BC 007 is capable of selectively neutralizing functionally active pathological autoantibodies directed against G protein-coupled receptors. The development of many deliberating diseases appears to be associated with the presence of these functional autoantibodies, such as heart diseases, Long COVID and others. Targeting functional autoantibodies with agents like BC 007 offers a unique therapeutic opportunity to treat such diseases.
Autoantibodies are antibodies that mistakenly target and react with the body's tissues, cells, or molecules, instead of foreign invaders like bacteria or viruses. In other words, the body's immune system fails to distinguish between “self” and “non-self.
Functional autoantibodies (fAABs) can interact with the body's own G protein-coupled receptors (GPCRs) and “switch on” certain cellular processes in an uncontrolled way that can lead to the development of many diseases.
There is strong scientific evidence that fAABs play a key role in the pathogenesis of many debilitating diseases. Developing compounds that specially neutralize fAABs is a unique approach as it addresses the cause of the disease which may lead to significant beneficial effects.
Dr Johannes Mülller was one of the first to demonstrate a causal relationship between heart failure and the presence of functional autoantibodies. Dr Müller could show the removal of fAABs using immunoadsorption in subjects with heart failure resulted in a clinically meaningful improvement in heart function. Moreover, study subjects were followed for a period of 12 years and a 3-fold increase in 5-year survival was observed. The study also demonstrated that BC 007 has a high level of safety and tolerability.
While immunoadsorption proved to be a very effective means of fAAB removal, it is poorly suited for routine use. It is expensive, requires multiple applications and is technically challenging to implement.
Through extensive research efforts, Berlin Cures has identified a compound that achieves the same results as immunoadsorption and can be considered as a therapeutic equivalent. This compound, BC 007 is a non-modified 15 mer single-strand DNA oligonucleotide described as an Aptamer that folds into a defined architecture BC 007 has been demonstrated to be highly effective at targeting and neutralizing autoantibodies directed against G protein-coupled receptors.
Extensive pre-clinical studies have demonstrated that BC 007 is well-tolerated and safe. These findings are further supported by clinical studies in subjects with heart failure where BC 007 demonstrated a significant positive effect on heart function and life expectancy. No adverse events were observed throughout the whole study period.
In May 2021, researchers at the University Clinic Erlangen, Germany, in collaboration with Berlin Cures, initiated a compassionate use program under which four cases of subjects suffering severely from the Long COVID Syndrome were treated with BC 007. The results were profound. After a single infusion of BC 007, all patients completely recovered from their symptoms of Long COVID.
These data enabled Berlin Cures to initiate a Phase II clinical study in subjects with Long COVID. The study is currently ongoing.
Berlin Cures is also targeting other diseases of significant unmet medical need that are causally linked to the presence of functional autoantibodies. Results from a controlled Phase IIa clinical study in subjects with heart failure demonstrated that treatment with BC 007 resulted in a clear and clinically meaningful improvement in their heart ejection fraction. Furthermore, long-lasting neutralization of functional autoantibodies of more than 12 months was observed following treatment. Encouraged by these clinical observations, Berlin Cures plans to conduct a Phase IIb in subjects with advanced heart failure.
Berlin Cures has developed a specific bioassay that is used to test if a subject is positive for the presence of functional autoantibodies (fAABs) from a small blood sample. This proprietary test is performed in the laboratories at Berlin Cures and is an integral part of the Phase II clinical study.
The test is also used to monitor the neutralization effect of BC 007 on functional autoantibodies in subjects that have been treated with BC 007. This enables Berlin Cures to effectively monitor the therapeutic effect of BC 007 on an individual basis for Long COVID and other diseases caused by the presence of fAABs, providing a more personalized medicine approach.