Friday, April 19, 2019

Zymeworks moves bispecific to Phase IIa

Bispecifics are seen as the next evolution in antibody biologics development. Zymeworks has just progressed their first HER2 bispecific mAb into Phase IIa development.

Zymeworks is attempting to use two different binding regions both targeting different aspects of the HER2 epitope. In this way, the synergistic effect should lead to higher binding on lower expression strains of HER2

In addition to this trial, Zymeworks has multiple more bispecific molecules in the development pipeline targeting multiple different tumor targets.

To further extend the therapeutic window, Zymeworks is also integrating ADCs based on the ZLA (Zymelink Auristatin) Technology in order to further increase the potential therapeutic window of these bispecific mAbs.

The bispecific idea can be applied to ADCs effectively as well.  This was demonstrated here:
Molecular Cancer Therapeutics

The researchers are from UCSF and showed that bispecifics are able to separate the cancer target antigen into one target, and the rapid internalization aspect into a second target.
In this way they were able to demonstrate improved internalization over the individual mAbs or a mixture of the two.

It will be interesting to watch the progression. In the meantime, are bispecifics the future of antibody technology, or do they double the chances of off-target binding?

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