BC-007

BC-007, whose international nonproprietary name is Rovunaptabin, is an oligonucleotide aptamer, a synthetic DNA compound designed to bind other chemicals. BC-007 is in early-stage clinical trials as a lead compound intended for the potential treatment of heart failure or long COVID.

History
Since the 1990s, the binding of G protein coupled receptors to autoantibodies (GPCR-AABs) was investigated as a possible factor in the pathology of several diseases, including heart disease. In parallel, treatment strategies to remove GPCR-AABs were investigated, initially using proteins or peptides to bind the antibodies.

In 2012, scientists from the Max Delbrück Center and the Charité Heart Center obtained a patent in the United States for using aptamers as a therapy or diagnosis of autoimmune diseases. Beginning in 2013, the research group focused on the treatment of dilated cardiomyopathy in people positive for beta-1 adrenergic receptor autoantibodies. In 2015–16, scientists reported that two aptamers might bind and inhibit GPCR-AABs.

The biotechnology company Berlin Cures pursued the development of the aptamer with the nucleotide sequence GGT TGG TGT GGT TGG under the codename BC-007 for the inhibition of autoantibodies in cardiomyopathy.

Properties
BC-007 is a 15-nucleotide single-stranded DNA molecule consisting of nine unmodified deoxy-guanosines and six corresponding deoxythymidines with the sequence 5'-GGT TGG TGT GGT TGG-3'. Its three-dimensional structure allows it to wrap around the target structure of G-protein-coupled receptor autoantibodies and neutralize their activity.

BC-007 is synthetic, enabling it to be produced in high volumes quickly. It is stable and suited for long-term storage. It has shown no side effects in early clinical studies, and does not trigger immunological responses. As it is water soluble, it can be formulated as inhalation or as nasal spray. In some human studies, it was given by intravenous infusion, displaying an in vivo half-life in blood of about 4 minutes.

Heart failure
The removal of pathogenic functional autoantibodies through a medical blood purification procedure, known as immunoadsorption, can stabilize heart function in people with dilated cardiomyopathy who are awaiting heart transplantation. In 2018, a Phase I clinical trial found that BC-007 was well-tolerated, with no serious adverse events reported. Phase IIa trials demonstrated that BC-007 could neutralize the activity of functional autoantibodies in most subjects treated.

Long COVID
BC-007 is under investigation as a possible agent for treating disorders of long COVID.