Profile of OmniAb Transgenic Platforms

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OmniAb® human therapeutic antibody platforms, OmniRat®, OmniMouse® and OmniFlic® are based on novel, transgenic rodents that produce highly diversified antibody repertoires and enable discovery and development of human therapeutic antibodies by Ligand’s partners. OmniAb antibodies offer several advantages, including accelerated discovery, in vivo optimization for therapeutic efficacy and manufacturability, and fully human sequences for safety and reduced immunogenicity. A wide range of large, mid-size and small companies presently utilize OmniAb animals in their therapeutic antibody discovery and development efforts. Most OmniAb licensees have unlimited or multi-target access and could yield multiple funded development programs or marketed products.

Several transgenic mice expressing human antibodies were available the late-1990’s and 2000’s using embryonic stem cell technology. The technology underlying OmniAb is the first based on inactivation of endogenous immunoglobulin (Ig) genes in rats. This was achieved using transient expression of zinc-finger nucleases in single-cell rat embryos and resulted in the generation of homozygous knock-out rats with no detectable levels of Ig. This important breakthrough was featured in the journal Science in 2009. In 2011, the scientists that developed the OmniAb platform created the first rat expressing a diversified repertoire of antibodies with fully human idiotypes.

OmniRat produces a diverse repertoire of antibodies with human idiotypes. It has been demonstrated that transgenic immunoglobulin loci in OmniRat are fully functional and support normal development of B-cells and high expression of antibodies. The frequency of immunoglobulin gene rearrangement in OmniRat is similar to that in humans and results in antibodies with similar CDR3 lengths and normal hyper mutation. Immunization of OmniRat results in the generation of antigen-specific antibodies with high binding affinities.

OmniMouse complements OmniRat and broadens the epitope coverage of OmniAb. Similar to the genetic engineering of OmniRat, transgenic immunoglobulin loci were integrated in the OmniMouse genome randomly. Therefore, OmniMouse offers freedom-to-operate advantages over transgenic mice with endogenous immunoglobulin loci that have been modified by insertion of human genes.

OmniFlic is a rat expressing antibodies with a single common human kappa light chain. The heavy chain immunoglobulin locus in OmniFlic is the same as in OmniRat. OmniFlic is designed for generation of bispecific human antibodies and also has freedom to operate advantages.

Therapeutic targets are scarce, limited by proven biology. Single antibody platforms, whether in vitro or in vivo, limit the utilization of scarce targets to what each such platform is able to deliver. In contrast, the OmniAb suite enables creation of better antibodies from multiple species with multiple genetics backgrounds and in multiple formats, whether mono- and bispecifics, naked or loaded, single antibodies or antibody cocktails, etc.

OmniAb animals are bred and kept in master colonies hosted by Charles River Labs and Taconic. This provides Ligand’s partners with on-demand, robust and scalable access to animals.

OmniAb has leading antibody drug discovery technology and is believed to be the only company in the world offering three transgenic animal platforms for license. OmniAb is owned by Ligand Pharmaceuticals.