Arca Biopharma Inc., of Westminster, Colo., is developing AB-201, a selective inhibitor of tissue factor (TF), as a treatment for COVID-19-associated coagulopathy, abnormal blood clotting and related inflammatory response. The move gave the company new life Thursday.
The development sparked such interest in the company stock (NASDAQ:ABIO) that it spiked 386.33% upward Thursday to close at $19.21 per share. The uptick comes after Arca reported in its first-quarter earnings report that it would need to raise additional capital and/or complete a partnership or other strategic transaction to fund future operations and develop Gencaro, (bucindolol hydrochloride), its investigational beta blocker and mild vasodilator, “or any other product candidates.” Arca reported a net loss of $1.3 million, or 83 cents per share, for the quarter.
AB-201 has undergone clinical testing through phase II in more than 700 patients for other indications and generated substantial safety data, the company said. AB-201 (rNAPc2), a single-chain, 85 amino acid, recombinant protein, was tested as an antithrombotic agent in acute myocardial infarction, where it showed efficacy in inhibiting the TF pathway and was well-tolerated at therapeutic doses.
Arca said recent research suggests the disease syndrome caused by the coronavirus may have much in common with other coagulopathic disorders, such as when blood clotting is impaired by the consumption of clotting factors. The company noted that filovirus infections such as Ebola are characterized by dysregulated activation of the TF pathway. The result, the company added, can be abnormal systemic coagulation and related inflammation, which can lead to organ failure and death.
COVID-19 is associated with coagulation-related adverse events that include stroke, myocardial infarction, pulmonary emboli and disseminated intravascular coagulation.
The company said it anticipates filing an IND in the third quarter of 2020 and, pending FDA concurrence and obtaining trial funding, it would start late-stage clinical testing by year-end.
Arca said it will collaborate with the Colorado Prevention Center, the University of Colorado's Academic Research Organization, in a phase IIb/III trial protocol that is being developed for hospitalized COVID-19 patients with elevated D-dimer levels. D-dimer tests assess coagulation activation, which is elevated in about half of hospitalized COVID-19 patients.
The company said AB-201’s efficacy against COVID-19 may not be affected by potential SARS CoV-2 virus mutations, would be additive with therapeutics that inhibit viral-cell binding or viral RNA polymerase, and may be effective against other coagulopathy-associated viruses.
Gencaro had received fast track designation from the FDA. Then, in February, the FDA granted Gencaro a special protocol assessment agreement for a single phase III trial. The company said it has identified common genetic variations that it believes predict individual patient response to Gencaro, adding that it has the potential to be the first genetically targeted atrial fibrillation prevention treatment.
In early May, phase II data from Arca’s study of Gencaro for treating atrial fibrillation in patients with heart failure showed the beta-blocker decreased cumulative atrial fibrillation (AF) burden by 26% compared to metoprolol succinate (p<0.001). Compared to metoprolol, Gencaro decreased a composite endpoint of AF interventions and cardiovascular adverse events by 30% (p=0.008) and decreased AF interventions by 33% (p=0.009).
Arca is also developing AB-171, a thiol-substituted isosorbide mononitrate as a genetically targeted treatment for heart failure and peripheral arterial disease.