In this mouse BT-474 xenograft study, trastuzumab-based ADCs prepared using Synaffix’s proprietary SYNtecan E™ linker-payload demonstrated an efficacy profile equivalent to deruxtecan-based ADCs. SYNtecan E™ is an exatecan-based linker-payload that contains the HydraSpace™ polar spacer technology, a conventional dipeptide cleavable linker and is conjugated, in this study, to the native antibody glycan using GlycoConnect™. Deruxtecan is the linker-payload used in Enhertu®, the FDA-approved ADC indicated for previously treated, HER-2 positive unresectable or metastatic breast cancer.
Following just a single dose, both HER-2-targeting ADCs, which have the same drug-to-antibody ratio (DAR) and administered at the same dose level, achieved complete tumor regression.
A poster of the data will be presented at the World ADC Digital conference on Thursday, 17 September 2020 at 3:30p-4:00p EDT.
“Given the recent clinical and commercial success observed with deruxtecan-based ADCs, we have been very excited with our first data for ADCs with the same mechanism of action.” – Floris van Delft, CSO of Synaffix said:
“Exatecan mesylate has completed Phase 3 studies as a single agent already and comes with a well-understood toxicology profile. That said, its relatively challenging biophysical properties have likely contributed to limited exploration within the ADC context to date, despite its high potency and putative bystander killing potential. We have resolved the ADC aggregation issue by combining exatecan with our highly polar HydraSpace™ technology, providing highly stable and efficacious ADCs. We look forward to presenting further data on this new linker-payload and introducing it to our collaborators in due course.”
Deruxtecan and SYNtecan E™ both belong to the family of camptothecins and are potent DNA topoisomerase 1 inhibitors that release DXd and exatecan as the active catabolite respectively.
SYNtecan E™ represents one of multiple options within the toxSYN™ linker-payload platform, which spans multiple mechanisms of action and can be evaluated in combination with GlycoConnect™ and HydraSpace™ technologies. This consolidated ADC platform enables any company with an antibody to rapidly co-discover an ADC with Synaffix and then develop and market the resulting ADC as part of its own pipeline under a license agreement.