To our next fireside chat. Again, my name is James Molloy, biotech and specialty pharmaceutical analyst here at AGP. In this chat, we're talking about another of our coverage companies, BioCardia, which we have as a buy-rated with a $6 price target. BioCardia is a late-stage development company with an autologous stem cell therapy for ischemic heart failure and chronic myocardial ischemia. That's in two phase, it's in two separate phase III trials currently. With us today from BioCardia is CEO Peter Altman. Thank you for joining us here today, Peter. Thank you, Jim. Glad to be here. Perhaps you can start with just a brief overview of BioCardia for our listeners. Sure. BioCardia is a small publicly traded company located in Sunnyvale, California, focusing on cell and cell-derived therapies for cardiovascular and pulmonary disease. We have currently, as you know, four separate clinical programs at various stages of advancement. The lead indication is the lead, we think, correct me if I'm wrong, but is the heart failure, the BCDA01 CardiAmp phase III trial. Could you walk our listeners through this disease state and how the autologous stem cell therapy could be helpful? Absolutely. Heart failure is an enormous unmet disease out there, which I've spent much of my lifetime working on. All cardiac disease essentially ends in heart failure. What we're doing in this program is we are taking autologous cells that typically respond to injury in the heart, and we're delivering very high dosages of these cells directly into the heart muscle. The cells have been shown in preclinical models to reduce fibrosis and enhance capillary density, the small microvasculature in the heart. The strategy is one of really treating microvascular dysfunction. The preclinical work is extremely supportive with fabulous safety in these supportive efficacy readouts. In the clinical studies to date, we've seen in three studies some pretty positive signals and a great safety profile. The therapy itself is unique in that it has a selection diagnostic really on the front end, essentially to screen out patients who really are not appropriate for the therapy because of the nature of their cells. They cannot achieve sufficient therapeutic dosage. It incorporates a point of care in one procedure, cell harvest, processing, and delivery with proprietary technologies that really presents a comprehensive approach to delivering these cells to the heart. We are able to achieve higher dosages directly at the regions where we wish to have these cells. So far, our results have been pretty solid across our trials. Let's touch on it. Let's walk through. You had some data out in March from the heart failure one trial. If you could walk our listeners through that, please. Absolutely. In March, at the late-breaking clinical trial session at the American College of Cardiology meeting in Chicago, end of March, March 29th, we had a presentation of the primary outcomes in the study. The key takeaway, this is a study that we knew we were not going to hit the primary endpoint because in its composite structure, the third component of the endpoint, how far a patient could walk, we had confounders so that all patients could walk farther. However, we showed reduced mortality. We showed reduced major adverse cardiac and cerebrovascular events such as stroke, heart attack, hospitalization. We saw improved quality of life in these patients in a randomized, double-blind, placebo-controlled 115-patient clinical trial in which we are selecting patients, harvesting and processing their cells, and delivering them at 10 locations in the heart muscle. In a subgroup analysis, which is the patients with elevated markers of heart stress that are used in all heart failure clinical trials, we saw the results demonstrated statistical significance in the endpoint, which had three tiers where the third tier is quality of life. We also saw that all of the components of the primary and secondary endpoints, the survival, the reduction in major adverse cardiac events, the quality of life, and the six-minute walk distance improved for the treated patients over the controlled patients. It is a data set that we're pretty thrilled with. This is a one-time dosage of these cells. After the procedure, the only thing we've left behind in these patients is essentially very high concentrations of their own cells at the regions of damage to promote this reduced fibrosis and enhanced capillary density. The data set that we have is really solid. It was two-year follow-up that we had, Jim. That supports that this is a robust effect that we're seeing that has staying power. The six-minute walk, the data looked really good. That is what you're going forward with in the second phase III trial. That's correct. The FDA has in December, soon after we decided to put this trial on pause, we secured an approval from the FDA to do a subsequent trial in which we solved the six-minute walk issues. We've been waiting for final data before we put enormous momentum behind it. We have three active centers today. We are actively enrolling patients. In fact, we will hear today whether another patient passes the screening assay. In this new trial, this is a 250-patient randomized placebo-controlled double-blinded trial of patients with ischemic heart failure. There have been a couple of modifications in the study design based on learnings from the earlier trial. We're focusing in on the patients who had elevated markers of heart stress, which showed fabulous outcomes in the previous trial. We also have a way to use that screening assay. Instead of excluding patients, we actually have the ability now to modify the dosing. We expect very few patients will be excluded. The trial this time around will have the support of all that experience, but also the physicians will have the data from the previous trial, which we think is going to really enhance the enrollment process ahead. That is the primary effort we're advancing here in the United States today. What are the next catalysts we should be looking for from the heart failure two trial? From heart failure two, I think we will have regular enhancements to the enrollment. We'll be adding, we have up to 40 centers to add to this trial. We do expect to add Canada, and we are thinking about adding sites in Europe as well. All of that momentum will come together. That trial actually is a backdrop for some of the other activities we're doing on the regulatory front ahead. I know that the heart failure one trial, some of the challenges with enrollment and COVID did not help at all. What learnings have you taken from the heart failure one to the heart failure two to help spur enrollment? I mean, quite simply, we've worked now with 25 centers across the United States. We're starting heart failure two, CardiAmp HF2, with the leading centers in the initial CardiAmp heart failure trial. The modification of the selection element where we would exclude roughly 35% of the patients has been modified. We think that that modification will actually double the rate of enrollment alone. Those are two initial primary value adds. I also think that the experience, as we onboard sites, they've not only been trained up, but they've actually treated patients with this approach. I think the biggest factor by far is the data that we have. We have a 115-patient randomized placebo-controlled trial that shows all the details I just shared with you initially. That's compelling for physicians to refer their patients into the study. Additionally, the Japanese PMDA is looking at a potential for an expedited approval, which would be wonderful. Could you walk our listeners through how that could go? Yeah. Right now, our strategy is we are advancing two regulatory submissions right now based on the results from the CardiAmp heart failure trial. There's going to be probably two submissions in the coming weeks. One will be into Japan PMDA pursuing approval for CardiAmp cell therapy for the treatment of ischemic heart failure. The Japanese regulatory body, Pharmaceutical Medical Device Agency, is extremely rigorous. We've already met with them four times on this study. This next meeting will be a preliminary clinical consultation in which they will be reviewing all of the data and hopefully our draft submission for approval. There will be other consultations ahead, but they will go through all of the data that we now have. They've seen all of our previous data. The strategy is really to help them to realize the value proposition of CardiAmp cell therapy for their patients. I note that our cell processing platform is already approved for therapeutic purposes in Japan. Japan has taken a leading role in cell therapy. They have previously approved a cell therapy based on seven patients for ischemic heart failure. They have two more therapies that are before PMDA, I expect in the year ahead. One based on eight patients that I do expect approval, and the second on 10 patients. We are coming to them with close to 200 patients with CardiAmp in our phase I, phase II, and phase III trial. We are also coming to them with an autologous therapy that fits into the culture of the wholeness of the individual in Japan, where they do not do much transplantation of other subjects' tissues. At the same time, it is a minimally invasive procedure, whereas the other therapies that are approving require open chest surgical access. As it's autologous, there's no need for chronic immunosuppression, which we expect the other therapies to require. There are lots of really compelling reasons for PMDA when they look at risk-benefit versus CardiAmp versus the other therapies we expect them to approve to provide support for CardiAmp. The timeline will be hopefully to get the submission for approval in this year, but it will take, I would estimate, at least nine months and probably 12 months for full approval to come together. They are extremely rigorous. On the FDA side, our initial submission is actually for the delivery system. We have fabulous safety data in the CardiAmp heart failure trial. Our first step with FDA is to secure approval of our delivery system, which we think has value for revenue-generating for partners. We will continue conversations with them on CardiAmp approval ahead. In the United States, current regulations are such that we expect it to require both CardiAmp HF and CardiAmp HF2 for approval. Maybe move it over to the CardiAmp CMI for chronic myocardial ischemia, BCDA02. Could you walk our listeners through this disease state and again, how stem cell therapy will help here? Yeah, absolutely. CardiAmp CMI, the CMI stands for chronic myocardial ischemia. This is chronic myocardial ischemia with refractory angina or chest pain. It's the hallmark of having severe pain in your heart because you have poor perfusion. This is often a hallmark where patients go in and have an angioplasty or bypass surgery. Because this is chronic myocardial ischemia, the patients are not eligible for those therapies. It's primarily believed to be due to microvascular dysfunction, which is what we're treating in CardiAmp heart failure. We're targeting the ischemic etiology patients, the patients who've had poor blood supply that's caused their heart failure. Here, we're moving upstream, and it's a disease indication that's poorly met. There's at least 1 million patients in the United States. To date, no therapy has done as well as cell therapy. There was a leading cell therapy advanced by Baxter Healthcare some time ago, which generated some fabulous results. Although the problem with that whole therapeutic program was the enormous cost of goods the way Baxter was pursuing it. They would have had to charge, I estimate, $100,000 just for their therapy to be successful. Even then, they would have probably pretty low margins. What we're doing sort of solves that by not selecting the cells and processing them remotely, but rather having a means to select the patients with good cells and treat them in a single session, we've collapsed the cost of goods for this therapy. This is important for CardiAmp chronic myocardial ischemia, but also for heart failure. The CardiAmp cell therapy has potential to be the least expensive cardiac cell therapy ever with minimally invasive delivery, point-of-care cell processing. Because of that, it will have staying power. If CardiAmp gets approved, even if another therapy comes to market, it will likely have to show it's as good or better than CardiAmp. Unless it's drastically better, the payers will always likely say, "Okay, well, let's start with CardiAmp because its cost profile is going to be so attractive to society." We have solved those issues that Baxter has. In fact, we've published that we have higher cell counts of what they were delivering in their trial in our trial with our unique approach. Right now, we have the last patient coming in in the low-dose cohort. We're working on a manuscript, and we're working on a scientific publication of that early data, Jim. Yeah, you've got the six-month data here, the last patient for the roll-in cohort, hitting the six-month endpoint just recently. There should be data coming out near term. When should we be looking for that? When we get it out there, right? Our top priority are the FDA and Japan PMDA submissions, as we said in our recent earnings call. Once we get those done with bows on them and feel really good about them, we'll be working on a lot of the other paperwork associated with CardiAmp CMI. What are the next steps after that for CMI? I mean, right now, we're exploring the value proposition of CardiAmp HF is enormous. I think what CardiAmp CMI has in place with its Medicare reimbursement, I think we'll probably pursue maybe a breakthrough designation for it like we have for CardiAmp HF. I mean, we'll continue to seek ways to advance that program. I think we're going to be pretty focused on CardiAmp HF in the short term. We'll see where we go on the other side of getting these regulatory submissions in and getting CardiAmp HF2 up, running, and humming along. Your pipeline continues. You've got BCDA03, CardiAlo for ischemic heart failure, phase I/II, BCDA04, allogeneic NK1R-positive MSCs for COVID. What is sort of the latest on these trials? What should we expect coming out of them? Yeah. So the CardiAmp platform is our autologous platform. We have an allogeneic platform as well, which just recently had a Data Safety Monitoring Board readout in a heart failure indication. That data is a very nice data set to have. We have been focusing on, we have approved INDs for that therapy for both the cardiac applications and the respiratory applications. Right now, we're focusing on cardiac. We're looking to partner out the pulmonary indication today. I note that in the pulmonary indication, a peer company is actually going to receive approval for that indication in Japan, which is for acute respiratory distress, as you noted. This effort for these therapies is really to continue to add data. As a small company, we have to be focused on our lead program to make sure it's meeting its timelines. There is a lot of opportunity to advance these projects ahead. We expect the cardiac allogeneic program to move to the next higher dosage now that we have completed this DSMB review. Right now, the pulmonary indication is on hold, although it is an indication we completely believe in. It is evidenced by the approval that is anticipated for our peer company in Japan shortly for that indication. How would you characterize the partnership environment currently for potentially licensing or partnering? We have a number of partner activities that are active. I think CardiAmp, the focus is on a distribution pathway in Japan. I think the value proposition for the allogeneic platform is we can go into many different indications as we have solved manufacturing with clinical data. Then on the other front, on our biotherapeutic delivery platforms, we have active conversations with pretty much everybody who is active in cell and gene therapy to the heart. I do expect that we will have some nice things to announce in the months ahead. As you know, deals are challenging. I think that the concern over market stability and deployment of capital has had an impact in the pharmaceutical sector. We will see ahead. Our assets are proven and in the clinic, and our intellectual property estate is strong. If there are partners listening, we have a great pipeline. There's a lot of interesting avenues to advance here at BioCardia. All right. With that, we're at the end of our Fireside Chat. I'd like to thank Peter from BioCardia for joining us this afternoon and for all of you for listening as well. Please stay tuned for the next Fireside Chat coming up right after this. Thank you. Thank you.