Working alongside disease area experts at the University of Oxford and funded by the Dementia Discovery Fund, we are exploring Bicycles as potential therapies for neurodegenerative disease.
The dual challenge is to develop potential Bicycle modulators to novel targets in dementia and to deliver these through the blood brain barrier to the CNS using our precision guidance technology.
Neuroscience has historically presented a significant challenge for drug discovery, as the therapeutic targets have often proved difficult to drug, or at least to drug selectively with small molecules, which can be engineered to cross the blood brain barrier (BBB) and enter the CNS; while biologics, which are more selective, are also unable to cross the BBB.
In May 2019, Bicycle formed a collaboration with the Dementia Discovery Fund (DDF) to use Bicycle technology for the potential development of novel therapeutics for neurodegenerative diseases.
DDF is a specialized venture capital fund focused on discovering and developing novel therapies for dementia. In October 2019, the collaboration was expanded to include Oxford University’s ARUK Oxford Drug Discovery Institute, one of three institutes within the Alzheimer’s Research UK Drug Discovery Alliance and a leading institution studying diseases of the central nervous system.
One of the most genetically validated targets in neurodegeneration is TREM2, which is involved in removing b-Amyloid from the CNS. Bicycle applied its technology and successfully identified TREM2 agonists which activate the protective effects of TREM2 on microglia . These compounds are being evaluated in a range of pre-clinical assays to further determine their therapeutic utility. As part of the same collaboration, Bicycle was funded to screen TfR1(CD71), a well characterized mechanism that facilitates compound trafficking into the CNS, and identified high potency Bicycles for this target. These TfR1 molecules, which Bicycle retains all rights to outside of the license granted for use with targets defined within the DDF collaboration, may be developed into a bispecific Bicycle therapeutic to potentially deliver optimised TREM2 agonists into the CNS. Bicycle and DDF have the option to jointly establish a new company to further develop these compounds.