Capricor Therapeutics Inc (CAPR) 2025 Q3 法說會逐字稿

Good afternoon, ladies and gentlemen, and welcome to the Capricor Therapeutics third-quarter 2025 conference call.

女士們、先生們，下午好，歡迎參加 Capricor Therapeutics 2025 年第三季電話會議。

(Operator Instructions) This call is being recorded on Monday, November 10, 2025.

（操作員指示）本次通話於2025年11月10日星期一進行錄音。

I would now like to turn the conference over to our CFO, AJ Bergmann, for the forward-looking statement. Please go ahead.

現在我將把會議交給我們的財務長 AJ Bergmann，讓他發表前瞻性聲明。請繼續。

Thank you very much, and good afternoon, everyone.

非常感謝，大家下午好。

Before we start, I would like to state that we will be making certain forward-looking statements during today's presentation. These statements may include statements regarding, among other things, the efficacy, safety, and intended utilization of our product candidates, our future R&D plans, including our anticipated conduct and timing of preclinical and clinical studies, our enrollment of patients in our clinical studies, plans to present or report additional data, plans regarding regulatory filings, potential regulatory developments involving our product candidates, potential regulatory inspections, revenue and reimbursement estimates, projected terms of definitive agreements, manufacturing capabilities, potential milestone payments, our financial position, and our possible uses of existing cash and investment resources.

在開始之前，我想聲明，在今天的演講中，我們將做出一些前瞻性陳述。這些聲明可能包括有關我們候選產品的功效、安全性和預期用途、我們未來的研發計劃（包括我們預期開展的臨床前和臨床研究的時間安排）、我們在臨床研究中招募患者、提交或報告更多數據的計劃、有關監管申報的計劃、涉及我們候選產品的潛在監管進展、潛在的監管檢查、收入和報銷

These forward-looking statements are based on current information, assumptions and expectations that are subject to change and involve a number of risks and uncertainties that may cause our actual results to differ materially from those contained in the forward-looking statements. These and other risks are described in our periodic filings made with the SEC, including our quarterly and annual reports.

這些前瞻性陳述是基於當前資訊、假設和預期，但這些資訊、假設和預期可能會發生變化，並且涉及許多風險和不確定性，這些風險和不確定性可能導致我們的實際結果與前瞻性陳述中包含的結果有重大差異。這些風險以及其他風險已在我們的定期向美國證券交易委員會提交的文件中進行了描述，包括我們的季度報告和年度報告。

You are cautioned not to place undue reliance on these forward-looking statements, and we disclaim any obligation to update such statements. With that, I'll turn the call over to Linda Marban, CEO.

請注意，不要過度依賴這些前瞻性陳述，我們也不承擔更新此類陳述的任何義務。接下來，我將把電話交給執行長琳達·馬爾班。

Good afternoon, and thank you for joining us on Capricor's third-quarter 2025 conference call. This has been a very busy time for Capricor, as we are just weeks away from a major milestone, the top line readout from our HOPE-3 Phase III clinical study of deramiocel, our investigational cell therapy for the treatment of Duchenne muscular dystrophy. This pivotal study represents the culmination of nearly a decade of scientific development, all aimed at helping boys and young men living with this devastating disease.

下午好，感謝各位參加 Capricor 2025 年第三季電話會議。對 Capricor 來說，這段時間非常忙碌，因為我們距離一個重要的里程碑——治療杜氏肌肉營養不良症的在研細胞療法 deramiocel 的 HOPE-3 III 期臨床研究的主要結果公佈——僅剩幾週時間。這項關鍵性的研究代表了近十年科學發展的巔峰，其目的都是為了幫助患有這種毀滅性疾病的男孩和年輕男性。

Importantly, HOPE-3 focuses primarily on non-ambulant individuals, a patient population that has historically had limited clinical research dedicated to it. HOPE-3 was conducted across 20 leading academic and clinical centers in the United States.

重要的是，HOPE-3 主要關注非行走患者，而歷史上針對這群患者的臨床研究非常有限。HOPE-3 研究在美國 20 個領先的學術和臨床中心進行。

The trial enrolled 105 participants and is one of the largest double-blind placebo-controlled studies ever conducted in the Duchenne population. The study was designed with a 1:1 randomization and is statistically powered to detect changes in both upper limb function -- as measured by the performance of the upper limb version 2.0, and cardiac function -- as measured by left ventricular ejection fraction, measured by cardiac MRI, as well as several secondary and exploratory endpoints.

該試驗招募了 105 名參與者，是迄今為止在杜氏肌肉營養不良症患者群體中進行的最大規模的雙盲安慰劑對照研究之一。研究採用 1:1 隨機分組設計，並具有足夠的統計效力來檢測上肢功能（透過上肢 2.0 版的表現來衡量）和心臟功能（透過心臟磁振造影測量的左心室射血分數來衡量）的變化，以及幾個次要和探索性終點的變化。

These 105 patients enrolled in HOPE-3 represent two cohorts: Cohort A, which received deramiocel manufactured from our Los Angeles clinical facility; and Cohort B, which receives products manufactured at our commercial GMP facility in San Diego. As a reminder, the FDA required the addition of Cohort B to evaluate the efficacy of the commercial scale product. While we have demonstrated nonclinical comparability, Cohort B provides the opportunity to generate direct evidence of efficacy for the commercial material.

HOPE-3 研究中招募的 105 名患者分為兩組：A 組接受由我們洛杉磯臨床設施生產的 deramiocel；B 組接受由我們聖地牙哥商業 GMP 設施生產的產品。提醒一下，FDA 要求增加 B 組受試者，以評估商業規模產品的療效。雖然我們已經證明了非臨床可比性，但 B 組提供了產生商業材料療效直接證據的機會。

The San Diego facility was built to meet commercial manufacturing standards operating under elevated quality and compliance requirements to support commercial deramiocel production. Because the San Diego manufactured product is intended for commercialization, the statistical analysis plan for HOPE-3 includes analyses designed to evaluate efficacy, both across the combined cohorts and independently within Cohort B.

聖地牙哥工廠的建設符合商業製造標準，並在更高的品質和合規要求下運行，以支援商業化毛棉生產。由於聖地牙哥生產的產品旨在商業化，HOPE-3 的統計分析計劃包括旨在評估療效的分析，包括跨合併隊列的療效分析以及在 B 隊列內的獨立療效分析。

We believe -- in alignment with our biostatisticians and clinicians who designed our statistical analysis plan with us -- that while the aggregated data are informative, demonstrating efficacy of the commercial scale product represents the most direct regulatory path to potential approval. From the standpoint of safety -- which, of course, is the most important aspect of the clinical study -- safety data from the trial have been regularly reported to the FDA, and no new or emerging safety signals have been observed.

我們相信——與和我們一起制定統計分析計劃的生物統計學家和臨床醫生一致——雖然匯總數據很有參考價值，但證明商業規模產品的有效性才是獲得潛在批准的最直接監管途徑。從安全性的角度來看——這當然是臨床研究最重要的方面——試驗的安全數據已定期向 FDA 報告，並且沒有觀察到任何新的或正在出現的安全信號。

Across our entire program, we have now administered more than 800 infusions to, approximately, 150 boys and young men with Duchenne, with deramiocel continuing to demonstrate a strong and consistent safety profile.

在我們的整個計畫中，我們已經為大約 150 名患有杜氏肌肉營養不良症的男孩和年輕男性進行了 800 多次輸液，德拉米奧塞持續表現出強勁而穩定的安全性。

At Capricor, our mission remains clear: To bring forward the first therapy that directly addresses Duchenne muscular dystrophy associated cardiomyopathy. Nearly every patient with Duchenne develops cardiomyopathy, which remains the leading cause of death in these boys and young men.

在 Capricor，我們的使命依然明確：推出首個直接針對杜氏肌肉營養不良症相關心肌病變的療法。幾乎所有患有杜氏肌肉營養不良症的患者都會患上心肌病變，而心肌病變仍然是這些男孩和年輕男性死亡的主要原因。

Deramiocel has been shown to help preserve both cardiac and skeletal muscle function, and our goal will be to emphasize to the FDA the life-limiting cardiovascular impact of this disease. Should deramiocel be approved, it would represent a first-in-class therapeutic option for this critical unmet medical need. We are now in the final stages of data preparation.

Deramiocel 已被證明有助於保護心肌和骨骼肌功能，我們的目標是向 FDA 強調這種疾病對心血管造成的生命限制性影響。如果 deramiocel 獲得批准，它將成為滿足這一關鍵未滿足醫療需求的首創治療方案。我們現在正處於資料準備的最後階段。

Our statistical analysis plan has been submitted to the FDA, and the comment period passed without additional feedback. We plan to unblind the study once all data management processes are finalized, which, as noted, will occur within the next several weeks. The process has required review of more than 300 MRIs by independent external readers, who are fully blinded both to treatment allocation and sequence, a process that requires additional time to collect and analyze the data set.

我們的統計分析計畫已提交給FDA，意見徵詢期已過，未收到其他回饋。我們計劃在所有資料管理流程完成後揭盲這項研究，正如前面提到的，這將在接下來的幾週內完成。這個過程需要由獨立的外部閱片者審查 300 多張 MRI 影像，這些閱片者對治療分配和順序完全不知情，這一過程需要額外的時間來收集和分析資料集。

To remind you, after our pre-BLA meeting with the FDA in 2024, we submitted a BLA based on existing data from our HOPE-2 and HOPE-2 open-label extension trials compared to an external control comparator from the cardiac consortium. At that time, the purpose of HOPE-3 was to support potential ex-US.

提醒一下，在 2024 年與 FDA 舉行 BLA 前會議後，我們根據 HOPE-2 和 HOPE-2 開放標籤擴展試驗的現有數據，與心臟聯盟的外部對照比較，提交了 BLA。當時，HOPE-3 的目的是支持潛在的前美國公民。

expansion, as well as label expansion. However, following receipt of the CRL in July, the role of HOPE-3 shifted. The CRL primarily cited the need for additional substantial evidence of effectiveness and certain CMC clarifications. Importantly, most of the CMC issues had already been addressed in prior information request responses. And the remainder were resolved shortly after the receipt of the CRL.

擴張，以及標籤擴張。然而，在 7 月收到 CRL 後，HOPE-3 的角色發生了轉變。CRL 主要指出需要提供更多實質的有效性證據以及某些 CMC 澄清。重要的是，大多數 CMC 問題已經在先前的資訊請求回覆中解決。其餘問題在收到 CRL 後不久即解決。

While the CRL was unexpected, we were well positioned with HOPE-3 to provide the additional safety and efficacy data requested by the FDA. During our Type A meeting in August of this year, the FDA indicated that the HOPE-3 results could be submitted to address the issues raised in the CRL.

雖然收到 CRL 出乎意料，但我們憑藉 HOPE-3 項目，能夠提供 FDA 要求的額外安全性和有效性數據。在今年 8 月的 A 類會議上，FDA 表示 HOPE-3 研究結果可以提交給 CRL 以解決提出的問題。

A key element of that meeting was our request to keep the current BLA open and maintain the indication for DMD-associated cardiomyopathy. To advance that path, we proposed designating left ventricular ejection fraction -- LVEF -- as the primary efficacy endpoint. While the FDA did not allow this formal change, they agreed to exercise regulatory flexibility in reviewing the HOPE-3 data.

那次會議的一個關鍵內容是我們要求保持目前的生物製品許可申請 (BLA) 有效，並維持其用於治療 DMD 相關心肌病變的適應症。為了推進這一進程，我們建議將左心室射血分數（LVEF）指定為主要療效終點。雖然 FDA 沒有允許這種正式的改變，但他們同意在審查 HOPE-3 資料時行使監管彈性。

Accordingly, we plan to submit the HOPE-3 results as a formal complete response to the CRL, with the goal of receiving a rapid review by the FDA and a new PDUFA date. As of now, FDA has classified the resubmission as type 2, which means the review period can be up to six months, but there is precedent for faster review times.

因此，我們計劃將 HOPE-3 研究結果作為對 CRL 的正式完整回應提交，目標是獲得 FDA 的快速審查和新的 PDUFA 日期。目前，FDA已將重新提交的申請歸類為2型，這意味著審查期可能長達六個月，但也有審查時間更快的先例。

We will make every effort to advance deramiocel toward approval as efficiently as possible in 2026. To remind you, we are eligible to receive a priority review voucher if approved -- if approval is obtained prior to September 30, 2026, and PRVs may become increasingly valuable as the program approaches its statutory sunset. While we cannot predict the exact timing of approval, we remain highly motivated to achieve approval as early as possible in 2026, well ahead of that deadline.

我們將盡一切努力，爭取在 2026 年以最高效的方式推進 deramiocel 的審批流程。提醒您，如果獲得批准，我們將有資格獲得優先審查券——如果在 2026 年 9 月 30 日之前獲得批准，並且隨著該計劃接近其法定終止日期，優先審查券可能會變得越來越有價值。雖然我們無法預測確切的審批時間，但我們仍然充滿動力，爭取在 2026 年儘早獲得批准，遠早於該截止日期。

This consistency demonstrated across multiple clinical studies underscores deramiocel's potential to stabilize disease progression and preserve both muscle and heart function. We now look forward to seeing whether the data from HOPE-3 confirms these benefits in a larger, rigorously controlled pivotal trial.

多項臨床研究均證實了這種一致性，凸顯了 deramiocel 在穩定疾病進展和保護肌肉及心臟功能方面的潛力。我們現在期待看到 HOPE-3 的數據是否能在更大規模、嚴格控制的關鍵性試驗中證實這些好處。

As we approach our quiet period, I will remind you that we expect to report top-line data within the next few weeks. And we will do everything we can to keep both the market and the DMD community informed of our further plans with respect to this program and the release of the data. We also recently published a peer-reviewed paper in Biomedicines, detailing new mechanistic insights into deramiocel's mechanism of action.

在我們即將進入靜默期之際，我提醒各位，我們預計在未來幾週內公佈主要數據。我們將盡一切努力，讓市場和 DMD 社群了解我們關於該計劃和數據發布的後續計劃。我們最近也在《生物醫學》雜誌上發表了一篇同行評審論文，詳細介紹了 deramiocel 作用機制的新機制見解。

The study described in the paper demonstrated that cardiosphere-derived cells, CDCs, the active components of deramiocel, release exosomes and soluble factors that suppress fibrotic gene expression, collagen 1 and collagen 3 in human fibroblasts. These findings were consistent across more than 100 manufacturing lots, validating deramiocel's antifibrotic and immunomodulatory properties and further supporting its mechanism of action.

論文中描述的研究表明，心球衍生細胞（CDCs，即 deramiocel 的活性成分）會釋放外泌體和可溶性因子，從而抑制人類成纖維細胞中纖維化基因、膠原蛋白 1 和膠原蛋白 3 的表達。這些結果在 100 多個生產批次中均得到證實，驗證了 deramiocel 的抗纖維化和免疫調節特性，並進一步支持了其作用機制。

To complement this publication, we also released a scientific video illustrating deramiocel's mechanism of action, which is available on our website, reinforcing the biologic rationale and consistency that underline our entire development program for deramiocel. Now focusing for a moment on the CMC front, following acceptance by the FDA of all findings from our pre-license inspection or PLI, our San Diego commercial facility is fully operational and preparing for GMP production activities. Our manufacturing and quality systems are fully implemented and all CMC-related items cited in the CRL have been addressed.

為了配合本次出版物，我們還發布了一段科學視頻，闡述了 deramiocel 的作用機制，該視頻可在我們的網站上觀看，從而強化了 deramiocel 整個開發計劃所依據的生物學原理和一致性。現在讓我們暫時關註一下CMC方面，在FDA接受了我們上市前檢查（PLI）的所有調查結果後，我們位於聖地亞哥的商業設施已全面投入運營，並準備開展GMP生產活動。我們的生產和品質系統已全面實施，CRL 中提到的所有 CMC 相關事項均已解決。

This achievement reflects the strength of our operations and represents a critical milestone in ensuring readiness for commercialization and long-term product consistency. In parallel, we continue to prepare for launch with advancing initiatives in physician education, patient services, market access and reimbursement.

這項成就體現了我們營運的實力，也是確保商業化準備就緒和產品長期穩定性的關鍵里程碑。同時，我們持續推動醫師教育、病患服務、市場准入和報銷等方面的舉措，為產品上市做好準備。

We are engaging both neurology and cardiology specialists to ensure an integrated approach to patient care should deramiocel receive approval. While our immediate focus remains on US approval, we are also laying the groundwork for potential global expansion and we'll share updates as appropriate.

如果 deramiocel 獲得批准，我們將與神經病學和心臟病學專家合作，以確保採取綜合方法為患者提供護理。雖然我們目前的重點仍然是獲得美國批准，但我們也正在為潛在的全球擴張奠定基礎，我們將在適當的時候分享最新進展。

We are closely monitoring evolving US and international pricing policies, including the current administration stance on most favored nation frameworks and we'll adapt our global strategy accordingly. Now I'd like to spend the next few minutes talking about our exosome platform.

我們正在密切關注不斷變化的美國和國際定價政策，包括本屆政府對最惠國待遇框架的立場，並將據此調整我們的全球策略。接下來我想花幾分鐘時間談談我們的外泌體平台。

We continue to advance our StealthX program under Project NextGen, a US government-funded initiative led by HHS and the National Institutes of Allergy and Infectious Disease to develop next-generation vaccines for COVID-19 and other potential infectious threats.

我們繼續推進 StealthX 項目，該項目隸屬於「下一代計劃」（Project NextGen），這是一項由美國政府資助、美國衛生與公眾服務部 (HHS) 和國家過敏症和傳染病研究所 (NIAID) 牽頭的計劃，旨在開發針對 COVID-19 和其他潛在傳染病威脅的下一代疫苗。

The NIAID sponsored Phase I clinical trial remains ongoing and is evaluating multiple dose levels of the monovalent vaccine, targeting the spike or S antigen with an additional planned arm that will utilize a multivalent vaccine construct targeting spike S and the nucleocapsid N antigens, pending separate FDA clearance. We expect initial data in the first quarter of 2026, subject to completion of the trial by NIAID.

由美國國家過敏症和傳染病研究所 (NIAID) 贊助的 I 期臨床試驗仍在進行中，該試驗正在評估單價疫苗的多個劑量水平，該疫苗針對刺突蛋白或 S 抗原；此外，還計劃增加一個試驗組，該試驗組將使用多價疫苗構建體，該構建體針對刺突蛋白 S 和核衣殼蛋白 N 抗原，目前正在等待美國食品疫苗管理局的藥物。我們預計將於 2026 年第一季獲得初步數據，前提是美國國家過敏和傳染病研究所 (NIAID) 完成試驗。

The goal is to validate StealthX as a versatile non-mRNA adjuvant-free platform capable of delivering native proteins safely and efficiently, a model that could potentially extend to infectious and rare diseases alike. While vaccines are not our core business, this program serves as a critical proof of concept for the StealthX platform. Positive results could open the door to strategic collaborations and highlight the platform's potential for targeted therapeutic delivery well beyond vaccinology.

目標是驗證 StealthX 作為一種多功能的非 mRNA 無佐劑平台，能夠安全有效地遞送天然蛋白質，這種模型有可能擴展到傳染病和罕見疾病領域。雖然疫苗不是我們的核心業務，但該計畫為 StealthX 平台提供了一個重要的概念驗證。積極的結果可能會為策略合作打開大門，並凸顯該平台在疫苗學之外的標靶治療遞送方面的潛力。

With that, I will now turn the call over to AJ, to run through the financials. AJ?

接下來，我會把電話交給 AJ，讓他來介紹一下財務狀況。AJ？

Thanks, Linda. This afternoon's press release provided a summary of our third-quarter 2025 financials on a GAAP basis. And you may also refer to our quarterly report on Form 10-Q, which we expect to become available shortly and will be accessible on the SEC website, as well as the Financial Section of our website. Let me start with our cash position. As noted, as of September 30, 2025, our cash, cash equivalents and marketable securities totaled approximately $98.6 million.

謝謝你，琳達。今天下午的新聞稿概述了我們 2025 年第三季的財務狀況（按美國通用會計準則計算）。您也可以參考我們的季度報告（10-Q 表格），我們預計該報告很快就會發布，屆時您可以在 SEC 網站以及我們網站的財務版塊查閱。首先讓我介紹一下我們的現金狀況。如前所述，截至 2025 年 9 月 30 日，我們的現金、現金等價物和有價證券總額約為 9,860 萬美元。

We believe that based on our current operating plan and financial resources, our available cash, cash equivalents and marketable securities will be sufficient to cover anticipated expenses and capital requirements into the fourth quarter of 2026. Turning briefly to the financials. Revenue for the third quarter of '25 were zero compared to approximately $2.3 million for the third quarter of 2024.

我們相信，根據我們目前的營運計畫和財務資源，我們現有的現金、現金等價物和有價證券足以支付預期支出和資本需求，直至 2026 年第四季。接下來簡單看一下財務狀況。2025 年第三季的營收為零，而 2024 年第三季的營收約為 230 萬美元。

Additionally, revenue for the first three quarters of 2025 were zero compared to approximately $11.1 million for the first three quarters of 2024. I'd like to point out that the source of revenue in 2024, was the ratable recognition of the $40 million we have received under our US.

此外，2025 年前三個季度的收入為零，而 2024 年前三個季度的收入約為 1,110 萬美元。我想指出，2024 年的收入來源是我們根據美國稅法收到的 4000 萬美元的按比例確認收入。

distribution agreement with Nippon Shinyaku, which had been fully recognized as of December 31, 2024. Turning to our operating expenses for the third quarter of 2025. Excluding stock-based compensation, our research and development expense were approximately $18.1 million compared to approximately $11 million in Q3 2024.

與日本新藥株式會社的經銷協議已於 2024 年 12 月 31 日得到全面認可。接下來我們來看看2025年第三季的營運費用。不計股權激勵費用，我們的研發費用約為 1,810 萬美元，而 2024 年第三季約為 1,100 萬美元。

And for the first three quarters of 2025, excluding stock-based compensation, our research and development expenses were approximately $54.4 million compared to approximately $32.8 million in the first three quarters of 2024. Again, excluding stock-based compensation, our G&A expenses were approximately $4.1 million in Q3 2025, and approximately $2.2 million in Q3 2024.

2025 年前三個季度，不包括股票選擇權費用，我們的研發支出約為 5,440 萬美元，而 2024 年前三個季度約為 3,280 萬美元。再次強調，不包括股票選擇權費用，我們2025年第三季的一般及行政費用約為410萬美元，2024年第三季約為220萬美元。

For the first three quarters of '25, excluding stock-based comp, our general and administrative expenses were approximately $11.1 million and approximately $5.7 million for the first three quarters of 2024. Net loss for the third quarter of '25 was approximately $24.6 million compared to a net loss of approximately $12.6 million for the third quarter of 2024.

2025 年前三個季度，不包括股票選擇權激勵，我們的一般及行政費用約為 1,110 萬美元；2024 年前三個季度，該費用約為 570 萬美元。2025 年第三季淨虧損約 2,460 萬美元，而 2024 年第三季淨虧損約 1,260 萬美元。

And net loss for the first three quarters of '25 was approximately $74.9 million compared to a net loss of approximately $33.4 million for the first three quarters of 2024. With that, I'll turn the call back over to Linda.

2025 年前三個季度的淨虧損約為 7,490 萬美元，而 2024 年前三個季度的淨虧損約為 3,340 萬美元。這樣，我就把電話轉回琳達了。

Thanks, AJ.

謝謝你，AJ。

As AJ just mentioned, we ended the quarter with approximately $100 million in cash, providing a solid foundation to continue executing on our near-term objectives and advancing our key programs.

正如 AJ 剛才提到的，我們本季末擁有約 1 億美元的現金，為我們繼續執行近期目標和推進關鍵項目奠定了堅實的基礎。

Let me just remind you that if deramiocel is approved, we remain eligible to receive $80 million milestone payment from NS Pharma, and a priority review voucher, which represents significant non-dilutive capital opportunities that would strengthen our balance sheet and extend our runway well into 2027 and beyond.

我在此提醒各位，如果 deramiocel 獲得批准，我們仍有資格從 NS Pharma 獲得 8000 萬美元的里程碑付款和優先審評券，這代表著重要的非稀釋性資本機會，這將增強我們的資產負債表，並將我們的資金支持延長至 2027 年及以後。

We will now open the line for questions.

現在我們將開放提問通道。

(Operator Instructions)

（操作說明）

Ted Tenthoff, Piper Sandler.

泰德·滕索夫，派珀·桑德勒。

Great. Excited for the upcoming HOPE-3 data. I just want to get a sense for what we should expect from that in terms of what will be actually released in the initial data reporting in the top-line data.

偉大的。非常期待即將發布的HOPE-3數據。我只是想了解一下，就初步數據報告中的整體數據而言，我們應該期待些什麼。

Ted, always great to hear your voice. Yes, the top-line data will be primary and key secondary endpoints. We will release those as soon as we have them. And we'll host a conference call to explain them and help the markets, as well as the key opinion leaders help explain the ramifications of that data.

泰德，很高興再次聽到你的聲音。是的，主要終點數據和關鍵次要終點將是總體數據。我們一拿到這些資訊就會立刻發布。我們將召開電話會議來解釋這些數據，並幫助市場以及關鍵意見領袖解釋這些數據的影響。

Just one quick follow-up, if I may. With the consideration of left ventricular ejection fraction as a key secondary, are there any statistical changes in this study because of elevating LVEF tanks?

如果可以的話，我再補充一個問題。考慮到左心室射血分數作為關鍵次要因素，提高左心室射血分數是否會導致本研究出現統計上的變化？

No, Ted. So thanks for that. So the great thing is the study was always powered with the idea that we were well overpowered to measure ejection fraction. We had such strong results from HOPE-2 and HOPE-2 open-label extension that it really wasn't an issue. We have tremendous powering for ejection fraction.

著名的。謝謝。所以最棒的是，這項研究從一開始就基於這樣一個理念：我們有足夠的能力來測量射血分數。HOPE-2 和 HOPE-2 開放標籤擴展研究取得了非常顯著的成果，所以這真的不是問題。我們擁有強大的射血分數提升能力。

It was powered for PUL, but that the overarching power is quite strong for the cardiac as well.

它為 PUL 供電，但其整體功率對於心臟來說也相當強勁。

Leland Gershell, Oppenheimer.

利蘭·格謝爾，奧本海默。

I wanted to ask just a bit further on HOPE-3 and the SAP. We're in this unique circumstance of having a BLA that's for the cardiomyopathy, but the primary endpoint of the trial is the PUL 2.0. So wondering how the SAP designates treatment of the LVEF secondary endpoint in the situation in which you miss significance on the primary?

我想再問一下關於 HOPE-3 和 SAP 的問題。我們目前的情況比較特殊，BLA 是針對心肌病變的，但試驗的主要終點是 PUL 2.0。所以我想知道，在主要終點未達到顯著水準的情況下，SAP 如何定義 LVEF 次要終點的治療？

Yes. Leland, thanks so much. So this has obviously been an issue that we've spent a lot of time thinking about, working with the FDA. And we've brought in several very well-respected statistical consultants to help us build an SAP that allows for both of those parameters, right? So the Food and Drug Administration said we want the primary to remain the performance of the upper limb.

是的。萊蘭，非常感謝。顯然，這個問題我們已經花了很多時間思考，並與美國食品藥物管理局（FDA）進行了合作。我們已經聘請了幾位備受尊敬的統計顧問來幫助我們建立一個能夠同時滿足這兩個參數的 SAP 系統，對吧？因此，美國食品藥物管理局表示，我們希望主要目標仍然是上肢功能。

We left it as a performance of the upper limb. The way that the primary is being analyzed, as I mentioned in my remarks. We'll look at the combined cohorts A and B.

我們將其保留為上肢的表演形式。正如我在發言中提到的，初選的分析方式。我們將考察合併後的 A 組和 B 組。

But we're going to focus then also on looking specifically at Cohort B, because that's going to provide strength in the manufacturing facility that we have built and passed PLI with. The alpha is going to be used in the primary endpoint, as would be in any other situation.

但我們接下來也將重點放在 B 組，因為這將增強我們已經建成並通過 PLI 認證的製造工廠的實力。alpha 值將用於主要終點，就像在其他任何情況下一樣。

And should we achieve statistical significance and that alpha passes through to the secondaries and continues along until you miss a secondary. The key secondary of ejection fraction, we did not reserve any specific alpha for.

如果我們達到統計顯著性，並且該 alpha 值傳遞到次要節點，並繼續傳遞，直到錯過某個次要節點。對於射血分數這個關鍵次要因素，我們沒有預留任何特定的α值。

But we know from our Type A meeting that the FDA was interested in looking at all of the data in its totality. So the SAP is a pretty traditional one and actually fairly simple with which we think we have a lot of great opportunity to utilize the performance of the upper limb and then also ejection fraction. Now just to add a little bit of color to what you asked, because our open BLA is for cardiomyopathy.

但從我們的 A 類會議中我們了解到，FDA 有興趣全面審視所有數據。所以，SAP 是一種相當傳統的，實際上也相當簡單，我們認為它為我們提供了很大的機會來利用上肢的表現以及射血分數。現在，為了讓您提出的問題增添一些色彩，因為我們開放的 BLA 是用於治療心肌病變的。

We are not going to ask -- at least in first iteration -- to expand the indication to skeletal muscle until we are assured that we're going to get the indication and label of cardiomyopathy.

我們不會——至少在第一階段——要求將適應症擴大到骨骼肌，直到我們確信能夠獲得心肌病變的適應症和標籤。

Once we have achieved that with the agency, we will then assuming that we have statistical significance in the primary, we'll then ask to expand to skeletal muscle as well.

一旦我們與該機構達成一致，假設我們在主要方面具有統計意義，我們將要求將範圍擴大到骨骼肌。

Also just a question with respect to the cardiac MRI review procedure. Could you just run us through that? Are all of these reviewed by an external review? Or is there an adjudication process? If you wouldn't mind just summarizing that.

另外，我也想問一下關於心臟磁振造影報告審查流程的問題。能給我們簡單介紹一下嗎？這些都經過外部審查嗎？或是否存在裁決程序？如果你不介意的話，能否幫我總結一下？

Yes. So that's obviously very important and something that we have a charter in place that was signed off on, which is multifaceted. So first, an outside CRO reviews every single MRI, they're first quality controls. So everybody looks at them, at the CRO to make sure that the image meets the standards of being able to be reviewed and analyzed.

是的。所以這顯然非常重要，我們已經制定並簽署了相關章程，該章程涉及多個方面。首先，由外部 CRO 對每一張 MRI 影像進行審核，這是第一道品質控制關卡。所以大家都會查看 CRO，以確保影像符合審查和分析的標準。

Once that happens, then they're read by a primary reader, a secondary reader; and then anywhere the primary reader and the secondary reader disagree by a certain number, which is of relevance that could not possibly change that much over a certain time period, there is a third reader that comes in for adjudication.

一旦這種情況發生，它們就會由一名主要讀者和一名次要讀者閱讀；然後，如果主要讀者和次要讀者之間的分歧達到一定程度（在一定時間段內不可能發生太大變化），則會由第三名讀者進行裁決。

And then the three of them look at it together to decide which, in fact, would be the appropriate read. So there's a tri-level measurement procedure. And they are independent to time point. So they don't know which time point it is and also to patient ID and obviously, the treatment group.

然後他們三人一起查看，決定究竟哪種解讀才是真正適合的。所以，這裡採用的是三級測量程序。而且它們與時間點無關。所以他們不知道是哪個時間點，也不知道病人 ID，當然也不知道治療組。

Joseph Pantginis, H.C. Wainwright.

約瑟夫·潘特吉尼斯，H.C. 溫賴特。

Linda, I just wanted to clarify something quickly before my question. So depending on the primary endpoint, you said you're going to continue to look for cardiomyopathy and then if statistically significant, expand to skeletal, if I heard you correctly. Would that be in the form of an sBLA?

琳達，在提問之前，我想先澄清一件事。所以，根據主要終點，您說您會繼續尋找心肌病，如果具有統計意義，則會擴展到骨骼肌疾病，如果我理解正確的話。那會是以sBLA的形式嗎？

Yes. So interesting that you asked that. We don't really know exactly how we're going to go about that yet. It's going to involve conversations with the agency. So right now, we have a CRL.

是的。你問這個問題真有意思。我們目前還不清楚具體該如何著手。這需要與相關機構進行溝通。所以目前，我們有一個 CRL。

The CRL said we want to see more data. We're going to give them more data as a response to the CRL. We're going to provide all the data, which includes the primary and the key secondary endpoints, which we've also agreed that we would provide publicly.

CRL表示，我們希望看到更多數據。我們將向他們提供更多數據，以回應 CRL。我們將提供所有數據，包括主要終點和關鍵次要終點，我們也同意公開提供這些數據。

So you'll get to see them too. And then in those conversations, we'll decide how we're going to do the label expansion of skeletal should that be appropriate.

所以你們也能看到它們。然後，在這些對話中，我們將決定如果合適的話，我們將如何擴展骨骼的標籤。

I just wanted to make sure I understood. Because it looks like with regard to the analyses, you're going to be looking at the two manufacturing cohorts of A and B versus B alone. Does that include any alpha spend at all? Or how should we view those in general impacting the SAP or not?

我只是想確認我理解了。因為看起來，就分析而言，你們將要比較 A 和 B 這兩個製造群體與單獨的 B 群體。這是否包括任何超額收益支出？或者我們應該如何看待那些對 SAP 有影響或沒有影響的因素？

Yes. So the way that the analysis is built is a statistical analysis that's very commonly used, called the Hochberg analysis, which basically does not utilize alpha spend if you prespecify which group you are going to be directing your alpha towards.

是的。因此，這種分析方法是一種非常常用的統計分析，稱為霍赫伯格分析，它基本上不使用 alpha 支出，只要你預先指定要將 alpha 投入到哪個群體即可。

So if you are, for instance, going to say A or B and we'll take either one, that's an alpha spend so that you would then have a 0.025 going into your secondary. But if you actually direct it prespecified, you save all your alpha and therefore, you have it to use in your secondaries.

例如，如果你要選擇 A 或 B，我們會選擇其中任何一個，這就是 alpha 支出，這樣你就會在你的二級市場投入 0.025。但如果你事先指定方向，你就能節省所有 alpha 值，因此你可以在輔助武器中使用它。

Maybe a question for AJ, and if you'd like to fill in, that would be great. I wanted to get a sense now with regard to your burn going forward. You have a couple of things coming down, a few things potentially going up.

也許可以問AJ一個問題，如果你願意回答，那就太好了。我想了解你接下來的燒傷情況。有些東西會下降，有些東西可能會上升。

You'll have HOPE-3 wrapping up in the clinical trial expenses around that. I wanted to see about discussing manufacturing expenses that might be increasing, personnel and then maybe a gradual increase in exosomes.

HOPE-3 的臨床試驗費用將大致包含在這些費用中。我想探討製造成本可能會增加、人員配備以及外泌體產量可能會逐漸增加等問題。

Maybe some views on how the expenses might be going forward.

或許可以談談對未來開支狀況的看法。

Yes. Thanks, Joe. Obviously, our expenses in the third quarter were higher than they had been. But we were moving towards pretty much a PDUFA date as we moved -- got -- received our CRL in July. A lot of the expenses you just said correctly have gone into the execution of the HOPE-3 trial, which is winding down.

是的。謝謝，喬。顯然，我們第三季的支出比以往都要高。但隨著我們在 7 月收到 CRL，我們幾乎已經朝著 PDUFA 日期邁進了一步。您剛才說的很多費用都用於執行 HOPE-3 試驗，而該試驗即將結束。

So we'll see those expenses hopefully continue to wind down. But they're going into the manufacturing and the development of the commercial product as we prepare and continue to prepare for a commercial launch.

所以我們希望這些開支能夠持續減少。但他們正在投入商業產品的製造和開發中，因為我們正在為商業發布做準備，並且會繼續為商業發布做準備。

So we're maintaining and cautiously watching our burn in every area we can. We're building out our team in areas that are absolutely necessary. And then obviously, following the results of the data and our next steps with FDA.

因此，我們正在盡一切可能控制和謹慎地監控各個領域的支出。我們正在絕對必要的領域擴充團隊。然後，很顯然，我們將根據數據結果以及與 FDA 的後續步驟進行調整。

We'll continue to put the dollars to work where they need to go. So we feel very comfortable with where we're at. And we're putting -- diligently investing in where we hope to drive value. Exosome, same type of answer. Just to point out, NIAID is obviously funding that study.

我們將繼續把資金用在最需要的地方。所以我們對現狀感到非常滿意。我們正在認真地投資我們希望創造價值的領域。外泌體，答案同上。需要指出的是，NIAID顯然正在資助這項研究。

We've said that many times. We've already made the doses necessary for that. So that's well off our balance sheet, which hopefully will be a nice value driver and catalyst for us in the early part of 2026.

我們已經說過很多次了。我們已經製備了所需的劑量。這樣一來，這筆支出就完全從我們的資產負債表中剔除了，希望這能在 2026 年初成為我們公司價值成長和發展的催化劑。

Kristen Kluska, Cantor.

克里斯汀克魯斯卡，坎托爾。

I'm sending you all my best in the next few weeks ahead for the company. So on the statistical analysis plan, my understanding was when you originally designed the Phase III study, you powered it based off of Cohort A in terms of patient size number. And now that you will be using Cohort B, it's essentially the same size anyway. Is my understanding correct here?

接下來幾週，我向公司全體員工致上最誠摯的問候。所以，關於統計分析計劃，我的理解是，當你們最初設計 III 期研究時，你們是根據 A 組的患者人數來確定其統計功效的。既然你們要使用 B 組，那麼它的規模基本上也是一樣的。我的理解正確嗎？

Yes, pretty close, Kristen That's exactly right. So we combined them. It's been a long journey, right? So we started with Cohort A, then we were told by FDA we needed to add Cohort B for efficacy. Then when we were filing the BLA on the existing data, we combined A and B into one clinical trial because they agreed to nonclinical comparability between the sites.

是的，差不多了，克莉絲汀。你說得完全正確。所以我們把它們結合起來了。這真是一段漫長的旅程，對吧？所以我們先進行了 A 組試驗，然後 FDA 告訴我們，為了評估療效，我們需要增加 B 組試驗。然後，當我們根據現有數據提交 BLA 時，我們將 A 和 B 合併為一個臨床試驗，因為他們同意各試驗點之間具有非臨床可比性。

But now especially with some of the things that's going on with the administration, the fact that our manufacturing plant in San Diego has passed PLI, we've answered their CMC issues. We feel that it was important to be able to highlight the potential efficacy of Cohort B.

但現在，尤其是考慮到政府的一些舉措，以及我們在聖地牙哥的製造工廠已經通過了PLI認證，我們已經解決了他們的CMC問題。我們認為，強調 B 組的潛在療效非常重要。

And yes, the powering is pretty much the same. Cohort B is a little smaller with an 80% powering. Cohort A was a 90% powering.

是的，供電方式基本上相同。B組樣本量略小，統計效力為80%。A組樣本的統計效力為90%。

But we still feel that we're well within the range of ability to achieve efficacy.

但我們仍然認為我們完全有能力達到預期效果。

I know in the past, you've shared with us a little bit of the baseline characteristics amongst these patients, including the percent that had cardiomyopathy. As we now divide it between A and B, would you say that, that statement is still true? Or is there one cohort where the baselines are skewing a little bit differently?

我知道過去您曾與我們分享過這些患者的一些基本特徵，包括患有心肌病變的百分比。如果我們現在將其分為 A 和 B 兩部分，你認為之前的說法仍然成立嗎？或是否存在某個群體，其基線數據略有不同？

Yes. So the baseline characteristics are pretty much identical across the cohorts. We didn't change inclusion/exclusion criteria for either one. And really, it didn't work out in any specific way that it was heavily weighted one way or the other. We have seen and obviously, I don't know the data from HOPE-3.

是的。因此，各組人群的基線特徵幾乎完全相同。我們沒有改變這兩項研究的納入/排除標準。實際上，結果並沒有以任何具體方式顯示它對某一方有很大的權重。我們已經看到了，顯然，我並不了解 HOPE-3 的數據。

But we've seen from HOPE-2 open-label extension from John Soasllow's natural history study that those patients that get treatment with ejection fraction over 45% seem to do specifically well compared to those that are worse off. So we're definitely trying to get to these guys as early in the pathogenesis of the cardiomyopathy as possible.

但從約翰·索斯洛的自然史研究 HOPE-2 開放標籤擴展研究中我們可以看出，在射血分數超過 45% 的患者接受治療後，其治療效果似乎比射血分數較低的患者要好得多。所以我們肯定會儘早介入，在心肌病變的發病機制中儘早發現並治療這些患者。

I think when we did the analysis of Cohort A and B together in preparation for the CRL response, we had over 70 that would have had diagnosed cardiomyopathy. One thing that's really nice about Cohort B is we're also measuring scar as measured by late gadolinium enhancement.

我認為，當我們一起對 A 組和 B 組進行分析，準備應對 CRL 時，我們發現有 70 多人被診斷出患有心肌病變。B組的一個優點是，我們也透過晚期钆增強來測量瘢痕。

So we'll also be able to do a correlation between the amount of damage that looks visible in the heart as well as ejection fraction and/or volumes, which is going to be very important for the field moving forward to understand what the tipping points are in terms of scar aggregation and function.

因此，我們也可以將心臟中可見的損傷程度與射血分數和/或容積進行關聯，這對於該領域未來的發展非常重要，有助於了解瘢痕聚集和功能的臨界點。

Catherine Novack, Jones Trading.

凱瑟琳·諾瓦克，瓊斯貿易公司。

I just have a question on -- when you mentioned FDA intended to exercise regulatory flexibility. At what point would -- do you intend to ask them to exercise this flexibility? There's a possibility that you don't see statistical significance on PUL, but there is some apparent benefit on LVEF. Is this a situation in which you would want the FDA to try to look at the totality of the data going forward?

我有個問題－您提到FDA打算行使監管彈性的時候。你打算在什麼情況下要求他們行使這種彈性？PUL 可能沒有統計意義，但 LVEF 似乎有一些明顯的益處。在這種情況下，您是否希望FDA嘗試全面檢視所有數據？

Yes. So you hit it exactly. We are obviously anxiously awaiting the data. The easiest story will be if we hit PUL and we hit ejection fraction. If for some reason, we miss on PUL.

是的。你擊中了要害。我們顯然正焦急地等待著數據。最簡單的解釋就是，如果我們達到 PUL 並達到射血分數目標。如果由於某種原因，我們錯過了 PUL。

And I think there's a lot of information that's being discussed both in the Cognizente arenas in terms of the performance of the upper limb, what its utility is, how good of a measure it is, the lability of it, that thing. If for some reason, we miss on PUL, but we hit hard on cardiac, that would be where we would ask for that regulatory flexibility.

我認為在認知領域，關於上肢的表現、其效用、其測量效果如何、其不穩定性等等，有很多資訊正在被討論。如果由於某種原因，我們在 PUL 方面有所疏忽，但在心臟病方面取得了重大進展，那麼我們就會要求監管方面的靈活性。

And we're hopeful that based on what we have in the Type A minutes, what we have educated the FDA about with the performance of the upper limb and the key opinion leaders that we would still be able to succeed in getting the label for cardiomyopathy.

我們希望，根據我們在 A 型心肌病變治療方案中取得的進展，以及我們向 FDA 提供的關於上肢功能和關鍵意見領袖的信息，我們仍然能夠成功獲得心肌病變的適應症標籤。

Then if there's anything you can share specifically what -- about what FDA did say when it comes to regulatory flexibility. We've obviously seen them be more stringent when it comes to statistics in recent decision-making. If there's anything you can give us to -- any more specific detail you can give us about what FDA has said about what it means to exercise regulatory flexibility?

那麼，如果您能具體分享FDA在監管靈活性方面說了些什麼，那就太好了。很明顯，在最近的決策中，他們對統計數據的要求更加嚴格了。如果您能提供一些資訊—關於FDA對行使監管彈性的具體表述—您能否提供更具體的細節？

Yes. I think when we put out our press release on our Type A meeting, we actually provided a quote in there that came directly from the minutes, which basically said, we want you to submit all of your data from HOPE-3. We're not willing to change the primary to ejection fraction.

是的。我認為，當我們發布關於 A 類會議的新聞稿時，我們實際上在其中引用了會議記錄中的一段話，這段話大意是：我們希望你們提交 HOPE-3 的所有數據。我們不願改變主要射血分數。

But we will regard all of the data and make decisions based on pretty much the preponderance of all the data. They did not give us specifics.

但我們會考慮所有數據，並根據絕大多數數據做出決定。他們沒有提供具體細節。

We did have a hallway conversation in which one of the reviewers assured the mother, Mindy Leffler. That came with us to our Type A meeting that they would be very sure to look at the cardiac data very carefully as they recognize that this was the unmet medical need with no approved therapeutics for that patient population.

我們確實在走廊上進行了一次談話，其中一位評論員向母親 Mindy Leffler 保證了這一點。我們帶著這個想法參加了 A 類會議，他們一定會非常仔細地查看心臟數據，因為他們認識到這是尚未滿足的醫療需求，目前還沒有針對該患者群體的批准療法。

Madison El-Saadi, B. Riley Securities.

Madison El-Saadi，B. Riley Securities。

A couple from us. Do you have a sense that from the FDA's position, how did they view Cohort B? Is it more importance than the aggregate PUL? And then secondly, maybe what is the bar to achieve a more rapid review time that you alluded to? And has that been a request that has been made?

我們中的一對夫婦。您認為從FDA的角度來看，他們是如何看待B組的？它比總 PUL 更重要嗎？其次，您提到的更快的複習速度的標準是什麼？已經有人提出過這樣的請求嗎？

Or is that something that you would request alongside the submission of HOPE-3 data?

或者，這是您希望在提交 HOPE-3 資料時一併提出的要求嗎？

Yes, yes. All really good questions. So the reason that we're focusing a little bit more on Cohort B, which we might not have done had the original plan of the existing data been accepted.

是的，是的。都是很好的問題。因此，我們之所以更加關注 B 組，是因為如果接受現有數據的原始計劃，我們可能不會這樣做。

And we had approval already for the cardiomyopathy is because we knew that there was some question regarding the manufacturing of the product from San Diego that it was a shift from a clinical facility to a commercial facility and we passed the PLI. So we've seen, frankly, a lot of CRLs being issued in the last few months around CMC-related concerns.

我們已經獲得了心肌病變的批准，因為我們知道該產品在聖地亞哥的生產存在一些問題，即從臨床設施轉向商業設施，而我們通過了PLI（產品生命週期影響評估）。坦白說，在過去的幾個月裡，我們看到許多 CLC 相關問題都引發了 CRL 問題。

And so we wanted to obviate that by targeting our efficacy data to our approved facility. We thought that would be the safest way to go about it. And since the powering was basically the same. We thought that would be one of the best ways to assure the fastest path to approval.

因此，我們希望透過將療效數據限制在我們已獲批准的設施內來避免這種情況。我們認為這是最安全的做法。而且供電方式基本上相同。我們認為這是確保最快獲得批准的最佳途徑之一。

In terms of timelines and speeding it up, that, again, is going to be based on what we see in the data, where we can convince the agency to move a little bit quicker.

至於時間安排和加快進度，這也取決於我們從數據中看到的情況，以及我們能否說服相關機構加快速度。

We have seen them do it. They did it with Calvista. They did it with Stealth. They are typically falling back on as long a review period as possible. And part of that, I think, is just because they are so understaffed and going through so many changes themselves that speed is hard for them.

我們親眼見過他們這樣做。他們和Calvista一起做到了。他們用隱形技術做到了。他們通常會盡可能延長審查週期。我認為部分原因是因為他們人手嚴重不足，而且自己也在經歷很多變革，所以速度對他們來說很困難。

But we certainly will work with them and try and get this to PDUFA as quickly as we possibly can.

但我們一定會與他們合作，盡我們所能盡快將此事提交給 PDUFA。

If I may ask one more to clarify. I think you answered this a couple of questions back. But could you clarify the LGE stratification, if that was balanced across both cohorts? Or is that a Cohort B specific stratification that was reached?

我可以再問一個問題來澄清一下嗎？我想你之前已經回答過這個問題了。但是，您能否解釋 LGE 分層情況，看看兩個隊列之間的分層是否平衡？或者這是針對 B 組族群的特定分層？

Yes. So we didn't measure LGE in HOPE-2 or Cohort A. And that was largely because there was a little bit of a haze at the time that LGE might cause aggregation of the brain, that there might be some bad side effects. And so we didn't really want to jump into that pool of messiness. But several things happened along the way.

是的。因此，我們在 HOPE-2 或 A 組隊列中沒有測量 LGE。這主要是因為當時人們對 LGE 可能導致腦組織聚集、可能產生一些不良副作用有些疑慮。所以，我們並不想貿然跳進那團亂麻之中。但在過程中發生了一些事情。

One, those substantiations were not proven to be true. LGE is safe. And two, our cardiology leaders convinced us that since we know that the pathogenesis of the cardiomyopathy associated with DMD is very different than what would be considered an adult dilated cardiomyopathy.

第一，這些佐證並未被證實為真。LGE是安全的。第二，我們的心臟科醫生說服了我們，因為我們知道與 DMD 相關的心肌病變的發病機制與成人擴張型心肌病變的發病機制非常不同。

It would be really interesting to be able to correlate scar, how much, where, when and then how it potentially correlates with ejection fraction. So it's an exploratory endpoint.

如果能夠將瘢痕的大小、位置、時間以及它與射血分數之間的潛在關聯聯繫起來，那將非常有趣。所以這是一個探索性的終點。

But one as a cardiac physiologist, I'm very excited to see because it could provide some very important answers in developing treatment paradigms for Duchenne muscular dystrophy.

但身為心臟生理學家，我對此感到非常興奮，因為它可能為杜氏肌肉營養不良症的治療模式的發展提供一些非常重要的答案。

(Operator Instructions)

（操作說明）

Boobalan Pachaiyappan, ROTH Capital Partners.

Boobalan Pachaiyappan，羅仕資本合夥人。

So I just have a couple starting from the type 2 classification. I think this is the first time you're articulating that type 2 is likely. And obviously, this is going to garner a review period of six months.

所以我只有幾個從第二類分類開始的例子。我想這是你第一次明確表示可能是 2 型。顯然，這將經過六個月的審查期。

So I wonder if there were any recent developments between you and the FDA that made you believe or the Class 1 resubmission is impossible. I just wanted to know when this decision on type 2 was like set in stone.

所以我想知道，您和FDA之間最近是否有任何進展，讓您認為重新提交1類藥物申請是不可能的。我只想知道關於 2 型糖尿病的決定何時才能最終確定。

Yes, yes. So thanks for your question. I think I pretty much answered it when Madison asked a similar question a moment ago. So we know that most people are getting Class 2 resubmissions. That's what we're expecting.

是的，是的。謝謝你的提問。我覺得剛才麥迪遜問類似問題的時候，我已經回答了。所以我們知道大多數人都會收到 2 類重新提交的申請。這就是我們所預期的。

That's what we've been told we should expect. In terms of being able to speed it up, I think that's going to be incumbent upon the strength of the data. Our conversations with the agency and other imponderable factors that I cannot answer until I have not only seen the data, but also met with the agency.

我們被告知，我們應該預料到這種情況。至於能否加快速度，我認為這將取決於數據的品質。我們與該機構的對話以及其他一些難以預料的因素，在我不僅看到數據，而且與該機構會面之前，我無法回答。

But we'll go as fast as we can. We obviously are looking for a quick PDUFA as well.

但我們會盡力加快速度。我們顯然也在尋求快速的PDUFA（處方藥用戶付費法案）。

Secondly, can you discuss whether the potency assay adequately fulfills the FDA's guidance of potency test for cellular product expectations?

其次，您能否討論一下，此效力測定是否充分符合 FDA 對細胞產品效力測試的指導原則？

Yes. So we're very proud of the way that we have developed the potency assay profile for deramiocel. One of our goals was always to make deramiocel a drug product and not a hand-waving cell therapy. It works, but we really don't know how it works. And so our science team did a methodical multiyear program in which they looked at the data from HOPE-2.

是的。因此，我們對我們開發的 deramiocel 效力測定方案感到非常自豪。我們的目標之一始終是將 deramiocel 打造成一種藥品，而不是一種空泛的細胞療法。它確實有效，但我們真的不知道它是如何運作的。因此，我們的科學團隊開展了一項有條不紊的多年計劃，研究了 HOPE-2 的數據。

They then were able to identify the master cell banks that we use in order to treat the patients in HOPE-2, so we know it works. And then they took those specific cell banks. And they put it through some pretty rigorous RNA-seq assays looking at 166 genes.

然後，他們能夠識別我們在 HOPE-2 中用於治療患者的主細胞庫，因此我們知道它是有效的。然後他們提取了那些特定的細胞庫。他們對其進行了非常嚴格的 RNA-seq 分析，並檢測了 166 個基因。

And all of this, by the way, is in a very nice by tactic few minute overview on our website. Looking at those 166 genes, then, use bioinformatics to basically quantify those that identify CDCs as a completely unique cell type and then identify which ones were up and which ones were down.

順便一提，所有這些內容都可以在我們網站上找到一個非常簡潔明了的幾分鐘概述。然後，觀察這 166 個基因，利用生物資訊學方法對那些將 CDC 識別為完全獨特的細胞類型的基因進行量化，然後確定哪些基因表現上調，哪些基因表現下調。

Once we have identified which ones are CDCs by their genotype, we then put them through an antifibrosis assay, one of the stated mechanisms of action. Looking at the production of collagen 1 and collagen 3 or in this case, the knockdown of collagen 1, collagen 3.

一旦我們透過基因型確定了哪些是 CDC，我們就對它們進行抗纖維化試驗，這是已知的作用機制之一。觀察膠原蛋白 1 和膠原蛋白 3 的生成，或在本例中，觀察膠原蛋白 1 和膠原蛋白 3 的抑制情況。

The main product of fibrosis. And each and every lot has to pass that by a certain quantification in order to be considered effective deramiocel. So we feel very confident in our potency assay profile.

纖維化的主要產物。每一批產品都必須經過一定的量化標準才能被認為是有效的纖維素。因此，我們對自身的效力測定結果非常有信心。

It's now been published. And again, if you're interested in more details, Dr. Christy Elliott, our Chief Science and Operating Officer, does a nice job explaining it in more detail on our website.

現已出版。如果您想了解更多細節，我們的首席科學營運長克里斯蒂·艾略特博士在我們的網站上對此進行了更詳細的解釋。

Matthew Venezia, AGP/Alliance Global Partners.

Matthew Venezia，AGP/Alliance Global Partners。

Just one quick one on the potential label expansion. Is there any chance at first launch if an approval were to be granted that you could get a cardiac and skeletal label? Or are you mostly looking at label expansion further down the line?

關於唱片公司潛在的擴張計劃，我只想簡單提一下。如果獲得批准，首次上市時是否有可能獲得心臟和骨骼標籤？還是你們主要著眼於未來唱片公司的擴張？

No, I think we'll obviously enter into those conversations during our labeling discussions with the agency. Of course, it's all incumbent upon what the data shows.

不，我認為我們顯然會在與該機構討論標籤問題時進入這些主題。當然，這一切都取決於數據如何顯示。

But certainly, if we achieve statistical significance in skeletal and cardiac in our labeling discussions, we will ask for the label to have both parameters.

但可以肯定的是，如果我們在骨骼和心臟的標籤討論中取得了統計意義，我們將要求標籤同時包含這兩個參數。

Just to switch gears a little bit to the exosomes platform. For the COVID vaccine program, we've seen Vaxart recently sell their COVID vaccine program to Dynavax. What are the partnership opportunities that you potentially see? Has there been any inbound? Is there anything you could share on that front for the exosomes platform?

讓我們稍微轉換一下話題，談談外泌體平台。在新冠疫苗計畫方面，我們看到 Vaxart 最近將其新冠疫苗計畫出售給了 Dynavax。您認為潛在的合作機會有哪些？有進貨嗎？關於外泌體平台，您能否分享一些相關資訊？

Yes. So we're all waiting with bated breath for the data to come through from the NIAID study. Obviously, the government shutdown has not helped that. We are looking forward to getting that data. I think once we have that data, we'll be on a more directed shopping expedition for the appropriate partner.

是的。所以我們都屏息以待，等待美國國家過敏與傳染病研究所（NIAID）的研究數據出爐。顯然，政府停擺對此毫無幫助。我們期待獲得這些數據。我認為一旦我們掌握了這些數據，我們就能更有針對性地尋找合適的合作夥伴。

This vaccine is fantastic. It's a native protein vaccine. We use no adjuvant. The lipid that encompasses it is an exosome, which is a natural product. So you don't have to worry about gumming up the liver or the spleen.

這款疫苗太棒了。這是一種天然蛋白質疫苗。我們未使用任何佐劑。包裹它的脂質是外泌體，外泌體是一種天然產物。所以你不用擔心會堵塞肝臟或脾臟。

And if the antibody response and T cell response is anything similar to what we saw preclinically, it should have really tremendous value -- plus because of the little bit of protein that we need to evoke a strong immune response. We can do multivalent vaccines, not only with multivalence for COVID.

如果抗體反應和 T 細胞反應與我們在臨床前觀察到的結果類似，那麼它應該具有巨大的價值——此外，因為我們只需要少量蛋白質就能引發強烈的免疫反應。我們可以研發多價疫苗，不只限於新冠病毒多價疫苗。

For instance, but we could do a COVID plus flu plus RSV and all of those are in the planning stages. So we're pretty excited to see that data. And we'll provide updates as the data becomes available.

例如，我們可以進行新冠肺炎、流感和呼吸道合胞病毒的聯合免疫接種，所有這些都在計劃階段。所以我們非常期待看到這些數據。我們會根據數據情況提供更新資訊。

Joseph Pantginis, H.C. Wainwright.

約瑟夫·潘特吉尼斯，H.C. 溫賴特。

Linda, I want to make sure I'm absolutely sure on this. So forgive me if there's any repetition here. And this goes to the SAP around HOPE-3 and I'm getting questions on this as well. So obviously, you need the primary to hit to be able to trigger LVEF, if I heard that correctly, number one.

琳達，我想確保我完全確定這一點。如果內容有重複，請見諒。這牽涉到 HOPE-3 的 SAP 項目，我也收到了一些關於這方面的問題。所以很明顯，你需要主動脈瓣膜擊中才能觸發左心室射血分數（LVEF），如果我沒聽錯的話，這是第一點。

Is that a question? Or did you just miss Joe?

這是個問題嗎？還是你只是想念喬？

Is that the -- like I just want to make sure that's correct. You have to hit the primary in order to trigger the analysis of LVEF. And if you don't hit the primary, how would LVEF be analyzed? And what would you say would be the hurdle for success there?

是嗎？ ——我只是想確認一下是否正確。您必須點擊主要目標才能觸發 LVEF 分析。如果沒有達到主要目標，如何分析左心室射血分數（LVEF）？那麼，您認為實現這目標的障礙是什麼？

Yes, yes, yes. So this is where the colloquium of regulatory flexibility becomes the open-ended question. It depends on how far we miss on the PUL. Let's say, if we did and then what the p-value independently of ejection fraction would be.

是的，是的，是的。因此，監管靈活性的討論就變成了一個懸而未決的問題。這取決於我們在PUL上的偏差有多大。假設我們這樣做，那麼與射血分數無關的 p 值是多少？

I think we would go in there and fight really hard if we missed by a little on PUL and achieved really nice p-values on ejection fraction.

我認為，如果我們在 PUL 方面稍微失手，但在射血分數方面取得了非常好的 p 值，我們就會全力以赴地去爭取。

It depends on how dogmatic the agency is going to want to be on statistical analyses, which typically use up your alpha in your primary.

這取決於該機構對統計分析的堅持程度，而統計分析通常會消耗掉你在初選中的 alpha 值。

But in this situation, because they had said they would be flexible, that they would look through to the cardiac data, that they know that the applications for cardiac and the BLA, they were looking for more cardiac data. There may be a lot more windows of opportunity than just strict statistical dogma.

但在這種情況下，因為他們曾表示會靈活處理，會仔細審查心臟數據，他們知道心臟申請和生物製品許可申請（BLA）需要更多心臟數據。除了嚴格的統計學教條之外，可能還有更多的機會窗口。

There are no further questions at this time.

目前沒有其他問題了。

I will now turn the call back to Capricor management for their closing remarks. Please go ahead.

現在我將把電話轉回給 Capricor 管理層，請他們作總結發言。請繼續。

Thank you so much for all of your questions and also for participating today.

非常感謝大家提出的所有問題，也感謝大家今天的參與。

Obviously, the coming weeks will be transformative for Capricor, as we prepare to announce the HOPE-3 top-line results. These data will define the next chapter for deramiocel and for our company, as we advance toward our goal of delivering a life-changing therapy to patients and families affected by Duchenne muscular dystrophy.

顯然，接下來的幾週對 Capricor 來說將是具有變革意義的，因為我們將準備公佈 HOPE-3 的主要結果。這些數據將決定 deramiocel 和我們公司的下一個篇章，我們將朝著為受杜氏肌肉營養不良症影響的患者及其家庭提供改變人生的療法的目標邁進。

We remain steadfast in our mission and continue to execute with discipline, scientific rigor, and readiness across every area of our business.

我們始終堅定不移地履行使命，並在業務的各個領域繼續秉持嚴謹的紀律、科學的嚴謹性和充分的準備。

To the DMD community, your courage and partnership continue to inspire everything we do.

致杜氏肌肉營養不良症（DMD）患者群體：你們的勇氣和合作精神一直激勵著我們所做的一切。

We look forward to sharing this important next step with you soon.

我們期待盡快與您分享這項重要的下一步進展。

Thank you so much for joining us today. We will be in touch soon.

非常感謝您今天能來參加。我們將盡快與您聯繫。

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.

女士們、先生們，今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線了。