Discussion

Peptides and proteins offer a differentiated therapeutic approach compared to monoclonal antibodies. However, transforming such molecules into patient-friendly and safe medicines presents a challenge due to their short plasma half-life through their rapid elimination via the kidneys. Artificially increasing the hydrodynamic size of the peptide or protein can circumvent this limitation.

Here, we describe a versatile best-in–class 2nd generation serum-half life extending platform technology – the AlbudAbTM -, which can be fused genetically or chemically to various therapeutic agents, including peptides and proteins.

AlbudAbsTM are small single domain antibodies (12 kDa) which act as a tag to extend the systemic exposure of the conjugated therapeutic agent through the ability to bind serum albumin. The transient therapeutic-AlbudAbTM complex with serum albumin is protected from renal excretion by its high molecular weight as well as the endogenous FcRn-mediated system for recycling serum albumin. Accordingly, the biodistribution profile and elimination rates of AlbudAbsTM approach those of albumin and IgGs.

GSK is committed to developing the AlbudAbTM as a best-in-class 2nd generation platform. We have generated a wealth of preclinical data for three assets including PYY and exendin-4 AlbudAbTM, both individually and in combination. Excitingly, data from a successful Phase I study of a peptide AlbudAb provided convincing evidence that weekly dosing of peptide - AlbudAbTM is at least equivalent to frequent dosing regimens required using the peptide alone. Hence, the peptide - AlbudAbTM offers a patient friendly, safe and, considering cost of goods, a potentially cheaper medicine.

In order to understand how best to apply the AlbudAbTM platform for maximum clinical effect, we are keen to engage with the academic and external research community to explore the development of potential peptide or protein therapeutic molecules which could benefit from the AlbudAbTM half-life extension technology.