Ladies and gentlemen, thank you for standing by. Good afternoon, and welcome to the BioCardia 2022 Yearend Conference Call. At this time, all participants are in a listen-only mode. [Operator Instructions] I would now like to turn the conference over to [indiscernible] of BioCardia Investor Relations. Please go ahead, [indiscernible].

Good afternoon, and thank you for participating in today's conference call. Joining me from BioCardia'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 BioCardia's expectations for future performance and operational results, references to management's intentions, beliefs, projections, outlook, analogies or 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 BioCardia's reports 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 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 Peter Altman, PhD, BioCardia's President and CEO. Peter, please go ahead.

Thank you, Moranda [ph], and good afternoon to everyone on the call. We had a great fiscal year in 2022, but, before we get into the details, I always like to take a few moments to review what we're doing and why we're doing it. BioCardia's 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're 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 77% 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 CardiAMP cell therapy, is being advanced…

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 Bluerock relationship Peter just mentioned. Our revenues today contribute to reducing our burn rate and they have the potential to develop in the 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 modestly to $8.8 million in 2022 compared to $8.6 million in 2021, primarily due to increased expenses in support of the CardiAMP cell 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 used in operations totalled $10.6 million in 2022, comparable to the $10.6 million in 2021. While CardiAMP ended the year with cash and cash equivalence totalling $7.4 million, which provides runway 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.

[Operator instructions] And our first question here comes from Joe Pantginis with H.C. Wainwright. Please go ahead.

Hey guys, good afternoon. Thanks for taking the question. Have three questions, one of which hopefully will be based on getting some, I believe important perspective. So maybe I'll start with that one. So, Peter, when we look at the blinded echo data for the roll in at ACC, 35% overall improvement in LVF, maybe can you give the perspective of how that would compare, to the inclusion criteria of the patient population and how that would relate to their natural history?

Joe, thank you for -- no, Joe, great question 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 II and III ischemic etiology heart failure with reduced ejection fraction patients. Ejection fraction is also 20% to 40% of these patients. So this lines up well with what has been done in some of the other larger trials, whereas the data I shared and mortality of -- cardiac mortality of 7% to 8% in all caused 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 conceivably 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, it's a 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 on Phase I and in Phase II were patients approved across 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, 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 your ability to serve your larger studies right now and your additional initiatives versus, 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 BCDA-01 and BCDA-02, and the allogeneic BCDA-03 and BCDA-04. We have taken -- 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, and our partnering with others could result in greater need, but most of the folks we're partnering with are not as far as 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 BCDA-02. So I also note that as BCDA-02 enrollment accelerates, we can handle the manufacturing here at our facility. We're currently only one and running one shift in both of our capabilities and we have rooms, for example, on the cell manufacturing. We can add incubators as we can do things to expand out our capabilities.

Got it. No, very helpful. And then my last question with regard to the 01 study in heart failure, obviously right now, based on your comments and what we've obviously been discussing for a while, lot of moving parts. So, 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 be essentially look at everything futility, safety, efficacy, is there, or what is the alpha spend around that or how would it impact the current statistical analysis plan -- analysis plan ahead of any changes from an adaptive design?

Yeah, that's a -- it's a great question and that's the -- one of the great challenges of these adaptive statistical analysis. I think the alpha spend is going to be very low and for folks that don't have a PhD on the call like Joe does, the alpha spend is what level of the p-value are you going to lose in order to have statistical significance. So right now, 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 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 they were going to wind up in a good place. There's a lot of experienced folks that we're working with on the design, the 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, 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, when you're going after an approval, and this is why we've brought in some very experienced folks, 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.

Understand. Thanks a lot for the color.

No, great questions, Joe, really appreciate them.

And our next question will come from Kumaraguru 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 the 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% at 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 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 part, and I'm excluding left ventricular assists 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 group that doesn't have that therapy and they're showing that they're better than that control group. Here in this rolling 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 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 patients to 126 patients and in that context you also have eight patients under active consent and 15 patients under pre-consent. So with regard to the timing of the next DSMB, what would be the number of patients that would be analysed?

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, to have a heart failure trial and this early is -- would be very exciting, but at the same time, it's a success if the DSMB with the number of patients we have in all the additional follow-up data set keep going. That's a success. Yes, there's a brass ring if they stop the trial or recommended stop early for efficacy. At our last DSMB review, we said that they have already looked at a 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, which we provided more color. One of the interesting things is the larger trial design was meant to address issues associated with patients lost a follow up or greater variability in measures in the trial because of it being many more centers doing the measurements in different, 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, not only did we have a larger number, greater than a 100 aggregate patients, pass the primary endpoint and saw many of the endpoints improving in actually clinically meaningful levels, but there weren't patients lost a follow up and there was actually arguably a reduced variation in some of the baseline measures than we would've expected. So, there's some interesting things here, and I don't wanna oversell this. This is, reading tea leaves [ph] to a degree, but the implementation of the adaptive statistical analysis plan, will rightsize the trial and if we are -- 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 enrolment is looks like it's taking up nicely, but it's not done till it's done. And I guess the last thing I'd share, as you think about this adaptive statistical analysis plan, 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 DSMB 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.

[Operator instructions] Our next question will come from James Molloy with Alliance Global Partners. Please go ahead.

Hey guys, thanks for taking my questions. I was -- I know we talked you through it a little bit, but can you sort of game out the 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 O2, you said you get the 10 patients consented for the roll in. What's you expect -- what's the next steps on that and are we still anticipating the first 100 in O2 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 will -- 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 is -- has no safety ramifications. It's really a trial design issue. And we fully expect that the agency will say that that they're not comfortable with a smaller trial for approval. They 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. Just remind us that we have this breakthrough designation that lets us conduct 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 let us get it dialled 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…

Thank you for that answer. That dovetail nicely actually. 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 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 datasets that we need after we've manufactured the cells that delayed the timeline. We had the -- we decided to prioritize the cardiac because we have those patients already. So as you might expect being a 100-plus odd patients downstream in BCDA-01 that with a cell population analysis, it roughly excludes 30% of the patients. That would mean we have 30-plus patients that would like cell therapy for the ischemic heart failure and can't have it. And that have already presented at the centers. 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 lead program as well.

Great. Thank you for taking the questions.

Appreciate 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 closure 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 lines.