Aptamers are short, single-stranded oligonucleotides (either DNA or RNA) that fold into defined architectures and bind specifically to target molecules such as autoantibodies and proteins. They are often described as “chemical antibodies,” and are synthetically made, allowing precise control over their composition in a scalable and compliant process, have a high degree of stability.
Aptamers belong to a new class of emerging innovative drugs including aptamer–siRNA chimeras and CRISPR-targeting aptamers that may impart potential advantages over traditional therapies such as high precision to target binding, low to non-immunogenicity, reduced off-target effects and improved therapeutic index.
Rovunaptabin is a single-stranded DNA aptamer which binds with high affinity and specificity to pathogenic regulatory autoantibodies (RAbs), blocking their uncontrolled activation of G protein-coupled receptors (GPCRs).
Rovunaptabin is currently in development for the treatment of heart failure and post viral infectious diseases (PVIDs).
One of the most well-studied GPCRs in cardiovascular physiology is the β-adrenergic receptor. These receptors respond to catecholamines like epinephrine (adrenaline) and norepinephrine (noradrenaline) and are central to the regulation of cardiac output.
Chronic stimulation of the β1-adrenergic receptor can lead to hypertrophy, cell death, and adverse cardiac remodeling all of which are hallmarks of heart failure.
There is substantial clinical evidence that implicates regulatory autoantibodies (RAbs) as a key player in the development of cardiovascular diseases as they can specifically activate β1-adrenergic receptors directly on cardiomyocytes often for extended periods of time leading to apoptosis of the cardiomyocytes and subsequently heart failure.
Clinical observations have shown that higher titers of RAbs are associated with worse cardiac function (lower ejection fraction) and poorer outcomes in patients with dilated cardiomyopathy and models of passive transfer have indicated a causal role for RAbs in disease development.
In a recently completed phase 2 study in 30 patients with heart failure, rovunaptabin demonstrated encouraging results in heart function.
“The Persistence of Autoantibody Neutralisation by BC 007 in Patients With Chronic HFrEF and Autoantibodies Against the Beta1-Adrenergic Receptor.”
There is substantial clinical evidence that post-viral infectious diseases can frequently trigger dysregulation of regulatory autoantibodies (RAbs) that target G- protein coupled receptors. This dysregulation can persist long after the infection has subsided, causing symptoms lasting for months or even years.
Two independent phase 2 clinical studies in subjects with long-term effects of the SARS-CoV-2 virus have been completed with encouraging results.
“To Investigate Efficacy, Pharmacodynamics, and Safety of BC 007 in Participants With Long COVID (BLOC).”
“Prospective, explorative, randomized, controlled, double-blind, cross-over phase IIa clinical trial to investigate safety and tolerability as well as potential clinical effects of BC007 in patients with post-COVID syndrome.”
Many promising therapies fail not because they are ineffective, but because they are tested in patient populations that are too broad or misclassified.
Developing robust diagnostic tools needed to identify the right patients most likely to benefit from a specific intervention, can be very challenging but necessary to increase the chance of success in clinical trials and accelerate the approval of effective therapies.
APTA Therapeutics will work with specialized research teams to develop a molecular profiling approach to better define RAbs in patients with heart failure and post-viral infectious diseases.