ARCA biopharma announced a new development program to evaluate AB201 (rNAPc2), a potent, selective inhibitor of tissue factor (TF), as a potential treatment for COVID-19 associated coagulopathy (CAC) and the related inflammatory response. CAC is one of the most serious adverse effects seen in COVID-19 patients. AB201 has previously undergone clinical testing through Phase 2 in more than 700 patients for other indications, generating substantial safety data, which the Company believes may enable more rapid development. ARCA anticipates filing an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) in the third quarter and initiating late-stage clinical testing in the second half of this year.

TF is the protein responsible for initiating the primary or extrinsic coagulation pathway. TF has been identified as playing a central role in the inflammatory response to viral infections and in the process of viral dissemination. AB201 (rNAPc2), a single-chain, 85 amino acid, recombinant protein, has previously undergone Phase 1 and Phase 2 testing in more than 700 patients, including as an anti-thrombotic agent in the setting of acute myocardial infarction (MI), where it showed efficacy in inhibiting the TF pathway and was well tolerated at therapeutic doses. Recent research suggests that the disease syndrome caused by coronavirus may have much in common with other coagulopathic disorders in which the blood's ability to coagulate (form clots) is impaired by consumption of clotting factors (disseminated intravascular coagulation, DIC). For example, filovirus infections such as Ebola and other hemorrhagic fevers are characterized by dysregulated activation of the TF pathway, resulting in abnormal systemic coagulation and related inflammation, leading to organ failure and mortality. Recent mechanistic discoveries, as well as data from studies in non-human primates (NHPs) given lethal doses of Ebola or Marburg filoviruses demonstrating mortality reductions, decreases in inflammatory biomarkers and reduction in viral load, indicate that AB201 may have important antiviral and anti-inflammatory activity in addition to its anticoagulant effects. Collectively, the Company believes these observations provide a strong rationale for investigating AB201 as a treatment for COVID-19, the disease caused by SARS CoV-2 virus.

COVID-19 disease is associated with a significant incidence of coagulation-related adverse events, including stroke, MI (i.e., heart attack), pulmonary emboli, and disseminated intravascular coagulation (DIC), a condition in which small blood clots develop throughout the bloodstream. A commonly used biomarker for assessing coagulation activation is a D-dimer test, which is elevated in approximately 50% of hospitalized COVID-19 patients and is directly associated with adverse clinical outcomes. In Ebola or Marburg NHP models, AB201 inhibited the DIC process, as measured by lowered D-dimer levels, which the Company believes provides further support for its therapeutic potential for CAC. The Company believes the efficacy of AB201 against COVID-19 disease may not be affected by potential mutations of the SARS CoV-2 virus, would be additive with therapeutics inhibiting virus-cell binding or viral RNA polymerase, and could be effective against other coagulopathy-associated viruses.

“Our research, combined with the accumulating evidence on the clinical importance of large and small vessel thromboses in the COVID-19 infected patients, points to a potentially important role for the tissue factor pathway in viral infection, inflammatory response and the development of coagulopathy. With its properties in modulating the TF pathway and the evidence from its prior development, rNAPc2 has the potential to be a uniquely beneficial therapy for patients with COVID-19,” Dr. Wolfram Ruf, Scientific Director of the Center for Thrombosis and Hemostasis at the Johannes Gutenberg University Medical Center Mainz, Germany, and Professor at Scripps Research, La Jolla, CA, said.