The UNICORN CAPITAL venture fund is investing in Troy Bio, which is developing a unique platform to deliver enzyme replacement therapy across the blood-brain barrier (BBB) based on an antibody to the transferrin receptor (TfR1).

Modern therapy for monogenic orphan diseases is based on enzyme-replacement therapy (ERT) – when a “defective” or missing enzyme is replaced with its genetically engineered version. Currently, over 50 monogenic orphan storage diseases are known. However, the existing ERT is ineffective against neurocognitive (and partly muscular) disorders due to low efficiency of the corresponding delivery systems.

Today, the use of TfR1 is the most effective and the only clinically validated approach for delivering enzyme replacement therapy via blood-brain barrier (BBB).

TfR1 is a transferrin receptor that is involved in intracellular delivery of iron through internalization of the Fe3+-transferrin complex. TfR1 is characterized by widespread expression in various tissues, including endothelium of brain capillaries (which is the part of BBB), cardiomyocytes and skeletal muscle cells. Rapid internalization with subsequent recycling makes TfR1 a target for the development of effective intracellular delivery system.

Conjugation of enzymes with anti-TfR1 antibodies increases bioavailability for the central nervous system (as well as for muscles) and create a more effective new generation of ERT, which will greatly increase the effectiveness of treatment of orphan monogenic diseases with neurocognitive and other manifestations.