Good day, and welcome to the BioCardia 2022 Third Quarter Conference Call. [Operator Instructions]. I would now like to turn the conference over to Jules Abraham of CORE IR, the Company's Investor Relations firm. Please go ahead, sir.

Thank you, Chuck. Good afternoon, everyone, and thank you for participating in today's conference call. Joining me from BioCardia's leadership team today 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 or 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 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 the Form 8-K filed with the -- and Form 8-K filed with the SEC and particularly the cautionary statements within. The content of this call contains time-sensitive information that is accurate only as of today, November 9, 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. It's now my pleasure to turn the call over to Peter Altman, PhD, the company's President and CEO. Peter, please go ahead.

Thanks, Jules, and good afternoon to everyone on the call. We have had a great quarter. But before I get into the details, let's take a few moments to review what we are doing and why we are doing it. BioCardia's efforts are focused on advancing 2 cell therapy platforms to treat significant unmet cardiovascular and pulmonary diseases. Specifically, ischemic heart failure, chronic myocardial ischemia and acute respiratory distress. All of our cell-based therapies involve local delivery of the therapeutic cells to the heart or lungs, where we intend them to act locally. In the heart, our own proprietary Helix minimally invasive delivery system, a third platform, 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 target tissues. Heart failure is the first problem we are going after. It is an enormous unmet need that affects more than 26 million people worldwide. The latest blockbuster drugs and pretty much the same indication we are going after don't 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 CardiAMP cell therapy, is being advanced in 2 cardiac clinical indications. In preclinical studies, cardiac…

Thank you, Peter. In the first 3 quarters of 2022 we had revenues of approximately $1.2 million on a net loss of $8.9 million, which compares favorably to the first 3 quarters of 2021, where we had revenues of $0.9 million with a net loss of $9.2 million. This increase in revenues and decrease in net loss is primarily due to the increased collaboration revenues. I'd like to reiterate that the potential value of collaboration revenues is far greater than the dollars we receive when we enter into them. Partnering programs provide additional pathways for BioCardia to participate in the upside of partner development programs. And the value, if we can help them be successful, should be meaningful for shareholders. Research and development expenses increased modestly with $6.6 million reported in the 9-month period ending September 30, 2022, compared to $6.4 million in the 9 months ended September 30, 2021. SG&A expenses of $3.5 million for the 9 months decreased from $3.7 million from the same period in 2021. The company ended the second quarter with cash totaling $6.7 million, which provides runway into the second quarter of 2023. To extend our runway, we are working on business development activities with a focus on nondilutive financing. We're now ready to take questions. Operator?

[Operator Instructions] The first question will come from Joe Pantginis with H.C. Wainwright.

Peter, my first question is a bit multipronged. And I guess it's -- I mean it's housekeeping related, but it really goes into the weeds regarding the adaptive design plan that you're currently working on. So hopefully, you can provide some more information. So I guess, what are the -- really the stage of the discussions now with the FDA with regard to outstanding topics, that's #1. Is there -- how would we consider the alpha spend around any of the adaptive components that you have here, especially if it's lower enrollment -- and I guess it's really related there with regard to the outstanding topics with the FDA, what else is on your wish list, excuse me, in getting this over the finish line with the FDA.

So I can share with you that we are in the process. So Joe, first off, thank you for the question. But to jump straight to the answer, the discussions with the FDA are still early. We have not yet had a Q-sub meeting with them. We are in the process of preparing the submission with the appropriate detail that's really needed for them to understand it and wrap their heads around it. But in this situation, this is being recommended by the Data Safety Monitoring Board. And my sense is the agency will undoubtedly raise concerns about a smaller number of patients enrolled in the trial. So 1 of the advantages we have is the breakthrough designation from FDA that does give us the ability, I understand, to if we need additional safety data for such a significant indication, to potentially capture that in a post-marketing scenario. We are working with two very prestigious groups who have actually cross recommended 1 another. One is a world-class group in developing adapter statistical analysis plans. And the other is a very high-profile regulatory consulting group that includes a number of former senior FDA directors. And so we're pulling this team together and having regular meetings. But I guess the first thing is dialing in the adaptive statistical analysis plan in order to understand what the cost of alpha may be. But my sense is it's not going to be a significant cost of alpha here, because our expectation is we're going to do a design that looks at the question of how large should the trial be, not asking what are the results from the trial. And that changes the equation and makes it so there's not an enormous alpha cost. So that's where we're at. This is a very active effort today. And I note in parallel to the regulatory and the statistics work, we have a significant ongoing effort to have all of the data cleaned so that at the next Data Safety Monitoring Board meeting, they're looking at very clean data so that we can rely upon the input that they provide on the other side of this. So it's pretty exciting. But that said, as I shared in our comments, there's no guarantees here. Fundamentally, this trial may just continue. And we are working diligently in ways to enhance enrollment in the trial as well as enhance the experience of all the physicians participating in the trial.

Got it. No, those are all fair comments. I appreciate it. And then moving to sort of David's comments and even your list about business development goals, I guess I would ask it this way, and I would never ask you to predict timing. That's always a bad thing. But how would you describe the level of maturities of the list of those 4 different components of ongoing BDs?

I would say that we've had significant discussions on all 4 of them. I would say that our focus right now is really on the first and the third of them. That is the OUS CardiAMP and the partnering on biotherapeutic delivery with others. We, in the last quarter, did enter into an arrangement with Bluerock Therapeutics. And that is a time-limited option that they have, that we may see some progress on in the year ahead. So this is sort of the nuances of what we've done historically. And remember, previous -- to David's comments, the value of these partnerships, we have a number of partners with significant data sets with our delivery system. And when you're developing efforts, those are value propositions we have that could quickly grow into other value propositions ahead.

Got it. Got it. And then my last question, if I just skip to the end of the pipeline for 04 and use of the allogeneic cells in our platform in ARDS, I guess, maybe the broader concept of look, the COVID landscape is dramatically changing. It will still be sticking around based on the broad consensus. So I guess at this status of COVID, if you will, just the rationale of why doing this study at this standpoint and also while finances are important.

So the indication -- so great question, Joe. The indication we're going after is patients essentially recovering from COVID. And there's actually a very significant gap there. There are right now really no therapies targeted for patients when they come off respirator. And so there's something out there that we've all heard about with chronic inflammation. A lot of folks will refer to it as long COVID. And that's not the indication per se that we're going after, but there are sustained inflammatory impact of COVID-induced ARDS. I also note that in other etiologies of acute respiratory distress or ARDS, there's also a gap in what happens to a patient at the tail end of being on respirator. And so there's a space where they don't have anything. And what we're doing is a relatively routine therapy. On the economic side, Joe, great question. So these trials, as they start with Phase I, Phase II, typically start with a dose escalation cohort with great care to protect the patient. And so there's not a significant number of centers that's going to be added to either of these trials. So basically, think of it as we're cleaning out all of the safety issues and optimizing the maximum tolerated dose for these 2 therapies, BCDA-03 and BCDA-04, with the expectation that's not going to be a significant burn. We're manufacturing the cells ourselves here at BioCardia. For the ARDS effort, it has a very short end point for efficacy, based on a lot of the other trials that have been out there. So we're feeling pretty good about the direction we're going, and I don't think it's going to substantially impact the burn rate for the Phase I portion. As we move into later stage Phase II portion, yes, the burn rate would increase significantly there. But that's something to be decided on in the future.

The next question will come from Michael Okunewitch with Maxim.

Peter. I wanted to see if you could provide a bit more color and kind of walk me through how you conducted the analyses on the blinded data? And then if you could just give us a bit more on how we should be interpreting that.

Yes. So the blinded data, so it was -- a normal process for a data safety monitoring board review, Michael, is that you will receive an open session package that looks at all of the data on all of the patients. So it's aggregate data. So we are blinded to the data. We don't know whether 1 group is different from another group. But what stands out when we look at the data is that the patients are improved. And we're going after heart failure, which is a chronic condition. And in our Phase II trial, the treated patients improved, but the control patients deteriorated over time, which is what you would expect. And it was -- it just sort of jumped out at us as we looked at the data. Now if you -- I mentioned the animation of the trial at cardiamp.com. And even in that animation, we call out the fact that patients typically do better in a clinical trial. So we may just be seeing all of the patients together doing better in the clinical trial. But I note that the mortality rate is also significantly less than we would expect based on the related literature in the field. And again, we don't have a way to compare it because we're blinded as to the patients, which are in which group. And so this was the status of the data at the last DSMB. The DSMB recommended the adaptive statistical analysis plan, in part because of slow enrollment during COVID. Typically adaptive designs are used for trials that either are enrolling slowly or have a very short endpoint. But we also have a significant number of patients past the primary endpoint. And so -- and coupled with that, we also have a breakthrough designation. And so one of my great concerns, even if we did have a wonderful ability to say we've already reached efficacy in the future before we completed the full enrollment in the trial, would be that in heart divisions there is such a significant indication you want to make sure that you've treated enough patients so that everybody has comfort with respect to safety. But our breakthrough designation gives us a pathway to collect that additional data on the other side of approval. So that's it at a high level. Have I addressed your question appropriately, Michael?

Yes, you did. I'd just like to drill down on -- a little bit deeper on 1 point in particular. When you're saying that you're -- you saw a greater survival rate compared to other large pivotal trials, that's comparing aggregate data to the aggregate data from other similar pivotal trials? Is that the idea?

That actually would be considered a fair assessment, Michael, because the trials that have been out there aren't really showing a reduction in mortality. And this is one of the topics that's a great discussion at conferences such as Heart Failure Society of America, that the mortality problem is still out there. But actually, when I talk about the comparison, in order to be fair, and this is always dangerous when you're comparing apples to oranges, our trial to other trials that are out there, because they're not the same trials. They're not the exact same patients. They're not the exact same therapies. But what we're comparing it to is really the successful positive arm of the trial in, I think I'll call it out, the SGLT2 I trials that have just come out in New England Journal of Medicine. And we referenced that in a previous press release. So again, this is not an apples-to-apples comparison, this is an apples to oranges and the things that we're doing are very different. But it's a striking reduction in mortality across an aggregate population for us. And so is that more in 1 group than the other? We don't know. But it's interesting. That's all I'm sharing.

All right. And then just 1 more follow-up. I'd like to just see if you could touch on how the biotherapeutic delivery platform benefits Bluerock's cell therapy candidate. What kind of attracted them to your particular platform? And then what sort of other therapeutics or indications could benefit from the device?

Yes. So I can't comment on anything with respect to Bluerock. But I can tell you that our Helix transendocardial biotherapeutic delivery system has a couple of advantages. First, it's the only intramyocardial delivery system I'm aware of that is in clinical use today. It is approved in Europe, although we don't sell it in Europe, we only partner it. And it also is -- its safety profile, which has been in the published literature, is far superior to that of our previous competitors who have since left the arena, and that would be small companies such as Johnson & Johnson and Boston Scientific. I also note that its efficiency of delivery, which we believe is due to the stability of the Helix in the myocardium and its stability in yielding control over delivery enhances really the retention in the heart tissue after delivery. So multiple data sets on multiple different classes of therapies have shown, we have roughly threefold the retention or threefold the dosing with our delivery system that others have had with a simple straight needle intramyocardial approach. And so that's also helpful. So lastly, is the ease of use of the system. We have no capital equipment involved in this product. And in the past, we had a number of larger entities that wanted to work with us primarily because of the absence of capital equipment that would slow their own sales cycle, or their ability to train and work with physicians around the world. So those are really the key advantages. And I guess, I would say the last thing is folks are going after indications. BioCardia today is focused on heart failure and chronic myocardial ischemia. We have a partner in Europe [indiscernible] that's going after acute myocardial infarction or maybe sub-acute, soon after myocardial infarction. And those are really the 3 big indications today. There is a fourth indication out there, which is heart failure with preserved ejection fraction. And it's 1 that we're eyeing with great interest because a number of very sophisticated folks have made clear that if we're successful in ischemic heart failure and/or chronic myocardial ischemia, our 2 indications today, that heart failure with preserved ejection fraction is also in great need. And because folks view preserved ejection fraction heart failure as due to microvascular disruption, there's potential to go in that direction as well. So those are really the 4 indications that it would be used for. And amongst those 4 indications, it's the leading cause of death in the Western world. I can quote the CEO of Johnson & Johnson, who just recently bought a biomed for $16 billion. And he has said that all forms of heart disease wind up in heart failure. And they see the greatest opportunity for their efforts in helping hearts recover. And frankly, we couldn't agree with them more. That's exactly where we are and what we're doing.

The next question will come from James Molloy with Alliance Global Partners.

I had a question on the O2 interim look, we're anticipating here, enrolling [indiscernible] first quarter '23. Is that the 100 patients? Or is that a subset of 100 patients? And when will the 100-patient cohort out of the 343 be enrolled?

So we are working to complete enrollment in that next year. We are in the process currently -- so James, first off, thank you for the question. And it's a good eye. We are actually -- so for that rolling cohort, we've already got patients enrolled. The results from that rolling cohort are probably not going to be available until Q1 next year. But the results are rather phenomenal in the patients that have been treated. And our expectation is we're still pushing hard to have that get to the full 100 patients by next year. So again...

In the rolling cohort.

I'm sorry.

How many patients are in the rolling cohort? You just said you're reporting first year on '23

Right. The rolling cohort protocol is 10 patients.

Okay. And you anticipate enrolling the remaining 100 in '23 with the data -- when were you anticipating potentially having data from the first 100 and then potentially the final 343rd patient in this trial?

Right. So -- so again, we've long said this is -- you're very -- being very attentive here, Jim. The -- we're expecting that the -- so we've talked about an adaptive statistical analysis plan for BCDA-02. And that's part of the plan with the agency. The conversations there have focused on having that be a 6-month follow-up endpoint, which the agency has approved. We are in the process. So one of the things you do in a rolling cohort is you try and learn every way you can to potentially make the trial easier to perform and more likely to be successful before you roll it out. We're also in a situation where we have centers across the United States and actually now coming online across Canada that are all trained up for the heart failure program. So it's the same logistics. It's the same training. It's very much many of the same study reference documents that support both of these programs. And so the idea is right now, we're not doing this at centers that are -- actually, I take that back. We have centers that are active in the trial. We're adding additional centers that are not active in the heart failure trial. And then at some point, we will probably expand it to all of the centers that are doing well in the heart failure program, but we're just not at that point yet. And these are the patients...

So that's you so it's 100 in '23 and it's a 6-month follow-up means you'd be looking for mid-'24 for the first 100 data?

I would say it's going to take longer than that to get the data for efficacy. 6-month follow-up is correct, but it will take time to clean that data and prep and go through some stuff. So you should probably add a year on the other side of the completion of enrollment.

Then on the BCDA-03, the IND filing here hopefully approved in December. The 04 IND was approved on April 12 with the expectation the trial would start in third quarter '22. That's now first quarter of '23. Should we expect a similar 3-quarter delay between the IND approval for 03 and the Phase I/II trial for the BCDA-03?

Actually, no. We don't expect nearly the delay. So for BCDA-04, the steps involved the clinical manufacturing of cells, and the cells were substantially manufactured in Q3, but there's long -- there's a couple of elements in the manufacturing process that have long lead time to make sure that the cells are safe for patients. And we're still -- even today with clinical cells on ice awaiting 1 of those long lead time items. So all of that work on the cells we've manufactured today will benefit BCD03 from BCD04. I also note, Jim, BCD03 will have the advantage of all the patients we've already identified in the BCD01 program. So the idea is to take that to the patients that have been excluded from BCD01. The decision process here at BioCardia is going to be very interesting, because we could treat a large number of patients in BCDA-03 if we weren't concerned about the focus on BCDA-01 and other trajectory items. So right now, our focus is we're going to do the rolling cohort on BCDA-03 probably pretty quickly, but we're going to assess where we're at before we launch into the Phase II portion of that study, because that will be more expensive. And once you make a commitment to a phase of a study as a sponsor, you need to have the responsibility to complete it. We have that nicely with BCDA-01 and 2 with the Medicare reimbursement. For BCDA-03, it won't benefit from that reimbursement. And so we need to be thoughtful before we move into the Phase II program. Also, since it's the same physicians, we don't want to distract them from BCDA-01 significantly. Even though they're different patients, having a patient working through the system does consume time in the cath lab. And physicians have a sense of I'm treating patients in your trial, but we're right now prioritizing BCDA-01 over BCDA-03 by far. I know that's lot of complicated -- James, it's a complicated interaction but I think it's the value of the synergy we have with these programs, because as a small company, we can manage all 4 of these programs at this stage.

Last question for David real quick. What's with the reporting the 9 months data and not having the numbers for the quarter in the press release?

Can you say again, Jim?

Why don't you guys put your numbers for the third quarter into your press release instead of just sort of putting the 9-month reporting? It's atypical.

Well, we put the 9 -- I think the 9 months numbers are more meaningful whereas we're trending now towards the end of the year versus the fluctuation of quarter-to-quarter. They're pretty flat. We could have shown both and they're presented in the tables.

Yes, all the data is in the tables. And it's -- our revenues are lumpy with partnerships. So where do -- we have the greatest revenues we've ever had this year so far.

This concludes our question-and-answer session. I would like to turn the conference back over to Mr. Peter Altman for any closing remarks. Please go ahead, sir.

Thank you, Chuck. I just want to thank all of you for participating in 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 for attending today's presentation. You may now disconnect.