Capricor Therapeutics Inc (CAPR) 2023 Q2 法說會逐字稿

Good afternoon, ladies and gentlemen, and welcome to the Capricor Therapeutics second-quarter 2023 financial results and corporate update call. (Operator Instructions) As a reminder, this conference call is being recorded. I would now like to turn the conference over to our host, Mr. AJ Bergmann, Capricor's Chief Financial Officer.

女士們、先生們，下午好，歡迎參加 Capricor Therapeutics 2023 年第二季度財務業績和公司更新電話會議。 （操作員說明）謹此提醒，本次電話會議正在錄音。現在我想將會議交給我們的東道主 Capricor 首席財務官 AJ Bergmann 先生。

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; plans to present or report additional data; our plans regarding regulatory filings; potential regulatory developments regarding our product candidates; manufacturing capabilities; potential milestone payments and other possible uses of existing cash and investment resources.

謝謝大家，大家下午好。在開始之前，我想聲明，我們將在今天的演示中做出某些前瞻性陳述。這些聲明可能包括有關我們候選產品的功效、安全性和預期用途等的聲明；我們未來的研究和開發計劃，包括我們預期的臨床前和臨床研究的進行和時間安排；計劃提供或報告額外數據；我們有關監管備案的計劃；有關我們候選產品的潛在監管發展；製造能力；潛在的里程碑付款以及現有現金和投資資源的其他可能用途。

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

這些前瞻性陳述基於當前信息、假設和預期，這些信息、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包含的結果存在重大差異。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進行了描述，包括我們的季度和年度報告。請您注意不要過分依賴這些前瞻性陳述，我們不承擔更新此類陳述的義務。

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

接下來，我會將電話轉給首席執行官琳達·馬班 (Linda Marbán)。

Thank you, AJ. Good afternoon, and thank you for joining our second-quarter 2023 conference call. Today, I would like to begin by reiterating our deep commitment to optimizing patient-focused medicine and in the first half of 2023, we continued to make steady progress across our pipeline and are well positioned to deliver on important clinical and regulatory milestones for our Duchenne muscular dystrophy program as well as continue to advance our exosome platform technology.

謝謝你，阿傑。下午好，感謝您參加我們的 2023 年第二季度電話會議。今天，我首先要重申我們對優化以患者為中心的醫療的堅定承諾，在2023 年上半年，我們繼續在我們的產品線中取得穩步進展，並做好了充分準備，為我們的Duchenne 實現重要的臨床和監管里程碑肌營養不良症計劃以及繼續推進我們的外泌體平台技術。

I am extremely pleased with the recent additions of two new members to our Board of Directors with the additions of doctors, Philip Gotwals and Paul Auwaerter. Dr. Gotwals most recently served as the Global Head, Vice President of Business Development and Licensing at Novartis Institute for Biomedical Research and has nearly 30 years of experience in drug development, research, corporate strategy and business development.

我對最近董事會新增兩名新成員以及醫生 Philip Gotwals 和 Paul Auwaerter 感到非常高興。 Gotwals 博士最近擔任諾華生物醫學研究所全球負責人、業務開發和許可副總裁，在藥物開發、研究、企業戰略和業務開發方面擁有近 30 年的經驗。

Dr. Auwaerter brings over 30 years of internal medicine and infectious disease experience as the Sherrilyn and Ken Fisher Professor of Medicine at the Johns Hopkins University School of Medicine serving as the Clinical Director for the Division of Infectious Diseases and the Director of the Sherrilyn and Ken Fisher Center for Environmental Infectious Diseases. Both Dr. Gotwals's and Auwaerter's deep industry experience will be invaluable as we continue to enhance our strategic and business development priorities across both of our programs.

Auwaerter 博士作為約翰霍普金斯大學醫學院的 Sherrilyn 和 Ken Fisher 醫學教授，擁有 30 多年的內科和傳染病經驗，擔任傳染病科的臨床主任以及 Sherrilyn 和 Ken Fisher 的主任費舍爾環境傳染病中心。隨著我們繼續加强两個項目的戰略和業務發展優先事項，Gotwals 博士和 Auwaerter 深厚的行業經驗將非常寶貴。

Our late-stage clinical development program for CAP-1002 in patients with DMD continues to advance through development and key priorities include enrollment of our Phase 3 HOPE-3 clinical trial, which I will give more details on in the next few minutes, as well as continuing discussions with the FDA regarding the proposed path towards submissions of a biologics license application. Building on this momentum, we believe we are well positioned to execute our corporate objectives throughout the remainder of the year.

我們針對 DMD 患者的 CAP-1002 後期臨床開發計劃在開發過程中不斷取得進展，關鍵優先事項包括註冊我們的 3 期 HOPE-3 臨床試驗，我將在接下來的幾分鐘內提供更多詳細信息與FDA 繼續討論提交生物製劑許可申請的擬議途徑。在此勢頭的基礎上，我們相信我們有能力在今年剩餘時間內實現我們的企業目標。

I will now dive into our programs and provide an update on recent activity. Let me provide you an update on our recent FDA interactions. Earlier this year, as part of our RMAT designation, we held a Type-B CMC or chemistry, manufacturing, and controls-related meeting with FDA, where we outlined our plans for production of commercial-scale GMP CAP-1002. The outcome of this meeting was positive and that FDA clearly outlined for us the deliverables necessary for the CMC portion of our BLA.

我現在將深入了解我們的計劃並提供近期活動的最新情況。讓我向您介紹我們最近與 FDA 互動的最新情況。今年早些時候，作為 RMAT 指定的一部分，我們與 FDA 舉行了 B 型 CMC 或化學、製造和控制相關會議，會上我們概述了商業規模 GMP CAP-1002 的生產計劃。這次會議的結果是積極的，FDA 為我們明確概述了 BLA 的 CMC 部分所需的可交付成果。

As we previously have reported, there also was a discussion concerning the possible inclusion of additional patients who would need to be treated with product from our San Diego GMP facility in order to support commercial product manufacturing at this site. As this request would have likely extended the timeline for the completion of our pivotal trial and therefore, the time to BLA, we requested a subsequent Type-B clinical meeting with FDA to determine if there was a more efficient and expeditious path to BLA due to the great unmet medical need of this patient population.

正如我們之前報導的那樣，還討論了是否可能納入更多需要使用我們聖地亞哥 GMP 工廠的產品進行治療的患者，以支持該工廠的商業產品生產。由於這一請求可能會延長完成我們關鍵試驗的時間，從而延長 BLA 的時間，因此我們請求隨後與 FDA 舉行 B 型臨床會議，以確定是否有更有效、更快捷的 BLA 路徑，因為該患者群體巨大的未滿足的醫療需求。

The advocacy community believes as we do that CAP-1002 attenuates disease progression, and they have continued to raise awareness of our program within the FDA and specifically CBER. And as the FDA continues to highlight the importance of patient perspective, they have continued to pay close attention to our program.

倡導團體和我們一樣相信 CAP-1002 可以減緩疾病進展，並且他們繼續提高 FDA 特別是 CBER 內對我們項目的認識。隨著 FDA 不斷強調患者觀點的重要性，他們也繼續密切關注我們的計劃。

To that end, the FDA granted our request to discuss our program in more detail, and this meeting occurred in July of this year. The goal was to further outline a plan for an expedited path to BLA for CAP-1002 for the treatment of later-stage DMD. And I'm happy to share that FDA seemed generally supportive of this plan.

為此，FDA 同意了我們的請求，更詳細地討論我們的計劃，這次會議於今年 7 月舉行。目標是進一步概述用於治療晚期 DMD 的 CAP-1002 快速獲得 BLA 的計劃。我很高興地告訴大家，FDA 似乎普遍支持這一計劃。

Currently, we are awaiting the final minutes from FDA, which we expect this month. We have already had another informal meeting with FDA to further design certain aspects of our program, and we are greatly appreciative of the FDA's guidance to optimize the HOPE-3 clinical trial design to support our path to potential approval.

目前，我們正在等待 FDA 的最後會議記錄，預計本月發布。我們已經與 FDA 舉行了另一次非正式會議，以進一步設計我們項目的某些方面，我們非常感謝 FDA 優化 HOPE-3 臨床試驗設計的指導，以支持我們獲得潛在批准的道路。

Next, I'll provide an update on HOPE-3, our Phase 3 clinical trial. I am very pleased to inform you that as of today, we have randomized 48 subjects across 17 active sites. And based on the currently designed sample size of 68 patients, we are on track to be fully enrolled early in the fourth quarter of this year. Furthermore, we remain on track to conduct an interim analysis on HOPE-3 in the fourth quarter of this year, which will primarily focus on a futility analysis.

接下來，我將提供有關我們的 3 期臨床試驗 HOPE-3 的最新信息。我很高興地通知您，截至今天，我們已經在 17 個活動站點隨機分配了 48 名受試者。根據目前設計的 68 名患者樣本量，我們有望在今年第四季度初全面入組。此外，我們仍有望在今年第四季度對 HOPE-3 進行中期分析，主要關注無效性分析。

I am very enthusiastic about the rate of enrollment, which has been strong throughout the summer, and propelled by the positive feedback from patients and families, including the anecdotal reports of disease attenuation. Additionally, we are extremely pleased by the safety profile of CAP-1002 and the overall support of our investigators and families.

我對整個夏季的入學率感到非常興奮，並且受到患者和家庭的積極反饋（包括疾病減弱的軼事報告）的推動。此外，我們對 CAP-1002 的安全性以及我們的研究人員和家人的總體支持感到非常滿意。

Now for an update on our most recent HOPE-2 open-label extension or OLE results presented at this year's Parent Project for Muscular Dystrophy Annual Conference. To remind you, we presented positive statistically significant two-year follow-up results from this study.

現在更新我們在今年的肌營養不良症家長項目年會上公佈的最新 HOPE-2 開放標籤擴展或 OLE 結果。提醒您，我們提供了這項研究的具有統計學意義的積極的兩年隨訪結果。

As you may recall, the HOPE-2 OLE study previously met its primary endpoint at the one-year time point on the PUL version 2.0 scale. At the 24-month time point, the data continued to show statistically significant differences in the PUL -- performance of the upper limb -- version 2.0 in the open-label extension treatment group when compared to the original rate of decline of the placebo group from HOPE-2 after one year.

您可能還記得，HOPE-2 OLE 研究之前在 PUL 2.0 版量表的一年時間點達到了主要終點。在 24 個月的時間點，數據繼續顯示，與安慰劑組的原始下降率相比，開放標籤擴展治療組的 PUL（上肢表現）2.0 版本存在統計學顯著差異一年後來自 HOPE-2。

Even more profound were the cardiac findings we observed. While the natural history of DMD cardiomyopathy suggests a steady decline in cardiac function as measured by ejection fraction, in HOPE-2 OLE, we observed improvements in heart function in six of nine patients. Over time, we also observed an increasing correlation with the performance of the upper limb version 2.0 and ejection fraction results.

更深刻的是我們觀察到的心臟發現。雖然 DMD 心肌病的自然史表明通過射血分數測量的心臟功能穩步下降，但在 HOPE-2 OLE 中，我們觀察到 9 名患者中有 6 名的心臟功能有所改善。隨著時間的推移，我們還觀察到 2.0 版上肢表現和射血分數結果之間的相關性越來越強。

The two-year results from this open-label study are tremendously impactful for DMD patients -- so in cardiac and skeletal functional benefits, which underscores the potential long-term benefits of CAP-1002 treatment in DMD. The disease-modifying potential, together with the favorable safety and tolerability profile, further positions CAP-1002 as a potential anchor therapy for DMD patients. We are thankful to the patients and their families for their continuous commitment to working with us on demonstrating the potential benefits of CAP-1002.

這項開放標籤研究的兩年結果對 DMD 患者產生了巨大影響，包括心臟和骨骼功能的益處，這強調了 CAP-1002 治療 DMD 的潛在長期益處。改善疾病的潛力，加上良好的安全性和耐受性，進一步將 CAP-1002 定位為 DMD 患者的潛在錨定療法。我們感謝患者及其家人持續致力於與我們合作，展示 CAP-1002 的潛在益處。

Now turning to our partnership strategy. Now that we have secured commercial and distribution rights in the US and Japan with our partner, Nippon Shinyaku, we continue to focus on securing additional partners in other markets around the world with Europe being a key priority and now have several companies evaluating the opportunity.

現在轉向我們的合作夥伴戰略。現在，我們已經與合作夥伴Nippon Shinyaku 在美國和日本獲得了商業和分銷權，我們將繼續專注於在世界其他市場尋找更多合作夥伴，其中歐洲是重中之重，現在有幾家公司正在評估這一機會。

Another focus I would like to briefly touch upon is the opportunity to evaluate new indications where CAP-1002 might provide benefits to additional patients. While we haven't committed any resources to this development area yet, this opportunity would provide another potential avenue for partnering, licensing, or even sole development, leveraging on the capabilities we have built at Capricor for CAP-1002.

我想簡要提及的另一個重點是評估 CAP-1002 可能為更多患者帶來益處的新適應症的機會。雖然我們尚未向該開發領域投入任何資源，但利用我們在 Capricor 為 CAP-1002 構建的功能，這一機會將為合作、許可甚至單獨開發提供另一種潛在途徑。

Lastly, I would like to provide on our update on our GMP manufacturing facility. We have designed this GMP manufacturing facility to produce commercial-scale GMP CAP-1002 doses. We see this facility as a versatile and cost-effective way to bring CAP-1002 to market efficiently.

最後，我想介紹一下我們 GMP 生產設施的最新情況。我們設計這個 GMP 生產設施是為了生產商業規模的 GMP CAP-1002 劑量。我們認為該設施是一種多功能且經濟高效的方式，可以將 CAP-1002 高效推向市場。

In anticipation of CAP-1002 obtaining market approval, we built this facility because we believe having the ability to manufacture in-house will greatly increase our margins and will support the early launch of this product. I am pleased to report that the San Diego facility is up and running. Engineering runs are underway, and we remain on track to be able to release clinical doses in the third quarter of this year. Overall, I am very pleased with the progress of our DMD program. We look forward to sharing further updates from our interactions with FDA, our progress with HOPE-3, and the development of potential additional partnerships in new territories.

為了預期 CAP-1002 獲得市場批准，我們建造了這個工廠，因為我們相信擁有內部製造能力將大大增加我們的利潤，並將支持該產品的早期推出。我很高興地報告，聖地亞哥工廠已建成並投入運行。工程運行正在進行中，我們仍有望在今年第三季度發布臨床劑量。總的來說，我對我們 DMD 項目的進展感到非常滿意。我們期待分享我們與 FDA 的互動、我們與 HOPE-3 的進展以及在新領域潛在的其他合作夥伴關係的發展的進一步更新。

We have two new additions to our senior leadership team, enhancing our regulatory and CMC internal expertise. Dr. Yushi Feng has assumed his role as Vice President of Regulatory, overseeing all regulatory activities. Dr. Feng previously worked at the FDA, WAVE Life Sciences, and Codiak Biosciences. Each of these companies have overlapping areas -- are overlapping with our areas of focus.

我們的高級領導團隊新增了兩名新成員，增強了我們的監管和 CMC 內部專業知識。馮於時博士擔任監管副總裁，負責監督所有監管活動。馮博士曾在 FDA、WAVE Life Sciences 和 Codiak Biosciences 工作。這些公司中的每家都有重疊的領域——與我們的重點領域重疊。

Additionally, Jonathan Tayco has joined us as Vice President of Program Management and Business Operations, overseeing CMC development. Prior experience for Mr. Tayco included Kite Pharma, where he played an integral role in the BLA approval of Yescarta, one of the first approved cell therapy treatments for large B-cell lymphoma. I am very pleased to welcome these two new members to our team.

此外，Jonathan Tayco 已加入我們，擔任項目管理和業務運營副總裁，負責監督 CMC 開發。 Tayco 先生此前曾在 Kite Pharma 工作過，在 Yescarta 獲得 BLA 批准過程中發揮了不可或缺的作用，Yescarta 是首批獲得批准的大 B 細胞淋巴瘤細胞療法之一。我非常高興地歡迎這兩位新成員加入我們的團隊。

Now turning to our exosome platform technology, which leverages the natural cell-to-cell communication of the body. We are harnessing exosomes to serve as a novel drug delivery system with broad therapeutic applications. And our proprietary StealthX expression platform is at the core of our exosome program, which is focused on the development of two broad modalities: infectious disease and precision therapeutics.

現在轉向我們的外泌體平台技術，該技術利用了身體的自然細胞間通訊。我們正在利用外泌體作為一種具有廣泛治療應用的新型藥物遞送系統。我們專有的 StealthX 表達平台是我們外泌體計劃的核心，該計劃專注於兩種廣泛模式的開發：傳染病和精準治療。

As previously stated, we believe that exosomes are the future of drug delivery. They are able to deliver contents directly to the cell, avoid detection by the immune system, and can be targeted. However, one of the issues that the field has been grappling with is the ability to manufacture a large volume of a relatively homogeneous formulation similar to lipid nanoparticles.

如前所述，我們相信外泌體是藥物輸送的未來。它們能夠將內容物直接傳遞到細胞，避免被免疫系統檢測到，並且可以成為目標。然而，該領域一直在努力解決的問題之一是是否能夠製造大量類似於脂質納米顆粒的相對均勻的製劑。

We have focused a significant amount of time and energy into manufacturing and targeting of exosomes. And I'm delighted to share with you that we have made paradigm-shifting progress on these objectives. This development step allows for rapid and efficient development of future exosome product.

我們投入了大量的時間和精力來製造和靶向外泌體。我很高興與大家分享，我們在這些目標上取得了範式轉變的進展。這一開發步驟可以快速有效地開發未來的外泌體產品。

To that end, I'm very pleased to report that we have recently begun work with an undisclosed pharma company looking at enhancing delivery of ASOs using exosomes as the delivery vehicle. I look forward to providing more details on this in the coming months as this is a very important step for Capricor as we begin to leverage our platform, StealthX. We look further to exploring the applications of our StealthX platform as we expand into precision-based therapeutics and are working in targets, primarily in neuromuscular diseases at this time.

為此，我很高興地報告，我們最近開始與一家未公開的製藥公司合作，研究使用外泌體作為遞送載體來增強 ASO 的遞送。我期待在未來幾個月內提供更多相關細節，因為這對於 Capricor 來說是非常重要的一步，因為我們開始利用我們的平台 StealthX。隨著我們擴展到基於精確的治療方法並致力於目標（目前主要是神經肌肉疾病），我們希望進一步探索 StealthX 平台的應用。

Additionally, we recently published data in bioRxiv, a journal featuring two vaccine candidates that were generated with StealthX. Exosomes were engineered to express influenza H3 or SARS-CoV-2 spike. When administered individually, both StealthX H3, and StealthX spike introduce a strong immunization with the production of a potent humoral and cellular immune response.

此外，我們最近在 bioRxiv 上發布了數據，該雜誌收錄了使用 StealthX 生成的兩種候選疫苗。外泌體被設計用於表達流感 H3 或 SARS-CoV-2 刺突。當單獨給藥時，StealthX H3 和 StealthX 尖峰都會產生強烈的免疫作用，產生有效的體液和細胞免疫反應。

These effects were obtained with administration of nanograms of protein and without adjuvant or lipid nanoparticles. To test the potential benefits of the bivalent vaccine, hemagglutinin H3 and SARS-CoV-2 spike proteins were individually engineered on the exosome surface and mixed before injection. This combination approach also induced a strong immune response in mice with both antibody and T-cell response.

這些效果是通過施用納克蛋白質而不使用佐劑或脂質納米顆粒獲得的。為了測試二價疫苗的潛在益處，在外泌體表面分別設計了血凝素 H3 和 SARS-CoV-2 刺突蛋白，並在註射前混合。這種組合方法還通過抗體和 T 細胞反應在小鼠中誘導了強烈的免疫反應。

Additionally, there were no detectable immune competition between antigens. By combining multiple targets in a single vaccine formulation, these results support the potential therapeutic utility and versatility of our StealthX platform in addressing a broad range of infectious diseases. Our current plans continue to focus on leveraging business development and partnering strategies as well as non-dilutive grant funding for our exosome platform technology.

此外，抗原之間沒有可檢測到的免疫競爭。通過將多個靶點結合在單一疫苗配方中，這些結果支持了我們的 StealthX 平台在解決廣泛的傳染病方面的潛在治療效用和多功能性。我們目前的計劃繼續側重於利用業務發展和合作戰略以及我們的外泌體平台技術的非稀釋性贈款資金。

In closing, we are pleased with the advancements across the organization as we remain focused on becoming a commercial-scale company with CAP-1002 as our lead asset and development of our exosome technology. We are entering the second half of the year in a position of strength. I look forward to working with our new Board members and capitalizing on their deep industry experience and forward-looking vision, which we feel will be invaluable as we continue to execute on the key priorities for CAP-1002 and our exosome platform.

最後，我們對整個組織的進步感到高興，因為我們仍然專注於成為一家商業規模的公司，以 CAP-1002 作為我們的主要資產和外泌體技術的開發。進入下半年，我們處於強勢地位。我期待與我們的新董事會成員合作，並利用他們深厚的行業經驗和前瞻性願景，我們認為這對於我們繼續執行 CAP-1002 和我們的外泌體平台的關鍵優先事項將是無價的。

Now with that, I will turn the call over to our Chief Financial Officer, AJ Bergmann, to run through our financial results for the second quarter of 2023.

現在，我將把電話轉給我們的首席財務官 AJ Bergmann，他會詳細介紹我們 2023 年第二季度的財務業績。

Thank you, Linda. This afternoon's press release provided a summary of our second-quarter 2023 financials on a GAAP basis. 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 financials section of our website.

謝謝你，琳達。今天下午的新聞稿提供了我們按 GAAP 計算的 2023 年第二季度財務狀況摘要。您還可以參考我們的 10-Q 表格季度報告，我們預計很快就會提供該報告，您可以在 SEC 網站以及我們網站的財務部分訪問該報告。

As of June 30, 2023, the company's cash, cash equivalents, and marketable securities totaled approximately $37.8 million compared to approximately $41.4 million on December 31, 2022. Based on our current operating plan, the company's cash position is expected to be sufficient to support operations through the third quarter of 2024. I would like to note that this expectation excludes any additional potential milestone payments under our exclusive commercialization and distribution agreement with Nippon Shinyaku that may become due, which would extend our cash runway.

截至2023年6月30日，公司的現金、現金等價物和有價證券總計約3780萬美元，而2022年12月31日約為4140萬美元。根據我們目前的運營計劃，公司的現金狀況預計足以支持運營至 2024 年第三季度。我想指出的是，這一預期不包括根據我們與 Nippon Shinyaku 的獨家商業化和分銷協議可能到期的任何額外潛在里程碑付款，這將延長我們的現金跑道。

Turning to the financials, revenues for the second quarter of 2023 were approximately $3.9 million compared with zero for the second quarter of 2022. The primary source of revenue was from the ratable recognition of the $30 million upfront payment in accordance with our US exclusive commercialization and distribution agreement we received from Nippon Shinyaku.

談到財務數據，2023 年第二季度的收入約為 390 萬美元，而 2022 年第二季度的收入為零。收入的主要來源是根據我們在美國的獨家商業化和我們從日本新藥收到了經銷協議。

Moving to our operating expenses for the second quarter of 2023, excluding stock-based compensation, our research and development expense was approximately $8.4 million compared to approximately $4.7 million in Q2 2022. Again, excluding stock-based compensation, our general and administrative expenses were approximately $1.7 million in Q2 2023 and approximately $1.4 million in Q2 2022.

轉向我們2023 年第二季度的運營費用，不包括基於股票的薪酬，我們的研發費用約為840 萬美元，而2022 年第二季度約為470 萬美元。同樣，不包括基於股票的薪酬，我們的一般和管理費用為2023 年第二季度約為 170 萬美元，2022 年第二季度約為 140 萬美元。

Net loss for the second quarter of 2023 was approximately $7.4 million compared to a net loss of approximately $7.1 million for the second quarter of 2022. Net loss for the first half of 2023 was approximately $15.1 million compared to a net loss of approximately $14.9 million for the first half of 2022.

2023 年第二季度的淨虧損約為740 萬美元，而2022 年第二季度的淨虧損約為710 萬美元。2023 年上半年的淨虧損約為1,510 萬美元，而2023 年上半年的淨虧損約為1,490 萬美元。 2022年上半年。

And with that, we will now open the line up for questions. Thank you very much.

至此，我們現在開始提問。非常感謝。

Thank you, sir. Ladies and gentlemen, we will now begin the question-and-answer session. (Operator Instructions) Joe Pantginis, H.C. Wainwright.

謝謝你，先生。女士們、先生們，我們現在開始問答環節。 （操作員說明）Joe Pantginis, H.C.溫賴特。

Hi. Good afternoon, Linda and AJ. Thanks for taking the questions. So I know there's a lot of working parts here. And I know my questions will revolve around some things that you might not be able to detail because the FDA minutes are not out yet, but I'm still going to ask them.

你好。下午好，琳達和 AJ。感謝您提出問題。所以我知道這裡有很多工作部件。我知道我的問題將圍繞一些你可能無法詳細說明的事情，因為 FDA 會議紀要還沒有出來，但我仍然會問他們。

With that said, I guess as San Diego comes online this quarter, if I heard you correctly, do you have a general range of the number of patients that would be required from that facility to start with?

話雖如此，我想隨著聖地亞哥本季度上線，如果我沒聽錯的話，您是否有該設施需要的患者數量的大致範圍？

Yeah, Joe. Hey. Good to talk to you, and you're correct. There's very little we can say until we get the final minutes. But what I can tell you is that once we get them, we plan on doing a public release in some way, either via press release and/or call to sort of update the market and the community as to exactly the path forward.

是的，喬。嘿。很高興與你交談，你是對的。在最後幾分鐘之前我們無話可說。但我可以告訴你的是，一旦我們得到它們，我們計劃以某種方式進行公開發布，無論是通過新聞稿和/或呼籲更新市場和社區的確切前進道路。

What I can tell you is that FDA has worked really closely with us. They're very supportive of this program. Several of our patients' families have reached out to FDA in order to ask them to take a really careful look at Capricor and help move the program forward because they feel that their sons are feeling and functioning better. And so we're confident that the answers that we get back from FDA will be the best ones possible to move the products towards BLA.

我可以告訴你的是，FDA 與我們合作非常密切。他們非常支持這個計劃。我們的一些患者家屬已經聯繫 FDA，要求他們仔細研究 Capricor 並幫助推進該計劃，因為他們覺得他們的兒子感覺和功能都更好了。因此，我們相信從 FDA 得到的答案將是使產品走向 BLA 的最佳答案。

That makes sense. And I guess for my next question, it's sort of in the same realm, but I'll ask it sort of scenario-based. So you do have the type -- you do have the minutes that you are awaiting right now. You also have the upcoming interim analysis in the fourth quarter for HOPE-3, which you said is primarily based on futility. However, does one of the potential scenarios include the positive feedback from the minutes with regard to the data you might see in the interim that could allow for the acceleration or resetting of the timelines positively for HOPE-3?

這就說得通了。我想對於我的下一個問題，它有點屬於同一領域，但我會根據場景來問它。所以你確實有這樣的類型——你確實有你現在正在等待的會議記錄。你們還即將對 HOPE-3 進行第四季度的中期分析，你們說這主要是基於徒勞。然而，潛在的場景之一是否包括會議記錄中關於您可能在過渡期間看到的數據的積極反饋，從而可以積極加速或重置 HOPE-3 的時間表？

Yeah. That was a pretty impressive question asked, Joe. Good work. I can tell you've been doing this a long time. So the answer to that is, futility is the metric that we're looking at for the interim analysis. FDA has been pretty clear with us that they want to keep this trial very tightly regulated, really carefully monitored because they believe in the product too. We can tell from their feedback for us. And so we're probably not going to use the interim for accelerated approval opportunity.

是的。喬，這是一個令人印象深刻的問題。幹得好。我可以看出你已經這樣做很長時間了。所以答案是，徒勞性是我們在中期分析中考慮的指標。 FDA 已經向我們明確表示，他們希望對這項試驗進行非常嚴格的監管，非常仔細地監控，因為他們也相信這個產品。我們可以從他們對我們的反饋中看出。因此，我們可能不會利用這一過渡時期來加速批准的機會。

I can tell you that I am laser focusing on opportunities where we may be able to take advantage of an earlier look to look for an accelerated approval. I cannot disclose now how we might do that, but that is something we're definitely thinking about.

我可以告訴你，我正在密切關注我們可能能夠利用早期審查來尋求加速批准的機會。我現在無法透露我們將如何做到這一點，但這是我們肯定正在考慮的事情。

Got it. And I guess my other questions are strictly logistical. In the conduct of HOPE-3, you're obviously encouraged by the enrollment rates that you've been seeing, if I understand correctly. What are the prominent reasons for screening failure of patients? Or what does the patient -- and also, what does the patient pipeline look like for potential enrollment?

知道了。我想我的其他問題都是嚴格意義上的後勤問題。如果我理解正確的話，在 HOPE-3 的實施過程中，您顯然對所看到的入學率感到鼓舞。患者篩查失敗的主要原因有哪些？或者患者是什麼樣的——以及潛在入組的患者渠道是什麼樣的？

Yeah, Joe. Great question. So screen fail rate, which has really come down a lot, thanks to our really -- very strong new clinical team that we put in place. And the primary reason that people fail out typically is that they don't have inclusion criteria of the performance of the upper limb score 2 to 5.

是的，喬。很好的問題。因此，屏幕故障率確實下降了很多，這要歸功於我們建立的非常強大的新臨床團隊。人們通常失敗的主要原因是他們沒有上肢評分 2 至 5 分的納入標準。

And so what we typically see is some of these guys whose scores are too low -- and let me just say from a human level, it's heartbreaking because they have to have the ability to use their hands and bring it to their mouth unassisted. And we probably get two or three calls a week from people saying, well, what if they need help? What if they use their other hand to boost it? So people want CAP-1002 desperately.

所以我們通常看到的是一些得分太低的人 - 讓我從人類的角度說，這是令人心碎的，因為他們必須有能力用手並在沒有幫助的情況下將其送到嘴裡。我們可能每週都會接到兩三個電話，人們問，好吧，如果他們需要幫助怎麼辦？如果他們用另一隻手來推動它怎麼辦？所以人們迫切需要 CAP-1002。

So that leads into the answer to your second question. The pipeline of potential patients is very rich. There's a lot of energy around this open-label extension data. At the PPMD meeting, we were by far one of the busiest booths, second only to Sarepta with the gene therapy. And so we are looking to build with Sarepta, with all of the gene therapies that could come along as anchor therapy for CAP-1002. And so the families see it that way as well. So we do not see any potential turndown or downturn in patient opportunities moving forward.

這就引出了你第二個問題的答案。潛在患者的管道非常豐富。這個開放標籤擴展數據有很多能量。在 PPMD​​ 會議上，我們是迄今為止最繁忙的展位之一，僅次於基因療法的 Sarepta。因此，我們希望與 Sarepta 一起構建所有可以作為 CAP-1002 錨定療法的基因療法。所以家人也是這麼看的。因此，我們認為未來患者機會不會出現任何潛在的下降或下降。

Got it. And then lastly, going away from HOPE-3 and DMD, you did give us a little bit of a tease again about additional CAP-1002 opportunities. And I was just curious here. Any potential for going back to any of the prior indications that you've worked on in the cardiovascular arena or any teasing you might want to give us now with regard to newer indications? Or is this a wait and see?

知道了。最後，除了 HOPE-3 和 DMD，你們確實再次給我們帶來了關於額外 CAP-1002 機會的一點戲弄。我只是對此感到好奇。是否有可能回到您之前在心血管領域研究過的任何適應症，或者您現在可能想就新的適應症向我們提供任何取笑？還是這是一種觀望？

Yeah. So I think the best way to answer that is we are very pleased with the progress of CAP-1002 in DMD. I think it's very clear that there seems to be disease-modifying and a very strong treatment effect that persists after years. Our patients have done really well on a repeated exposure.

是的。所以我認為回答這個問題的最好方法是我們對 CAP-1002 在 DMD 方面取得的進展感到非常高興。我認為很明顯，似乎有緩解疾病的作用，而且治療效果非常強，而且可以持續多年。我們的患者在反复暴露後表現非常好。

We have open-label extension patients that are in their third year and coming into their fourth year of treatment. And so it's very safe. The infusions are easy. So we are opening the door internally to look at potential opportunities for CAP-1002. We're exploring those now and we'll provide updates as we have them to where we will likely deploy CAP-1002 next.

我們有開放標籤延伸患者，他們已經進入治療的第三年，即將進入第四年的治療。所以它非常安全。輸液很容易。因此，我們正在向內部敞開大門，尋找 CAP-1002 的潛在機會。我們現在正在探索這些，我們將在我們下一步可能部署 CAP-1002 的地方提供更新。

But what I can tell you if you're sort of looking into your crystal ball, we've seen really nice data in an inflammatory cardiomyopathy, skeletal muscle disease, neuromuscular disease. We know that CAP-1002's primary mode of action is immunomodulatory and pro-regenerative. So we're going to continue to explore indications set -- so the disease pathogenesis would be highlighted by those two processes.

但我可以告訴你，如果你正在觀察你的水晶球，我們已經在炎症性心肌病、骨骼肌疾病、神經肌肉疾病方面看到了非常好的數據。我們知道 CAP-1002 的主要作用方式是免疫調節和促再生。因此，我們將繼續探索既定的適應症，以便通過這兩個過程來強調疾病的發病機制。

Got it. Thank you, Linda. Appreciate it.

知道了。謝謝你，琳達。欣賞它。

Thanks, Joe. Take good care. I'll see you soon.

謝謝，喬。多保重。一會兒見。

(Operator Instructions) Alan Leong, BioWatch News.

（操作員說明）Alan Leong，BioWatch News。

Linda, AJ, it's great to be back. And what wonderful commentary. Linda, your commentary extends way beyond the release and love to hear it. And also, shout out to Joe, the last analyst, for the great questions. I had a couple of sets of questions. You're into really low-volume, high-margin products. Although, Linda, you caught my ear about the breakdowns into scalability.

琳達，AJ，很高興回來。多麼精彩的評論啊。琳達，你的評論遠遠超出了發布範圍，我很喜歡聽它。另外，請向最後一位分析師喬提出好問題。我有幾組問題。您喜歡的是小批量、高利潤的產品。不過，琳達，你引起了我對可擴展性崩潰的關注。

Is the pilot manufacturing model a possible template for Capricor's future path for vertical integration? In other words, are you considering this your usual modus operandi going forward? If you could simply replicate pilot-size facilities, your product is soon to be in that sweet spot. But I wonder if you could provide any commentary on that.

試點製造模式是否是 Capricor 未來垂直整合路徑的可能模板？換句話說，您是否認為這是您今後的慣用做法？如果您可以簡單地複制試點規模的設施，您的產品很快就會達到最佳狀態。但我想知道你能否對此發表評論。

Are you talking, Alan -- by the way, it's great to hear your voice, and I hope you're continuing to do well. But are you talking primarily about exosomes or CAP-1002 in terms of pilot manufacturing expansion?

你在說話嗎，艾倫——順便說一句，很高興聽到你的聲音，我希望你繼續表現出色。但就試點生產擴張而言，您主要談論的是外泌體還是 CAP-1002？

Both. If I understand the manufacturing, you don't need a large footprint for either to accomplish what you need.

兩個都。如果我了解製造過程，那麼您不需要很大的佔地面積來完成您的需要。

Right. So they're similar but different, obviously. With CAP-1002, we really have put several manufacturing scale out and scale up opportunities in place so that we can reduce the footprint necessary and create more cells that's been pretty effective. And that's largely been the focus of the transfer to the San Diego GMP facility. We're working really closely with FDA and their CMC group in order to make sure that the product is the same as we produce in the pilot facility, which is why we're working right now to get those out there and into the clinic.

正確的。所以顯然它們相似但又不同。借助 CAP-1002，我們確實已經實現了多個製造規模擴大和規模擴大的機會，這樣我們就可以減少必要的佔地面積並創建更多非常有效的電池。這在很大程度上是轉移到聖地亞哥 GMP 工廠的重點。我們正在與 FDA 及其 CMC 小組密切合作，以確保該產品與我們在試點設施中生產的產品相同，這就是為什麼我們現在正在努力將這些產品推向臨床。

So yes, we expect that we can expand this. And it won't exactly be as I think you're envisioning, which is we take 10 little pilot facilities and turned it into 100 little pilot facilities. It will be an expanded facility, but some manufacturing processes will be largely the same. Cell therapy manufacturing opportunities has really expanded in the past couple of decades. So there's a lot of good opportunity there. So not exactly how you envision, but almost.

所以，是的，我們希望能夠擴大這一範圍。它不會完全像我想像的那樣，即我們將 10 個小型試點設施變成 100 個小型試點設施。這將是一個擴建的工廠，但一些製造工藝將基本相同。在過去的幾十年裡，細胞療法的製造機會確實擴大了。所以那裡有很多好機會。所以不完全是你想像的那樣，但也差不多。

In terms of exosomes, that is one of the areas of great pride for us. As I mentioned in my prepared remarks, one of the things that have held back exosomes is, how are you going to make these? How are you going to make them homogeneous? How are you going to turn them into a product? And we believe that we have done that.

就外泌體而言，這是我們非常自豪的領域之一。正如我在準備好的發言中提到的，阻礙外泌體發展的因素之一是，你將如何製作這些？你要如何使它們同質化？你打算如何將它們變成產品？我們相信我們已經做到了。

We have taken sort of the state of the art and what is known about exosomes, making lipid nanoparticles as well as some of the other engineering constructs and are building a really good manufacturing paradigm that also should be buildable and not really pilot plant expansion. That one will be more like big bubbling bioreactors and that kind of thing as we move it forward. But that's a procedure that can easily go from a couple of mLs to 100 mLs to liters and to larger volumes than that, if that makes any sense to you, Alan.

我們採用了最先進的技術和已知的外泌體知識，製造脂質納米顆粒以及其他一些工程結構，並正在構建一個非常好的製造範例，該範例也應該是可建造的，而不是真正的試點工廠擴張。當我們向前推進時，這個反應器將更像是大型冒泡生物反應器之類的東西。但這個過程可以很容易地從幾毫升到 100 毫升到升，甚至更大的體積，如果這對你有意義的話，艾倫。

It does. You also caught my ear about the ASO undisclosed pharma interest. But I want to go more general. Can I get more commentary on the general pharma and suitor interest because I've been watching this? How much pursuit from suitors are combination trials? Because if I read -- some of the literature -- if I'm wrong, feel free to bat me on the head. There's an assertion -- serious assertion issues of the current gene and cell therapies. And this is our -- CAP-1002 potentially becomes one plus one equals three and not two. That exerts a lot of interest from those who are in that space. Can you further comment on that in general?

確實如此。您還引起了我對 ASO 未公開的製藥公司興趣的關注。但我想更籠統一些。因為我一直在關注這個問題，所以我可以獲得更多關於一般製藥公司和追求者興趣的評論嗎？組合嘗試有多少追求者的追捧？因為如果我讀了一些文獻，如果我錯了，請隨意拍我的頭。有一個斷言——當前基因和細胞療法的嚴重斷言問題。這就是我們的——CAP-1002 有可能成為一加一等於三而不是二。這引起了那個領域的人們的很大興趣。您能否進一步對此發表評論？

You mean with the exosomes in terms of their partnering potential?

你的意思是外泌體的合作潛力？

Yes.

是的。

Yeah, absolutely. This is one of the great opportunities in biotechnology, and pharma is well aware of it. I think everybody knows that lipid nanoparticles can only take you so far. We've been working as a field -- and I say we because this even predates my own career in science -- on delivery and targeted delivery of therapeutics to cells. We know how important that is, and we can now harness something that the body makes naturally to do that.

是的，絕對是。這是生物技術領域的巨大機遇之一，製藥公司也清楚地意識到這一點。我想每個人都知道脂質納米粒子只能帶你到目前為止。我們一直致力於將治療藥物遞送和靶向遞送到細胞的領域——我說我們是因為這甚至早於我自己的科學職業生涯。我們知道這有多重要，現在我們可以利用身體自然產生的東西來做到這一點。

And so that's why Capricor has really turned our focus over the past two years towards an engineered exosome platform, not working specifically with exosomes made by a cell. CAP-1002 makes perfectly wonderful exosomes. We think they mediate the mechanism of action of CAP-1002. But what we really want to do is turn exosomes into a drug product.

這就是為什麼 Capricor 在過去兩年中真正將我們的注意力轉向了工程外泌體平台，而不是專門研究細胞產生的外泌體。 CAP-1002 可以產生完美的外泌體。我們認為它們介導 CAP-1002 的作用機制。但我們真正想做的是將外泌體變成藥物產品。

And so you engineer an exosome, you put what you want on the inside and you tell it where to go on the outside -- it's like putting a zip code on it. And of course, pharma is very interested in that. And we have a very active business development program right now. And one of the main hurdles was this manufacturing staff, which we have succeeded in doing. So we look forward to great opportunities with the exosomes moving forward.

所以你設計了一個外泌體，你把你想要的東西放在裡面，然後告訴它外面去哪裡——就像在上面放一個郵政編碼一樣。當然，製藥公司對此非常感興趣。我們現在有一個非常活躍的業務發展計劃。主要障礙之一是製造人員，我們已經成功做到了這一點。因此，我們期待外泌體的發展帶來巨大的機遇。

Last question, but this is for AJ. I guess for both of you, this will be a fun question, but it does get to some interesting things. You've got $10 million more upfront cash in the last agreement. If you got a grant or another agreement that brings another $10 million, how would you like it used?

最後一個問題，但這是針對 AJ 的。我想對於你們倆來說，這將是一個有趣的問題，但它確實涉及到一些有趣的事情。在上一份協議中，您多了 1000 萬美元的預付款。如果您獲得一筆贈款或另一項協議，可以帶來另外 1000 萬美元，您希望如何使用它？

Yeah, thanks, Alan, and nice to hear from you. I mean, obviously, bringing in non-dilutive capital is a big focus for us as you heard Linda articulate, both from a potential in our approach to vaccinology as well as the next steps, which is targeted therapeutics.

是的，謝謝，艾倫，很高興收到你的來信。我的意思是，顯然，引入非稀釋性資本是我們的一個重點，正如您聽到琳達所闡述的那樣，無論是從我們疫苗學方法的潛力還是下一步（即靶向治療）來看。

Where exactly would we like to deploy it? If I had my wish list, it would be great to use that non-dilutive capital to move into these types of new indications that we're hinting at here, whether it's new neuromuscular targets, potentially using the exosome as a targeted vehicle. That would be my wish list and taking those non-dilutive capital dollars in the door is a big area that we're putting a lot of energy in. I don't know if Linda wants to articulate anything else.

我們到底想將其部署在哪裡？如果我有我的願望清單，那麼使用非稀釋資本進入我們在這裡暗示的這些類型的新適應症將是很棒的，無論是新的神經肌肉目標，還是可能使用外泌體作為靶向載體。這將是我的願望清單，將這些非稀釋性資本收入納入大門是我們投入大量精力的一個重要領域。我不知道琳達是否還想闡明其他內容。

Yeah. Cash is king as you are in product development mode. And so what we would definitely do is use it in a laser-focused, targeted way to move our programs forward. So CAP-1002 is at the front of the line right now. All major dollars being spent are being spent on getting CAP-1002 approved. And then the few dollars leftover go towards the exosome program as we move that forward.

是的。當你處於產品開發模式時，現金為王。因此，我們肯定會以激光聚焦、有針對性的方式使用它來推動我們的項目向前發展。所以 CAP-1002 目前處於領先地位。所有主要資金都用於獲得 CAP-1002 的批准。然後，隨著我們的推進，剩下的幾美元將用於外泌體計劃。

If the dollars come in and are specifically requested to build a program, we will obviously work on that. For instance, if there was a deal where they wanted to build the engineered exosome, that's where a good proportion of those dollars we've got. So to that end, we are focusing on what we need to do. AJ maintains a very tight ship in terms of managing our resources. And that explains why we've been able to stay alive through some pretty difficult time.

如果資金到位並且特別要求建立一個項目，我們顯然會致力於此。例如，如果有一筆交易他們想要構建工程外泌體，那麼我們就可以得到很大一部分資金。為此，我們專注於我們需要做的事情。 AJ 在管理我們的資源方面保持著非常嚴格的紀律。這解釋了為什麼我們能夠度過一段相當困難的時期。

Well, I look forward in the immediate future, Linda, to walk into your office. The future looks bright for both of us. And I'm (multiple speakers) pleased with what I hear. Yeah.

好吧，琳達，我期待在不久的將來走進您的辦公室。我們倆的未來都是光明的。我（多位發言者）對我所聽到的感到滿意。是的。

That's wonderful news. The future is bright for Capricor. But if the future is bright for you, that's great news, Alan. So let's see each other soon.

這是個好消息。摩羯座的未來是光明的。但如果你的未來是光明的，那是個好消息，艾倫。那麼我們很快就能見面了。

Thank you. Looking forward to it.

謝謝。期待它。

All right. Take care.

好的。小心。

Take care, Alan.

保重，艾倫。

Take care.

小心。

(Operator Instructions) There seems to be no further questions at this time. I'd now like to turn the call back over to Capricor management for any closing remarks.

（操作員說明） 目前似乎沒有進一步的問題。我現在想將電話轉回 Capricor 管理層，請其發表結束語。

Thank you. Overall, I am confident that the company's upcoming catalysts provide a solid foundation for execution and value creation. We remain focused on driving our late-stage clinical development program forward for CAP-1002 in DMD.

謝謝。總的來說，我相信公司即將推出的催化劑為執行和價值創造奠定了堅實的基礎。我們仍然專注於推動 CAP-1002 治療 DMD 的後期臨床開發計劃。

Before we conclude today's call, I want to extend my sincere appreciation to the clinicians, patients, and their families who are working with us to bring CAP-1002 to closer to potential approval. Again, thanks to everyone who joined us this afternoon. And now you may disconnect your line.

在我們結束今天的電話會議之前，我想向與我們一起努力使 CAP-1002 更接近獲得批准的臨床醫生、患者及其家屬致以誠摯的謝意。再次感謝今天下午加入我們的所有人。現在您可以斷開線路了。