G protein-coupled receptors (GPCRs) is a large family of cell receptors, characterized with 7-transmembrane domains, an extracellular N-terminus and an intracellular C-terminus. Ligands that bind and activate GPCRs include light-sensitive compounds, odors, pheromones, hormones, and neurotransmitters, range from small molecules to peptides to proteins. GPCRs are involved in various physiological functions, such as: sensory function (vision, taste and smell), CNS function (neurotransmitters), immune system and inflammation (chemokines and beyond), autonomic nervous system and tumor metastasis.
GPCRs are premium target repertoire for drug discovery. From the 1578 FDA approved drugs, 33% of the small molecule drugs are targeting GPCRs. There are over 800 human GPCRs, more than half of that are sensory receptors (e.g. olfactory receptors and opsins/rhodopsin-related receptors) that are not suitable for drug targets. Among the 369 GPCRs as potential drug targets, 46 of them have already been successfully targeted by drugs, leaving 323 GPCRs as potential new targets.
Nature Reviews | Drug Discovery | Dec. 2016
GPCRs have been well known as “difficult targets" for antibodies. Around 80 out of the 369 drug targets GPCRs are suitable for antibody discovery. There are 2 approved GPCR Abs up to date, Mogamulizumab/Poteligeo (Kyowa Hakko Kirin Co.) in Japan, and Erenumab-aooe/Aimovig (Amgen & Novartis). The reason behind is that there are several technical hurdles for Ab generation:
1) difficult antigen, such as limited extracellular domain, low expression on cell membrane, natural functional protein hard to purify, etc.
2) screening method: functional assays to select therapeutic candidates
Gmax has built up a proprietary platform with systemic approach to develop GPCR MAb: effective GPCR MAb generation, screening and development. Gmax has successfully generated a series of functional antibodies in various stages of development.
Gmax has built up an in-house antibody development platform which enables the antibody screening, humanization, and engineering, to obtain the antibody candidates with excellent drugability and developability.