Netherlands-bases biotechnology company Synaffix BV, which exclusively focuses on the development of novel antibody-drug conjugate (ADC) technology,  confirmed that a new set of head-to-head data demonstrates the potential of its technology to significantly expand the therapeutic index vs cysteine-engineered ADCs.  Supporting data presented during a plenary presentation at the World ADC event in Berlin on Tuesday, February 21, 2017.

“…Our proprietary technology has now demonstrated enhanced therapeutic index also vs what is widely regarded as the most advanced clinical-stage, site-specific ADC technology…”

Conventional antibody-drug conjugates or ADCs produced using earlier conjugation methodologies conjugate a cytotoxic drug to an antibody through the side chains of either surface-exposed lysines or free cysteines generated through reduction of interchain disulfide bonds. Since antibodies contain many lysine residues and cysteine disulfide bonds, the process of conventional conjugation generally produces a heterogeneous mixtures of chemically distinct molecules that vary in both drugs-antibody ratio (DAR) and conjugation sites. This, in turn, presents analytical characterization and manufacturing challenges, resulted from the presence of a mixture of covalent and noncovalently associated light chain and heavy chain subdomains.  The sub-optimal properties of heterogeneous ADCs, each exhibiting different pharmacokinetic, efficacy, and safety profiles, have led to an ongoing effort in improving ADC technology

Researchers at Synaffix have succeeded in doing so and presented data showing superiority of their vs conventional conjugation methodologie. The data they presented resulted from a series of preclinical studies performed in rodents and non-human primates, in a comparative assessment, by an undisclosed collaborator. In these studies different ADCs comprising the same antibody and cytotoxic payload were assembled with either Synaffix’ proprietary GlycoConnect™ and HydraSpace™ technologies or a cysteine-engineered methodology.

Synaffix’ technologies have demonstrated compatibility with all ADC payload classes and all IgG isotypes without requiring antibody engineering.

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GlycoConnect™ is a site-specific and stable antibody conjugation technology that involves proprietary enzymes and metal-free click conjugation reagents. Research has shown tat GlycoConnect™ is capable of significantly enhancing the therapeutic index of any antibody-drug conjugate on its own.

HydraSpace™ is an ADC-enhancing spacer technology.  The highly polar properties of HydraSpace™ improve the solubility and stability of the resulting ADC product, thus further enhancing the therapeutic index of the ADC.

Enhanced therapeutic Index
“After showing superiority vs the earlier conjugation methodologies used in the currently marketed ADCs, our proprietary technology has now demonstrated enhanced therapeutic index also vs what is widely regarded as the most advanced clinical-stage, site-specific ADC technology” said Floris van Delft, CSO of Synaffix.

“With more than ten engineered-cysteine based ADC programs currently in clinical trials, the new data cultivate further confidence towards the clinical performance of ADCs built using our proprietary technology, as we prepare for the manufacturing of the first clinical batches that will be delivered to patients next year,” Van Delft added.

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