Bispecific delivery using recombinant human albumin as a versatile platform
For many new biotherapeutics, the ability to bind two different receptors or ligands and elicit the required biological responses simultaneously, is critical for full therapeutic effect. It is therefore vital that the employed delivery platform offers effective control for the generation of such bispecific entities.
Multiple molecular formats have been developed using antibodies, with varying success in creating a stable and homogeneous bispecific molecule that can be easily scaled for commercial manufacturing.
Albumin offers an attractive alternative to bispecific antibodies with its stable and simple molecular architecture. Coupled with the added half-life and payload capacity benefits of our engineered albumin variants (Veltis®), this alternative protein scaffold design offers a versatile platform for bispecific drug delivery:
- Optimized drug performance, compliance and safety profile through modulatation of drug half-life using our engineered albumins displaying a significantly higher affinity for the natural receptor of albumin, FcRn.
- Generation of bispecific albumin drug conjugates with a DAR (Drug Albumin Ratio) of up to three, achievable through site-specific conjugation to albumin variants with strategically placed conjugation sites.
- Tissue specific delivery at sites of inflammation and/or solid tumors through passive and active targeting.
- The intrinsic structural nature of albumin makes it a simple and stable molecular format for development of homogeneous bispecifics, with an established and scalable manufacturing path.
- Broad design flexibility for creation of bispecifics, through fusion and conjugation to engineered albumin variants, while preserving the high stability of albumin.
Broad design flexibility for creation of albumin-based bispecifics
Engineered recombinant human albumins from Albumedix have several options available for the design of bispecific molecules. By combining site specific conjugation to one or more thiols, with N and/or C-terminal fusion to albumin, it is possible to design a multitude of bispecific albumin drug constructs.
Bi-specific albumin drug construct design by fusion and conjugation to Veltis® albumin variants
Bispecific delivery design:
- Albumin fusion: We have, with success, made both C and N-terminal albumin fusions individually and combinations thereof.
- Conjugation at Cys34: Albumin conjugation enables the generation of other drugs, over natural amino acids in single linear design, as required for fusion proteins. Learn more here
- Conjugation at engineered surface thiol sites: Our engineered albumin, as to make it carry two additional free cysteine thiols, enabling the generation of albumin drug conjugates with a DAR (Drug Albumin Ratio) of up to three, read more here.
It should be noted that the positions of these cysteines are distributed as to minimally influence the albumin’s ability to bind to the FcRn, whereby not compromising the achievable half-life extension of improved albumin binders, even when multiple drugs are loaded on the albumin protein. Learn more about half life extension here