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PUBLICATION: Enzymatic Strategies for (near) Clinical Development of ADCs

Authors: Sander S.van Berkela & Floris L.van Delftab

Abstract

Target-specific killing of tumor cells with antibody-drug conjugates (ADCs) is an elegant concept in the continued fight against cancer. However, despite more than 20 years of clinical development, only four ADC have reached market approval, while at least 50 clinical programs were terminated early. The high attrition rate of ADCs may, at least in part, be attributed to heterogeneity and instability of conventional technologies. At present, various (chemo)enzymatic approaches for site-specific and stable conjugation of toxic payloads are making their way to the clinic, thereby potentially providing ADCs with increased therapeutic window.

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Protein Conjugates

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Just like our ADC technology, we can easily attach peptide and protein-based payloads to your antibody.

 

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HydraSpace™ Polar Spacer

Forming an integral part of every toxSYN™ linker-payload, HydraSpace™ bears a negative charge at physiological pH and improves:

  1. Therapeutic efficacy
  2. Tolerability
  3. PK
  4. Manufacturability
Key publication about HydraSpace

GlycoConnect™ design easily matches payload potency with the most appropriate drug-antibody ratio (DAR).

Key publications about GlycoConnect™

toxSYN™ Linker-Payloads

Choose from the following linker-payloads, attach to your antibody under a technology evaluation and go straight into ADC product development following positive POC.
toxSYN™
Linker-Payload
Mode-of-Action Payload
(Active Catabolite)
1. SYNtecan E™*Topoisomerase 1 inhibitor Camptothecin-based
2. SYNeamicin D™*DNA
damaging agent
Calicheamicin-based
3. SYNeamicin G™*
4. SYN-PNU™*Nemorubicin-based
5. SYNstatin E™Microtubule
inhibitors
Auristatin-based
6. SYNstatin F™
7. SYNtansine™ Maytansine-based

* Patent protection filed by Synaffix, beyond the claims of GlycoConnect™ and HydraSpace™

** N-6-aminohexanoyl-maytansine (Ahx-maytansine)