Ladies and gentlemen, thank you for standing by. Good morning, and welcome to the BioCardia 2022 clinical leadership and management call on the CardiAMP heart failure trial. 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 and then one on your telephone keypads. To withdraw your questions, you may press star and 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 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, President and Chief Executive Officer, Dr. Sujith Shetty, the Chief Medical Officer, and Ms. Debby Holmes-Higgin, the 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 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 Form 8-K filed with the SEC, particularly the cautionary statements in them. The content of this call contains time-sensitive information that is accurate only as of today, October 5th, 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 CardiAMP 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.
Good morning, and I'm pleased to be able to give you an update on our 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 three, the progress of the trial is depicted. As you can see, the trial started 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 entered a fairly rapid enrollment phase. As you can see, the patients consented, accumulated until we were impacted in early 2020 by the pandemic, as all clinical trials were impacted 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, were 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 four months, that embargo was relieved at our site, but at many of our participating sites, it continued. The downstream effects of shifting personnel from research positions to take care of the sick patients with COVID-19 has been very long-lasting and has impacted essentially all clinical trials.
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. 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 three to two, three to the active cell product and two 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 thirtieth. 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 enable 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. There are a number of opportunities, and that plan is currently under negotiations and discussions or plans with FDA. I wanna 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. Thank you everyone for attending. 2022 has seen some tremendous progress in the CardiAMP heart failure trial in two fronts. BioCardia has been very responsive to the executive steering committee's recommendations and so forth, moving forward. Those two accelerations are in developing a regulatory path that may be more accelerated, as well as looking to accelerate enrollment through a couple of mechanisms. In January 2022, the FDA 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. That's a major win for the trial and for the therapy. In addition, you know, this is a trial that's funded through hybrid sources of funding, BioCardia as well as CMS and insurance funders. One of the challenges was patients' 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. BioCardia has done a phenomenal job of trying to address both of those areas.
CMS issued a reimbursement code and allowed for reimbursement for both treated and control patients, and also covered the OIG advisory opinion, which helped to support BioCardia's coverage 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 can kind of attest to the varying sites that are now going to be included in the overall trial program. Subsequently, we've also had two-year data on the 10-patient roll-in cohort. This is an open label cohort that Carl will describe, I think, in a little minute.
Of course, there's been some new patient-directed materials, all in an effort to enhance enrollment. Go to the next slide. Really, the 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 CardiAMP Heart Failure trial, who is gonna benefit the most. This is in an era where we have four drugs and at least two devices that can also be beneficial in this patient population. 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. We know that it's a substantial number, but quantifying that poses some challenges.
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 one that Tim's 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. He provides a very unique and interesting perspective from a patient's testimonial perspective of his impressions of things. I think if one 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 the various drugs that are being used, for example, in the PARADIGM-HF, the EMPEROR-Reduced and the DAPA-HF, looking at the Entresto SGLT2 inhibitors, you can still see that there is an unmet need. 13% deaths from cardiovascular causes and readmissions still existed in the treatment group. Similar numbers in both of the other studies. This is a follow-up of 16-27 months. Our study is, you know, going to be following patients out for 24 months, and how these numbers unfold in this patient population is still yet to be determined.
As you can see, there's still quite a substantial number of patients. When you think about the end, 6.5 million Americans have heart failure. Of those, half of those have heart failure with reduced ejection fraction, and the majority of those have heart failure because of chronic myocardial ischemia from coronary artery disease. You can see that we're talking about a substantial number of patients still. 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.
Thank you, Amish. The next few slides describe the results of those 10 patients who were in the roll-in cohort, all of whom received the active cell product. In the demographic table that's provided to you can see that the average age was 67 years. Unfortunately, nine of the 10 patients were male, so we have very little information relative to women. 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. Likewise, the frequency of guideline-recommended medication use was also as anticipated. It's a very well-treated group.
Essentially all the patients 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 two years are summarized in the next slide. Recall that the current primary outcome is the six-minute walk distance, and the secondary outcomes are the New York Heart Association heart failure class, the Minnesota Living with Heart Failure score, and the echo-derived ejection fraction and wall motion parameters. 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 no deaths through the first two years of follow-up.
There were only two hospitalizations out of the 10, patients over two years, essentially one per year. Both of those, one was related to heart failure progression, and the other patient had multiple, recurrent admissions and an acute myocardial infarction. These are the outcomes of the rolling cohort. What's also interesting relative to the primary outcome is the six-minute walk distance. This slide summarizes the six-minute walk distance at six months, nine months, 12 months, and 24 months. The change in the six-minute walk distance is all very favorable and in the expected direction, with an improvement ranging from about 6% to as high as a 14% increase. Also remarkable is the ejection fraction.
This is the fraction of blood ejected from the left ventricle with each heartbeat. As you can see from a median of 27, the ejection fraction progressively increases over time to about 37% at 24 months. The improvement in ejection fraction is attributed to an improvement in contraction of the cardiac muscle in the various segments. As you can see, the improved segments are shown 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. 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.
To conclude, at the final two-year follow-up of the 10-patient open label cohort, cardiac cell therapy was well tolerated and safe, with no treatment related adverse events and no observed deaths. The six-minute walk distance, the quality of life, and the LV ejection fraction all remained stable or improved. 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 gonna be handled by Debby Holmes-Higgin.
Actually, Carl, we'll take questions from the.
Yep.
Well, thank you, Carl. Thank you, Amish. We'll take questions from the operator, and the operator will manage the questions going ahead. Operator?
At this time, we will open the call to questions. Should you wish to ask a question on today's conference, you will need to press the star key followed by the number one on your telephones. If your question has been answered and you wish to withdraw your request, you may do so by pressing star and two. If you are using a speakerphone, we do ask that you please pick up your handset before entering the request and speaking on the conference. One moment for our first question. Our first question today comes from Joe Pantginis from H.C. Wainwright. Please go ahead with your question.
Hey, good morning, everybody, and thanks for the update. Appreciate all the details. Maybe first a question for the investigators, if you don't mind. Obviously these are pretty intriguing.
Sure thing.
24-month data. I was just curious, you know, one of the, I think exciting things to me is that seven of the 10 patients saw no changes in their background therapy over the two years. I was curious, you know, how you can potentially emphasize that point or not, you know, to the importance of how that might read through to the randomized portion.
That's a very interesting question, which I'll start with and then turn it over to Amish. Recall that these patients were all screened and actually it was mandated by protocol that they be optimally treated using guideline recommended therapy. 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 did so in the absence of need for a readmission to the hospital, except for those two patients that I mentioned over the two years. I think that's remarkable.
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?
Yeah, 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, you know, Johns Hopkins, University of Florida, and University of Wisconsin that have very robust heart failure programs. Subsequently, all of the randomized sites have a similar robust heart failure program. So these patients are all, you know, 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, and that a few of those patients have a reduced, you know, a medication burden, I think is 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. It's very interesting otherwise. Thank you for the question.
No, I appreciate that. You know, for the company and maybe everyone on the call, wanted to see if you could provide any more color with regard to your comments about the statistical analysis plan going forward for the randomized portion. I guess I would ask it, you know, 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 it. Sujith.
Good morning. 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 ensure that taking a look at our signal currently will allow us to, 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. 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. Really that's what the key pieces of the adaptive design will allow us to do.
I understand. Just, do you have a timeline for next potential discussion with the FDA?
We would definitely like to have that discussion relatively soon. We plan within a six-month timeline to have hopefully most of the work done that will allow us to present this to the DSMB at our next DSMB meeting.
Great. Thanks for the added color, guys.
Thank you, Joe.
Once again, if you would like to ask a question, please press Star and one. Our next question comes from Michael Okunewitch from Maxim. Please go ahead with your question.
Hey, guys. Thank you for taking the question, and thanks for providing this update. In the two-year data, you saw an improvement in the stage of heart failure in 50% of patients, plus improvements in the six-minute walk and ejection fraction. I'd like to see how common is it for this effect to occur spontaneously?
I would pass that to. Go ahead, Carl. Perfect.
Yeah. It's a good question, and thank you for it. 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. 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. We look at their control groups, and we see even with the therapeutic group, there's always a decline in mortality and function. You know, that's you know to have something stable for two years, although again, not randomized, is actually a positive thing in my opinion.
Thank you. I'd like to see then if you could help us, you know, interpret what this may mean at the tissue level. Does this suggest that there is an actual healing effect and an improvement in that scar tissue to make it more functional? Is this thought to be, you know, potentially responsible for the potential mortality benefit that you saw among the 10 patients in this early data?
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 hypokinetic and the akinetic segments. That hypokinetic means they weren't moving normally, their movement was reduced. In the akinetic, it means that they weren't moving at all. 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.
My belief is the BioCardia cell preparation allows those segments to recover.
Thank you. One last, I'd just like to ask a bit about the enrollment to see if you could provide a bit more color. It seems that, in the second half, still has been a bit challenging. 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 COVID 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 and lingering. As you know, there's a tremendous shortage of nurses, and at our institution alone, 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 heightened part of the COVID pandemic. Also, the issue of adding nurses to the workforce pool is continuing, is not going away. Those are areas that we have to deal with. Our hope is that we can slowly change this over the ensuing months.
All right. Thank you very much.
Michael?
Yes.
Yeah, Michael, thank you. Debby, do you wanna 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. Yeah. We have recognized some of these huge effects of COVID-19. Three of the things that we're working on are to, you know, basically get around some of those drawbacks we've seen. You know, one is to add new sites, including those in Canada. 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, you know, basically there are focused efforts to work with them to improve efficiencies in finding patients or identifying patients, consenting patients, you know, helping the sites because they have the limited bandwidth to be more efficient and optimize their processes. That's a huge ongoing effort as well.
The third is you know new patient recruiting materials you know enhanced ones. So we have you know one of the slides showed that basically we have new videos and things that are you know will help the coordinator reach out to patients more easily you know with enhanced products or tools.
Maybe if you don't mind, I can add something there, just real quick. This is Amish Raval. You know, the effect of COVID has not just affected nurses, echo techs, as well as research coordinators. A lot of the efforts initially for research were directed towards COVID-directed therapies, and so a lot of, you know, resources were pulled in that way. Now things are coming back and, you know, it's, although it's delayed, you know, the coordinators are coming back online. We're getting echo techs back in, you know, in-house. Things are starting to ramp back up again. It's been more delayed than, you know, going to the grocery store, but ultimately, I'm optimistic that we'll be in good shape through this winter.
All right. Thank you very much.
Thank you for that, Amish.
The thorough answers.
I think that's our last question. I wanna 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. With that, we'll end the call.
Thanks.
Ladies and gentlemen, with that, we will end today's presentation. We thank you for joining. You may now disconnect your lines.