Anavex Life Sciences Corp (AVXL) 2025 Q4 法說會逐字稿

(audio in progress) Please note that this conference is being recorded, and the call will be available for replay on Anavex's website at www.anavex.com. With us today is Dr. Christopher Missling, President and Chief Executive Officer; and Sandra Boenisch, Principal Financial Officer.

（音訊進行中）請注意，本次會議正在錄音，錄音回放可在Anavex公司網站www.anavex.com上觀看。今天出席會議的有總裁兼執行長克里斯托弗·米斯林博士和財務長桑德拉·博尼施。

Before we begin, please note that during this conference call, the company will make some projections and forward-looking statements. These statements are only predictions based on current information and expectations and involve a number of risks and uncertainties. We encourage you to review the company's filings with the SEC that include, without limitation, the company's Forms 10-K and 10-Q, which identify the specific factors that may cause actual results or events to differ materially from those described in these forward-looking statements.

在會議開始之前，請注意，在本次電話會議中，公司將做出一些預測和前瞻性聲明。這些陳述只是基於當前資訊和預期的預測，涉及許多風險和不確定性。我們鼓勵您查閱公司向美國證券交易委員會提交的文件，包括但不限於公司的 10-K 表格和 10-Q 表格，其中列明了可能導致實際結果或事件與這些前瞻性聲明中描述的結果或事件存在重大差異的具體因素。

These factors may include, without limitation, risks inherent in the development and/or commercialization of potential products, uncertainty in the results of clinical trials or regulatory approvals, need and ability to obtain future capital and maintenance of intellectual property rights. This conference call discusses investigational uses of agents in development and is not intended to convey conclusions about efficacy or safety, and there is no guarantee that any investigational uses of such products will successfully complete clinical development or gain health authority approval.

這些因素可能包括但不限於潛在產品的開發和/或商業化過程中固有的風險、臨床試驗結果或監管審批的不確定性、未來獲得資金的需求和能力以及智慧財產權的維護。本次電話會議討論的是正在研發中的藥物的研究用途，並不旨在傳達有關療效或安全性的結論，也不保證此類產品的任何研究用途都能成功完成臨床開發或獲得衛生監管機構的批准。

And with that, I would like to turn the call over to Dr. Missling.

接下來，我將把電話交給米斯林博士。

Thank you, Clint, and good morning, everyone. Thank you for being with us today to review our Q4 financial results and quarterly business update. We are fully committed to bringing oral blarcamesine and oral ANAVEX 3-71 to patients. We are dedicated to delivering on the value of our pipeline and maximizing its potential for patients, investors and our employees. Over the coming months, we will continue to focus on progressing our clinical trials and regulatory actions.

謝謝你，克林特，大家早安。感謝各位今天蒞臨，與我們一同審閱我們的第四季財務業績和季度業務更新報告。我們全力以赴為患者帶來口服 blarcamesine 和口服 ANAVEX 3-71。我們致力於實現我們研發管線的價值，並最大限度地發揮其對患者、投資者和員工的潛力。在接下來的幾個月裡，我們將繼續專注於推進臨床試驗和監管工作。

At the same time, we're aiming to extending our collaborative initiatives and strategic partnership activities. As previously announced, through our update on the status of the regulatory filing of blarcamesine in Europe, we expect the CHMP to adopt a negative opinion on the MAA at its December meeting. We intend to request a reexamination of the CHMP opinion upon its formal adoption based on feedback and continued guidance from the CHMP, EMA and the Alzheimer's disease community.

同時，我們致力於拓展合作專案和策略夥伴關係活動。正如先前宣布的那樣，透過我們更新的關於在歐洲提交的 blarcamesine 監管申請的狀態，我們預計 CHMP 將在其 12 月的會議上對該上市申請發表否定意見。我們打算在人用藥品委員會 (CHMP)、歐洲藥品管理局 (EMA) 和阿茲海默症界的反饋和持續指導下，在 CHMP 正式採納該意見後，要求對其進行重新審查。

EMA procedures adopted by the CHMP allow an applicant to request reexamination of its decision, which would be undertaken by a different set of reviewers that conduct a new examination independent from the first opinion. Our expert advisers, investigators as well as patients and their caregivers encourage us in our commitment to continue working in partnership with global regulatory bodies to advance science and potentially new treatment options for patients and their families.

EMA 的 CHMP 程序允許申請人請求對其決定進行重新審查，重新審查將由另一組審查員進行，這些審查員將獨立於第一次意見進行新的審查。我們的專家顧問、研究人員以及患者及其照護者都鼓勵我們繼續與全球監管機構合作，推動科學發展，並為患者及其家人提供新的治療方案。

As part of the MAA review process, we have successfully undergone a full good clinical practice GCP inspection of the trial data by EMA. The manufacturing package has passed the EMA review as well. A good clinical practice GCP inspection is an official review by a regulatory authority of a clinical trials documents, facilities, records and other resources to ensure compliance with GCP guidelines.

作為 MAA 審查流程的一部分，我們已成功通過 EMA 對試驗數據的全面良好臨床實踐 (GCP) 檢查。生產資料包也已通過EMA審核。良好臨床實踐 (GCP) 檢查是由監管機構對臨床試驗文件、設施、記錄和其他資源進行的正式審查，以確保符合 GCP 指南。

We're looking forward to working closely with the EMA and other stakeholders to advance our investigational therapy for early Alzheimer's disease. Importantly, we also announced that we had initial contacts with the authorities in the US regarding our Alzheimer's disease program, and we intend to provide further updates on our interaction with the FDA as they become available.

我們期待與歐洲藥品管理局 (EMA) 和其他利益相關者密切合作，推進我們針對早期阿茲海默症的研究性療法。重要的是，我們還宣布，我們已就我們的阿茲海默症計畫與美國當局進行了初步接觸，我們將在獲得更多資訊後，提供有關我們與 FDA 互動的最新進展。

Going forward, we will provide both regulatory and clinical trial updates on blarcamesine in other indications such as Parkinson's disease, Rett syndrome and Fragile X. This will include the disclosure of planned future clinical trial designs as we continue to advance our therapeutic pipeline.

未來，我們將提供關於blarcamesine在其他適應症（例如帕金森氏症、雷特氏症和脆性X染色體症候群）的監管和臨床試驗最新進展。這包括揭露我們計劃進行的未來臨床試驗設計，因為我們將繼續推動我們的治療產品線。

During the most recent quarter, we announced several new scientific and medical publications, which includes a peer-reviewed publication in the journal Neuroscience Letters titled Prevention of Memory Impairment and Hippocampal Injury with blarcamesine in an Alzheimer's disease model. This study shows that pretreatment with blarcamesine prevented amyloid beta-induced memory impairment and brain oxidative injury, suggesting that blarcamesine is an attractive candidate for Alzheimer's disease pharmacological prevention.

在最近一個季度，我們宣布了幾項新的科學和醫學出版物，其中包括在《神經科學快報》雜誌上發表的一篇同行評審出版物，題為《在阿茲海默症模型中使用 blarcamesine 預防記憶障礙和海馬損傷》。這項研究表明，使用 blarcamesine 進行預處理可以預防澱粉樣蛋白β引起的記憶障礙和腦氧化損傷，這表明 blarcamesine 是阿茲海默症藥物預防的一個有吸引力的候選藥物。

A peer-reviewed publication in the journal of iScience ascertaining the precise autophagy mechanism of sigma-1 receptor through blarcamesine activation titled Conserved LIR-specific interaction of Sigma-1 receptor and GABARAP. A publication Oral Blarcamesine Phase IIb/III trial Confirms Identified Precision Medicine Patient Population - Significant Broad Clinical and Quality of Life Improvements for Early Alzheimer's Disease Patients to be available online as a preprint and in submission to a peer-reviewed medical journal.

一篇發表在 iScience 雜誌上的同行評審文章，題為“Sigma-1 受體和 GABARAP 的保守 LIR 特異性相互作用”，透過 blarcamesine 活化確定了 sigma-1 受體的精確自噬機制。一項關於口服 Blarcamesine IIb/III 期試驗的出版物證實了已確定的精準醫療患者群體——早期阿茲海默症患者在臨床和生活品質方面取得了顯著的廣泛改善，該出版物將以預印本的形式在線發布，並已提交給同行評審的醫學期刊。

Anavex announced the latest published scientific results for blarcamesine on all standard scales for measuring Alzheimer's disease and cognitive decline after 48 weeks, the defined precision medicine population, ABCLEAR3, consisting of early Alzheimer's disease patients with confirmed and progressed pathology taking 30-milligram once-daily oral blarcamesine demonstrated barely detectable decline. This was comparable to minimally perceptible decline in prodromal, which is pre-dementia aging with adults. On October 29, we announced additional long-term clinical data for blarcamesine.

Anavex 公佈了 blarcamesine 的最新科學研究結果，該研究在所有用於測量阿茲海默症和認知能力下降的標準量表上，經過 48 週的治療，在 ABCLEAR3 中，由早期阿茲海默症患者（病理已確診且病情進展）組成的精準醫療人群，每天口服 30 毫克 blarcamesine，結果顯示認知能力下降。這與前驅期（即成年癡呆症前期的衰老）中輕微可察覺的衰退相當。10 月 29 日，我們公佈了更多 blarcamesine 的長期臨床數據。

This new data demonstrated continued long-term benefit from oral blarcamesine compared to decline observed in the Alzheimer's disease neuroimaging initiative control group, also called ADNI, a control group established by a clinical research project launched by NIH in 2004. In the intent-to-treat population, significantly less cognitive decline was observed for the blarcamesine participants compared to the ADNI control group at 48 weeks, with a significant and clinically meaningful difference in mean change from baseline at ADAS-Cog13 total score of minus 2.68 points.

這項新數據表明，與阿茲海默症神經影像學計畫對照組（也稱為 ADNI）觀察到的病情惡化相比，口服 blarcamesine 具有持續的長期益處。 ADNI 是由美國國立衛生研究院 (NIH) 於 2004 年啟動的一項臨床研究計畫建立的對照組。在依意圖治療族群中，與 ADNI 對照組相比，接受 blarcamesine 治療的參與者在 48 週時認知能力下降明顯較少，ADAS-Cog13 總分較基線平均變化有顯著且具有臨床意義的差異，為 -2.68 分。

Over the course of the open-label extension study at [10.96] weeks, these two groups further diverged sharply with statistical significant differences in mean change in ADAS-Cog13 total score at 96 weeks of minus 6.41 points. The difference between groups continues to increase at 144 weeks to ADAS-Cog13 total score difference of minus 12.78 points. The results provide evidence of the significant beneficial therapeutic effect of blarcamesine, which positively separates from the ADNI control group with duration of treatment.

在開放標籤擴展研究的 [10.96] 週期間，這兩組進一步急劇分化，在 96 週時 ADAS-Cog13 總分的平均變化存在統計學上的顯著差異，為 -6.41 分。到第 144 週時，各組之間的差異繼續增大，ADAS-Cog13 總分差異為 -12.78 分。結果證明，布拉卡美辛具有顯著的治療效果，隨著治療時間的延長，其療效與 ADNI 對照組明顯不同。

This significant beneficial therapeutic effect of blarcamesine compared to decline observed in the ADNI control group translates into 17.8 months of time saved with oral blarcamesine, allowing for longer independence of the patients by approximately over 1.5 years. Looking ahead, Anavex will be presenting additional data and scientific findings at upcoming conferences and in publications. These include the direct relationship between cognitive function and reduced brain region atrophy with blarcamesine.

與 ADNI 對照組觀察到的病情惡化相比，布拉卡美辛具有顯著的治療效果，口服布拉卡美辛可節省 17.8 個月的時間，使患者能夠獨立生活的時間延長約 1.5 年。展望未來，Anavex 將在即將舉行的會議上和出版物中展示更多數據和科學發現。其中包括認知功能與腦區萎縮減少之間的直接關係，以及布拉卡美辛的作用。

Oral blarcamesine for early symptomatic Alzheimer's, robust effect size through precision medicine and analysis of the ANAVEX 2-73-AD-004 randomized trial. Also, newly identified precision medicine gene, Collagen 24A1 with over 70% prevalence, which establishes effective treatment of early Alzheimer's disease with blarcamesine and also continued long-term benefit from oral blarcamesine compared to delayed start analysis and decline compared to natural history studies.

口服 blarcamesine 治療早期症狀性阿茲海默症，透過精準醫學和 ANAVEX 2-73-AD-004 隨機試驗分析，得出顯著療效。此外，新發現的精準醫療基因膠原蛋白 24A1 的盛行率超過 70%，證實了使用 blarcamesine 治療早期阿茲海默症的有效性，並且與延遲開始分析相比，口服 larcamesine 具有持續的長期益處，並且與自然史研究相比，病情有所下降。

With regard to ANAVEX 3-71 in October, Anavex announced positive top-line results from its placebo-controlled Phase II clinical study evaluating ANAVEX 3-71 for the treatment of schizophrenia in adults on stable antipsychotic medication. The study successfully achieved its primary endpoint, demonstrating that ANAVEX 3-71 was safe and well tolerated. The safety profile was consistent with previous studies of ANAVEX 3-71 in healthy volunteers with no serious or severe treatment-emergent adverse events reported in either Part A or Part B of the study.

關於 ANAVEX 3-71，Anavex 於 10 月宣布，其安慰劑對照 II 期臨床研究取得了積極的初步結果，該研究評估了 ANAVEX 3-71 用於治療正在服用穩定抗精神病藥物的成年精神分裂症患者的療效。該研究成功達到了主要終點，證明 ANAVEX 3-71 安全且耐受性良好。安全性概況與先前對健康志願者進行的 ANAVEX 3-71 研究一致，在研究的 A 部分或 B 部分中均未報告嚴重或嚴重的治療期間出現的不良事件。

In addition to meeting the primary safety endpoint, secondary and exploratory analysis revealed encouraging trends in several outcome measures. Our other oral medicine candidate, ANAVEX 3-71, represents therefore a transformative opportunity in neuropsychiatric drug development, leveraging its unique dual sigma-1 agonist M1 PAM mechanism to address multiple high-value indications through a unified neuroinflammatory biomarker platform.

除了達到主要安全性終點外，次要和探索性分析還揭示了幾個結果指標中令人鼓舞的趨勢。因此，我們的另一款口服候選藥物 ANAVEX 3-71 代表了神經精神藥物開發領域的變革性機遇，它利用其獨特的雙重 sigma-1 激動劑 M1 PAM 機制，透過統一的神經發炎生物標記平台來解決多種高價值適應症。

Further detailed analysis of randomized strictly double-blind and placebo-controlled clinical trial, ANAVEX 3-71-SZ-001 revealed very encouraging data in patients suffering from schizophrenia. Following successful Phase II results from the SZ-001 study, while confirming the excellent safety profile of ANAVEX 3-71, the study demonstrated reduction in GFAP and YKL-40 neuroinflammatory markers.

對隨機、嚴格雙盲、安慰劑對照臨床試驗 ANAVEX 3-71-SZ-001 的進一步詳細分析顯示，該試驗在精神分裂症患者中取得了非常令人鼓舞的數據。在 SZ-001 研究的 II 期試驗中取得成功結果後，該研究證實了 ANAVEX 3-71 具有良好的安全性，並表明 GFAP 和 YKL-40 神經發炎標記物有所減少。

GFAP is a structural protein of astrocytes in the brain represents apparent activation of astrocytes, the major brain glial cell lineage. Astrocytes participate in brain neural function in multiple ways, amongst them, critical modulation of synaptic relay between neurons in neural circuits. Its dysfunction, a key pathogenesis mechanism in schizophrenia.

GFAP 是腦內星狀細胞的結構蛋白，代表了星狀細胞（腦內主要的膠質細胞譜系）的明顯活化。星狀細胞以多種方式參與大腦神經功能，其中包括對神經迴路中神經元之間突觸傳遞的關鍵調節。其功能障礙是精神分裂症的關鍵發病機制。

This positions ANAVEX 3-71 to advance into pivotal trials with the once-daily modified release oral tablet, enabling once-daily dosing across depression and psychosis indications, where current therapies have failed or shown limited efficacy.

這使得 ANAVEX 3-71 能夠推進到關鍵性試驗階段，採用每日一次的緩釋口服片劑，從而實現每日一次給藥，用於治療抑鬱症和精神病，而目前的療法在這些疾病中失敗或療效有限。

In addition to schizophrenia, one high unmet need opportunity would be depression in Alzheimer's disease with currently no approved therapies. Up to 40% of people with Alzheimer's experience significant depression, especially in early and middle stages of the disease. Depression in Alzheimer's is associated with worse quality of life, accelerated cognitive decline and earlier onset of dementia symptoms. The neuroinflammatory biomarker strategy positions ANAVEX 3-71 to potentially achieve disease modification claims beyond symptomatic treatment, representing a paradigm shift in neuropsychiatric drug development.

除了精神分裂症之外，阿茲海默症憂鬱症也是亟待解決的重大需求，目前尚無核准的治療方法。高達 40% 的阿茲海默症患者會出現嚴重的憂鬱症狀，尤其是在疾病的早期和中期階段。阿茲海默症患者的憂鬱症與生活品質下降、認知能力加速衰退和失智症狀提前出現有關。神經發炎生物標記策略使 ANAVEX 3-71 有可能實現超越症狀治療的疾病改善效果，這代表了神經精神藥物開發的範式轉移。

And now I would like to direct the call to Sandra Boenisch, Principal Financial Officer of Anavex, for a financial summary of the recently reported quarter.

現在，我想請 Anavex 的財務長 Sandra Boenisch 為大家介紹最近公佈的季度財務概況。

Thank you, Christopher, and good morning to everyone here. I am pleased to share with you today our fourth-quarter financial results for our 2025 fiscal year. Our cash position at September 30 was $102.6 million, and we had no debt. During the quarter, we utilized cash and cash equivalents of $8.6 million in our operating activities after taking into account changes in noncash working capital accounts. As of today, with the current cash balance of over $120 million, we anticipate that at the current cash utilization rate, our cash runway is more than three years.

謝謝你，克里斯托弗，各位早安。今天我很高興與大家分享我們 2025 財年第四季的財務表現。截至9月30日，我們的現金餘額為1.026億美元，且沒有債務。本季度，在扣除非現金營運資本帳變動後，我們在經營活動中使用了現金及現金等價物860萬美元。截至今日，公司現金餘額超過 1.2 億美元，以目前的現金使用率計算，預計現金儲備可維持三年以上。

Our research and development expenses for the quarter were $7.3 million as compared to $11.6 million in the comparable quarter of last year. General and administrative expenses were $3.5 million as compared to $2.7 million for the comparable quarter of last year.

本季我們的研發費用為 730 萬美元，去年同期為 1,160 萬美元。一般及行政費用為 350 萬美元，去年同期為 270 萬美元。

Compared to the same quarter of fiscal 2024, we saw a decrease in operating expenses, mostly driven by the completion of a large manufacturing campaign of blarcamesine and a decrease in clinical trial activities as a result of the completion of our open-label extension studies and our ANAVEX 3-71 Phase II study in schizophrenia. And lastly, we reported a net loss of $9.8 million for the quarter, which is $0.11 per share.

與 2024 財年同期相比，我們的營運支出有所下降，這主要是由於完成了 blarcamesine 的大規模生產活動，以及由於完成了開放標籤擴展研究和 ANAVEX 3-71 精神分裂症 II 期研究，臨床試驗活動有所減少。最後，我們公佈本季淨虧損 980 萬美元，即每股虧損 0.11 美元。

Thank you. And now I will turn the call back to Christopher.

謝謝。現在我把電話轉回給克里斯多福。

Thank you, Sandra. In summary, we are focused on continuing to advance our precision medicine compounds. We are excited to be potentially making a difference for individuals suffering from these diseases by presenting a scalable treatment alternative alongside the ease of oral administration.

謝謝你，桑德拉。總而言之，我們致力於持續推動精準醫療化合物的研發。我們很高興能夠透過提供一種可擴展的治療方案以及口服給藥的便利性，為患有這些疾病的人們帶來潛在的改變。

I would now like to turn the call back to Clint for Q&A.

現在我想把電話轉回給克林特，讓他回答問題。

(Event Instructions) Michael Obodai, H.C. Wainwright.

（活動說明）Michael Obodai，H.C. Wainwright。

So I'll be asking the questions on behalf of Ram Selvaraju from H.C. Wainwright. I have a couple of questions for the management. And the first question is, what is the likely commercial impact of the failure of semaglutide on the outlook for blarcamesine in Alzheimer's disease?

所以，我將代表 H.C. Wainwright 的 Ram Selvaraju 來提出問題。我有幾個問題想問管理階層。第一個問題是，索瑪魯肽的失敗可能會對布拉卡美辛在阿茲海默症治療中的前景產生怎樣的商業影響？

The second one is, when is the next formal discussion of blarcamesine scheduled to take place with the FDA? And the third question is, what initiatives does Anavex plan near term to pursue blarcamesine approval in regions beyond the European Union and the United States?

第二個問題是，下次與FDA正式討論布拉卡美辛的會議安排在什麼時候？第三個問題是，Anavex 近期計劃採取哪些措施來尋求在歐盟和美國以外的地區獲得 blarcamesine 的批准？

I appreciate the questions. So to answer the first question about the impact of the semaglutide results. We understand there's an unmet medical need here. And this is certainly further highlighted by the recent setback by the two EVOKE studies from Novo Nordisk and also by other companies, including other large pharma companies recently with also with anti-tau injectables. So there's a lack of upcoming pipeline certainly.

感謝大家的提問。那麼，為了回答關於索瑪魯肽結果影響的第一個問題。我們了解到這裡存在著尚未滿足的醫療需求。諾和諾德的兩項 EVOKE 研究最近遭遇挫折，以及其他公司（包括其他大型製藥公司）最近在抗 tau 注射劑方面遭遇挫折，這無疑進一步凸顯了這一點。所以，目前確實缺乏新的專案儲備。

We also understand that the EVOKE semaglutide GLP-1 finding highlight the complexity of Alzheimer's disease biology and the challenges of expecting the metabolic pathway alone to meaningfully alter neurogenerative processes. But Alzheimer's is more complex, involves impaired proteostasis, autophagy dysfunction, synaptic failure and multiple converging mechanism. So therapeutic effects seen in related conditions do not always translate into cognitive benefit here.

我們也了解到，EVOKE 索馬魯肽 GLP-1 的研究結果凸顯了阿茲海默症生物學的複雜性，以及僅憑代謝途徑就對神經退化過程產生實質改變的挑戰。但阿茲海默症更為複雜，涉及蛋白質穩態受損、自噬功能障礙、突觸衰竭和多種匯聚機制。因此，在相關疾病中觀察到的治療效果並不總是能轉化為認知方面的益處。

However, we have with oral once-daily blarcamesine, with this upstream mechanism of action, which restores autophagy, which precedes these pathologies I just summarized and has demonstrated in early Alzheimer's disease patients, clinically meaningful efficacy of slowing cognitive decline, significant amounts, in some cases, over 50%, with an acceptable safety profile with no ARIA and as demonstrated in the Phase IIb/III study. So the answer to the question is this makes it more clear that this is a complex disease, and there's a lack of compounds near term available for patients to address this unmet need.

然而，我們每天口服一次的 blarcamesine，透過其上游作用機制，恢復了自噬，而自噬先於我剛才總結的這些病理，並且在早期阿爾茨海默病患者中已證明，具有臨床意義的療效，可以減緩認知能力的下降，在某些情況下，療效顯著，超過 50%，並且具有可接受的安全性，沒有 ARIA，正如 IIb/III 期的研究中所證明所證明的安全性，並沒有可接受的安全性，以及 ARIA，正如 IIb/III 期。所以這個問題的答案是，這更清楚地表明這是一種複雜的疾病，而且近期內缺乏可供患者使用的化合物來滿足這種未被滿足的需求。

Second question is about timing. So we provide, as we stated, updates what will follow-up in the initial discussion with the US regulators, and we'll provide updates as we receive them. But we're very excited about the initiation of these discussions.

第二個問題是關於時間安排的。正如我們所說，我們將提供與美國監管機構初步討論的後續進展，並在收到最新消息後及時更新。但我們對這些討論的啟動感到非常興奮。

Regarding the third question, we are continuing to now explore other regulatory geographies as well as moving forward where we can see fit to address open questions. So I trust this addresses the question.

關於第三個問題，我們正在繼續探索其他監管區域，並在我們認為合適的地方推進工作，以解決懸而未決的問題。所以我相信這已經解答了這個問題。

Tom Bishop, BI Research.

Tom Bishop，BI Research。

From the press release, the CHMP seems to have given you some guidance about the additional information they need to see, for example, biomarker. But can you elaborate what this includes?

從新聞稿來看，人用藥物委員會 (CHMP) 似乎已經就他們需要查看的其他資訊（例如生物標記）給出了一些指導。但您能詳細說明一下這包括哪些內容嗎？

So we want to proceed with the reexamination because we owe it to the patient and we get the feedback also from investigators that the unmet need is very high. And it boils down to demonstrating to the CHMP the benefit outweighs the risks of the drug to be on the market. And that discussion includes all available data. And it might be to make the glass half full that additional correlation or information about objective biomarker, which are not subject to influence, might be helping in getting to that point. So that is the background of biomarker, including biomarker assessments.

因此，我們希望繼續進行複查，因為我們有責任為患者服務，而且我們也從調查人員那裡得到回饋，認為未滿足的需求非常高。歸根究底，就是要向人用藥品委員會證明，該藥物上市的益處大於風險。而且，討論內容涵蓋了所有可用的數據。往好的方面想，或許可以這樣說：額外的相關性或關於客觀生物標記的資訊（不受影響）可能有助於達到這一目標。以上就是生物標記的背景知識，包括生物標記評估。

Well, there was no particular biomarkers that you hope to bring up?

那麼，您沒有特別希望提出的生物標記嗎？

We have communicated and it's been published that we have a very strong biomarker of the pathology, which is the analogy of oncology where tumor growth and you look at the size of the tumor, which is measurable objectively, can be measured objectively and it cannot be influenced by a patient or by anybody else. And the same is in Alzheimer's disease is the brain shrinks. So the brain gets smaller, the brain mass shrinks, and we can measure that as well. And it's a very objective marker of neurodegeneration. And we demonstrated that this marker of neurodegeneration is significant.

我們已經溝通並公佈了，我們擁有非常強大的病理生物標誌物，這類似於腫瘤學中的腫瘤生長，你可以觀察腫瘤的大小，這是可以客觀測量的，並且不會受到患者或任何其他人的影響。阿茲海默症也是如此，患者的大腦會萎縮。所以大腦體積變小，腦質量縮小，我們也可以測量到這一點。而且它是神經退化性疾病的一個非常客觀的標誌。我們已經證明，這種神經退化性標誌物具有重要意義。

The less or even halted in some patients with active oral blarcamesine, while in the placebo arm, this shrinking of the brain continues, which is the clear definition of the advancement of the Alzheimer's pathology. And we like to include, of course, that as well in the discussion.

一些服用活性口服布拉卡美辛的患者病情有所減輕甚至停止，而安慰劑組的患者則繼續出現腦萎縮，這清楚地表明了阿茲海默症病理的進展。當然，我們也希望把這一點納入討論中。

What about the ABCLEAR data? I mean, that was very compelling with 48% to 86% slowing depending on the gene biomarker or combination. I guess this was not considered by the CHPT as it came out MP because it came out kind of late. But can this be included for consideration on reexamination?

ABCLEAR 數據如何？我的意思是，根據基因生物標記或組合的不同，有 48% 到 86% 的人速度減慢，這非常令人信服。我猜想，由於 CHPT 發布的時間比較晚，所以它沒有被考慮在內。但這一點能否納入重新審查的考量？

So it's a good question. So we like to emphasize our focus is on each individual patient affected by Alzheimer's. And we see that very clear beneficial signal of cognitive, but also clinically meaningful effect in both cognitive and functional, but also in all the other endpoints, consistent improvement and significant improvement of the clinical outcomes that is the CGI-I, that is the Quality of Life, NPI-Q, MMSE in all the measures, ADAS-Cog13, CDR Sum of Boxes, ADCS-ADL. In all this ABCLEAR and 3 populations, we see a clearly clinically meaningful and significant improvement. So we would like to also point that out. And that is really a good data set to have and to put this forward.

所以，這確實是個好問題。因此，我們想強調的是，我們關注的是每位受阿茲海默症影響的患者。我們看到了非常明顯的認知益處訊號，而且在認知和功能方面也具有臨床意義，此外，在所有其他終點方面，臨床結果也得到了持續改善和顯著改善，這些臨床結果包括 CGI-I（生活品質）、NPI-Q（所有測量指標）、MMSE（所有測量指標）、ADAS-Cog13（認知障礙評估量表）、CDR 總分）。在所有這些 ABCLEAR 和 3 族群中，我們看到了明顯的、具有臨床意義和顯著的改善。所以我們也想指出這一點。這是一份非常好的數據集，值得我們提出來。

And also last but not least, making the point about the focus on each individual patient, we see a reversal of the negative trajectory of Quality of Life of the patients in 70% of the patients, in the trial. That means the Quality of Life is better after one year than at the start of the trial. And that's very impactful because that's what is really impacts the individual patient.

最後但同樣重要的是，為了強調對每位患者的關注，我們在試驗中看到 70% 的患者的生活品質出現了逆轉，這反映了對每位患者的關注。這意味著一年後患者的生活品質比試驗開始時好。這影響非常大，因為這才是真正影響到個別患者的因素。

Okay. If the approval ultimately came from the EMA, and let's assume perhaps it was conditional, is there a rule of thumb or how long you would have to do a conditional trial?

好的。如果最終獲得 EMA 的批准，假設批准是有條件的，那麼有沒有什麼經驗法則或者說，需要進行多長時間的有條件試驗？

It's really hard to speculate about this, but we would like to make sure we want to point out we are motivated and driven by the fact that there's a huge significant unmet need for a drug with these features today, and we pointed out the recent pipeline failures.

對此很難做出推測，但我們想強調的是，我們之所以有動力和動力，是因為目前對具有這些特性的藥物存在巨大的未滿足需求，而且我們也指出了最近一些研發管線的失敗案例。

And also, I want to point out that between '20 and '25 this year in 2030, there will be more than $300 billion of large pharma revenue at risk from loss of exclusivity with over 40% of top pharma sales exposed, creating an estimated $90 billion growth gap even after internal pipeline contributions. So that means there's also a huge unmet need, not only for this indication, but also for overall pipeline to be filled by large pharma.

此外，我還想指出，從 2020 年到 2025 年，到 2030 年，大型製藥公司將有超過 3000 億美元的收入因失去獨家銷售權而面臨風險，超過 40% 的頂級製藥公司銷售額將受到影響，即使考慮到內部研發管線的貢獻，預計仍將造成 900 億美元的增長缺口。所以這意味著不僅在這一適應症方面，而且在大型製藥公司需要填補的整體產品線方面，都存在巨大的未滿足需求。

Well, that's interesting that you brought that up because I wanted to ask about how you're coming with exploring your options if you get approval, for example, large pharma sales organizations and so forth to take blarcamesine to market?

嗯，你提到這一點很有意思，因為我想問，如果獲得批准，例如與大型製藥銷售機構等合作，將 blarcamesine 推向市場，你打算如何探索各種選擇？

Yes. So we pointed out just in this call that one of the key things we are focusing on now is expanding the corporate development partnership activities. And we mentioned that we are presenting at the most important conference every year, which takes place in San Francisco in early January, and we are presenting company on Wednesday on -- at that conference itself and that allows for more meaningful discussions, which is the hotspot for business development activities at this conference, and we will make sure we are present in that regard.

是的。因此，我們在這通電話中指出，我們現在關注的重點之一是擴大企業發展夥伴關係活動。我們提到，我們將在每年最重要的會議上進行演講，該會議於一月初在舊金山舉行。我們將在周三——也就是會議現場——進行公司演講，這將使更有意義的討論成為可能，這是本次會議業務發展活動的熱點，我們將確保我們在這方面有所作為。

Okay. Well, I think it'd be a real tragedy for Alzheimer's patients to not see this drug approved because especially the ABCLEAR data to me is so convincing that -- and the risks are so low and it's oral that I just can't fathom that it wouldn't get approved, but that's just me. I wish I had a vote.

好的。我認為，如果這種藥物沒有獲得批准，對阿茲海默症患者來說將是一場真正的悲劇，因為尤其是 ABCLEAR 研究的數據對我來說非常有說服力——而且風險很低，還是口服的，我簡直無法想像它不會被批准，但這只是我個人的看法。我真希望我有投票權。

We would agree. Thank you for your vote as well.

我們同意。感謝您的投票。

Tom, are you there?

湯姆，你在嗎？

Yes. As long as I'm still on, is there a mechanism of action for COL24A1?

是的。既然我還在服用，COL24A1 的作用機轉是什麼？

Yes, there is. And this will be now published in a peer-reviewed paper. But in summary, I can say that Collagen 24A1 is the key ingredient of the extracellular matrix called ACM. And when you look at pictures of brain neurons or astrocytes, you always see this very nice connections or network like a spider web description or pictures. And in the background, it's always like pitch black.

是的，有。這項研究成果將發表在同行評審論文中。但總而言之，我可以說膠原蛋白 24A1 是細胞外基質（稱為 ACM）的關鍵成分。當你觀察大腦神經元或星狀細胞的圖片時，你總是會看到非常漂亮的連結或網絡，就像蜘蛛網一樣（描述或圖片）。背景總是漆黑一片。

And you're wondering this is how the brain looks like. And of course, it doesn't. It does not. And this background is actually the extracellular matrix, and that's where these neurons and astrocytes are sitting on in your brain. And if you have a mutation of this extracellular matrix, then your response to blarcamesine is impaired.

你是不是在想，這就是大腦的樣子？當然，事實並非如此。並非如此。而這個背景其實是細胞外基質，你的大腦中的神經元和星狀細胞就位於其中。如果你的細胞外基質發生突變，那麼你對布拉卡美辛的反應就會受損。

The autophagy flux, the autophagy restoration, which is the recycling mechanism of the neurons, which precedes a better in tau, so it's further upstream, closer to the origination of the pathology of Alzheimer's, if you like, that is impaired. And for that reason, we found that patients with a wild type, with not mutated collagen genes, they respond extremely well. And we see effects of, in ADAS-Cog13, minus 4.7 in the patients with that effect, with that wild-type gene. And in the CDR Sum of Boxes, the scores go up to 1.4, minus 1.4.

自噬通量、自噬恢復，即神經元的回收機制，先於 tau 蛋白的修復，因此它更靠近阿茲海默症病理的起源，如果你願意這麼說的話，它處於更上游的位置。因此，我們發現，對於膠原蛋白基因未發生突變的野生型患者，他們的治療效果非常好。我們看到，在 ADAS-Cog13 中，具有這種效應的患者（攜帶野生型基因）的得分降低了 4.7 分。在 CDR 盒子總和中，得分最高為 1.4，最低為 1.4。

And these are really very unprecedented effects of benefit. And we pointed out that that means patients are actually almost not declining or declining less than prodromal patients, which are less impaired. So that's quite impactful. And so this is really intriguing science, and it will be published in a major peer-reviewed paper very soon. So extremely intriguing and also consistent with the mechanism of blarcamesine.

這些都是前所未有的益處。我們指出，這意味著患者的病情實際上幾乎沒有惡化，或者惡化程度比前驅期患者要輕，而前驅期患者的病情受損程度較輕。所以這影響相當大。所以，這真是一項引人入勝的科學研究，它很快就會在重要的同行評審論文中發表。這非常有趣，也與blarcamesine的作用機制相符。

Great. Okay. Well, that's it for me. I'm just excited to see this ABCLEAR data get examined by the CHMP as well.

偉大的。好的。好了，我的故事就到這裡。我很期待看到 CHMP 也對 ABCLEAR 數據進行審查。

I appreciate it. Thank you.

謝謝。謝謝。

Thank you for the questions, Tom. The next question is going to come from Jesse Silveira with Spirit of the Coast Analytics.

謝謝你的提問，湯姆。下一個問題將來自海岸精神分析公司的傑西·西爾維拉。

Can you hear me all right?

你聽得清楚我說話嗎？

Yes, you're fine. Go ahead, Jesse.

是的，你沒事。傑西，你繼續。

This is Jesse Silveira from Spirit of the Coast Analytics. Some of these questions you've kind of addressed a little bit earlier, but hopefully you can maybe provide some additional color on some of them. Yes, just to reiterate kind of one of your previous points.

我是來自海岸精神分析公司的傑西·西爾維拉。你之前已經稍微談到過其中一些問題，但希望你能對其中一些問題補充一些細節。是的，我只是想重申你之前提到的觀點之一。

So my first question is sort of an assumption, though I think you got at it earlier. But considering the CHMP review is ongoing, and a final decision hasn't even been rendered yet, is it safe to say that you can't discuss the reasons for negative CHMP trending or give details on the strategy going into the reevaluation?

所以我的第一個問題其實是個假設，不過我覺得你之前已經提到過了。但考慮到 CHMP 審查仍在進行中，甚至還沒有做出最終決定，是否可以說您不能討論 CHMP 負面趨勢的原因或提供有關重新評估策略的細節？

That's correct. That's correct.

沒錯。沒錯。

Okay. Got that. And perhaps adjacent to that conversation, do you think you can give more detail on a statement that was found in the 14 November press release that stated, quote, the company intends to request a reexamination of the CHMP opinion upon its formal adoption, including providing relevant biomarker data based on feedback and continued guidance from the CHMP, EMA and the Alzheimer's-disease community.

好的。明白了。或許可以藉此機會，就 11 月 14 日的新聞稿中的一段話做更多細節說明，該段話指出，公司打算在正式採納 CHMP 的意見後，要求對其進行重新審查，包括根據 CHMP、EMA 和阿爾茨海默病界的反饋和持續指導，提供相關的生物標誌物數據。

I think it was Tom that was getting at this earlier, but can you comment any further on the biomarker data? I think I saw in your press release this morning that you plan to publish maybe a paper about brain atrophy and its direct correlation to cognition. Is that accurate? And is that some of the data that you may or may not be presenting to the EMA?

我認為湯姆之前已經提到過這一點，但您能否就生物標記數據做進一步評論？我今天早上在您的新聞稿中看到，您計劃發表一篇關於腦萎縮及其與認知能力直接相關性的論文。準確嗎？這些是您可能向歐洲藥品管理局 (EMA) 提交或不提交的資料嗎？

That's accurate. So the advantage of the biomarker is that the biomarker endpoint is objective and it cannot be influenced by a patient, by the caregiver or the physician or anybody else, as a matter of fact, because it's objective. And I pointed out that in analogy to oncology, where you get drugs approved purely by the effect of the brain measure -- sorry, of the tumor measurement and while, for example, the clinical effect was not yet significant. And that is something which we like to point out that the analogy is in Alzheimer's, the clear pathological shrinking of the brain, which is one of the first features Alzheimer himself actually identified in his patients with Alzheimer's, the first patient he assessed. Subsequent later on, when he looked into the brain, he found this additional apparent features of proteins then identified as a better plaque or tau.

沒錯。因此，生物標記的優點在於，生物標記終點是客觀的，事實上，它不會受到病人、照護人員、醫生或任何其他人的影響，因為它本身就是客觀的。我指出，以腫瘤學為例，有些藥物的核准只是基於對腦部（抱歉，是腫瘤）的影響，而臨床效果卻不顯著。我們想指出的是，這種類比與阿茲海默症相似，即大腦明顯的病理性萎縮，這是阿茲海默症本人在他評估的第一位阿茲海默症患者身上發現的首批特徵之一。後來，當他研究大腦時，他發現了這些蛋白質的額外明顯特徵，後來被鑑定為斑塊或 tau 蛋白。

But the first thing he identified was really that the brain shrinks and the holes, the gaps widen in the brain. And that's really the pathological logical consequence of a declining brain, less functional brain and it's like a lemon which is drying up. You cannot squeeze anything out of it. And that is really a strong objective biomarker and biomarker endpoint for demonstrating an objective effect of a drug, and that was demonstrated with blarcamesine. So we just want to make sure that gets visibility.

但他首先發現的是，大腦會萎縮，大腦中的孔洞、縫隙會變大。這就是大腦功能衰退、大腦功能減弱的必然結果，就像檸檬乾裂一樣。你從中榨不出任何東西。而這確實是一個強而有力的客觀生物標記和生物標記終點，可以證明藥物的客觀效果，而布拉卡美辛就證明了這一點。所以我們只是想確保這件事能被更多人看到。

And part of this is also a correlation analysis that we are able to find that not only that there's a shrinking -- less shrinking of the brain going along with blarcamesine treatment, but also that shrinking of the brain correlates with each patient with an improvement in the respective regions of the brain's activities of the ADAS-Cog13 subdomains, for example.

其中一部分還涉及相關性分析，我們發現，不僅隨著布拉卡美辛治療，大腦的萎縮程度有所減輕，而且大腦的萎縮程度與每位患者大腦相應區域在 ADAS-Cog13 子域中的活動改善程度相關。

For example, learning and reading and writing is in one area of the brain that is improved in the clinical trial for the patient, and that same region of the brain responsible for that, that also is less impaired in the active blarcamesine treatment arm compared to placebo. And if you can find this, this further confirms the true effect of the drug, and that will be convincing in our opinion.

例如，在臨床試驗中，患者的大腦中負責學習、閱讀和寫作的區域得到了改善，而負責這些功能的同一大腦區域，在接受活性 blarcamesine 治療的組中，其受損程度也低於安慰劑組。如果你能找到這一點，這將進一步證實該藥物的真實效果，我們認為這將很有說服力。

Yes. I think that's really interesting. I'm definitely looking forward to that. And I think kind of related in light of the semaglitude failure is that they reported that the drug had improved biomarkers, amyloid, maybe tau, I don't recall about tau, but -- the improved amyloid, but had no clinical effect, no improvement on CDR Sum of Boxes. And I think that I'm not sure exactly when there needs to be -- if there will be a time where regulators will no longer see amyloid equals better cognition or whatever.

是的。我覺得這很有趣。我非常期待。鑑於訊號強度失敗，我認為與之相關的是，他們報告稱該藥物改善了生物標誌物，澱粉樣蛋白，也許還有 tau 蛋白，我不記得 tau 蛋白的情況了，但是——澱粉樣蛋白有所改善，但沒有臨床效果，CDR Sum of Boxes 沒有改善。而且我不太確定何時——監管機構是否會有那麼一天——不再認為澱粉樣蛋白等於更好的認知能力或其他什麼。

But moving along kind of on September 9, the company PRed really impressive ABCLEAR3 comparisons to prodromal populations and had a detailed follow-on analysis of ABCLEAR2 and ABCLEAR3 subpopulations in a GWAS preprint a little bit later. ABCLEAR3, in particular, appears to showcase an effective functional cure in early Alzheimer's patients.

但到了 9 月 9 日，該公司公佈了 ABCLEAR3 與前驅人群的令人印象深刻的比較結果，並在稍後的 GWAS 預印本中對 ABCLEAR2 和 ABCLEAR3 亞群進行了詳細的後續分析。特別是 ABCLEAR3，似乎在早期阿茲海默症患者中展現出有效的功能性治癒作用。

And you covered the mechanisms of these earlier. But can you give further color on ABCLEAR1 versus ABCLEAR2 and ABCLEAR3, specifically, whether they were prespecified or exploratory and how regulators may or may not view these subpopulations in light of being exploratory or being prespecified. Is this something you can talk about?

您之前已經介紹過這些機制了。但是，您能否進一步說明 ABCLEAR1 與 ABCLEAR2 和 ABCLEAR3 的區別，特別是它們是預先指定的還是探索性的，以及監管機構可能會如何看待這些亞群體，因為它們是探索性的還是預先指定的？這是你能談談的話題嗎？

Yes. So the definition of ABCLEAR1, which basically is the wild-type sigma-1 gene, which was identified already in the beneficial effect of that gene in the previous preceding Phase IIa study, which was published 2020, where we identified that patients with the sigma-1 wild type, which represents 70% of the population had a better response to blarcamesine than those with the respective mutation.

是的。因此，ABCLEAR1 的定義基本上是指野生型 sigma-1 基因，該基因的有益作用已在先前的 IIa 期研究中得到證實，該研究於 2020 年發表，我們發現，攜帶 sigma-1 野生型基因的患者（佔總人口的 70%）對 blarcamesine 的反應比攜帶相應突變的患者更好。

It's a point mutation, and that's how biology is. 30% of overall population, that's not patients, but overall population has a point mutation, RS180866 and this one mutation changes the confirmation of the gene, makes it a little bit less viable or effective in its ability to restore homeostasis, increase autophagy, which is the mechanism of the activation of blarcamesines through sigma-1 activation as its ultimate effect. And so the patients with the wild type, the fully functional non-mutated gene respond better. So this was identified in the Phase IIa.

這是一個點突變，生物學就是這樣。 30% 的人口（並非患者，而是整個人口）都攜帶一個點突變，即 RS180866。這個突變改變了基因的構象，使其恢復體內平衡的能力略有下降，自噬作用增強，而自噬作用正是透過激活 sigma-1 來激活 blarcamesines 的機制，這是其最終效果。因此，攜帶野生型、功能完全正常的未突變基因的患者療效較好。這是在 IIa 期中發現的。

So we prespecified the analysis of the primary endpoints as well as the secondary and exploratory endpoints. With this in mind, how would patients do in the Phase IIb/III study with the wild-type sigma-1. And that was prespecified, and we now define this as ABCLEAR1. And we did indeed demonstrate, or it was demonstrated, that indeed, that was confirmed blarcamesines increased effect of patients with that 70%, roundabout the number of patients, which improved better than the patients with the mutation. And that is improving. So now ABCLEAR2 was the result of a preplanned in the trial.

因此，我們預先設定了主要終點以及次要終點和探索性終點的分析。考慮到這一點，患者在 IIb/III 期研究中接受野生型 sigma-1 治療的效果會如何？這是預先設定的，我們現在將其定義為 ABCLEAR1。我們確實證明，或者說已經證明，布拉卡美辛確實增強了約 70% 患者的療效，這些患者的病情改善程度優於攜帶突變的患者。情況正在改善。所以，ABCLEAR2 是試驗中預先規劃的結果。

We did a whole genomicome analysis. That means we looked at all patients in the study and analyzed their genes and genes expression and response to the drug based on the genetic profile as well. That is the DNA of all patients. And in this analysis, which was preplanned, we found, to our surprise unexpectedly, one gene showing up as an extremely strong driver of efficacy, and that gene turned out to be the collagen 24A1 gene. And that gene, I explained it just before, is involved in the buildup of the extracellular matrix. And that's really, really intriguing novel science and underappreciated or overlooked up to now in the field because everybody always looks at the neurons or the astrocytes or the areas of active involved in the brain.

我們進行了全基因組分析。這意味著我們研究了所有患者，並根據基因譜分析了他們的基因、基因表現以及對藥物的反應。那就是所有患者的DNA。在這項預先規劃的分析中，我們出乎意料地發現，有一個基因成為了療效的極強驅動因素，而這個基因竟然是膠原蛋白 24A1 基因。正如我剛才解釋過的，這個基因與細胞外基質的形成有關。這真是一項非常有趣的新科學，但迄今為止，它在該領域一直未得到應有的重視或忽視，因為每個人都總是關注神經元、星形膠質細胞或大腦中活躍的區域。

But the extracellular matrix is where all these neurons and astrocytes are residing or sitting on. It's like a pavement, like a street. And if that street is not smooth, like a highway or like a pavement, then these neurons cannot function well. And we were able to find them because the patients with the mutation of this collagen, in this extracellular matrix, did not respond so well to blarcamesine, representing that they're not as viable as the respective wild-type carriers. And the good news, though, is the collagen wild-type represents 71% of the overall population.

但所有這些神經元和星狀細胞都存在於細胞外基質中或位於其上。它就像人行道，就像街道。如果這條路不像高速公路或人行道那麼平坦，那麼這些神經元就無法正常運作。我們之所以能夠找到他們，是因為這種細胞外基質中的膠原蛋白發生突變的患者對布拉卡美辛的反應不太好，這表明他們的生存能力不如相應的野生型攜帶者。不過，好消息是，野生型膠原蛋白佔總人口的 71%。

And that was also found in our trials. We had roundabout 70% with patients with this collagen wild-type gene. So very intriguing new data, and that was, as a consequence, was preplanned in the study. Of course, not prespecified because we found it in the analysis of the Phase IIb/III study.

我們的試驗也發現了這一點。我們發現約有 70% 的患者帶有這種膠原蛋白野生型基因。所以，這些新數據非常有趣，因此，這是研究預先計劃好的。當然，這並非預先設定好的，而是我們在 IIb/III 期研究的分析中發現的。

Okay. And it's my understanding that Leqembi and Kisunla were both approved after a CHMP reexam, and that subpopulation data enriched their filing by conferring a more desirable like safety efficacy access. Is that true? And is this any way relevant to Anavex's current position with some of this data, the ABCLEAR2 and ABCLEAR3 data?

好的。據我了解，Leqembi 和 Kisunla 都是在 CHMP 重新審查後獲得批准的，並且亞人群數據豐富了它們的申請，賦予了它們更理想的安全性和有效性。是真的嗎？這與 Anavex 目前對部分數據（ABCLEAR2 和 ABCLEAR3 數據）的立場有任何關聯嗎？

It's correct, both lecanemab and donanemab, and these are run by large pharma companies. They had been, although prior approved in the US, reached the same point as we did just as we communicated a few weeks ago, and they underwent the same reexamination and were able to get approval.

沒錯，lecanemab 和 donanemab 都是由大型製藥公司生產的。雖然他們之前已在美國獲得批准，但正如我們幾週前溝通的那樣，他們也遇到了和我們一樣的問題，他們接受了同樣的重新審查，並最終獲得了批准。

I don't want to, I would say, make that this is a guarantee for us because every review is complex, and we are not able to anticipate or know the outcome of this reexamination process. But what it boils down to in the assessment of lecanemab and donanemab was the assessment and the judgment of benefit needs to outweigh the risk. And our drug is safe, has safety, has no ARIA, and we talk about the efficacy, which we just discussed. But we cannot anticipate, of course, an outcome of the regulatory review.

我想說，我並不想把這當作我們的保證，因為每一次審查都很複雜，我們無法預料或知道這次復審的結果。但對 lecanemab 和 donanemab 的評估歸根結底是，評估和判斷的益處需要大於風險。我們的藥物安全可靠，沒有 ARIA，而且我們剛才也討論了它的療效。當然，我們無法預料監管審查的結果。

Okay. Understood. And moving forward, will you be immediately refiling for the EMA reevaluation? To my knowledge, it took about 3.5 to 4 months for the CHMP to give Leqembi and Kisunla their next opinions, respectively. So maybe we could see something around April. Is that about what you're projecting?

好的。明白了。接下來，您是否會立即重新提交EMA重新評估申請？據我所知，CHMP 分別花了大約 3.5 到 4 個月的時間才分別向 Leqembi 和 Kisunla 給出下一步意見。所以或許我們可以在四月左右看到一些消息。這就是你想要表達的意思嗎？

That's correct. We will immediately ask for the reexamination as soon as possible. And again, while there's never certainty to obtain approval from regulators, we remain highly excited about the science and the data.

沒錯。我們將盡快要求重新審查。再次強調，雖然永遠無法保證一定能獲得監管機構的批准，但我們仍然對相關的科學和數據感到非常興奮。

Okay. And being a small company with a unique mechanism of action, it's probably difficult for you to garner support from the community. I recall that the European Alzheimer's Disease Consortium, Alzheimer's Europe and even the US Alzheimer's Association kind of put together persuasive arguments for the CHMP to consider during the Leqembi and Kisunla reevaluations. Does Anavex have any support like this? Are you aware of any organizations, key opinion leaders or even patients from the trial attempting to persuade the CHMP to reconsider? Do you have that support from the community?

好的。而且，作為一家規模較小、作用機制獨特的公司，您可能很難獲得社群的支持。我記得歐洲阿茲海默症聯盟、歐洲阿茲海默症協會，甚至美國阿茲海默症協會都曾為CHMP在Leqembi和Kisunla重新評估期間提出過一些有說服力的論點。Anavex有類似的支援嗎？您是否了解有任何組織、關鍵意見領袖，甚至是參與試驗的患者，試圖說服人用藥品委員會重新考慮？你是否得到了社區的支持？

It's really not for us to make that move. And the community is aware of our drug, and we let them basically do what they think is appropriate. And what we only can do is point out the data, and this is a process, and we are committed to this process.

我們真的不應該做出那樣的決定。社區了解我們的藥物，我們基本上讓他們做他們認為合適的事情。我們所能做的只是指出數據，這是一個過程，而我們致力於這個過程。

But also very importantly, with this process, we gain also confidence with the regulators. We are doing this in a partnership. We are doing this in an open discussion. And we are also getting the -- the ability to get feedback, which we need to move this forward in what way it takes to help patients addressing this unmet medical need.

但同樣重要的是，透過這個過程，我們也贏得了監管機構的信任。我們正在以合作的方式進行這項工作。我們正在透過公開討論的方式來解決這個問題。而且我們也獲得了獲得回饋的能力，我們需要這些回饋來推進這項工作，了解需要以何種方式幫助病患解決這個未被滿足的醫療需求。

Okay. Well, I see that we're nearing time. So to conclude for me, at least, it's pretty obvious to anyone paying attention that blarcamesine should likely be approved for early Alzheimer's patients and the efficacy has been absolutely unprecedented in these megalithic effect sizes were achieved in a really small population, which should theoretically make it more difficult to do.

好的。看來時間快到了。所以，至少對我來說，結論是，任何關注此事的人都很清楚，布拉卡美辛很可能應該被批准用於治療早期阿茲海默症患者，而且其療效是前所未有的，在如此小的人群中取得瞭如此巨大的療效，這在理論上應該會使治療更加困難。

So I think it's a clear win for patients, caregivers and payers. And I think part of the problem the first time around may have been that it was sort of piecemeal analysis and you're introducing analysis as you were going. But now that you have all analysis at your disposal and a clear narrative, it's my hope that the company will use the reexamination to tell blarcamesine story and earn the approval it deserves.

所以我認為這對患者、照護者和支付方來說都是一個明顯的勝利。我認為第一次出現問題的部分原因可能是分析是零散的，你是在進行分析的同時才引入分析方法的。但現在你們已經掌握了所有分析結果和清晰的敘述，我希望公司能夠利用這次重新審查的機會，講述 blarcamesine 的故事，並贏得它應得的批准。

So thank you for taking may call and I hope you have a good rest of the day.

感謝您接聽我的電話，祝您今天餘下的時間過得愉快。

We appreciate the kind words. And our expert advisers advises us also to proceed, and so do the patients and investigators, they also advise us to proceed, and we remain committed to do our best. Thank you.

感謝您的讚揚。我們的專家顧問建議我們繼續進行，患者和研究人員也建議我們繼續進行，我們將繼續盡最大努力。謝謝。

Yes. Thank you, Jesse. And Dr. Missling, I don't see any further questions at this time.

是的。謝謝你，傑西。米斯林博士，目前我沒有看到其他問題了。

Thank you. So we are thankful for your continued interest and trust in Anavex and wishing you a happy and blessed Thanksgiving. But in closing, we'd like to continue to point out our focus on execution as we advance our therapeutic pipeline to potentially improve patients' lives living with these devastating conditions. Oral once daily blarcamesine has the potential to address high unmet medical need in early Alzheimer's patients with a clinically meaningful efficacy profile of slowing cognitive decline by more than 30% and sometimes even higher for certain populations and its acceptable safety profile as demonstrated in the Phase IIb/III program. Thank you very much, and again, happy and blessed Thanksgiving.

謝謝。因此，我們感謝您一直以來對 Anavex 的關注和信任，並祝您感恩節快樂平安。最後，我們想繼續強調，我們將專注於執行，推動我們的治療方案研發，以期改善患有這些毀滅性疾病的患者的生活。每日一次口服的 blarcamesine 有潛力滿足早期阿茲海默症患者的高未滿足醫療需求，其具有臨床意義的療效，可減緩認知能力下降 30% 以上，有時對某些人群的療效甚至更高，並且在 IIb/III 期項目中已證明其安全性良好。非常感謝，再次祝您感恩節快樂平安。

Thank you, ladies and gentlemen. This will conclude today's conference call. We appreciate you participating, and you may now disconnect.

謝謝各位女士、先生。今天的電話會議到此結束。感謝您的參與，您現在可以斷開連接了。