual results could differ materially from those anticipated in these forward-looking statements for many reasons, including, without limitation, the factors described in Uniqure's most recent SEC filings. Given these risks, you should not place undue reliance on these forward-looking statements, and we assume no obligation to update these statements even if new information becomes available in the future.

由於許多原因，包括但不限於Uniqure最近向美國證券交易委員會（SEC）提交的文件中所述的因素，我們的實際業績可能與這些前瞻性聲明中預期的業績存在重大差異。鑑於這些風險，您不應過分依賴這些前瞻性聲明，即使未來出現新的信息，我們也不承擔更新這些聲明的義務。

Now let me introduce Matt Kapusta, Uniqure's CEO.

現在讓我來介紹一下 Uniqure 的執行長 Matt Kapusta。

Thanks, Chiara, and good morning, everyone. Thank you for joining today's third-quarter conference call. As you know, in the third-quarter, we announced positive top line data from our pivotal Phase I/II study of AMT-130 in Huntington's disease, the first gene therapy to demonstrate statistically significant slowing of disease progression in Huntington's disease. These groundbreaking results represent an important milestone not only for Uniqure, but also for patients and families who have long awaited a potential disease-modifying therapy.

謝謝Chiara，大家早安。感謝各位參加今天的第三季電話會議。如各位所知，在第三季度，我們公佈了AMT-130治療亨丁頓舞蹈症的關鍵性I/II期研究的積極頂線數據。 AMT-130是第一個在亨丁頓舞蹈症治療中顯示出統計學意義上顯著延緩疾病進展的基因療法。這些突破性成果不僅對Uniqure公司而言是一個重要的里程碑，對長期以來一直期盼這種潛在疾病修飾療法的患者及其家人來說也是如此。

As previously disclosed, we met with the FDA in late October to review our data and discuss the potential submission of a BLA for AMT-130. Based on discussions at the meeting, we believe the FDA currently no longer agrees that the data from the Phase I/II studies of AMT-130 in comparison to an external control may be adequate to provide primary evidence in support of a BLA submission.

如先前披露，我們於10月下旬與FDA會面，審查了我們的數據並討論了AMT-130生物製品許可申請（BLA）的潛在提交事宜。根據會議討論，我們認為FDA目前不再認為AMT-130 I/II期研究與外部對照相比的數據足以提供支持BLA申請的主要證據。

Consequently, the timing of a BLA submission for AMT-130 is now uncertain. This feedback represents a notable shift from prior communications with the FDA during multiple Type B meetings over the past year. We plan to urgently engage with the FDA to discuss next steps, and we expect to receive the formal meeting minutes within the next 30 days.

因此，AMT-130的生物製品許可申請（BLA）提交時間目前尚不確定。這項回饋與過去一年FDA多次B類會議期間的溝通情況截然不同。我們計劃盡快與FDA接洽，討論後續步驟，並預計在未來30天內收到正式會議紀要。

While the latest FDA feedback is certainly surprising and disappointing, we continue to strongly believe that AMT-130 has the potential to provide significant benefit to patients. We believe the data presented to date, widely recognized as the most compelling ever generated in Huntington's disease, provides substantial evidence of therapeutic effect. Every year, thousands of Americans die because of Huntington's disease and thousands more newly diagnosed. We believe AMT-130 has the potential to significantly slow disease progression and exemplifies the type of transformative innovation in rare diseases the FDA has pledged to support.

儘管FDA的最新回饋令人意外和失望，但我們仍然堅信AMT-130具有為患者帶來顯著益處的潛力。我們認為，迄今為止公佈的數據（被廣泛認為是亨廷頓舞蹈症領域迄今為止最令人信服的數據）提供了強有力的治療效果證據。每年，數千名美國人死於亨廷頓氏症，另有數千人被新確診。我們相信AMT-130有潛力顯著延緩疾病進展，並體現了FDA承諾支持的罕見疾病領域變革性創新。

We remain fully committed to our partners, investigators and, most importantly, to Huntington's patients and their families and to working collaboratively with the FDA to bring this therapy to Huntington's patients in the US as rapidly as possible. We will continue to act with urgency, transparency, and discipline as we work to deliver on the promise of gene therapy to transform lives.

我們始終堅定地致力於服務我們的合作夥伴、研究人員，以及最重要的，亨廷頓病患者及其家屬，並與美國食品藥品監督管理局（FDA）密切合作，盡快將這種療法帶給美國的亨廷頓病患者。我們將繼續以緊迫感、透明度和嚴謹的態度行事，努力實現基因療法改變生命的承諾。

I will now turn the call over to Walid.

現在我將把通話轉給瓦利德。

Thank you, Matt. Good morning and good afternoon, everyone. I would like to start by reiterating that the recent feedback from discussions at our pre-BLA meeting does not change our belief in the data. We continue to believe that the AMT-130 represents the most compelling therapeutic data set generated in Huntington's disease to date.

謝謝馬特。大家早安，下午好。首先我想重申，我們在生物製品許可申請（BLA）前會議上討論的近期回饋並不會改變我們對數據的信心。我們仍然認為，AMT-130代表了迄今為止在亨廷頓氏症治療領域最令人信服的治療數據。

The two highlights of the third-quarter was the positive top line data from our pivotal Phase I/II studies of AMT-130 in Huntington's disease. Before I go on, I want to thank our employees, investigators, partners and especially the patients and families who have been participating in the [ CACI ] natural history studies and our clinical studies. It is thanks to their deep commitment and efforts that we have been able to achieve such progress.

第三季的兩大亮點是我們在亨丁頓舞蹈症關鍵性I/II期臨床試驗中AMT-130所取得的正面初步數據。在此之前，我要感謝我們的員工、研究人員、合作夥伴，特別要感謝參與[CACI]自然史研究和我們臨床研究的病人及其家屬。正是由於他們的深切投入和不懈努力，我們才能如此進展。

In September, we reported top line data that the high dose of AMT-130 demonstrated a statistically significant 75% slowing of disease progression as measured by the composite unified Huntington's disease rating scale, or cUHDRS in the three years compared to a propensity score matched external control derived from the enrolled HD natural data set, meeting the pivotal study's prespecified primary endpoint.

9 月，我們公佈了初步數據，高劑量 AMT-130 在三年內，透過綜合統一亨廷頓病評定量表 (cUHDRS) 測量，在疾病進展方面表現出統計學意義上的顯著減緩 75%，與從入組的 HD 自然數據集得出的傾向評分匹配的外部對照相比，達到了關鍵研究預先設定的主要終點。

Equally important, patients treated with high-dose AMT-130 demonstrated a statistically significant 60% slowing of disease progression at three years as measured by the total functional capacity, a key secondary endpoint. Moreover, cerebrospinal fluid neurofilament light chain, a well-characterized and supported biomarker measuring neurodegeneration, was below baseline at 36 months in patients treated with high-dose AMT-130. The top line data from the high dose were supported by consistent results and multiple sensitivity analyses demonstrating the robustness of these findings.

同樣重要的是，接受高劑量 AMT-130 治療的患者在三年時，以總功能能力（關鍵的次要終點）衡量，疾病進展速度顯著減緩了 60%。此外，腦脊髓液神經絲輕鏈（一種特徵明確且有充分證據支持的神經退化性生物標記）在接受高劑量 AMT-130 治療的患者中，36 個月時低於基線水平。高劑量組的初步數據得到了其他研究結果的一致支持，多項敏感性分析也證實了這些發現的穩健性。

We believe these results provide the first clinical evidence of gene therapy and potentially alter the course of Huntington's disease. In keeping with the spirit of full transparency for the scientific and medical communities, we are working diligently on a comprehensive publication strategy, started with publishing our full data results in a well-respected peer-reviewed medical journals.

我們相信這些結果首次提供了基因療法的臨床證據，並有可能改變亨丁頓舞蹈症的病程。秉持著對科學界和醫學界完全透明的原則，我們正在積極制定全面的發表策略，首先是在一家備受尊敬的同行評審醫學期刊上發表我們完整的數據結果。

As Matt noted earlier, we met with the FDA for a PBLA meeting in October. And based on discussions of the meeting, we believe that the FDA currently no longer agrees that data from the Phase I/II studies of AMT-130, in comparison to an external control, may be adequate to provide primary evidence in support of a BLA submission. This feedback was unexpected. We believe AMT-130 has the potential to significantly slow disease progression. We plan to urgently interact with the FDA and are fully committed to working with the agency to find an expeditious path forward.

正如Matt之前提到的，我們在10月份與FDA舉行了PBLA會議。根據會議討論，我們認為FDA目前不再認為AMT-130的I/II期研究數據（與外部對照相比）足以作為支持BLA申請的主要證據。這項回饋出乎我們的意料。我們相信AMT-130具有顯著延緩疾病進展的潛力。我們計劃盡快與FDA溝通，並全力配合FDA尋求快速推進的途徑。

Turning now to AMT-260 for mesial temporal lobe epilepsy. In May, we announced initial data from the first treated patients with five months of follow-up. At that time, we observed promising reduction in seizure frequency over the first five months of follow-up, with no serious adverse events. This data generated enthusiasm among investigators and potential patients. We have now activated 17 recruiting sites in the United States and completed enrollment of the first three patients in the first cohort.

現在我們來談談用於治療內側顳葉癲癇的AMT-260。今年5月，我們公佈了首批接受治療的患者在五個月追蹤後的初步數據。當時，我們觀察到在前五個月的追蹤期間，癲癇發作頻率顯著降低，且未出現嚴重不良事件。這些數據激發了研究人員和潛在患者的積極性。目前，我們已在美國啟動了17個招募中心，並完成了首批三名患者的入組。

Following a favorable review by the independent data monitoring committee, recruitment has now expanded into mesial temporal lobe epilepsy in the dominant hemisphere and the initiation of a second cohort at a higher dose for the protocol. We expect to provide updated data from the study in the first half of 2026.

在獨立數據監測委員會的積極審查之後，目前已將招募範圍擴大至優勢半球內側顳葉癲癇患者，並啟動了第二組更高劑量方案的受試者。我們預計將於2026年上半年提供研究的最新數據。

Moving to Fabry disease. In September, we also reported encouraging results from the ongoing Phase I/IIa trial of AMT-191, which were presented at the International Congress of inborn errors of metabolism in Kyoto. Across the four patients treated in the first cohort, we observed supraphysiological alpha-Gal A expression enzyme activity, lower patients successfully withdrawn from enzyme replacement therapy, while maintaining stable plasma lyso-Gb3 levels through the July 24, 2025, data cutoff date.

接下來談談法布瑞氏症。 9 月，我們還報告了正在進行的 AMT-191 I/IIa 期臨床試驗的令人鼓舞的結果，這些結果已在京都舉行的國際先天性代謝缺陷大會上公佈。在首批接受治療的四名患者中，我們觀察到 α-半乳糖苷酶 A 表達酶活性超生理水平，成功退出酶替代療法的患者人數減少，同時截至 2025 年 7 月 24 日數據截止日期，血漿溶酶體 Gb3 水平保持穩定。

These results, together with a manageable safety and tolerability profile, reinforce the potential of AMT-191 to be a onetime dose gene therapy for Fabry disease. Enrollment in the second lower-dose cohort has been completed, with a third cohort currently enrolling. We expect to (technical difficulty) updated data in the first half of 2026. I will now touch on some additional pipeline updates.

這些結果，加上其可控的安全性和耐受性，進一步證實了AMT-191作為法布瑞氏症單次給藥基因療法的潛力。第二組低劑量組的受試者招募工作已完成，第三組正在招募中。我們預計（由於技術原因）將於2026年上半年更新數據。接下來，我將介紹一些其他研發管線進展。

We have voluntarily paused enrollment in the Phase I/II EPISOD1 trial of AMT-162 for SOD1 ALS based on the recommendation of the independent data monitoring committee following a September 2025 review of the preliminary data related to the safety and efficacy of AMT-162 in the context of a dose-limiting toxicity that was observed in one patient in the second cohort. This event resulted in a serious adverse event determined to be related to AMT-162. At this time, we will continue to collect and evaluate data from the patients treated with AMT-162.

根據獨立資料監察委員會在2025年9月對AMT-162治療SOD1 ALS的安全性和有效性初步數據進行審查後提出的建議，我們已主動暫停AMT-162治療SOD1 ALS的I/II期EPISOD1試驗的患者招募。審查的原因是，在第二組患者中觀察到一例劑量限制性毒性。該事件導致一例嚴重不良事件，判定與AMT-162相關。目前，我們將繼續收集和評估接受AMT-162治療的患者的數據。

To summarize, the third-quarter marked a milestone for AMT-130 with a positive top line data from our pivotal Phase I/II studies. The recent feedback from the FDA has introduced uncertainty into the path forward, but we believe in our data and we are focused on working with the agency to define the next steps.

總而言之，第三季對於AMT-130而言是一個里程碑，我們關鍵的I/II期臨床試驗取得了正面的初步數據。儘管FDA近期的回饋為未來的發展帶來了不確定性，但我們對我們的數據充滿信心，並將專注於與FDA合作，共同製定下一步計畫。

Now I will turn the call over to Kylie to discuss our recent patient advocacy work. Kylie?

現在我將把電話交給凱莉，讓她來談談我們最近在病人權益倡議方面的工作。凱莉？

Thank you, Walid. As both Matt and Walid have said, our commitment to the HD community remains unwavering. Following our September data announcement, we experienced a groundswell of hope and support from patients, patient advocacy groups, clinicians, and scientists alike. We understand and deeply appreciate the concern and disappointment expressed by the community following our announcement last week regarding the pre-BLA meeting with the FDA. We are reminded, however, that every step of this journey, including moments like this, reflect the seriousness of our mission and the importance of getting this right for HD patients.

謝謝瓦利德。正如馬特和瓦利德所說，我們對亨廷頓病患者群體的承諾始終堅定不移。繼九月公佈數據後，我們收到了來自患者、患者權益組織、臨床醫生和科學家的熱烈支持和鼓勵。我們理解並深切體會到，上週我們宣布與FDA舉行生物製品許可申請（BLA）前會議後，患者群體所表達的擔憂和失望。然而，我們始終銘記，這段旅程中的每一步，包括此刻的困境，都體現了我們使命的嚴肅性，以及為亨廷頓病患者做好一切準備的重要性。

During this period, commercial and medical teams continue to thoughtfully plan and execute with discipline and focus. Our primary focus continues to be on stakeholder engagement and education, including treatment centers of excellence, payers, and patient advocacy, to best position us to be fully prepared for a strong and informed potential launch of AMT-130. Concurrently, as we have a focus on building the foundational strategy for the US market for a potential launch of AMT-130, we are also looking to additional potential markets outside of the US, such as the EU and the UK

在此期間，商業和醫療團隊將繼續以嚴謹的態度和專注的精神，周密地進行規劃和執行。我們的首要任務仍然是與利益相關者進行溝通和教育，包括與卓越治療中心、支付方和患者權益倡導組織合作，以便為AMT-130的潛在上市做好充分準備。同時，在著力建構AMT-130在美國市場潛在上市的基礎策略的同時，我們也正在關注美國以外的其他潛在市場，例如歐盟和英國。

The feedback we are receiving from the physician and patient community reinforces both the high level of unmet need and the enthusiasm for the potential of AMT-130. Their support continues to motivate our team, and we remain committed to maintaining open communication and collaborating with the community as we plan next steps. We believe deeply in our science, the data we have generated to date and the impact this therapy could have for HD patients.

我們從醫師和病患群體收到的回饋，既印證了目前亟待滿足的巨大需求，也展現了他們對AMT-130潛在療效的極大熱情。他們的支持持續激勵我們的團隊，我們將繼續致力於與業界保持開放的溝通與合作，共同規劃下一步。我們對我們的科學研究、迄今為止所獲得的數據以及該療法可能為亨廷頓氏症患者帶來的益處充滿信心。

Now I will turn the call over to Christian for a financial update. Christian?

現在我將把電話轉給克里斯蒂安，請他報告財務狀況。克里斯蒂安？

Thank you, Kylie. I'll now be sharing financial highlights of the third-quarter of 2025. Please refer to the earnings press release issued this morning and our quarterly filing with the SEC for additional detail.

謝謝凱莉。接下來我將分享2025年第三季的財務亮點。更多詳情請參閱今天早上發布的盈利新聞稿以及我們向美國證券交易委員會提交的季度報告。

Revenue for the three months ended September 30, 2025, was $3.7 million, compared to $2.3 million in the same period in 2024. The increase of $1.4 million in revenue results from a $1.5 million increase in license revenues and a decrease of $0.1 million in collaboration revenues.

截至 2025 年 9 月 30 日的三個月，營收為 370 萬美元，而 2024 年同期為 230 萬美元。收入增加 140 萬美元，其中授權收入增加 150 萬美元，合作收入減少 10 萬美元。

Cost of contract manufacturing revenues were nil for the three months ended September 30, 2025, compared to $0.8 million for the same period in 2024. Following the divestment of the Lexington facility in July 2024, cost of contract manufacturing revenues are recorded net of revenue within other expenses.

截至 2025 年 9 月 30 日止的三個月，合約製造收入成本為零，而 2024 年同期為 80 萬美元。在 2024 年 7 月剝離萊剋星頓工廠後，合約製造收入成本已扣除收入併計入其他費用。

Research and development expenses were $34.4 million for the three months ended September 30, 2025, compared to $30.6 million during the same period in 2024. The $3.8 million increase was driven by an increase of $10.1 million in direct research and development expenses, of which $6.6 million related to the preparation for the BLA submission of AMT-130, offset by a decrease of $3.4 million in severance costs and a $3 million decrease in costs related to disposables, facilities and other expenses.

截至 2025 年 9 月 30 日的三個月內，研發費用為 3,440 萬美元，而 2024 年同期為 3,060 萬美元。增加的 380 萬美元主要來自直接研發費用的增加 1010 萬美元，其中 660 萬美元與 AMT-130 的生物製品許可申請 (BLA) 的準備工作有關；但同時也被遣散費減少 340 萬美元以及與耗材、設施和其他費用相關的成本減少 300 萬美元所抵消。

Selling, general and administrative expenses were $19.4 million for the three months ended September 30, 2025, compared to $11.6 million during the same period in 2024. The $7.8 million increase was primarily related to a $2.4 million increase in employee related expenses and a $4.9 million increase in professional fees, including $3 million incurred to support the preparation of a potential commercialization of AMT-130 in the United States.

截至 2025 年 9 月 30 日止三個月，銷售、一般及行政費用為 1,940 萬美元，而 2024 年同期為 1,160 萬美元。增加的 780 萬美元主要與員工相關費用增加 240 萬美元和專業費用增加 490 萬美元有關，其中包括為支持 AMT-130 在美國潛在商業化而產生的 300 萬美元費用。

Cash, cash equivalents and investment securities totaled $649.2 million as of September 30, 2025, compared to $376.5 million as of December 31, 2024. The increase is primarily related to the net proceeds of $404.2 million from our public offerings this year. With this strong balance sheet, we believe Uniqure is well positioned to execute its clinical and operational priorities. We expect cash, cash equivalents and investment securities will be sufficient to fund operations into 2029.

截至2025年9月30日，現金、現金等價物及投資證券總額為6.492億美元，截至2024年12月31日為3.765億美元。成長主要源自於今年首次公開募股所得淨收益4.042億美元。憑藉如此強勁的資產負債表，我們相信Uniqure能夠更好地執行其臨床和營運重點項目。我們預期現金、現金等價物及投資證券足以支持公司營運至2029年。

I'll now turn the floor back over to Matt.

現在我把發言權交還給馬特。

Thank you, Christian. As you've heard today, the third-quarter of 2025 was a pivotal one for Uniqure, and we continue to have strong conviction in both the compelling data set and therapeutic potential for AMT-130. Our focus now is on working with the FDA to clarify next steps and determine the most expeditious path to bring AMT-130 to patients in the US.

謝謝克里斯蒂安。正如您今天所聽到的，2025年第三季對Uniqure公司來說至關重要，我們仍然對AMT-130的強大數據和治療潛力充滿信心。我們現在的重點是與FDA合作，明確後續步驟，並確定將AMT-130盡快帶給美國患者的最快路徑。

In parallel, we will plan to advance discussions with other regulatory agencies, including those in the European Union and the United Kingdom. As we move forward, we do so with confidence in our science, clarity and our mission and a deep determination to make a meaningful difference for patients and families affected by Huntington's disease.

同時，我們將計劃推動與其他監管機構的磋商，包括歐盟和英國的監管機構。我們滿懷信心地推進各項工作，對我們的科學、清晰的願景和使命充滿信心，並堅定決心為亨廷頓舞蹈症患者及其家庭帶來實際改變。

Before we open up for questions, I'd like to note that because we have not yet received the final meeting minutes from our pre-BLA meeting with the FDA, and out of respect for the agency and our shared goal of advancing AMT-130 for patients with Huntington's disease, we will strictly limit our responses about that meeting to the information disclosed in our November 3, 2025 press release. We appreciate your understanding and are happy to address other questions you may have.

在正式開始提問環節之前，我想說明一點：由於我們尚未收到與FDA就生物製品許可申請（BLA）召開的會議的最終會議紀要，並且出於對FDA的尊重以及我們共同推進AMT-130用於治療亨廷頓病患者的目標，我們將嚴格限制對該會議的回應，僅限於我們在2025年11月3日中披露的信息。感謝您的理解，我們很樂意回答您可能提出的其他問題。

Operator, please go ahead and open the call.

接線員，請接通電話。

(Operator Instructions)

（操作說明）

Joe Schwartz, Leerink Partners.

Joe Schwartz，Leerink Partners。

So the treatment effect you've reported out to three years is quite large. So I'm wondering, to what extent have you stress tested the results in order to see what a very conservative rendition of the results would look like? For example, could you remind us how you constructed the external control arm to consider whether there were any potential sources of bias?

您報告的三年追蹤治療效果相當顯著。我想知道，您在多大程度上對這些結果進行了壓力測試，以了解非常保守的結果會是什麼樣子？例如，您能否回顧一下您是如何建立外部對照組的，以考慮是否存在任何潛在的偏差來源？

Thanks, Joe. Walid, do you want to answer that one?

謝謝你，喬。瓦利德，你想回答這個問題嗎？

Guys, can you hear me? You can. I'm sorry. I wasn't sure if I'm muted or not.

各位，你們聽得到我說話嗎？能聽到。抱歉，我不確定自己有沒有靜音。

Yes, we can.

是的，我們可以。

Yes. Thank you. All right. Thanks for the question. So actually, what we have done is essentially follow a rigorous way to do the propensity score matching with enrolled HD. I think enrolled HD lends itself to provide a fairly robust data because of the size of it. You get very good matches.

是的，謝謝。好的，謝謝你的提問。實際上，我們所做的基本上是採用嚴謹的方法，利用已登記的HD患者進行傾向評分配對。我認為，由於HD患者樣本量龐大，因此能夠提供相當可靠的數據。這樣可以得到非常好的配對結果。

And what we have done in discussion with the FDA prepared a series of sensitivity testing evaluating propensity score matching, using different types of matching, the propensity score weighting. We've also looked at a smaller number of variables, which was part of an SAP that we have proposed much earlier in the process during the RMAT application.

在我們與FDA討論後，準備了一系列敏感性測試，評估傾向評分匹配，包括使用不同類型的匹配方法和傾向評分加權。我們也研究了較少數量的變量，這是我們在RMAT申請早期階段提出的SAP的一部分。

We looked at regional differences. We looked at comorbidities based on medication and so on and so forth. And last but not least, we compared to a track and predict, a statistical analysis, again, as part of the pre-agreed types of sensitivity analyses with the agency. And across a variety of these analyses, the results were very consistent, demonstrating the robustness of these findings. And that's why we have really strong confidence in the results that we've seen.

我們考察了區域差異，研究了基於藥物的合併症等等。最後，我們也進行了追蹤預測和統計分析，這也是我們與相關機構預先商定的敏感度分析項目之一。在各種分析中，結果都非常一致，證明了這些發現的穩健性。正因如此，我們對目前的結果充滿信心。

But regardless, if you also look at the numerical change from baseline in our patient population and compare it to a number of data that's being published by a number of studies that are on in that space and comparable patients, you see that the magnitude of the change from baseline at three years is very small compared to one we'd expect in placebo treated subjects.

但無論如何，如果你也看一下我們患者群體與基線相比的數值變化，並將其與該領域許多研究發表的類似患者的數據進行比較，你會發現，三年時與基線相比的變化幅度非常小，與我們預期在安慰劑治療的受試者中觀察到的變化幅度相比。

Uy Ear, Mizuho.

Uy Ear，瑞穗。

Maybe just help us understand a little bit about what happened in AMT-162. Could you kind of remind us what -- whether it's -- what the [vectors] was and whether it was similar to the other pipeline studies? And along with that, what was the dose difference between the first cohort and the second cohort?

或許您可以幫我們稍微了解一下AMT-162試驗的狀況。您能否提醒我們一下，它使用的載體是什麼？它是否與其他在研項目類似？另外，第一批和第二批受試者的劑量差異是多少？

Yes. Thanks for the question. We haven't quite disclosed all of the data about the dose so far. But with this product, we have seen previously in a compassionate use that was the case of dorsal root ganglion toxicity. It's a known adverse event, particularly for this route of administration.

是的，謝謝您的提問。目前我們還沒有完全公開劑量方面的數據。但就該產品而言，我們先前在同情用藥案例中觀察到過背根神經節毒性。這是一種已知的不良反應，尤其是在這種給藥途徑下。

And we knew and we were monitoring very carefully with this. Unfortunately, we've seen that at the middle dose, which I can tell you is about threefold higher than the low dose. And as a result, we backed down. But now we're monitoring the data and to see over time how this will evolve. And we will have a discussion with the experts and the IDMC to determine the next steps for this program. We should be able to come back in the first half of next year with some answers on this.

我們對此有所了解，並一直在密切監測。不幸的是，我們發現中等劑量組（我可以告訴你們，其風險大約是低劑量組的三倍）的風險較高。因此，我們不得不降低劑量。但現在我們正在監測數據，觀察其隨時間推移的發展。我們將與專家和獨立數據監測委員會 (IDMC) 進行討論，以確定該計畫的下一步措施。我們應該能夠在明年上半年就此問題給出一些答案。

And just to be clear, Uy, this is totally different capsid than what we use in our other programs and a different mode of administration.

Uy，需要說明的是，這與我們在其他項目中使用的衣殼完全不同，而且給藥方式也不同。

Salveen Richter, Goldman Sachs.

薩爾文·里克特，高盛。

This is Lydia on for Salveen. Could you just talk to what details you hope to learn from the final meeting minutes here in the next 30 days?

這裡是莉迪亞，代表薩爾文。請問您希望在接下來的30天內從最終會議紀錄中了解到哪些細節？

Yes. I think what I would say is we don't want to speculate on what will be in the minutes. We assume that they'll reflect mostly the conversation that we had in Washington, D.C. But most importantly, we hope it will give a sense of the concerns that the FDA has and give us an outline for how to address those concerns in a subsequent meeting with the FDA.

是的。我想說的是，我們不想對會議紀要的內容妄加猜測。我們預計紀要主要反映我們在華盛頓特區進行的討論。但最重要的是，我們希望紀要能展現FDA的擔憂，並為我們在與FDA的後續會議上如何解決這些擔憂提供想法。

Joseph Thome, TD Cowen.

Joseph Thome，TD Cowen。

I guess are you able to kind of confirm that prior meeting minute documents did confirm the ability to file for accelerated approval based on the cUHDRS maybe like the meeting minutes from the RMAT meeting at the end of 2024? Was that officially documented in what they send to you? And maybe how much detail do they go into in these meeting minute documents around the definition of the statistical analysis plan and the external comparator?

我想請您確認一下，先前的會議紀錄文件是否確認了可以根據cUHDRS申請加速審批，例如2024年底RMAT會議的紀要？他們寄給您的文件裡有正式紀錄嗎？另外，這些會議紀要文件對統計分析計畫和外部對照的定義有多詳細？

Yes. So I can confirm that in our November 2024 multidisciplinary meeting with the FDA and the written comments that we received, the FDA stated that the data from the Phase I/II study in comparison to an external control may serve as the primary basis of a BLA submission. They also confirmed that the composite UHDRS would be considered an acceptable intermediate clinical endpoint to support accelerated approval.

是的。我可以確認，在2024年11月我們與FDA的多學科會議以及我們收到的書面意見中，FDA表示，I/II期研究與外部對照試驗的數據可以作為生物製品許可申請（BLA）的主要依據。他們也確認，綜合UHDRS評分將被視為可接受的中期臨床終點，以支持加速審批。

In that particular meeting, they didn't get into specifics on the statistical analysis plan, but had recommended that we prespecify stats plan, and that was discussed in detail as well as the natural history protocol in our April 2025 meeting with the FDA.

在那次會議上，他們沒有具體討論統計分析計劃，但建議我們預先制定統計計劃，我們在 2025 年 4 月與 FDA 的會議上詳細討論了該計劃以及自然史方案。

Luca Issi, RBC Capital Markets.

伊西 (Luca Issi)，加拿大皇家銀行資本市場部。

Great. Maybe, Matt, again, I appreciate the situation is still fluid here, but can you just talk about what needs to happen from here over the next few weeks in order for you to continue to invest capital in Huntington? I guess what I'm trying to ask here is, where do you draw the line between continuing to fight this versus just give up? Like any color there, much appreciated.

好的。馬特，我知道目前情況還在變化，但你能否談談接下來幾週需要做些什麼，才能讓你繼續在亨廷頓投資？我想問的是，你如何界定繼續抗爭和徹底放棄之間的界線？非常感謝你的任何意見。

Yes. I wouldn't characterize this as a fight. I think that we are 100% committed to continuing to collaborate and partner with the FDA to determine an expedited path to submit a BLA. I think we strongly believe that AMT-130 can meaningfully benefit patients. I think -- we feel that we have what is considered to be the most compelling data set in the field of Huntington's with three years of clinical outcomes data showing a meaningful slowing of disease progression. And we think that if there are concerns or issues, that they ought to be addressed in a proper review.

是的。我不會把這描述成一場鬥爭。我認為我們百分之百致力於繼續與FDA合作，共同尋找加快提交生物製品許可申請（BLA）的途徑。我們堅信AMT-130能夠顯著造福患者。我們認為，我們擁有目前亨廷頓舞蹈症領域最令人信服的數據集，三年的臨床結果數據顯示，AMT-130能夠顯著延緩疾病進展。我們認為，如果有任何疑慮或問題，都應該在正式的審查過程中解決。

And so we will continue to work with the FDA to address any concerns they have with the hope of having an expeditious submission of a BLA in the near future. That is the pathway that we're going to be focused on. And we are committed -- we believe we have a drug that works. We have a patient group that has an urgent need. And we're committed to doing everything we can to bring this to them as quickly as possible.

因此，我們將繼續與FDA合作，解決他們提出的任何疑慮，希望能在不久的將來盡快提交生物製品許可申請（BLA）。這是我們將重點關注的途徑。我們堅信我們擁有有效的藥物，並且有患者群體迫切需要這種藥物。我們將竭盡所能，盡快將這種藥物帶給他們。

Yanan Zhu, Wells Fargo.

朱亞楠，富國銀行。

Great. Just first, a quick clarification. For the ALS program, is it intrathecal delivery? And if so, is the AE, the dorsal root ganglion AE previously known to this route? Then maybe just on the Huntington's program, just wondering, can you characterize how motivated or mobilized the patient and doctor community is on this issue and how that could help move the issue along?

好的。首先，請您快速澄清一下。對於ALS項目，是鞘內給藥嗎？如果是的話，背根神經節AE（一種標靶藥物）之前是否已知可透過此途徑給藥？另外，關於亨廷頓舞蹈症項目，您能否描述一下患者和醫生群體對此事的積極性和參與度，以及這如何能推動問題的解決？

Okay. Walid, do you want to answer the first one, and then I'll kick it to Kylie to do the second?

好的。瓦利德，你想先回答第一個問題嗎？然後我把第二個問題交給凱莉回答。

Thanks, Matt. On the first question, the answer is yes to both. So intrathecal delivery. And it's dorsal root ganglion toxicity, which, again, as I said, unfortunately, is associated with this mode of administration, and we knew this was a risk. So yes.

謝謝，馬特。關於第一個問題，兩個問題的答案都是肯定的。所以是鞘內給藥。而且是背根神經節毒性，正如我之前所說，不幸的是，這種毒性與這種給藥方式有關，我們也知道有這種風險。所以，是的。

Over to you, Kylie.

接下來就看你的了，凱莉。

Thanks, Walid. Yes. As I just said, the patient and physician community are very motivated. They have a huge unmet medical need. And collaboratively working together to look at how to move this forward.

謝謝，瓦利德。是的。正如我剛才所說，患者和醫生群體都非常積極。他們面臨著巨大的未滿足的醫療需求，並且正在共同努力，探討如何推進這項工作。

I think one of the things that's important is we received a big expression of hope and excitement coming out of the data. And then to have this disappointment a few weeks later is a bit of an emotional rollercoaster for the community. But I think they're working together to look forward and say, how do we bring this therapy to patients.

我認為重要的是，我們從數據中看到了巨大的希望和興奮。然而幾週後卻遭遇了這樣的失望，這對整個群體來說無疑是一場情緒的過山車。但我相信他們正在齊心協力地展望未來，思考如何將這種療法帶給患者。

Patrick Trucchio, H.C. Wainwright.

派崔克·特魯基奧，H.C. 溫賴特。

This is (technical difficulty) on for Patrick. I was just wondering if you could clarify if you've received any EMA or MHRA preliminary feedback on accepting the same data set and external control for AMT-130 as primary evidence? And could you see ex-US submissions proceeding ahead of FDA approval?

派崔克這邊（技術故障）無法正常進行。我想請問一下，您是否收到過EMA或MHRA關於接受AMT-130的相同資料集和外部對照作為主要證據的初步回饋？您認為美國以外的申請是否會在FDA批准之前進行？

Walid, do you want to answer that?

瓦利德，你想回答這個問題嗎？

Sure. So we have not yet engaged in the UK or EMA -- MHRA or EMA. That is the plan to go next; we were prioritizing the FDA. But I will say that we are committed to work with the FDA also to continue to find a path forward, and also with other regulatory agencies. And we will advance as quickly as possible on all these fronts to bring this therapy to patients as quickly as possible.

當然。我們目前還沒有與英國或歐洲藥品管理局（MHRA）接洽。這是我們下一步的計劃；我們之前優先考慮的是FDA。但我可以肯定的是，我們致力於與FDA以及其他監管機構合作，繼續尋找前進的方向。我們將盡最大努力在各方面推進，盡快將這種療法帶給患者。

(Operator Instructions)

（操作說明）

Paul Matteis, Stifel.

Paul Matteis，Stifel。

As it relates to the meeting, again, answer whatever you're comfortable with. But given that your dialogue here, I guess, as I understand it has been with a relatively similar group of people across the spring meeting and then last November last year. When they came out and told you that they didn't think this path was no longer supportive of a BLA, did you ask them why and what exactly had changed?

關於會議內容，再次強調，請隨意回答您覺得合適的問題。但鑑於您先前的對話，據我了解，您與春季會議以及去年11月會議的參與者基本上相同。當他們告訴您他們認為這條路不再支持BLA時，您是否詢問過他們原因以及究竟發生了什麼變化？

And then just separately, can you clarify for us what specific data have you shared with the FDA at this point? And have they seen more data from this three-year analysis than we have?

另外，您能否單獨說明一下，目前為止您向FDA提供了哪些具體數據？他們是否看到了比我們更多的來自這項為期三年的分析的數據？

Yes, Paul. Unfortunately, we're not going to be able to comment on the details of the specific meeting, but we do hope for clarity once we do receive minutes. And to the extent that there are material updates, we'll endeavor to update investors and analysts. So I think that's the answer to your first question.

是的，保羅。很遺憾，我們無法就此次會議的具體細節發表評論，但我們希望在收到會議紀要後能夠了解情況。如果會議記錄中包含任何實質更新，我們將盡力及時向投資者和分析師通報。我想這就是你第一個問題的答案。

And then the second question? Okay, yes. On the data. No, the data that was submitted to the FDA was consistent with the data that we've shared publicly a number of weeks ago. Obviously, there's some additional data like sensitivity analyses that haven't been presented, but there was no new follow-up or additional data that was provided to the agency.

那麼第二個問題呢？好的，關於數據。不，提交給FDA的數據與我們幾週前公開的數據一致。顯然，還有一些額外的數據，例如敏感性分析，尚未提交，但我們沒有向FDA提供任何新的後續數據或補充數據。

We have no further questions. This will conclude today's question-and-answer session and today's call. You may now disconnect.

我們沒有其他問題了。今天的問答環節和電話會議到此結束。您可以掛斷電話了。