KCNK13

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.

Financing round led by Agent Capital, Bioluminescence, and Double Point Ventures, with participation from new investors MQB Partners and others Proceeds will advance Cerevance’s first-in-class pre-clinical and clinical programs, including initiation of the Phase 3 clinical trial for CVN424 BOSTON, April 25, 2024 (GLOBE NEWSWIRE) -- Cerevance, a company focused on developing precision novel therapeutics for central nervous system (CNS) diseases, today announced an initial closing of its Series B-1 Extension financing round that will add $47 million to the $51 million previously raised bringing the total Series B-1 raise to $98 million. The financing is led by Agent Capital, Bioluminescence Ventures, and Double Point Ventures, with participation from new investors MQB Partners and LifeRock Ventures and existing investors Gates Frontier, GV (Google Ventures), and Lightstone Ventures. In conjunction with the financing, Campbell Murray, MD, MPP, MBA, Partner at Agent Capital and Kouki Harasaki, Ph.D., MBA, Founder and Managing Partner at Bioluminescence Ventures, have joined the Cerevance Board of Directors. “The support from new and existing investors underscores the ongoing advancements made by Cerevance,” said Craig Thompson, chief executive officer of Cerevance. “This upcoming year marks a crucial phase as we embark on the Phase 3 clinical trial for our flagship therapy, CVN424, and continue in discovering innovative, precision CNS treatments that will enrich our extensive pipeline.” Proceeds from this financing will support the upcoming Phase 3 clinical trial for CVN424, a first-in-class non-dopamine therapy for patients with Parkinson’s disease, as well as the advancement of a pipeline of novel treatments for other CNS disorders, including Alzheimer’s disease, Amyotrophic lateral sclerosis, and frontotemporal dementia. “There is a clear need for groundbreaking, innovative therapies for Parkinson's disease,” shared Campbell Murray, MD, MPP, MBA, Partner at Agent Capital. “We are confident that Cerevance's lead program, CVN424, holds promise in delivering significant benefits to individuals. We look forward to working with this talented management team and distinguished board of directors to further advance the development of new therapies for patients with CNS disorders." The NETSseq (Nuclear Enriched Transcript Sort sequencing) platform is a powerful tool that pinpoints uniquely expressed, novel target proteins, which may be exclusive to particular brain circuits or exhibit altered expression levels in diseased brains. Cerevance has tackled one of the most significant hurdles in CNS drug discovery — the identification of novel, highly specific targets — and has devised a clinically proven approach for target discovery and subsequent drug development. “We strongly believe that Cerevance is at the forefront of revolutionizing the research and treatment of CNS disorders,” said Kouki Harasaki, Ph.D., MBA, Founder and Managing Partner at Bioluminescence. “The remarkable NETSseq platform is accelerating innovation and tangible clinical benefits are emerging from Cerevance's precision approach to CNS therapies. We are incredibly pleased to partner with Cerevance in this next phase of development." Cerevance is advancing a robust and expanding pipeline of clinical and preclinical programs, including the lead program, CVN424, a first-in-class, oral, non-dopaminergic compound acting on a novel target (GPR6). Currently undergoing Phase 2 evaluation as a monotherapy for patients with early Parkinson’s disease yet to receive any Parkinson’s medications, CVN424 holds promise not only in alleviating motor fluctuations more effectively than existing oral therapies but also in potentially improving non-motor symptoms without the adverse effects associated with current treatments. In parallel, Cerevance is advancing CVN293 which targets KCNK13 for the potential treatment of neurodegenerative conditions such as Amyotrophic lateral sclerosis, Alzheimer’s disease, and frontotemporal dementia. Topline data from the ongoing Phase 1 clinical trial is expected in Q2 2024. The company’s earlier-stage pipeline includes multiple first-in-class opportunities in preclinical development, including programs focused on disease modification in Parkinson’s disease and Alzheimer’s disease. About Cerevance Cerevance 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

Selective CVN293 may have treatment potential in multiple neurodegenerative conditionsBOSTON, April 22, 2024 (GLOBE NEWSWIRE) -- Cerevance, a company focused on developing precision novel therapeutics for central nervous system diseases, today announced that the peer-reviewed journal, ACS Medicinal Chemistry Letters, has published the manuscript titled “Discovery of CVN293, a Brain Permeable KCNK13 (THIK-1) Inhibitor Suitable for Clinical Assessment”. CVN293, currently in a Phase 1 study in healthy volunteers, targets the NETSseq-identified, potassium (K+) ion channel, KCNK13, which is specifically expressed in human microglia. Elevated KCNK13 levels have been observed in post-mortem human brain tissue from individuals with Alzheimer’s disease and other neurodegenerative conditions. Developed as a potent, selective, and brain-permeable therapeutic agent, CVN293 aims to modulate KCNK13 for potential application in a range of neurodegenerative conditions, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and frontotemporal dementia. “We are delighted to publish the discovery of CVN293 as we anticipate its ability to selectively suppress neuroinflammation while mitigating impacts on the peripheral immune system,” said Mark Carlton, Ph.D., chief scientific officer for Cerevance. “Preserving the integrity of the peripheral immune system is of paramount importance, particularly for patients experiencing immunosenescence, the age-related decline in immune function commonly observed in elderly individuals managing neurodegenerative conditions.” The publication can be found at the following link: https://pubs.acs.org/doi/10.1021/acsmedchemlett.4c00035 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 that selectively modulate the discovered targets. These treatments are progressing 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