Capricor Therapeutics Inc (CAPR) 2025 Q2 法說會逐字稿

Good afternoon, ladies and gentlemen, and welcome to the Capricor Therapeutics second-quarter 2025 conference call. (Operator Instructions) This call is being recorded on Monday, August 11, 2025.

女士們、先生們，下午好，歡迎參加 Capricor Therapeutics 2025 年第二季電話會議。（操作員指示）此通話於 2025 年 8 月 11 日星期一錄製。

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

現在，我想將會議交給財務長 AJ Bergmann 來發表前瞻性聲明。請繼續。

Thank you and good afternoon, everyone. 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 research and development plans, including our anticipated conduct and timing of preclinical and clinical studies, our enrollment of patients in our clinical studies, our plans to present or report additional data, our 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, and our financial position, and possible uses of existing cash and investment resources.

謝謝大家，下午好。在我們開始之前，我想聲明一下，我們將在今天的演講中做出一些前瞻性的陳述。這些聲明可能包括關於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（包括我們預期進行的臨床前和臨床研究及其時間安排、我們在臨床研究中招募的患者、我們展示或報告額外數據的計劃）、我們關於監管備案的計劃、涉及我們候選產品的潛在監管發展、潛在的監管檢查、收入和報銷成本

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 actual results to differ materially from those contained in the forward-looking statements.

這些前瞻性陳述是基於當前資訊、假設和預期，可能會發生變化，並涉及許多風險和不確定性，可能導致實際結果與前瞻性陳述中的結果有重大差異。

These and other risks are described in our periodic filings made with the SEC, including our quarterly and annual reports. You're cautioned not to place undue reliance on these forward-looking statements. We disclaim any obligation to update such statements.

這些風險和其他風險在我們向美國證券交易委員會提交的定期文件中有所描述，包括我們的季度報告和年度報告。請注意不要過度依賴這些前瞻性陳述。我們不承擔更新此類聲明的任何義務。

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

說完這些，我將把電話轉給琳達馬班 (Linda Marban)。

Thank you, AJ. Good afternoon, everyone, and thank you for joining us on our second-quarter conference call.

謝謝你，AJ。大家下午好，感謝大家參加我們的第二季電話會議。

At Capricor, our mission remains unchanged and clear, to bring transformative therapies to patients with rare and life-limiting diseases. While this past quarter has presented us with some unique challenges, it has also reinforced our conviction that we have in deramiocel for the treatment of DMD, the agility of our team, and of course, the promise of our pipeline.

在 Capricor，我們的使命始終不變且明確，那就是為患有罕見和危及生命的疾病的患者提供變革性的治療方法。雖然上個季度給我們帶來了一些獨特的挑戰，但它也增強了我們的信心，即我們對 deramiocel 治療 DMD 的能力、我們團隊的敏捷性，當然還有我們產品線的前景。

In particular, for the Duchenne community, we remain unwavering in our commitment to deliver the first approved therapy aimed at specifically treating the cardiomyopathy that affects nearly every patient with Duchenne Muscular Dystrophy and remains the leading cause of death in this devastating disease.

特別是對於杜氏肌肉營養不良症患者群體，我們始終堅定不移地致力於提供首個獲批的療法，專門治療影響幾乎所有杜氏肌肉營養不良症患者的心肌病，這種心肌病仍然是這種毀滅性疾病的主要死亡原因。

Now for the latest update on our biologics license application, or BLA. As previously disclosed, we received a complete response letter from the FDA in July. The CRL stated that the BLA, in its current form, does not meet the statutory requirements for substantial evidence of effectiveness and also referenced certain CMC items, most of which we had already responded to, but which were not reviewed by the FDA due to the issuance of the CRL.

現在介紹一下我們的生物製品許可申請（BLA）的最新進展。如同先前所披露的，我們在 7 月收到了 FDA 的完整回覆信。CRL 指出，目前形式的 BLA 不符合有效性實質證據的法定要求，並且還引用了某些 CMC 項目，其中大部分我們已經做出回應，但由於 CRL 的發布而未通過 FDA 審查。

As a reminder, approximately one year ago in our pre-BLA meeting with the FDA, we requested to switch the primary efficacy endpoint of our ongoing Phase 3 HOPE-3 study to left ventricular ejection fraction or LVEF.

提醒一下，大約一年前，在我們與 FDA 的 BLA 前會議上，我們要求將正在進行的 3 期 HOPE-3 研究的主要療效終點改為左心室射血分數或 LVEF。

And the agency responded by encouraging us to submit on currently available data from our HOPE-2 and HOPE-2 open label extension trials matched to an external natural history comparator and then use the data from our HOPE-3 trial to support potential label expansion in the future. This became the plan that we implemented.

該機構的回應是鼓勵我們提交 HOPE-2 和 HOPE-2 開放標籤擴展試驗的現有數據，並與外部自然歷史比較器進行匹配，然後使用 HOPE-3 試驗的數據來支援未來潛在的標籤擴展。這成為了我們實施的計劃。

While the FDA response contained in the CRL was certainly disappointing, we stand behind the strength of our submission and the substantial progress made throughout the review process, from a successful pre-license inspection or PLI to completion of our mid-cycle review with no deficiencies noted, and timely responses to more than 50 information requests from the FDA. We believe we consistently met the agency's expectations throughout the review process.

儘管 FDA 在 CRL 中的回應確實令人失望，但我們對我們提交的資料的力度和整個審查過程中取得的實質進展充滿信心，從成功的許可前檢查或 PLI 到完成中期審查且未發現任何缺陷，並及時回應了 FDA 提出的 50 多項資訊請求。我們相信，在整個審查過程中我們始終滿足了該機構的期望。

The complete response letter was unexpected given the trajectory of positive interactions. While the FDA continues to evolve under new leadership and its approach to novel therapies to treat rare diseases, we remain focused on working constructively with the FDA to define the clearest and most efficient path forward for deramiocel and the patients who need it.

考慮到正向互動的軌跡，完整的回覆信是出乎意料的。儘管 FDA 在新的領導下不斷發展，並採用新療法治療罕見疾病，但我們仍將專注於與 FDA 進行建設性合作，為 deramiocel 和需要它的患者確定最清晰、最有效的前進道路。

I would like to emphasize that our HOPE-3 trial is still blinded and will not be unblinded until we have clarity on the path to potential approval from FDA.

我想強調的是，我們的 HOPE-3 試驗仍處於盲法階段，在我們明確獲得 FDA 批准的途徑之前，不會揭曉。

Let me take a minute to remind you of the features of the HOPE-3 trial. The study is fully enrolled with the last patient last visit occurring in June of this year. HOPE-3 is a double blind, placebo-controlled clinical trial with a 1 to 1 randomization which enrolled 104 patients consisting of two arms, Cohort A and Cohort B. The combined power of this trial using both cohorts is greater than 90%, with the original primary efficacy endpoint being the performance of the upper limb or the PUL version 2.0.

請容許我花一點時間來提醒您 HOPE-3 試驗的特點。這項研究已全部招募完畢，最後一位患者的最後一次就診於今年 6 月。HOPE-3 是一項雙盲、安慰劑對照的臨床試驗，採用 1:1 隨機分組，共招募了 104 名患者，分為 A 組和 B 組。本試驗使用兩個隊列，其綜合功效大於 90%，最初的主要療效終點是上肢表現或 PUL 2.0 版。

Based on a multitude of reasons, not the least of which is the tremendous unmet need of DMD cardiomyopathy, we have submitted a protocol amendment to designate left ventricular ejection fraction, or LVEF, as the primary efficacy endpoint and the skeletal muscle endpoint performance of the upper limb or PUL, as a pre-specified secondary endpoint.

基於多種原因，其中最重要的是 DMD 心肌病變的巨大未滿足需求，我們提交了一份協議修正案，將左心室射血分數 (LVEF) 指定為主要療效終點，將上肢或 PUL 的骨骼肌終點表現指定為預先指定的次要終點。

This change is based on multiple factors. One, the objectivity of LVEF as measured by cardiac MRI. Remember, there is no volition in cardiac function as measured by MRI, as well as the relevance of left ventricular ejection fractions to the pathophysiology of DMD cardiomyopathy, which has only been recently elucidated by the work of Dr. Jonathan Soslow from Vanderbilt University and the DMD Cardiac Consortium in a study funded by the Office of Orphan Products of the FDA and the NHLBI.

這項變化基於多種因素。一、心臟MRI測量LVEF的客觀性。請記住，透過 MRI 測量的心臟功能中沒有意志力，左心室射血分數與 DMD 心肌病變的病理生理學的相關性也是一樣，這一點直到最近才由范德堡大學的 Jonathan Soslow 博士和 DMD 心臟聯盟在由 FDA 和 NHLBI 孤兒產品辦公室資助的研究中闡明。

In addition, HOPE-3 is well powered to detect the treatment effect on cardiac function. I want to remind you that Capricor developed deramiocel specifically to address heart disease, particularly the cardiomyopathy associated with DMD.

此外，HOPE-3 還能很好地檢測治療對心臟功能的影響。我想提醒您，Capricor 開發了 deramiocel 專門用於治療心臟病，特別是與 DMD 相關的心肌病變。

However, until Dr. Soslow's study and its subsequent publication, there were no established efficacy benchmarks in DMD cardiomyopathy for the FDA to use in defining clinical benefits.

然而，直到 Soslow 博士的研究及其隨後發表之前，FDA 尚未建立 DMD 心肌病變的療效基準來定義臨床益處。

Our entire regulatory path, including the current BLA, was built on the FDA's guidance on how efficacy should be defined in this patient population. We have always intended for ejection fraction to serve as our primary efficacy endpoint. So while this may appear to be a change in strategy, it is in fact a return to the original goals we set early in the development of deramiocel.

我們的整個監管路徑，包括目前的 BLA，都是建立在 FDA 關於如何定義該患者群體療效的指導之上的。我們一直致力於將射血分數作為我們的主要療效終點。因此，雖然這看起來像是戰略上的改變，但實際上它是對我們早期開發 deramiocel 時設定的目標的回歸。

To that end, with our Type A meeting with the FDA now scheduled, we have submitted a comprehensive briefing package that addresses the concerns raised in the CRL and outlines several potential paths to approval.

為此，我們已安排與 FDA 舉行 A 類會議，並提交了一份全面的簡報，其中解決了 CRL 中提出的問題，並概述了幾種可能的批准途徑。

These include, first and foremost, the continued review of our previously filed BLA, which we believe meets the applicable regulatory requirements for approval, as well as supplementing the current BLA with additional data from HOPE-3 if needed.

這些措施首先包括繼續審查我們先前提交的 BLA，我們認為該 BLA 符合適用的監管批准要求，以及在需要時使用 HOPE-3 的額外數據補充當前的 BLA。

We believe the current handling of our submission is inconsistent with our interpretation of the FDA written guidances for cell and gene therapies, as well as recent public statements addressing the approval of safe and effective therapies for rare disease populations.

我們認為，目前對我們提交資料的處理方式與我們對 FDA 細胞和基因療法書面指南的解讀以及最近關於批准針對罕見疾病人群的安全有效療法的公開聲明不一致。

We are hopeful that FDA will exercise a patient-focused and science-driven approach in rare disease approvals in which they have been emphasizing in the media, as well as highlighting in the FDA Direct Podcasts based on the comments of Secretary Kennedy and Commissioner Makary, approving deramiocel for the treatment of DMD cardiomyopathy seems directly in line with their goals.

我們希望 FDA 在罕見疾病審批中採取以患者為中心、以科學為導向的方法，他們一直在媒體上強調這一點，並在 FDA Direct Podcasts 中根據肯尼迪部長和馬卡里局長的評論強調，批准 deramiocel 用於治療 DMD 心肌病似乎與他們的目標直接一致。

In conclusion, about a year ago, we received FDA feedback that shaped our decisions to submit the BLA based on cardiac endpoints. We provided the requested data and analysis and fully expected any differences in interpretation to be addressed at an advisory committee meeting, one that was ultimately canceled by the FDA without explanation.

總之，大約一年前，我們收到了 FDA 的回饋，決定我們根據心臟終點提交 BLA。我們提供了所要求的數據和分析，並完全期望任何解釋上的分歧都能在諮詢委員會會議上得到解決，但該會議最終被 FDA 取消，且沒有任何解釋。

We are concerned with how our file has been managed because we believe there were opportunities during the review period for the agency to raise the specific issues cited in the CRL before issuing the letter.

我們對我們的文件的管理方式感到擔憂，因為我們認為，在審查期間，該機構有機會在發出信函之前提出 CRL 中提到的具體問題。

We have long worked aside the DMD community and understand their calls, both to continue treatment with deramiocel and to gain access if it becomes commercially available.

我們長期以來一直與 DMD 社群合作，理解他們的呼聲，既希望繼續使用 deramiocel 進行治療，也希望在其商業化後獲得使用權。

We will continue to urge the FDA to recognize that cardiomyopathy is a leading cause of death in DMD and a far more severe consequence than the loss of arm function. Deramiocel has demonstrated a strong safety profile, and the data indicate it can help stabilize the inevitable decline in cardiac function for people living with DMD.

我們將繼續敦促 FDA 認識到心肌病變是 DMD 患者死亡的主要原因，其後果遠比手臂功能喪失嚴重得多。Deramiocel 已證明具有強大的安全性，數據表明它可以幫助穩定 DMD 患者不可避免的心臟功能衰退。

With regard to the CMC and commercial -- pre-commercial aspects of our program, I am pleased to announce that the FDA has now formally accepted all 483 items from our pre-licensed inspection. This milestone further validates the strength of our quality systems, manufacturing capabilities, and overall commercial readiness.

關於我們計劃的 CMC 和商業——商業化前階段，我很高興地宣布，FDA 現已正式接受我們許可前檢查的所有 483 個項目。這一里程碑進一步驗證了我們的品質系統、製造能力和整體商業準備的實力。

In addition, the CMC-related items noted in the CRL have either been addressed prior to the issuance of the CRL or have been internally addressed since. We have prepared formal responses which we plan to submit with our response to the CRL.

此外，CRL 中提到的與 CMC 相關的事項要么在 CRL 發布之前就已解決，要么在發布之後已在內部解決。我們已經準備好正式回复，並計劃與 CRL 的回復一起提交。

Our manufacturing facility in San Diego remains fully operational and in production, and we are being disciplined in our commercial manufacturing investments to ensure we are fully prepared while managing resources wisely.

我們在聖地牙哥的製造工廠仍在全面運作和生產，並且我們在商業製造投資方面嚴格要求，以確保我們在明智地管理資源的同時做好充分的準備。

In parallel, we are diligently and strategically investing in launch readiness activities including physician education, patient services, market access planning, and reimbursement. We've also begun working closely with treating physicians across the field of neurology and cardiology who will ultimately collaborate in prescribing deramiocel to patients with DMD cardiomyopathy if approved.

同時，我們正在勤勉且策略性地投資於啟動準備活動，包括醫生教育、病患服務、市場准入規劃和報銷。我們也開始與神經病學和心臟病學領域的治療醫生密切合作，如果獲得批准，他們最終將合作為患有 DMD 心肌病變的患者開出 deramiocel 處方。

Many of these clinicians are already familiar with the therapy through their participation in the HOPE-2 and HOPE-3 studies, and we are committed to ensuring a smooth transition to commercial use if approved. At this time, we are focused on seeking approval for deramiocel in the US, and with respect to our global expansion plans, we will provide updates as they become available.

許多臨床醫生透過參與 HOPE-2 和 HOPE-3 研究已經熟悉了這種療法，我們致力於確保該療法在獲得批准後順利過渡到商業用途。目前，我們正致力於在美國尋求對 deramiocel 的批准，至於我們的全球擴張計劃，我們將在獲得最新資訊後提供更新。

Now turning to our exosome program, to remind you, in 2024 we were selected to participate in Project NextGen, an initiative led by the US Department of Health and Human Services, aimed at advancing next generation vaccines for COVID-19 and other potential infectious diseases.

現在談談我們的外泌體計劃，提醒您，2024 年我們被選中參加 NextGen 項目，這是一項由美國衛生與公眾服務部領導的計劃，旨在推進針對 COVID-19 和其他潛在傳染病的下一代疫苗。

Under this program, the National Institute of Allergy and Infectious Disease, NIAID, will be sponsoring the Phase 1 clinical trial of our StealthX vaccine. Within the last several weeks, we reached a significant milestone for this program, which was the clearance of the IND and initiation of the trial using StealthX, our exosome platform technology.

根據該計劃，美國國家過敏和傳染病研究所 (NIAID) 將贊助我們的 StealthX 疫苗的第一階段臨床試驗。在過去的幾週內，我們為這個計畫取得了一個重要的里程碑，即批准了 IND 並啟動了使用我們的外泌體平台技術 StealthX 的試驗。

The Phase 1 study is being conducted and overseen by NIAID's Division of Microbiology and Infectious Disease, DMID. And I am pleased to report we have already supplied them with our clinical material for use in the trial.

第一階段研究由 NIAID 微生物學和傳染病科 (DMID) 進行和監督。我很高興地告訴大家，我們已經向他們提供了試驗的臨床材料。

The Phase 1 study is assessing our COVID-19 vaccine product. The trial is divided into three arms comprised of three escalating doses of the Spice -- Spike, or S antigen, and a combined high dose S plus the nucleocapsid or N antigen, the multivalent vaccine we have been developing.

第一階段研究正在評估我們的 COVID-19 疫苗產品。試驗分為三個組，包括三種劑量遞增的 Spice - Spike 或 S 抗原，以及組合高劑量 S 加核衣殼或 N 抗原（我們一直在開發的多價疫苗）。

NIAID is starting with the S first because previous COVID vaccines are mainly S-based, and they wanted to have a basis for comparison with our vaccine candidate using similar antigenic profiles. The end goal is for the adoption of the N plus S, which is our multivalent vaccine, and we will provide more updates on this developing program as they become available.

NIAID 首先從 S 開始，因為先前的 COVID 疫苗主要基於 S，並且他們希望使用相似的抗原譜與我們的候選疫苗進行比較。我們的最終目標是採用 N + S，即我們的多價疫苗，我們將在此開發計劃的更多更新中提供這些資訊。

We believe that StealthX has the characteristics of a vaccine product that Secretary Kennedy would find acceptable. It contains no adjuvants. It is not mRNA-based, uses a native protein antigen, and can be rapidly produced if needed. We've long believed that this type of vaccine checks all the boxes for a safe and effective platform as supported by multiple pre-clinical studies. And upcoming clinical data will allow us to confirm or challenge that hypothesis. This platform also has the potential to address multiple disease areas, including influenza and RSD.

我們相信 StealthX 具有甘迺迪國務卿可以接受的疫苗產品的特性。它不含任何佐劑。它不是基於 mRNA，而是使用天然蛋白質抗原，並且可以在需要時快速生產。我們一直相信，這種疫苗符合安全有效的所有條件，並且得到了多項臨床前研究的支持。即將發布的臨床數據將使我們能夠證實或質疑這一假設。該平台還具有解決多種疾病領域的潛力，包括流感和呼吸道疾病。

While vaccines are not a core focus for us, if our candidate meets US government criteria and demonstrates efficacy, it could potentially open meaningful business development opportunities. Just as importantly, it would serve as strategic proof for our exosome platform, which we hope to advance as a versatile therapeutic engine for rare diseases and beyond.

雖然疫苗不是我們的核心關注點，但如果我們的候選疫苗符合美國政府的標準並證明有效，它可能會開啟有意義的業務發展機會。同樣重要的是，它將成為我們外泌體平台的策略證明，我們希望將其發展成為治療罕見疾病及其他疾病的多功能治療引擎。

While the majority of our efforts this year have been focused on securing approval for deramiocel, an additional reason we recruited Dr. Michael Binks as our Chief Medical Officer was his expertise in translational science and medicine.

雖然我們今年的大部分努力都集中在獲得 deramiocel 的批准上，但我們聘請 Michael Binks 博士擔任首席醫療官的另一個原因是他擁有轉化科學和醫學方面的專業知識。

He is now leading efforts to advance our exosome pipeline with the goal of forging strategic partnerships to expand the platform into and beyond vaccines. We believe the differentiated features of exosomes, including low immunogenicity, scalable manufacturing, and targeted delivery, position Capricor for unique potential opportunities in the therapeutic delivery space. We look forward to sharing updates as they become available.

他目前正領導推動我們的外泌體管道工作，目標是建立戰略合作夥伴關係，將該平台擴展到疫苗領域及其他領域。我們相信外泌體的差異化特徵，包括低免疫原性、可擴展製造和靶向遞送，使 Capricor 在治療遞送領域具有獨特的潛在機會。我們期待分享最新更新。

Thank you. And with that, I will now turn the call over to AJ to run through our financials.

謝謝。現在，我將把電話交給 AJ 來介紹我們的財務狀況。

Thanks, Linda. This afternoon's press release provided a summary of our second-quarter 2025 financials on a GAAP basis. We 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.

謝謝，琳達。今天下午的新聞稿根據 GAAP 提供了我們 2025 年第二季財務狀況的摘要。我們也可以參考我們的 10-Q 表季度報告，預計該報告將很快發布，並可在美國證券交易委員會網站以及我們網站的財務部分查閱。

Let me start with our cash position. As of June 30, 2025, our cash, cash equivalent to marketable securities totaled approximately $122.8 million. Turning into the financials, revenues for the second quarter of 2025 were zero compared to approximately $4 million for the second quarter of 2024.

讓我先從我們的現金狀況開始。截至 2025 年 6 月 30 日，我們的現金、現金等價物及有價證券總額約為 1.228 億美元。從財務角度來看，2025 年第二季的營收為零，而 2024 年第二季的營收約為 400 萬美元。

Additionally, revenues for the first half of 2025 were zero compared to approximately $8.9 million for the first half of 2024. I'd like to point out that the source of revenue for 2024 was the ratable recognition of the $40 million we had received under our US distribution agreement with Nippon Shinyaku, which has been fully recognized as of December 31, 2024.

此外，2025 年上半年的收入為零，而 2024 年上半年的收入約為 890 萬美元。我想指出的是，2024 年的收入來源是我們根據與日本新藥達成的美國分銷協議收到的 4000 萬美元的按比例確認，截至 2024 年 12 月 31 日已完全確認。

Moving to our operating expenses for the second quarter of 2025, excluding stock-based compensation, our research and development expenses were approximately $20.1 million compared to approximately $11.7 million for Q2 2024. For the first half of 2025, excluding stock-based compensation, our research and development expenses were approximately $36.3 million compared to approximately $21.8 million for the first half of 2024.

轉到 2025 年第二季的營運費用（不含股票薪酬），我們的研發費用約為 2,010 萬美元，而 2024 年第二季約為 1,170 萬美元。2025 年上半年，不含股票薪酬，我們的研發費用約為 3,630 萬美元，而 2024 年上半年約為 2,180 萬美元。

Moving into general and administrative expenses, excluding stock-based compensation were approximately $4 million in Q2 2025 and approximately $1.8 million in Q2 2024. And for the first half of '25, also excluding stock-based compensation, our general administrative expenses were approximately $7 million for the first half of '25 and $3.6 million for the first half of 2024.

2025 年第二季的一般及行政支出（不含股票薪酬）約為 400 萬美元，2024 年第二季約為 180 萬美元。而在 2025 年上半年，不包括股票薪酬，我們的一般管理費用在 2025 年上半年約為 700 萬美元，在 2024 年上半年約為 360 萬美元。

Net loss for the second quarter of '25 was approximately $25.9 million compared to a net loss of approximately $11 million for the second quarter of '24. The net loss for the first half of '25 was approximately $50.3 million compared to a net loss of approximately $20.8 million for the first half of 2024.

25 年第二季淨虧損約 2,590 萬美元，而 24 年第二季淨虧損約 1,100 萬美元。2025 年上半年淨虧損約 5,030 萬美元，而 2024 年上半年淨虧損約 2,080 萬美元。

I will now turn the call back over to Linda for some closing remarks.

現在我將把電話轉回給琳達，請她做一些結束語。

Again, thank you, AJ. Just to reinforce AJ's points on our financial position, with over $120 million in cash, we are well positioned to support operations until late 2026 and continue to advance our key pipeline objectives. Additionally, if we receive approval, we would still be eligible to receive a priority review voucher as well as a milestone payment of $80 million from Nippon Shinyaku, representing additional significant non-dilutive capital opportunities to further strengthen our balance sheet.

再次感謝你，AJ。為了強化 AJ 對我們財務狀況的觀點，憑藉超過 1.2 億美元的現金，我們完全有能力支持營運直至 2026 年底，並繼續推進我們的關鍵管道目標。此外，如果我們獲得批准，我們仍然有資格獲得優先審查憑證以及來自日本新藥的 8000 萬美元的里程碑付款，這代表著進一步加強我們資產負債表的額外重要非稀釋性資本機會。

This is an important moment for Capricor. While we have faced recent regulatory headwinds, we are advancing deliberately, strategically, and with confidence in our data, our team, and our path forward. We continue to believe that deramiocel represents a major step forward for patients with DMD cardiomyopathy and that our exosome platform is well positioned to deliver value through continued innovation and partnerships.

對 Capricor 來說，這是一個重要的時刻。雖然我們最近面臨監管阻力，但我們正在有意識地、有策略地前進，並且對我們的數據、我們的團隊和前進的道路充滿信心。我們始終相信，deramiocel 對於 DMD 心肌病變患者來說代表著向前邁出的重要一步，並且我們的外泌體平台能夠透過持續的創新和合作實現價值。

To the Duchenne Muscular Dystrophy community, thank you for your ongoing trust and support. We remain grounded in the science, (technical difficulty) on execution, and committed to building a company that delivers meaningful and lasting impact for all DMD patients.

對於杜氏肌肉營養不良症社區，感謝您一直以來的信任與支持。我們始終立足於科學（技術難度）和執行，並致力於建立一家為所有 DMD 患者帶來有意義和持久影響的公司。

I will now open up the line for questions.

我現在開始回答問題。

(Operator Instructions) Ed Tenthoff, Piper Sandler.

（操作員指示）Ed Tenthoff，Piper Sandler。

Great. Thank you so much for taking my question and I appreciate all of your hard work to keep fighting for these boys and get them a therapy that's going to help them with their heart function. I wanted to get a sense for the plan for next steps in terms of unblinding HOPE-3. Is the plan to get confirmation from the FDA on that first? Just maybe reiterating what the plan is. Thanks.

偉大的。非常感謝您回答我的問題，我感謝您為這些男孩的治療所做的一切努力，並為他們提供有助於他們心臟功能的治療。我想了解 HOPE-3 揭盲的下一步計畫。是否計劃先獲得 FDA 的確認？也許只是重申一下計劃是什麼。謝謝。

Thanks, Ed. Always a pleasure even during these crazy, crazy times. Yeah. So we are waiting for adjudication from FDA as to what their requirements will be for HOPE-3. And then, we will submit a statistical analysis plan and proceed with unblinding only after that has been accepted. We just don't want to muddy or cloud the waters with any thoughts that we had unblinded early. So our plan is to stay quiet until we have plans from them.

謝謝，艾德。即使在這些瘋狂的時刻，也總是很開心。是的。因此，我們正在等待 FDA 裁決其對 HOPE-3 的要求。然後，我們將提交一份統計分析計劃，只有在該計劃被接受後才能進行揭盲。我們只是不想讓任何我們早先揭示的想法變得混亂或混淆。因此我們的計劃是保持沉默，直到他們提出計劃為止。

Great. And when do you expect to hear back from the FDA or get that query?

偉大的。您預計什麼時候能收到 FDA 的回覆或詢問？

Well, obviously from the rescheduling of our earnings call today, our Type A meeting is this week. We anticipate to have a really good conversation with the FDA. We're looking forward very much to meeting with them. We certainly -- August is our month. August of 2024 was when this whole plan was put in place, so I'm very excited for this meeting. And in terms of providing clarity and updates to the markets, that probably won't be until I get the official feedback in writing, especially with the liability of our current situation and times. So hopefully [Adam Pierte] won't report on it before I do.

嗯，顯然，從我們今天重新安排的收益電話會議來看，我們的 A 類會議是在本週舉行。我們期待與 FDA 進行非常好的對話。我們非常期待與他們會面。我們當然——八月是我們的月份。整個計劃是在 2024 年 8 月開始實施的，所以我對這次會議感到非常興奮。至於向市場提供清晰度和更新，可能要等到我收到書面官方回饋後才能實現，尤其是考慮到我們當前的情況和時代責任。所以希望 [Adam Pierte] 不會在我之前報道此事。

Thanks so much, Linda. Good luck.

非常感謝，琳達。祝你好運。

Thanks, Ed.

謝謝，艾德。

Leland Gersel, Oppenheimer.

利蘭·格塞爾、奧本海默。

Thanks, Linda, for the update and taking our questions. There's just a couple here. So just to be further from from Ed's inquiry. So if you go with the plan to not unblind HOPE-3 but continue with with the current BLA as it is, would there then be supplemental OLE data that could go into what the FDA has on file versus what had been submitted? I guess if you could share just what incremental, data ex-HOPE-3 that that could become available to them that would be different from what they had reviewed previously.

謝謝琳達的更新和回答我們的問題。這裡只有一對夫婦。只是為了進一步了解 Ed 的詢問。因此，如果您按照計劃不解盲 HOPE-3，而是繼續使用當前的 BLA，那麼是否會有補充 OLE 資料可以納入 FDA 已存檔的資料與已提交的資料之間？我想，如果您可以分享 HOPE-3 以外的增量數據，那麼這些數據將與他們之前審查過的數據有所不同。

Yeah, Leland. So actually I don't -- haven't really thought about submitting supplemental lead data, though of course, it continues to support our safety profile and the efficacy. If you look at the long term efficacy of deramiocel, it's actually quite extraordinary, and we're very proud of that record in our OLE patients. And I don't know of another clinical effort in DMD that has as long of a record post-studies as we do.

是的，利蘭。所以實際上我並沒有真正考慮過提交補充主要數據，儘管它當然繼續支持我們的安全性和功效。如果你看一下 deramiocel 的長期療效，它實際上是非常非凡的，我們對 OLE 患者的這一記錄感到非常自豪。我不知道在 DMD 領域還有哪項臨床研究能像我們一樣擁有如此長的後期研究紀錄。

Having said that, I think the meeting with FDA will define what they will want for data for either the reopening and resubmission of this BLA. And so I don't have an answer on that. My current plan is to have everything ready, then they have an opportunity to select what they think would be most efficient in determining efficacy for approval.

話雖如此，我認為與 FDA 的會議將確定他們希望獲得哪些數據以重新開放和重新提交此 BLA。所以我對此沒有答案。我目前的計劃是把一切都準備好，然後他們就有機會選擇他們認為最有效的方法來確定批准的功效。

Okay. And I guess, I have to ask, with Vinay Prasad now back at CBER, how does -- does that inform your thinking is -- are the people who you're interacting with the FDA, is there a different team now with Nicole Verdun out of the picture since the last few weeks? How should we think about who your counterparties are at FDA at this point?

好的。我想，我不得不問，Vinay Prasad 現在回到了 CBER，這是否說明了您的想法——您與 FDA 互動的人，現在是否有另一個團隊，而 Nicole Verdun 自過去幾週以來就不再參與其中了？此時我們該如何看待你們在 FDA 的交易對手是誰？

Thanks, Leland. It's interesting. I think the last few years, I've been thinking about this a lot, people have become much more focused on who the review team is and exercising political capital and regulatory flexibility and all of this lingo that has become very popular.

謝謝，利蘭。這很有趣。我想，過去幾年，我一直在思考這個問題，人們越來越關注審查團隊是誰，以及行使政治資本和監管靈活性以及所有這些變得非常流行的術語。

I'm going back to old school. We have good clinical data. We have great safety data. We have guidance from the agency in writing as to what they wanted. We provided it. And now really I think it's up to them to decide who is best suited within that agency to make the decision of adjudication and all of the factors that go into it.

我要回到原來的學校。我們有良好的臨床數據。我們擁有出色的安全資料。我們收到了該機構的書面指導，以了解他們想要什麼。我們提供了它。現在我真正認為應該由他們來決定誰最適合在該機構內做出裁決並考慮其中涉及的所有因素。

So I tell my team, I'll tell the markets, we are proud of our data. We see it in terms of the long-term efficacy in our patients and safety, and we sincerely hope that the agency gives us a good path forward to get this to those patients as quickly as possible.

所以我告訴我的團隊，我會告訴市場，我們對我們的數據感到自豪。我們從患者的長期療效和安全性的角度看待它，我們真誠希望該機構能為我們提供一條良好的前進道路，以便盡快將其提供給這些患者。

Okay. All right. Thanks very much for taking the questions.

好的。好的。非常感謝您回答這些問題。

Thanks, Leland. Always a pleasure.

謝謝，利蘭。總是很高興。

Joe Pantginis, H.C. Wainwright.

喬潘特吉尼斯、H.C. 溫賴特。

Hi, Linda and AJ. Thanks for taking the questions. Good afternoon. So just to press the envelope a little bit, obviously, things could change incrementally or dramatically this week and about a month after that when you provide the details from the minutes to the Street.

你好，Linda 和 AJ。感謝您回答這些問題。午安.因此，稍微挑戰一下極限，顯然，本週以及大約一個月後，當你向華爾街提供會議記錄中的細節時，情況可能會發生逐步或顯著的變化。

But with language in the press release and what you talked about today, you're talking about resubmitting in its current form, you're saying maybe not really having any incremental data from the OLE that you just discussed in the last question. So what would you expect that could be potentially different?

但是根據新聞稿中的措辭以及您今天所談論的內容，您談論的是以當前形式重新提交，您說的可能是實際上沒有從您剛才在上一個問題中討論的 OLE 中獲得任何增量數據。那麼您認為可能存在哪些不同呢？

Well, again, we have given the FDA a variety of opportunities in our briefing document. We remain open to resubmission of the BLA as it is. We didn't feel that the CRL was founded. The data that we submitted was exactly what they asked for, and the graphs themselves are interpretable as statistically and clinically significant.

好吧，我們再次在簡報文件中為 FDA 提供了各種機會。我們仍然願意接受重新提交 BLA。我們並不認為 CRL 已經成立。我們提交的數據正是他們所要求的，並且圖表本身俱有統計和臨床意義。

So that's, of course, our number one goal is explaining to them why perhaps their interpretation was wrong. So then everything that follows from that, accelerated approval with the submission of HOPE-3 data in support of that and a variety of other opportunities that they can help us adjudicate and that's why we're looking forward to this Type A meeting.

因此，我們的首要目標當然是向他們解釋為什麼他們的解釋可能是錯的。因此，隨之而來的一切，加速批准，提交 HOPE-3 數據來支持這一點，以及他們可以幫助我們裁決的各種其他機會，這就是我們期待這次 A 類會議的原因。

So with that in mind, we go in with open hearts to meet with the agency and look forward to having them understand that developing and approving therapeutics for rare diseases, especially pediatrics ones, does require you're looking at the data in a more holistic fashion, and we're hoping that that is exactly what happens this week.

因此，考慮到這一點，我們以開放的心態與該機構會面，並希望他們理解，開發和批准罕見疾病（尤其是兒科疾病）的治療方法確實需要以更全面的方式查看數據，我們希望這正是本週發生的事情。

All right, and so that's fair. And so maybe just another question starting at the -- or from the back end of your comments around StealthX. So it's great that it's getting into the clinic now. Any visibility with regard to what might be next with regard to an indication? Obviously, you mentioned influenza as a potential and how would you describe the early cost maturity levels of potential BD around StealthX?

好的，這很公平。因此，也許這只是從您對 StealthX 的評論的後端開始的另一個問題。所以現在它能夠進入臨床真是太好了。對於接下來可能出現的跡象，您有沒有什麼預見性？顯然，您提到流感是一種潛在的疾病，您如何描述 StealthX 周圍潛在 BD 的早期成本成熟度？

Yeah. Thanks Joe. So you know our StealthX program is our little engine that could. We just kept on moving it forward. Our vaccine program is really exciting in the sense that, as I mentioned in my remarks, this type of vaccine, which we've always believed in is exactly what Secretary Kennedy has advocated as would be a much better vaccine candidate, no adjuvants, native protein, rapidly produced, no mRNA, that kind of thing.

是的。謝謝喬。所以你知道我們的StealthX專案就是我們能夠做到的小引擎。我們只是繼續向前推進。我們的疫苗計劃確實令人興奮，正如我在演講中提到的那樣，我們一直相信的疫苗正是肯尼迪國務卿所倡導的，它將是一種更好的候選疫苗，不含佐劑、天然蛋白質、快速生產、不含 mRNA 等等。

So we're very excited about that and we're looking forward to the NIAID data. They're very excited about it because it's a program that does fit that criteria, and we'll see where that goes.

因此我們對此感到非常興奮，並期待 NIAID 的數據。他們對此感到非常興奮，因為這個計畫確實符合這個標準，我們將會看看它的發展。

In terms of Capricor's interest in developing vaccine technology, that's something that I've always said would be a business development opportunity. We think it's wiper than ever based on the criteria I just put forth.

就 Capricor 對開發疫苗技術的興趣而言，我一直認為這是一個商業發展機會。根據我剛才提出的標準，我們認為它比以往任何時候都更具影響力。

In terms of therapeutic indications, we haven't disclosed some of the ones that we've been working on internally. As I've mentioned many times, we've focused most of our efforts in our capital on deramiocel and look forward to providing updates on where we're going to be taking the exosome program as we further develop that therapeutic pipeline.

在治療適應症方面，我們還沒有透露一些我們內部正在研究的適應症。正如我多次提到的，我們將大部分精力集中在 deramiocel 上，並期待在進一步開發該治療管線時提供有關外泌體計劃進展的最新資訊。

Got it. Looking forward to more visibility out of the program and good luck with the meeting this week.

知道了。期待該計劃能得到更多的關注，並祝本週會議順利。

Thanks, Joe. Always a pleasure.

謝謝喬，很高興見到你。

Kristen Kluska, Cantor.

克里斯汀·克魯斯卡（Kristen Kluska），領唱。

Hi, Linda and AJ. Also sending you best wishes for your meeting this week. A few questions for me. First. I was pleasantly surprised to see that you received the acceptances of responses related to the Form 483 observations. I guess, can you just comment on that? Because typically after we see CRLs, the FDA isn't so much as engaged in responding to those things until you resubmit. So can you explain that timeline for us?

你好，Linda 和 AJ。也向您致以本週會議的良好祝愿。我有幾個問題。第一的。我很高興地看到您收到了與 483 表格觀察結果相關的回應的接受。我想，您能對此發表評論嗎？因為通常在我們看到 CRL 後，FDA 並不會過度回應這些問題，直到您重新提交為止。那麼您能為我們解釋一下這個時間表嗎？

Yeah. So this has been an unorthodoxed review process, as I've mentioned in my remarks as we've talked about in our disclosures and other companies have gone through similar situations. So we passed our PLI. They issued the 483s. We responded to the 483s, and that review team, independent of the CRL, provided feedback that we had cleared our 483s and we are on the path for approval of our CMC and our manufacturing plant for GMPUs.

是的。因此，這是一個非傳統的審查過程，正如我在評論中提到的，我們在披露中也討論過，其他公司也經歷過類似的情況。所以我們通過了 PLI。他們發布了 483 份文件。我們對 483 做出了回應，獨立於 CRL 的審查小組提供了回饋，表示我們已經通過了 483 審核，並且正在爭取 CMC 和 GMPU 製造工廠的批准。

So that is where that situation is. As I mentioned in the CRL, there were several several CRL issues related to CMC. Many of those had already been addressed in information request responses that we provided prior to the issuance of the CRL, but they had stopped reviewing in anticipation of issuing the CRL. The rest of them have already been addressed, and we look forward to providing those in our response to the CRL.

情況就是這樣的。正如我在 CRL 中提到的，有幾個與 CMC 相關的 CRL 問題。我們在發布 CRL 之前提供的資訊請求回覆中已經解決了其中的許多問題，但他們已經停止審查，準備發布 CRL。其餘問題已經解決，我們期待在對 CRL 的回應中提供這些問題。

Okay. Thank you. And just want to confirm that the new timeline guidance for Q versus 3Q for HOPE-3 is just solely driven by the fact that you haven't started the unblinding yet because, again, you're waiting for this meeting and that clarity?

好的。謝謝。只是想確認一下，HOPE-3 的 Q 與 3Q 的新時間表指導僅僅是因為您尚未開始揭盲，因為您還在等待這次會議和澄清？

Absolutely, yes. Everything's on time with HOPE-3, and we just are waiting for feedback from FDA. Let's go.

絕對是的。HOPE-3 一切進展順利，我們只在等待 FDA 的回饋。我們走吧。

Okay. Thank you. And then just lastly, I guess in a nutshell, what are the key things that you hope to align from after this meeting takes place this week? Is it just understanding specifically what's required? If it is HOPE-3, do you expect to have full understanding of what that primary endpoint will be?

好的。謝謝。最後，我想簡而言之，本週會議結束後，您希望達成哪些關鍵共識？是否只是了解具體需要什麼？如果是 HOPE-3，您是否希望完全了解該主要終點是什麼？

And then, even their blessing that if HOPE-3 is successful on that endpoint that could potentially be sufficient enough to support an approval. Thanks, again.

然後，甚至他們祝福，如果 HOPE-3 在該終點上取得成功，這可能足以支持批准。再次感謝。

Yeah. So exactly what you hypothesized. So we're looking for feedback on exactly what it's going to take to get this approved. As I mentioned in a previous question, we believed in the data that we submitted. We believed that the CRL was unfounded. We were going towards the PDUFA very directly because there were no issues raised in the midcycle review meeting.

是的。所以這正是你所假設的。因此，我們正在尋求回饋，以了解究竟需要採取哪些措施才能獲得批准。正如我在上一個問題中提到的，我們相信我們提交的數據。我們認為 CRL 是沒有根據的。我們直接針對 PDUFA 採取行動，因為中期審查會議上沒有提出任何問題。

We thought we were in a pretty good position. When the AdCom was canceled, I didn't really take too much issue with that because I felt like in the late stage meeting, we would be able to address any concerns they might have. So my first plan is to try and understand what their resistance is to the currently available data, and if that is maintained, then what it will take to get to approval.

我們以為我們處於相當有利的位置。當 AdCom 被取消時，我並沒有太過擔心，因為我覺得在後期會議上，我們將能夠解決他們可能的任何擔憂。因此，我的第一個計劃是嘗試了解他們對目前可用資料的抵觸情緒，如果這種抵觸情緒持續存在，那麼需要採取什麼措施才能獲得批准。

Thank you. Sending you the best.

謝謝。送你最好的。

Thank you so much.

太感謝了。

Madison El-Saadi, B. Riley Securities.

麥迪遜·埃爾薩迪 (Madison El-Saadi)，B. Riley 證券。

Hey, Linda and AJ. Thanks for taking our question. I was just curious, has there been any informal agency communication? I believe post-CRL, you had noted there was an opportunity for an informal teleconference, and just wondering what the takeaways were there and if that contributed to your decision to resubmit? Thank you.

嘿，琳達和 AJ。感謝您回答我們的問題。我只是好奇，有任何非正式的機構溝通嗎？我相信在 CRL 之後，您已經注意到有機會進行非正式電話會議，只是想知道會議的要點是什麼，以及這是否促使您決定重新提交？謝謝。

Yeah. So we did have a short informal meeting with them based on their guidance from their leadership. It was primarily to align on timelines of this Type A meeting and what would potentially be submitted and then to clarify the CMC-related issues, neither clinical nor stats were part of that meeting. So this Type A meeting is very important because it allows us to meet with the agency and really flesh it out.

是的。因此，我們確實根據其領導層的指導與他們進行了一次簡短的非正式會議。其主要目的是協調 A 類會議的時間表以及可能提交的內容，然後澄清與 CMC 相關的問題，臨床和統計都不屬於該會議的一部分。因此，這種 A 類會議非常重要，因為它使我們能夠與該機構會面並真正充實會議內容。

In terms of our decision to reply or respond to the CRL, that's always been our intent. We'd like feedback from them so that we can keep it smooth and steady and work our way to the quickest state of a PDUFA as possible, but we will see what happens this week.

就我們決定回覆或回應 CRL 而言，這一直是我們的意圖。我們希望得到他們的反饋，以便我們能夠保持平穩，並儘可能快地完成 PDUFA，但我們將看看本週會發生什麼。

Got it. Thanks. And then do you expect to get an answer on the primary endpoint change at the August meeting? I believe you said you were expecting an answer on that.

知道了。謝謝。那麼您是否希望在八月份的會議上得到有關主要終點變化的答案？我相信您說過您期待對此的答案。

Yeah. So that's been one of our primary questions. We are looking to get that worked out during this meeting.

是的。這是我們的主要問題之一。我們希望在這次會議上解決這個問題。

Got it. Well, good luck this week at the meeting.

知道了。好吧，祝本週會議順利。

Thank you.

謝謝。

Aydin Huseynov, Ladenburg Thalmann.

艾丁‧侯賽諾夫，拉登堡‧塔爾曼。

Hi. Good afternoon, Linda. AJ. Thanks for taking questions and appreciate all the work you're doing. A couple from us. So first, I want to clarify and apologize if this has been addressed, but I want to clarify the the timeline of the upcoming events. So the fourth quarter, you're going to readout HOPE-3, resubmit the BLA. And how do we treat this BLA? Is it -- if it is the same BLA, what is the review process typical for this kind of reapplications? Is it two months acceptance and review months? Just curious your thoughts on the timeline.

你好。下午好，琳達。AJ。感謝您回答問題並感謝您所做的一切工作。我們中的一對夫婦。因此，首先，我想澄清一下，如果這個問題已經解決，我深感抱歉，但我想澄清一下即將發生的事件的時間表。因此，第四季度，您將讀出 HOPE-3，重新提交 BLA。那我們該如何處理這個 BLA呢？如果是相同的 BLA，這種重新申請的典型審核流程是怎麼樣的？接受和審查是兩個月嗎？只是好奇你對時間軸的想法。

Yeah. So that's one of the issues that we're going to be taking on with the agency during this meeting, obviously, there's a lot of timeline issues that were predicated on: how they want to update the BLA; whether or not they would require a new BLA; what that does to priority review.

是的。所以這是我們在這次會議上要與該機構討論的問題之一，顯然，有很多時間表問題取決於：他們想如何更新 BLA；他們是否需要新的 BLA；這對優先審查有何影響。

We are still eligible for the PRV, the voucher that comes with approval for a pediatric indication independent of timeline but -- and our RMAT allows us certain benefits in terms of submission and also return on feedback, but we'll have to figure that out during this meeting with them, and we'll disclose that as soon as it becomes available to us.

我們仍然有資格獲得 PRV，這是與時間表無關的兒科適應症批准附帶的憑證，但是 - 我們的 RMAT 為我們在提交和反饋回報方面提供了某些好處，但我們必須在與他們的這次會議期間弄清楚這一點，我們會在獲得後立即披露。

Okay. I appreciate that. And regarding the left ventricular ejection fraction as the primary advocacy endpoint for HOPE-3. Could you walk us through your thought process as to why you chose this endpoint? I think the HOPE-2 had multiple cardiac endpoints I think 21 cardiac measures. And could you also remind us any prior successful or unsuccessful left ventricular ejection fraction primary input submissions so that we can model based on those precedents?

好的。我很感激。並將左心室射血分數作為HOPE-3的主要倡導終點。您能否向我們介紹一下您選擇這個終點的思考過程？我認為 HOPE-2 有多個心臟終點，我認為有 21 個心臟測量。您能否提醒我們之前任何成功或不成功的左心室射血分數主要輸入提交，以便我們可以根據這些先例進行建模？

Yeah. Really important question. So left ventricular ejection fraction is obviously one of the most important indicators of cardiac function, and clinicians, cardiologists use it all the time to define where their patients sit in terms of cardiac function and also what their likely outcomes are going to be.

是的。確實很重要的問題。因此，左心室射血分數顯然是心臟功能的最重要指標之一，臨床醫生和心臟科醫生一直使用它來確定患者的心臟功能狀況以及可能的結果。

So cardiologists know that below and above certain points you're either at greater risk for morbidity and mortality or in a reasonable position for stabilization of your cardiac function. We've known that for a long time.

因此，心臟科醫生知道，低於或高於某些點，您患發病率和死亡率的風險就會增大，或者您的心臟功能就會處於合理的穩定狀態。我們早就知道這一點。

The reason that ejection fraction -- and this answers your last question along with your first one, has not been used as a primary efficacy endpoint in clinical studies is because up until recently, it's really been considered a surrogate.

射血分數（這回答了您的最後一個問題以及第一個問題）之所以沒有被用作臨床研究中的主要療效終點，是因為直到最近，它才真正被認為是一種替代指標。

It has not been directly tied to clinically relevant events such as mortality, hospitalization, exercise performance, those types of things.

它與死亡率、住院率、運動表現等臨床相關事件沒有直接關聯。

The most amazing thing -- and this is why the change in our submission occurred from a clinical endpoint of skeletal muscle to cardiac ejection fraction was in collaboration with the agency because, while everybody knew that cardiomyopathy was the leading cause of death currently for Duchenne Muscular Dystrophy, up until John Soslow's study with the Cardiac Consortium, there really were not general evidence of what would be the predicting facts for mortality, hospitalization, those kinds of things.

最令人驚訝的是——這也是為什麼我們在提交的材料中將臨床終點從骨骼肌改為心臟射血分數是與該機構合作進行的，因為雖然每個人都知道心肌病是目前杜氏肌營養不良症的主要死因，但直到約翰·索斯洛與心臟聯盟進行研究之前，確實沒有關於死亡率、住院率等預測因素的普遍證據。

And in Duchenne, it's super hard. You're dealing with a rare disease with a small patient population and a pediatric disease. So in order to do a mortality study, you'd probably have to do like a 20-year study globally in order to be able to gather enough information.

而在杜氏肌肉營養不良症中，這非常困難。您正在處理一種患者人數較少的罕見疾病，並且是一種兒科疾病。因此，為了進行死亡率研究，您可能需要在全球範圍內進行 20 年的研究才能收集足夠的資訊。

So the Office of Orphan Products understood this paradigm -- or paradox as the NHLBI, National Heart, Lung and Blood Institute. So they funded John's study which allowed them to look at what would be the predictive factors of either morbidity or mortality in Duchenne Muscular Dystrophy cardiomyopathy. And along with what our data suggested, ejection fraction was the most important feature.

因此，孤兒藥辦公室將這種模式——或者說悖論理解為 NHLBI（國家心肺血液研究所）。因此，他們資助了約翰的研究，使他們能夠了解杜氏肌肉營養不良症心肌病變發病率或死亡率的預測因子。根據我們的數據表明，射血分數是最重要的特徵。

So there's also left ventricular end systolic and end diastolic volumes. We're measuring those. Those are secondary endpoints, as well as some biomarkers that John had, which was like BNP and one or two other paradigms -- or one or two other endpoints that would suggest the paradigm of morbidity and mortality.

因此也有左心室收縮末期容積和左心室舒張末期容積。我們正在測量這些。這些是次要終點，以及約翰所擁有的一些生物標誌物，例如 BNP 和一兩個其他範例 - 或一兩個其他終點，可以表明發病率和死亡率的範例。

And what we actually were able to demonstrate with the presentation of this data is that deramiocel attenuated and may have even reversed the path of that decline in ejection fraction, therefore predicting morbidity and mortality. Because, again, highlighting what I just said, it's a pediatric disease and it's rare, doing those types of large studies that will sometimes require thousands of patients to look at mortality risk, this is good for rare disease.

透過展示這些數據，我們實際上能夠證明，德拉米奧塞爾可以減弱甚至逆轉射血分數下降的路徑，從而預測發病率和死亡率。因為，再次強調我剛才所說的，這是一種兒科疾病，而且很罕見，進行這類大型研究有時需要數千名患者來研究死亡風險，這對罕見疾病來說是件好事。

And so the agency at the time, and hopefully still, is willing to understand that ejection fraction is probably the best way of predicting where this patient population could go should it not be stabilized.

因此，當時的機構（希望現在仍然）願意理解，射血分數可能是預測如果病情不穩定，患者群體走向何方的最佳方法。

It is very helpful. I appreciate it, Linda. Just to summarize this maybe. Essentially, LVEF was a surrogate endpoint and it requires a little bit of innovative thinking on FDA side to make it like a primary endpoint going forward. Would that be fair summarization here?

這非常有幫助。我很感激，琳達。也許只是為了總結一下這一點。本質上，LVEF 是一個替代終點，FDA 方面需要一點創新思維才能使其成為未來的主要終點。這算是公正的總結嗎？

I don't agree because, again, with the understanding of the new data that has come forth and the, again, rare disease population, there really is no other opportunity for adjudication of a primary efficacy endpoint. So if you really want to hear -- I'm passionate about this as you can probably tell from my voice, but if you really want to understand the risk and benefit here, please listen to our Parent Project Muscular Dystrophy webinar that we did about a week ago.

我不同意，因為根據對新數據和罕見疾病族群的了解，確實沒有其他機會來裁定主要療效終點。所以，如果你真的想聽——我對此充滿熱情，你可能從我的聲音中聽出來了，但如果你真的想了解這裡的風險和好處，請聽聽我們大約一周前舉辦的“家長項目肌肉萎縮症”網絡研討會。

Dr. Chet Villa talked about the unmet need in cardiomyopathy, and what Dr. Villa, who sees these patients all day, every day at Cincinnati Children's, talks about is there is no other way of measuring efficacy in this particular patient population that would be fair and safe for human beings.

切特·維拉博士談到了心肌病變領域尚未滿足的需求，維拉博士每天都在辛辛那提兒童醫院探望這些患者，他表示，對於這一特定患者群體，沒有其他公平且對人類安全的療效衡量方法。

Very helpful. Thank you so much. And one final question on Becker Muscular Dystrophy, my favorite one because part of our model modeling is based on that. So, but all these discussions, what takeaways it has for BMD? I mean, would you have to run another HOPE-3-style large trial in BMD to get a similar potential label as in DMD? And would left ventricular ejection fraction serve also a primary endpoint for BMD? Thank you.

非常有幫助。太感謝了。最後一個問題是關於貝克爾肌肉營養不良症的，這是我最喜歡的問題，因為我們的部分模型建模是基於此的。那麼，所有這些討論對於 BMD 有什麼啟示呢？我的意思是，您是否必須在 BMD 中進行另一次 HOPE-3 風格的大型試驗才能獲得與 DMD 類似的潛在標籤？左心室射血分數是否也是 BMD 的主要終點？謝謝。

So a sideways answer to that because I don't know directly at this point what the agency will require is it's very early in this administration to understand what they're actually going to do in moving rare disease approvals forward.

因此，由於我目前還不清楚該機構將要求什麼，因此只能從側面回答這個問題，因為本屆政府還處於早期階段，需要了解他們實際上將採取哪些措施來推動罕見疾病的審批。

Our plan previously, which I have discussed with you and discussed publicly as well, is that we were going to try and use the Duchenne data to build the Becker program because the pathophysiology of the cardiomyopathy is identical, just somewhat slower progressing in the Becker patients. And, in fact, as the Becker patients get older, it becomes more and more of a risk factor for morbidity and mortality.

我們之前的計劃（我已經與您討論過並且也公開討論過）是，我們將嘗試使用杜氏數據來構建貝克爾程序，因為心肌病的病理生理學是相同的，只是貝克爾患者的進展速度稍慢一些。事實上，隨著貝克爾氏症患者年齡的增長，它越來越成為發病和死亡的風險因素。

I don't know my current plan with Becker because I need to get understanding from the agency of how they're going to view the current Duchenne data, and then I'll be able to make more educated comments on it as I achieve clarity there.

我不知道我目前與貝克爾的計劃，因為我需要從該機構了解他們將如何看待當前的杜氏肌肉營養不良症數據，然後當我獲得明確的答案後，我才能對其做出更有根據的評論。

Thank you. Thanks so much for your comments and good luck with your meetings with the FDA. Thank you.

謝謝。非常感謝您的評論，祝您與 FDA 的會議順利。謝謝。

Thank you so much. We really appreciate it.

太感謝了。我們非常感激。

Boobalan Pachaiyappan, ROTH Capital.

Boobalan Pachaiyappan，羅斯資本。

Yeah. Thanks for taking the call. I'm [Amanisa] dialing in for Boobalan. So we have a couple of questions. The first question is, so do you regard the upcoming Type A meeting as an opportunity for the FDA to clarify their change of stance with respect to deramiocel's BLA or a bellwether for investors in predicting the future outcomes of potential resubmission with the HOPE-3 data?

是的。謝謝您接聽電話。我是 [Amanisa]，正在為 Boobalan 撥號。我們有幾個問題。第一個問題是，您是否認為即將舉行的 A 類會議是 FDA 澄清其對 deramiocel 的 BLA 立場變化的機會，還是投資者預測 HOPE-3 數據潛在重新提交的未來結果的風向標？

Also, we are curious to know whether you'll be open to sharing the Type A meeting minutes to investors to the extent you can, to be comprehensive and elaborate.

此外，我們也很好奇，您是否願意盡可能地向投資者分享 A 類會議記錄，使其全面而詳細。

Yeah. In terms of your first question, yeah, we expect to share the data as as it becomes available and the information as as it becomes available.

是的。關於您的第一個問題，是的，我們希望在數據可用時分享數據，並在資訊可用時分享資訊。

In terms of providing meeting minutes to investors, that becomes a little bit of a as needed basis. I can tell you right now, as you heard, our cash position is very strong. We're not outraising money. We don't anticipate needing to raise money. We're focusing on approval of deramiocel in DMD, and so we'll see if the situation calls for it, we would definitely discuss it directly with that investor.

就向投資者提供會議記錄而言，這有點按需提供。我現在可以告訴你，正如你所聽到的，我們的現金狀況非常強勁。我們不會籌集過多的資金。我們預計不需要籌集資金。我們專注於 DMD 中 deramiocel 的批准，因此我們會看看情況是否需要，我們肯定會直接與該投資者討論。

Okay. Another question. So some investors are wondering about the scope and the pragmatic value of the early and the midcycle of the review processes in relation with the overall review process. So what are your general thoughts on that?

好的。另一個問題。因此，一些投資者對審查過程的早期和中期相對於整體審查過程的範圍和實際價值感到疑惑。那麼您對此有什麼看法？

I'm sorry, could you ask that question again? I'm not sure I understood the question.

抱歉，您能再問一次這個問題嗎？我不確定我是否理解了這個問題。

Okay. So some investors are wondering about the scope and the pragmatic value of the early and the midcycle FDA review processes in relation with the overall review process. So what are your general thoughts on that?

好的。因此，一些投資者對 FDA 早期和中期審查流程相對於整體審查流程的範圍和實際價值感到疑惑。那麼您對此有什麼看法？

Well, we had -- a BLA was accepted and we had a very successful midcycle review, so I guess the takeaway for investors is, in our situation, anyway, it wasn't predictive of what was coming next.

嗯，我們的 BLA 已被接受，而且我們進行了非常成功的中期審查，所以我想投資者可以得到的啟示是，在我們的情況下，無論如何，它都無法預測接下來會發生什麼。

Okay. And one last question. So in terms of the ex-US clinical pathway for development and for approval, particularly in the UK, we were wondering if Capricor could be eligible to take advantage of the IRP to seek UK authorization at some point, provided the future FDA decision was favorable so?

好的。最後一個問題。因此，就美國以外的臨床開發和批准途徑而言，特別是在英國，我們想知道，如果未來 FDA 的決定是有利的，Capricor 是否有資格利用 IRP 在某個時候尋求英國授權？

What was -- what decision?

是什麼——什麼決定？

So we were wondering if in terms of the ex-US clinical pathway whether Capricor could be eligible to take the IRP, which is the International Recognition Procedure to seek the UK authorization at some point, given that the future FDA decision is going to be favorable.

因此，我們想知道，就美國以外的臨床途徑而言，如果未來 FDA 的決定是有利的，Capricor 是否有資格採取 IRP（即國際認可程序），以便在某個時候尋求英國授權。

Yeah. Thanks. So as I mentioned in my prepared remarks, we're focusing on US approval right now. Our global strategy is emerging. A lot of it will be based on some of the feedback we received from FDA and what our path forward is, and please stay tuned. We'll provide updates on our ex-US strategies as they become available.

是的。謝謝。正如我在準備好的演講中提到的那樣，我們現在關注的是美國的批准。我們的全球戰略正在形成。其中許多將基於我們從 FDA 收到的一些反饋以及我們的前進方向，請繼續關注。我們將及時提供美國以外地區策略的更新資訊。

Okay. Okay. Thank you so much and best of luck, yeah.

好的。好的。非常感謝，祝你好運，是的。

Thanks.

謝謝。

Catherine Novack, Jones.

凱瑟琳·諾瓦克，瓊斯。

Hi, Linda. Thanks for taking my question. So one question was when the FDA responded to your request for Type A meeting, gave you the date, did they give any substantive reply to your meeting request, particularly around positive or negative wording around the LVEF?

你好，琳達。感謝您回答我的問題。所以一個問題是，當 FDA 回應您的 A 類會議請求並告知您日期時，他們是否對您的會議請求給出了任何實質性答复，特別是有關 LVEF 的正面或負面措辭？

No. So, typically, when they accept a meeting request they just say, they accept your meeting request and then they send over a date. We submitted a briefing package and we're waiting feedback on that and we'll discuss the ramifications of what we asked when they respond in the meeting.

不。因此，通常情況下，當他們接受會議請求時，他們只會說，他們接受您的會議請求，然後發送一個日期。我們提交了一份簡報，正在等待回饋，當他們在會議上回應時，我們將討論我們所問的問題的後果。

Got it. And then the R&D expense for 2Q, what accounts for the increase? Does this build up of product inventory ahead of potential launch, or is this due to ongoing clinical studies we should expect to see continued growth on that line?

知道了。那麼第二季的研發費用增加的原因是什麼？這是在潛在上市之前累積的產品庫存嗎？還是由於正在進行的臨床研究，我們應該預期該產品線會繼續成長？

Yeah. Thanks, Catherine. I mean, it encompasses a little bit of both of what you said. We're obviously in the end stages of HOPE-3, but those patients, 104 of them, are ongoing in that clinical development expense line item. We're also, obviously, preparing for the CMC endeavor, so that's where it's at. Obviously, when we get more clarity and feedback from FDA and announce more plans, I think we'll have more granular items on the burn rate moving forward. But it really encapsulates both of those areas. That's the main areas of spend.

是的。謝謝，凱瑟琳。我的意思是，它包含了你所說的兩點。我們顯然正處於 HOPE-3 的最後階段，但其中 104 名患者仍在該臨床開發費用項目中。顯然，我們也在為 CMC 努力做準備，所以現在情況就是這樣。顯然，當我們從 FDA 獲得更清晰的資訊和反饋並宣布更多計劃時，我認為我們將在未來的燒錢率方面有更詳細的資訊。但它確實涵蓋了這兩個領域。這是主要的支出領域。

Okay. All right. Thanks. That's it for us.

好的。好的。謝謝。對我們來說就是這樣。

Thank you.

謝謝。

Thank you.

謝謝。

(Operator Instructions) Matthew Venezia, AGP.

（操作員指示）Matthew Venezia，AGP。

Hi, Linda. Hi, AJ. Thank you for taking our questions. So just looking for a little clarity on the FDA review process to date, has -- obviously, there's been turnovers since the new administration, but has there been any turnover since Prasad's leaving the FDA and then him coming back? And has the team that you've been engaging with at the FDA changed at all in that time?

你好，琳達。你好，AJ。感謝您回答我們的問題。因此，只是想稍微澄清一下迄今為止 FDA 的審查流程，顯然，自新政府上任以來，已經出現了一些人員變動，但是自從普拉薩德離開 FDA 又回來之後，還有沒有人員變動呢？在此期間，您所合作的 FDA 團隊有什麼改變嗎？

Really don't know. We'll know more this week. So the big change with Dr. Prasad leaving and now Dr. Prasad returning. We don't know the ramifications of his exit or return on our program, but what I can say for sure is that we're looking forward to working directly with him and with the team, and we do not think that the data should be interpreted differently by any teammate that are different.

真的不知道。本週我們將會了解更多。因此，普拉薩德博士離開和現在普拉薩德博士回歸帶來了巨大的變化。我們不知道他的離開或回歸會對我們的專案產生什麼影響，但我可以肯定地說，我們期待與他和團隊直接合作，我們不認為任何不同的隊友應該對數據做出不同的解讀。

Got it. And just a little bit on the run rate, do you expect it to taper off in 2026 once you get clarity, regulatory wise and potential launch wise as HOPE-3 winds down, and should R&D come down and maybe G&A go up a little bit?

知道了。關於運行率，您是否預計在 HOPE-3 專案結束後，一旦監管和潛在發布情況明朗化，運行率會在 2026 年逐漸下降，研發費用是否會下降，而 G&A 費用是否會略有上升？

Yeah. I think that's fair. Thanks, Matt. I mean, obviously, again, as I articulated, what the next steps and HOPE-3 is a big aspect to that. But should we achieve approval, we'll have some pretty serious capital injections around the potential sale of the PRV and $80 million from Nippon Shinyaku that will allow us, of course, to invest in CMC expansion and everything we want to do around the launch for commercial endeavors.

是的。我認為這是公平的。謝謝，馬特。我的意思是，顯然，正如我所闡述的，下一步該做什麼，而 HOPE-3 是其中一個重要的面向。但如果獲得批准，我們將獲得一些相當可觀的資本注入，包括 PRV 的潛在出售以及來自日本新藥的 8000 萬美元，這當然將使我們能夠投資於 CMC 擴張以及我們想在商業啟動方面所做的一切。

So that's how we're looking at it. Obviously, more granular level can be discussed in the future, but we expect the capital to go right where it needs to be, which is preparing for the launch.

這就是我們看待它的方式。顯然，未來可以討論更細粒度的問題，但我們預計資金將流向需要的地方，即為發布做準備。

Al right. Got it. Thank you, guys, for taking my questions and good luck at the Type A meeting.

好吧。知道了。謝謝你們回答我的問題，祝 A 類會議一切順利。

Thanks, Matt.

謝謝，馬特。

Thank you.

謝謝。

[Chris Lemos, Nala].

[克里斯·萊莫斯，娜拉]。

(technical difficulty) at the Type A meeting.

（技術難度）在 A 類會議上。

I'm sorry?

對不起？

All right, well thank you so much. I guess we lost the question. I want to thank you for joining today's call. We look forward to updating on our progress over the coming months, although, this is a big week for us, so we will update as soon as we get feedback from the FDA and look forward to a positive review of deramiocel. Thank you so much and have a great day.

好的，非常感謝。我想我們忘記這個問題了。感謝您參加今天的電話會議。我們期待在未來幾個月內更新我們的進展，儘管這對我們來說是重要的一周，所以我們會在收到 FDA 的反饋後立即更新，並期待對 deramiocel 的積極評價。非常感謝您，祝您有愉快的一天。

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

女士們、先生們，本次電話會議到此結束。謝謝大家的參與。您現在可以斷開連線。