PermaLink ™

Glythera’s PermaLink™ technology is a controlled, stable conjugation platform composed of a portfolio of linker designs. PermaLink™ can be employed for the selective and stable functionalization and conjugation of various cargos to proteins and peptides.

Due to its increased stability and selectivity, PermaLink™ offers significant benefits in the development of next generation biologics:

Antibody Drug Conjugates

(ADCs) are highly potent biologics composed of a tumour specific antibody linked via a linker to a cytotoxic drug. One of the crucial requirements for improving the therapeutic window of ADCs is specific and stable attachment of a potent cytotoxic agent to the antibody via the linker. Benefits of using PermaLink™:

  • Highly specific for the sulfhydryl groups of cysteine residues which are a primary site for cytotoxic drug attachment in many ADCs currently in clinical development
  • Enhanced stability provided by a stable thioether bond which is resistant to biological and chemical degradation
  • Compatible with a diverse range of cytotoxic payloads due to the ability to be tailored to generate both “non-cleavable” and “cleavable” linkers for efficient release of active drug following antigen-mediated internalization
Conjugate vaccines

Conjugate vaccines are composed of antigenic capsular polysaccharides conjugated to a carrier protein which enhances the induction of protective antibodies. Vaccines based only on carbohydrates induce less robust and short-lived immune responses as they are often poorly immunogenic. Conjugation to protein and enhanced antigen presentation enables the generation of high affinity antibodies and subsequently long lived immune responses.

Benefits of using PermaLink™:

  • Greater control over the conjugation process due to its specificity, limiting the number of attachment points between the protein and the polysaccharide
  • Enables the application of mild conjugation protocols
PEGylation

PEGylation has been used for enhancing the bioavailability and efficacy of a wide range of biotherapeutics. The most common method for PEG conjugation utilises the amine groups of lysine side chains.

Benefits of using PermaLink™:

  • Targets less abundant cysteine residues resulting in a more homogenously modified protein
  • Enables conjugation of PEG to free thiols of cysteine residues with ~ 90% yield

PermaLink™ offers a number of otherbenefits including:

  • Comparative model system
  • Controlled Drug to Antibody Ratio (DAR)
  • Improved linker stability compared to maleimide based technologies
  • Comparable in vitro activity
  • Low immunogenic potential