GPRC5D x CD3 bispecifics for targeting multiple myeloma

The Target: GPRC5D

GPRC5D is a receptor protein expressed at high levels in multiple myeloma, a bone marrow cancer. With the exception of hair follicles, where it is expressed at a lower level, it is absent from most healthy tissue.

Its restricted expression profile makes GPRC5D an optimal target for potent therapeutic modalities, including bispecifics.

A simple model of a GPRC5D protein molecule. Seven transmembrane domains span a lipid bilayer, with the N-terminus outside the cell and the C-terminus on the inside.
GPRC5D is a complex membrane protein expressed in multiple myeloma cells.

Therapeutic Potential: Optimized format for targeting multiple myeloma

Using our proprietary MPS Antibody Discovery platform, we generated and selected highly specific, humanized GPRC5D MAbs. We combined these with a selection of formats and CD3-binding partner arms to build a diverse panel of GPRC5D x CD3 bispecific molecules.

We screened the panel for target binding, T cell-directed cytotoxicity, and cytokine release and selected candidate molecules with the best properties for targeting multiple myeloma. Lead candidates show picomolar potency and low cytokine release.

To ensure specificity, we screened the lead candidates using our Membrane Proteome Array™. They are highly specific to the intended target, with no off-target binding, minimizing the risk of off-tissue toxicity.

A large antibody represents a common format for a panel of bispecifics. The left binding arm, labeled anti-GPRC5D, is from one of several highly specific MAbs by Integral Molecular. The right binding arm, labeled anti-CD3, is one of several well-characterized anti-CD3 gamma delta partner arms.

The Opportunity: Highly specific humanized GPRC5D x CD3 bispecifics

We have a lead molecule and back-ups ready for preclinical development. These are potent, highly specific molecules optimized for killing multiple myeloma cells.

For more information about the promise of GPRC5D as a therapeutic target, see Smith et al., 2019.

For more assets available to license, visit our Therapeutic Pipeline page

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