BioCardia, Inc.

Good afternoon, ladies and gentlemen. Thank you for standing by. Welcome to the Biocardia Third Quarter 2024 Financial Results and Business Update Conference Call. At this time, all participants are in a listen-only mode. If you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, it will be an opportunity to ask questions. To ask a question, you may press star and then one using a touch and telephone. Draw 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 the call. I would now like to turn the floor over to Miranda Pato of Biocardia Investor Relations. Please go ahead, Miranda.

Thank you. Good afternoon and thank you for participating in today's conference call. Joining me from Biocardia's leadership team are Peter Altman, 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, references to management's intentions, beliefs, projections, outlook, analyses, and current expectations. Such factors include, among others, the inherent uncertainties associated with developing new products, technologies, and obtaining regulatory approvals. That forward-looking statement 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 and cautionary statements described in Biocardia's report on Form 10-K, filed with the SEC on March 27th, 2024, and in subsequently filed Form 10-Qs. The contents of this call contains time-sensitive information that is accurate only as of today, November 13th, 2024. 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, Biocardia's president and CEO. Peter, please go ahead.

Thank you, Miranda, and good afternoon to everyone on the call. Biocardia continues to advance our targeted cellular precision medicines for cardiovascular disease. Our clinical-stage cell-based therapies are targeted, and we are delivering our therapeutic candidates locally to the target tissues where they are most needed, and with a precision medicine perspective for specific patients that may benefit, identified by biomarkers. These biomarkers characterize a patient's disease state, and in the case of our autologous cardiac mononuclear cell therapies, the potential of the patient's own cells for providing therapeutic benefit. Our lead autologous cardiac cell therapy for the treatment of heart failure, which has been granted food and drug administration, breakthrough designation, and is reimbursed by the Center for Medicare and Medicaid Services, is being studied today in two active clinical trials. The mechanism of action of cardiac cell therapy is viewed as microvascular repair by promoting increased capillary density and reduced fibrosis in the heart tissue where these cells are delivered, both of which have been demonstrated in preclinical studies. Cardiamp cell therapy is a one-time treatment in which the patients who qualify based on the critical selection criteria have their own mononuclear cells aspirated and delivered to the heart in high concentrations in a single minimally invasive catheter-based procedure. The procedure avoids the need for cardiac surgery to deliver the cells, and no immunosuppression is required to prevent rejection of a patient's own cells. I will now provide detail on the status of our two cardiamp cell therapy trials for the treatment of heart failure. The Cardiamp Heart Failure 1 trial is a randomized placebo procedure-controlled study on 115 patients with 10 additional role in subjects. We will soon have final data where patients will have a minimum of one year and a maximum of two-year follow-up of the outcome measures with approximately 92% of the patients not lost a follow-up having two-year follow-up results. Only 4% of patients have been lost a follow-up in this study. We are conservatively optimistic that results anticipated for release in Q1 2025 will be similar to results seen in the interim review last year. This interim review data showed trends of improved survival, reduced major adverse cardiac events, and improved quality of life in those who received therapy. Final Cardiamp Heart Failure 1 results expected in Q1 2025 will be based on data that has had source data verification completed and will include an additional 13 randomized patients and patients with an additional year of follow-up outcome measures. These Cardiamp Heart Failure 1 trial results are enormously important as the data from this trial is intended to provide support for future product approvals and commercialization of the Cardiamp cell therapy in the United States and Japan. As we work to deliver these results from the 125 patients enrolled in the Cardiamp Heart Failure 1 trial, we are advancing a second confirmatory clinical study in the Cardiamp Heart Failure 2 trial. The Cardiamp Heart Failure 2 trial is a 250 patient pivotal study at up to 40 centers. It advances the same therapeutic approach and focuses on the remarkable benefits seen in patients treated with elevated NT-proBNP, a well-established biomarker of active heart failure. The FDA recently approved an important protocol amendment to personalized treatment plans in this therapy based on the Cardiamp cell population analysis expected to considerably increase the number of patients eligible for the trial. Simply put, the protocol amendment enables patients who would previously fall short of treatment requirements due to the nature of their cells to receive a higher dosage of cells. Multiple consented patients are in the screening queue today and study sites are being actively onboarded. Enrollment in the Cardiamp Heart Failure 2 trial is expected to be significantly enhanced because of the positive data and experience from the Cardiamp Heart Failure 1 trial. Additionally, efforts we have taken to streamline the clinical study, implement the treatment planning approach that enables more patients to be eligible based on the nature of their cells, and leverage the enormous experience in the broader Cardiamp clinical team are all expected to enhance trial enrollment. Beyond our lead autologous cell therapy program in heart failure, which I've just detailed, we have also made progress this quarter in other programs. This quarter, the last rolling cohort patient in the Cardiamp cell therapy and chronic myocardial ischemia trial, or BCD02, was enrolled, which means the primary six-month follow-up endpoint for all patients in this study cohort will be reached in Q1 2025. We have also secured FDA and IRB approval to enroll patients in our CardiAlo-Alogenaic Mesenchymal Stem Cell Therapy in ischemic heart failure, or BCD03, without requiring them to have been excluded from the Cardiamp Heart Failure trial. We expect the last low-dose cohort patient to be enrolled this quarter in the single-center dose escalation phase 1-2 study. On the Helix biotherapeutic delivery partnering front, we have no updates to share at this time on current and future partners. We continue to be focused on long-term partnerships where our contributions to the success of partners will reward our shareholders. One element of the Helix delivery system is our proprietary MorphDNA steerable introducer platform. This MorphDNA product family design has performed well for our CardiAmp and CardiAlo procedures and has potential to enhance many other clinical procedures as a commercial product with a broader product family configuration. We received FDA approval for this product family this past quarter. The product is intended to provide a pathway through which medical instruments such as balloon dilation catheters, guide wires, or other therapeutic devices may be introduced into the peripheral vasculature or chambers and coronary vasculature of the heart. The clearance covers an array of 16 products in lengths of 30, 45, 71, and 90 centimeters in five, six, seven, and eight French introducer sheet equivalent diameters. Marketing materials are currently available on the company's website in preparation for commercial release of the initial products. We are reaching out to senior management at other companies who don't have these products to support their own interventional procedures and inviting their sales teams to be aware of the MorphDNA products. We will also soon be reaching out to many leaders in interventional cardiology, cardiac electrophysiology, vascular surgery, and interventional radiology to obtain first in man procedures on the many applications of this elegant enabling commercial platform. We do not expect any significant revenues in the near term, but do expect to have news here ahead as we make progress. On the business development front, we have active partnering discussions with potential to be meaningful for our business with respect to all four of our platforms, Cardiam, Cardialo, Helix, and MorphDNA. For Cardi-AMP cell therapy business development, we expect the final data from Cardi-AMP Heart Failure 1 will enhance interest by distribution partners and strategics. It is noteworthy that interventional therapies for heart failure are receiving more and more attention because there are many patients who remain symptomatic, even on -the-art guideline-directed medical therapy. For Cardialo business development, our Allogeneic cell therapy, currently in the clinic for heart failure, we have extensive clinical experience from three trials. We've had discussions around partnering these cells for other clinical indications beyond our current plans in cardiac and pulmonary disease. I note that the FDA has set a prescription drug user fee act date of January 7th, 2025 for a peer company with very similar cells in another indication, whose anticipated success will likely enhance our partnering discussions around our clinical stage Allogeneic cell therapy platform. For our Helix biotherapeutic delivery platform, potential biotherapeutic delivery partners who wish to have access to our delivery experience, products, and support capabilities remain active in discussions. Current partners realize that minimally invasive delivery not only enhances future commercialization, but it is also seen as a critical means for clinical development, enabling much faster enrollment, thus significantly reducing their operational costs by shortening timelines for their therapeutic development. Lastly, partner therapeutics are expected to benefit enormously from our threefold efficiency of delivery and the enhanced pharmacokinetics with our Helix system supported by data from many groups. We believe this advantage is due to the stability of the Helix and the beating heart and the self-sealing helical pathway into the tissue. We encourage all partners to perform pharmacokinetic studies, including a surgical delivery control so they will have their own data supporting what we have seen. On the more front, the recent FDA approval has us open for business in a competitive but real market. Physician usage is the first step towards any distribution or commercial partnership. In summary, we have delivered five of the six milestones detailed in our last conference call. We had expected to treat the first patients in cardiac heart failure two trial and begin demonstrating that we can enroll in this trial quickly with our world-class clinical partners. Two hurricanes in Florida this quarter have had an impact on this goal. The patients are in the queue and this goal will be realized soon. We are working to complete the following before the end of this quarter, Q4 2024. One, have a consultation with Japan PMDA and Cardi-AMP Cell Therapy. Two, complete data lock on the Cardi-AMP Heart Failure One trial data set. Three, begin treatments and activate an additional three centers in the Cardi-AMP Heart Failure Two trial. Four, enroll the last low dose patient in the Cardi-Alo Heart Failure trial. And five, put first commercial morph DNA products on the shelf and perform first procedures. I will now pass the call to David McClung, our CFO, who will review our third quarter 2024 financial results. David.

Thank you, Peter. And good afternoon, everyone. In September, we closed our $7.2 million public offering, bringing us into compliance with NASDAQ's listing requirements. This extends our runway past our expected results in the pivotal Cardi-AMP Heart Failure trial in Q1 2025. Total expenses decreased 41% quarter over quarter to $1.8 million in Q3 2024, compared to $3.0 million in Q3 2020-30. Research and development expenses decreased to $931,000 during the third quarter of 2024, compared to $1.9 million for the third quarter of 2023, primarily due to the completion of enrollment in the Cardi-AMP Heart Failure One trial, coupled with related reductions in clinical and supporting functional expenses. We expect R&D expenses to increase modestly as the Cardi-AMP Heart Failure Two trial ramps up beginning in the fourth quarter of 2024. As Peter mentioned, the Cardi-AMP cell therapy for the treatment of heart failure qualifies for Medicare coverage, with covered costs including patient screening, the investigational Cardi-AMP cell therapy system, the procedure, and the clinical follow-up at $17,000 for both the treatment and the control arms. This substantially reduces the expense of accelerating enrollment in the Cardi-AMP Heart Failure Two trial. Selling, general, and administrative expenses decreased to $825,000 for the three months ended September 2024, down from $1.1 million from the same period in 2023, primarily due to the reductions in personnel expenses. We expect SG&A expenses to remain close to the current run rate. Biocardi's net loss decreased to $1.7 million for the third quarter 2024, down from $2.6 million in the prior year's third quarter, primarily to those reductions in R&D and SG&A expense. Net cash used in operation for the third quarter 2024 totaled $2.6 million compared to $2.4 million in the third quarter of 2023. The increases are due to the settling of trade payables and accrued liabilities following the closing of the $7.2 million public offering in September. For perspective, cash flows for the nine months ended September 2024, or $5.5 million. That's $2.6 million less than the same period, nine month period in 2023. We expect our cash burn will increase moderately over the coming year, continuing our track record of operating efficiently and carefully managing the use of capital. This concludes management's prepared comments, but we're happy to take now questions from attendees.

Ladies and gentlemen, at this time, we'll begin the question and answer session. To ask a question, you may press star and then one on your telephones. Your question has been answered. 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 the handset prior to pressing the numbers to ensure the best sound quality. Once again, that is star and then one to join the question queue. We'll pause momentarily to assemble the roster. In our first question today, it comes from Joe Pandigenis from H.C. Wainwright. Please go ahead with your question.

Hey everybody, good afternoon. Thanks for taking the questions. So Peter, I wanna start at the back end of your prepared comments if you don't mind. You gave a lot of great details around morph DNA and I guess, what are your potential options other than individual partnerships or company partnerships or broader partnerships or even monetizing the entire program? What are your options that you're looking at?

Well, Dr. Pandigenis, thank you for the question. It is a good question. So morph DNA is a product that we realize because we recognize the advantages it provides for all of our procedures on the cardiac cell therapy side and with partners using Helix. And it's an elegant, durable introducer sheath platform. The market here is actually quite large. I'm actually aware of one hospital, a single hospital in the United States that uses 250,000 units of this type per year for one clinical indication of transeptal access for performing atrial fibrillation procedures. So it's a quite large market opportunity across the board. It's very competitive in the electrophysiology space. In the last year in the electrophysiology space, primarily we saw Medtronic buy a company for roughly 100 million. We saw Boston Scientific buy a company with other assets for crossing the heart wall for 1.2 billion based on these steerable introducer assets. We're earlier in the commercial pathway here, but we have a very compelling technology advantage to those other catheter systems and that our morph DNA has a rotating tendon element that goes down the length of the catheter, which you can see in the product brochure that's available on our website. And what that does is it eliminates WIP when using this device in a patient's heart or in their vasculature. And WIP is the tendency for the catheter to be stable in one position, but unstable in another position so that it jumps to the stable position. And so that technical advantage is one of the things that we're going to be proving out. If you look at the brochure on our website, what we call the naked man, an anatomical model of all the different places that this can be used in the clinic today based on the approvals we have and the configurations we have. We are going to be populating that image with case reports from world leading physicians in the months ahead. And if there is a perception that this provides a compelling benefit for the physicians who use it, our options to answer your question, Joe, will be far more numerous. There'll be options for distribution, there'll be options for selling this business unit outright. I think our perspective as a company is we are open to pathways where we can sell this business unit far more at present than we are to pathways where we would enter into a distribution agreement. And that's one of the reasons why today we've reached out to executives at companies that sell into these physician groups today to say, hey, are products available? You right now are recommending potentially a product of your competitors and you could recommend a product of a company that if it resonates for you could be a potential tuck-in acquisition for you ahead. So our plan right now is we're trying to demonstrate that the physician utility over existing product and in parallel to developing analyses to either support expanding our manufacturing and commercial footprint, we'll also be exploring pathways where we can divest this business in a fashion that brings in significant non-dilutive capital for our other efforts, which is our main focus. I note that any divestment that we would consider would have to guarantee that Biocardia retains exclusive rights to this platform technology for biotherapeutic intervention because it is a significant advantage that we have. And I note that the products, if you look at our website, we only offer this available in 90 centimeters length commercially. And yet our platform that we use in all of our procedures today is 110 centimeters in length. And that sort of puts a little barrier into there for anyone that wishes to use our commercial product for what we do on the cell therapy side. So it's a long-winded answer, Joe, forgive me, but

we've had some good thoughts

on it and it's underway.

Absolutely, yeah, no, they were very, very helpful details and I appreciate all the options that you have. So if you don't mind, I'd like to switch gears to your XUS efforts regarding Cardi-AMP and want to get sort of a general concept regarding the process and timing in Japan. And then just curious because, seeing other examples for cellular therapies, I mean, since you have breakthrough therapy in the US, I believe the designation or similar designation in Japan is called Sakagaki status. And I'm just curious if you were looking for that as well.

So yeah, great question on Japan. And I know who you're thinking of with you, you think of Sakagaki status. And Sakagaki is named after one of their first satellites. So we've had great interactions with Japan PMDA and with the FDA here in the United States. In Japan, the process ahead is we have our next clinical consultation scheduled for this month with PMDA, Pharmaceutical and Medical Device Agency in Japan. And in that consultation, we're talking about the desire that we have to provide our data based on what to them are foreign trials, i.e. our trials in the United States and Japan. And my sense is they're pretty supportive of that at present, we're answering a number of questions that they raised in our clinical consultation in November of last year and detailed in written minutes in December of last year. And many of those questions tie into our cardiac heart failure data. Quite a few of the questions end with the statement of, please address this in your application for approval or your submission for approval. And that's really where we'd like to get you. So it's really a couple step process here. The first step is this next consultation is to tee up the clinical consultation. And it is a significant hurdle if they say, yes, we would like you to come in for a formal clinical consultation to review your data, which was really the second to last step before they say, yes, you can submit for approval. And so that is a really big hurdle. So the next significant hurdle there is, will they allow us to submit and have a clinical consultation? So we will submit all of the data from cardiac heart failure one and engage with them on that data and answer quite a few questions they have on how that fits into standard care in heart failure in Japan, which we've already addressed extensively. They're very detail oriented, but they've given us some pretty positive signals so far. And so our hope is that after that clinical consultation, our first hope is to get to a clinical consultation. That's a significant hurdle. In the clinical consultation expected in roughly Q1 or the submission in Q1, if they invite us to effectively apply for approval, that's a really big deal. That means we're on a pathway to approval in a not too distant future for a cell therapy in Japan in heart failure. And I note that you asked about Sakagaki. Sakagaki is often tied into more the biologic therapies. And in Japan, cardiac is going to be regulated as a device system, similar to the way it's regulated in the United States. They get into the cell-based therapy and the selection of patient elements, which are all biologic. But as the cells are manufactured in a device at the patient's bedside, it will be regulated as a device-based system. And that means that our approval, should we get it in Japan, would be a full approval. So that's sort of the timeline ahead. So we are hopeful, very hopeful early next year that we'll have the clinical consultation with Japan PMDA. And after that clinical consultation, in the minutes that they provide from that clinical consultation, looking at the data from all three of our trials and answering all of the questions they've had here to four, that all of the questions they ask us will end with. And please address this in your application for approval.

Extremely helpful again, and appreciate the clarification on Sakagaki. If you would indulge me one last question. When you look at the cellular therapy space, the regenerative medicine and all that, there's always good, bad, or ugly, a lot of investment. And this goes for many different therapeutic approaches or technology approaches, basket thinking. All cells are alike or in different indications or what have you. So you referenced in your prepared comments an upcoming PDUFA date. And of course, this is for mesoblasts and for GVHD. So I'm just curious, I know it's difficult to talk about, say competitor products or what have you on calls like this, but can you point to any similarities or differences in your cells that can help if they have a positive outcome for a positive basket approach?

Yeah, so if you go back to an earnings call we had probably, gosh, over a year ago, two years ago, I was asked the question of what did I think of mesoblasts chances at panel in their indication for pediatric graft versus host disease. And I was a big supporter. I was surprised that the panel did not approve it at that time or the agency didn't. I think panel supported it, the agency didn't because graft versus host disease is one of the most significant worst ways to die out there. That said, their cells in that indication are very similar to the cells that we are advancing. That program was initially begun by Osiris Therapeutics many years ago. Biocardia has worked with Osiris many years ago. So we're very familiar with, these are allogenetic, culture expanded, bone marrow derived, mesenchymal stem cells. Now mesenchymal stem cells are characterized by the process because each manufacturing process can be slightly different. But fundamentally, we're delivering very similar cells. And so their success in their PDUFA meeting ahead is likely to significantly enhance interest in partners around both their programs and other indications, but also our clinical grade cells for many of those same indications. So I think it's a real opportunity that we have this ready. We have FDA approved INDs for both an inner tissue cardiac delivery, but also for an intravenous delivery for our PULM LO project. So my sense is their success, rising tide lifts all boats, will enhance interest in our allogeneic platform as well.

Excellent. Peter, thank you very much for all the details and looking forward to the upcoming Cardiap1 data.

I appreciate it, Joe. Thank you so much for the questions.

Our next question comes from Kumar Raja from Rookline Capital Markets. Please go ahead with your question.

Good afternoon and thanks for taking my questions. First, with regard to the protocol amendment in the Cardiap2 trial, what percentage of patients would pick this profile and how are similar patients who had similar nature of cells, how were they treated in the Cardiap1 trial?

Great question, Kumar. So I call that amendment approval, I call it the $20 million amendment here at Biocardia because of how significantly it's gonna change, how easy it is to enroll patients in the trial. Previously, if a patient didn't meet the pre-specified cell population analysis criteria, they were excluded from the trial. Now, we took measures throughout the trial and in our analysis of the Cardiap1 heart failure cell population analysis data for both patients who didn't make it into the trial and the patients who did make it into the trial, we saw that there was a large portion of the patients that were just really under the threshold, within say 35% of the threshold. And so we went to the agency and we presented a plan whereby for those patients to help ensure that they have potential to reach the target dosage instead of excluding them, we are going to give them 35% more deliveries. So currently we treat patients with 10 dosages around damage and infarct site. For those patients that are in a class that doesn't meet the full cell population analysis score, those that fall below but are greater than 65% will then be targeted with the 10 dosages plus an additional five dosages to get them to the optimal target dosing. And so we're pretty excited about this. We're not detailing the exact numbers and all the details and changes yet because again, we don't yet have final data in the trial, but our expectation is that we will still exclude patients based on not having appropriate cells for therapy. But my expectation and I should say our expectation of the team is that about 85% of the patients will pass that threshold and a number of them will wind up having 15 deliveries to get to the target dosage versus the 10. So this is truly personalized medicine where we're assessing a patient's own autologous tissue, looking at it for its composition and then developing a treatment plan which now has three arms. One arm is I'm sorry, your cells don't qualify you for treatment. The other arm is yes, your cells qualify you for treatment. And the third arm is your cells qualify you for treatment but because of the nature of your cells, we're gonna provide an additional five dosages. So that's what we're rolling out now and all the paperwork's been implemented here at Biocardi. We have IRB approval. The full Cardi-AMP Heart Failure 2 trial will incorporate that element.

That's great, that's very helpful. And with regard to Japan, what would be your commercialization strategy? Are you looking for partners there or what is the plan there?

Absolutely, so in Japan, my expectation is that we will partner in Japan and when and how we partner will depend upon the progress ahead. We have a world-class group of folks and we have world-class physicians involved. The first step post-approval is expected to be a really a post-marketing study to enhance awareness, to develop additional data. So that first year, think of it as a slow rollout. In Japan, distribution's a little different than it is here in the States. Each and every hospital sort of has a transitionary distributor for these types of products that takes essentially 10% of the value proposition and manages the interaction within the hospital. There are other distributors who then tell into those distributors. And there are some larger players in Japan where we have active conversations on what we're doing with this therapy and how it might fit into their commercial efforts. And we continue to have these conversations. I think in Japan, being able to be approved without a clinical trial is viewed as quite valuable because clinical trials in Japan are notoriously expensive and take a very, very long time. I'll do a cross question comment here. I believe that the program that Dr. Panjiannis was referring to was one that had Sakagaki, but it couldn't complete enrollment just because clinical trial enrollment in Japan is quite difficult. And so by getting approval without that requirement, I think it enables us to move forward. So in addition, I'll share with you that in Japan today, there are two other companies who have asserted publicly that they're gonna be applying for approval based on a total of 10 patients treated in a surgically-based cell therapy for heart failure, which requires chronic immunosuppression. And the advantages we bring to the table are not requiring those things, minimally invasive access, no immunosuppression, is a really compelling advantage for physicians as well as for patients. And so my sense is on the other side of approval, there will be a lot of interest in this therapy. So determining exactly how to distribute it is TBD, but there's lots of conversations ongoing. And the PMDA saying, yes, you can apply for approval, that will turn on a lot of green lights. So we'll take it from there.

Great, thank you. Thank you, Kumar, appreciate the question.

And ladies and gentlemen, at this time, I would like to end today's question and answer session and turn the floor back over to Peter Altman for any closing remarks.

Thank you, Jamie. I thank everyone who has helped our mission to develop and enhance therapies to treat cardiovascular disease. Investors should know that we have potential to achieve enormous success with their support. And that our market capitalization today presents a remarkable investment opportunity and a company with many ways to win that is able to do great things on modest capital. We expect to deliver a rewarding end to 2024 and an incredible 2025 if we are successful in our efforts. Have a great afternoon and thank you for your continued interest and support of Biocardia.

Ladies and gentlemen, with that, we'll conclude today's conference call and presentation. We do thank you for joining. You may now disconnect your lines.