BioCardia, Inc.

Ladies and gentlemen, thank you for standing by. Good afternoon, and welcome to the BioCardia 2022 year-end conference call. At this time, all participants are in a listen-only mode, and should you need any assistance during the call, 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 telephone keypad. To withdraw a question, please press star, then 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 through June 29th, 2023. I would now like to turn the call over to Miranda Pato of BioCardia Investor Relations. Please go ahead, Miranda.

Good afternoon, and thank you for participating in today's conference call. Joining me from BioCardio's leadership team are Peter Altman, PhD, 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 BioCardio'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. 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 and cautionary statements described in BioCardio's report on Form 10-K filed with the SEC this morning. The content of this time call contains time-sensitive information that is accurate only as of today, March 29, 2023. Except as required by law, the complaint 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 Peter Altman, PhD, BioCardius President and CEO. Peter, please go ahead.

Thank you, Miranda. And good afternoon to everyone on the call. We've had a great fiscal year in 2022. But before we get into the details, I always like to take a few moments and review what we are doing and why we are doing it. Biocardius efforts are focused on advancing two cell therapy platforms to treat significant unmet cardiovascular and pulmonary diseases. Specifically, ischemic heart failure, chronic myocardial ischemia, and acute respiratory distress syndrome. All of our cell-based therapies involve local delivery of the therapeutic to the heart or lungs, where we intend them to act locally. In the heart, our own proprietary Helix minimally invasive delivery system is used to deliver the cells to target regions of damage. For the lungs, we intend to use intravenous delivery, which will result in the investigational cells being localized in the small blood vessels of the lungs. Local delivery of therapeutics to the target location where their action is desired maximizes their effective dosage within the tissues where delivered and minimizes potential negative effects remote from the target tissues. Heart failure is the first problem we are going after. Heart failure is an enormous unmet need that affects more than 26 million people worldwide. The latest blockbuster drugs in ischemic heart failure of reduced ejection fraction provide great benefits to patients but don't appear to have much of an impact on mortality. Patients in the published results of the pivotal trials for these new drugs have a cardiac mortality of roughly 7% and an all-cause mortality of 10% per year, regardless of whether they were treated or controlled patients. This data makes clear that heart failure is still a problem in great need of new therapeutic solutions. Our autologous mononuclear cell therapy platform which we call cardiac cell therapy, is being advanced into cardiac clinical indications. In preclinical studies, cardiac mononuclear cell therapy has been shown to release proteins locally within the tissue to facilitate cardiac recovery after heart damage with improvements in heart perfusion and contractile function. All known previous clinical studies, similar to the approach we are taking in our two lead cardiac cell therapy programs, have shown patient benefits on average. In some of these studies, including our own, the benefits have been remarkable. The FDA has supported this promise by granting breakthrough device designation to CARDI-AMP cell therapy in the indication of ischemic heart failure reduced ejection fraction. Advancing this and our other three therapeutic candidates is what we are all about. Our efforts to complete the CARDI-AMP autologous cell therapy pivotal clinical trials for the indications of heart failure, or BCD-A01, and chronic myocardial ischemia, or BCD-A02, are furthest along clinically, with an estimated combined 1.6 million patients in a reachable U.S. market. The Cardiac Cell Therapy Heart Failure Trial, or BCD-A01, is a Phase III 260-patient randomized controlled clinical study intended to provide the primary data to support safety and efficacy in pursuit of market clearance. Clinical investigators at 22 active partner sites across the United States and Canada have enrolled 119 patients today with 10 additional control patients having crossed over to receive therapy. We currently have eight active consents and 15 additional patients in the pre-consent queue. There is clearly increased momentum here. potentially driven by the clinical data. Data published to date has shown improved functional capacity and quality of life in treated patients. Earlier this month, clinical investigators presented blinded echocardiography data from the Yale University Core Laboratory from the open-label Rowland cohort of the cardiac heart failure trial at the annual meeting of the American College of Cardiology. Results presented showed a 35% improvement in left ventricular ejection fraction as compared to baseline, with 100% survival at two-year follow-up. These are remarkable results in this population, and the scientific poster presentation is available on our website if you are interested. The Independent Data Safety Monitoring Board completed both its fifth and sixth prespecified data reviews in 2022. including a risk-benefit assessment with more than 100 patients past the primary clinical readout. Following the review, the Data Safety Monitoring Board indicated that it had no significant safety concerns and recommended that the study continue as designed. The Data Safety Monitoring Board also supported the company implementing an adaptive statistical analysis plan, which could enable an early readout for study treatment efficacies. Working with distinguished consultants, including former FDA leaders and a respected statistical consulting group, we have developed and submitted a supplement with a proposed adaptive statistical analysis plan to the FDA in February 2023. We have a meeting scheduled to discuss the FDA's comments on March 31, 2023, which is this Friday. The next pre-specified formal data safety monitoring board review is anticipated in the second quarter of 2023, and we believe it is likely we will be able to have the adaptive statistical analysis plan in place for the meeting. The specific details of any potential adaptive statistical analysis plan, in combination with any modifications to the Data Safety Monitoring Board charter, will dictate what happens at the next subsequent Data Safety Monitoring Board reviews. As the CAR-DM cell therapy trial on heart failure was over 90% powered for success with a range of 86 to 126 patients, there is potential that the trial could meet its primary efficacy endpoint on the patients that have been enrolled to date. However, when the Data Safety Monitoring Board next meets, they may also recommend that the trial continue per plan, be stopped for safety, or be stopped for futility if the data does not support that achieving the primary endpoint is possible. Our second therapeutic program with the same autologous cell therapy for the treatment of chronic myocardial ischemia with refractory angina, or BCO2. The CARDIAMP chronic myocardial ischemia trial is a phase three multi-center, randomized, double-blinded, controlled study of up to 343 patients at up to 40 clinical sites. The phase three pivotal trial is also designed to provide the primary support for the safety and efficacy of the CARDI-AMP cell therapy system for this indication. It uses many of the same novel aspects of the CARDI-AMP heart failure trial and is expected to leverage our experience and investment in the heart failure trial. This program benefits from the 2022 Center for Medicaid and Medicare Services, or CMS, reimbursement for both treatment and control procedures at up to $20,000 for both trials. A significant number of patients to complete the open label rolling cohort, excuse me, a sufficient number of patients to complete the open label rolling cohort have already been consented. It is anticipated this trial will report out the open label rolling results in 2023. Trial design modifications to enhance enrollment efficiency for the randomized cohort are being planned for submission to FDA. As we've shared previously in July, we had our second consultation with Japan's Pharmaceutical and Medical Device Agency regarding registration of cardiac cell therapy for ischemic heart failure. After working with distinguished physician leaders, BioCard expects to complete its formal submission for Japanese approval in the second quarter of 2023. As I've mentioned in previous calls, Japanese researchers established the building blocks to this therapy many years ago. The therapeutic approach we are pursuing was first studied in the preclinical model by physician scientists in Yokohama. This early work was performed in parallel to another Japanese vascular biology scientist who identified important aspects of bone marrow-derived mononuclear cells and tissue repair. Their early efforts underlie our cardiac cell therapy, and we hope to be able to provide this therapy to the many in Japan who could benefit from it. Now I'd like to move to our two allogeneic cell therapy product candidates. based on our allogeneic neurokinin-1 receptor-positive mesenchymal stem cell platform. These are off-the-shelf cells from young healthy donors intended to be expanded to produce many doses for many patients. The neurokinin-1 receptor-positive mesenchymal stem cells are particularly interesting as neurokinin-1 is the primary receptor for substance P, an important neuropeptide mediator of inflammation which plays a central role in both heart failure and regenerative processes following myocardial injury. I encourage listeners to Google substance P to understand why advancing the mesenchymal stem cells that bind to this neuropeptide is exciting. Our allogeneic mesenchymal stem cell program in ischemic etiology heart failure of reduced ejection fraction is designated as BCD03. This is a phase one, two, multi-center, randomized, double-blind, controlled study of up to 69 patients designed to assess the safety and efficacy of this therapeutic candidate. The investigational new drug application was approved by the FDA in December 2022. The trial is designed for patients with New York Heart Association class two and three ischemic heart failure of reduced ejection fraction whose own cell composition, makes them ineligible for the company's phase three cardiac heart failure trial studying autologous cell therapy or BCDL1. Clinical grade allogeneic cells for this program have been manufactured in our Sunnyvale facility and are ready for use. These cells will be delivered under the protocol with our proprietary minimally invasive biotherapeutic delivery system. We expect to begin enrolling patients in the second quarter of 2023. Our allogeneic mesenchymal stem cell program in patients recovering from acute respiratory distress syndrome secondary to COVID, which we have designated BCO4, was approved by the FDA in April 2022 to treat patients. The trial is a phase one multi-center open label study of up to nine patients. While the number of patients with COVID-induced ARDS has decreased, ARDS unrelated to COVID is still significantly impacting patients. The company intends to work with the FDA to modify the study eligibility criteria to include these patients. In this trial, increasing dosages of the cells will initially be evaluated, and then the optimal dose will be taken to Phase II in a randomized study in adult patients recovering from ARDS. This therapy is intended to address the enormous unmet need to sustain local and systemic inflammation after a patient is taken off respiratory support. with the goals of accelerating recovery, enhancing survival, and reducing both relapse and rehospitalization. Clinical-grade cells are also ready for use in this study. The ARCH trial is expected to commence following the initiation of BCA03, studying the allogeneic mesenchymal stem cells for heart failure-reduced ejection fraction. In summary, we are advancing four clinical-stage therapeutic product candidates that address important unmet cardiac and pulmonary diseases, based on our autologous and our allogeneic cell therapy platforms. From these therapeutic development efforts, we now have four active business development initiatives. First is partnering our cardiac cell therapy platform internationally. Second is licensing out our clinical stage neurokinin-1 receptor-positive mesenchymal stem cell platform for other clinical indications, which have shown promise with other mesenchymal stem cell preparations. Third, is licensing our catheter-based biotherapeutic delivery system for cell, gene, and protein therapy candidates to the heart, such as in the Blue Rock relationship we began last year. And fourth is monetizing our Avance transeptal introducer sheath product. Our steerable sheath assets were initially developed to help navigate our biotherapeutic delivery systems, and we use these products in every cardiac cell therapy procedure today. There have been recent acquisitions of established product offerings similar to our Avance product offering for between $70 million to $1.5 billion. Our Avance is our first FDA-approved offering for this transeptal indication and incorporates patented technology that may provide compelling benefits. Next week, we expect to announce the issuance of two additional new patents related to these steerable sheath assets. We are also looking forward to announcing an additional patent issuance related to our neurokinin-1 receptor-positive mesenchymal stem cells that has been allowed, and a patent that we expect soon to be allowed related to our Helix biotherapeutic delivery platform. I will now pass the call to David McClung, our CFO, who will review our 2022 financial results.