BioCardia Inc (BCDA) 2023 Q1 法說會逐字稿

Good day ladies and gentlemen. Thank you for standing by. Good afternoon and welcome to the BioCardia 2023 first-quarter conference call. (Operator Instructions)

女士們先生們，美好的一天。謝謝你的支持。下午好，歡迎參加 BioCardia 2023 年第一季度電話會議。 （操作員說明）

Participants of this call are advised that the audio of this conference call is being broadcast live over the Internet and is also being recorded for playback purposes. A webcast replay of the call will be available approximately one hour after the end of the call through August 10, 2023.

本次電話會議的參與者請注意，本次電話會議的音頻正在通過互聯網進行現場直播，並且還被錄製用於回放。電話會議的網絡直播重播將在電話會議結束後大約一小時內進行，直至 2023 年 8 月 10 日為止。

I would now like to turn the call over to Miranda Peto of BioCardia, Investor Relations. Please go ahead, Miranda.

我現在想將電話轉給 BioCardia 投資者關係部門的米蘭達·佩托 (Miranda Peto)。請繼續，米蘭達。

Good afternoon and thank you for participating in today's conference call. Joining me for BioCardia's leadership team are Peter Altman, PhD, President and Chief Executive Officer; and David McClung, the company's Chief Financial Officer.

下午好，感謝您參加今天的電話會議。與我一起加入 BioCardia 領導團隊的是 Peter Altman 博士、總裁兼首席執行官；以及該公司首席財務官戴維·麥克朗 (David McClung)。

During this call, management will be making forward-looking statements, including statements that address BioCardia's expectations for future performance and operational results, reference to management's intentions, belief, projections, outlook, analysis and current expectations. Such factors include, among others, the inherent uncertainties associated with developing new products, technologies and obtaining regulatory approvals.

在本次電話會議中，管理層將做出前瞻性聲明，包括涉及 BioCardia 對未來業績和運營結果的預期的聲明，參考管理層的意圖、信念、預測、前景、分析和當前預期。這些因素包括與開發新產品、技術和獲得監管部門批准相關的固有不確定性等。

Forward-looking statements involve risks and other factors that may cause actual results to differ materially from these statements. For more information about these risks, please refer to the risk factors and cautionary statements described in BioCardia's reports on Form 10-K filed on March 29, 2023.

前瞻性陳述涉及風險和其他因素，可能導致實際結果與這些陳述存在重大差異。有關這些風險的更多信息，請參閱 BioCardia 於 2023 年 3 月 29 日提交的 10-K 表格報告中描述的風險因素和警示聲明。

The content of this call contains time-sensitive information that is accurate only as of today, May 10, 2023. Except as required by law, the company disclaims any obligation to publicly update or revise any information to reflect events or circumstances that occur after this call.

本次電話會議的內容包含時效性信息，僅截至今天（2023 年 5 月 10 日）準確。除非法律要求，否則公司不承擔公開更新或修改任何信息以反映此後發生的事件或情況的義務。稱呼。

It is now my pleasure to turn the call over to Dr. Peter Altman, PhD, BioCardia's President and CEO. Peter, please go ahead.

現在我很高興將電話轉給 BioCardia 總裁兼首席執行官 Peter Altman 博士。彼得，請繼續。

Thank you, Miranda, and good afternoon to everybody on the call. It has only been six weeks since our last call at the end of March, and BioCardia is steady as she goes. We have some near-term catalysts that we can detail progress towards as well as the broader opportunities for success ahead.

謝謝你，米蘭達，祝所有與會的人下午好。距離我們三月底的最後一次通話才過去六週，BioCardia 的發展一直很穩定。我們有一些近期的催化劑，我們可以詳細說明這些進展以及未來更廣泛的成功機會。

BioCardia's current efforts are focused on advancing its autologous and its allogeneic cell therapy platforms to treat significant unmet cardiovascular and pulmonary diseases, specifically ischemic heart failure, chronic myocardial ischemia, and acute respiratory distress syndrome. All of our cell-based therapies involve local delivery of the therapeutic to the heart or lungs where we intend them to act locally.

BioCardia 目前的工作重點是推進其自體和同種異體細胞治療平台，以治療重大的未滿足的心血管和肺部疾病，特別是缺血性心力衰竭、慢性心肌缺血和急性呼吸窘迫綜合徵。我們所有基於細胞的療法都涉及將治療藥物局部遞送至心臟或肺部，我們希望它們在局部發揮作用。

Heart failure is an enormous unmet need that affects more than 26 million people worldwide. The latest blockbuster drugs in ischemic heart failure, a reduced ejection fraction, provide great benefits to patients but don't appear to have much of an impact on mortality.

心力衰竭是一個巨大的未滿足需求，影響著全世界超過 2600 萬人。治療缺血性心力衰竭的最新重磅藥物（降低射血分數）為患者帶來了巨大的好處，但似乎對死亡率沒有太大影響。

Patients in the published results of the pivotal trials for these new drugs have a cardiac mortality of roughly 7% and an all-cause mortality of 10% per year regardless of whether they were treated or control patients. This makes clear that heart failure is still a problem in great need of new therapeutic solutions.

在這些新藥的關鍵試驗中公佈的結果中，患者每年的心臟死亡率約為 7%，全因死亡率為 10%，無論他們是接受治療的患者還是對照患者。這清楚地表明，心力衰竭仍然是一個非常需要新的治療解決方案的問題。

Our autologous mononuclear cell therapy platform, which we call CardiAMP Cell Therapy, is being advanced in two cardiac clinical indications. In preclinical studies, cardiac mononuclear cell therapy has been shown to release proteins locally within the tissues to facilitate cardiac recovery after heart damage with improvements in heart perfusion and contractile function.

我們的自體單核細胞治療平台（我們稱之為 CardiAMP 細胞療法）正在兩種心臟臨床適應症中取得進展。在臨床前研究中，心臟單核細胞療法已被證明可以在組織內局部釋放蛋白質，以促進心臟損傷後的心臟恢復，同時改善心臟灌注和收縮功能。

All known previous clinical studies, similar to the approach we are taking in our two lead CardiAMP Cell Therapy programs, have shown patient benefits on average. In some of these studies, including our own, the benefits have been remarkable.

所有已知的先前臨床研究（與我們在兩個領先的 CardiAMP 細胞治療項目中採用的方法類似）均已顯示出患者的平均獲益。在其中一些研究中，包括我們自己的研究，好處是顯著的。

The FDA has supported this promise by granting breakthrough device designation to CardiAMP Cell Therapy in the indication of ischemic heart failure, a reduced ejection fraction. Advancing this and our other three therapeutic candidates is what we are all about.

FDA 通過授予 CardiAMP 細胞療法突破性設備稱號來支持這一承諾，用於治療缺血性心力衰竭（射血分數降低）。推進這一藥物和我們的其他三種治療候選藥物是我們的全部目標。

Our efforts to complete the CardiAMP autologous cell therapy pivotal clinical trials for the indications of heart failure, or BCDA-01, and chronic myocardial ischemia, or BCDA-02, are furthest along clinically. The CardiAMP Cell Therapy Heart Failure trial, or BCD-01, is a Phase III, 260-patient, randomized, controlled clinical study intended to provide the primary data to support safety and efficacy in pursuit of marketed clearance.

我們為完成針對心力衰竭（BCDA-01）和慢性心肌缺血（BCDA-02）適應症的 CardiAMP 自體細胞療法關鍵臨床試驗所做的努力在臨床上取得了最大進展。 CardiAMP 細胞治療心力衰竭試驗（BCD-01）是一項 III 期、260 名患者的隨機對照臨床研究，旨在提供主要數據來支持尋求上市許可的安全性和有效性。

Clinical investigators at 20 active partner sites across the United States and Canada have enrolled 120 patients to date, with 10 additional control patients having crossed over to receive therapy. We feel there is clearly increased momentum here, potentially driven by the clinical data presented at the American College of Cardiology in March, showing 100% survival and patient benefits across many endpoints at two years, including a 35% increase in the heart left ventricular ejection fraction.

迄今為止，美國和加拿大 20 個活躍合作夥伴中心的臨床研究人員已招募了 120 名患者，另外 10 名對照患者已交叉接受治療。我們認為這裡的勢頭明顯增強，這可能是由 3 月份美國心髒病學會公佈的臨床數據推動的，該數據顯示兩年內許多終點的生存率和患者獲益為 100%，包括心臟左心室射血增加 35%分數。

As many know, we have been working on implementing an adaptive statistical analysis plan to the trial, with distinguished consultants, including former FDA leaders and a respected statistical consulting group. In our last March 29 call, we were headed into a meeting scheduled to discuss the FDA's comments on March 31. That meeting went well. The discussion of the adaptive statistical analysis plan, as provided, was well-received by the agency's statisticians.

正如許多人所知，我們一直在與傑出的顧問合作，為試驗實施適應性統計分析計劃，其中包括前 FDA 領導人和一個受人尊敬的統計諮詢小組。在我們 3 月 29 日的最後一次電話會議中，我們計劃參加一次會議，討論 FDA 3 月 31 日的評論。那次會議進展順利。所提供的適應性統計分析計劃的討論受到了該機構統計人員的好評。

The FDA's primary concern was whether we would have enough safety data to support approval in an indication as large as ischemic heart failure, with reduced ejection fraction, if the heart -- if the trial was stopped early for efficacy. The agency's primary concern with safety was with respect to the safety of the delivery of the cells.

FDA 主要擔心的是，如果為了療效而提前停止試驗，我們是否會有足夠的安全數據來支持批准諸如射血分數降低的缺血性心力衰竭這樣的適應症。該機構對安全的主要關注是細胞運輸的安全性。

We shared with the FDA that we feel we do have sufficient data already, with 353 interventions with our delivery system in the clinical indication of ischemic heart failure of reduced ejection fraction to date, and 129 patients treated so far, with the cells being advanced in the CardiAMP trial. The FDA was unaware of this more expensive data set, and we agreed to detail it for them. We also worked with them on creative ideas to further enhance the safety experience ahead.

我們與 FDA 分享，我們認為我們確實已經擁有足夠的數據，迄今為止，我們的輸送系統在射血分數降低的缺血性心力衰竭的臨床適應症中進行了 353 次干預，迄今為止已治療 129 名患者，細胞在CardiAMP 試驗。 FDA 不知道這個更昂貴的數據集，我們同意為他們提供詳細信息。我們還與他們合作提出創意，以進一步增強未來的安全體驗。

After summarizing minutes from our perspective and acceptance of the FDA minutes provided, we submitted a revised supplement for the adaptive statistical analysis plan, incorporating all of the comments from the agency on April 26. We now anticipate a response from the agency on May 26.

在從我們的角度總結會議記錄並接受 FDA 提供的會議記錄後，我們提交了適應性統計分析計劃的修訂補充，其中納入了該機構 4 月 26 日提出的所有意見。我們現在預計該機構將於 5 月 26 日做出答复。

The next pre-specified formal Data Safety Monitoring Board review is anticipated the end of June 2023. We still believe it is likely we will be able to have the adaptive statistical analysis plan in place for the meeting. The specific details of any potential adaptive statistical analysis plan, in combination with any modifications to the Data Safety Monitoring Board charter, will dictate what happens at this next and subsequent Data Safety Monitoring Board reviews.

下一次預先指定的正式數據安全監測委員會審查預計將於 2023 年 6 月結束。我們仍然相信，我們將能夠為會議制定自適應統計分析計劃。任何潛在的自適應統計分析計劃的具體細節，以及對數據安全監測委員會章程的任何修改，將決定下一次和後續數據安全監測委員會審查時會發生什麼。

As the CardiAMP Cell Therapy Heart Failure trial was over 90% powered for success, with a range of 86 to 126 patients, there is potential that the trial could meet its primary efficacy endpoint on the patients that have been enrolled to date. Although the next data review event has potential to be a great success if the trial is stopped early for efficacy, the review will also be a success should the trial continue as planned.

由於 CardiAMP 細胞治療心力衰竭試驗的成功率超過 90%，患者範圍為 86 至 126 名，因此該試驗有可能在迄今為止已入組的患者中達到其主要療效終點。儘管如果為了療效而提前停止試驗，下一次數據審查活動有可能取得巨大成功，但如果試驗按計劃繼續進行，審查也將取得成功。

Our second therapeutic program is with the same autologous cell therapy for the treatment of chronic myocardial ischemia with refractory angina or BCDA-02. The CardiAMP Chronic Myocardial Ischemia trial is a Phase III, multi-center, randomized, double-blinded, controlled study of up to 343 patients at up to 40 clinical sites. A sufficient number of patients to complete the open-label roll-in cohort have already been consented. It is anticipated this trial will report out the open-label roll-in cohort results in 2023.

我們的第二個治療方案是使用相同的自體細胞療法治療慢性心肌缺血伴難治性心絞痛或BCDA-02。 CardiAMP 慢性心肌缺血試驗是一項 III 期、多中心、隨機、雙盲、對照研究，涉及多達 40 個臨床中心的多達 343 名患者。已經有足夠數量的患者同意完成開放標籤轉入隊列。預計該試驗將於 2023 年報告開放標籤轉入隊列結果。

As we have shared previously, in July we had our second consultation with Japan's Pharmaceutical and Medical Device Agency regarding registration of CardiAMP Cell Therapy for ischemic heart failure. BioCardia still expects to complete a formal submission towards Japanese approval in the second quarter of 2023.

正如我們之前所分享的，7 月份，我們就 CardiAMP 細胞療法治療缺血性心力衰竭的註冊事宜與日本藥品醫療器械管理局進行了第二次諮詢。 BioCardia 仍預計在 2023 年第二季度完成正式提交以獲得日本批准。

In Japan, another autologous cell therapy has received conditional approval for heart failure based on seven patients treated, and these treatments require open-heart surgery to access the heart. Although our clinical data is from overseas, we have treated far more patients in rigorous controlled trials and have a minimally invasive procedure with our Helix biotherapeutic delivery system.

在日本，另一種自體細胞療法已獲得基於治療七名患者的心力衰竭的有條件批准，這些療法需要進行心臟直視手術才能進入心臟。儘管我們的臨床數據來自海外，但我們在嚴格的對照試驗中治療了更多的患者，並使用我們的 Helix 生物治療輸送系統進行了微創手術。

Our cell-processing platform is approved in Japan already for therapeutic applications for non-cardiac indications by our partner Zimmer Biomet, and our minimally invasive Helix biotherapeutic delivery system is approved in the European Union. Our feeling is that there are many reasons that Japan PMDA should be inclined to approve CardiAMP Cell Therapy for the benefit of patients and to continue to advance Japan's leadership in regenerative medicine therapies.

我們的細胞處理平台已在日本獲得我們的合作夥伴 Zimmer Biomet 批准用於非心臟適應症的治療應用，我們的微創 Helix 生物治療輸送系統已在歐盟獲得批准。我們的感覺是，日本 PMDA 應出於多種原因傾向於批准 CardiAMP 細胞療法，以造福患者並繼續提升日本在再生醫學治療領域的領導地位。

Now I'd like to move to our two allogeneic cell therapy product candidates based on our allogeneic Neurokinin-1 receptor positive mesenchymal stem cell platform. These are off-the-shelf cells from young, healthy donors intended to be expanded to produce many doses for many patients.

現在我想談談我們基於同種異體 Neurokinin-1 受體陽性間充質乾細胞平台的兩種同種異體細胞治療候選產品。這些是來自年輕健康捐贈者的現成細胞，旨在擴大規模，為許多患者生產多種劑量。

The Neurokinin-1 receptor positive mesenchymal stem cells are particularly interesting as Neurokinin-1 is the primary receptor for substance P, an important neuropeptide mediator of inflammation which plays a central role in both heart failure and regenerative processes following myocardial injury. I encourage listeners to Google substance P to understand why advancing the mesenchymal stem cells that bind to this neuropeptide is exciting.

Neurokinin-1 受體陽性間充質乾細胞特別令人感興趣，因為 Neurokinin-1 是 P 物質的主要受體，P 物質是一種重要的炎症神經肽介質，在心力衰竭和心肌損傷後的再生過程中發揮著核心作用。我鼓勵聽眾通過谷歌搜索 P 物質，了解為什麼推進與這種神經肽結合的間充質乾細胞是令人興奮的。

Our allogeneic mesenchymal stem cell program in ischemic etiology heart failure of reduced ejection fraction is designated as BCD-03. This is a Phase I/II, multi-center, randomized, double-blinded, controlled study of up to 69 patients designed to assess the safety and efficacy of this therapeutic candidate. The investigational new drug application was approved by the FDA in December 2022. And the trial is designed for patients ineligible for the company's Phase III CardiAMP Heart Failure trial studying autologous cell therapy.

我們針對射血分數降低的缺血性心力衰竭的同種異體間充質乾細胞項目被指定為 BCD-03。這是一項 I/II 期、多中心、隨機、雙盲、對照研究，共有 69 名患者參與，旨在評估該候選治療藥物的安全性和有效性。該研究性新藥申請於 2022 年 12 月獲得 FDA 批准。該試驗是針對不符合該公司研究自體細胞療法的 III 期 CardiAMP 心力衰竭試驗的患者而設計的。

Clinical-grade allogeneic cells have been manufactured in our Sunnyvale facility and are ready for use. These cells will be delivered under the protocol with our proprietary minimally invasive biotherapeutic delivery system. We still expect to begin enrolling patients in the second quarter of 2023, which has seven weeks remaining.

臨床級同種異體細胞已在我們的桑尼維爾工廠生產並可供使用。這些細胞將根據我們專有的微創生物治療輸送系統的協議進行輸送。我們仍預計在 2023 年第二季度開始招募患者，此時還剩七週。

Our allogeneic mesenchymal stem cell program in patients recovering from acute respiratory distress syndrome, which we have designated BCD-04, was approved by the FDA in April 2022 to treat patients. The trial is a Phase I, multi-center, open-label study of up to nine patients. While the number of patients with COVID-induced ARDS has decreased, ARDS unrelated to COVID is still significantly impacting patients. The company intends to work with the FDA to modify the study eligibility criteria to include these patients.

我們針對急性呼吸窘迫綜合徵康復患者的同種異體間充質乾細胞項目（我們將其命名為 BCD-04）於 2022 年 4 月獲得 FDA 批准用於治療患者。該試驗是一項 I 期、多中心、開放標籤研究，涉及最多 9 名患者。雖然因新冠肺炎引起的急性呼吸窘迫綜合徵 (ARDS) 患者數量有所減少，但與新冠肺炎無關的急性呼吸窘迫綜合徵 (ARDS) 仍然對患者產生重大影響。該公司打算與 FDA 合作修改研究資格標準以納入這些患者。

In this trial, increasing dosages of the cells will be initially evaluated and then the optimal dose will be taken to Phase 2 in a randomized study in adult patients recovering from ARDS. This therapy is intended to address the enormous unmet need of sustained local and systemic inflammation after a patient has taken off respiratory support, with the goals of accelerating recovery, enhancing survival, and reducing both relapse and rehospitalization.

在這項試驗中，將首先評估細胞劑量的增加，然後在對從 ARDS 中恢復的成年患者進行的隨機研究中，將最佳劑量用於第二階段。該療法旨在解決患者停止呼吸支持後持續局部和全身炎症的巨大未滿足需求，目標是加速康復、提高生存率並減少復發和再住院。

Clinical-grade cells are also ready for use in this study. The ARDS trial is expected to commence following the initiation of BCD-03, studying these allogeneic mesenchymal stem cells for heart failure.

臨床級細胞也可用於本研究。 ARDS 試驗預計將在 BCD-03 啟動後開始，研究這些同種異體間充質乾細胞治療心力衰竭的效果。

In summary, we are advancing four clinical-stage therapeutic product candidates that address important unmet cardiac and pulmonary diseases based on our autologous and our allogeneic cell therapy platforms. From these therapeutic development efforts, we now have four active business development initiatives.

總之，我們正在開發四種臨床階段的候選治療產品，這些產品基於我們的自體和同種異體細胞治療平台來解決重要的未滿足的心臟和肺部疾病。通過這些治療開發工作，我們現在有四項積極的業務開發計劃。

First is partnering our CardiAMP Cell Therapy platform internationally. Second is licensing out our clinical-stage Neurokinin-1 receptor positive mesenchymal stem cell platform for other clinical indications which have shown promise with other mesenchymal stem cell preparations.

首先是與我們的 CardiAMP 細胞治療平台進行國際合作。其次是授權我們的臨床階段 Neurokinin-1 受體陽性間充質乾細胞平台用於其他臨床適應症，這些適應症已與其他間充質乾細胞製劑一起顯示出前景。

Third is licensing our catheter-based biotherapeutic delivery systems for cell gene and protein therapy candidates to the heart, such as in the BlueRock relationship we began last year. And fourth is monetizing our AVANCE transseptal introducer sheath product. We are looking forward to announcing an additional patent issuance related to our Helix biotherapeutic delivery platform and feel very good about our broader intellectual property estate.

第三是授權我們基於導管的生物治療輸送系統，用於心臟細胞基因和蛋白質治療候選藥物，例如我們去年開始的 BlueRock 關係。第四是我們的 AVANCE 房間隔導引鞘產品的貨幣化。我們期待宣布與我們的 Helix 生物治療交付平台相關的額外專利發行，並對我們更廣泛的知識產權感到非常滿意。

I will now pass the call to David McClung, our CFO, who will review our Q1 2023 financial results. David?

我現在將把電話轉給我們的首席財務官 David McClung，他將審查我們 2023 年第一季度的財務業績。大衛？

Thank you, Peter, and good afternoon, everyone. Revenues were approximately $64,000 for the three months ended March 31, 2023, comparable to the $60,000 for the three months ended March 31, 2022.

謝謝你，彼得，大家下午好。截至2023年3月31日止三個月的收入約為64,000美元，而截至2022年3月31日止三個月的收入為60,000美元。

Research and development expenses increased to approximately $2.4 million in the first quarter of 2023, compared to approximately $2.2 million in the first quarter of 2022, primarily due to expected increases in support of the CardiAMP Heart Failure trial. SG&A expenses remained at approximately $1.2 million in the first quarter of 2023, comparable to the same amount in the first quarter of 2022. Our net loss was approximately $3.6 million in Q1 2023 as compared to $3.3 million in the first quarter of 2022.

2023 年第一季度的研發費用增加至約 240 萬美元，而 2022 年第一季度的研發費用約為 220 萬美元，這主要是由於 CardiAMP 心力衰竭試驗的支持預期增加。 2023 年第一季度的銷售管理及行政費用保持在約 120 萬美元，與 2022 年第一季度的水平相當。2023 年第一季度的淨虧損約為 360 萬美元，而 2022 年第一季度的淨虧損為 330 萬美元。

And net cash used in operations during the quarter was approximately $2.6 million, as compared to approximately $2.9 million in the first quarter of 2022. BioCardia ended the quarter with approximately $4.9 million in cash and cash equivalents, providing runway into Q3 without additional capital or funding from business development activities that Peter touched on in his remarks.

本季度運營中使用的淨現金約為 260 萬美元，而 2022 年第一季度約為 290 萬美元。BioCardia 在本季度結束時擁有約 490 萬美元的現金和現金等價物，無需額外資本或資金即可進入第三季度彼得在講話中提到的業務發展活動。

This concludes management's prepared comments. We're ready to take questions.

管理層準備好的評論到此結束。我們準備好回答問題。

Thank you. We will now begin the question-and-answer session. (Operator Instructions)

謝謝。我們現在開始問答環節。 （操作員說明）

Joe Pantginis, H.C. Wainwright.

喬·潘吉尼斯，H.C.溫賴特。

Hey guys, good afternoon. Thanks for taking the question. Two primary questions, Peter. So first, with regard to BCDA-01, nice to hear you're making progress with your FDA discussions. So for the current patients enrolled, you said you had 10 control patients that had crossed over. So can you remind us the criteria for crossover? And then following crossover, what could be the potential impact of new or concomitant meds?

嘿伙計們，下午好。感謝您提出問題。兩個主要問題，彼得。首先，關於 BCDA-01，很高興聽到您與 FDA 的討論取得了進展。因此，對於當前入組的患者，您說有 10 名對照患者已經交叉。那麼您能提醒我們一下交叉的標準嗎？那麼交叉後，新藥或聯合用藥可能產生什麼潛在影響？

Okay, so thank you, Joe. I was waiting for a second question there and I think I've got the breakdown. So first on the -- I appreciate the question and I really appreciate you being on the call. So on BCD-01, the 10 crossover patients crossed over after they met their two-year follow-up endpoint in the trial and essentially exited the trial.

好的，謝謝你，喬。我在那裡等待第二個問題，我想我已經找到了答案。首先，我很欣賞這個問題，也非常感謝您接聽電話。因此，在 BCD-01 中，10 名交叉患者在達到試驗中的兩年隨訪終點後進行了交叉，並基本上退出了試驗。

The requirement for those patients is substantially what it is to be included in the trial, although I think the workup is a little bit less because some of them may have deteriorated. There is actually a patient that you can see who has crossed over on our patient-facing website, which is cardiamp.com.

對這些患者的要求基本上就是納入試驗的要求，儘管我認為檢查要少一些，因為其中一些患者可能已經惡化。實際上，您可以在我們面向患者的網站（cardiamp.com）上看到一位已跨界的患者。

And so yeah, we've had 10 patients cross over. The FDA approved this last year, I think, or maybe it was the year before, because of the safety profile they're seeing in the trial and the sense that these patients enrolled in the trial should be given the option if they and their physicians think it makes sense for them to proceed.

是的，我們已經有 10 名患者交叉了。我認為 FDA 去年批准了這一計劃，或者可能是前年批准的，因為他們在試驗中看到了安全性，並且認為如果這些參加試驗的患者和他們的醫生應該給予他們選擇的感覺認為他們繼續下去是有意義的。

The last piece is these patients are then followed for another year. And so for the trial, they provide additional safety data for us, which as you heard on my FDA comments, is valuable for the FDA. And I actually may use that to note that if you consider the FDA comments I shared, those comments were all around stopping the trial early. They want to have sufficient safety, but that's fundamentally to provide support for approving the therapy. So that's actually a really nice conversation to be having.

最後一部分是對這些患者進行一年的隨訪。因此，對於試驗，他們為我們提供了額外的安全數據，正如您在我的 FDA 評論中聽到的那樣，這對 FDA 很有價值。實際上我可以用它來指出，如果你考慮我分享的 FDA 評論，這些評論都是關於提前停止試驗。他們希望有足夠的安全性，但這從根本上是為了為批准治療提供支持。所以這實際上是一次非常愉快的談話。

No, that's good. Thanks. And then the second question really is around those FDA discussions. Obviously, I know you can't be too specific right now since it's ongoing and it's iterative. But just curious if you could take some broad strokes about, I guess, your prepared comment surrounding ideas to enhance the safety package, since you can't increase patient numbers.

不，那很好。謝謝。第二個問題實際上是圍繞 FDA 的討論展開的。顯然，我知道你現在不能太具體，因為它正在進行中並且是迭代的。但我只是好奇，您是否可以對您準備好的圍繞增強安全方案的想法進行評論，因為您無法增加患者數量。

Well, I guess, yes, I can share that. So, well, actually, it's probably best to wait until we have the final details from the agency. It is only a few weeks out and we can share it then. But the key is patient numbers for approving the therapy. And I'll share with folks when we designed this trial, that was one of the primary considerations because of the power we had going into it, is that we wanted to have enough patients to enroll in the trial, to enable the agency to have comfort to approve the therapy.

嗯，我想，是的，我可以分享這一點。所以，實際上，最好等到我們從該機構獲得最終細節。只剩幾週時間了，我們就可以分享了。但關鍵是批准該療法的患者數量。當我們設計這個試驗時，我將與大家分享，這是主要考慮因素之一，因為我們擁有參與該試驗的權力，我們希望有足夠的患者參加試驗，以使該機構能夠安慰批准治療。

Again, our goal here at BioCardia is not just to deliver a positive trial. Our goal is to deliver a product for these patients and the physicians who care for them. And at that point in time, the dialogue was around what number would be acceptable for the agency. And they wouldn't provide us with a specific number.

再次強調，我們 BioCardia 的目標不僅僅是提供積極的試驗。我們的目標是為這些患者和照顧他們的醫生提供產品。當時，對話的重點是該機構可以接受多少數字。他們不會向我們提供具體數字。

But as we've gone downstream, it's our safety profile in this program and in our second program that also help us. So, I guess, let me detail the results of the adaptive statistical analysis plan when we have the FDA's blessing for it. And I'm hopeful that that will be in just a few short weeks here.

但隨著我們向下游發展，我們在這個計劃和第二個計劃中的安全狀況也對我們有所幫助。因此，我想，當我們獲得 FDA 的批准時，讓我詳細介紹適應性統計分析計劃的結果。我希望這將在短短幾週內實現。

Fair enough. Appreciate the feedback.

很公平。感謝您的反饋。

Thank you, Joe. Appreciate the questions.

謝謝你，喬。感謝您提出的問題。

Kumar Raja, ROTH Capital.

庫馬爾·拉賈（Kumar Raja），羅斯資本。

Thanks for taking my questions and congratulations, Peter, on all the progress. With respect to the feedback that is expected from the FDA at the end of June, the expectation is that you have taken care of whatever the questions they had and the feedback they have given before. And we are pretty much close to the final stage in terms of getting an agreement with the FDA with regard to the adaptive statistical plan.

感謝您提出問題，並祝賀彼得所取得的所有進展。關於預計 FDA 在 6 月底收到的反饋，我們希望你們已經解決了他們提出的任何問題以及他們之前給出的反饋。我們已經接近與 FDA 就自適應統計計劃達成協議的最後階段。

So, thank you, Kumar, for the question and also for being on the call. That is our sense. For those who have been involved with conversations with the FDA, they ask more questions than they provide real clear guidance on where to go next.

所以，庫馬爾，謝謝你提出問題並接受電話採訪。這就是我們的感覺。對於那些參與與 FDA 對話的人來說，他們提出的問題多於他們提供的關於下一步該做什麼的真正明確的指導。

But we have a pretty sophisticated team that's come into this conversation. We are working with literally a world-class regulatory group, our own internal regulatory team, which is nothing short of phenomenal, and perhaps the most respective statistical analysis plan developers with respect to an adaptive design from the agency's perspective.

但我們有一個非常成熟的團隊參與了這次對話。我們正在與一個名副其實的世界級監管機構、我們自己的內部監管團隊合作，該團隊堪稱非凡，而且從該機構的角度來看，在自適應設計方面，也許是最有針對性的統計分析計劃開發人員。

So my sense is we went into this very seriously, and I think the agency recognized that. So every single question that they raised and that which we discussed, I think, was extremely well addressed.

所以我的感覺是我們非常認真地對待這個問題，我認為該機構認識到了這一點。因此，我認為他們提出的每一個問題以及我們討論的每一個問題都得到了很好的解決。

So that said, we can never predict the future with the agency. They are trying to do their best by all the folks in the United States. And if they do come back to us with follow-on questions, we will address them. But our hope is that they will come back to us and bless the statistical analysis plan, and then we will roll it into the next Data Safety Monitoring Board review, which is currently being scheduled for the end of June.

也就是說，我們永遠無法預測該機構的未來。他們正在努力讓美國全體人民盡力而為。如果他們確實向我們提出後續問題，我們將予以解答。但我們希望他們會回來支持我們的統計分析計劃，然後我們會將其納入下一次數據安全監測委員會審查，目前計劃於 6 月底進行。

Okay. So the expectation is that by that meeting, you will have more clarity. And also, with regard to the PMDA submission, maybe you can just provide us a little bit with regard to once you submit it, what is the expectation and the timelines there. And also, in that context, you mentioned about two out-licensing or product distribution opportunities. Maybe you can talk a little bit about that. Thanks so much.

好的。因此，我們期望通過這次會議，您會更加清楚。另外，關於 PMDA 提交，也許您可以向我們提供一些有關提交後的期望和時間表的信息。此外，在這種情況下，您提到了兩個向外許可或產品分銷的機會。也許你可以談談這一點。非常感謝。

Appreciate the questions, Kumar. So on PMDA submission, so we've had two separate consultations with -- this is the Pharmaceutical and Medical Device Agency in Japan. And this is around securing an approval for the CardiAMP Cell Therapy platform for the treatment of ischemic etiology heart failure of reduced ejection fraction, which is our lead program.

感謝您提出的問題，庫馬爾。關於 PMDA 提交，我們與日本藥品和醫療器械管理局進行了兩次單獨的磋商。這是為了確保 CardiAMP 細胞治療平台獲得批准，用於治療射血分數降低的缺血性病因心力衰竭，這是我們的主導項目。

And the conversations we've had with the agency so far have been all focused on really the same question, is we are keen on securing approval based on the data that we already have in hand. Not waiting to complete the pivotal trial in the United States, but rather based on the quite significant data sets and experience and the number of approvals we already have.

到目前為止，我們與該機構的對話都集中在同一個問題上，即我們熱衷於根據我們現有的數據獲得批准。不是等待在美國完成關鍵試驗，而是基於相當重要的數據集、經驗以及我們已經擁有的批准數量。

And so all of the questions from PMDA and our two consultations have been focused around clarity of certain issues, certain procedural elements. We've been impressed by them, and they've been rather sophisticated. But the submission process we're in the midst of does have some challenges with respect to translation delays, because a rather large document will be provided to them containing substantially the information which they've already seen in different formats in Japanese for them to consider.

因此，PMDA 提出的所有問題以及我們的兩次磋商都集中在明確某些問題和某些程序要素上。他們給我們留下了深刻的印象，他們相當老練。但我們正在進行的提交過程確實在翻譯延遲方面存在一些挑戰，因為將向他們提供相當大的文檔，其中包含他們已經看到的不同日語格式的信息，供他們考慮。

Our expectation is, after we submit this to them, that we will have them come back to us with a series of questions, which we'll have to respond to in short order. And our hope is that, at the end of the day, the key issue is, will they approve this without pre-approval data in Japan?

我們的期望是，在我們向他們提交此信息後，他們會向我們提出一系列問題，我們必須在短時間內做出答复。我們希望，歸根結底，關鍵問題是，他們會在沒有日本預先批准數據的情況下批准這一計劃嗎？

And the four words we are aiming for are, your proposal is acceptable.

我們的目標是四個字：你的建議可以接受。

And so that's really where we're headed for on this. And we think we've got all of the support we need, but again, we're working with regulators that complicates it.

這就是我們真正的目標。我們認為我們已經獲得了所需的所有支持，但我們正在與監管機構合作，這讓事情變得更加複雜。

So that's about all I can share at this point in time. Again, as is BioCardia's approach, we have multiple different experienced consultants we're working with. We have incredibly distinguished co-national principal investigators in Japan that we're hoping to be working with on a post-marketing study after we have approval, in addition to just incredibly distinguished folks on the regulatory and processes in Japan. So it's been a delight.

這就是我目前能分享的全部內容。同樣，正如 BioCardia 的方法一樣，我們與多名經驗豐富的顧問合作。我們在日本擁有非常傑出的聯合首席研究員，我們希望在獲得批准後與他們合作進行上市後研究，此外還有日本監管和流程方面非常傑出的人員。所以這真是令人高興。

On out-licensing, I detailed the various categories of out-licensing we have. We have a lot of activity currently. And our sense is, we have capital to get through a couple of deals, as well as all of these milestones we're detailing for BCD-01, -02, and -03. So I'd say stay tuned on the out-licensing.

關於對外許可，我詳細介紹了我們擁有的各類對外許可。目前我們有很多活動。我們的感覺是，我們有資金來完成幾筆交易，以及我們為 BCD-01、-02 和 -03 詳細說明的所有這些里程碑。所以我想說請繼續關注對外許可。

Unfortunately, they're similar to the FDA, that we can't be guaranteed what their timelines are, what their response is going to be. But by being buttoned up, it helps. And I think we are a buttoned-up organization.

不幸的是，他們與 FDA 類似，我們無法保證他們的時間表是什麼，他們的反應是什麼。但把釦子扣好會有幫助。我認為我們是一個保守的組織。

So again, I'll have to say stay tuned for those discussions. They do involve out-licensing products and distribution deals around product candidates that we have that don't really reduce the value of anything we're currently doing in the United States. They're all additional value propositions.

所以，我不得不再說一遍，請繼續關注這些討論。它們確實涉及圍繞我們擁有的候選產品進行產品許可和分銷交易，但這並沒有真正降低我們目前在美國所做的任何事情的價值。它們都是額外的價值主張。

Very helpful. Thanks so much.

很有幫助。非常感謝。

I appreciate the questions, Kumar. Have a great afternoon.

我很欣賞這些問題，庫馬爾。祝你有個愉快的下午。

(Operator Instructions) Laura Suriel, Alliance Global Partners.

（操作員說明）Laura Suriel，Alliance Global Partners。

Hello. This is Laura calling in for Jim Molloy from AGP. Thank you for taking our questions. So for the BCDA-02 trial, it was mentioned in the previous call that trial design modifications were being planned in order to speed up enrollment. So what's the overall status on any of these changes that are being proposed to the FDA? And then also, for the BCDA-04 trial, when do you expect to meet with the FDA as well to modify the study eligibility?

你好。我是勞拉 (Laura) 給 AGP 的吉姆·莫洛伊 (Jim Molloy) 打電話。感謝您接受我們的提問。因此，對於 BCDA-02 試驗，在之前的電話會議中提到，正在計劃修改試驗設計，以加快入組速度。那麼，向 FDA 提議的這些變更的總體狀況如何？另外，對於 BCDA-04 試驗，您預計什麼時候與 FDA 會面並修改研究資格？

Good questions, Laura. I appreciate you being on the call. So I have easy answers, but I'll give you more color. So BCD-02, we're not going to engage the FDA in changing the trial design until we complete the initial roll-in cohort, which is imminent. And that trial design is going to involve substantial structural changes in the inclusion, exclusion, as well as the primary endpoint.

好問題，勞拉。感謝您接聽電話。所以我有簡單的答案，但我會給你更多的色彩。因此，BCD-02，在我們完成即將到來的初始轉入隊列之前，我們不會讓 FDA 改變試驗設計。該試驗設計將涉及納入、排除以及主要終點方面的重大結構性變化。

This trial, I guess I would say for folks on the call, is substantially equivalent to the trial that Baxter Healthcare advanced in this indication, focused solely on CD34 cells. And everybody criticized Baxter Healthcare for how long the trial took for them to enroll 90 patients, and then they ultimately just stopped the trial and walked away from it, even though they had great efficacy signals that ultimately were published.

我想我會對參加電話會議的人說，這項試驗基本上相當於 Baxter Healthcare 在該適應症中推進的試驗，僅針對 CD34 細胞。每個人都批評 Baxter Healthcare 花了很長時間才招募 90 名患者，然後他們最終停止了試驗並放棄了試驗，儘管他們最終發布了很好的療效信號。

We now understand the difficulties Baxter was having. And so unlike Baxter Healthcare walking away from it, we're going to drill into it and solve it. And we're eminently confident that we can do that because we're working with some of the world experts in this space. So that's ongoing, working with our KOLs and physicians and pursuing the realm of what's possible.

我們現在了解巴克斯特所面臨的困難。因此，與百特醫療保健公司放棄它不同，我們將深入研究它並解決它。我們非常有信心能夠做到這一點，因為我們正在與該領域的一些世界專家合作。因此，我們正在與我們的 KOL 和醫生合作，不斷追求可能的境界。

And my sense today is we're going to go after an endpoint that's primarily image and self-assessment driven, i.e., probably using PET and using Seattle Angina Questionnaire versus using the cardiopulmonary exercise time. And the good thing for investors is eliminating the cardiopulmonary exercise time criteria, which we may still measure at baseline and follow-up, but making it less important, will greatly reduce the cost of this trial. And that's another nice advantage.

我今天的感覺是，我們將追求一個主要由圖像和自我評估驅動的終點，即可能使用 PET 和使用西雅圖心絞痛問卷，而不是使用心肺鍛煉時間。對投資者來說，好處是消除了心肺運動時間標準，我們仍然可以在基線和隨訪中進行測量，但使其不那麼重要，將大大降低本次試驗的成本。這是另一個很好的優勢。

So the trial will go faster, we'll have data that's more objective for physicians. And we expect that on every front, it will be advantageous to us. So that's on the BCD-02.

因此試驗會進行得更快，我們將為醫生​​提供更客觀的數據。我們希望這在各個方面都對我們有利。這就是 BCD-02 上的情況。

On BCD-04, the dynamic there is really easy. That's a quick supplement to the agency. And I do not expect any agency pushback whatsoever. Essentially, when we launched that program, we were going after patients who had acute respiratory distress syndrome, secondary to having COVID.

在 BCD-04 上，動態非常簡單。這是對該機構的快速補充。我預計不會有任何機構的阻力。本質上，當我們啟動該計劃時，我們正在尋找繼發於新冠肺炎的急性呼吸窘迫綜合徵患者。

Since then, as we all know, there's not a whole lot of patients with COVID who are winding up on ventilator with acute respiratory distress syndrome. And so by eliminating the requirement to have had COVID before, we'll be going after a classic ARDS population.

眾所周知，從那時起，沒有多少新冠肺炎患者因急性呼吸窘迫綜合徵而需要使用呼吸機。因此，通過取消之前感染過新冠病毒的要求，我們將針對典型的急性呼吸窘迫綜合徵人群。

We're also awaiting -- there's a very large NIH study coming out shortly in this space, being led by the University of California in San Francisco. And so as we make that supplement, we're also awaiting that data. So just because of bandwidth issues, we haven't pulled the trigger on that modification, but that's a very easy modification to the trial for the agency.

我們也在等待——由舊金山加利福尼亞大學領導的美國國立衛生研究院（NIH）不久後將在這一領域開展一項大型研究。因此，當我們進行補充時，我們也在等待這些數據。因此，僅僅因為帶寬問題，我們還沒有啟動該修改，但對於該機構來說，這是對試驗的一個非常簡單的修改。

And I'd be literally shocked if there was any concerns on the agency's part. We just haven't gotten around to submitting it, in part because we see that program as after the BCD-03 trial getting started.

如果該機構有任何擔憂，我真的會感到震驚。我們只是還沒有抽出時間提交它，部分原因是我們認為該計劃是在 BCD-03 試驗開始之後進行的。

Got it. Thank you for taking the questions.

知道了。感謝您提出問題。

No, I appreciate them, Laura.

不，我很欣賞他們，勞拉。

As we have no further questions, I would now like to turn the conference back over to Peter Altman for any closing remarks.

由於我們沒有其他問題，我現在想將會議轉回彼得·奧爾特曼（Peter Altman）發表閉幕詞。

I want to thank all of you for participating in today's call and for your interest in BioCardia. We do look forward to sharing our continued progress. Stay healthy, be kind, and have a wonderful afternoon.

我要感謝大家參加今天的電話會議以及對 BioCardia 的興趣。我們確實期待分享我們不斷取得的進展。保持健康，友善，並度過一個美好的下午。

The conference has now concluded. Thank you for attending today's presentation. You may all now disconnect.

會議現已結束。感謝您參加今天的演講。你們現在可以斷開連接了。