BioCardia, Inc. (BCDA) Earnings Call Transcript & Summary

Ladies and gentlemen, thank you for standing by. Good morning, and welcome to the BioCardia2022 Clinical Leadership and Management call on the CardiAMP Heart Failure trial. [Operator Instructions]. 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 1 hour after the end of today's conference. At this time, I'd like to turn the floor over to Scott Gordon, President of CORE IR. Sir, please go ahead.

Thank you, Jamie. Good morning, and thank you for joining in today's conference call. Joining me today are the Co National principal investigators in the CardiAMP Heart Failure trial, Dr. Carl Pepine of the University of Florida at Gainesville, and Dr. Amish Raval of the University of Wisconsin at Madison. Also joining from BioCardia are Dr. Peter Altman, the President and Chief Executive Officer; Dr. Sujith Shetty, the Chief Medical Officer; and Ms. Debby Holmes-Higgin, Vice President of Clinical. During this call, management may 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, analyses or current expectations. Such factors include, among others, the inherent uncertainties associated with developing new products with technologies and obtaining regulatory approvals. Forward-looking statements involve risks and other factors that may cause actual results to differ materially from those statements. For more information about these risks, please refer to the risk factors described in BioCardia's most recently filed periodic reports on Form 10-K, Form 10-Q and Form 8-K filed with the SEC, particularly in cautionary statements in them. The content of the call contains time-sensitive information that is accurate only as of today, October 5, 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 is now my pleasure to turn the call over to Dr. Peter Altman, the company's President and CEO. Peter, please go ahead.

Dr. Altman, this is the conference operator. I just want to make sure that your line is unmuted. Thank you.

Thanks, Scott, and good morning to everyone on the call. Today, we have an update for you on our lead program, BCDA-01, the cardiac cell therapy heart failure trial that is actively enrolling in the United States and Canada. This call is intended to be primarily an update from our globally recognized co-national principal investigators, Dr. Carl Pepine and Dr. Amish Raval. There are slides available on the webcast that we will use. And as many of you may be only on the telephone, I will ask that we call out the slide numbers as we go through the presentation. It is now my pleasure to turn the call over to Dr. Carl Pepine, Co-National Principal Investigator in the CardiAMP heart failure trial. Carl, please go ahead.

I'm pleased to be able to give you an update on our regenerative medicine study in heart failure, CardiAMP HF. You should all know that this is the first personalized medicine approach in cell-based therapy for heart failure using an approach that requires a cell potency assay for patients to qualify for the trial. In this slide that you should be able to view now, which is labeled Slide 3, the progress of the trial is depicted. As you can see, the trial started in late '19 -- in late 2017, with the enrollment of the FDA-mandated 10-patient cohort. Each of these patients received the active cell product. Their data has been presented and has also been presented in abstract form, and it may be familiar to you. We then entered a fairly rapid enrollment phase. As you can see, the patients consented accumulated until we were impacted in early 2000 by the pandemic. As all clinical trials were impacted were -- that were in operation at this time. The impact has been much longer lasting than any of us anticipated. Many of the sites, including our own or embargoed at the time by our local authorities to conduct only what was deemed essential research, which meant research related to COVID-19. After about 4 months, that embargo was relieved at our site, but at many of our participating sites, it continued. And the downstream effects of shifting personnel from research positions to take care of the sick patients with COVID has been very long lasting and has impacted essentially all clinical trials. So as we speak today or at least when this slide was summarized, 114 patients were enrolled, which is well below the target, which is depicted in blue. Now we summarize in the next slide the number of patients and the reasons why they may have been excluded. In this diagram, you'll see there were 259 patients who were consented and 104 of those met all eligibility criteria. The major reason for exclusion related to failure to qualify with the cell potency assay. Also note on this slide that at 24 months, the patients who had been randomized to sham. Remember, this is a trial that randomizes 3 to 2, 3 to the active cell product and 2 to a sham procedure those who were randomized to the sham procedure were offered the opportunity to cross over to the active cell product, of which 10 patients have done so. In the next slide, you'll see that we have had our most recent data safety monitoring committee meeting on August 30. And their recommendations were briefly that the study should continue as designed and no change or actions were required. They did ask that we provide an updated statistical analysis plan that would include an adaptive design. In response to that, BioCardia has engaged groups that have done adaptive statistical analysis plans. And that plan is currently under evaluation. The adaptive design would enlable the trial size to be informed relative to enrollment and outcomes and then could be used to either shorten the trial or make decisions relative to the slow enrollment. It could also identify signals for early efficacy in which case we may want to enrich the patients who are being enrolled. But there are a number of opportunities and that plan is currently under negotiations and discussions are planned with FDA. So I want to introduce to you my co-national PI, Dr. Amish Raval, and he will tell you about some of the study enhancements that have occurred this year.

Thank you, Carl, and thank you, everyone, for attending. 2022 has seen some tremendous progress in the cardiac clinical trials in 2 fronts, the attempts so BioCardia's been very responsive to the executive steering committee recommendations and so forth. -- moving forward. And those 2 accelerations are developing regulatory path that are more accelerated as well as looking to accelerate enrollment through a couple of mechanisms. So in January 2022, the breakthrough [indiscernible] adjudicated a breakthrough device designation. This is a kind of a designation that was formerly an expedited pathway type designation that allows this technology to be fast tracked through, of course, pending the trial results, but still preserves the regulatory integrity of the FDA through it. So that's a major, major win for the trial and for the therapy. In addition, this is a trial that's funded through hybrid sources of funding by Cardia as well as CMS and insurance funders. And one of the challenges was the patient's co-pays, patients had to kind of contribute to their own co-pays for certain procedures and certain costs were declined from an insurance perspective. And BioCardia has done a phenomenal job of trying to address both of those areas. So CMS issued a reimbursement code and allowed for reimbursement for both treated and control patients and also cover the Inspector General advisory opinion helped to support BioCardia's cover and co-pays, which we've taken advantage of here at the University of Wisconsin. In addition, in an effort to further boost enrollment BioCardia has obtained Health Canada approval. And I think Debby towards the end, kind of attest the varying sites that are now going to be included in the overall trial program. And then subsequently, we've also had a 2-year data on the 10-patient rolling cohort. This is an open-label cohort that Carl will describe I think, in a little minute. And then, of course, there's been some new patient-directed materials all in an effort to enhance enrollment. So let's go to the next slide. Really, one of the efforts that's being made right now is to define what is the patient population that's best going to be treated or be optimized for the cardiac parts of the trial who is going to benefit the most. And this is in an era where we have 4 drugs and at least 2 devices that can also be beneficial in this patient population. And so BioCardia and others and sites are trying to learn about what patients are still left who are still in a sort of need for this therapy. And we know that it's a substantial number, but quantifying that poses some challenges -- and so recent efforts are being made to try to define that better. In terms of new patient directed material on the next slide, there are a number of new video links that are done in sort of layman's terms. They're all really well done and put together the 1 that Tim story is a patient of mine that actually went through the trial. He was a crossover patient. So he actually was randomized initially to a sham arm and then got crossed over. So he provides a very unique and interesting perspective from a patient's testimonial perspective of his impressions of things. And I think if 1 were to kind of look through those, you'd find it quite intriguing and interesting. There's still a great unmet need -- next slide. We know this, again, trying to quantify this. If we look at the various more recent studies of paradigm of the various drugs that are being used, for example, in the PARADIGM heart failure study, the Emperor and the DAPA heart failure study, looking at the Entresto SGLT2 inhibitors. You can still see that there is an unmet need, 13% death from cardiovascular causes and readmissions still existed in the treatment group, similar numbers in both of the other studies. And this is a follow-up of 16 to 27 months. And so this is a -- our study is going to be following patients up for 24 months. And how these numbers unfold in this patient population still has to be determined. But as you can see, there's still quite a substantial number of patients. When you think about the 6.5 million Americans have heart failure. Of those, half of those have heart reduced ejection fraction. And the majority of those have heart failure because of chronic myocardial ischemia from coronary disease you can see that we're talking about a substantial number of patients still. And I think that's it for my slides. I think we're handing it back over to Carl, Dr. Pepine, to describe the results of the rolling cohort through 24 months.

So the next few slides describe the results of those 10 patients who were in the rolling cohort, all of whom received the active cell product. In the demographic table, that's provided to you, you can see that the average age was 67 years. Unfortunately, 9 of the 10 patients were male, so we'd have very little information relative to women. And all of the 10 patients were white. The comorbidities are not unusual for patients with ischemic heart disease and heart failure. I would say they're exactly what was anticipated. And likewise, the frequency of guideline recommended medication use was also as anticipated. It's a very well treated group. Essentially, all of the patients had, had some attempt at revascularization of their coronary artery disease, generally by PCI or CABG or both. The clinical outcomes in these 10 patients over the first 2 years are summarized in the next slide. Recall that the current primary outcome is the 6-minute walk distance and the secondary outcomes are the New York Heart Association heart failure class in Minnesota living with heart failure code and the echo derived ejection fraction and wall motion parameters, and they're all summarized in this slide for you. Basically, the remarkable thing is that in patients with very serious heart disease and very impaired cardiac function, there were new deaths through the first 2 years of follow-on. And there were only 2 hospitalizations out of the 10 patients over 2 years, essentially 1 per year. And both of those, 1 was related to heart failure progression. And the other patient had multiple recurrent admissions in acute myocardial infarction. So these are the outcomes of the rolling cohort. What's also interesting relative to the primary outcome is the 6-minute walk distance -- and this slide summarizes the 6-minute walk distance at 6 months, 9 months, 12 months and 24 months. And they're all -- the change in the 6-minute walk distance is all very favorable and in the expected direction with an improvement ranging from about 6% to as high as 14% increase. Also remarkable is the ejection fraction. This is the fraction of the bullet injected from the left ventricle with each heartbeat. And as you can see from a median of 27, the ejection fraction progressively increases over time to about 37% at 24 months. And the improvement in ejection fraction is attributed to an improvement in contraction of the cardiac muscle in various segments. And as you can see, the improved segments are showing here from baseline to 24 months. I call your attention to the green part of the pie, which shows now a substantial fraction of patients who have normalized their cardiac function and call your attention to the yellow, which were the hypokinetic segments, and they have decreased considerably as have the akinetic segments, which are shown in brown. So to conclude, at the final 2-year follow-up of the 10-patient open-label cohort, CardiAMP cell therapy was well tolerated and safe with no treatment-related adverse events and no observed deaths. The 6-minute walk distance, the quality of life in the LV ejection fraction all remains stable or improved. And as I've shown you, remarkably, most of them improved. These results support the safety and potential efficacy of this cell therapy product, which is under investigation for patients with ischemic heart disease and heart failure in the larger Phase III pivotal trial called CardiAMP Heart Failure. A manuscript is under development to present these results. We now move into question-and-answer period, which is going to be handled by Debby Holmes.

Actually, Carl, we'll take questions from the -- well, thank you, Carl. Thank you, Amish. We'll take questions from the operator and the operator will manage the questions going ahead. Operator?

[Operator Instructions] Our first question today comes from Joe Pantginis from H.C. Wainright.

Thanks for the update. I appreciate all the details. Maybe first, a question for the investigators, if you don't mind. So obviously, these are pretty intriguing 24-month data. And I was just curious, 1 of the, I think, exciting things to me is that 7 of the 10 patients saw no changes in their background therapy over the 2 years. So I was curious how you can potentially emphasize that point or not to the importance of how that might read through to the randomized portion?

So that's a very interesting question, which I'll start with and then turn it over to Amish. So recall that these patients were all screened and actually, it was mandated by protocol that they be optimally treated using guideline-recommended therapy. So the fact that for a naturally progressive disease like heart failure related to coronary artery disease, that they did not have any progression to the use, for example, of resynchronization or additional therapies and they did so in the absence of need for readmission to the hospital except for those 2 patients that I mentioned over the 2 years. So I think that's remarkable. And if we could extend that to the major portion of the patients in the 260 cohort that we're randomizing now, that would be a very, very great step forward. Amish?

Yes. This is Amish. The only thing I would add to that is that the 10 patients that were enrolled in this rolling cohort were drawn or seen in the facilities of the Johns Hopkins University of Florida and the University of Wisconsin that have very robust heart failure programs. Subsequent -- subsequently all of the randomized sites have a similar robust heart failure programs. So these patients are all as part of their entry criteria, very optimally treated to the point where there's likely no more room to move on those medications. The fact that they don't have to have more medications adjusted is a good thing in that a few of those patients have a reduced medication burden, I think, it's a good thing. It creates an interesting paradigm potentially going forward, if we can rescue heart function through the cell therapy, will they then need the same number of therapies. Well, 10 patients not going to answer that. Of course, we don't have a blinded randomized sham control group to compare to here. That's why we're doing the trial, but it's very interesting otherwise, but thank you for the question.

I appreciate that. And then for the company and maybe everyone on the call, I wanted to see if you could provide any more color with regard to the -- your comments about the statistical analysis plan going forward for the randomized. And I guess I would ask it, what is your -- even if it's rough at this point, your wish list with regard to your discussion for the regulators, like what kind of outcomes would you like to see, might not get, but would like to see?

Joe, that's a great question. This is Peter. I'll have Dr. Sujith Shetty address this. Suji? .

Thank you for the question. as we talk about the adaptive design with our statistical analysis group and also with the FDA in the near future. I think our ultimate goal will be to sure that taking a look at our signal currently will allow us to at least the DSMB will allow the DSMB to potentially either ensure that we have a statistical plan that will allow for success at the end of the study. And that will be able to be enhanced by either based on the current data of whether or not we can stop the study early, continue on to the end with a known success, whether it be at the current number of patients or even an increased amount of patients if necessary. Really, what we're trying to do is make sure that we have powered the study sufficiently based on the data that we're currently seeing. And really, that's what the key pieces of the adaptive design will allow us to do.

I understand. And then just do you have a time line for next potential discussion with the FDA?

We would definitely like to have that discussion relatively soon. We plan within a 6-month time line to have hopefully most of the work done that will allow us to present this to the DSMB at our next DSMB meeting.

[Operator Instructions] Our next question comes from Michael Okunewitch from Maxim.

Thanks for providing this update. So in the 2-year data, you saw an improvement in the stage of heart failure and 50% of patients plus improvements in the 6-minute walk and ejection fraction. So I'd like to say how common is it for this effect to occur spontaneously.

I would pass that to -- go ahead, Carl. Perfect.

Yes. So it's a good question, and thank you for it. So really this is something you don't see spontaneously in very many patients when the etiology of the heart failure is due to a prior myocardial infarction and ischemic heart disease. That means that there's generally a scar, a large scar that has replaced functioning myocardium. And so this is uncommon to see in patients with ischemic heart disease as the etiology for their heart failure.

I would say -- maybe I would add some light to this, the natural history of this patient population is such that their outcome over the ensuing several years, is quite poor in general. A number of patients will succumb to mortality. We see this in Kaplan-Meier survival curves with other trials involving therapies. When we look at their control groups, and we see even with the therapeutic group, there's always a decline in mortality and function. And that's to have something stable for 2 years although, again, not randomized, is actually a positive thing in my opinion.

And then I'd like to see then if you could help us interpret what this may mean at the at the tissue level, does it suggest that there is an actual healing effect and an improvement in that scar tissue to make it more functional? And is this thought to be potentially responsible for the potential mortality benefit that you saw among the 10 patients in this early data?

So it's likely to be the reason for the benefit that we saw. If you remember the slide that I showed, looking at the wall motion in the various cardiac segments, most of the improvement occurred in the hyperkinetic and the akinetic segments. So that hyperkinetic means they weren't moving normally, their movement was reduced. And in the akinetic. It means that they weren't moving at all. So in general, there's usually a border zone and there are some islands of viable cells in these patients who have had a myocardial infarction and are left with heart failure. And so my belief is the BioCardia cell preparation allows those segments to recover.

And then one last, I'd just like to ask a bit about the enrollment, if you could provide a bit more color. It seems that in the second half, still has been a bit challenging. And could you discuss in a bit more detail the factors driving that? I know you touched on that Dr. Pepine. But given that much of the hood effects have worked themselves out of other areas of life, could you just provide a bit more detail?

Well, unfortunately, the COVID effects are continuing in lingering. As you know, there's a tremendous shortage of nurses. And at our institution alone, and we have had many of our dedicated research nurses moving over to take care of other sick patients. not only the COVID patients, but the patients who had a need for hospital care that was put off during the hike tightening part of the COVID pandemic. And also the issue of adding nurses to the workforce pool is continuing, is not going away. So those are areas that we have to deal with, and our hope is that we can slowly change this over the ensuing months.

Michael. Thank you. Debby, do you want to add another comment on the enrollment and efforts that you're pursuing to advance it at all the sites?

Sure. I'd love to add that. Yes, we have recognized some of the huge effects of COVID-19. And 3 of the things that we're working on are to basically it around some of those drawbacks we've seen. One is to add new sites, including those in Canada. So there's huge effort inside to get those sites on board as quickly as possible. Another effort is to focus efforts with the sites that basically their focused efforts to work with them to improve efficiency so that the efficiencies in finding patients are identifying patients, consenting patients, helping the sites because they have the limited bandwidth to be more efficient and optimize their processes. So that's a huge ongoing effort as well. And then the third is new patient recruiting materials, enhanced ones. So we have 1 of the slides showed that basically we have new videos and things that are -- will help the coordinator reach out to patients more easily with enhanced products or tools.

Maybe if you don't mind, I can add something there. Just real quick. This is Amish Raval. The effect of COVID has not just affected nurses, Ecotec as well as research coordinators A lot of the efforts initially for research were directed towards COVID-directed therapies. And so a lot of resources are pulled in that way. But now things are coming back. And although it's delayed, the coordinators are coming back online or getting Ecotec back in-house. And so things are starting to ramp back up again. It's been more delayed than going to the grocery store. But ultimately, I'm optimistic that we'll be in good shape through this winter.

So I think that's our last question, and I want to thank all of you for participating in today's call and for your interest in BioCardia and our efforts to advance a new therapeutic program for the treatment of heart failure. We look forward to sharing our continued progress ahead. Thanks, stay healthy, be kind and have a wonderful day. And with that, we'll end the call.

Ladies and gentlemen, with that, we will end today's presentation. We thank you for joining. You may now disconnect your lines.