Boston, MA – January 9, 2023 – Cerevance, a private, clinical-stage drug discovery and development company focused on central nervous system (CNS) diseases, today announced positive results from its Phase 1 study of CVN766 in healthy subjects. The trial was a randomized, double-blind, placebo-controlled study evaluating the safety, tolerability and pharmacokinetics (PK) of escalating single and multiple doses of CVN766 in 64 healthy subjects. This data, along with earlier preclinical studies, supports developing CVN766 as a potential treatment for negative and cognitive symptoms of schizophrenia.
CVN766 was well tolerated with an excellent safety profile across all dose groups: Data across all dose cohorts showed that CVN766 was well tolerated with a favorable safety profile. There were no serious adverse or dose-limiting adverse events (AEs), treatment-related discontinuations, or meaningful changes in clinical laboratory parameters or physical exams. All treatment emergent adverse events (TEAEs) were classified as mild or moderate with no dose-dependent trend in the frequency, severity, or type of TEAEs observed. TEAEs occurring in >5%of subjects included headache (10.9%), dizziness (7.8%) and presyncope (6.2%). None of the presyncope AEs were deemed treatment-related.
Unlike most orexin receptor antagonists, CVN766 showed no evidence of somnolence: The most common adverse effects of other orexin 1 receptor (Ox1R) antagonists, which have lower levels of selectivity over the orexin 2 receptor (Ox2R), include somnolence and fatigue. In this Phase 1 study, there was no increase of somnolence or fatigue in subjects dosed with CVN766 versus placebo, potentially demonstrating a benefit of CVN766 over other Ox1R antagonists.
Robust PK profile and confirmed CNS exposure: In both the SAD and MAD cohorts, exposure (Cmax and AUC) increased with dose in a generally dose proportional manner. Steady state was achieved following 4 or 5 days of dosing with robust safety exposure margins at or above anticipated therapeutic dose levels. CNS exposure was confirmed with CSF Kp,uu values similar to rodent models. Taken together, the data generated and PK profile support CVN766 once a day dosing.
“We are encouraged with the safety and pharmacokinetics profiles observed in the Phase 1 trial for CVN766,” said Craig Thompson, chief executive officer of Cerevance. “These data for CVN766 build on the significant momentum we’ve achieved throughout 2022. We are well-positioned to continue to advance our strategy of bringing forth potentially transformative treatments to patients with brain diseases in 2023.”
Based on the data, Cerevance intends to initiate a Phase 2 study in Q2 2023 to assess CVN766 for the treatment of negative and cognitive symptoms in schizophrenia.
CVN766 is a potent antagonist of the Ox1R with high selectivity over Ox2R (>1000 fold). Ox1R has genetic links to domains of psychiatric disorders and is expressed in areas of the brain important for regulating emotion, fear, anxiety and motivation. To date, Cerevance’s Nuclear Enriched Transcript Sort sequencing (NETSseq) technology platform has confirmed Ox1R expression in cell types relevant to schizophrenia in humans. Orexin A, the endogenous ligand for Ox1R, is dysregulated in patients with various psychiatric conditions including schizophrenia.
CVN766 has demonstrated efficacy in multiple preclinical models of cognition and negative symptoms of schizophrenia and in models of dependency type behaviors and anxiety. These include efficacy in executive function/attentional set shifting paradigms of cognition, reversal of phencyclidine (PCP) induced social interaction deficits, reduction in amphetamine induced dopamine release, efficacy in binge eating, alcohol and nicotine-dependency models and efficacy in the marmoset human threat test of anxiety.
Schizophrenia is a severe neurodevelopmental disorder that interferes with a person’s ability to think clearly, manage emotions, make decisions and relate to others. Approximately 1% of the population are affected by schizophrenia with a similar global prevalence. Patients with schizophrenia experience a variety of symptoms which are broadly clustered into three primary symptom domains, positive symptoms, negative symptoms and cognitive deficits. Whilst positive symptoms can be largely managed with existing medication, negative symptoms and cognitive deficits are not well treated and can be predictors of patient outcome. Negative symptoms include social withdrawal, anhedonia, blunted effect, alogia and avolition, whilst cognitive deficits include problems in speed of processing, attention and vigilance, working memory, verbal and visual learning and social cognition.
Cerevance is a private pharmaceutical company with a focus on CNS disorders. CVN424, Cerevance’s lead therapeutic, is a first-in-class, oral, non-dopaminergic compound acting on a novel target (GPR6), demonstrated significant and clinically meaningful efficacy in a 135-patient Phase 2 study in patients with Parkinson’s disease. The company uses its proprietary NETSseq technology platform to identify highly selectively expressed, novel target proteins that are either specific to certain brain circuits or are over- or under-expressed in diseased brains. Partnering with over 25 brain banks and evaluating more than 12,000 human post-mortem brain tissue samples, Cerevance is advancing a robust pipeline of targeted treatments for patients with neurodegenerative diseases, including Parkinson’s disease, Amyotrophic Lateral Sclerosis and Alzheimer’s disease. For additional information, please visit www.cerevance.com.
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