OX1R

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, Oct. 08, 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, announced the achievement of the second milestone in its research collaboration with Merck, known as MSD outside of the United States and Canada. The research collaboration, which was announced in August of 2022, focuses on the identification and validation of novel therapeutic targets for Alzheimer’s disease. The achievement of this milestone triggers a payment from Merck to Cerevance. “We are very pleased with the progress we continue to make in our research collaboration with Merck,” said Craig Thompson, chief executive officer of Cerevance. “This milestone highlights the potential of our proprietary Nuclear Enriched Transcript Sort sequencing platform to identify novel targets for Alzheimer’s disease and other neurological disorders.” Under the collaboration, Cerevance identifies targets using NETSseq from which Merck may select an undisclosed number of targets to advance to target validation. About CerevanceCerevance 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, Nuclear Enriched Transcript Sort sequencing (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 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

Late-breaking poster presentation of non-human primate (NHP) data support ORX142 as novel drug candidate for the treatment of excessive daytime sleepiness (EDS) in select neurological, neurodegenerative, and psychiatric disorders BOSTON and LONDON, Sept. 26, 2024 (GLOBE NEWSWIRE) -- Centessa Pharmaceuticals plc (Nasdaq: CNTA), a clinical-stage pharmaceutical company that aims to discover and develop medicines that are transformational for patients, today shared new preclinical data from non-human primate (NHP) studies of ORX142, an investigational, novel, orexin receptor 2 (OX2R) agonist being advanced for the treatment of excessive daytime sleepiness (EDS) in select neurological, neurodegenerative and psychiatric disorders. ORX142 is the second drug candidate from the Company’s growing pipeline of OX2R agonists and is in IND-enabling studies. The preclinical data were featured today in a late-breaking poster presentation entitled, “ORX142, an Oral, Highly Potent and Selective Orexin Receptor 2 Agonist, Promotes Wakefulness in Non-Human Primates,” by Sarah Wurts Black PhD, Head of Biology for Centessa’s Orexin Agonist Program, at the 27th Congress of the European Sleep Research Society (Sleep Europe 2024) in Seville, Spain. “ORX142 has shown significant activity in promoting wakefulness at very low doses in highly predictive and translational preclinical models,” said Saurabh Saha MD PhD, Chief Executive Officer of Centessa. “More specifically, the preclinical data showed ORX142 achieved significant increases in wake times at 0.03 mg/kg, the lowest oral dose tested in the NHP model. We’re excited to share these data at ESRS highlighting the breadth of ORX142’s potential as a novel treatment for individuals living with EDS in select neurodegenerative, neurological and psychiatric disorders. Based on the totality of data from our OX2R agonist program and the significant potential market opportunity for ORX142, we are focused on rapidly moving ORX142 through IND-enabling studies.” Overview of ORX142 Preclinical Poster Presentation at Sleep Europe 2024: ORX142 is a full OX2R agonist designed by Centessa with the aid of high-resolution crystallography and cryo-EM structural chemistry capabilities.ORX142 potently activated the human OX2R with an EC50 of 0.069 nM and > 13,000-fold selective over the human orexin receptor (hOX1R).1In highly predictive, translational NHP models, oral administration of ORX142 showed significant activity at the lowest dose tested, which was 0.03 mg/kg.ORX142 induced sustained increases in wakefulness that suppressed NREM and REM sleep at the lowest dose tested, 0.03 mg/kg.Wakefulness induced by ORX142 was associated with normal physiological arousal and EEG power spectra signatures of enhanced alertness and attention.No significant pharmacological activity was observed in GPCR selectivity and in vitro safety panels. References: 1. Fluorescent imaging plate reader (FLIPR) assay with Chinese hamster ovary (CHO) cells stably expressing recombinant human OX1R or OX2R; OXA EC50 at hOX2R = 0.035 nM; ORX142 EC50 at hOX1R = 930 nM. Additional meeting information can be found on the Sleep Europe 2024 website at https://esrs.eu/sleep-congress/. The poster will also be available on the Centessa website at https://investors.centessa.com/events-presentations after the conference concludes. About Centessa’s Orexin Agonist ProgramOrexin is a neuropeptide that regulates the sleep-wake cycle, leading to arousal and promoting wakefulness. Low levels of orexin result in excessive daytime sleepiness (EDS) and poor regulation of rapid eye movement (REM) sleep and, in narcolepsy type 1 (NT1), cataplexy and other symptoms. Centessa is developing a pipeline of potential best-in-class orexin receptor 2 (OX2R) agonists, including ORX750 for the treatment of sleep-wake disorders, including NT1, narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH), and ORX142 for the treatment of EDS in select neurological, neurodegenerative, and psychiatric disorders. ORX750 is in a Phase 1 clinical study. ORX750 and ORX142 have not been approved by the FDA or any other regulatory authority. About Centessa Pharmaceuticals Centessa Pharmaceuticals plc is a clinical-stage pharmaceutical company that aims to discover and develop medicines that are transformational for patients. Our most advanced programs include a hemophilia program, an orexin agonist program for the treatment of narcolepsy and other sleep-wake disorders, and an immuno-oncology program focused on our LockBody® technology platform. We operate with the conviction that each of our programs has the potential to change the current treatment paradigm and establish a new standard of care. For more information, visit www.centessa.com, which does not form part of this release. Forward Looking Statements This press release contains forward-looking statements. These statements may be identified by words such as “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “objective,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “continue,” “ongoing,” “aim,” “seek,” and variations of these words or similar expressions that are intended to identify forward-looking statements. Any such statements in this press release that are not statements of historical fact may be deemed to be forward-looking statements, including statements related to the Company’s ability to discover and develop transformational medicines for patients; its expectations for executing on the Company's pipeline; the timing of commencement of new studies or clinical trials or clinical and preclinical data related to ORX750 and ORX142; its ability to identify, screen, recruit and maintain a sufficient number of or any subjects in its existing and anticipated studies or clinical trials including in respect of ORX750 and ORX142; its expectations on executing its research and clinical development plans and the timing thereof, including its ability to rapidly move ORX142 through IND-enabling studies; its expectations as to the potential results and impact of each of its clinical programs and trials; the Company’s ability to differentiate ORX750 and ORX142 from other treatment options; the development, design and therapeutic potential of ORX750 and ORX142; and regulatory matters, including the timing and likelihood of success of obtaining regulatory clearance, obtaining authorizations to initiate or continue clinical trials. Any forward-looking statements in this press release are based on our current expectations, estimates, assumptions and projections only as of the date of this release and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, risks related to the safety and tolerability profile of our product candidates, including ORX750 and ORX142; whether ORX750 and ORX142 could be shown to be ineffective; our ability to identify, screen and recruit a sufficient number of or any subjects in our existing and anticipated new studies or clinical trials including ORX750 and ORX142 or within anticipated timelines; our expectations relating to the further clinical development of ORX750 and ORX142 including initiation of phase 1 and/or phase 2 studies, including the predicted timing of enrollment, the predicted efficacious doses of ORX750 and ORX142 and our ability to successfully conduct our clinical development of ORX750 and ORX142; whether preclinical and initial clinical results for ORX750 and ORX142 will be predictive of results of further clinical trials; our ability to protect and maintain our intellectual property position; business (including commercial viability), regulatory, economic and competitive risks, uncertainties, contingencies and assumptions about the Company; risks inherent in developing product candidates and technologies; future results from our ongoing and planned clinical trials; our ability to obtain adequate financing, including through our financing facility with Oberland, to fund our planned clinical trials and other expenses; trends in the industry; the legal and regulatory framework for the industry, including the receipt and maintenance of clearances to conduct or continue clinical testing; our operating costs and use of cash, including cash runway, cost of development activities and conducting clinical trials, future expenditures risks; the risk that any one or more of our product candidates will not be successfully developed and/or commercialized; the risk that the historical results of preclinical studies or clinical studies will not be predictive of future results in ongoing or future studies; economic risks to the United States and United Kingdom banking systems; and geo-political risks such as the Russia-Ukraine war or the Middle East conflicts. These and other risks concerning our programs and operations are described in additional detail in our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and our other reports, which are on file with the U.S. Securities and Exchange Commission (SEC). We explicitly disclaim any obligation to update any forward-looking statements except to the extent required by law. Contact: Kristen K. Sheppard, Esq.SVP of Investor Relations investors@centessa.com