Long Live Proteins
Glycome BioPharma is developing a novel glycan half-life extension platform to enable improved or new biologic therapies. Our approach aims to exploit the benefits of existing approaches while avoiding their major limitations.
Inherently, proteins are sensitive to renal clearance and proteases which results in shorter half-lives and the need for more frequent doses. PEGylation has traditionally been the adopted strategy to improve pharmacokinetic profiles of therapeutic agents for the past >25years.
PEGylation increases hydrodynamic radius (size in solution), which prolongs circulatory time by reducing renal clearance. PEGylation can also provide water solubility to hydrophobic drugs and proteins. Lipidation and genetic fusions as half-live extension strategies are being utilised for the same purpose.
Limitations of PEGylation & existing half-life extension strategies
Our technology delivers rationally designed and targeted glycosylation modifications to protein therapeutics for augmentation of its pharmacological properties. Early indicators of this technologies have indicated significant potential to revolutionise the field of biotherapeutics.
For PEGylation, immunogenicity associated risks remain a problem with repeated doses in lifetime patients and can increase the risk of an immune response to the ‘new’ fused protein, even if it consists of a protein that may pose no risk by itself. The development of antibodies against PEG has been recorded and suspected to induce rapid clearance for certain drugs. The non-biodegradable nature of PEG results in toxic accumulation in tissue and vacuolation in macrophages has been observed.
PEGylation and other adopted conjugates continue to provide sub-optimal characteristics that no other technology has yet overcome.