Gencaro™ Pharmacogenetic Effect Paper Published in Peer Reviewed Journal

ARCA biopharma, Inc., a biopharmaceutical company developing genetically-targeted therapies for atrial fibrillation and other cardiovascular diseases, announced that the paper "Combinatorial pharmacogenetic interactions of bucindolol (Gencaro) and beta-1, alpha-2c adrenergic receptor polymorphisms” was published in PLOS ONE (https://dx.plos.org/10.1371/journal.pone.0044324), an international, peer-reviewed, open-access, online publication. Analyses in the paper demonstrate that two previously described adrenergic receptor polymorphisms that have been shown to pharmacogenetically interact with the anti-adrenergic agent and beta-blocker Gencaro (bucindolol hydrochloride) appeared to behave in specific, pharmacologically-determined ways when individual genetic monotypes are combined. The paper details the combined research efforts of three leading cardiologists and/or pharmacogeneticists: • Christopher O'Connor, M.D., Professor of Medicine, Director of the Duke Heart Center, Duke University Medical Center, lead author of the paper; • Steven Liggett, M.D., Associate Vice President for Personalized Medicine, Morsani College of Medicine University of South Florida in Tampa, a senior author of the paper whose laboratory discovered and characterized the two adrenergic receptor polymorphisms; and, • Michael Bristow, M.D., Ph.D., President and CEO of ARCA biopharma and Professor of Medicine (Cardiology) at the University of Colorado Anschutz Medical Campus, the senior author of the paper in whose academic laboratory the mechanism for the described pharmacogenetic interaction was discovered and characterized. Dr. Bristow commented, “These data demonstrate that combinatorial pharmacogenetic interactions may be used to increase the predictive power of genetic biomarkers to identify subpopulations of patients that appear to respond either better or worse than the general population of patients. In the case of Gencaro, in this review of study data, adrenergic receptor combinatorial pharmacogenetics appear to identify a substantial subpopulation of patients in the study, approximately 45–50% of the total, in which responses appear to exceed outcomes reported for other studies with other beta-blockers in U.S. heart failure populations. These pharmacogenetic findings also identify a smaller subpopulation, approximately 10–15%, where the drug did not appear to be useful in preventing heart failure in this study. The ability to identify these subpopulations may allow for more efficient drug development and potentially improved targeted therapies for cardiovascular patients, if regulatory approval is obtained." Dr. O’Connor added, "The data in this paper show how clinically unpredictable and yet pharmacologically deterministic the interaction of two drug target affecting polymorphisms can be, emphasizing how pharmacogenetic interactions can be complex but understood if extensively investigated and published." ARCA has been granted patents in the U.S., Europe, and other jurisdictions for methods of identifying and treating patients with the specific genotype analyzed in this paper. In a planned Phase 3 clinical trial, the Company intends to evaluate Gencaro as a potential treatment for the prevention of atrial fibrillation in patients with the same specific genotype discussed in the paper because the potential prevention of atrial fibrillation by Gencaro appears to follow the same pharmacogenetic pattern as the one associated with the prevention of heart failure in the paper. About ARCA biopharma ARCA biopharma is dedicated to developing genetically-targeted therapies for cardiovascular diseases. The Company's lead product candidate, Gencaro™ (bucindolol hydrochloride), is an investigational, pharmacologically unique beta-blocker and mild vasodilator being developed for atrial fibrillation. ARCA has identified common genetic variations that it believes predict individual patient response to Gencaro, giving it the potential to be the first genetically-targeted atrial fibrillation prevention treatment. ARCA has a collaboration with the Laboratory Corporation of America (LabCorp), under which LabCorp has developed a companion genetic test for Gencaro. For more information, please visit www.arcabiopharma.com.