Cerevance announced positive results from its Phase 1 trial of CVN293, a novel KCNK13 inhibitor targeting neuroinflammation, at the American Academy of Neurology (AAN) 2025 Annual Meeting in San Diego. The data demonstrated that CVN293 was generally well-tolerated in healthy adults and showed evidence of robust brain penetration, supporting its potential utility in treating neurodegenerative diseases characterized by neuroinflammation.
The randomized, double-blind, placebo-controlled Phase 1 single/multiple ascending dose (SAD/MAD) study evaluated the safety, tolerability, and pharmacokinetics of oral CVN293 in 72 healthy adult volunteers. In the single ascending dose portion, participants received a single dose of CVN293 up to 1,000 mg or placebo, while those in the multiple ascending dose part received repeated doses of CVN293 up to 750 mg (375 mg twice daily) or placebo over 14 days.
"The favorable tolerability and pharmacokinetic profile observed with CVN293 in this first-in-human study are promising indicators for its potential as a disease-modifying intervention for neurodegenerative diseases driven by neuroinflammation," said Sagar Vaidya, M.D., Ph.D., chief medical officer of Cerevance. "We look forward to advancing our family of KCNK13 inhibitors for the treatment of neurodegenerative disorders characterized by neuroinflammation, where new therapeutic options are urgently needed."
Key Study Findings
Results showed that CVN293 was generally well-tolerated following both single and 14-day multiple dosing regimens, with 100% of participants completing the trial. The safety profile was favorable, with:
- No severe or dose-limiting adverse events
- No treatment-related discontinuations
- No clinically meaningful changes in vital signs or laboratory parameters
- All treatment-related adverse events classified as mild
Pharmacokinetic data demonstrated that CVN293 plasma exposure increased in a generally dose-proportional manner in both the SAD and MAD portions of the study. Importantly, cerebrospinal fluid (CSF) sampling confirmed high levels of central nervous system (CNS) exposure with CVN293, a critical factor for a drug targeting neurological disorders.
Novel Mechanism of Action
CVN293 is an investigational, highly selective oral inhibitor of the potassium two pore domain channel subfamily K member 13 (KCNK13). By selectively inhibiting KCNK13, which is a potentially novel regulator of NLRP3 inflammasome activation, CVN293 aims to reduce neuroinflammation and slow disease progression in various neurodegenerative disorders. This mechanism may provide a disease-modifying approach for challenging CNS disorders and potentially obesity.
The target was identified using Cerevance's proprietary Nuclear Enriched Transcript Sort sequencing (NETSseq) platform, which allows the company to identify targets that are expressed at very low levels, present in rare cell types, or change over time as a disease progresses.
Additional Cerevance Presentations at AAN 2025
At the same meeting, Cerevance presented a poster demonstrating the potential of its proprietary NETSseq platform to identify and validate cell-specific gene targets and provide biological insight into human brain disorders. The poster detailed two clinical-stage novel therapeutic targets with specific expression in the brain that resulted from NETSseq: solengepras and CVN293.
Another poster presentation detailed the novel mechanism of action of solengepras, an oral, non-dopaminergic therapy in clinical development for Parkinson's disease. As a brain-penetrant, specific inhibitor of GPR6, solengepras is designed to selectively target and modulate brain circuits controlling motor and non-motor functions without directly affecting dopaminergic pathways.
This novel approach is designed to reduce motor complications such as dyskinesia, decrease periods of symptomatic worsening (known as "OFF" time), and improve functional non-motor symptoms. The poster described primary results from the randomized, double-blind, placebo-controlled Phase 2 ASCEND study of solengepras as monotherapy in patients with early, untreated Parkinson's disease.
Advancing the Pipeline
Solengepras, Cerevance's most advanced investigational treatment, is currently in Phase 3 development and has the potential to be a first-in-class, oral non-dopaminergic therapy for both motor and non-motor symptoms of Parkinson's disease. It is being evaluated as a once-daily, oral treatment for use as an adjunctive therapy to levodopa and other anti-Parkinsonian medications in the Phase 3 ARISE trial.
The company's second investigational therapy, CVN766, is designed to be a highly selective oral antagonist of the orexin 1 receptor for the potential treatment of binge eating disorder and schizophrenia.
With CVN293 now showing promising early results, Cerevance continues to build a diverse pipeline of novel therapeutics targeting neurodegenerative, psychiatric, and central nervous system-controlled metabolic disorders, addressing significant unmet medical needs in these areas.
About Cerevance
Cerevance is a clinical-stage biopharmaceutical company focused on advancing cell type-specific therapies for the treatment of neurodegenerative, psychiatric, and central nervous system-controlled metabolic disorders. The company's approach leverages its proprietary NETSseq platform to identify targets with high specificity and potential for therapeutic intervention.
The positive Phase 1 results for CVN293 represent another step forward in the company's mission to develop innovative treatments for complex neurological conditions where new therapeutic options are urgently needed.
