AdAlta - Model i-body - Human Protein
From Technology
An i-body is a human protein that belongs to the class of next generation antibodies. The i-body is built on the scaffold of a human protein and engineered with two loops that mimic the shape of shark antibodies. These loops are responsible for binding or interacting with a particular target (in circulation or on a cell) that is causing disease. i-bodies are identified and developed using our proprietary technology platform.
Product Details
Similar to the antibody of a shark, one of the two i-body binding loops is very long – up to twice the length of human antibodies. This long loop gives the i-body a superior ability to access groves and cavities compared to traditional monoclonal antibodies and many other next generation antibodies in development can’t access. The size of a traditional monoclonal antibody is around 150,000Da, whereas an i-body is less than one-tenth of that size at approximately 12,000Da.
Why use i-bodies?
The unique structure of the i-body provides competitive advantages over other classes of pharmaceuticals such as small molecules and antibodies.
The i-body binds with high affinity and specificity to a drug target, like a traditional monoclonal antibody, reducing the off-target side effects commonly associated with small molecule drugs.
The i-body, with its small size and long binding loop, provides access to drug targets that evade traditional monoclonal antibodies. These include G-protein-coupled receptors (GPCRs), currently the most heavily investigated class of drug targets in the body, as well as Ion Channels, a class with significant untapped potential.
Customising the i-body
The i-body can be customised to increase the duration of the time the drug stays in the body, called the half-life. AdAlta has successfully produced i-bodies using various half-life extension technologies including PASylation, PEGylation and as well as by adding the i-body to an Fc-Fragment, which is the format of AdAlta’s lead candidate, AD-214.
The i-body platform
Identifying and developing new i-body therapeutics
AdAlta has utilised the unique structure of the i-body to develop a proprietary library containing over 20 billion i-body compounds. The library can be rapidly screened against a disease target of choice, to identify i-bodies specific for a range of therapeutically-relevant targets, and develop treatments for many conditions.
Once an i-body is identified to have affinity and specificity with a drug target of interest, its effectiveness is evaluated in cell based assays (in vitro) and in animal experiments (in vivo).
AdAlta has screened the i-body library to find a match with approximately 20 drug targets to date, and has identified i-bodies that bind to the target in each instance.
Undruggable Targets
A number of diseases remain difficult to treat due to the complexity of the target responsible for the disease pathology. These complex target molecules include G protein-coupled receptors (GPCRs) and Ion Channels, both representing large classes for potential therapeutic intervention.
Modern medicine typically drugs these complex targets using small molecules, but this approach is not specific or efficient, resulting in unwanted side effects and underwhelming effectiveness. The i-body, with its long loop for greater access and high specificity for its target, provides an opportunity to selectively modulate and drug these previously undruggable targets.
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