GPR6

BOSTON, Oct. 21, 2024 (GLOBE NEWSWIRE) -- Cerevance, a clinical-stage biopharmaceutical company advancing multiple cell type-specific therapies for the treatment of neurodegenerative, psychiatric, and central nervous system-controlled metabolic disorders, has published the full results from the Phase 2 clinical trial of solengepras, in eClinicalMedicine , a peer-reviewed journal published by The Lancet Discovery Science Suite . The results demonstrated that solengepras, a potentially first-in-class, oral, once-daily, non-dopaminergic, GPR6 inverse agonist, significantly reduced OFF time in individuals with Parkinson’s disease and was generally well-tolerated. The Phase 2 clinical trial met the key efficacy endpoint and demonstrated a reduction in average daily OFF time from baseline at Day 27, as recorded over two days using a self-reported patient motor diary. On Day 27, the change from baseline in daily OFF time was -1.6 hours (p 5%) were headache and nausea which were generally mild and transient. “We are excited to share the results of this important Phase 2 study with the broader scientific community through this publication in eClinicalMedicine,” said chief executive officer, Craig Thompson. “The data demonstrated solengepras’ potential to be a meaningful therapeutic option for individuals with Parkinson’s disease, addressing not only motor symptoms but also overall quality-of-life.” For more information on the Phase 2 clinical trial and to access the full publication, visit About Solengepras (CVN424) Solengepras is designed to provide a potentially novel approach to the treatment of Parkinson’s disease. Unlike dopaminergic therapies, which primarily act by replenishing, enhancing, or mimicking dopamine, solengepras is designed to selectively address the indirect pathway by modulating the GPR6 receptor. By inhibiting GPR6, solengepras aims to restore both motor and non-motor function without directly affecting dopamine levels or signaling, improving the relative balance between the direct and indirect pathways, and potentially reducing the risk of common side effects associated with dopaminergic therapies, such as dyskinesias and motor fluctuations. Solengepras is currently being evaluated as a once-daily, oral treatment for use as both a monotherapy (Phase 2 ASCEND clinical trial) and as an adjunctive therapy to levodopa and other anti-Parkinsonian medication (Phase 3 ARISE clinical trial). About Parkinson’s Disease Parkinson’s disease is a progressive neurodegenerative disorder that is characterized by both motor symptoms, such as tremor, rigidity, and bradykinesia/akinesia, and non-motor symptoms, such as mood changes, apathy, and cognitive deficits. Globally, Parkinson’s disease is the fastest growing neurological disorders, affecting more than ten million people worldwide and approximately one million people in the United States. The current standard of care has primarily relied on dopaminergic therapies, which lose effectiveness over time and are associated with side effects that result in challenging risk-benefit pro About Cerevance Cerevance is focused on advancing cell type-specific therapies for the treatment of neurodegenerative, psychiatric and central nervous system (“CNS”)-controlled metabolic disorders. Our proprietary platform, N uclear E nriched T ranscript S ort seq uencing (NETSseq), allows us to identify targets that are expressed at very low levels, that are present in rare cell types, or that change over time as a disease progresses. Our most advanced product candidate, solengepras (CVN424), is currently in Phase 3 development and has the potential to be a first-in-class, oral non-dopaminergic therapy for both the motor and non-motor symptoms of Parkinson’s disease. Our second product candidate, CVN766, is designed to be a highly selective oral antagonist of the orexin 1 receptor that we plan to evaluate in a Phase 2 study for the potential treatment of binge eating disorder and schizophrenia. Our third product candidate, CVN293, is a highly selective investigational oral inhibitor targeting potassium two pore domain channel subfamily K member 13 (KCNK13) and represents a potentially novel intervention point for neurodegenerative disorders by reducing neuroinflammation. We plan to evaluate CVN293 in a Phase 2 study for the potential treatment of frontotemporal dementia. Contacts Cerevance: Johnna Simões, ir@cerevance.com Media: Andrew Mielach, amielach@lifescicomms.com, +1-646-876-5868

BOSTON, May 09, 2024 (GLOBE NEWSWIRE) -- Cerevance, a company focused on developing precision novel therapeutics for central nervous system (CNS) diseases, will present an oral presentation at the upcoming International Association of Parkinsonism and Related Disorders (IAPRD) XXIX World Congress on Parkinson’s Disease and Related Disorders, taking place in Lisbon, Portugal from May 19-22, 2024. Presentation details Title: CVN424, a Novel GPR6 Inverse Agonist Demonstrates Efficacy in an Adjunctive Parkinson’s Disease Phase 2 Clinical TrialOverview: In a Phase 2 clinical trial, CVN424, a novel, non-dopaminergic, GPR6 inverse agonist, demonstrated a significant reduction in OFF time and was safe and well tolerated with low rates of mostly mild and moderate adverse events. Patients also reported enhanced motor functionality in daily activities, as assessed by the UPDRS Part II. These findings enhance the confidence in CVN424's potential to address both motor and non-motor symptoms of Parkinson’s disease, consistent with observations in pre-clinical models, potentially heralding a transformative non-dopaminergic therapy.Presenter: Karl Kieburtz, MD, MPHSession Date and Time: Monday, May 20; 9:35 – 10:20am Session Title: PD Therapy I About CerevanceCerevance is focused on the development of precision treatments for central nervous system (CNS) disorders, including chronic neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, frontotemporal dementia, and amyotrophic lateral sclerosis. Utilizing a large and growing repository of over 15,000 human brain tissue samples, Cerevance is generating an unprecedented level of expression and epigenetic data thereby enabling the company to identify the most promising targets for the next generation of treatments for CNS disorders. The company uses its proprietary Nuclear Enriched Transcript Sort sequencing (NETSseq) platform and advanced machine learning techniques to uncover the gene expression profiles of select cell types to identify novel targets that are uniquely expressed in relevant circuits affected by diseases or are altered in disease states. With the information obtained from its research, combined with the expertise of its team of scientists and drug developers, Cerevance is advancing multiple therapeutics through clinical development, with CVN424, CVN766, and CVN293 being the furthest along in the pipeline. CVN424 is a first-in-class non-dopamine therapy that shows promise in improving both motor and non-motor symptoms of Parkinson's disease and may also have disease-delaying effects. CVN766 is a potent and highly selective antagonist of the orexin 1 receptor which may benefit various psychiatric conditions including schizophrenia, anxiety/panic, binge eating/obesity, substance use disorder, and Prader-Willi Syndrome. CVN293 is a novel blocker of potassium efflux in glia, regulating the inflammasome in individuals living with neurodegenerative diseases. Cerevance’s robust pipeline aims to transform the lives of patients affected by CNS diseases. Contacts Cerevance: Johnna Simoes, ir@cerevance.com Media: Andrew Mielach, amielach@lifescicomms.com, +1-646-876-5868

Cerevance’s CVN424 is a non-dopamine G protein-coupled receptor 6 (GPR6) inhibitor. Image Credit: Pla2na / Shutterstrock. US-based Cerevance has secured $47m in Series B-1 extension funding to finance the upcoming Phase III trial for its lead therapy, CVN424. The financiers included multiple US-based venture capital firms such as Google Ventures, Agent Capital, Bioluminescence Ventures, and Double Point Ventures. CVN424 is a non-dopamine therapy that inhibits G protein-coupled receptor 6 (GPR6), which is an orphan receptor as it has no naturally produced agonist that activates the receptor. The GPR6 inhibition can potentially improve motor and non-motor manifestations of Parkinson’s. The drug was discovered using Cerevance’s NETSseq (Nuclear Enriched Transcript Sort sequencing) platform. CVN424 is being evaluated in a placebo-controlled Phase II ASCEND trial (NCT06006247) in patients with early untreated Parkinson’s. The study is expected to enrol approximately 62 participants and conclude in February 2025, as per ClinicalTrial.gov . In February, Cerevance raised $51m in Series B to fund the Phase II trial. The primary endpoint of the study is CVN424’s ability to improve Parkinson’s disease motor symptoms and the impact of those symptoms on activities of daily living. This is measured by Parts II and III of the Movement Disorder Society’s Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) after 12 weeks of administration. The trial is expected to inform the design for the Phase III study. See Also: Regeneron and Mammoth team up to develop gene editing therapies The therapies for Parkinson’s disease are expected to generate $6.3bn in sales across the seven major markets, including the US, Japan, France, Germany, Italy, Spain, and the UK, as per the GlobalData analysis . GlobalData is the parent company of Pharmaceutical Technology . Cerevance’s pipeline consists of other central nervous system therapies including CVN293, a KCNK13 potassium channel inhibitor. It is being developed as a potential treatment for neurodegenerative conditions such as amyotrophic lateral sclerosis, Alzheimer’s disease, and frontotemporal dementia. CVN293 is being evaluated in healthy volunteers in a Phase I trial, with topline data expected in the second quarter of this year. CVN766 is a selective antagonist of the orexin 1 receptor. Cerevance is developing the drug for various psychiatric conditions including schizophrenia, anxiety/panic, binge eating/obesity, substance use disorder, and Prader-Willi Syndrome. Another therapy in Cerevance’s pipeline is CVN293, which inhibits potassium efflux in the glia (non-neuronal cells in the brain), thereby, regulating the inflammasome in individuals living with neurodegenerative diseases.