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    5.  » Specialized Linkers

Antibody-drug Conjugates & Bioconjugates

SPECIALIZED LINKERS

scientistData generated from SMARTag-designed ADCs to date demonstrate conjugate stability – even with cleavable linkers – to deliver efficacy with improved tolerability and a wider therapeutic window.

NONCLEAVABLE LINKERS

RED-106, a proprietary noncleavable linker with a maytansine payload, is used in a Phase 1 clinical trial (TRPH-222) offering:

  • Stable payload attachment to mAb
  • No bystander effect, reducing off-target toxicities
  • Maintains potency in cells with upregulated P-glycoprotein
  • Can induce immunogenic cell death in target cells
  • Improved tolerability and efficacy as compared to conventional maytansine linkers (e.g., Kadcyla®)

noncleavable linkers

TANDEM-CLEAVAGE LINKERS

Traditional cleavable linkers require one “key” for payload release and can lead to release during circulation, while SMARTag® tandem-cleavage linkers require two “keys” for payload release where tumor cells have both keys. This offers superior stability and reduced toxicity in vivo.

tandem-cleavage

Publications

Bioconjugate Chemistry: Hydrazino-Pictet-Spengler ligation as a biocompatible method for the generation of stable protein conjugates

Molecular Cancer Therapeutics: A novel HER2-targeted antibody-drug conjugate offers the possibility of clinical dosing at trastuzumab-equivalent exposure levels

Bioconjugate Chemistry: Tandem-cleavage linkers improve the in vivo stability and tolerability of antibody-drug conjugates

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