Boehringer Ingelheim will partner with Domain Therapeutics to discover new drugs designed to treat Central Nervous System (CNS) disorders by targeting G Protein-Coupled Receptors (GPCRs), Domain said today, through a collaboration whose value was not disclosed.

Also undisclosed was how many targets the companies plan to discover.

Domain said the partnership will combine its expertise in discovering GPCR-targeting drugs for CNS, oncology, and immuno-oncology indications with Boehringer Ingelheim’s discovery and clinical development know-how.

Domain plans to use its proprietary DTect-All™ and BioSens-All™ platforms, both designed to enable screening and characterization of potential lead compounds through comprehensive characterization of small molecule GPCR binders.

In addition to the platforms, Domain said, it will bring into the collaboration’s discovery phase its network of GPCR experts.

Domain cited two of its experts. One is Brigitte Kieffer, Ph.D., scientific director at the Douglas Mental Health University Institute in Montreal, whose lab focuses on GPCRs in mental health and disease: “Emphasis is (i) on opioid receptors, to study reward processing and implication in addiction, depression and autism syndrome disorders, and (ii) selected orphan GPCRs (oGPCRs), whose functions in the brain remain unknown, for discovery programs.”

The other expert cited by Domain was Michel Bouvier, Ph.D., FCAHS, FRSC, CEO of the University of Montreal’s Institute for Research in Immunology and Cancer (IRIC), whose lab research program focuses on the molecular mechanisms controlling the efficacy and the selectivity of GPCR signaling: “A better understanding of these receptors would make it possible to improve many existing drugs, as well as develop new, more effective medications in many clinical fields and in particular for cancer treatment.”

Domain said it will receive from Boehringer Ingelheim an upfront payment, as well as payments tied to achieving discovery, development, and commercial milestones. Boehringer Ingelheim also agreed to pay Domain royalties on sales.

Bolstering CNS Research

“This collaboration helps us to bolster our CNS research efforts,” Bernd Sommer, Ph.D., global head, CNS diseases research at Boehringer Ingelheim, said in a statement. “We have a valuable partner with complementary expertise and key technologies that allow us to accelerate research and development in this area of great unmet medical need.”

CNS is one of Boehringer Ingelheim’s four therapeutic research areas; the other three are immunology and respiratory diseases, cardiometabolic diseases, and oncology. According to its website, Boehringer Ingelheim’s CNS discovery research focus includes psychiatric diseases such as schizophrenia and depression, as well as Alzheimer’s disease.

Boehringer Ingelheim and Domain reason that they can capitalize on an underexploited market for GPCR-targeting drugs since they represent about 40% of all treatments on the market, yet only address 15% of GPCRs.

Domain noted that GPCRs are widely expressed in the central nervous system where they play key roles in regulating brain functions. However, a significant number of GPCRs are orphan receptors with no known ligand—and are too complex to be addressable through conventional drug discovery approaches, making drug discovery efforts especially challenging, and in need of dedicated technologies such as Domain’s platforms.

According to Domain, BioSens-All is designed to characterize the signaling complexity associated with GPCR activation. It consists of a combination of more than 25 bioluminescence resonance energy transfer (BRET)-based biosensors, each designed to follow one specific signaling event upon GPCR activation.

DTect-All is a binding technology designed for the identification of every compound interacting with the 7-transmembrane (7-TM) domain of engineered GPCRs. The corresponding fluorescence resonance energy transfer (FRET)-based assays, developed on stable cell lines, are screened in the presence of fluorescent probes that act as surrogate markers of the GPCR change of conformation.

“We believe that our approach and technologies will allow for the identification of new drug candidates against these challenging targets, and, coupled with Boehringer Ingelheim’s strength and expertise, their rapid advancement into the clinic,” added Domain CEO Pascal Neuville.

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