BCDA: 3Q2023 Results

“We have increased confidence in the potential of our autologous CardiAMP Cell Therapy program in ischemic heart failure based on the recent interim data from 136 procedures and in Chronic Myocardial Ischemia based on the first four patients enrolled. We are also focused strategically on advancing these two clinical programs in a cash neutral fashion with the benefit of the Medicare reimbursement obtained previously. Similarly, we are working to secure grants and partnerships around our allogeneic programs to support their clinical development, and implementing a recurring revenue biotherapeutic delivery partnering model with our experienced world class team and our Helix biotherapeutic delivery system” said Peter Altman, President and CEO of BioCardia. “The success of these efforts will be evidenced by reductions to our net loss with increases in partnering and grant revenues, while delivering significant clinical data on our therapeutic candidates.”

RECENT BUSINESS HIGHLIGHTS:

CardiAMP® Autologous Cell Therapy for Patients with Ischemic Heart Failure (BCDA-01)

The CardiAMP Cell Therapy Trial for Heart Failure is an ongoing randomized, double-blinded, controlled clinical trial in the United States that was approved for up to 260 patients at up to 40 clinical centers. On July 21, 2023, the study’s Data Safety Monitoring Board (DSMB) recommended that enrollment in the trial be paused based on an analysis of trial data and the primary endpoint assessment, unrelated to any emergent safety events, and pending an outcome analysis of patients currently completing one year follow-up as well as the interim results of newly enrolled patients completing their imminently scheduled treatment. Further, the DSMB recommended that the blind not be broken to protect the integrity of the outcomes yet to be collected and to ensure the study may be restarted without compromise after completion of the one-year data analysis.

The Company has determined that it would be difficult, if not impossible, to restart the trial as currently designed after completing the one-year data analysis in the fourth quarter of 2024. During the third quarter of 2023, BioCardia worked with the DSMB to unblind a small committee within the Company to review the closed session DSMB report of interim study results to better understand the rationale behind their recommendation. After reviewing the interim dataset as presented to the DSMB, along with the finding that the primary endpoint at one year was unlikely to be met with the current study design, management concurs with the DSMB recommendation to follow patients through one-year follow-up, while maintaining the study double-blind to protect the integrity of the outcomes yet to be collected for the one-year data analysis anticipated late next year.

In the interim data from the July DSMB review, 102 randomized patients in the CardiAMP Cell Therapy trial followed for up to 24 months showed a 37% relative risk reduction of cardiac death equivalents and an 18% relative risk reduction in major adverse cardiac and cerebrovascular events (MACCE).

In addition, the available interim data showed that for an important subset of patients who presented at the screening/baseline visit with higher levels of NT-proBNP, a well-established biomarker of increased heart failure and stress to the heart, the reduction in heart death equivalent and MACCE were even greater. In patients with NT-pro BNP levels greater than 500 pg/ml at baseline, an analysis of all available data up to two years shows improvements over controls including a 59% relative risk reduction in mortality and a 54% relative risk reduction of MACCE. Further, all clinical outcomes included in this subset analysis favored cell therapy including improved quality-of-life as measured using the Minnesota Living with Heart Failure Questionnaire, reduction of NT-proBNP levels, greater Six Minute Walk distance, and improved left ventricular ejection fraction, left ventricular end systolic volume and left ventricular end diastolic volume. Both the reduced heart death equivalents (p=.028) and improved quality of life as measured using the Minnesota Living with Heart Failure Questionnaire (p=0.016) demonstrated statistical significance favoring therapy.

On October 11, 2023, after an additional four patients were randomized subsequent to the DSMB review, the Company announced completion of enrollment in the CardiAMP Cell Therapy Heart Failure Trial and initiation of a discussion with the FDA on a second pivotal study protocol adapted for the responders in the initial trial with the objective of gaining FDA marketing approval.

BioCardia has submitted a proposed CardiAMP Heart Failure II study protocol for FDA review, which includes an eligibility requirement that enrolled patients have an NT-proBNP at baseline greater than 500 pg/ml. The proposed primary endpoint is also modified from the primary endpoint in the currently ongoing study. The new endpoint proposed is a similar hierarchical composite endpoint consisting of all-cause death, the cardiac death equivalents of heart transplant and left ventricular assist device (LVAD) implantation, heart failure hospitalizations, worsening heart failure events treated as an outpatient, and change in quality-of-life with a follow-up duration ranging from a minimum of 12 to a maximum of 24 months. Should this study protocol be approved by the FDA and advanced by BioCardia, it may be possible to significantly offset clinical costs with the Medicare reimbursement of up to $20,000 now in place for both the control and treatment arms of this investigational therapeutic study.

In June 2023, the Company completed its submission of the CardiAMP Cell Therapy System to Japan’s Pharmaceutical and Medical Device Agency (PMDA) towards approval for the indication of ischemic heart failure with reduced ejection fraction (HFrEF) based on existing safety and efficacy data. In July, the formal consultation was reviewed and accepted by the PMDA for the consultation with some clarifying questions, which have been addressed. In October, the Company provided an update at PMDA’s requests on the current Phase III study status in the United States, and a formal consultation is scheduled for November 21, 2023. While subsequent interactions and consultations with the PMDA are expected, the CardiAMP Cell Therapy System has potential to be the first minimally invasive catheter-based cell therapy available in Japan.

CardiAMP® Autologous Cell Therapy for Patients with Chronic Myocardial Ischemia (BCDA-02)

The CardiAMP Cell Therapy Trial for Chronic Myocardial Ischemia is a Phase III, multi-center, randomized, double-blinded, controlled study of up to 343 patients at up to 40 clinical sites. The trial has been activated at two clinical sites and four patients have been treated. The Company expects to complete the roll-in cohort of patients in the fourth quarter of 2023 and begin the randomized phase of the trial.

CardiALLO™ Allogeneic Cell Therapy for Ischemic HFrEF (BCDA-03)

The CardiALLO Allogeneic Cell Therapy for Ischemic HFrEF is a first-in-human Phase I/II 69 patient clinical trial designed to patients with New York Heart Association Class II and III ischemic heart failure with ischemic HFrEF, including those whose own cell composition makes them ineligible for the Company’s Phase III CardiAMP Heart Failure Trial. The first patient is expected to be treated in the fourth quarter of 2023. This study follows three previous clinical trials with MSCs cosponsored by the Company in ischemic heart failure with 93 patients treated using the Helix delivery system.

Helix TM Biotherapeutic Delivery System

BioCardia’s Helix Biotherapeutic Delivery System (Helix) delivers therapeutics into the heart muscle with a penetrating helical needle from within the heart. It enables local delivery of cell and gene-based therapies, including BioCardia’s own cell therapies. The delivery platform includes proprietary approved steerable guide systems, approved delivery catheters, and investigational imaging navigation.

The Company’s biotherapeutic delivery team has active discussions with current and prospective partners regarding programs utilizing the Helix platform and expects to finalize up to two licensing and development relationships during the fourth quarter of this year. These relationships are intended to share the costs of ongoing maintenance of and advances in the valuable enabling platform, and for BioCardia shareholders to benefit from the future success of these partnered programs. In September, CellProthera announced completion of enrollment in the Phase I/II cell therapy study in post-myocardial infarction.

Third Quarter 2023 Financial Results:

ANTICIPATED UPCOMING MILESTONES AND EVENTS:

BCDA-01: CardiAMP Cell Therapy for Heart Failure Phase III Trials
Q4 2023: CardiAMP HF Trial II FDA Protocol Approval
Q4 2023: Japan PMDA Formal Consultation
BCDA-02: CardiAMP Cell Therapy for Chronic Myocardial Ischemia Phase III Trial
Q4 2023: Completion of Roll-in Cohort and Transition to Randomized Pivotal Trial
BCDA-03: NK1R+ MSC Allogeneic Cell Therapy in Ischemic HFrEF Phase I/II Trial
Q3 2023: Completion of Low Dose Cohort
Helix Biotherapeutic Delivery System
Q4 2023: Update on Licensing / Partnerships

About BioCardia®

BioCardia, Inc. , headquartered in Sunnyvale, California, is developing cellular and cell-derived therapeutics for the treatment of cardiovascular and pulmonary disease. CardiAMP™ autologous and NK1R+ allogeneic cell therapies are the Company’s biotherapeutic platforms that enable four product candidates in development. BioCardia also partners with other biotherapeutic companies to provide its delivery systems and development support to their programs studying therapies for the treatment of heart failure, chronic myocardial ischemia and acute myocardial infarction. The CardiAMP Cell Therapy Trial for Heart Failure has been supported financially by the Maryland Stem Cell Research Fund and the Center for Medicare and Medicaid Services. For more information visit: www.BioCardia.com .

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