Boehringer inks pact with Domain for GPCR neurology drugs

French-Canadian biotech Domain Therapeutics has another big pharma partner, signing a deal with Germany’s Boehringer Ingelheim to develop new drugs for central nervous system (CNS) disorders.

Domain says (PDF) it will work with Boehringer to apply its G protein-coupled receptor (GPCR) capabilities to multiple targets in the collaboration, but for now those are being kept under wraps, along with the financial terms of the deal.

Boehringer isn’t a major player in CNS at the moment, although it already sells products for Parkinson’s disease and has made the category one of its R&D priorities, pitching at Alzheimer’s disease (AD), schizophrenia and depression. It says adding Domain will beef up its early-stage discovery capabilities, including input from Canadian GPCR specialists Brigitte Kieffer and Michel Bouvier, who act as advisers to Domain.

At the moment, the German drugmaker’s most advanced asset in the CNS area is mid-stage candidate BI 409306, an inhibitor of phosphodiesterase 9A that remains in trials for schizophrenia—despite disappointing data on cognition scores earlier this year—but has been discontinued in AD after failed studies. Following after is GlyT1 inhibitor BI 425809 for AD and schizophrenia, which is in a phase 2 trial in AD due to report in 2020.

Boehringer has committed itself to the sector despite "setbacks outweighing clinical trial successes" of late, according to Jan Poth Ph.D., who heads up the company’s R&D programs in CNS and immunology. The company has adopted a "symptom-led" approach to CNS drug development which takes aim at brain pathologies that are relevant across multiple diseases.

Last year, Domain signed a $250 million-plus deal with Merck KGaA that will apply its GPCR expertise to the development and testing of drugs targeting adenosine receptors, thought to have a role in cancer.

The two companies had previously collaborated on a glutamate receptor program for diseases including Parkinson’s disease, that eventually became Merck Serono spinout Prexton Therapeutics.

GPCRs are a broad class of membrane receptor whose members bind a variety of signaling molecules and are involved in a wide range of functions in the human body.

Researchers estimate that between one-third and one-half of all marketed drugs act by binding to GPCRs, according to Nature, and that has made them a big target for drug developers although many GPCRs are "orphan," meaning their precise roles and ligands in the body are unknown. Boehringer and Domain will focus on orphan GPCRs in their alliance.

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