GPR52

Antipsychotic medications used to treat schizophrenia don’t work for all patients, and even when they do, side effects lead many people to stop taking them. Sosei Heptares is developing a novel drug that could bring patients better efficacy along with fewer side effects, and that potential has caught the interest of Boehringer Ingelheim. The German pharmaceutical company has inked a deal for an exclusive option on Sosei Heptares’s schizophrenia drug candidate, which is in early clinical development. Under deal terms announced Monday, Boehringer is paying its new partner €25 million up front. Sosei Heptares’s schizophrenia research address a G protein-coupled receptor (GPCR) called GPR52. This particular receptor is highly expressed in the brain, making it a valuable drug target for treating neurological and neuropsychiatric disorders. But it’s also an orphan receptor, meaning it does not have any known substances in the body that can bind to it to spark an effect. Lacking endogenous ligands makes it hard to understand orphan receptors and how to drug them. Sosei’s StaR technology platform stabilizes a GPCR, enabling scientists to better understand its structure in order to discover molecules that can target it. The company has developed small molecules that can selectively bind to and activate GPR52, potentially addressing various symptoms of schizophrenia. The most advanced of these programs, HTL0048149, is a once-daily oral drug is designed to selectively target GPR52. In addition to treating schizophrenia symptoms, the molecule is also intended to minimize adverse effects associated with currently available antipsychotic drugs. A Phase 1 clinical trial began in the United Kingdom last year assessing single- and multiple-ascending doses in healthy volunteers. Preliminary data are expected next year. Under the deal terms, Sosei Heptares will continue development of HTL0048149 through Phase 1b clinical testing. After that, Boehringer may exercise its option to license the molecule to continue its clinical development. In addition to HTL0048149, the license covers back-up compounds designed by the Sosei Heptares technology. If the German pharma company exercises its option on schizophrenia drug candidate, the deal calls for an additional payment of €60 million. Depending on the progress of the research, Boehringer could pay out up to €670 million, plus royalties from sales of an approved schizophrenia drug. “We’re very excited to enter this partnership with Sosei Heptares with this novel approach, which aims to address a huge unmet need of those living with schizophrenia,” Hugh Marston, global head CNS discovery research at Boehringer Ingelheim, said in a prepared statement. “This partnership is highly complementary to our other development programs aiming to bring a new precision medicine approach to the treatment of mental health disorders with therapies, which we hope will transform the lives of those living with schizophrenia.” Boehringer’s schizophrenia work includes a collaboration with Click Therapeutics, a digital therapeutics developer. The partnered program, CT-155, is a smartphone app intended to augment standard of care therapy to treat the behavioral aspects of schizophrenia. This program has reached Phase 3 testing. At the time the deal was announced in 2020, the companies did not break out specific financial details but said the combined upfront and milestone payments could reach $500 million. Public domain image by Flickr user SciTechTrend

Boehringer Ingelheim partnered with Sosei Heptares to develop a schizophrenia treatment targeting the G protein-coupled receptor GPR52 in the hopes of addressing all three symptom clusters associated with the condition.Under the agreement, Boehringer Ingelheim has an option to exclusively license Sosei’s portfolio of GPR52 agonists following the completion of an ongoing Phase Ia trial and a subsequent Phase Ib study of the lead candidate, dubbed HTL0048149. Initial data from the early-stage study of HTL0048149 – a once-daily, oral drug - are expected in 2025.The portfolio also contains a number of differentiated back-up compounds designed by Sosei using its StaR technology and structure-based drug design (SBDD) platform.Boehringer Ingelheim will make an upfront payment of €25 million ($27 million), with Sosei set to receive a further €60-million ($66 million) option exercise payment, as well as further milestones totalling up to €670 million ($733 million) and tiered sales royalties.Matt Barnes, head of UK R&D at Sosei, remarked “this collaboration highlights the significant potential GPR52 has shown in preclinical research.” The companies noted that the receptor is located in the two areas of the brain that drive the positive and the negative and cognitive symptoms of schizophrenia.

Boehringer Ingelheim and UK-based Sosei Heptares have entered a global collaboration and option-to-license agreement to develop and commercialize Sosei’s portfolio of GPR52 agonists for schizophrenia. Under the terms of the deal, Boehringer has the exclusive option to license Sosei's GPR52 agonists, a novel G protein-coupled receptor target, following the completion of Sosei’s ongoing phase 1 and subsequent phase 1b trial and phase 2 enabling activities with HTL0048149, a first-in-class GPR52 agonist. Sosei Heptares will sponsor the trials until the option exercise, estimated in 2025. According to Boehringer, the development of a new schizophrenia treatment targeting GPR52 has the potential to address all three aspects of schizophrenia — ‘positive’ symptoms (psychosis, delusions and hallucinations), ‘negative’ symptoms (social withdrawal and apathy) and cognitive symptoms (attention, planning and memory deficits). In the deal, Sosei will receive an upfront payment of $27.3 million (€25 million) from Boehringer, and is eligible for an option exercise payment of $65.6 million (€60 million) and further development, regulatory and commercialization milestone payments totaling up to $732.7 million (€670 million). Boehringer Ingelheim has inked several deals since the start of 2024. In January , the German drugmaker signed at $2 billion+ deal with Suzhou Ribo Life Science subsidiary Ribocure Pharmaceuticals to develop treatments for nonalcoholic or metabolic dysfunction-associated steatohepatitis (NASH/MASH). This was quickly followed by a second research partnership with 3T Biosciences — this time for $538.5 million — to develop first-in-class immuno-oncology treatments.