Cerevance, a UK-based pharmaceutical company, has announced positive results from its Phase I clinical trial of CVN293, a drug candidate aimed at treating neurodegenerative conditions. The first-in-human study, which included single-ascending dose (SAD) and multiple-ascending dose (MAD) segments, involved 72 healthy volunteers and demonstrated that CVN293 was generally well-tolerated and exhibited favorable brain penetration.
The Phase I trial included a SAD portion where 48 participants were administered a single dose of CVN293, ranging from 3mg to 1,000mg, or a placebo. The MAD segment involved 24 participants who received doses from 50mg to 750mg or a placebo over 14 days. The study's primary goal was to assess the safety and tolerability of CVN293.
Key findings from the trial indicated that CVN293 was generally well-tolerated at all doses, with no serious adverse events reported. The trial also observed dose-dependent increases in CVN293 exposure, with plasma concentrations reaching levels deemed clinically relevant based on preclinical studies. Cerebrospinal fluid sampling further confirmed high brain penetrance of CVN293, suggesting the drug effectively crosses the blood-brain barrier.
Targeting Neuroinflammation
CVN293 targets KCNK13, a potassium two pore domain channel subfamily K member 13 linked to the activation of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome, a component believed to contribute to neuroinflammation. KCNK13 is selectively expressed in microglia, the primary immune cells of the brain, with minimal expression in peripheral tissues. This selectivity may allow CVN293 to modulate neuroinflammation with reduced systemic side effects.
Mark Carlton, co-founder and chief scientific officer of Cerevance, stated, "We are very encouraged by the clinical data for CVN293, observing that it was generally well-tolerated and achieved favorable brain penetration. CVN293 selectively inhibits KCNK13, a gene selectively expressed in microglia with minimal expression in peripheral tissues. CVN293 may offer a disease-modifying approach for challenging CNS disorders."
Potential for Phase II Trials
The positive outcomes from this Phase I trial support the progression of CVN293 into Phase II trials for neurodegenerative conditions characterized by neuroinflammation, such as frontotemporal dementia, amyotrophic lateral sclerosis (ALS), and Alzheimer’s disease. These conditions represent significant unmet medical needs, with limited effective treatments currently available.
Cerevance recently secured $47 million in a Series B-1 extension round to fund a Phase III trial of CVN424, its drug candidate for treating Parkinson’s disease, highlighting the company's commitment to developing novel therapies for neurological disorders.
