MorphoSys, a biotechnology company focused on fully human antibodies, and Heptares Therapeutics, a developer of new medicines targeting G protein-coupled receptors (GPCRs), have signed an agreement to discover novel antibody therapeutics targeting GPCRs—membrane proteins involved in a broad range of biological processes and diseases.

Heptares will generate stabilized receptors (StaRs) for a set of GPCR disease targets proposed by MorphoSys. MorphoSys will then apply its Ylanthia antibody library to discover and develop antibody therapeutics against these StaRs. MorphoSys has the right to sublicense to third parties access to these targets in conjunction with therapeutic antibody candidates. Heptares will receive upfront and research funding payments, plus a share of future sublicensing revenues generated by MorphoSys. Heptares also chose Ylanthia to develop and commercialize one therapeutic antibody created by MorphoSys against a GPCR target selected by Heptares. In this case, MorphoSys is eligible to receive license fees, milestones and royalties on any Ylanthia antibody developed by Heptares.

"GPCRs comprise the single largest class of targets for pharmaceuticals currently on the market. Technical challenges have meant that GPCRs have been largely intractable to therapeutic antibody development,” said Dr. Simon Moroney, CEO of MorphoSys. “We believe that by combining Heptares' unique StaR platform for generating stable GPCRs as antigens with our antibody discovery technology, we will be able to unlock the immense potential of therapeutic antibodies against GPCRs.”

Heptares' StaRs offer a breakthrough solution to the main challenge associated with making antibodies against GPCRs, namely producing purified and properly folded protein for use as an antigen against which antibodies are raised. StaRs enable antibody discovery by stabilizing the GPCR protein outside the cellular membrane in the correct conformation. StaRs preserve biologically relevant epitopes thereby enabling generation of a diverse panel of functional antibodies. This has previously proved very difficult for GPCRs, which lose their conformational and functional integrity when removed from their natural environment in cell membranes.

MorphoSys's Ylanthia antibody library comprises more than 100 billion distinct, fully human antibodies, which makes it the industry's largest known antibody Fab library. Ylanthia's genetic composition translates into unprecedented structural diversity of the antibodies and offers optimized developability features. The library's diversity is expected to result in antibodies against previously inaccessible target molecules and to provide unique epitope coverage.

The GPCR superfamily plays a central role in many biological processes and is linked to a wide range of disease areas. GPCRs are expressed in every type of cell in the body where their function is to transmit signals from outside the cell across the membrane to signaling pathways within the cell, between cells and between organ systems. There are over 375 non-chemosensory GPCRs encoded in the human genome, of which 225 have known ligands and 150 are orphan targets. GPCRs are the site of action of 25-30% of currently approved drugs. Six of the top 10 and 60 of the top 200 best-selling drugs in the U.S. in 2010 target GPCRs. Seven of 37 drugs approved in 2012 by the FDA target GPCRs. By the end of 2012, 37 therapeutic antibodies had been approved and are being marketed in countries around the world. However, to date only one GPCR-targeting antibody has been approved.