Good day and welcome to the BioCardia CardiAMP Chronic Myocardial Ischemia Trial Conference Call. All participants will be in 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 touch-tone phone. To withdraw your question, please press star, then two. Please note this event is being recorded. I would now like to turn the conference over to Peter Altman, CEO and President of BioCardia. Please go ahead.
Thank you, Cindy, and good afternoon to everyone on the call. As many of you know, our lead platform at BioCardia is our autologous mononuclear cell therapy intended for two related clinical indications of ischemic heart failure and chronic myocardial ischemia. Both of these programs are approved by Medicare for reimbursement, and both programs qualify as pivotal clinical studies in our efforts to provide important evidence to support marketing approval from the FDA. We've had a great deal of recent news on our lead program in ischemic heart failure, and today I am honored to be able to introduce you to two world-class physician scientists who will share our clinical efforts together for advancing autologous cardiac cell therapy as a treatment for chronic myocardial ischemia to help patients suffering from refractory angina.
With us today are Dr. Carl Pepine, Professor of Medicine at the University of Florida at Gainesville, and Dr. Amish Raval, Professor of Medicine at the University of Wisconsin-Madison. These gentlemen will help us appreciate the critical impact of chronic myocardial ischemia and refractory angina from both the patients' and clinicians' perspectives, cell therapy as a potential solution for this clinical problem, the promising cardiac cell therapy clinical data seen to date for these patients, and directions for the pivotal randomized controlled trial ahead. Both Dr. Pepine and Dr. Raval will speak to selected topics during our time today. Dr. Pepine will begin the presentation. There will be an opportunity to ask questions at the end of their presentation of the slides that follow. Dr. Pepine, I turn it over to you.
Good afternoon. The problem is chronic myocardial ischemia. This is a tremendous burden and a considerable unmet need. It's characterized by a disabling effort-limiting chest discomfort referred to as refractory angina. Patients suffer from poor perceived health status, tremendous psychosocial and psychological distress, so much so that many have termed it as post-traumatic stress disorder. They also have an impaired quality of life, and they represent a tremendous burden to the healthcare system due to a consumption of significant resources. It's estimated that 600,000 to 1.8 million Americans suffer from refractory angina, with approximately 75,000 new cases each year. We have very minimal treatment options, basically four or five drugs, and all those therapies have considerable limitations and are associated with only a minimal reduction in angina. Thus, there's a large group of patients with angina who remain unrevascularized, who have a poor quality of life.
Although their mortality is not necessarily high, largely because they have preserved left ventricular function, their resource use is extraordinary. Now, the therapies for refractory angina are summarized on this slide, and as we'll say at the end of it, there is considerable room for improvement, and cell-based therapy has shown great promise. The most recent addition over 20 years ago is a drug called ranolazine. It is reasonably effective. However, it also has difficulties with being poorly tolerated. We also have enhanced external counterpulsation. This does not require any invasive interruption, but it is very inconvenient. The patient must go to the center to receive the treatment. The treatment typically consists of about an hour of external pulsation, and they generally are treated 3-5 days a week. It's extraordinarily costly and inconvenient. And thirdly, we have G-CSF-mobilized cells.
This is a treatment which releases angiogenic cells from the patient's bone marrow. This is investigational. Three trials have evidence to support some benefit. However, the exact mechanism of action is believed to be angiogenesis, but it may not be curative for this particular problem, and we estimate that it costs about $100,000 per treatment. Other small molecules, gene therapies, implantable device therapies are in development, but they will be challenged to have the same safety profiles as autologous cell-based therapies. Now, CardiAMP is using a therapy that Dr. Raval will discuss with you.
Thank you, Carl. So the CardiAMP CMI program is modeled after the CardiAMP heart failure program, and so some people may have seen this slide 4 image before. In this particular workflow, we identify patients who we believe are most likely to benefit from CardiAMP CMI therapy, and this involves a screening series of tests that identify patients who have disabling chest pain or angina with objective evidence of coronary artery ischemia and myocardial ischemia, as well as an angiographic evidence of blood flow limitation to the heart. In addition, these patients, once prescreened, undergo a small sample bone marrow aspirate to identify whether or not they have the requisite cell content, cellular content, that we think are active in this therapy. That cell amount gets tested and evaluated, and if that patient then screens through, they're invited to return back for a larger bone marrow aspirate.
This is a simple procedure performed at the bedside where a needle is advanced into the bone in the pelvis called the iliac crest, and in this particular case, the treatment involves aspirating out approximately 60 ml of bone marrow content. That content is then processed using the CardiAMP processing system, and ultimately, the cell product is then aliquoted into small syringes. We then, in the same venue, roll the patient from their side approach, which is how a bone marrow aspirate is usually done, to their back, and we advance a catheter through the groin. This is through the femoral artery, and this is the BioCardia helical catheter that is advanced through along with the Morph steerable element that allows it to be steered around in the heart.
Once the catheter is within the heart chamber, the left ventricular chamber, we then go ahead and advance the needle into the muscle, and the novelty of this particular catheter is that it has a helical-shaped needle that allows you to corkscrew the needle in, and this has the advantage of improving retention of cellular products. Once a series of 10 injections are performed, the needle is withdrawn as is the catheter, and the patient recovers. They spend a night with us, and then there's a series of follow-ups that occurs at 30 days, 60 days, and all the way up to one year at least. The final randomized trial is still to be designed, but we think we're going to be monitoring these patients for at least a year and probably two years.
The advantage of this CardiAMP cell therapy is that it allows us to tap into that rich resource of cells that's in our bone marrow that seem to offer benefits in earlier studies, as Dr. Pepine mentioned, but also even before that, what led to how this field kind of started in an important paper in science in 1997 where the concept of CD34 cells to be an angiogenic cell factor came into light.
The safety of this approach is supported by numerous trials that have used similar bone marrow products in the heart without any safety adverse events, but the challenges of all of those other programs were fraught with challenges including the use of adjunctive medications like the G-CSF program that Dr. Pepine mentioned that causes immobilization, as well as the addition of other cells that may not have such benefits, and so we're really trying to enrich the population of patients who have these particular cell types that we think are important.
Go to the next slide. Can you go to the next slide? So in the next slide, in slide six, the trial design that has so far been done has been the open-label roll-in cohort. We have permitted two centers. 19 patients have been screened, and 14 have screen failed, a variety of reasons for that. Six-month data is available on four patients, and the randomized control trial will be up to 40 centers involving 333 patients, we think, and the primary endpoint will be total exercise time at about six months. We'll also track anginal episodes as a secondary endpoint.
If you can go back one slide, I seem to have to go back to slide five. There seems to be a delay. Okay, well, we'll go to slide seven then. Carl?
Yes. So the demographics of the patients that have been enrolled thus far are summarized on this slide. They're all men between the ages of 60 and 83 years old who experienced angina with short walking distance or even at rest. They were Canadian Cardiovascular Society score 3s or 4s, all reported having seven or more angina episodes a week, approximately once daily. Angina occurred despite using maximal tolerated doses of multiple anti-anginal drugs, which included beta-blockers, calcium channel blockers, nitrates, and ranolazine. All of these patients had obstructive coronary artery disease that was unsuitable for additional conventional coronary revascularization. All demonstrated evidence of inducible myocardial ischemia on their baseline stress tests. The next slide, please. This is an example of some of the coronary angiograms that we saw in the group.
As you can see, they're clearly unsuitable for additional revascularization with diffuse disease and diffuse narrowing of multiple vessels. In the next slide, the results are further summarized of 19 subjects screened thus far. There were 14 screen failed. Our plan is to greatly reduce the screen fails going forward by adjusting the screening criteria. As far as angina episodes from the patients' own diaries, the screening data revealed an average of 9 to 18 episodes of angina per week. At six months, the angina was reduced to an average of 1-2 episodes per week after treatment with the active cell product. No angina episodes decreased. I'm sorry, angina episodes decreased by 8.4 per week on average, and in addition, no changes in their anti-anginal medications were noted.
Relative to exercise tolerance testing, on average, 7.2 minutes were tolerated on the treadmill at baseline, and at six months after treatment, on average, 8.9 minutes were tolerated on the treadmill. In terms of screening and baseline data, exercise was stopped due to angina, fatigue, or dyspnea at baseline. At six months on the treadmill, exercise was stopped due to fatigue or dyspnea. Angina was not reported by any of those patients as a reason for stopping at month six. Amish?
Yeah. So I'm not sure who's moving the slides, but I think there's a delay in the presentation, so whoever is moving the slides, if they can go back to slide five just for a moment, and then we'll go back to 10 because I think that one got missed over. And it's an important slide that tells us that the CardiAMP heart failure the CardiAMP process in selecting cells is predicted to enhance our CD34 cell dosage in a much greater extent than previous studies that have looked at bone marrow cell products, including several important trials, the REPAIR- AMI trial, the PRESERVE- AMI trial, FOCUS- CCTRN, and the RENEW trial. When taking into account our enrichment strategy and trying to identify those right patients, exactly, as well as taking into account the retention properties using that helical catheter.
So I wanted to make sure we covered that. If we go back to slide 10, if we kind of leap forward again, to reiterate what Carl has said, in the patients that the CardiAMP CMI have gone through so far in this small, relatively small open-label cohort, if we look at other studies of other therapies, including the ranolazine therapies, the ERICA, and the CARISA, as well as the EECP trial and the CD34 trials, we see that the CardiAMP CMI trial has a greater reduction in the number of anginal episodes per week than all of these trials, and there was 100% of patients who seemed to respond favorably to CardiAMP CMI. If we go to the next slide, we see this demonstrated again with the change in exercise tolerance time.
This is patients going on a treadmill and tracking how long they last on that treadmill under certain standardized conditions. What we see is that at three months and six months, the CardiAMP therapies are allowing these patients to exercise longer than other studies have been able to accomplish. You'll notice, however, in this study, in this graph on the x-axis, the darker blue are the control groups, and you'll see that there is a favorable improvement in the control groups also, and so that suggests there is a bit of a placebo effect that can occur. We'll need to do a randomized trial to make sure that there is an incremental benefit over what might be that placebo effect. Next slide.
So the early results are compelling for both improved exercise tolerance time and anginal episode reduction, which has only been shown with cell therapy products in general, as well as the CD34 studies. This CardiAMP CMI seems to have a very favorable outlook. Implementing changes to enhance speed of enrollment and eliminate screen fails is really our goal as we think about the randomized pivotal trial and how this will be designed. The benefits of BioCardia's efforts with CMS is that reimbursement from CMS can help support the patient research costs and allow us to more efficiently do this trial. The hope is to enroll, as mentioned previously, close to over 300 patients, but there is a plan to have an adaptive statistical analysis plan for an early readout at or roughly before 100 patients.
We think that it would be very interesting from an FDA submission to evaluate these patients at 100 patients because if we see a very dramatic benefit, it can make a very meaningful impact on how the rest of the clinical trial would go. This is precision medicine. We think it's high dose and high retention, efficient delivery. It's autologous, so we do not have to worry about things like immunosuppression, and the costs have been significantly reduced by this point-of-care product. I think that's our last slide. Thank you for your attention. Are we still on the call?
Yes. Are you ready for questions?
We are. Yes, Cindy, we are.
Okay. Okay. We will now begin the question-and-answer session. To ask a question, you may press star, then one on your touch-tone phone. If you are using a 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 Pantginis of H.C. Wainwright. Go ahead, please.
Hi, everybody. Thanks for taking the questions. So a couple of questions first for the physicians on the call, and then maybe one for the company if you don't mind. Thanks for all the details. Obviously, the data are quite encouraging to be able to move forward into the pivotal study here. So maybe you'd like to dive into the weeds first on the enrollment criteria. You were talking about changing or adjusting to change the screen failure rates. Can you be a little more specific on what kind of criteria you're looking to change?
Do you want to take that, Amish?
Sure. Yeah. So I think part of the screen failure rates that were kind of high in the open-label cohort related to the number and the timing several steps, the number and timing of how the preceding stress test had to have been done within the screening window. It's complicated in the sense that we had a lower and upper threshold to how much these patients should be able to walk and not walk beyond in order to have an upper threshold. So we're contemplating removing that upper threshold because we realize this is a complicated type of patient. Patients who suffer from chronic, stable angina, who are refractory to medications and who have angina all the time and often take nitroglycerins, often tailor their exercise to not really achieve their maximum exercise effort in order to curb their anginal events.
So we really think just looking at their baseline and then follow-up exercise tolerance time without having an upper cutoff in the screening phase will be important. There are some discussions about altering the potency threshold to enable more patients to be able to get entered into the program as well. There are some extending out some of the prescreening requirements for things like cardiac catheterization, which previously had to have been done within a year. Some of these patients haven't had a cath for a few years, but they were deemed non-revascularizable before, and there's really no reason to believe that they can't be now. So there's just a number of things that are sort of simple, easy steps that we can take to make sure that we can enroll these patients.
No, that's really helpful. No, sure. I appreciate the color. So I guess maybe a little bit of a broader question also for the physicians is the overall profile of CardiAMP and the process. So you guys are the experts here, and I guess how do you view the expanded potential use into the broader cardiovascular community, or what requirements of specialization do you need, say, for the helical catheter and the MORPH system and any additional training that might be needed, and also being able to have the education curve be relatively light, if you will, with regard to the overall cell collection and processing factors?
Well, perhaps I'll take on the second part of that, and maybe Carl can talk about the first part. So the first part, I think, related to sort of the broader community and how the CardiAMP might fit and maybe there are other avenues, but the second part was more related to the catheter, which is my expertise. And so the catheter designed by BioCardia is a very teachable catheter. It's a very straightforward procedure. It's done over a guidewire. It's safe. The catheter can be manipulated within the left ventricle, and it's very teachable. And BioCardia's reach involving multiple previous clinical trials and having to train multiple individuals around the world is a testament to how straightforward this procedure is with a very low risk of complications. So I think that is probably not a big issue. I think it'll be disseminated in centers that have cardiac cath labs.
So that's sort of a kind of a basic requirement. But the nature of the cell therapy that's involved here is it can all be kind of contained. So you don't have to have specialized bone marrow transplant centers to do this kind of procedure. It can be done kind of generalizably. Carl, do you want to talk about the first part of it?
Yeah. Additionally, essentially, all major hospital centers have facilities for performing the bone marrow aspirate to harvest the cells, a standard procedure. It doesn't require any additional effort or any additional specialties on the surface for the hospital. Additionally, BioCardia has a bedside cell processor. It's about the size of a small laptop, perhaps. Easily, we keep ours in the catheterization laboratory, but it can go any place near there. And this processor doesn't require any of the other sophisticated cell separation devices that we used in a lot of other cell therapy trials. It has the ability to sort the cells and provide a cell product that is enriched in these CD34 cells that Amish mentioned, as well as CD133s and also some other products that are believed to be important relative to angiogenesis and repair of ischemic damaged tissue.
It's not going to require any additional training or expensive equipment on the part of the center that uses it.
Very helpful comments. Thank you very much. And then maybe just, like I said, one last for the company, if you don't mind. So Peter, maybe you could remind us because even with Dr. Pepine saying expensive equipment as an example, I don't want to say unique because that's too absolute a term, but I'll just say very interesting, and you don't hear it too much, the fact that many components of your efforts and in your clinical trials are Medicare reimbursed. So maybe you can just remind us about that and the advantages to have that, especially with regard to cost savings.
Yeah. Thank you, Dr. Pantginis. The Medicare reimbursement we have is unique. I think we actually have the first C code that Medicare ever issued for an investigational product, and it's under the category B designation. The reimbursement is currently at around, I believe, $17,500 per treatment or control procedure. And so that's helpful in offsetting clinical trial costs for the company. And that reimbursement is for the investigational trial. And the code as written by CMS covers both the ischemic heart failure program as well as the chronic myocardial ischemia program we're talking about today.
Great. Thank you for all the added comments, gentlemen.
Thank you. Thank you, Joe.
Our next question comes from George Wells, a private investor. Go ahead, please.
Hello. Yes. Thank you for taking my call. I just have one question. This is probably jumping ahead quite a bit here, but ultimately, if this treatment ends up being successful, is there anything up until this point that you've seen that would give any concern for the thought of actually being able to experience retreatment of the CardiAMP therapy? So in two years or three, a patient's treated one year, it's successful. And two, three years, let's say angina is experienced again by the patient, they could come back in for an additional treatment. So after so many years, they could continue to come back in and be retreated if need be. Is there anything, I guess, up until this point that you've seen that would give you any concern for that thought?
I think that. No, there's absolutely no signal that retreatment would be harmful or impair the patient's response. And in fact, although we're not doing it here, some studies, another study that BioCardia is working on, can store cells and also can freeze those cells and use them at a later date. So we don't do that in this current trial that we're talking about. If we should scale this and it should become a popular treatment, that's certainly something that can be done.
Okay. Thank you.
Again, if you have a question, please press star, then one. This concludes our question-and-answer session. I would like to turn the conference back over to Peter Altman for any closing remarks.
Thank you, Cindy. I would like to reiterate my sincere thanks to Dr. Pepine and to Dr. Raval for taking valuable time out of their clinic day to share their perspective on this clinical program. We will announce the results presented today and provide a link to the slides that were shared. There will also be details on our development plans in the coming quarterly report ahead. I thank all who have joined this call for your interest and support of our mission to develop and enhance cell therapies to treat cardiovascular disease. Have a wonderful day today.
The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.