Getting ahead with GPCRs

MorphoSys-Heptares deal advances as Heptares exercises option

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MARTINSREID, Germany—In keeping with a 2013 antibody alliance between MorphoSys AG and U.K.-based Heptares Therapeutics, a wholly owned subsidiary of Sosei Group Corp., Heptares has exercised an option to begin a therapeutic antibody program, which will leverage MorphoSys’ Ylanthia antibody library to generate novel antibody leads and address a G-protein-coupled receptor (GPCR) target selected by Heptares.
GPCRs are a leading target of interest in a variety of indications and the single largest class of targets for pharmaceuticals currently on the market. These membrane proteins play a role in a broad range of biological processes and diseases, such as inflammatory disease, neurological disease, metabolic diseases and cancer. Targeting them has proven difficult, however, and Heptares’ StaR technology offers a new approach by enabling the purification of properly folded and functional proteins removed from the cell membrane. StaR proteins are also capable of preserving epitopes from the desired pharmacological state of the GPCR (active or inactive).
“The expertise at Heptares in GPCRs and MorphoSys’ antibody discovery capabilities form a powerful combination to unlock GPCR-targeted antibody discovery. We are delighted with the progress that has been made in the alliance and to be adding this first antibody development program to our pipeline. This achievement highlights the power and versatility of our StaR technology in both small-molecule and biologics discovery for expanding our own pipeline and in partnerships,” Malcolm Weir, CEO of Heptares, remarked in a statement.
The ongoing agreement stipulates that Heptares will generate stabilized receptors (StaRs) for a set of GPCR disease targets proposed by MorphoSys, which will apply its Ylanthia library to discover and develop antibody therapeutics against the StaRs. MorphoSys will have the right to sublicense access to the targets in conjunction with therapeutic antibody candidates to third parties, and Heptares stands to receive a share of future sublicensing revenues as well as upfront and research funding payments. In the case of Heptares exercising its option, MorphoSys stands to receive license fees, milestones and royalties on any Ylanthia antibody Heptares develops as a result of this program. Specific financial details were not released.
“Antibodies developed with our Ylanthia platform are increasingly gaining a foothold in the GPCR target space. MorphoSys has already successfully applied its comprehensive capabilities to generate functional antibodies against GPCRs in several projects,” noted Dr. Marlies Sproll, chief scientific officer of MorphoSys. “We are now looking forward to seeing the progress of this first therapeutic antibody program driven by Heptares as part of our very productive discovery collaboration with them.”
The Ylanthia antibody library is the industry’s largest known Fab library, consisting of more than 100 billion distinct, fully human antibodies. The genetic composition of the library offers significant structural diversity in terms of antibodies as well as optimized developability features.
MorphoSys announced another GPCR collaboration in early August, sharing the news that it had signed an agreement with G7 Therapeutics AG to collaborate on novel antibody therapeutics targeting GPCRs and potentially other disease-related transmembrane proteins like ion channels. The agreement stipulates that G7 Therapeutics will generate a set of disease-relevant receptors proposed by MorphoSys, who will then apply the Ylanthia library to discover and develop antibody therapeutics against the receptors. As with its agreement with Heptares, MorphoSys will have the right to sublicense access to the targets to third parties.
“G7 Therapeutics’ approach using directed evolution technologies broadens our existing development capabilities in this innovative area of research. High-quality therapeutic antibodies targeting GPCRs and other transmembrane molecules represent a promising addition to our proprietary development pipeline,” said Sproll.

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