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spk04: Ladies and gentlemen, thank you for standing by. Good afternoon and welcome to the BioCardia 2021 year-end conference call. At this time, all participants are in a listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star then one on your telephone keypad. To withdraw your question, please press star then two. 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 June 29, 2022. I would now like to turn the call over to Jules Abraham of CoreIR, the company's investor relations firm. Please go ahead.
spk07: Thank you, Andrea. Good afternoon, everyone, and thank you for participating in today's conference call. Joining me today from BioCardio's leadership team are Peter Altman, Ph.D., 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 BioCardio's expectations for future performance or operational results, references to management's intentions, beliefs, projections, outlook, analyses, or current expectations. Such factors include, among others, the inherent uncertainties associated with developing new products or technologies and obtaining regulatory approvals. 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 described in BioCardia's most recently filed periodic reports on Form 10-K, Form 10-Q and Form 8-K, followed with the SEC, particularly the cautionary statement in them. The content of this call contains time-sensitive information that is accurate only as of today, March 29, 2022. Except as required by law, BioCardia disclaims any obligation to publicly update or revise any information to reflect events or circumstances that occur after this call. With that, it's now my pleasure to turn the call over to Peter Alton, Ph.D., the company's president and CEO. Peter, please go ahead.
spk05: Thank you, Jules, and good afternoon to everyone on the call. BioCardia continues to execute in its efforts to advance its meaningful pipeline of cell and cell-derived therapeutics to treat significant cardiovascular and pulmonary diseases. 2021 was a big year for BioCardia's team. We have progressed significantly in the development of all four of our therapeutic candidates based on our autologous and allogenic cell therapy platforms. I'm going to touch on each of these four programs in turn. First, our efforts to complete the CARDI-AMP autologous cell therapy pivotal clinical trials for the indications of heart failure, or BCD01, and chronic myocardial ischemia, or BCD02, have had some nice milestones. These include the receipt of an FDA breakthrough designation, successful data safety monitoring board reviews, a Health Canada no objection letter, and the issuance of a new CMS reimbursement code to support both pivotal cardiac cell therapy clinical trials. The FDA grant of breakthrough designation for the cardiac cell therapy system in heart failure is an enormous accomplishment that has been years in the making. This FDA breakthrough designation means that after the FDA performed an extensive review of all of the available patient-by-patient data, the agency made a formal assessment that the cardiac cell therapy has potential to be better than standard of care for patients with ischemic heart failure. Physicians that care for these patients and the patients themselves can benefit from this independent review by the FDA when they consider the cardiac cell therapy as an option. Although we have said that signals of patient safety and benefit are compelling all along, it adds greatly to the credibility of the therapy for all involved that the FDA's granting of breakthrough designation aligns with this perspective. It also shows that the FDA recognizes that current therapies haven't addressed the enormous need that exists for these patients. The breakthrough designation results in our having significant advantages in our FDA interactions ahead, but most importantly, it is FDA saying that the autologous cell therapy we are advancing for these patients is important. Although the cardiac cell therapy trials are covered by CMS, many private insurers don't follow CMS's lead. As a result, Many patients with heart failure who would qualify for our trial clinically have been excluded from receiving this FDA-designated breakthrough cell therapy because of insurance. Although the breakthrough designation may increase the frequency that private insurers support covering the cardiac cell therapy, we have set out to solve this in three ways. First, After significant sequential filings with both the biologics and the device group at Health Canada, the cardiac cell therapy and heart failure was issued a no-objection letter. This letter allows the trials to advance in Canada, where there are world-class sites we seek to bring into this trial. These clinical leaders are expected to help the program toward completion, as BioCardi will be paying for all patients enrolled without the logistical challenges with respect to private insurance reimbursement that exists in the United States. Second, as sponsor, we are now providing sites with CMS approved coverage of standard clinical costs for patients whose private insurer has declined to cover our investigational FDA designated breakthrough cell therapy for patients with heart failure. This can allow all patients to receive therapy regardless of insurance and is expected to double the number of eligible subjects in the trial in the United States. Third, we sought additional clarity from CMS in the form of a reimbursement code supporting both the treatment and control arm of the CARDI-AMP cell therapy procedure. CM has issued such a new procedure code, C9782, which applies to the CARDI-AMP cell therapy clinical trials. in both indications. We are thankful for the efforts of Health Canada, FDA, and CMS on these initiatives related to the cardiac cell therapy platform, which enhances the attractiveness of the trial and the therapy for centers, physicians, and patients. In 2021 and 2022, we have had three data safety monitoring board reviews of the blinded cardiac heart failure trial results. In all instances, the Data Safety Monitoring Board has said the trial should continue as planned. These initiatives and continued good data, coupled with the waning of COVID-19 at clinical sites throughout the country, are operationally important for completion of the CARDI-AMP autologous cell therapy trials in the United States and in Canada. As the last item on the CARDI-AMP cell therapy, we have initiated a discussion with Japan's Pharmaceutical and medical device agency regarding registration of CARDI-AMP cell therapy based on the quality of our clinical data and the regulatory approvals that exist around all of the elements of the CARDI-AMP cell therapy system in Japan, the United States, and the European Union. Now I'd like to move to our two allogenic cell therapy product candidates, both supported by our allogenic neurokinin-1 receptor-positive culture-expanded mesenchymal stem cell platform, which has progressed greatly over the last year. Our allogenic neurokinin-1 receptor-positive culture-expanded mesenchymal stem cell program in heart failure, which we have designated as BCO3, is targeted to the patients who have been excluded from our lead program due to the nature of their cells. This program has completed the chemistry manufacturing controls validation, and is completing additional pharmacology and toxicology study in animals. Our allogenic program on the same neurokinin-1 receptor-positive cultured expanded mesenchymal cells in acute respiratory distress syndrome has also completed chemistry manufacturing controls validation. It's pharmacology and toxicology studies. And in March of this year, we submitted an IND to the FDA. We expect news. in April from the FDA that this therapy may proceed to treat patients or will be placed on clinical hold with additional items to work through. In summary, we are advancing four therapeutic cell therapy product candidates based on our autologous and our allogenic platforms. The therapeutic delivery systems we have created for our own programs are actively being used by partner programs, and we believe that both patients and our shareholders will benefit from the success of our partners. I will now pass the call to David McClung, our CFO, who will provide some financial perspectives. David. Thank you, Peter.
spk09: Our financials show that we are disciplined and strategic in the use of capital. Revenue for the year ended December 31st, 2021, totaled just over a million dollars compared to $145,000 for the year ended December 31st, 2020. The $870,000 increase was primarily due to collaborations with corporate partners. This financial contribution helps reduce our operating burn, and each of these collaborations has the potential to blossom into a significant collaboration for the company. Net loss for 2021 was $12.6 million, compared to a net loss of $15 million in 2020. Net cash used in operations operating activities in 2021 was only $10.4 billion compared to that cash used in 2020 of $12.4 million. This represents a decrease in overall spending for operations of approximately $2 million through the end of the year, December 31st, 2021, compared to December 31st, 2020. And we ended 2021 with just under $13 billion in cash and equivalents, which we anticipate is sufficient with our other planned activities to carry us through 2022. We have also completed the transition of our laboratories and manufacturing to our new Sunnyvale facility, which has been designed to accommodate our clinical, commercial manufacturing, and office needs for both our cell and cell drive therapies and our device delivery systems. Most of this transition and construction expenses were borne in 2021. And with our new Sunnyvale lease, we have reduced annual facility expense by roughly $500,000 going forward, while significantly enhancing our facilities and capabilities. The two deals we entered into in 2021 have gone well from our perspective. One of these has been extended, and the other is ongoing. We look forward to continuing expanding all of our collaborations as our partners advance and their strategies evolve. I will now pass the call back to Peter for some final thoughts before we open the call to questions. Peter? Thank you, David.
spk05: In closing, you know, our team has worked hard in 2021. While in the middle of a pandemic, we advanced all of our programs. Year over year, we increased our modest revenues by sevenfold and decreased our operating cash burn by 16%. We delivered on strategic initiatives to enhance our manufacturing capabilities and reduce costs. We invested in our team, our technology, and our relationships. We intend to complete the clinical trials before us with scientific rigor, prioritizing patient safety, and with speed, as we believe there are enormous benefits these therapies can bring to patients and their families. Our goals for 2022 include significantly accelerating both autologous cardiome cell therapy clinical programs, treating first patients with our allogenic neurokinin-1 receptor positive mesenchymal stem cell therapy, and growing our partnering and commercial product revenues. We are targeting 2023 to complete enrollment in the heart failure trial and to have the chronic myocardial ischemia trial reach enrollment to support planned adaptive readout. We are now ready to take questions. Operator?
spk04: At this time, we will open the call to questions. Should you wish to ask a question on today's call, you will need to press the star key, then the number one on your telephone. If your question has been answered and you wish to withdraw your request, you may do so by pressing the star key followed by two. If you are using a speakerphone, please pick up your handset before entering your request and speaking on the call. One moment please for the first question. And our first question comes from Kumar Raja of Brookline Capital Markets. Please go ahead.
spk01: Thanks for taking my questions and also congratulations on all the progress including the breakthrough device designation. So first with regard to the four sites in Canada, how soon do you think you will be able to start recruiting patients there? And in the U.S., What are you seeing in terms of the impact in terms of enrollment? How soon do you think we will get to the pace which we had before the COVID pandemic started? Thank you, Kumar.
spk05: I appreciate you joining the call, and I appreciate the question. So first, on sites in Canada, how soon do we expect them to be activated and enrolling? The Canadian team, we have four different sites we're working with in Canada, and we have been working with them throughout the entire back and forth with Health Canada on both the device side at Health Canada and the biologic side. So I don't think it will be very long for us to bring on all four sites in Canada. I think it will take some time after the approval for it to roll through administratively, but we're talking – a matter of, you know, a handful of weeks is how I would think about it. With respect to, in the United States, the impact on enrollment, almost everything we're doing is lined up to really try and reduce barriers for enrollment. And the breakthrough designation that you noted, you know, that addresses, you know, some of the the concerns on, you know, cell therapy and the, there is criticism on cell therapies because of other programs that have gone before. And having the FDA go through our data and say, yes, this is a breakthrough therapy the way you are doing it with the data that you have in these three clinical trials. You know, they went through our phase one, our phase two, and all of the data we have in phase three, as well as the reports from the Data Safety Monitoring Board. So, When management at BioCardius says the data is good, you know, the FDA has concurred to a degree. And so I guess that's my perspective on enrollment. We expected to be coming online much more rapidly with some acceleration. We had a consent I can share today. And that's really where it starts. The process for enrollment begins initially with patient being consented. And after that, they go through a series of tests. As we all know, we have this assay that we perform, the cell potency assay, that essentially identifies the patients who are most likely to respond to therapy. Unfortunately, that inclusion criteria results in us having 30% of those patients eliminated from the potential to be enrolled in the trial. And so, you know, the process for enrollment takes time to move through the inclusion-exclusion, but I can share with all on the call that, you know, COVID does appear to be waning across the nation. All of these regulatory elements that have come to us from FDA, CMS, and Health Canada make this trial easier to perform, easier to enroll, enhance physician comfort, and enhance patient comfort. And the DSMB review is further enhance physician comfort. So all of these pieces are coming together to really push these trials forward.
spk01: Thank you. And maybe you can talk a little bit about the next DSMB review and its expectations, and I'll get back in the line. Thank you.
spk05: Thank you, Kumar. So the next DSMB review is scheduled, I think, for I think the cusp of August, September, I don't know exactly when the date is yet, but we will update folks when we have it. And keep in mind, the DSMB review not only looks at all of the data of the treatment, but all of the follow-up data as well. And so we're working towards, I think that review will hopefully have the increased enrollment we're working towards, as well as some significant follow-up on these patients. And I'll just throw it also, we have crossover patients now. We've had seven crossover patients, those are open-label treatment. So we're going to be able to share data with folks on our crossover patients as they reach the endpoints in their subsequent trial, if you will. So next question.
spk04: The next question comes from Emanuela Branchetti of HC Wainwright & Co. Please go ahead.
spk03: Good afternoon, guys, and thank you for taking my questions. I was wondering, Peter, can you give us a sense on how many patients did not access the trial because of the lack of insurance coverage you were mentioning?
spk05: Yeah, so these are hard numbers to get at, Emanuela. Our expectation is, in this patient demographic, approximately 50% of the patients are Medicare patients. In addition, you know, the reimbursement that Medicare has put forth for us is typically followed by United and Aetna, and they cover about 150 million lives in the United States. So, you know, that's a pretty significant group, but it also, you know, when you're at a center and you have to go and pre-qualify a patient for a therapy, it becomes frustrating if they're not United or Aetna and the insurer denies them. And so the elements that we're putting together that will enhance that is first, you know, we're pointing out that, hey, this is available in Canada. Second, the reimbursement we're putting in place enables us as a sponsor to cover the decline costs of the insurers. And that's from a CMS report. It's an approach that CMS has blessed previously. And then lastly, with the reimbursement code, we're making it clear that we're able to – that both the control arm and the treatment arm are covered. And those three pieces all go together to address pretty much all the questions that any site has. So we're hopeful that we'll see these contribute to enrollment, but senses, you know, we're still going to see heavily – Medicare patients, and hopefully this will bring in the United and Aetna patients as well as other insurers who will follow this because of the breakthrough in part.
spk03: Got it, got it. Thank you. Yeah, maybe, you know, staying on these subjects, you're getting, it seems like you're getting feedback from investigators on the site. Are there any other elements you're working on to optimize the enrollment other than the one you just mentioned?
spk05: There are. We have a policy in place that there's an opinion that just came out at the Office of the Inspector General at Health and Human Services related to our ability to cover the co-pays of patients.
spk03: Got it.
spk05: That's a more esoteric element, but you know, we've hit this with a full court press to address every single issue that we think acts as a barrier to enrollment in this trial. And I think most, if not all of those barriers have been addressed, including the significant one of the waning of COVID.
spk03: Yeah, absolutely. And in fact, you know, my other question was around the COVID situation. And if you can give us a sense of, you know, what you're seeing in different centers and geography if you could give us more color on how the COVID situation is waning.
spk05: Sure. So for folks, there's two pieces to how COVID impacts clinical trials from our perspective. Remember, we only know our trials. And the first is centers can only do elective procedures for certain periods. Patients don't want to go to centers. It's all related to the potential for interactions around COVID. The second, though, is related to staffing. So a lot of folks got used to working from home. Coordinator staffing at different centers has been problematic across the country. And so how we're seeing that change, you know, there's one leading center that's been very quiet for us for a very long time. They now have three patients in the queue. Another center was very quiet, and they just appeared on the radar screen and said, yes, they've just approved the trial internally and they want to get into the trials. And so there's other centers that we're still bringing on board as well. So I think it's happening. As anybody on the call who's hired people know, the staffing process can take time. But I think that piece is evolving in our favor as well.
spk03: Makes sense. Thank you. And, you know, my last question, you know, the relevance of the potency assays has taken center stage recently. It's always been important, obviously, but it's taken center stage recently. I was wondering, for cell therapies, and I was wondering if you can give us a sense of how much dialogue have you had with the FDA regarding your potency assay?
spk05: So this is a cell selection assay in which we are identifying a number of biomarkers that, based on all of the data before us, support that the patient would have a high probability of benefiting. And so really, it's an inclusion-exclusion criteria in our trial. We have called it a cell potency assay, and it does relate to it, but it's different from a cell potency assay under the state of the terms that the agency would look at. And so I think, I know that cell potency assays are center stage for the agency with respect to many of the other advanced cell therapies out there. I think the things that we're doing We do have cell potency assay efforts that we're looking at. We assess not only the viability of cells in each and every procedure, but also their ability to form colony-forming units, and that has been used in other studies in the past as potency assay as well. So I think in total, the selection diagnostic aspect and the things that we're doing from a cell potency assay perspective support what our friends at CBER are looking for. But fundamentally, this is a regulated as a device system, and so it's probably not going to have the same criteria because we can't generate cell potency for a patient that's already been treated. It's something that we're doing after the patient is treated in our core laboratories.
spk03: Understood. Thank you very much.
spk05: However, just one more step, Emanuela, but for our allogenic programs, we absolutely will have a cell potency assay, and it will be derived from some of the knowledge we have on our lead programs and all of the work we've done on colony-forming units with respect to these expanded mononuclear cells in the lead program. They also feed into what we're doing on the neurokinin-1 allogenic cells in programs three and four.
spk03: Understood, thanks.
spk05: Appreciate the question.
spk04: The next question comes from Michael Okunovich of Maxim Group. Please go ahead.
spk02: Hey, thanks for taking my question. So I guess first I'd like to ask something just in the context of measles blast discussions with regulators. regarding their cell therapy and heart failure, specifically with moving into ischemic and diabetic patients, where they saw the greatest benefit in subgroup analyses. Can this be viewed as validating of your targeting of ischemic heart failure patients with BCDA-01, representing the right patient for a cell therapy product?
spk05: Well, Michael, so first, I want to acknowledge that mesoblast data at three-year follow-up in the New York Heart Association Class 2 patients and the ischemic etiology, as we've looked at the data sets that they've shared publicly, it's good data. Now, that's exciting. That's a signal that's stronger than any of the other pivotal trials we've seen for the latest heart failure therapies that are out there. it is a different therapy than we are advancing, and it uses a different delivery platform. However, the patients that they say responded greater in their trials does line up substantially with the patients we're targeting in our trials. So they're focusing on New York Heart Association Class 2, they've said, going forward. In our trial, I believe, I don't know if I'm allowed to say the numbers, but A large portion of the patients from New York Heart Association Class 2, the delta between what they're doing and what we're doing is they require hospitalization in the six months prior to treatment, and they require a high NT-proBNP level, which is a measure of the status of the heart failure. We don't require either of those. So I think we're leaning into patients who are less sick, which is what they've said they're going to do going forward. And the reason we've leaned in these patients all along is, The CAR-DM cell therapy is not an event-driven trial. We're not looking for the sickest of the sickest because we're big believers that the art of clinical trial design is optimizing signal to noise. And we think in these New York Heart Association class, two patients and the threes that are not so significantly sick that they have high NT-proBNP and they recently had a MACE event such as a hospitalization are the right patients to go after. And so they are saying, yes, Those are the patients they're going to go after going forward. It's too much, though, for us to rely on their data because, again, they're delivering a different cell therapy. They're delivering it with a different delivery system. But it is an intramyocardial bone marrow-derived cell therapy, which is what ours is. So I'm trying to support kind of what you're saying but also point to the limitations, which are significant.
spk02: Yeah, no, thank you. I appreciate the additional color. I'd also like to see if you could remind us of what the biomarkers in your cell selection potency assay are selecting for on a mechanistic level.
spk05: So we have a number of biomarkers we're looking at. The only one we detail publicly is the CD34 cell counts. And this is a marker that's been used in other clinical trials in the past. Just this past in 2021, we presented data on the dosage we're achieving in the current pivotal trial in heart failure, and the dosage we're able to achieve with the combination of the cell potency assay selecting patients with high CD34, the cell processing platform and its efficiency on only a 60cc marrow aspirate, and the efficiency of delivery is actually higher than every major cell therapy trial that has shown signs of efficacy based on CD34 cells. So I think it's promising from that perspective. The mechanisms that folks look to on CD34 is one often of androgenesis and enhanced microvascular elements. That may not be the only element that's going on. I mean, again, we're treating ischemic heart failure patients, which means there are diseases caused by ischemia but we are not treating actively ischemic patients as our focus. And that's an important delineation because we were the first group to say we want ischemic etiology and heart failure, and we don't need for them to be actively ischemic. So there's other mechanisms of action probably woven into this as well.
spk02: All right, thank you. And then just one last one. With the addition of you know, these Canadian trial sites coming online, do you think that the different reimbursement environment could make that easier to enroll than the U.S., or given the developments with CNS, they should be about equally as easy?
spk05: That's a great question. We don't know is the answer. We started the process in Canada in part because We know some great KOLs there, key opinion leaders who've done enormous work in this space historically and been involved in other trials. But there was also an element that it becomes a test case without having the reimbursement issues. And so we will have to pay for everything in Canada. It's not as expensive to do clinical trials in Canada, although the paperwork of going through two separate agencies for the approval process was daunting. Our expectation is that Canada enables us to test that question without necessarily sacrificing the value proposition of our reimbursement for both trials in the United States. And in addition to working on Health Canada, we were taking a belt and suspenders approach and we've worked through the nuances of what was causing sites some difficulties. And so we think that our friends at CMS have done, made good efforts to help us to get some of those issues resolved, and we think that that's going to roll through the system well going forward. So it will be interesting to see the impact of these different elements. At the end of the day, You know, we won't be able to tease out exactly which element is resulting in the enhanced enrollment at which site, but it's a sign that we at BioCard are constantly listening to our clinical sites and trying to understand what is a problem for them, how can we make this trial easier, provide more support for it from a scientific reimbursement perspective, while we also, you know, optimize the value propositions we have of the Medicare reimbursement.
spk02: All right, thank you very much. I appreciate you taking the time to answer my question.
spk05: Thank you, Michael. I appreciate it.
spk04: The next question comes from James Malloy of Alliance Global Partners. Please go ahead.
spk08: Thank you for taking my question. And thank you very much for all the insight into the expectations on the trial. On 01, you guys gave a guidance for expectations for another DSMB here, I think, fourth quarter. Any thoughts or is there a way to get an idea of when you look at the rapid trial, given how enrollment is getting better with COVID kind of waning?
spk05: So, yes. So, Jim, we're targeting, I think, third quarter for the DSMB review and BCD01, which is the cardiac cell therapy for ischemic heart failure. And we're targeting completing enrollment of that lead program in 2023. We're also targeting completion of enrollment, um, for the adaptive readout in the same therapy, but for the indication of chronic myocardial ischemia, um, in the same year. So 2023 is going to be a very big year for us. And, you know, I can't provide any more specificity on it than that. We'll find out, we will report out the enrollment as we go and, um, But, you know, as we budget things, we're budgeting for success here, so we are pushing hard on the enrollment activities today. And these are not the only things we're doing. The things that have happened in 2021 and subsequent to 2021, based on the efforts in 2021, there's a lot going on to make this trial be completed as soon as possible.
spk08: Excellent. And maybe how does the environment has obviously been a challenging environment the first half of the year. biotech across the board. Has the environment for potential acquisitions or partnerships changed, gotten more or less active, given what's been going on with some of the stocks, really getting down to dramatically low levels?
spk05: You know, Jim, I can only speak to the business development activities that we have underway. And those are not really tied into... M&A, although there is licensing on a couple elements. I'll recap them briefly. One of the efforts we have ongoing is identifying a partner for CardiAmp outside the United States, specifically in Japan. That would involve a partnership, not an acquisition, and I can share that there is interest in light of all the things that I've just shared that have been taking place. In our 10-K, we've detailed that we are meeting with PMDA in the near future. And so we'll be having conversations with them in parallel to having conversations with potential partners to help advance the cardiac cell therapy in Japan, where there's a million patients there with heart failure, and it's a great unmet need. And I also note that the only cardiac cell therapy that's approved that we're aware of is in Japan. And it has a reimbursement. This is the heart sheet by Tarumo. It has a reimbursement at, I think, $124,000 U.S. dollars, yen equivalent. So there's a support for regenerative medicine in Japan that also will hopefully put some wind behind the therapies we're advancing. So that's one. The second level of partnering that we're involved in is around our biotherapeutic delivery platforms. So today we actually feel we have the safest, most efficient at delivery and easiest to use delivery system that's appropriate for cell gene and protein delivery to the heart. And so all of the things we've solved are available for partners. And so we're trying to move more towards significant corporate partnerships and We would like to enable other significant entities to have their own delivery system. Even though it would compete with us and potentially be cannibalistic, our perspective is that these therapies will ultimately compete. And if our shareholders can benefit from both therapies, great. If patients can benefit from all that we've learned on delivery, great. So that's an area that we're very active in today. And that reflects the two deals we did in 2021. And the last area is in actually monetizing assets that we've developed that don't fit our core initiatives. And one of those assets is our Avance transeptal sheet, which is an FDA-cleared product. It's based on technology that is elegant. We use it, the technology, in research. are what we call our MorphDNA product, which is part of our biotherapeutic delivery systems. But the Avance addresses an existing market in the United States that's extremely competitive of around 500,000 procedures a year. And we're having conversations around identifying a partner to monetize that with the idea that we will enable them to have that technology and that product And at the same time, the dollars will come in and feed some of the other initiatives here at BioCardia. So those are really the three types of efforts we have. Of note, the international partnering and the Avance monetization activities, those can only be done with one partner. But the biotherapeutic delivery activities, you know, we can work with a number of partners. And we treat our partner information differently. It's strictly confidential. I think we have a very good relationship and reputation amongst our current and past partners. And sometimes programs don't go forward. It has nothing to do with delivery. It's often related to the therapy or funding for the therapy or other elements. But the programs last year are still ongoing, and we're optimistic that we'll be doing some nice partnering in the year ahead.
spk08: Great. Thank you for taking the questions.
spk05: Appreciate it, Jim.
spk04: The next question comes from Jason Colbert of Dawson James. Please go ahead.
spk06: Hi, Peter. Thank you. Most of my questions have been answered, but I'd like to talk a little bit about the endpoint of the trial. And can you help me understand kind of what the critical measures are associated? I think it's Finkelstein-Schoenfeld hierarchical analysis. What are the key critical aspects there, and what other significant drugs have been approved using that endpoint?
spk05: So, Jason, appreciate the question, and it is a good one. The Finkelstein-Schoenfeld three-tier composite endpoint that we're using in the trial is a hierarchical endpoint that includes mortality, major adverse cardiac events, and then functional capacity as measured by six-minute walk. There have been a number of other heart failure programs that have been advanced with that as an endpoint. And I think more important than identifying a specific other drug that's been approved, I would say the FDA recommended this endpoint to us and specifically guided us to use this endpoint. And I may have shared in the past, but this endpoint, we had something that was a little bit more sophisticated from a statistics perspective, but the agency did us a great service in nudging us to the Finkelstein-Schonfeld three-tier because it's something that clinicians understand. And what we had was something that was difficult to describe, even though it was probably more sophisticated and substantially equivalent. By moving it towards the Finkelstein-Schonfeld, we wind up with an endpoint that everybody understands and accepts because the way it works is, is the therapy better for the patient? So if a patient dies, they're in the worst rank. We want patients to live first and foremost. If there's a MACE event, that's the next rank. But if there's no death and no MACE in a patient, how do you know whether they're better or not? And the third tier of the functional capacity as measured by six-minute walk is how this plays out. And the results we have so far are good. Six-minute walk is a non-trivial endpoint. It can be subject to manipulation by a clinical trial coordinator who's cheering a patient on one day and not cheering the patient on the next day. We've been very disciplined in rolling this out, working with leadership at NHLBI related to six-minute walk, excuse me, National Heart, Lung, Blood Institute related to six-minute walk. Our sense is we're doing it as rigorously as we can do it, and combined, it's an endpoint that the FDA has effectively blessed by recommending it to us in the modification. And does that answer all your questions, or is there another element there that I may be missing?
spk06: Well, I'd like to just pick up on something you said, which is the data so far is pretty good. Can you expand upon that?
spk05: Well, so I don't – we don't see any of the data in the blinded – But if you look at, you know, published results so far for our, you know, our actually worse data is in our phase one where we had a 10% mortality rate at three years. And I note that 10% at three years. If you look at all of the data coming out of the very large drug trials, the mortality rates at three years are roughly 21%. I note that if you look at mesoblast data in their phase two, you know, I think they are under a 10% mortality at three years. So that's in the New York Heart Association class two. So, you know, our data in phase two is we had no patients lost at one-year follow-up. And in the phase three, I can only share the one-year data that was published, but we have no patients lost in that rolling cohort of the phase three trial.
spk06: Okay, sure, that makes sense. So it's encouraging, that's what you're saying.
spk05: Yeah, so again, these are very sick patients, and the fact that they're doing well in those metrics is great, but if you look at the other elements of those data sets, you know, the phase one, we saw improvement in exercise tolerance. We saw improvement in heart function. Phase two, we saw improvement in exercise tolerance. We saw improvement in heart function. Phase three, we see improvement in exercise tolerance, we see improvement in heart function, we see improvement in quality of life, it all holds together. So it's not as if we have a data set that doesn't include one element of those benefits. And these data sets are complicated. So we're hopeful if we repeat the results we had in phase two, we have potentially a new therapy for these patients. And these therapies that we're advancing, it's a one-time treatment of concentrating the patient's own cells around the damaged tissue in the heart. And so it's from a safety perspective, at the end of a procedure, if you get the safety check at the end of the procedure, we feel very good at the end of the day. There's no, you know, with normal drug trials, there's compartmentalization, and drugs get localized in the adipose tissue, and you can have toxicity events downstream. With other device therapies where you have an implant, you know, implants can erode. They can become infected. So we don't have any of those long-term safety ramifications in what we're doing in the CAR-D-AMP cell therapy programs. There are procedural risks, and, again, there are also risks for the cells that haven't been fully adjudicated. This is not an approved therapy, but as we think about it, we think that the safety profile is pretty compelling.
spk09: Thanks, Peter.
spk05: Thank you, Jason. Appreciate you being on the call.
spk04: This concludes our question and answer session. I would like to turn the conference back over to Peter Altman for any closing remarks.
spk05: Thank you, Andrea. I want to thank all of you participating on today's call and for your interest in biocardia. We look forward to sharing our continued progress. Thanks. Stay healthy. Be kind. And have a wonderful day.
spk04: The conference is now concluded. Thank you for attending today's presentation and you may now disconnect.
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