Our IntelliSelect® Transgenic platforms utilize the immune system’s natural mechanisms to create fully-human antibodies that are mature or evolved to be highly specific for their target. We have achieved this by creating several strains of mice in which a complete set of human antibody genes and their landscape of surrounding human genomic DNA was carefully reconstructed in the mouse.
The human antibody gene loci in our IntelliSelect® Transgenic platforms mirror those in a human because we utilize the full expanse of the sequence found in humans.
The order and orientation of the genes that encode the antibodies, as well as the intergenic DNA, have an important regulatory function which we recreate in the mouse. As a result, the human loci can function as if they are operating in a human B cell, even though the human genes are present in mouse B cells.
When immunised with human targets or pathogenic organisms, Kymab's mouse antibody platforms deliver a normal immune response and mature antibody drugs from their human building blocks. Because the human antibodies are produced through the normal and natural process of maturation, they evolve from molecules with good drug-like properties to drugs with exceptional potency, stability and solubility. Importantly, when these antibody genes are transferred into mammalian expression systems the recombinant molecules are reliably expressed at high levels.
When immunised with our target of choice, our platforms initiate tens of thousands of parallel antibody evolutionary processes in vivo, resulting in the creation of extensive family trees of affinity-matured human antibodies, which our IntelliSelect® Screening technology platform can then sequence, sort and evaluate.
Our modular antibody-discovery platforms can be modified further to support the discovery of highly differentiated antibodies and molecules with modes of action that would be unobtainable with other platforms. We invest in development of our platforms to facilitate specific drug-discovery efforts, such as target-locus knockouts and focusing of the repertoire by pre-setting the heavy or light chain to engineer bispecific antibodies. We have also generated mice with an enhanced average CDR3H length which will more effectively deliver antibodies against less-exposed epitopes.
We can further optimize our IntelliSelect® Transgenic platforms by inactivating the gene that encodes the protein that is the homolog of our selected drug target, also known as a knock-out, or KO.
Our gene inactivation capabilities allow our platforms to generate a greater diversity of antibodies that can bind to targets that have historically been difficult to reach. This allows us to isolate cross-reactive antibodies that target parts of antigens that are conserved between species.
Cross-reactivity also enables more efficient preclinical development of our product candidates because most animal efficacy models are rodent-based and therefore we can test the actual drug rather than a surrogate or mouse- equivalent using our platforms.