Cuộc họp công bố kết quả kinh doanh Q2 2026 của BioCardia (BCDA): Nộp hồ sơ CardiAMP tại Nhật Bản và tiến triển với FDA

BioCardia (NASDAQ: BCDA) tập trung cuộc họp báo cáo kết quả kinh doanh quý 2/2026 vào tiến trình pháp lý đối với Liệu pháp Tế bào CardiAMP và ống thông phân phối xuyên nội mạc cơ tim Helix. Công ty đã giảm chi phí và lỗ thuần so với cùng kỳ năm ngoái, trong khi đợt huy động vốn qua cơ chế ATM giúp kéo dài thời gian hoạt động tiền mặt sang năm 2027.

Điểm chính

• Cuộc tham vấn với PMDA của Nhật Bản hỗ trợ việc đưa Liệu pháp Tế bào CardiAMP tiến tới hồ sơ nộp xin phê duyệt lưu hành Shonin. BioCardia cho biết họ đang chuẩn bị nộp hồ sơ trong quý tới và dự kiến chỉ định ban đầu sẽ bao phủ khoảng 20.000 bệnh nhân.
• Biên bản cuộc họp với FDA xác nhận rằng thử nghiệm CardiAMP Heart Failure II đang diễn ra có thể hỗ trợ phê duyệt trước khi lưu hành. Ban quản lý cho biết cơ quan này xem đây là thử nghiệm xác nhận Giai đoạn III tập trung chủ yếu vào tính hiệu quả.
• Bốn trung tâm đang tích cực tuyển chọn bệnh nhân cho thử nghiệm CardiAMP Heart Failure II. Dự kiến sẽ có thêm ba bệnh nhân đủ điều kiện và hai thủ thuật đã được lên lịch trong tháng 8/2026, trong đó ban quản lý chưa ghi nhận bất kỳ vấn đề an toàn nào.
• Lỗ thuần quý 2 thu hẹp xuống còn 1,6 triệu USD từ mức 2,0 triệu USD của cùng kỳ năm trước. Tổng chi phí giảm xuống 1,6 triệu USD từ mức 2,1 triệu USD, chủ yếu do chi phí nghiên cứu và phát triển giảm.
• BioCardia đã thu về khoảng 4,9 triệu USD tiền ròng thông qua cơ chế ATM với mức giá trung bình là 1,22 USD/cổ phiếu. Tiền và các khoản tương đương tiền cuối quý đạt 4,1 triệu USD, đảm bảo nguồn vốn hoạt động sang năm 2027, theo ban quản lý.
• FDA đã xác định hai lộ trình cấp phép tiềm năng cho Helix, bao gồm phê duyệt cùng với CardiAMP và lộ trình De Novo khả thi. Biên bản cuộc họp chính thức vẫn đang chờ xử lý, mặc dù BioCardia cho biết một email từ FDA đã xác nhận sự hiểu biết của cơ quan này về cuộc thảo luận.

Dữ liệu Tài chính Chính

BioCardia kết thúc quý với 2,7 triệu USD vốn chủ sở hữu, điều mà ban quản lý tin rằng giúp công ty duy trì sự tuân thủ các tiêu chuẩn niêm yết của Nasdaq.

Kết quả Hoạt động và Kinh doanh

Lộ trình pháp lý của CardiAMP tại Nhật Bản

PMDA đã yêu cầu xác nhận rằng các bệnh nhân tham gia thử nghiệm đang nhận được điều trị y tế theo hướng dẫn và không đủ điều kiện để tái thông mạch máu. Cơ quan này cũng yêu cầu thông tin bổ sung về các trường hợp tử vong, ghép tim và cấy ghép thiết bị hỗ trợ thất trái, cùng với đề xuất ban đầu cho một nghiên cứu sau khi lưu hành.

BioCardia cho biết hầu hết thông tin được yêu cầu đã có sẵn. Ban quản lý đã xác định khoảng 8 hoặc 9 trường hợp trong số 115 bệnh nhân mà lý do không nhận được một trong bốn loại thuốc theo hướng dẫn vẫn cần phải được bổ sung hồ sơ.

Công tác chuẩn bị nộp hồ sơ bao gồm hoàn tất hồ sơ gốc thử nghiệm điện tử, tiến hành kiểm toán Thực hành lâm sàng tốt (GCP) tại Nhật Bản, chuyển đổi dữ liệu lâm sàng sang tiêu chuẩn CDISC và bổ nhiệm Đơn vị nắm giữ đăng ký lưu hành chỉ định (DMAH). Ban quản lý mô tả việc chuyển đổi CDISC là khối lượng công việc còn lại mất nhiều thời gian nhất.

Công ty dự kiến chỉ định ban đầu tại Nhật Bản sẽ phục vụ khoảng 20.000 bệnh nhân. Ban quản lý cho biết việc phê duyệt có thể diễn ra khoảng 12 tháng sau khi hoàn tất hồ sơ nộp Shonin, tùy thuộc vào quá trình xem xét của cơ quan quản lý. Các cuộc thảo luận về hoàn trả chi phí y tế sẽ diễn ra sau khi được phê duyệt.

BioCardia đã dẫn số liệu có khoảng 300.000 bệnh nhân suy tim do thiếu máu cục bộ và 250.000 ca can thiệp thông tim hàng năm tại Nhật Bản. Công ty cũng lưu ý rằng một liệu pháp tế bào khác cho cùng chỉ định đã nhận được mức hoàn trả 326.000 USD cho mỗi đợt điều trị vào tháng 7/2026. Những con số này được ban quản lý đưa ra làm ngữ cảnh cho cơ hội thị trường tiềm năng của CardiAMP, chứ không phải định hướng định giá của BioCardia.

CardiAMP Heart Failure II tại Hoa Kỳ

FDA đã xác nhận rằng CardiAMP Heart Failure II có thể hỗ trợ phê duyệt trước khi lưu hành và có thể đóng vai trò là thử nghiệm xác nhận cho chỉ định suy tim. Ban quản lý cho biết các cuộc thảo luận tiếp theo sẽ tập trung vào yếu tố chất lượng cuộc sống, vốn là tiêu chí cấp ba của tiêu chí đánh giá chính gộp, sau tỷ lệ tử vong do mọi nguyên nhân và các biến cố bất lợi tim mạch chính không tử vong.

BioCardia có kế hoạch tinh chỉnh nghiên cứu xoay quanh thước đo tiêu chí đánh giá chính. Ban quản lý cho biết việc tuyển chọn bệnh nhân chủ yếu bị hạn chế bởi nguồn lực triển khai và không tiến triển với tốc độ nhanh, do đội ngũ lâm sàng đang ưu tiên cho hồ sơ nộp tại Nhật Bản. Các trung tâm thử nghiệm bổ sung đang được đưa vào hệ thống.

Ống thông phân phối Helix

FDA không đưa ra lo ngại nào trong cuộc họp trước khi nộp hồ sơ liên quan đến độ an toàn của Helix, hiệu suất thiết bị hoặc tính tương thích với các nhóm chất điều trị chung. Lộ trình ưu tiên của cơ quan này là phê duyệt cùng với CardiAMP, trong khi một cuộc họp trước nộp hồ sơ tiếp theo có thể hỗ trợ cấp phép De Novo độc lập.

BioCardia cho biết Helix đã được sử dụng trong hơn một tá thử nghiệm lâm sàng liên quan đến khoảng 500 bệnh nhân và trước đó đã đạt chứng nhận CE để lưu hành tại thị trường Châu Âu. Ban quản lý tin rằng việc FDA cấp phép có thể hỗ trợ các quan hệ đối tác điều trị và đơn giản hóa các hồ sơ nộp lên cơ quan quản lý trong tương lai.

Thương mại hóa và đối tác

BioCardia đang tiến hành các cuộc thảo luận phát triển kinh doanh tích cực tại khu vực Châu Á - Thái Bình Dương bao gồm các liệu pháp tim mạch của mình. Ban quản lý cho biết một giao dịch tiềm năng có thể giúp tài trợ cho CardiAMP cho bệnh thiếu máu cục bộ cơ tim mạn tính và Liệu pháp Tế bào CardiALLO cho bệnh suy tim do viêm, mặc dù chưa có thỏa thuận nào được công bố.

Đơn vị DMAH triển vọng tại Nhật Bản sẽ cung cấp hỗ trợ pháp lý và chất lượng thay vì đóng vai trò là bên nhận giấy phép thương mại. BioCardia hiện có kế hoạch tự bán CardiAMP trong quá trình nghiên cứu sau khi lưu hành có thể bao gồm từ vài trăm đến 1.000 bệnh nhân. Các nhà phân phối của bệnh viện địa phương có thể nhận tới 10% giá trị sản phẩm.

Ban quản lý cũng đề cập đến các cuộc thảo luận sơ bộ về các mối quan hệ tiềm năng tại Brazil và Các Tiểu vương quốc Ả Rập Thống nhất, vốn có thể diễn ra sau khi được phê duyệt thành công tại Nhật Bản.

Triển vọng từ Ban quản lý

Ban quản lý tin rằng nguồn vốn hiện tại đủ để hoàn tất cột mốc nộp hồ sơ PMDA mang tính bước ngoặt tiềm năng. BioCardia cũng cho biết một đợt huy động vốn nhỏ với sự tham gia của các nhà đầu tư dài hạn có thể đẩy nhanh chương trình CardiAMP Heart Failure II.

Công ty dự kiến sẽ đào tạo các bác sĩ Nhật Bản và thiết lập hậu cần nghiên cứu sau khi lưu hành trong thời gian cơ quan quản lý xem xét. Ban quản lý kỳ vọng việc đưa sản phẩm vào sử dụng sẽ tương đối nhanh chóng nếu CardiAMP nhận được phê duyệt và hoàn trả chi phí y tế, nhưng kỳ vọng đó phụ thuộc vào sự cấp phép của cơ quan quản lý, sự sẵn sàng của các trung tâm và việc thực thi thành công nghiên cứu sau khi lưu hành.

Rủi ro và các yếu tố cần theo dõi

• Các yêu cầu còn đọng lại của PMDA phải được giải quyết trước hoặc như một phần của hồ sơ nộp Shonin, bao gồm tài liệu điều trị và hồ sơ chi tiết về biến cố lâm sàng.
• Việc hoàn tất dữ liệu theo định dạng CDISC, kiểm toán GCP tại Nhật Bản và hồ sơ gốc thử nghiệm điện tử có thể ảnh hưởng đến thời điểm nộp hồ sơ.
• Việc tuyển chọn bệnh nhân cho CardiAMP Heart Failure II vẫn phụ thuộc vào nguồn lực, và ban quản lý không đưa ra con số tổng số bệnh nhân tuyển chọn.
• Các cuộc thảo luận với FDA về tiêu chí chất lượng cuộc sống của thử nghiệm vẫn đang tiếp diễn, tạo ra khả năng thay đổi đề cương hoặc phương pháp thống kê.
• Biên bản cuộc họp chính thức của FDA cho cuộc họp trước nộp hồ sơ của Helix đã bị trễ so với ngày dự kiến 12 tháng 6.
• BioCardia có thể tìm kiếm nguồn vốn bổ sung để đẩy nhanh thử nghiệm xác nhận tại Mỹ, điều này có thể dẫn đến việc tiếp tục pha loãng cổ phần của cổ đông.
• Phê duyệt tại Nhật Bản, hoàn trả chi phí y tế, thiết kế nghiên cứu sau khi lưu hành và thương mại hóa diện rộng hơn vẫn phụ thuộc vào việc thực thi về mặt pháp lý và vận hành.

Điểm tin Q&A với Chuyên gia phân tích

Các chuyên gia phân tích tập trung mạnh vào lộ trình pháp lý và thương mại tại Nhật Bản. Ban quản lý cho biết chỉ định ban đầu cho 20.000 bệnh nhân có thể mở rộng nếu nghiên cứu sau khi lưu hành mang lại trải nghiệm tích cực cho bác sĩ và bệnh nhân.

BioCardia đã so sánh phương pháp tiếp cận tự thân, xâm lấn tối thiểu của CardiAMP với liệu pháp cạnh tranh ReHeart, vốn được ban quản lý mô tả là yêu cầu phẫu thuật cấy ghép và có thể phải ức chế miễn dịch mạn tính. Ban quản lý cũng nhấn mạnh kinh nghiệm lâm sàng lớn hơn của CardiAMP nhưng không đưa ra định hướng về giá cả.

Về mối quan hệ với DMAH, ban quản lý làm rõ rằng BioCardia sẽ trả phí cho tổ chức này đối với các dịch vụ pháp lý và chất lượng. Giấy phép vẫn có thể chuyển nhượng, giúp duy trì tính linh hoạt cho các thỏa thuận cấp phép hoặc phân phối trong tương lai.

Liên quan đến Helix, ban quản lý cho biết vấn đề chính còn vướng mắc là sự rõ ràng về các sửa đổi cần thiết cho hồ sơ nộp De Novo. Mặc dù việc được cấp phép De Novo thành công có thể biến Helix trở thành ống thông đầu tiên được FDA phê duyệt cho đường đưa thuốc này, nhưng nó cũng sẽ cho phép các đối thủ cạnh tranh thực hiện các hồ sơ nộp 510(k) tham chiếu đến giấy phép này.

Toàn văn Biên bản Cuộc họp Báo cáo Kết quả Kinh doanh

Toàn văn cuộc gọi công bố kết quả kinh doanh

Phần trình bày của ban lãnh đạo

Operator

Good day everyone and welcome to the BioCardia Q2 2026 Financial Results and Corporate Update Conference Call. [Operator Instructions] 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 1 hour after the end of today's conference.

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

Miranda Benvenuti

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

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

Forward-looking statements involve risks and other factors that may cause actual results to differ materially from those statements. For more information about these risks, please refer to the risk factors and cautionary statements described in BioCardia's report on Form 10-K filed with the SEC on March 24, 2026, and in our subsequently filed quarterly reports on Form 10-Q. The contents of this call contain time-sensitive information that is accurate only as of today, August 12, 2026. 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. It is now my pleasure to turn the call over to Dr. Peter Altman, BioCardia's President and CEO. Peter, please proceed.

Peter Altman

Thank you, Miranda, and good afternoon to everyone on the call. The highlights of this second quarter have been the positive outcomes of 3 important meetings with regulatory agencies in Japan and the United States on the approvability of our CardiAMP Cell Therapy for the treatment of ischemic heart failure and on the approvability of our Helix transendocardial delivery catheter, which we use in our therapeutic programs. Let's take each of these in turn.

In May, we announced that Japan's Pharmaceutical and Medical Device Agency, or PMDA, provided the consultation record of advice, which supports our advancing to Shonin pre-market regulatory submission for approval of the CardiAMP cell therapy. PMDA noted that the positive outcomes seen in our CardiAMP trials were credible. We have remaining questions to address before and as part of the submission for regulatory approval for this therapy. Specifically, PMDA requested BioCardia demonstrate that enrolled patients were on guideline-directed medical therapy and not eligible for revascularization procedures, both of which were required per the CardiAMP heart failure trial clinical protocol.

They also requested additional details for each incidence of all-cause death, heart transplantation, or left ventricular assist device implantation. PMDA also provided guidelines and requested an initial proposal for further developing the post-marketing study with details on center selection, physician selection, training, and outcomes to be assessed. BioCardia believes these requests will be addressed to PMDA's satisfaction and a post-marketing study to be developed together with PMDA and Japanese medical societies will be straightforward. In addition to answering these questions in great detail, BioCardia is preparing for the Shonin regulatory submission in Japan next quarter.

We are working to complete the electronic trial master file, conduct third-party Japanese good clinical practice audits to PMDA standards, and structure clinical research data in accordance with CDISC standards, which support data consistency, traceability, and regulatory compliance. We are reviewing extensive product documentation internally and expect to soon sign an agreement with a Designated Marketing Authorization Holder, or DMAH, to help finalize the submission as they will act as the local regulatory representative to enable BioCardia sales of CardiAMP cell therapy in Japan. Our expected initial indication will be for approximately 20,000 patients in Japan, with approval approximately 12 months after we complete our Shonin submission.

During this period, we would expect to be educating physicians and finalizing the details of the post-marketing study and its logistics so that we are ready to begin at all centers as soon as reimbursement has been established. Reimbursement in Japan follows Shonin approval and will be determined based on discussions with the Ministry of Health, Labor and Welfare. In Japan, another cell therapy for the same indication was approved in March of this year and has received confirmation that they have been approved for reimbursement in July at $326,000 per treatment. This underscores the need recognized in Japan for such a therapy. That cardiac cell therapy is now a real market in Japan, and the CardiAMP cell therapy has potential to be an enormously valuable therapy.

While these 2 cell therapies are different, we believe the minimally invasive delivery and autologous nature of CardiAMP, coupled with its greater clinical experience, will be attractive to both physicians and their patients. With approval and reimbursement, we would expect adoption to be relatively rapid in the post-marketing study with world-class physician leaders who have already been generous in their support of our efforts.

Although our initial approval is only expected to be for 20,000 patients in Japan, we know that there are approximately 300,000 patients in Japan with ischemic heart failure today. Japan's world-class interventional cardiologists perform 250,000 cardiac catheterization interventions per year. Our enhancing both physician and patient success in the post-marketing study, where there will be reimbursement, is likely to result in a significant business that has a very positive impact on patients and society in Japan.

Shonin approval of CardiAMP cell therapy, which includes the Helix biotherapeutic delivery catheter, may also help other developers of cardiac biologic therapy in Japan. It is worth noting that the 2 publicly traded peer companies in Japan advancing cardiac cell therapies each have market capitalizations of approximately $250 million. And to our knowledge, BioCardia has performed more than 20x as many clinical procedures as both of these firms combined. Each is pursuing a different catheter delivery approach, but we do feel we could be a valuable partner if we have not entered into an exclusive development agreement with a competitive party. We also have important issued patents on delivery in Japan.

In June, we announced the results of our second significant regulatory discussion, our Q-Sub Meeting with FDA's Center for Biologics Evaluation and Research. The meeting minutes from FDA confirmed that the ongoing CardiAMP Heart Failure II trial may support premarket approval for market clearance. This was significant as previously the FDA had not provided the support that 1 trial should be sufficient for approval for this large clinical indication. FDA said the data was interesting, and the message we are hearing is that the CardiAMP Heart Failure II trial is viewed as a confirmatory trial. There were no questions on safety or on delivery in the meeting, and our sense is that for the agency, the confirmatory trial is all about the efficacy of the study.

We are expected to have additional discussions with the agency on the outcome measures in the study, in particular around the third tier of the composite outcome of quality of life. We continue to actively enroll in the CardiAMP Heart Failure II trial to take this study to completion as our confirmatory Phase III study. Four clinical sites have enrolled in the study and are actively recruiting patients. Three additional patients are expected to qualify for the study this month, and 2 are scheduled for their procedures this month. There have been no safety issues of which management is aware. The rate of enrollment here is driven primarily by resources deployed, and we are actively onboarding additional centers.

In May, we had our third regulatory interaction on the De Novo Pre-Submission with FDA for the Helix transendocardial delivery catheter system. FDA agreed that there are 2 pathways for Helix marketing clearance and raised no concerns on Helix safety data, device performance or compatibility with general classes of agents. FDA's preferred route of Helix approval was simultaneous with the approval of the CardiAMP cell therapy system for the treatment of heart failure. FDA also suggested a follow-on pre-submission incorporating agency advice could enable Helix approval via the De Novo pathway.

However, we still don't have the formal meeting minutes from this meeting, which were expected June 12. We did hear from FDA this morning by e-mail that confirms our understanding, and FDA has said that they would have the formal minutes sent to us soon. Our assessment is that the Helix transendocardial delivery catheter system has the best safety, efficiency and ease of use of any catheter of its kind. It takes years to generate this level of data, which we have for more than a dozen clinical trials with approximately 500 patients. We feel it is unlikely that another transendocardial delivery system will be able to have this amount of data within the next 5 years. This catheter has been previously CE marked and approved for market release in Europe.

The key value propositions for the FDA approval of Helix are enhanced partnering for BioCardia around Helix and simpler regulatory submissions for therapeutic approvals, including our CardiAMP cell therapy in heart failure. On the business development front, we have active conversations in the Asia-Pacific region on our cardiovascular therapeutics. While BioCardia fully expects to have boots on the ground in Japan for the post-marketing study, as we transfer all of our experience to Japanese physician centers, the DMAH is transferable, and the broader commercialization will be enhanced by an experienced team.

Our expectation is that any deal has potential to include funding to advance CardiAMP for its second indication for chronic myocardial ischemia and our allogeneic CardiALLO cell therapy for inflammatory heart failure to market clearance as well. Such a deal would enhance our efforts in the United States on all 3 of these programs. Business development on biotherapeutic delivery is also active. We believe we can help many of those in development, particularly for gene-based therapy. There is a great deal more possible with intramyocardial delivery that is not well appreciated by many firms today. These possibilities are enhanced by the potential of Heart3D fusion imaging, which we are working diligently with our respected partner, CART-Tech, to bring to the clinic and to the market as soon as possible.

Today, we believe we have the capital to complete the significant and potentially transformative milestone of PMDA submission of CardiAMP cell therapy. And parallel to the deals we are working to realize, a modest financing with long investors would accelerate the confirmatory CardiAMP Heart Failure II program.

With that, I will now pass the call to David McClung, our CFO, who will review our second quarter 2026 financial results. David?

David McClung

Thank you, Peter, and good afternoon, everyone. I'll now review the highlights of our financial results for the quarter and 6 months ended June 30, 2026. Net cash used in operations during the 3 months ended June 2026, was approximately $1.7 million, increased slightly from the $1.6 million used in the 3 months ended June 2025. Net cash used in operations for the 6 months ended June 2026, of $3.4 million increased slightly from the $3.3 million used in the 6 months ended June 2025. These small increases are primarily due to the timing of supplier payments.

During the second quarter, BioCardia raised net proceeds of approximately $4.9 million under our "At-The-Market" facility at an average price of $1.22 per share. Funding from this facility has a lower cost of capital than traditional financing vehicles and does not involve the issuance of stock warrants or other dilutive securities. The company ended the quarter with cash and cash equivalents totaling $5.4 million (sic) [ $4.1 million ], providing runway into 2027. As we ended the quarter with -- we ended the quarter with $2.7 million in equity, which we believe keeps us compliant now with NASDAQ listing standards.

Total expense decreased by $0.4 million quarter-over-quarter to $1.6 million in the second quarter of 2026 compared to $2.1 million in the same quarter of 2025. For the 6 months ended June 2026, total expense decreased $0.9 million to $3.9 million from $4.8 million. The primary driver of these changes, research and development expense, decreased $0.5 million to $0.9 million in the second quarter of 2026 compared to $1.4 million in the second quarter of 2025. And it decreased $0.8 million to $2.1 million for the 6 months ended June 2026 compared to $2.9 million for that same period in 2025. The decreases relate primarily to the closeout of the CardiAMP Heart Failure Trial, partially offset by expenses for early enrollment in the CardiAMP Heart Failure II Trial and continuing regulatory activities to advance CardiAMP in Japan.

Selling, general, and administrative expenses remain consistent at $0.7 million quarter-over-quarter. For the 6-month period ended June 2026, SG&A decreased slightly to $1.8 million from $1.9 million for the 6 months ended June 2025. Our net loss was $1.6 million for the second quarter of 2026 compared to $2.0 million in the second quarter of 2025. For the 6-month period ended June 2026, our net loss was $3.9 million compared to $4.9 million for that period in 2025. The June SEC proposal to eliminate the baby shelf limitation that constrains access to registered offerings and ATM programs for smaller companies is expected to be beneficial for BioCardia when implemented. It would be great if this were available to BioCardia in Q1 2027.

This concludes management's prepared comments, and we're now ready to take questions from attendees.

Operator

[Operator Instructions] Our first question today comes from Joe Pantginis from H.C. Wainwright.

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Joseph Pantginis

So Peter, a couple things, I guess spanning geographies. Let me go backwards with regard to your prepared comments. So with regard to the pending FDA minutes, obviously, we'll wait to see what they say, but what would you say are the key points that are outstanding?

Peter Altman

Well, hello, Dr. Pantginis. It's great to speak with you, Joe, and thank you for the question. On the first element on this is the nuances for the De Novo submission for Helix. So we have some good clarity on how this has potential to be the first transendocardial biotherapeutic delivery catheter approved by FDA via the De Novo route. And really, the only thing we need clarity on is them to say, yes, that's the tweak for submission. The key issue with FDA is they have a very challenging time approving a delivery system for a biologic for a clinical indication and a route of administration for which no therapeutic has yet been approved. And they've found ways to do that with sort of a skirt around with other firms, with other routes of administrations historically.

Our conversation with them was approaching it head on, saying, look, this is what we're trying to do. This is what the data says. Our expectation is that their internal processes are so rigid that we're going to have to also do a similar end around for our approval for this catheter system. And we have the data to support it and the experience to support it. So it is a De Novo, so there is no other catheter approved with this route of administration. But for those on the call who may not be entirely familiar with the Helix transendocardial catheter, it's based on a design of active fixation pacing leads, which have been used in a million patients. And our data is second to none as published by independent parties.

So I've also -- we've raised with the agency that there are many folks who are pursuing routes of administration for their therapeutic development that either makes no sense or is driven by the great desire to not have an investigational delivery platform woven into their efforts. And so I think we can -- the agency appreciates the value proposition of enabling approval of Helix. As I said in my prepared comments, their first choice would be approval with the CardiAMP cell therapy. That's easy for them. That's easy for them, that's straightforward for them.

But I think they also recognize that by not having an approved delivery system, they're basically hampering the whole field of development. And so for all biologic interventions in cardiology. And my expectation and hope is that the Helix will be the first such product. The downside of a De Novo for BioCardia is that does enable others to then file a 510(k) referencing our De Novo, but our expectation is they'll have to demonstrate some of the performance characteristics that we can demonstrate. And so that will be a pretty significant barrier to entry still.

Joseph Pantginis

Got it. No, I appreciate that color a lot. So 2 more questions, if you don't mind, but going now to focus.

Peter Altman

Please. Welcome, Joe.

Joseph Pantginis

So the first one is 2-pronged. So if you get approval in Japan, you said the initial target market is about 20,000 patients. What efforts or what kind of components would be considered to expand that market, number 1. And the second part is, obviously you mentioned important, I guess, derivative there with regard to ReHeart and the reimbursement that they're getting for about $326,000. I know it's hard to talk about comps sometimes, but maybe you could do a bit of a compare-contrast beyond what your prepared comments said.

Peter Altman

Sure. So, on the 20,000 patients for the initial indication, I think the way that is expanded is by success in this post-marketing study. In Japan today, the patients that we will be treating truly have few options. They don't do a lot of heart transplantation in Japan because they don't like the concept of implantation of other people's organs in another patient. And that's an advantage for our autologous cell therapy. But it also means that left ventricular assist devices, which is an implanted device, also has some reservations by the patient community there. So the key thing to expand that 20,000 patients is to have this post-marketing study go as smoothly as possible to have the physician experience be akin to what it is today in the United States. And we think we can deliver that.

So that's, as we go to Japan, PMDA has said they want us to stay with this program as it advances. And we will definitely be involved as this post-marketing study is initiated and performed. But our sense is, with 250,000 percutaneous coronary intervention procedures done per year, they have a very hungry interventional cardiology community for new therapies, and they have a very large patient population that has no real options. And so our sense is that just by delivering a great experience in this post-marketing study and beginning to educate the physicians that working with PMDA, the indication will expand in short order.

And on the second comment on the -- how does this play with respect to the reimbursement and what are the differences between CardiAMP and the other ReHeart therapy that's approved. Well, today, ReHeart requires surgical implantation, which means that patient's chest has to be opened up as if you were doing a coronary artery bypass procedure or a heart transplantation procedure. And then the cells are laid on the surface of the heart. Because they are not autologous, our expectation is that they will require chronic immunosuppression. And immunosuppression in these patients who have just had cardiac surgery can introduce other issues.

Thirdly is what we're doing with our approach. The data we have is pretty robust. And their data -- we haven't seen their data, but my expectation is they have a total of 8 patients they've treated historically. So I think going in there with our experience and our data become compelling. And so as we look at their reimbursement that gives us a lot of room to have reasonable pricing. And my sense is that our confidence that our pricing will be strong for BioCardia is there completely. If they're reimbursed at that level, that's great for them and we wish their patients every positive. But I think it presents an opportunity where they're educating and they'll be learning over the next year as we will be working through the regulatory process.

And I think on the other side of this, they will be a great peer company. We may also actually, Joe, be able to help them on delivery. I mentioned that they're pursuing a different delivery approach today, but we have a great depth of experience. And so they are a potential partner to us as well as arguably a competitor today with a different cell therapy approach. Our approach, interestingly, is an autologous mononuclear cell preparation. Theirs is an induced pluripotent stem cell preparation where the cells are intended to become cardiomyocytes. But they don't speak of their mechanism of action as one of replacing heart cells, but rather of triggering an angiogenic response. So there's still a lot that we're going to learn about them and that they'll learn about us ahead and hopefully the physician community as well. But I'm pretty confident that CardiAMP has a real role in Japan and can help quite a few patients.

Joseph Pantginis

Thank you, Peter, for that. Can you hear me?

Peter Altman

Yes, I can, Joe.

Joseph Pantginis

Perfect. Because my call actually dropped off. I was able to get back on real quick, so I heard your answers. So I'm glad it was still connected. So my last question is regard to Japan, but more, I guess, expanding the concept. If you do get approved in Japan plus all the discussions and data that you have with Japan, how that might be applicable to additional geographies?

Peter Altman

It's a great question, Joe. Great question. So, Japan is considered a first world country. And I think we've said previously that their inspection of our facilities and their approval of CardiAMP carries weight in other countries around the world. So we have already had conversations around potential relationships in Brazil and United Arab Emirates, and those would arguably follow after we were successful with an approval in Japan. So I think Japan has potential to be much bigger than it is both in Japan, but also in rest of world. And it's tied into some of the harmonization on the inspection work that's been done, but yes, I think it has great potential.

Operator

Our next question comes from James Molloy from Alliance Global Partners.

James Molloy

I want to follow up a little more on Joe Pantginis's question about Japan. Can you walk me through sort of how the Designated Marketing Authorization Holder, how their partnership works? Is it like a traditional partnership you would have with a partner in any other geography where they sell, you get a royalty? Can you break down how that will work? And is that partner -- I think you say in the prepared remarks, hoping to sign them soon. Is that partner guaranteed to be signed? Or what sort of the next steps we should anticipate there?

Peter Altman

So, appreciate the question, Jim. Appreciate you being on the call. The DMAH, the Designated Marketing Authorization Holder, is a nuanced element of submission in Japan. So in this situation, this is actually a party that we contract with who essentially works for BioCardia to represent all of the regulatory and quality issues associated with the CardiAMP Cell Therapy in Japan. This is -- when we -- when you do a distribution deal or a partnership in Japan, oftentimes partners will want to own the authorization. They will want to be the marketing authorization holder because it becomes harder to transfer. But when you have a Designated Marketing Authorization Holder, it is completely transferable. So it does not prevent us from doing distribution deals or licensing deals more likely for these therapies and enable others to advance them.

And it's a party that we've already met with, we're already talking about the specifics, and we're working on budgeting and contracts, but it is a party that BioCardia will pay to support us from a regulatory perspective. And there'll be other parties that are involved on doing the good clinical practice audit of our information to support them so that they have a great deal of confidence as they help us pull together our dossier for the submission, that they will know that their related entities have done this work. And although we are not working with them yet today, they are plugged into this group that we are working with in Japan today. So through that, we have a good relationship and a high confidence that we have the right people that we're going to be working with downstream.

James Molloy

And how does it look, if you sell into this 20,000 patient market, $326,000, $6 billion if that was the math right, opportunity, that's probably a little high. But if you sell $100 million, does the Japanese partner, the DMAH, do they sell that and then they -- then you get a royalty of that? Or how does that work?

Peter Altman

No, actually, we -- yes, so they, they handle really fundamentally the regulatory and quality responsibilities. We can actually go and sell in Japan and work with -- so each and every hospital in Japan has a localized distributor. Even if you are a distributor of products, you still have to go through these localized distributors that take up to 10% of the total product value. But fundamentally, BioCardia at present, our plan is we will be the ones selling CardiAMP for the post-marketing study, which could be anywhere from a couple hundred patients to 1,000 patients, and we're relatively agnostic to that because we're doing substantially the same thing in all instances. And it'll be a great deal easier than what we're doing in CardiAMP trials in the United States because there's no control arm. Every patient is a treated patient, and some of the research science that we've done behind the scenes will not be taking place in Japan.

So it'll be much easier than what we're doing today, and it'll be relatively straightforward. Japan's not an enormous country geographically, so a small team can get around the country quite readily. And we haven't figured out all the logistics and nuances of it yet, but in Japan, I've said previously that when we had our meeting with PMDA, all -- we had a number of really distinguished, wonderful cardiologists in the room, both on our side of the table trying to help us and on PMDA's side of the table as their consultants helping them. And everybody in the room wants to be involved in this post-marketing study, which is a huge advantage because there's real leadership in the Japanese cardiovascular community in that room. So that's always the hardest part is to get the leadership support for advancing a program, and I think we've already got it very, very strongly.

So my sense is we'll work with PMDA and determine exactly how many centers will be in this post-marketing study. And after the submission is in, we'll work with those centers to educate them and train them and get them experience and aware. We'll also be attending Japanese society meetings for both the Japanese Heart Failure Society and the Cardiovascular Interventional Therapeutics Society and enabling physicians to conveniently be exposed to products and the data. And then by the time we have the approval and the reimbursement, all of those centers should be ready to go. And so we'll -- the post-marketing study should happen relatively quickly.

I've said in our corporate presentation or we've said in our corporate presentation, that we expect the adoption profile to be roughly on par or superior to that of what it has been for the percutaneous aortic valves. It's a new intervention for the interventionalists, but it's a therapy that treats a population. In fact, we may have an even more rapid adoption because I would describe our procedure is far more straightforward than the implantation of a valve percutaneously and that the patient population doesn't have the option of surgical delivery. And there's no surgeons who are competing with the interventionalists on those procedures for those patients. So I think the adoption profile will be actually quite compelling.

James Molloy

Great. And the final question for me, you do note that the CardiAMP HF II Trial, 4 sites enrolled in the study, actively recruiting 3 additional patients supposed to go in this month. Any updates on -- is it 4 centers total currently that are enrolling? And any updates on how many patients have enrolled in the trial to date?

Peter Altman

Yes, we're not putting out the total number of patients. The enrollment is not going at blazing speeds. We have these 4 centers all actively enrolling, all have patients in the queue. We have conversations with a number of other centers who want to come on board, and we're working through that process. And it's being done while our clinical team is addressing all of these issues for PMDA. So it will continue to accelerate over time, but really the main effort right now, milestone that we've got as our top priority is getting this PMDA submission in.

So -- and it's happening. We also mentioned -- and I mentioned in the call, that we're having conversations with the FDA on the primary outcome measure. The third tier in our composite. So we have 3 tiers, all-cause mortality, non-fatal cardiac MACE and then the third tier is quality of life, so that every patient contributes to the endpoint. And that third tier has had a lot of criticism in the scientific community in the last 6 months. And the FDA has pushed back on that criticism. But there's ways of handling data that are pretty sophisticated.

And we know that the FDA knows more about how best to handle that endpoint than anybody else on the planet. And so we're going to be engaging with the FDA and hopefully get some guidance from them on exactly how to specify the use of that endpoint within our primary outcome measure. We're also planning on streamlining the trial to really focus on that primary outcome measure, which will also enhance enrollment. And by not having all these other centers on board at this point, it just makes it easier for us to change these little nuances before we roll out more broadly.

Operator

[Operator Instructions]

Our next question comes from Deepankar Roy from Brookline Capital Markets.

Deepankar Roy

We had 2 questions. One about the PMDA's specific outstanding requests. So the question is how much incremental work would this require compiling this documentation? Is this pulling data from already collected? Or would it require like new source data verification? Because we believe this could push the Q4 2026 Shonin submission time line as well.

Peter Altman

Right. So this is -- so with -- so first, Deepankar, thank you for joining the call. I appreciate the question. The nuance here is we feel we've got all of the data that they would like to see pretty ready to us. One of the nuances of it, I think, one of the hardest things is on the guideline-directed medical therapy. So there are a couple of little things that we're chasing. So in our study, guideline-directed medical therapy, for those who work in heart failure, primarily means that they're on, today, the 4 pillars of heart failure therapy care. And those 4 pillars are 4 drugs that all patients should be on. In our trial, unless there's certain reasons one might not be on that -- on those medications.

So in our trial, we had better compliance than any of the other leading trials of the same era that we've looked at. So we definitely have great compliance, physician compliance to prescribing per the guideline-directed medical therapy. So that's the first thing. Very comfortable there.

The second thing is some of the patients, we don't have the exact details on why they weren't on guideline-directed medical therapy. And that is data that we are collecting. I think it totals out of the 115 patients on the 4 drugs, I think there's a total of like 8 patients or so or 9 patients where they each have 1 drug each we have to chase down because there's not the evidence in the record on exactly why they weren't on that. We don't know that we need it, we just know it's part of the PMDA question, so I think that's the only data that we don't already have in hand that we're chasing down and we think it's relatively straightforward to gather.

Deepankar Roy

All right. And my next question is on the DMAH selection. So what is the expected cost structure for that relationship? And would the Shonin submission time line depend on having that relationship before the submission can proceed?

Peter Altman

Tell me I understand the cost relationship. I'm missing. Can you repeat the question?

Deepankar Roy

The cost of having the DMAH...

Peter Altman

DMAH, yes, yes. I thought you said DMA. So it's relatively straightforward. It's not a significant cost. It will be a -- the initial cost -- so we already have a dossier that's pulled together but we've been developing with our regulatory consultants, and we'll separately be doing the good clinical practice audits with another group that our DMAH is close to. And so those 2 pieces will come together, and they're relatively straightforward. Not expensive, and I don't expect any delays. We've already met face-to-face. And we have common friends, so I think it's relatively straightforward.

Deepankar Roy

So the Shonin submission time line would not be affected?

Peter Altman

I don't think it will be affected. We have -- again, we have to complete the efforts to enable the good clinical practice audit. We've got to enable the PMDA to go through the answers to the questions that we've got. And then we need -- we are preparing formal CDISC data as if we were doing an FDA submission for approval. And I think the CDISC data is probably the longest pole in the tent. It hasn't been asked for, but we think it's good just as we put a bow on CardiAMP HF with the idea that it is also going to support what we do for CardiAMP HF II, we're going to put it in that format. So I think the CDISC format is the longest pole in the tent at present.

Operator

And with that being our final question, we'll be turning the floor back over to Dr. Altman for any closing comments.

Peter Altman

Thank you, Jamie. So for all on the call, our efforts advancing our cell-based therapies for ischemic heart failure are showing important benefits for patients through the treatment of microvascular dysfunction. The positive regulatory interactions we've just discussed for approval in Japan and the United States introduce potentially transformative milestones that are meaningful for patients, the physicians who are caring for them, but also for our shareholders. So on behalf of our entire BioCardia team, I thank all for their continued support. You make what we do possible, and I wish you all a great afternoon. Take care.

Operator

The conference has now concluded. We do thank you for attending today's presentation. You may now disconnect your lines.