The National Institute of Mental Health awarded Omeros a roughly $700,000 grant to support the application of its DTLacO platform for the development of orphan GPCR-targeting antibodies against neurological disorders. DTLacO is an ex vivo antibody discovery platform that combines an engineered chicken B cell line with antibody selection. The firm claims the DTLacO library is enhanced by the ability of DTLacO cells to mediate molecular diversification of antibody genes by reconfiguring elements of the antibody that control binding, enabling rapid maturation of selected antibodies to improve affinity, specificity, and function. The platform can thus generate antibodies with long CDR-H3 regions, which are suited for targeting difficult-to-bind epitopes including GOCRs.
“We are pleased that the NIMH has again awarded a grant to support our orphan GPCR research," comments Gregory A. Demopulos, M.D., chairman, and CEO. “Omeros’ DTLacO platform can generate antibodies that target a wide range of diseases, including multiple types of cancer. With respect to our orphan GPCR program, the DTLacO platform nicely complements our proprietary cellular redistribution assay (CRA) that, to date, has identified small molecules that functionally interact with 42 orphan GPCRs. For those few receptors that are recalcitrant to our high-throughput CRA approach, our DTLacO platform provides another avenue to discover and develop new drugs to benefit patients.
Omeros says that of the 363 nonsensory GPCRs identified, 240 have known ligands, and about half are targeted either by marked drugs (46 GPCRs) or by developmental candidates (about another 70 GPCRs). However, there are another 120 orphan GPCRs without a known ligand. Omeros is exploiting its high-throughput CRA platform to identify small-molecule agonists and antagonists against these orphan GPCRs, and effectively open them to drug development.