Capricor Therapeutics Inc (CAPR) 2023 Q4 法說會逐字稿

Good afternoon, ladies and gentlemen, and welcome to Capricor Therapeutics' fourth-quarter 2023 earnings call. (Operator Instructions)

女士們、先生們，下午好，歡迎參加 Capricor Therapeutics 的 2023 年第四季財報電話會議。（操作員說明）

This call is being recorded on Thursday, February 29, 2024.

此電話錄音於 2024 年 2 月 29 日星期四進行。

I would now like to turn the conference over to AJ Bergmann, CFO of Capricor. Please go ahead.

我現在想將會議交給 Capricor 財務長 AJ Bergmann。請繼續。

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

謝謝您，也謝謝您今天的加入。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；我們未來的研發計劃，包括我們預期的臨床前和臨床研究的進行和時間表；我們在臨床研究中招募病患；我們計劃提供或報告更多數據；我們有關監管備案的計劃、涉及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；我們的財務狀況；以及我們對現有現金和投資資源的可能用途。

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.

這些前瞻性陳述是基於當前資訊、假設和預期，這些資訊、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包含的結果有重大差異。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。請您注意不要過度依賴這些前瞻性陳述，我們不承擔更新此類陳述的義務。

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

接下來，我會將電話轉給執行長 Linda Marbán。

Thanks, AJ. Good afternoon and thank you for joining today's call. I'm encouraged with the progress we have made at Capricor in 2023 and into 2024. And today, I will outline our main priorities for our lead CAP-1002 program, as well as provide a brief update on our exosome platform technology.

謝謝，阿傑。下午好，感謝您參加今天的電話會議。我對 Capricor 在 2023 年和 2024 年取得的進展感到鼓舞。今天，我將概述我們領先的 CAP-1002 專案的主要優先事項，並提供有關我們的外泌體平台技術的簡要更新。

2023 was a big year for Capricor as we are now gearing up for a biologics license application and commercialization. To that end, Capricor has assembled a team primarily focused on executing in four main areas in order to prepare to bring our lead product, CAP-1002, to market for the treatment of DMD as expeditiously as possible. These are clinical manufacturing, BLA readiness, and commercial preparation. I will provide an overview of each area today.

2023 年對 Capricor 來說是重要的一年，因為我們現在正在為生物製品許可證申請和商業化做準備。為此，Capricor 組建了一個團隊，主要專注於四個主要領域的執行，以便準備將我們的主導產品 CAP-1002 盡快推向市場，用於治療 DMD。這些是臨床生產、BLA 準備和商業準備。今天我將概述每個領域。

First, let me provide a clinical update on our Phase 3 HOPE-3 pivotal trials, enrolling late-stage ambulant and non-ambulant young men with DMD across the United States. Late last year, we announced completion of enrollment in our Phase 3 pivotal HOPE-3 clinical trial where we enrolled 61 subjects randomized one-to-one to CAP-1002 or placebo.

首先，讓我提供 3 期 HOPE-3 關鍵試驗的臨床最新情況，該試驗招募了美國各地患有 DMD 的晚期流動和非流動年輕男性。去年年底，我們宣布完成 3 期關鍵 HOPE-3 臨床試驗的入組，其中我們入組了 61 名受試者，一對一隨機分配至 CAP-1002 或安慰劑組。

In December, we conducted a prespecified interim utility analysis and we were very pleased to announce that the trial was successfully deemed to not be futile with a positive recommendation to continue the trial. This analysis was based on an assessment by the Data Safety and Monitoring Board -- otherwise known, of course, as the DSMD -- of 30 subjects to reach a six-month time point at assessing their poll scores in a blinded fashion. This important positive outcome triggered our first milestone payment of $10 million from Nippon Shinyaku, further strengthening our balance sheet and extending our cash runway.

12 月，我們進行了預先指定的中期效用分析，我們非常高興地宣布試驗成功地被認為並非徒勞，並積極建議繼續試驗。這項分析是基於資料安全和監控委員會（當然也稱為 DSMD）對 30 名受試者進行的評估，以達到六個月的時間點以盲法評估他們的民意調查得分。這項重要的正面成果觸發了日本新藥向我們支付的第一筆里程碑式的 1000 萬美元款項，進一步加強了我們的資產負債表並擴大了我們的現金跑道。

Now, as you know, 2024 is a pivotal year for Capricor, as you will have data from Cohort A of our Phase 3 HOPE-3 clinical study at the end of the year, as well as fully enroll Cohort B by the second quarter of this year. To remind you, Cohort B was designed at the request of FDA to demonstrate comparable efficacy of CAP-1002 from our San Diego manufacturing facility to that produced in Los Angeles.

現在，如您所知，2024 年對Capricor 來說是關鍵的一年，因為您將在年底獲得我們3 期HOPE-3 臨床研究的隊列A 的數據，並在2024 年第二季度全面註冊隊列B 。今年。提醒您，隊列 B 是根據 FDA 的要求設計的，旨在證明我們聖地牙哥製造工廠生產的 CAP-1002 與洛杉磯生產的 CAP-1002 的功效相當。

This cohort, which is designed to enroll approximately 44 subjects, is enrolling very well. In fact, enrollment has proceeded even faster than predicted, partially based on the fact that there are no current therapeutics approved and very few in clinical trials for these later-stage non-ambulant patients.

該隊列旨在招募約 44 名受試者，目前招募情況非常好。事實上，入組的速度比預期的還要快，部分原因是目前還沒有批准的治療方法，而且針對這些晚期非流動患者的臨床試驗中的治療方法也很少。

The primary endpoint of HOPE-3 is a change from baseline in the Performance of the Upper Limb version 2.0, of course, commonly known as the PUL, at one year as well as various secondary skeletal and cardiac endpoints, including left ventricular ejection fraction. We have already seen efficacy in the PUL 2.0 and our Phase 2 HOPE-2 study where the data showed a 1.8 point improvement relative to placebo and was statistically significant.

HOPE-3 的主要終點是一年時上肢表現 2.0 版（當然，通常稱為 PUL）相對於基線的變化，以及各種次要骨骼和心臟終點，包括左心室射血分數。我們已經在 PUL 2.0 和我們的 2 期 HOPE-2 研究中看到了療效，其中數據顯示相對於安慰劑有 1.8 個百分點的改善，並且具有統計顯著性。

Even more validating, the data shown in our Lancet paper, multiple PUL endpoints, whether specific regions or combinations, showed improvements were statistically significant changes in multiple domains. Importantly, CAP-1002-treated patients saw improvements in left ventricular ejection fraction, which is the gold standard measure of cardiac function. We saw a 4% improvement in treated patients with a p-value of 0.002.

更驗證的是，我們的《柳葉刀》論文中顯示的數據，多個 PUL 終點，無論是特定區域還是組合，都表明多個領域的改進是統計上顯著的變化。重要的是，接受 CAP-1002 治療的患者左心室射血分數有所改善，這是衡量心臟功能的黃金標準。我們發現接受治療的患者病情改善了 4%，p 值為 0.002。

In addition, there were significant improvements in left ventricular end systolic and left ventricular end diastolic volume, further suggesting structural improvements in the heart. There are no approved therapeutics that we are aware of that directly address the cardiomyopathy associated with DMD. Therefore, the importance of CAP-1002 in this area of unmet medical need cannot be understated.

此外，左心室收縮末期容積和左心室舒張末期容積顯著改善，進一步顯示心臟的結構改善。據我們所知，目前還沒有批准的治療方法可以直接治療與 DMD 相關的心肌病變。因此，CAP-1002 在這一未滿足的醫療需求領域的重要性不可小覷。

We have long-term safety and efficacy data in this patient population as we are continuing to follow the patients from the HOPE-2 study in an open-label extension study into their fourth year, and we will plan to have the three-year results available in the second quarter of 2024.

我們擁有該患者群體的長期安全性和有效性數據，因為我們正在開放標籤擴展研究中繼續跟踪 HOPE-2 研究中的患者至第四年，我們將計劃獲得三年結果將於2024 年第二季度推出。

The two-year results shared last year continue to show statistically significant differences in the PUL 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.

去年分享的兩年結果繼續顯示，與安慰劑組一年後 HOPE-2 的原始下降率相比，開放標籤延伸治療組的 PUL 2.0 有統計學顯著差異。

Further, while the natural history of DMD cardiomyopathy suggests a steady decline in cardiac function as measured by ejection fraction, in the HOPE-2 open label extension, we observed improvements in heart function in 66% of patients. The two-year results underscore the potential long-term benefits of CAP-1002 treatment in DMD.

此外，雖然 DMD 心肌病變的自然史顯示透過射血分數測量的心臟功能穩定下降，但在 HOPE-2 開放標籤擴展中，我們觀察到 66% 的患者心臟功能得到改善。兩年的結果強調了 CAP-1002 治療 DMD 的潛在長期益處。

As we envisioned CAP-1002 as a multi-year treatment, this dataset will strengthen both our potential revenue modeling on payer discussions for long-term reimbursement. DMD has rapidly become an orphan disease that has garnered a lot of attention, not only because of the terrible nature of a disease that robs children of the ability to use their muscles more, but also because of the promise of disease modification by gene therapies and exon-skipping technologies to potentially allow modification at the dystrophy.

正如我們設想 CAP-1002 作為一種多年治療方法，該資料集將加強我們對付款人長期報銷討論的潛在收入模型。DMD 已迅速成為一種引起廣泛關注的孤兒疾病，不僅因為這種疾病的可怕性質會剝奪兒童更多地使用肌肉的能力，還因為基因療法和基因療法有望改變疾病。外顯子跳躍技術可能允許對營養不良進行修飾。

Many have thought that along with exon-skipping technologies, if the gene therapies are approved, there will no longer be a need for other treatments for DMD. Nothing could be further from the truth. The current gene therapy paradigm allows for a small, albeit potentially rather relevant amount of microdystrophin protein to be made.

許多人認為，除了外顯子跳躍技術之外，如果基因療法獲得批准，將不再需要其他 DMD 治療方法。沒有東西會離事實很遠。目前的基因治療範例允許製造少量但可能相當相關的微抗肌營養不良蛋白。

Current clinical data suggests there is an attenuation of disease progression from treatment with the gene therapy. However, we believe that it will require a multidrug paradigm to address all of the pathological consequences of DMD, primarily inflammation and fibrosis caused by the lack of [dystrophin].

目前的臨床數據表明，基因療法治療可以減緩疾病進展。然而，我們認為，需要一種多藥物範例來解決 DMD 的所有病理後果，主要是由於缺乏藥物而引起的發炎和纖維化。[肌肉營養不良蛋白]。

CAP-1002 is perfectly positioned to be a partner therapy for DMD as its stated mechanism of action, its immunomodulation, and reduction in fibrosis. In fact, some of the current subjects at HOPE-3 our post-gene therapy. But still qualify for CAP-1002 based on the study's inclusion and exclusion criteria. CAP-1002 has a strong safety profile and has a once-a-quarter infusion that has shown to be well tolerated. If CAP-1002 delay the disease progression, which years of data and multiple clinical trials have demonstrated, it is our hope that CAP-1002 would be a preferred treatment with gene or exon-skipping therapies.

CAP-1002 因其既定的作用機制、免疫調節和減少纖維化而完美地成為 DMD 的合作療法。事實上，HOPE-3 目前的一些受試者正在進行我們的後基因療法。但根據該研究的納入和排除標準，仍符合 CAP-1002 的資格。CAP-1002 具有很強的安全性，每季注射一次，且耐受性良好。如果 CAP-1002 能夠延緩疾病進展（多年的數據和多項臨床試驗已證明這一點），我們希望 CAP-1002 將成為基因或外顯子跳躍療法的首選治療方法。

Now I would like to take a few minutes to update you on our recent FDA interactions and regulatory goals for the program over the next several quarters. As you may recall, we met with FDA last year and aligned on the design of our current Phase 3 program with Cohort A being the primary dataset for the filing of the BLA and data from Cohort B to be used to transition to our San Diego manufacturing facility.

現在，我想花幾分鐘時間向您介紹我們最近與 FDA 的互動以及未來幾季該計劃的監管目標的最新情況。您可能還記得，我們​​去年與 FDA 會面，並就我們目前第 3 階段計劃的設計進行了協調，其中隊列 A 是提交 BLA 的主要數據集，隊列 B 的數據將用於過渡到我們的聖地亞哥製造設施。

Now that Cohort A has been fully enrolled and Cohort B is heading towards full enrollment, we have continued to discuss with FDA and the opportunity to expedite the filing of our BLA, keeping in mind that in order to successfully achieve BLA acceptance, a critical aspect is to meet all CMC requirements as outlined by FDA.

現在，隊列 A 已完全入組，隊列 B 即將完全入組，我們繼續與 FDA 討論以及加快提交 BLA 的機會，請記住，為了成功獲得 BLA 接受，一個關鍵方面是為了滿足FDA 概述的所有CMC 要求。

To that end, we have successfully established a potency assay for CAP-1002 based on the mechanism of action of the product, which is acceptable to FDA for our to-be marketed products and critical to the establishment of comparability between each of our manufacturing sites.

為此，我們根據產品的作用機製成功建立了 CAP-1002 的效力測定，該測定對於我們即將上市的產品來說是 FDA 可接受的，並且對於我們每個生產基地之間建立可比性至關重要。

As many of you know, FDA leadership has taken a great interest in helping move the field of treating DMD forward. And we continue to believe that we can work with them on a strategy to move CAP-1002 towards approval.

眾所周知，FDA 領導階層對幫助推動 DMD 治療領域的發展非常感興趣。我們仍然相信我們可以與他們合作制定一項策略，推動 CAP-1002 獲得批准。

Importantly, our San Diego manufacturing facility is now fully operational, staff and producing doses for clinical use. Currently, we can produce enough CAP-1002 in our San Diego facility to meet and exceeds NS Pharma's forecast for year one of product lines, if approved by FDA.

重要的是，我們的聖地牙哥製造工廠現已全面投入運營，配備人員並生產臨床使用的劑量。目前，如果獲得 FDA 批准，我們的聖地牙哥工廠可以生產足夠的 CAP-1002，以滿足並超過 NS Pharma 對產品線第一年的預測。

We also have plans in place to expand our San Diego facilities operations to support a larger demand as may be necessary, but further expansion or investment would be something we will look forward to do following potential BLA acceptance.

我們還制定了擴大聖地牙哥設施營運的計劃，以支持可能需要的更大需求，但在潛在的 BLA 獲得批准後，我們將期待進一步的擴張或投資。

I would like to highlight that we have expended a relatively small amount of capital to build our commercial manufacturing. This has also allowed us to strengthen our IP portfolio with additional process and method-based patent filings and know-how. We also are able to control COGS effectively to drive margins as high as possible on revenue and/or revenue shares.

我想強調的是，我們花了相對較少的資金來建立我們的商業製造。這也使我們能夠透過額外的基於流程和方法的專利申請和專有技術來加強我們的智慧財產權組合。我們也能夠有效控制銷貨成本，以盡可能提高收入和/或收入分成的利潤率。

Importantly, we can also potentially expand our CAP-1002 program to other indications while replicating our manufacturing modules. All of this taken together puts Capricor in a good position as we prepare for our potential initial commercial product in DMD. A majority of the investment into our facility operations and personnel has gone into preparations for this endeavor and I feel confident that we can deliver according to the timelines we have set forth.

重要的是，我們還可以在複製我們的製造模組的同時將我們的 CAP-1002 計劃擴展到其他適應症。所有這些加在一起使 Capricor 在我們為 DMD 潛在的初始商業產品做準備時處於有利地位。我們對設施運作和人員的大部分投資都用於為這項工作做準備，我相信我們能夠按照我們設定的時間表交付。

Now for an update on our commercial partnership with NS Pharma, who is already actively preparing for the potential launch of CAP-1002, assuming the data is positive, and we have an accepted BLA. We continue to work closely with them as we move closer to that goal.

現在介紹一下我們與 NS Pharma 的商業合作夥伴關係的最新情況，假設數據是積極的，並且我們有已接受的 BLA，NS Pharma 已經在積極準備 CAP-1002 的上市。我們將繼續與他們密切合作，並不斷接近這一目標。

As we have stated, subjects are continuing to report slowing of disease progression on CAP-1002, which is supported by the PUL data. This positive data, combined with the strong safety profile, has led to nearly four participants in open-label extension studies. Therefore, by the time of a potential BLA acceptance, we would expect to have approximately 120 patients already on CAP-1002 on an ongoing basis.

正如我們所說，受試者繼續報告 CAP-1002 疾病進展減慢，這得到了 PUL 數據的支持。這些積極的數據加上強大的安全性，吸引了近四名參與者參與開放標籤擴展研究。因此，到 BLA 可能被接受時，我們預計大約有 120 名患者已經在持續使用 CAP-1002。

These patients would likely become our first commercial patient. This potential revenue stream will be very supportive of a strong launch and will provide an initial commercial market for this product. Additionally, we are in the early stages of establishing a strong commercial team to support our partner at NS Pharma.

這些患者可能會成為我們的第一個商業患者。這種潛在的收入來源將非常支持該產品的強勁推出，並將為該產品提供最初的商業市場。此外，我們正處於建立強大商業團隊的早期階段，以支持我們的 NS Pharma 合作夥伴。

Now I'd like to briefly turn to provide an update on our exosome technology. Currently, we are pursuing two avenues of opportunity. One is our vaccine program using StealthX, our proprietary platform that is useful for engineering select proteins, either inside or on the surface of the exosome. And the other is using the same basic platform for the development of therapeutics.

現在我想簡單介紹一下我們的外泌體技術的最新情況。目前，我們正在尋求兩個機會。其中之一是我們使用 StealthX 的疫苗計劃，這是我們的專有平台，可用於工程選擇外泌體內部或表面的蛋白質。另一個是使用相同的基礎平台來開發治療方法。

One of our major achievements this year was being selected as part of the US government's Project NextGen, which is slated to detect vaccine candidates for potential use in preventing COVID-19 as well as prepare for future pandemics. The structure of the arrangement with NIAID, which is otherwise known as the National Institute of Allergy and Infectious Diseases, that Capricor will provide them with manufactured vaccine. The campaign for which is underway now. And they will conduct and fully fund a Phase 1 clinical trial. There will be three groups tested: a low dose S, a high dose S of the current strain of COVID-19, and then five valid candidates containing evidence of the nucleocapsid.

我們今年的主要成就之一是被選為美國政府 NextGen 計畫的一部分，該計畫旨在檢測可能用於預防 COVID-19 的候選疫苗，並為未來的大流行做好準備。根據與 NIAID（也稱為國家過敏和傳染病研究所）的協議結構，Capricor 將為他們提供生產的疫苗。目前該活動正在進行中。他們將進行一期臨床試驗並為其提供全額資助。將測試三組：目前 COVID-19 菌株的低劑量 S、高劑量 S，然後是包含核衣殼證據的五個有效候選者。

I am pleased to inform you that we have submitted an IND to the FDA for StealthX vaccine, which is currently under review. And we anticipate that once the IND has approved, that NIAID will initiate the clinical trial in late 2024. I will provide more specific timelines on this program as we progress through the year.

我很高興地通知您，我們已向 FDA 提交了 StealthX 疫苗的 IND，目前正在審查中。我們預計，一旦 IND 獲得批准，NIAID 將在 2024 年底啟動臨床試驗。隨著今年的進展，我將提供有關該計劃的更具體的時間表。

This will be the only multivalent candidate tested as far as we know. And we have high hopes for its success in terms of potential safety and efficacy. If NIAID finds that the vaccine meets this criteria for safety and efficacy, they may consider our program for a fully-funded Phase 2.

據我們所知，這將是唯一經過測試的多價候選藥物。我們對其在潛在安全性和有效性方面的成功寄予厚望。如果 NIAID 發現該疫苗符合安全性和有效性的標準，他們可能會考慮我們的計畫進行全額資助的第二階段。

This opportunity is very important for Capricor because it supports our exosome-based vaccine. And while we don't have intention to become a vaccine-focused company, it sets up the program nicely for partnering and other business development opportunities.

這個機會對 Capricor 來說非常重要，因為它支持我們基於外泌體的疫苗。雖然我們無意成為一家專注於疫苗的公司，但它為合作和其他業務發展機會很好地制定了該計劃。

As a reminder, the power of this technology is that it combines the speed of an mRNA vaccine with the potential efficacy of a competent protein-based vaccine. Should it work in humans as well as in preclinical animal studies, it could be a very important improvement in vaccinology.

提醒一下，這項技術的強大之處在於它結合了 mRNA 疫苗的速度和基於蛋白質的疫苗的潛在功效。如果它適用於人類以及臨床前動物研究，這可能是疫苗學的一個非常重要的進步。

Also on the exosome front, we are in discussions with several potential partners to develop the therapeutic arm of our engineered exosome technology. The strategy involves taking the same celltech platform and using it to target a specific tissue and then appropriately deliver a payload. Each early preclinical data suggests the strategy works, and we are looking forward to sharing more color on this important program as data becomes available.

同樣在外泌體方面，我們正在與幾個潛在合作夥伴進行討論，以開發我們的工程外泌體技術的治療臂。該策略涉及採用相同的細胞技術平台，並使用它來瞄準特定的組織，然後適當地傳遞有效負載。每個早期的臨床前數據都表明該策略是有效的，我們期待在數據可用時分享關於這個重要項目的更多資訊。

And finally, on the corporate side, we raised approximately $23 million late last year and an equity offering to support our balance sheet into 2025. This strategic financing was anchored by Nippon Shinyaku further cementing our strong relationship and their commitment to Capricor. As we think about moving through 2024 and into 2025, I want to remind you that our US agreement with Nippon Shinyaku comes with an additional $90 million of potential milestone payments up to the time of approval, which are triggered upon certain regulatory base achievements.

最後，在企業方面，我們在去年年底籌集了約 2,300 萬美元，並進行了股票發行，以支持我們的資產負債表持續到 2025 年。此次策略融資由 Nippon Shinyaku 提供支持，進一步鞏固了我們之間的牢固關係及其對 Capricor 的承諾。當我們考慮從2024 年邁入2025 年時，我想提醒您，我們與Nippon Shinyaku 達成的美國協議附帶了截至批准之時額外9000 萬美元的潛在里程碑付款，這些付款是在某些監管基礎成就時觸發的。

Following potential approval, there is an additional $605 million in potential milestone payments, which will be payable to Capricor based on various sales base targets being met. Furthermore, if we receive FDA approval for CAP-1002 for the treatment of DMD, we would be eligible to receive a priority review voucher or the PRV based on our previous receipt of a rare pediatric disease designation, which we retain full rights to and will look to sell to support our balance sheet.

在獲得批准後，將根據實現的各種銷售基礎目標向 Capricor 支付額外 6.05 億美元的潛在里程碑付款。此外，如果我們獲得 FDA 批准 CAP-1002 用於治療 DMD，我們將有資格獲得優先審評券或基於我們之前收到的罕見兒科疾病指定的 PRV，我們保留對此的全部權利並將尋求出售以支持我們的資產負債表。

Lastly, we are in active discussions with several parties related to the European rights of CAP-1002 for DMD. Our main goal is to continue to support our balance sheet, leveraging non-dilutive partnerships to fuel CAP-1002 towards potential approval and support the exosome program.

最後，我們正在與多個有關 CAP-1002 DMD 歐洲權利的各方進行積極討論。我們的主要目標是繼續支持我們的資產負債表，利用非稀釋性合作夥伴關係推動 CAP-1002 獲得潛在批准並支持外泌體計劃。

Overall, I want to thank you for your support. We continue to diligently manage our resources, focus our efforts on bringing CAP-1002 towards potential commercialization in the most expeditious way possible. We are very much looking forward to the next several months as we will be continuing our interactions with FDA announcing our three-year open-label extension data, completing enrollment for Cohort B, and presenting at various medical scientific and investor-related conferences.

總的來說，我要感謝您的支持。我們將繼續努力管理我們的資源，集中精力以盡可能最快的方式將 CAP-1002 實現潛在的商業化。我們非常期待接下來的幾個月，因為我們將繼續與 FDA 互動，宣布我們的三年開放標籤擴展數據，完成 B 組的註冊，並在各種醫學科學和投資者相關會議上發表演講。

I will now turn the call over to AJ to run through our financials. AJ?

我現在將把電話轉給 AJ 來了解我們的財務狀況。阿傑？

Thank you, Linda. This afternoon's press release provided a summary of our fourth-quarter and full-year 2023 financials on a GAAP basis. And you may also refer to our annual report on Form 10-K, which we expect to become available shortly, will be accessible on the SEC website, as well as our website.

謝謝你，琳達。今天下午的新聞稿總結了我們按 GAAP 計算的第四季度和 2023 年全年財務狀況。您也可以參考我們的 10-K 表格年度報告，我們預計很快就會提供該報告，您可以在 SEC 網站以及我們的網站上存取該報告。

Turning to the financials, let me start with our cash position. We ended December 31, 2023, with cash, cash equivalents and marketable securities of approximately $39.5 million. This excludes the $10 million milestone payment we received in January of '24 from Nippon Shinyaku under our distribution and commercialization agreement.

談到財務狀況，讓我從我們的現金狀況開始。截至 2023 年 12 月 31 日，我們的現金、現金等價物及有價證券約為 3,950 萬美元。這不包括我們在 2024 年 1 月根據我們的分銷和商業化協議從 Nippon Shinyaku 收到的 1000 萬美元里程碑付款。

Based on our recent operating results and projections, we expect our cash runway to extend into the first quarter of 2025. But this expectation excludes any additional potential milestone payments under our exclusive commercialization and distribution agreements with Nippon Shinyaku.

根據我們最近的營運業績和預測，我們預計我們的現金跑道將延續到 2025 年第一季。但這一預期不包括我們與 Nippon Shinyaku 的獨家商業化和分銷協議下任何額外的潛在里程碑付款。

In the fourth quarter of '23, our revenue was approximately $12.1 million compared to approximately $1 million for the fourth quarter of 2022, which was primarily attributable to the ratable recognition of the $40 million, which includes the upfront and milestone payment we have received in accordance with our US commercialization and distribution agreement with Nippon Shinyaku.

2023 年第四季度，我們的收入約為1,210 萬美元，而2022 年第四季約為100 萬美元，這主要歸因於4,000 萬美元的應納稅確認，其中包括我們在2022 年收到的預付款和里程碑付款。根據我們與 Nippon Shinyaku 的美國商業化和分銷協議。

Excluding stock-based compensation, our research and development expenses were approximately $9.4 million for the fourth quarter of 2023 compared to approximately $6 million for the fourth quarter of 2022. The increase in expenses of $3.4 million was primarily due to increased clinical and manufacturing costs associated with our Phase 3 HOPE-3 trial.

不含股票薪酬，我們 2023 年第四季的研發費用約為 940 萬美元，而 2022 年第四季的研發費用約為 600 萬美元。費用增加 340 萬美元主要是由於與我們的 3 期 HOPE-3 試驗相關的臨床和製造成本增加。

Excluding stock-based compensation, our general and administrative expenses were approximately $1.9 million for both the fourth quarter of '23 and 2022. Net loss for the fourth quarter of '23 was approximately $800,000 compared to a net loss of $7.7 million for the fourth quarter of 2022. And net loss for the full-year '23 was approximately $22.3 million compared to a net loss of approximately $29 million for the full-year 2022.

不包括股票薪酬，我們 2023 年第四季和 2022 年第四季的一般和管理費用約為 190 萬美元。23 年第四季的淨虧損約為 80 萬美元，而 2022 年第四季的淨虧損為 770 萬美元。23 年全年的淨虧損約為 2,230 萬美元，而 2022 年全年的淨虧損約為 2,900 萬美元。

And with that, we will now open the line up for questions. Operator, go ahead.

至此，我們現在開始提問。接線員，繼續吧。

Thank you. Ladies and gentlemen, we will now conduct the question-and-answer session. (Operator Instructions)

謝謝。女士們、先生們，我們現在進行問答環節。（操作員說明）

Joe Pantginis, H.C. Wainwright.

喬潘吉尼斯，H.C.溫賴特。

Hi, Linda and AJ. Thanks for taking the questions. Good afternoon. First off, so I wanted to talk about your regulatory discussions. So last year, you had some pretty clear frameworks that you shared with us again today about the need for Cohort A and giving some manufacturing comparability from Cohort B out of the San Diego facility. And you keep talking about ways to potentially expedite.

嗨，琳達和 AJ。感謝您提出問題。午安.首先，我想談談你們的監管討論。去年，你們有一些非常清晰的框架，今天再次與我們分享了關於隊列 A 的需求，並提供了聖地亞哥工廠的隊列 B 的一些製造可比性。您一直在談論可能加快速度的方法。

So I wanted to explore that a little bit. So first question is when you look at this, you have the RMAT status, is one of the potentials here a rolling BLA? Because you'll be able to start submitting data quicker as part of the filing and other options you might be considering?

所以我想對此進行一些探索。所以第一個問題是，當你看到這個時，你已經擁有 RMAT 狀態，這裡的潛力之一是滾動 BLA 嗎？因為您將能夠開始更快地提交數據，作為歸檔和您可能考慮的其他選項的一部分？

Joe, always a pleasure. Thanks for the question. So I'm going to start answering by saying I've been working on this therapeutic for 19 years. And where we are right now is just so staggeringly exciting to me that it's sometimes hard to express.

喬，總是很開心。謝謝你的提問。因此，我首先要回答說，我已經研究這種療法 19 年了。我們現在所處的位置讓我非常興奮，有時很難表達。

But what has been the best part of the last few months has been the careful attention that FDA has been paying to Capricor and to CAP-1002. They recognize the positive safety and efficacy data. They've looked at the open label extension data, the HOPE-2 data, and they're working very closely with us.

但過去幾個月最棒的部分是 FDA 對 Capricor 和 CAP-1002 的密切關注。他們認可積極的安全性和有效性數據。他們研究了開放標籤擴展數據、HOPE-2 數據，並且正在與我們密切合作。

So yes, all options are on the table right now in terms of how to get this across the line as fast as possible. As I mentioned, leadership within Sabre is aware of our program and really working very closely with us. We have RMAT. We have our rare pediatric disease designation, orphan disease designation. So we have a lot of the bells and whistles that will carry our program as quickly as possible into the arms of DMD patients.

所以，是的，關於如何盡快實現這一目標，所有選項都已擺在桌面上。正如我所提到的，Sabre 內部的領導層了解我們的計劃，並且確實與我們密切合作。我們有 RMAT。我們有罕見兒科疾病指定，孤兒疾病指定。因此，我們有許多附加功能，可以盡快將我們的計畫帶入 DMD 患者的懷抱。

Got it. And then just curiosity, for Cohort B, are you directly needing to show manufacturing comparability? Or do these patients need to be follow up for a certain timeframe?

知道了。然後只是好奇，對於 B 組，您是否直接需要展示製造可比性？或者這些患者是否需要在一定時間內進行追蹤？

So we felt since events suspended the program by building in a full one-to-one randomized clinical trial with safety and efficacy built-in. So basically, as a mirror image of Cohort A. We're working with FDA on what they're going to actually ask us for.

因此，自從事件暫停該計劃以來，我們認為透過建立一個具有安全性和有效性的完整的一對一隨機臨床試驗來進行。基本上，作為 A 組的鏡像。我們正在與 FDA 合作，了解他們實際要求我們提供的內容。

What we know and what we can guarantee on is that they are willing to accept the license application on Cohort A. What we're going to need from Cohort B is still what we're working with them on. But it really is almost something we've not only been prepared for, but something that comes along very naturally.

我們所知道並且可以保證的是，他們願意接受 Cohort A 的許可申請。我們需要從 Cohort B 獲得的仍然是我們正在與他們合作的內容。但這確實是我們不僅已經準備好的事情，而且是非常自然的事情。

So the trial, Cohort B -- let me reemphasize -- will be fully enrolled by second quarter of this year. And then we're going to be able to potentially position that as a post-marketing commitment for the program.

因此，讓我再次強調的是，B 組試驗將在今年第二季全部入組。然後我們將能夠將其定位為該計劃的上市後承諾。

Got it. And then my last question if you don't mind and thanks for bearing with me --

知道了。然後是我的最後一個問題，如果你不介意的話，謝謝你對我的耐心--

Absolutely.

絕對地。

-- we've been talking about this for several years because we've been excited about the data. So I guess how would you portray the role of the cardiovascular data you've been accumulating through HOPE-2 and beyond the evolution of your regulatory discussions? And how much that may or may not be coming into play to date?

——我們已經討論這個問題好幾年了，因為我們對這些數據感到興奮。所以我想你會如何描述你透過 HOPE-2 以及監管討論的演變所累積的心血管數據的作用？到目前為止，這可能會或可能不會發揮多大作用？

Yes. So obviously, one of the most important cornerstones of our regulatory strategy, but also in the eagerness of the community to get approval for CAP-1002. To remind you and I stated this, we saw a 4% improvement in ejection fraction, the gold standard of cardiac function in HOPE-2.

是的。顯然，這是我們監管策略最重要的基石之一，也是社區渴望獲得 CAP-1002 批准的原因。為了提醒您，我已經聲明了這一點，我們發現射血分數（HOPE-2 中心臟功能的黃金標準）提高了 4%。

In HOPE-2 open label extension, we didn't start measuring cardiac function until two years in. We'll have three-year data in the second quarter of this year. So stay tuned for that on cardiac function. But we're pretty convinced that it's going to be one of the major parts of what we're going to look for on our label. And the primary -- secondary endpoints that has been built into hopefully both Cohort A and Cohort B.

在 HOPE-2 開放標籤擴展中，我們直到兩年後才開始測量心臟功能。我們將在今年第二季獲得三年數據。因此，請繼續關注心臟功能。但我們非常確信，它將成為我們在品牌上尋找的主要部分之一。希望 A 組和 B 組都內建了主要和次要終點。

Got it. Thanks for the added details, Linda.

知道了。感謝您添加的詳細信息，琳達。

Absolutely, Joe. Always a pleasure.

絕對可以，喬。總是一種樂趣。

Kristen Kluska, Cantor Fitzgerald.

克里斯汀·克魯斯卡，坎托·費茲傑拉。

Hi, everyone. Thank you so much for taking my question.

大家好。非常感謝您回答我的問題。

Hi, Kristen. How are you?

嗨，克里斯汀。你好嗎？

I'm well. How are you doing?

我很好。你好嗎？

Good.

好的。

So speaking about the potential for combinations, I completely understand the need for that. But can you comment on what your expectations would be in terms of payer support?

因此，談到組合的潛力，我完全理解這樣做的必要性。但您能評論一下您對付款人支持的期望嗎？

And then either gene therapy typically requires a lot more upfront timing with different kind of big manufacturing, et cetera. Would it be your expectation that CAP-1002 would be the first therapy essentially given in this case? And would that be an advantage in case there is some payer pushback?

然後，任何一種基因療法通常都需要更多的前期時間與不同類型的大型製造，等等。您是否期望 CAP-1002 成為該病例中的第一種治療方法？如果付款人出現一些阻力，這會是個優勢嗎？

So we've had really positive feedback from payers, not just at Capricor, but also NS Pharma has done significant work in preparing for market launch. And the way that we're understanding it is that there's going to be therapy that would be necessary for sort of management of the dystrophinopathy. So the exon skippers and the gene therapies.

因此，我們從付款人那裡得到了非常積極的回饋，不僅是 Capricor，而且 NS Pharma 在準備上市方面也做了重要的工作。我們所理解的方式是，對於控制肌肉營養不良症，將有必要進行治療。所以外顯子船長和基因療法。

And because there's not an approved gene therapy, theoretically, yes, we don't really know how they're going to approach choosing those or both or whatever. But what we do know is that there needs to be adjunctive therapy that would manage -- and I've talked about this a lot, the immunomodulation or the inflammatory response caused by the constant breakdown of protein in the body due to the mutation, as well as manage the fibrosis and help to support perhaps the framework laid down by a gene therapy or an exon skipper, which would be a healthier protein.

因為還沒有批准的基因療法，從理論上講，是的，我們真的不知道他們將如何選擇這些或兩者或其他什麼。但我們所知道的是，需要有輔助治療來控制——我已經多次談論過這一點，由於突變而導致體內蛋白質不斷分解而引起的免疫調節或發炎反應，如以及控制纖維化，並有幫助於支持基因療法或外顯子跳躍者所奠定的框架，這將是一種更健康的蛋白質。

So we are very confident the payers that find it beneficial to cover both the dystrophinopathy management strategy, as well as CAP-1002 for the management of the inflammation and fibrosis.

因此，我們非常有信心付款人發現涵蓋肌肉營養不良症管理策略以及用於發炎和纖維化管理的 CAP-1002 是有益的。

Now in terms of the order in which the therapeutics are given, that we would sort of have to talk to some of the KOLs. We're already starting to do some of that market research obviously. Because we're going for our initial label for some of the later-stage patients, at least based on the HOPE-2 data, we reserve the right to ask FDA to go as young as possible.

現在就治療的順序而言，我們必須與一些 KOL 交談。顯然，我們已經開始做一些市場研究。因為我們要為一些晚期患者進行初始標籤，至少基於 HOPE-2 數據，所以我們保留要求 FDA 盡可能年輕的權利。

Colloquially, we always say time is muscle. And the data has shown that once people get on CAP-1002 to disease progression is significantly attenuated almost immediately. So in terms of the timing of how that's done, that remains to be seen, but we're very confident that will be part of the overall treatment paradigm addition.

通俗地說，我們總是說時間就是肌肉。數據顯示，一旦人們服用 CAP-1002，疾病進展幾乎立即顯著減弱。因此，就具體實施時間而言，還有待觀察，但我們非常有信心這將成為整體治療範式的一部分。

Thank you for that. And then we have seen quite bullish the four- to five-year old wrap the therapy which I think underscores the unmet need here. So I wanted to ask what your thoughts are about the cadence you might see in terms of patients wanting therapy, especially because you are going after that non-ambulatory population? And then what capacity would you be able to help with given this is half of the patients with DMD? Thanks again.

謝謝你。然後我們看到四到五歲的孩子對治療非常樂觀，我認為這強調了這裡未被滿足的需求。所以我想問一下，您對需要治療的患者可能會看到的節奏有何看法，尤其是因為您正在尋找那些無法流動的人群？那麼，考慮到一半的 DMD 患者，您能提供什麼幫助？再次感謝。

Yes. So thank you. So we plan on swinging the door wide open in terms of what we ask FDA for the benefit here. Unlike many therapeutics, we're going to come into BLA with four or five years' worth of safety data tracking children from, you know, theoretically age 10 and beyond. So we're going to open the door and see what the opportunity is.

是的。所以謝謝。因此，我們計劃向 F​​DA 請求利益敞開大門。與許多治療方法不同，我們將在 BLA 中提供四到五年的安全數據，追蹤理論上 10 歲及以上兒童的安全數據。所以我們要打開大門，看看有什麼機會。

Obviously, if I had a child with DMD, I want to get my child on CAP-1002 as young as possible. There's really no downside and potentially could even have impact on, who knows, things like steroid dosing and things that may have on ultimate impacts of side effects.

顯然，如果我的孩子患有 DMD，我想讓我的孩子盡可能年輕地接受 CAP-1002。實際上沒有任何負面影響，誰知道呢，甚至可能會對類固醇劑量以及可能對副作用的最終影響產生影響的事情產生影響。

In terms of what we're looking for, I think that was your second question, we're looking for utilization of CAP-1002 as early as it becomes available to the community. We're right there with it.

就我們正在尋找的內容而言，我認為這是您的第二個問題，我們正在尋找 CAP-1002 儘早向社群提供的利用。我們就在那裡。

Thank you.

謝謝。

Thank you. Thank you for your time.

謝謝。感謝您的時間。

Aydan Huseynov, Ladenburg.

艾丹侯賽諾夫，拉登堡。

Good afternoon, everyone. Good afternoon, Linda and AJ. Congratulations with the progress this quarter and staying on track with the guidance, the top line in fourth quarter '24.

大家下午好。下午好，琳達和 AJ。恭喜本季取得的進展，並與 24 年第四季的指導方針保持一致。

I have a couple of questions. First, I wanted to ask you about on the potential expansion of indication. I think you mentioned something in your remarks and the most natural expansion -- I think we talked about it is was the Becker dystrophy that we see a tremendous increase in value in other Becker companies.

我有一些問題。首先，我想問您有關適應症的潛在擴展的問題。我認為您在演講中提到了一些最自然的擴張——我認為我們討論的是貝克爾營養不良，我們看到其他貝克爾公司的價值大幅增加。

And given your cardiomyopathy focus and focus on improving skeletal cardiac muscle function, could you expand a little bit on any potential efforts that you are making regarding that expansion?

考慮到您的心肌病變重點和改善骨骼心肌功能的重點，您能否稍微擴展一下您在擴展方面所做的任何潛在努力？

Yes. Thanks, Aydan. And always, it's good to talk with you. So yes, we've been talking about this for a while. Obviously, there's tremendous opportunities for expansion. As I mentioned, the manufacturing paradigm is that we have a potency assay that's been accepted by FDA. We understand the mechanism of action and how to make the cells. We certainly are poised to expand our efforts.

是的。謝謝，艾丹。總是很高興與您交談。是的，我們已經討論這個問題有一段時間了。顯然，這裡存在著巨大的擴張機會。正如我所提到的，生產範例是我們擁有 FDA 接受的效力測定。我們了解作用機制以及如何製造細胞。我們當然準備好擴大我們的努力。

Becker is certainly one of the great interest, especially since the primary manifestation later in life is the cardiomyopathy, which as we've talked about it, is one of the main targets that CAP-1002 seems to ameliorate.

Becker 無疑是最受關注的人之一，特別是因為晚年的主要表現是心肌病，正如我們所討論的，心肌病變是 CAP-1002 似乎可以改善的主要目標之一。

Having said that, we are right now focusing almost all of our efforts on getting CAP-1002 across the line for DMD. We're working on the BLA. We're working on a launch strategy, commercialization strategy. And so indication expansion will come behind that. And I will provide more color to you and to the market as those opportunities become available.

話雖如此，我們現在幾乎所有的努力都集中在讓 CAP-1002 跨越 DMD 的界限。我們正在研究 BLA。我們正在製定啟動策略、商業化策略。因此，適應症擴張將隨之而來。當這些機會出現時，我將為您和市場提供更多的色彩。

Okay. Understood. Another question I have is regarding the HOPE-2 open extension -- open-label extension trial results in the second quarter. So what are your expectations regarding this?

好的。明白了。我的另一個問題是關於第二季度的 HOPE-2 開放擴展——開放標籤擴展試驗結果。那麼您對此有何期待？

Well, we have three-year data coming out in the second quarter of this year as I said. The two-year data was extraordinary. We presented that most recently at PPMD, and I will be sharing some more data at the Muscular Dystrophy Association Meetings next week in Orlando.

嗯，正如我所說，我們將在今年第二季公佈三年數據。兩年的數據非比尋常。我們最近在 PPMD​​ 上介紹了這一點，我將在下週於奧蘭多舉行的肌肉萎縮症協會會議上分享更多數據。

We have every expectation based on the anecdotes that we hear from the subjects and their families, that this trend of stabilization of disease and attenuation of disease progression will continue. We're really looking forward to seeing the MRI data because that will be two years of sequential cardiac function data. And we have every reason to believe that we should be able to stabilize heart function as well.

根據我們從受試者及其家人那裡聽到的軼事，我們完全期望這種疾病穩定和疾病進展減弱的趨勢將繼續下去。我們真的很期待看到 MRI 數據，因為這將是兩年的連續心臟功能數據。我們有充分的理由相信我們也應該能夠穩定心臟功能。

So we also have so many families that call us, that tell us that their sons are able to do what they weren't able to do before or they can't wait for their next infusion. Can we please get in sooner? Because we feel a wearing off after three months. So I'm very much looking forward to seeing that data, and then ultimately sharing it with all of you.

因此，我們也有很多家庭打電話給我們，告訴我們他們的兒子能夠做到他們以前無法做到的事情，或者他們迫不及待地等待下一次輸液。我們可以早點進去嗎？因為三個月後我們會感到疲倦。所以我非常期待看到這些數據，然後最終與大家分享。

Understood. Thank you for that. And the last question is regarding the European discussions, discussions with potential European partners. So in your discussions with them -- first of all, if you could give us a little bit of insight, are these like established players? Are these new players?

明白了。謝謝你。最後一個問題是關於歐洲的討論，與潛在的歐洲夥伴的討論。因此，在您與他們的討論中，首先，如果您能給我們一點見解，這些人是否是老牌玩家？這些是新玩家嗎？

And what are the typical questions that they have there? What is the -- which part of CAP-1002 data they are most interested in? If you could expand a little bit on this.

他們在那裡提出的典型問題是什麼？他們對 CAP-1002 資料的哪一部分最感興趣？如果你能對此進行擴展一點。

So you know, I think the European community is as interested in getting therapies across the line for DMD as is the US authorities. They have a little bit different strategy in Europe. As you probably are aware, there is a little bit different way of going about it.

所以你知道，我認為歐洲社會和美國當局一樣有興趣獲得 DMD 的治療方法。他們在歐洲的戰略略有不同。正如您可能知道的，有一些不同的方法來解決這個問題。

The parties that we're talking to are some new and some established. I think we've been on the radar for several larger companies for a long time now. And with the data coming around the corner, they were paying more attention.

我們正在交談的政黨有的是新政黨，有的是老牌政黨。我認為我們長期以來一直受到幾家大公司的關注。隨著數據即將到來，他們更加關注。

Perhaps one of the best things is that our San Diego manufacturing facility can be EMA qualified, so we can make doses here and ship them to Europe, which is an added benefit. And in terms of the questions that we get, I think would be the typical ones, which is regulatory strategy, getting capped to across the line, what clinical trial work will be needed. From our from our standpoint, it's probably going to be fairly straightforward and we definitely look forward to making CAP-1002 available worldwide.

也許最好的事情之一是我們的聖地牙哥製造工廠可以通過 EMA 認證，因此我們可以在這裡生產劑量並將其運送到歐洲，這是一個額外的優點。就我們收到的問題而言，我認為是典型的問題，即監管策略、跨界限制、需要哪些臨床試驗工作。從我們的角度來看，這可能會相當簡單，我們絕對期待在全球範圍內提供 CAP-1002。

Okay. Thank you so much and congratulations with the progress this quarter.

好的。非常感謝並祝賀本季的進展。

Thanks, Aydan. Take care.

謝謝，艾丹。小心。

(Operator Instructions)

（操作員說明）

There are no further questions at this time. I'm turning it over to the management for closing remarks.

目前沒有其他問題。我將把它交給管理階層做總結發言。

Before we conclude today's call, I wanted to extend my sincere gratitude to the patients, their families, the clinicians, and our partners at Nippon Shinyaku and NS Pharma, and of course, at FDA who continue to work with us to bring CAP-1002 closer to potential approval.

在我們結束今天的電話會議之前，我想向患者、他們的家人、臨床醫生以及我們在Nippon Shinyaku 和NS Pharma 的合作夥伴致以誠摯的謝意，當然還有FDA 的合作夥伴，他們繼續與我們合作推出CAP-1002更接近潛在的批准。

Again, thank you to everyone who joined us this afternoon, and I look forward to seeing you at meetings in the future.

再次感謝今天下午加入我們的所有人，我期待在將來的會議上見到你們。

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

女士們、先生們，今天的會議到此結束。感謝您的加入。您現在可以斷開連線。