BioCardia (BCDA) 2026财年第二季度业绩电话会：CardiAMP日本申报及FDA进展

BioCardia（NASDAQ: BCDA）在其2026财年第二季度业绩说明会上，重点介绍了CardiAMP细胞疗法与Helix经心内膜输送导管的监管进展。公司同比减少了费用支出并收窄了净亏损，同时一项按市价发售（ATM）融资将其现金流维持期延长至2027年。

核心要点

• 日本医药品医疗器械综合机构（PMDA）的咨询支持推动CardiAMP细胞疗法迈向Shonin上市前申报。BioCardia表示正准备在下一季度提交申请，预计初始适应症将覆盖约2万名患者。
• FDA会议纪要确认，正在进行的CardiAMP心力衰竭II期试验可支持上市前批准。管理层表示，监管机构将其视为一项主要关注疗效的确认性III期试验。
• 目前共有四个中心正在积极招募CardiAMP心力衰竭II期试验的受试者。预计2026年8月将有另外3名患者符合条件，并已安排2例手术，管理层未发现任何安全问题。
• 第二季度净亏损从上年同期的200万美元收窄至160万美元。总费用从210万美元下降至160万美元，主要是由于研发支出减少。
• BioCardia通过其ATM融资机制以每股1.22美元的平均价格募集了约490万美元的净收益。管理层表示，季度末的现金及现金等价物为410万美元，资金可维持至2027年。
• FDA为Helix确定了两种潜在的获批途径，包括与CardiAMP联合获批以及可能的De Novo途径。虽然正式的会议纪要尚未出炉，但BioCardia表示FDA的一封电子邮件确认了其对讨论内容的理解。

关键财务数据

BioCardia在该季度末拥有270万美元的股东权益，管理层认为这使公司保持符合Nasdaq上市标准。

业务与运营表现

CardiAMP在日本的监管途径

PMDA要求确认试验参与者正在接受指南推荐的药物治疗，并且不适合进行血运重建。它还索取了有关死亡、心脏移植和左心室辅助装置植入的补充信息，以及关于上市后研究的初步方案。

BioCardia表示大部分所需信息现已具备。管理层发现在115名患者中，约有8至9例未能接受四种指南推荐药物之一的原因仍需补充备案。

申报准备工作包括完成电子试验主文档、开展日本药物临床试验质量管理规范（GCP）审计、将临床数据转换为CDISC标准，以及指定一位制造销售上市许可持有人（DMAH）。管理层指出，CDISC数据转换是目前耗时最长的剩余工作流程。

公司预计其在日本的首个适应症将覆盖约2万名患者。管理层表示，视监管审查情况而定，获批可能发生在完成Shonin申报后的约12个月内。医保报销讨论将在获批后展开。

BioCardia引用数据称，日本每年约有300,000名缺血性心力衰竭患者和250,000例心导管介入治疗。公司还指出，针对同一适应症的另一种细胞疗法在2026年7月获得了每例治疗32.6万美元的医保报销。管理层呈报这些数字仅作为CardiAMP潜在市场机遇的背景参考，并不代表BioCardia的产品定价指导。

CardiAMP在美国的心力衰竭II期试验

FDA确认CardiAMP心力衰竭II期试验可支持上市前批准，并可作为心力衰竭适应症的确认性试验。管理层表示，后续讨论将集中在生活质量指标上，该指标是继全因死亡率和非致命性心脏主要不良事件之后，综合主要终点的第三层级。

BioCardia计划围绕主要终点指标简化该研究。管理层表示，由于临床团队正优先处理日本的申报事宜，受试者招募主要受限于现有的资源投入，目前进展较慢。公司正在引入额外的临床试验中心。

Helix输送导管

FDA在预申报会议上未对Helix的安全性、器械性能或与通用类治疗药物的兼容性提出任何异议。监管机构倾向的途径是与CardiAMP联合获批，而随后的预申报则可能支持其取得独立的De Novo准入。

BioCardia表示，Helix已在涉及约500名患者的十几项临床试验中使用，此前已获得欧洲市场上市的CE认证。管理层认为获得FDA准入有助于推动治疗合作，并简化未来的监管申报流程。

商业化与合作伙伴关系

BioCardia正在积极展开涵盖其心血管疗法的亚太区业务拓展谈判。管理层表示，潜在交易将有助于资助用于慢性心肌缺血的CardiAMP以及用于炎症性心力衰竭的CardiALLO细胞疗法，不过目前尚未宣布达成任何协议。

拟定的日本DMAH将提供监管和质量支持，而非担任商业被许可方。BioCardia目前计划在一项可能包含数百至1,000名患者的上市后研究中自行销售CardiAMP。当地医院分销商最多可获得产品价值10%的份额。

管理层还提到了在巴西和阿联酋建立潜在合作关系的初步讨论，这些合作可能会在日本成功获批后推进。

管理层展望

管理层相信现有资金足以完成PMDA申报这一具有潜在变革意义的里程碑。BioCardia还表示，与长期投资者合作进行适度融资可以加速CardiAMP心力衰竭II期项目。

公司预计将在监管审查期间开展日本医生的教育工作并建立上市后研究的物流体系。管理层预期，若CardiAMP获得批准和医保报销，其采用速度将相对较快，但这一预期取决于监管准入、中心就绪情况以及上市后研究的成功执行。

风险与关注事项

• PMDA未决的要求必须在Shonin申报前或作为其一部分予以解决，包括治疗备案文件和详细的临床事件记录。
• CDISC格式数据的完成、日本GCP审计以及电子试验主文档的整理可能会影响提交时间。
• CardiAMP心力衰竭II期试验的受试者招募仍依赖于资源投入，管理层尚未提供总招募人数。
• 与FDA关于该试验生活质量终点的讨论仍在进行中，存在修改方案或统计方法的可能。
• FDA关于Helix预申报会议的正式纪要已被推迟，超出了预期的6月12日。
• BioCardia可能会寻求额外融资以加速美国的确认性试验，这可能会导致股权进一步稀释。
• 日本的批准、医保报销、上市后研究设计以及更广泛的商业化仍受制于监管和运营执行情况。

分析师问答环节亮点

分析师高度关注日本的监管和商业化途径。管理层表示，如果上市后研究带来积极的医生和患者体验，初始覆盖2万名患者的适应症可能会有所拓展。

BioCardia将CardiAMP的微创、自体疗法与竞争对手ReHeart疗法进行了对比，管理层指出后者需要外科手术植入且可能需要长期免疫抑制。管理层还强调了CardiAMP拥有更广泛的临床经验，但未提供定价指导。

关于DMAH合作关系，管理层澄清称BioCardia将向该机构支付监管和质量服务费用。该许可授权仍保持可转让性，从而为未来的许可或许可分销协议保留灵活性。

关于Helix，管理层表示主要未决问题是明确De Novo申报所需的修改。虽然成功获得De Novo准入可以使Helix成为首款获得FDA批准用于此给药途径的导管，但这也将允许竞争对手参考该准入提出510(k)申请。

业绩说明会完整文字实录

---

完整财报电话会议逐字稿

管理层陈述

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.

分析师问答

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.