BioCardia, Inc.

Ladies and gentlemen, thank you for standing by. Good afternoon, and welcome to the BioCardia 2022 year-end conference call. At this time, all participants are in a listen-only mode, and should you need any assistance during the call, 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 a 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 29th, 2023. I would now like to turn the call over to Miranda Pato of BioCardia Investor Relations. Please go ahead, Miranda.

Good afternoon, and thank you for participating in today's conference call. Joining me from BioCardio's leadership team are Peter Altman, PhD, 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 and operational results, references to management's intentions, beliefs, projections, outlook, analyses, and current expectations. Such factors include, among others, the inherent uncertainties associated with developing new products, 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 and cautionary statements described in BioCardio's report on Form 10-K filed with the SEC this morning. The content of this time call contains time-sensitive information that is accurate only as of today, March 29, 2023. Except as required by law, the complaint 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 Peter Altman, PhD, BioCardius President and CEO. Peter, please go ahead.

Thank you, Miranda. And good afternoon to everyone on the call. We've had a great fiscal year in 2022. But before we get into the details, I always like to take a few moments and review what we are doing and why we are doing it. Biocardius efforts are focused on advancing two cell therapy platforms to treat significant unmet cardiovascular and pulmonary diseases. Specifically, ischemic heart failure, chronic myocardial ischemia, and acute respiratory distress syndrome. All of our cell-based therapies involve local delivery of the therapeutic to the heart or lungs, where we intend them to act locally. In the heart, our own proprietary Helix minimally invasive delivery system is used to deliver the cells to target regions of damage. For the lungs, we intend to use intravenous delivery, which will result in the investigational cells being localized in the small blood vessels of the lungs. Local delivery of therapeutics to the target location where their action is desired maximizes their effective dosage within the tissues where delivered and minimizes potential negative effects remote from the target tissues. Heart failure is the first problem we are going after. Heart failure is an enormous unmet need that affects more than 26 million people worldwide. The latest blockbuster drugs in ischemic heart failure of reduced ejection fraction provide great benefits to patients but don't appear to have much of an impact on mortality. Patients in the published results of the pivotal trials for these new drugs have a cardiac mortality of roughly 7% and an all-cause mortality of 10% per year, regardless of whether they were treated or controlled patients. This data makes clear that heart failure is still a problem in great need of new therapeutic solutions. Our autologous mononuclear cell therapy platform which we call cardiac cell therapy, is being advanced into cardiac clinical indications. In preclinical studies, cardiac mononuclear cell therapy has been shown to release proteins locally within the tissue to facilitate cardiac recovery after heart damage with improvements in heart perfusion and contractile function. All known previous clinical studies, similar to the approach we are taking in our two lead cardiac cell therapy programs, have shown patient benefits on average. In some of these studies, including our own, the benefits have been remarkable. The FDA has supported this promise by granting breakthrough device designation to CARDI-AMP cell therapy in the indication of ischemic heart failure reduced ejection fraction. Advancing this and our other three therapeutic candidates is what we are all about. Our efforts to complete the CARDI-AMP autologous cell therapy pivotal clinical trials for the indications of heart failure, or BCD-A01, and chronic myocardial ischemia, or BCD-A02, are furthest along clinically, with an estimated combined 1.6 million patients in a reachable U.S. market. The Cardiac Cell Therapy Heart Failure Trial, or BCD-A01, is a Phase III 260-patient randomized controlled clinical study intended to provide the primary data to support safety and efficacy in pursuit of market clearance. Clinical investigators at 22 active partner sites across the United States and Canada have enrolled 119 patients today with 10 additional control patients having crossed over to receive therapy. We currently have eight active consents and 15 additional patients in the pre-consent queue. There is clearly increased momentum here. potentially driven by the clinical data. Data published to date has shown improved functional capacity and quality of life in treated patients. Earlier this month, clinical investigators presented blinded echocardiography data from the Yale University Core Laboratory from the open-label Rowland cohort of the cardiac heart failure trial at the annual meeting of the American College of Cardiology. Results presented showed a 35% improvement in left ventricular ejection fraction as compared to baseline, with 100% survival at two-year follow-up. These are remarkable results in this population, and the scientific poster presentation is available on our website if you are interested. The Independent Data Safety Monitoring Board completed both its fifth and sixth prespecified data reviews in 2022. including a risk-benefit assessment with more than 100 patients past the primary clinical readout. Following the review, the Data Safety Monitoring Board indicated that it had no significant safety concerns and recommended that the study continue as designed. The Data Safety Monitoring Board also supported the company implementing an adaptive statistical analysis plan, which could enable an early readout for study treatment efficacies. Working with distinguished consultants, including former FDA leaders and a respected statistical consulting group, we have developed and submitted a supplement with a proposed adaptive statistical analysis plan to the FDA in February 2023. We have a meeting scheduled to discuss the FDA's comments on March 31, 2023, which is this Friday. The next pre-specified formal data safety monitoring board review is anticipated in the second quarter of 2023, and we believe it is likely we will be able to have the adaptive statistical analysis plan in place for the meeting. The specific details of any potential adaptive statistical analysis plan, in combination with any modifications to the Data Safety Monitoring Board charter, will dictate what happens at the next subsequent Data Safety Monitoring Board reviews. As the CAR-DM cell therapy trial on heart failure was over 90% powered for success with a range of 86 to 126 patients, there is potential that the trial could meet its primary efficacy endpoint on the patients that have been enrolled to date. However, when the Data Safety Monitoring Board next meets, they may also recommend that the trial continue per plan, be stopped for safety, or be stopped for futility if the data does not support that achieving the primary endpoint is possible. Our second therapeutic program with the same autologous cell therapy for the treatment of chronic myocardial ischemia with refractory angina, or BCO2. The CARDIAMP chronic myocardial ischemia trial is a phase three multi-center, randomized, double-blinded, controlled study of up to 343 patients at up to 40 clinical sites. The phase three pivotal trial is also designed to provide the primary support for the safety and efficacy of the CARDI-AMP cell therapy system for this indication. It uses many of the same novel aspects of the CARDI-AMP heart failure trial and is expected to leverage our experience and investment in the heart failure trial. This program benefits from the 2022 Center for Medicaid and Medicare Services, or CMS, reimbursement for both treatment and control procedures at up to $20,000 for both trials. A significant number of patients to complete the open label rolling cohort, excuse me, a sufficient number of patients to complete the open label rolling cohort have already been consented. It is anticipated this trial will report out the open label rolling results in 2023. Trial design modifications to enhance enrollment efficiency for the randomized cohort are being planned for submission to FDA. As we've shared previously in July, we had our second consultation with Japan's Pharmaceutical and Medical Device Agency regarding registration of cardiac cell therapy for ischemic heart failure. After working with distinguished physician leaders, BioCard expects to complete its formal submission for Japanese approval in the second quarter of 2023. As I've mentioned in previous calls, Japanese researchers established the building blocks to this therapy many years ago. The therapeutic approach we are pursuing was first studied in the preclinical model by physician scientists in Yokohama. This early work was performed in parallel to another Japanese vascular biology scientist who identified important aspects of bone marrow-derived mononuclear cells and tissue repair. Their early efforts underlie our cardiac cell therapy, and we hope to be able to provide this therapy to the many in Japan who could benefit from it. Now I'd like to move to our two allogeneic cell therapy product candidates. based on our allogeneic neurokinin-1 receptor-positive mesenchymal stem cell platform. These are off-the-shelf cells from young healthy donors intended to be expanded to produce many doses for many patients. The neurokinin-1 receptor-positive mesenchymal stem cells are particularly interesting as neurokinin-1 is the primary receptor for substance P, an important neuropeptide mediator of inflammation which plays a central role in both heart failure and regenerative processes following myocardial injury. I encourage listeners to Google substance P to understand why advancing the mesenchymal stem cells that bind to this neuropeptide is exciting. Our allogeneic mesenchymal stem cell program in ischemic etiology heart failure of reduced ejection fraction is designated as BCD03. This is a phase one, two, multi-center, randomized, double-blind, controlled study of up to 69 patients designed to assess the safety and efficacy of this therapeutic candidate. The investigational new drug application was approved by the FDA in December 2022. The trial is designed for patients with New York Heart Association class two and three ischemic heart failure of reduced ejection fraction whose own cell composition, makes them ineligible for the company's phase three cardiac heart failure trial studying autologous cell therapy or BCDL1. Clinical grade allogeneic cells for this program have been manufactured in our Sunnyvale facility and are ready for use. These cells will be delivered under the protocol with our proprietary minimally invasive biotherapeutic delivery system. We expect to begin enrolling patients in the second quarter of 2023. Our allogeneic mesenchymal stem cell program in patients recovering from acute respiratory distress syndrome secondary to COVID, which we have designated BCO4, was approved by the FDA in April 2022 to treat patients. The trial is a phase one multi-center open label study of up to nine patients. While the number of patients with COVID-induced ARDS has decreased, ARDS unrelated to COVID is still significantly impacting patients. The company intends to work with the FDA to modify the study eligibility criteria to include these patients. In this trial, increasing dosages of the cells will initially be evaluated, and then the optimal dose will be taken to Phase II in a randomized study in adult patients recovering from ARDS. This therapy is intended to address the enormous unmet need to sustain local and systemic inflammation after a patient is taken off respiratory support. with the goals of accelerating recovery, enhancing survival, and reducing both relapse and rehospitalization. Clinical-grade cells are also ready for use in this study. The ARCH trial is expected to commence following the initiation of BCA03, studying the allogeneic mesenchymal stem cells for heart failure-reduced ejection fraction. In summary, we are advancing four clinical-stage therapeutic product candidates that address important unmet cardiac and pulmonary diseases, based on our autologous and our allogeneic cell therapy platforms. From these therapeutic development efforts, we now have four active business development initiatives. First is partnering our cardiac cell therapy platform internationally. Second is licensing out our clinical stage neurokinin-1 receptor-positive mesenchymal stem cell platform for other clinical indications, which have shown promise with other mesenchymal stem cell preparations. Third, is licensing our catheter-based biotherapeutic delivery system for cell, gene, and protein therapy candidates to the heart, such as in the Blue Rock relationship we began last year. And fourth is monetizing our Avance transeptal introducer sheath product. Our steerable sheath assets were initially developed to help navigate our biotherapeutic delivery systems, and we use these products in every cardiac cell therapy procedure today. There have been recent acquisitions of established product offerings similar to our Avance product offering for between $70 million to $1.5 billion. Our Avance is our first FDA-approved offering for this transeptal indication and incorporates patented technology that may provide compelling benefits. Next week, we expect to announce the issuance of two additional new patents related to these steerable sheath assets. We are also looking forward to announcing an additional patent issuance related to our neurokinin-1 receptor-positive mesenchymal stem cells that has been allowed, and a patent that we expect soon to be allowed related to our Helix biotherapeutic delivery platform. I will now pass the call to David McClung, our CFO, who will review our 2022 financial results.

David? Thanks, Peter, and good afternoon, everyone. Today, I'll review our financial results for the year ended December 31, 2022. Revenues for the fiscal year 2022 increased to $1.4 million from $1.0 million in fiscal year 2021, primarily due to the increased revenue from new and existing collaborative partners, including the Blue Rock relationship Peter just mentioned. Our revenues today contribute to reducing our burn rate, and they have the potential to develop into meaningful licensing and royalty revenues if the underlying therapies prove to be effective and commercialized. The company continues to manage its financial resources carefully and economically. Total operating expenses were down approximately $300,000 year over year, $13.3 million in 2022 compared to $13.6 million in 2021. R&D expenses increased modestly to 8.8 million in 2022 compared to 8.6 million in 2021, primarily due to increased expenses in support of the cardiac assault therapy heart failure trial, particularly as our clinical sites continue to emerge from the effects of the pandemic. Selling general and administrative expenses decreased to 4.4 million in 2022 versus 5.1 million in 2021, even as we established and licensed our new cell therapy and device manufacturing facility. The decrease was primarily due to reduced professional service fees and lower stock compensation expense. Our net loss in 2022 was $11.9 million compared to a net loss of $12.6 million in 2021. And cash use and operations totaled $10.6 million in 2022, comparable to the $10.6 million in 2021. Alcardia ended the year with cash and cash equivalents totaling $7.4 million, which provides runaway into the third quarter without additional capital or funding from business development activities. This concludes management's remarks, and we're happy to take questions.

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 followed by the number 1 on your telephone keypad. If your question has been answered and you wish to withdraw your request, you may do so by pressing the star key followed by 2. If you are using a speakerphone, please pick up your handset before pressing the keys. One moment please for the first question. And our first question here comes from Joe Pangenis with HC Wainwright. Please go ahead.

Hey, guys, good afternoon. Thanks for taking the question. I have three questions, one of which hopefully will be based on getting some, I believe, important perspectives. So maybe I'll start with that one. So, Peter, when we look at the blinded echo data for the roll-in at ACC, you know, 35% overall improvement in LVEF,

um maybe can you give the perspective of how that would compare you know to the inclusion criteria of the patient population and how that would relate to their natural history yeah joe thank you for yeah no joe great question and uh and that's something that it always makes it difficult to compare one trial to another but in our population as we look at the data sets we're looking at new york heart association class two And three, ischemic etiology, heart failure with reduced ejection fraction patients. Ejection fraction is also 20% to 40% in these patients. So this lines up well with what has been done in some of the other larger trials where, as the data I shared, a mortality of cardiac mortality of 7% to 8% and all-cause mortality of 10% per year in these patients. Now, there are things that we're doing that could actually wind up excluding patients who are sicker. So, for example, the patients we're treating have to be eligible for cardiac catheterization. And that could considerably tilt us towards a healthier population. In addition, our cell population analysis selects patients who have really compelling potential for the autologous therapy. And there is potential that having superior autologous or patient's own cells could have an impact on their long-term prognosis. But, you know, it's 100% survival in a patient population that we should have seen a 10% mortality per year. And at the same time, we're seeing improvements in a patient population group that typically deteriorates. So we recognize it's a small data set. but it's completely in line with what we saw in phase one and in phase two, where patients approved across, you know, many metrics. And so the question that you pose is, how does this compare to a true placebo-controlled population or a controlled population? And that's what we're going to find out in this trial.

Great. No, that's helpful. Thank you. And then I guess, you know, especially when you talk about cost management right now, expense management and you have multiple ongoing studies and what have you I want to focus on manufacturing with regard to you know your ability to serve you know your larger studies right now and your additional initiatives versus you know do you have any immediate term or nearer term needs with regard to manufacturing capacity so right now

I actually think that our current manufacturing capabilities will be fine for all four clinical trials, for both the autologous BCO1 and BCO2 and the allogeneic BCDA03 and BCDA04. We have made the decision to own it and control it, so in our new facility that David mentioned, we are certified here for drug manufacturing as well as medical device manufacturing for those for the delivery of those drugs with our delivery systems. So our partnering with others could result in greater need, but most of the folks we're partnering with are not as far advanced as we are in the clinic. So they're aspiring to do a 10 patient trial while we're working towards a 343 patient trial in BCAO2. So I also note that as B-FETO2 enrollment accelerates, we can handle the manufacturing here in our facility. We're currently only running one shift in both of our capabilities, and we have rooms, for example, on the cell manufacturing. We can add incubators. We can do things to expand out our capabilities.

Got it. Very helpful. And then my last question, with regard to the O1 study and heart failure, Obviously, right now, based on your comments and what we've obviously been discussing for a while, a lot of moving parts. So, you know, a lot depends on what's coming up from your upcoming discussions with the FDA. So I guess I'd ask right now what we could know or would already be in place, the upcoming interim analysis. It is going to essentially look at everything, futility, safety, efficacy, and is there or what is the alpha spend around that or how would it impact the current statistical analysis plan ahead of any changes from an adaptive design?

Yeah, that's a great question, and that's, you know, one of the great challenges of these adaptive statistical analysis plans. I think the alpha spend is going to be very low, and for folks that don't have a Ph.D. on the call like Joe does, you know, the alpha spend is, you know, what – level of the p-value are you going to lose in order to have statistical significance? So right now, you know, as we're regulated as a device system for this autologous therapy, we're expecting to only have to achieve a p-value of less than 0.05 in one large well-controlled study. Again, the agency will look at the totality of data. We won't know what the alpha spend is until we get the adaptive statistical analysis plan reviewed and blessed by the agency. As I've shared, that is imminent. We have a call scheduled with the agency for this Friday. But as I'm sure you can appreciate, Joe, and others, it's typically a back and forth. We want to minimize the amount of alpha that we do spend, the amount of our, you know, power that we're going to lose. And so I'd much rather be facing a p-value of 0.05 than one of 0.001 because we spent all the alpha. But I think we're going to wind up in a good place. There's a lot of experienced folks that we're working with on the design of this adaptive statistical analysis plan. And we've brought in some pretty high-profile regulatory consultants to help the agency to appreciate this. I also note that in this trial, you know, we now have breakthrough designation for this lead program. And breakthrough designation can enable us to collect additional safety data on the other side of presenting results that meet the primary endpoint in the trial. And I think that's the key thing for, you know, when you're going after an approval, and this is why we brought in some very experienced folks. You know, you want to make sure. Our job here is not to get a success in the trial. Our job here is to get cardiac cell therapy approved and available for patients. And so we want to be very thoughtful in this process on maximizing our probability of technical success, but also near-term commercial success.

I understand. Thanks a lot for the color.

No, great questions, Joe. I really appreciate them.

And our next question will come from Tamar Raja with Roth Capital. Please go ahead.

Thanks for taking my questions. Again, with regard to the left ventricular ejection fraction, do you know what was the range at baseline and also the range at the one-year and two-year time point?

So, actually, I think All of that data is presented in the poster that's available on our website, Kumar. And I appreciate the question. I think the inclusion criteria is that the patient is 20% to 40%. In addition, the follow-up is the 35% would be on top of that. So in my mind, I'm estimating it's probably high 20% at baseline and probably wound up being high 30% follow-up, but I don't have the data right here before me.

I can shoot you that poster if you would like after this call. Okay. And also the range, it kind of fits in with the expected range of like, you know, 25% to 45% that is seen with other treatments for heart failure, I guess.

So I think in general, so the one therapy in heart failure that can really enhance your heart function is biventricular pacing in some patients with a left bundle branch block. But in truth, most of the heart failure therapies where you still have the native heart, and I'm excluding left ventricular assist devices and heart transplantation, but most of the therapies don't significantly improve LV ejection fraction. Typically, these patients are slowly deteriorating And so most other therapies in this space, in running a comparison, they're comparing it against a control group that doesn't have that therapy, and they're showing that they're better than that control group. Here, in this role in cohort, we show that the patients are actually better themselves than they were two years ago. That's not been done in heart failure. Now, this is a very small data set, and I don't want to over-interpret it, but it's it's worth looking at. And it was a blinded data set, I know, that the Yale ECHO Core Lab was blinded as to the time of these patients being treated, and these are the results that they came out with.

Okay. And with regard to the statistical analysis plan, you mentioned that it would require about 86 to 126 patients. And in that context, you also have eight patients under active consent and 15 under pre-consent. So with regard to the timing of the next DSMB, what would be the number of patients that would be, you know, analyzed?

So I don't have the exact answer there, Kumar, but that's a great question. So here's the way I would suggest that folks think about it. So, again, this is, you know, to have a heart failure trial end this early would be very exciting, but at the same time, it's a success if the DSMB with the number of patients we have and all the additional follow-up data say keep on going. That's a success. Yes, there's a brass ring if they stop the trial, a recommended stop early for efficacy. At our last DSMB review, we said that they have already looked at 100 patients past the primary endpoint. And so in light of the fact, and I also had a shareholder letter that we released at the end of December in which we provided more color One of the interesting things is the larger trial design was meant to address issues associated with patients lost to follow-up or greater variability in measures in the trial because of it being many more centers doing the measurements in slightly different approaches, even though they're all trying to do it in a very controlled fashion. And what we saw in that data was that You know, not only did we have a large number, you know, greater than 100 aggregate patients past the primary endpoint and saw many of the endpoints improving in actually clinically meaningful levels, but there weren't patients lost to follow-up. And there was actually arguably a reduced variation in some of the baseline measures than we would have expected. there's some interesting things here. And I don't want to oversell this. I mean, this is, you know, reading tea leaves to a degree. But the implementation of the adaptive statistical analysis plan, you know, will right-size the trial. And if we are already there, we will then pivot to completing the trial and going after approval and commercial. And if we're not, we will be continuing the trial. The enrollment is – Looks like it's ticking up nicely, but, you know, it's not done until it's done. And I guess the last thing I'd share, as you think about this adaptive statistical analysis plan, you know, we've gotten all of the data clean going into it. So even if we don't have the trial halted early for efficacy, this next ESMB review is going to be done on very, very clean data. So it'll be even more meaningful on its own.

That's very helpful. Thanks so much.

Appreciate you being on the call. Thank you.

Again, if you have a question, you may press star then one to join the queue. Our next question will come from James Malloy with Alliance Global Partners.

Please go ahead. Hey guys, thanks for taking my questions. I know we've talked you through it a little bit, but can you sort of game out expectations for Friday's call, or is that something you wouldn't want to do in advance of the call, any more detail? And then on 02, you said you get the 10 patients consented for the roll-in. What's the next steps on that, and are we still anticipating the first 100 in the 02 trial, potentially in 2025?

So James, thank you for being on the call and great questions. We're all walking around here wondering what we're going to be doing on Friday's call as well. So we have clarity on the design that we have before us. I will provide a little bit more color. So we are expecting today written comments from the agency. And those comments have not yet come to us. We have a whole series of meetings with a whole series of high profile folks. to review those comments and to prepare for the conversation with the agency, as well as you might expect calls scheduled for after the call to digest what the feedback was and to address any outstanding issues here. Implementing an adaptive statistical analysis plan has no safety ramifications. It's really a trial design issue, and we fully expect that the agency will say that they're not comfortable with a smaller trial for approval. They'd like to see a certain level of data with respect to patient safety. But that's one of the reasons why we have the folks coming into the conversation with us. And it's also a nice feature to just remind us that we have this breakthrough designation that lets us collect additional safety data after the completion of the trial. So that's sort of the color on it right now. We have been spending an enormous amount of time on it, and I could probably recite verbatim all of the details in the adaptive statistical analysis plan on the call. But as things may change, I think it's best to let us get it dialed in and implement it, and we'll share more likely on the other side. I do expect that we will have it in place in Q2 for the next DSMB, and the scheduling of that DSMB you know, may be very much gated on getting this in place. And if we don't get it in place, we'll still have a DSMB meeting, I expect, in Q2. But my expectation is we will get it in place. As regards to your second question on the status with BCDA-02 for the patients with chronic myocardial ischemia. So our expectation is the rolling cohort is up to 10 patients. And based on the experience we've had so far, the logistics of the therapy, there's really no issues. It's very much what we have been doing in the cardiac heart failure trial. There are some things with respect to patient inclusion, exclusion. And for folks on the call, this is a therapy that was initially advanced by Baxter Healthcare. They initiated a phase three review trial with a different cell therapy and different delivery of course, but it was an intramyo-cardio CD34 approach for chronic myocardial ischemia. And much of their data was excellent. But they stopped the trial for business reasons after they enrolled 100 patients. The answer is we kind of know why now. And so we are working through some of the issues in the trial design that we borrowed some of the significant elements from their effort because it was so successful. But we are also, in terms of efficacy for the patients, which is the goal, but we are looking at potentially modifying elements of the trial to make this go much smoother downstream and help the enrollment go much faster. Also, as we're pushing all these elements on the cardiac heart failure trial, you know, the third program of the neurokinin-1 selected mesenchymal excuse me, the neurokinin-1 receptor-positive mesenchymal stem cells that we're advancing, those we think are actually an enhanced enrollment in the LEAD program as well. And so a lot of these things dovetail nicely together. Patients who are excluded from CARDI-AMP because their ejection fraction is too high can qualify for the chronic myocardial ischemia trial. Patients who have poor bone marrow for therapy based on the data they can qualify for the allogeneic culture-expanded mesenchymal stem cell trial. So we're trying to do this in a way that really meets all of the patient's needs, and it gives us really three shots on goal.

Thank you for that answer. That dovetails nicely. You guys guide to second quarter 23 for getting the O3 trial kicking off, and then O4 you're saying is behind O3. Any guidance on that? How far behind?

At this point in time, I want to be humbler. The cell manufacturing last year, the long-term lot release testing, it wasn't the actual manufacturing, but it was some of the data sets that we need after we've manufactured the cells that delayed the timeline. We decided to prioritize the cardiac because we have those patients already. So as you might expect, being 100 plus odd patients downstream in BCD01, that with a cell population analysis that roughly excludes 30% of the patients, that would mean we have 30 plus patients that would like cell therapy for their ischemic heart failure and can't have it and that have already presented it to the center's So we have patients that we could potentially bring into that trial immediately. And so that's something that we're going to be starting with. And we think that enhances the LEAP program as well.

Great. Thank you for taking the questions. I appreciate it, James. You have a great day.

And this concludes our question and answer session. I would now like to turn the call back over to Dr. Peter Altman for any closing remarks.

Thank you, Joe. I want to thank all of you for 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.

The conference has now concluded. Thank you very much for attending today's presentation. You may now disconnect your line.