AdAlta is the pioneer of a novel technology platform that mimics the shape and engineers key stability features of the antigen binding domain of shark antibodies into human proteins to create unique compounds, known as i-bodies. Our technology platform can be used to identify novel therapeutics to a range of disease targets.
Drug discovery and manufacture process
We have developed i-bodies into proprietary phage libraries containing over 2 billion i-body protein compounds. This large diverse library contains i-bodies that can bind to a broad range of therapeutically-relevant targets and can be rapidly screened in the lab against disease targets. Once i-body binders have been identified they can then be readily further improved through a process known as affinity-maturation to enhance target binding and thereby generate therapeutic lead drug candidates.
i-bodies are manufactured in bacterial systems, a more cost effective and easier method than the types of human cell culture required for conventional monoclonal antibodies. In addition we have preliminary data demonstrating that functional i-bodies can be manufactured using peptide synthesis, removing the need for bacterial manufacturing.
Our lead i-body candidate AD-114 is being developed for idiopathic pulmonary fibrosis (IPF). Read more.
Generating differentiated therapeutics
The unique biophysical properties of i-bodies such as small size and exceptional stability combined with high specificity, affinity and the unique binding loop enables desirable properties to be engineered thereby creating differentiated therapeutics.
Because of the long binding loop of the i-body, that is lacking in traditional antibodies, i-bodies recognise and bind to a diverse range of different therapeutically-relevant targets including those that are difficult/intractable to access by current antibody therapies such as G-protein coupled receptors (GPCRs) and ion channels.
The small physical size, robustness and stability of i-bodies provide advantages for tissue and organ penetration as well as multiple delivery routes. These properties allows survival at the extreme conditions needed for drug nebulisation or even spray drying. In addition, i-bodies are more resistant to extremes of pH and temperature and resist attack by proteases to a greater degree than conventional antibodies. Some i-bodies have been shown to survive the harsh conditions of the stomach and intestine tissues and remain biologically active. This creates opportunities for orally delivered i-bodies or even pulmonary delivery opportunities in the area of fibrosis.
i-bodies can serve as building blocks to engineer therapeutics with tailored pharmacokinetic properties as a result of their small size and exceptional stability. We have demonstrated in mice that the half-life of the i-body protein can be engineered from hours to days; this should translate to several weeks in a humans.
i-body products that are unique and differentiated can be easily engineered into a variety of formats including monospecific and bispecifics as well as i-body drug conjugates (IDCs), thus tailoring them for different therapeutic purposes. The i-body is well suited to the delivery of payloads through the conjugation to cytotoxic agents. Antibody conjugated drugs are a growing area of drug development focus, coupling known therapeutic drugs with antibodies, enabling the delivery of smaller doses of drugs to specific areas of disease, increasing therapeutic effect and reducing side effects.