BioCardia, Inc.

Good day, ladies and gentlemen. Thank you for standing by. Good afternoon and welcome to the BioCardio 2023 first quarter 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 August 10, 2023. I would now like to turn the call over to Miranda Petto of BioCardia Investor Relations. Please go ahead, Miranda.

Good afternoon, and thank you for participating in today's conference call. Joining me from BioCardia's leadership team are Peter Allman, 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. Reference to management's intentions, belief, projections, outlook, analyses, and current expectations. Such factors include, among others, the inherent uncertainties associated with developing new products, technologies, and obtaining regulatory approvals. Overlooking statements involve risks and other factors that may cause actual results to differ materially from these statements. For more information about these risks, please refer to the risk factors and cautionary statements described in biorecordage reports on form 10-K filed on March 29, 2023. The content of this call contains time-sensitive information that is accurate only as of today, May 10, 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 Dr. Peter Altman, PhD, BioCardia's President and CEO. Peter, please go ahead.

Peter Altman, PhD, BioCardia's President and CEO Thank you, Miranda, and good afternoon to everybody on the call. It has only been six weeks since our last call at the end of March. and BioCardia is steady as she goes. We have some near-term catalysts that we can detail progress towards, as well as the broader opportunities for success ahead. BioCardia's current efforts are focused on advancing its autologous and its allogeneic 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 lungless where we intend them to act locally. Heart failure is an enormous unmet need that affects more than 26 million people worldwide. The latest blockbuster drugs in ischemic heart failure, a 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 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 CARDI-AMP Cell Therapy, is being advanced in two cardiac clinical indications. In preclinical studies, cardiac mononuclear cell therapy has been shown to release proteins locally within the tissues 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 of 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 BCDA01, and chronic myocardial ischemia, or BCDA02, are furthest along clinically. The CARDI-AMP Cell Therapy Heart Failure Trial, or BCD-01, is a Phase III 260-patient randomized controlled clinical study intended to provide the primary data to support safety and efficacy in pursuit of marketed clearance. Clinical investigators at 20 active partner sites across the United States and Canada have enrolled 120 patients to date, with 10 additional controlled patients having crossed over to receive therapy. We feel there is clearly increased momentum here, potentially driven by the clinical data presented at the American College of Cardiology in March, showing 100% survival and patient benefits across many endpoints at two years, including a 35% increase in the heart left ventricular ejection fraction. As many know, we have been working on implementing an adaptive statistical analysis plan to the trial. with distinguished consultants, including former FDA leaders and a respected statistical consulting group. In our last March 29 call, we were headed into a meeting scheduled to discuss the FDA's comments on March 31st. That meeting went well. The discussion of the adaptive statistical analysis plan as provided was well received by the agency's statisticians. The FDA's primary concern was whether we would have enough safety data to support approval in an indication as large as ischemic heart failure with reduced ejection fraction if the trial was stopped early for efficacy. The agency's primary concern with safety was with respect to the safety of the delivery of the cells. We shared with the FDA that we feel we do have sufficient data already with 353 interventions with our delivery system in the clinical indication of ischemic heart failure reduced ejection fraction to date, and 129 patients treated so far, with the cells being advanced in the CARDI-AMP trial. The FDA was unaware of this more expensive data set, and we agreed to detail it for them. We also worked with them on creative ideas to further enhance the safety experience ahead. After summarizing minutes from our perspective and acceptance of the FDA minutes provided, We submitted a revised supplement for the adaptive statistical analysis plan, incorporating all of the comments from the agency on April 26. We now anticipate a response from the agency on May 26. The next pre-specified formal data safety monitoring board review is anticipated at the end of June 2023. We still 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 this next and subsequent Data Safety Monitoring Board reviews. As the CAR-DAM cell therapy hard failure trial 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. Although the next data review event has potential to be a great success if the trial is stopped early for efficacy, the review will also be a success should the trial continue as planned. Our second therapeutic program is with the same autologous cell therapy for the treatment of chronic myocardial ischemia with refractory angina, or BCDAO2. The CAR-DM chronic myocardial ischemia trial is a Phase III multicenter randomized double-blinded controlled study of up to 343 patients at up to 40 clinical sites. 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 cohort results in 2023. As we have 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. BioCardia still expects to complete a formal submission towards Japanese approval in the second quarter of 2023. In Japan, another autologous cell therapy has received conditional approval for heart failure based on seven patients treated, and these treatments require open-heart surgery to access the heart. Although our clinical data is from overseas, we have treated far more patients in rigorous controlled trials and have a minimally invasive procedure with our Helix biotherapeutic delivery system. Our cell processing platform is approved in Japan already for therapeutic applications for non-cardiac indications by our partner, Zimmer Biomed. And our minimally invasive Helix biotherapeutic delivery system is approved in the European Union. Our feeling is that there are many reasons that Japan PMDA should be inclined to approve cardiac cell therapy for the benefit of patients and to continue to advance Japan's leadership in regenerative medicine therapies. 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 1-2 multicenter randomized double-blinded 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. And the trial is designed for patients ineligible for the company's Phase III cardiac heart failure trial, studying autologous cell therapy. Clinical-grade allogeneic cells 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 still expect to begin enrolling patients in the second quarter of 2023, which has seven weeks remaining. Our allogeneic mesenchymal stem cell program in patients recovering from acute respiratory distress syndrome, which we have designated BCD-04, was approved by the FDA in April 2022 to treat patients. The trial is a phase one multicenter 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 be initially evaluated, and then the optimal dose will be taken to phase two in a randomized study in adult patients recovering from ARDS. This therapy is intended to address the enormous unmet need of sustained local and systemic inflammation after a patient has taken off respiratory support with the goals of accelerating recovery, enhancing survival, and reducing both relapse and re-hospitalization. Clinical grade cells are also ready for use in this study. The ARDS trial is expected to commence following the initiation of BCD03, studying these allogeneic mesenchymal stem cells for heart failure. 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 systems for cell, gene, and protein therapy candidates to the heart, such as in the Blue Lock relationship we began last year. And fourth, is monetizing our Avance transeptal introducer sheath product. We are looking forward to announcing an additional patent issuance related to our Helix biotherapeutic delivery platform and feel very good about our broader intellectual property estate. I will now pass the call to David McClung, our CFO, who will review our Q1 2023 financial results. David?

David McClung Thank you, Peter, and good afternoon, everyone. Revenues were approximately $64,000 for the three months ended March 31st, 2023, comparable to the $60,000 for the three months ended March 31st, 2022. Research and development expenses increased to approximately $2.4 million in the first quarter of 2023 compared to approximately $2.2 million in the first quarter of 2022, primarily due to expected increases in support of the cardiac heart failure trials. SG&A expenses remained at approximately $1.2 million in the first quarter of 2023, comparable to the same amount in the first quarter of 2022. Our net loss was approximately $3.6 million in Q1 2023, as compared to $3.3 million in the first quarter of 2022. And net cash used in operations during the quarter was approximately $2.6 million, as compared to approximately $2.9 million in the first quarter of 2022. BioCardia ended the quarter with approximately $4.9 million in cash and cash equivalents, providing runway into Q3 without additional capital or funding for business development activities that Peter touched on in his remarks. This concludes management's prepared comments. We're ready to take questions.

Thank you. We will now begin the question and answer session. To ask a question, you may press star, then 1 on your touchtone phone. If you're using the speakerphone, please pick up your handset before pressing the keys. If at any time your question has been addressed and you would like to withdraw your question, please press star, then two. At this time, we will pause momentarily to assemble our roster. Our first question comes from Joe Panginis with HC Wainwright. Please go ahead.

Hey guys, good afternoon. Thanks for taking the question. Two primary questions, Peter. So first, with regard to BCDA01, nice to hear you're making progress with your FDA discussions. So for the current patients enrolled, you said you had 10 control patients that had crossed over. So can you remind us the criteria for crossover and then following crossover, what could be the potential impact of new or concomitant meds?

Okay, so thank you, Joe. I was waiting for a second question there, and I think I've got the breakdown. So first on the, so appreciate the question, and I really appreciate you being on the call. So on BCD01, the 10 crossover patients crossed over after they met their two-year follow-up endpoint in the trial and essentially exited the trial. The requirement for those patients is substantially what it is to be included in the trial, although I think the workup is a little bit less because some of them may have deteriorated. There is actually a patient that you can see who has crossed over on our patient-facing website, which is cardiamp.com. And so, yeah, we've had 10 patients cross over. The FDA approved this last year, I think, or maybe it was the year before, because of the safety profile they're seeing in the trial and the sense that, you know, these patients enrolled in the trial should be given the option if they and their physicians think it makes sense for them to proceed. Got it, got it. The patients... Sorry, sorry. No, it's all right. The last piece is these patients are then followed for another year. And so for the trial, they provide additional safety data for us which, you know, as you heard on my FDA comments, is valuable for the FDA. And I actually may use that to note that if you consider the FDA comments I shared, you know, those comments were all around, you know, stopping the trial early. They want to have sufficient safety, but that's fundamentally to provide support for approving the therapy. So that's actually a really nice conversation to be having.

No, that's good. Thanks. And then the second question really is around those FDA discussions. Obviously, I know you can't be too specific right now since it's ongoing and it's iterative. But, you know, just curious if you could take some broad strokes about, I guess, your prepared comment surrounding ideas to enhance the safety package since you can't increase patient numbers.

Well, I guess, yes, I can share that. So, Well, actually, it's probably best to wait until we have the final details from the agency. It is only a few weeks out, and we can share it then. But, you know, the key is patient numbers for approving the therapy. And I'll share with folks, when we designed this trial, you know, that was one of the primary considerations because of the power we had going into it, is that we wanted to have enough patients to enroll in the trial successfully. to enable the agency to have comfort to approve the therapy. Again, our goal here at BioCard is not just to deliver a positive trial. Our goal is to deliver a product for these patients and the physicians who care for them. And at that point in time, the dialogue was around what number would be acceptable for the agency, and they wouldn't provide us with a specific number. But as we've gone downstream, it's our safety profile in this program and in our second program that also help us. So I guess let me detail the results of the adaptive statistic analysis plan when we have the FDA's blessing for it. And I'm hopeful that that will be in just a few short weeks here.

Fair enough. Appreciate the feedback.

Thank you, Joe. Appreciate the questions.

The next question comes from Kumar Raja with Roth Capital. Please go ahead.

Thanks for taking my questions and congratulations, Peter, on all the progress. So with respect to the feedback that is expected from the FDA at the end of the June, the expectation is that you have taken care of whatever the questions they had and the feedback they have given before. we are pretty much close to the final stage in terms of, you know, getting an agreement with the FDA with regard to the adaptive statistical plan.

So thank you, Kumar, for the question and also for being on the call. That is our sense. For those who have been involved in conversations with the FDA, they ask, more questions than they provide real clear guidance on where to go next. But we have a pretty sophisticated team that's come into this conversation. Um, we are working with, um, literally a world-class regulatory group, our own internal regulatory team, which is nothing short of phenomenal. And, um, perhaps the most respective, uh, statistical analysis plan developers with respect to an adaptive design that, uh, from the agency's perspective. So my sense is we went into this very seriously and I think the agency recognized that. And so they, everything, every single question that they raised and that which we discussed, I think was extremely well addressed. So that said, you know, we can never predict the future with the agency. They're trying to do their best by, you know, you know, all the folks in the United States, and if they do come back to us with, you know, follow-on questions, we will address them. But our hope is that, you know, they will come back to us and bless the statistical analysis plan, and then we will roll it into the next Data Safety Monitoring Board review, which is currently being scheduled for the end of June.

Okay, so the expectation is that by that meeting, you will have more clarity And also with regard to the PMDA submission, maybe you can just provide us a little bit with regard to once you submit it, what is the expectation and the timelines there. And also in that context, you mentioned about two out licensing or product distribution opportunities. Maybe you can talk a little bit about that. Thanks so much.

Appreciate the questions, Kumar. So on PMDA submission, so we've had two separate consultations with, this is the Pharmaceutical and Medical Device Agency in Japan. And this is around securing an approval for the cardiac cell therapy platform for the treatment of ischemic etiology heart failure of reduced ejection fraction, which is our lead program. And The conversations we've had with the agency so far have been all focused on really the same question, is we are keen on securing approval based on the data that we already have in hand, not waiting to complete the pivotal trial in the United States, but rather based on the quite significant data sets and experience and the number of approvals we already have. And so all of the questions from PMDA and our two consultations have been focused around clarity of certain issues, certain procedural elements. We've been impressed by them and they've been rather sophisticated. But, you know, the submission process we're in the midst of, you know, does have some challenges with respect to translation delays because a rather large document will be provided to them containing substantially the information which they've already seen in different formats in Japanese for them to consider. Our expectation is, after we submit this to them, that we will have them come back to us with a series of questions, which we'll have to respond to in short order. And our hope is that, at the end of the day, the key issue is, will they approve this without pre-approval data in Japan. And, you know, the four words we are aiming for are, your proposal is acceptable. And so that's really where we're headed for on this. And we think we've got all of the support we need, but, you know, again, it's a, we're working with regulators that complicates it. So, and that's about all I can share at this point in time. Again, as is BioCardia's approach, we have multiple different experienced consultants we're working with. We have incredibly distinguished co-national principal investigators in Japan that we're hoping to be working with on a post-marketing study after we have approval, in addition to just incredibly distinguished folks on the regulatory and processes in Japan. So it's been a delight. On out-licensing, I detailed the various categories of out-licensing we have. We have a lot of activity currently. And our sense is we have, you know, capital to get through a couple of deals as well as all of these milestones we're detailing for BCO1, 2, and 3. So, you know, I'd say stay tuned on the out-licensing. Unfortunately, they're similar to the FDA that we can't you know, be guaranteed what their timelines are, what their response is going to be. But by being buttoned up, you know, it helps. And I think we are a buttoned up organization. So, again, I'd have to say stay tuned for those discussions. They do involve out-licensing products and distribution deals around product candidates that we have that don't really reduce, the value of anything we're currently doing in the United States. They're all additional value propositions. Very helpful. Thanks so much. I appreciate the questions, Kumar. Have a great afternoon.

Again, as a reminder, if you have a question, please press star, then one to be joined into the queue. Our next question comes from Laura Suriel with Alliance Global Partners. Please go ahead.

Hello, this is Laura calling in for Jim Malloy from AGP. Thank you for taking our questions. So for the BCDA-02 trial, it was mentioned in the previous call that trial design modifications were being planned in order to speed up enrollment. So what's the overall status on any of these changes that are being proposed to the FDA? And then also for the BCDA-04 trial, when do you expect to meet with the FDA as well to modify the study eligibility?

Boy, good questions, Laura. Appreciate you being on the call. So the answers, I have easy answers, but I'll give you more colors. So BCD02, we're not going to engage the FDA in changing the trial design until we complete the initial role in cohort, which is imminent. And that trial design is going to involve substantial structural changes in the inclusion, exclusion, as well as the primary endpoint. This trial, I guess I would say for folks on the call, is substantially equivalent to the trial that Baxter Healthcare advanced in this indication, focused solely on CD34 cells. And everybody criticized Baxter Healthcare for how long the trial took for them to enroll 90 patients, and then they ultimately just stopped the trial and walked away from it, even though they had great efficacy signals that ultimately were published. We now understand that. the difficulties Baxter was having. And so unlike Baxter Healthcare walking away from it, we're going to drill into it and solve it. And we're eminently confident that we can do that because we're working with some of the world experts in this space. So that's ongoing, working with our KOLs and physicians and pursuing the realm of what's possible. And my sense today is we're going to go after an endpoint that's primarily image and self-assessment driven, i.e., probably using PET and using, you know, Seattle Angina questionnaire versus using the cardiopulmonary exercise time. And the good thing for investors is eliminating the cardiopulmonary exercise time criteria, which we may still measure at baseline and follow-up, but making it less important, will greatly reduce the cost of this trial. And that's another nice advantage. So the trial will go faster. We'll have data that's more objective for physicians. And, you know, we expect that on every front, it will be advantageous to us. So that's on the BCD-02. On BCD-04, the dynamic there is really easy. That's a quick supplement to the agency. And I do not expect any agency pushback whatsoever. Essentially, when we launched that program, we were going after patients who had acute respiratory distress syndrome secondary to having COVID. Since then, as we all know, there's not a whole lot of patients with COVID who are winding up on ventilator with acute respiratory distress syndrome. And so by eliminating the requirement to have had COVID before, We'll be going after a classic ARDS population. We're also awaiting, there's a very large NIH study coming out shortly in this space, being led by the University of California in San Francisco. And so as we make that supplement, we're also awaiting that data. So just because of bandwidth issues, we haven't pulled the trigger on that modification, but that's a very easy modification to the trial. for the agency. And I'd be literally shocked if there was any concerns on the agency's part. We just haven't gotten around to submitting it, in part because we see that program as after the BCD03 trial getting started.

Got it. Thank you for taking the question.

No, I appreciate them, Laura.

As we have no further questions, I would now like to turn the conference back over to Peter Altman for any closing remarks.

I want to thank all of you for participating in today's call and for your interest in biocardia. We do look forward to sharing our continued progress. Stay healthy, be kind, and have a wonderful afternoon.

The conference has now concluded. Thank you for attending today's presentation. You may all now disconnect.