Zyngenia's technology is applied to create a new class of monoclonal antibody (mAb)-based therapeutics, called Zybody™ therapeutics. Zybodies are engineered to express multiple modular recognition domains (MRDs) that enable simultaneous binding to multiple disease targets (two to five specificities) with tunable valency (two to ten valencies). Initially, Zyngenia's proprietary programs have been built on foundations of mAb drugs with proven markets, with the strategy being to enhance efficacy and broaden the potential patient populations for these established mAbs. To date, Zyngenia has achieved preclinical proof-of-concept with bi-specific and tri-specific programs in cancer and inflammation.
Zyngenia's therapeutics are readily constructed from the core scaffold mAbs, to which one or more target-specific MRDs have been genetically fused.Technology Approach Illustration.
The core scaffold mAbs used with Zyngenia's technology can be chimeric, humanized or human. Importantly, no alterations are made to the mAb scaffold that change its inherent function. Thus, each Zybody retains the essential drug-like properties of the parent mAb, including affinity, binding specificity and valency. Additionally, the scaffold retains FcRn binding and all Fc-receptor effector functions. Zybodies are produced and purified in the same way as traditional mAbs and have CMC properties and stabilities that are comparable to commercially validated mAbs.
Each MRD consists of a short (usually 20-50aa) target-binding peptide that is genetically constructed as part of the core antibody scaffold. The MRDs are easily engineered (as part of the gene) to the C or N termini of heavy or light chains of the antibodies, and thisĀ "plug and play" nature allows rapid construction (three months) of new therapeutics by the use of existing MRDs fused onto new scaffold antibodies. Zyngenia has designed many proprietary libraries of MRDs that possess sequence diversity greater than 1010. The MRD sequences are selected so as to minimize potential immunogenicity and instability (in vitro and in vivo) and selection strategies have been successfully applied to both soluble and cell surface targets.