Cerevance’s CVN293 Demonstrated Positive Phase 1 Results in Healthy Volunteers

November 11, 2024

• CVN293 was generally well-tolerated in healthy volunteers for up to 14-days of continuous dosing
• Dose-dependent exposure was observed with evidence of robust brain penetration
• Data supports potential advancement into Phase 2 for neurodegenerative diseases characterized by neuroinflammation such as Frontotemporal Dementia, Amyotrophic Lateral Sclerosis, and Alzheimer’s Disease

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‍Boston, MA – November 11, 2024   – 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 reported positive results from its Phase 1 single ascending dose (SAD) and multiple ascending dose (MAD) clinical study of CVN293 in healthy volunteers. CVN293 is designed to inhibit KCNK13, a potentially novel target involved in activating the NLRP3 inflammasome, with the aim of reducing neuroinflammation and attenuating disease progression in a variety of neurodegenerative disorders. KCNK13 was identified by Cerevance’s proprietary NETSseq platform.

“We are very encouraged by the clinical data for CVN293, observing that it was generally well-tolerated and achieved favorable brain penetration,” said Mark Carlton, Ph.D., chief scientific officer and co-founder of Cerevance. “CVN293 selectively inhibits KCNK13, a gene selectively expressed in microglia with minimal expression in peripheral tissues. This selective targeting may contribute to its favorable tolerability profile. By inhibiting KCNK13 to reduce NLRP3 activation, CVN293 may offer a disease-modifying approach for challenging CNS disorders.”

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Summary of Key CVN293 Phase 1 Results

• CVN293 was generally well-tolerated in healthy participants with single doses up to 1000mg and multiple doses of up to 375mg twice daily for 14 days.
• No serious adverse events were reported and all participants completed the study. All related treatment-emergent adverse events were mild.
• Dose-dependent increases in CVN293 exposure were observed, achieving plasma concentrations that align with clinically relevant levels as indicated by preclinical studies.
• CSF sampling demonstrated high brain penetrance of CVN293.
• Clinical safety and pharmacokinetic profile of CVN293 is favorable for potential advancement into Phase 2 studies.

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About the Phase 1 Clinical Trial of CVN293 in Healthy Volunteers

The Phase 1 study of CVN293 was a first-in-human, randomized, placebo-controlled, single-center, SAD and MAD study in 72 healthy adult volunteers. The primary objective of the study was to evaluate the safety, tolerability, and pharmacokinetics of oral CVN293. In the SAD portion of the study, a single dose of CVN293 ranging from 3 mg to 1000 mg or placebo were administered to 48 healthy adult participants (CVN293 n=36; placebo n=12). In the MAD portion of the study, CVN293 doses from 50 mg (25 mg twice daily) to 750 mg (375 mg twice daily) or placebo were administered to 24 healthy adult participants (CVN293 n=18; placebo n=6) over 14 consecutive days.

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About CVN293

CVN293 is a highly-selective oral inhibitor targeting KCNK13, a potassium two pore domain channel subfamily K member 13, which is implicated in neuroinflammation and central nervous system disorders. By targeting KCNK13, identified to be solely expressed in microglia with Cerevance’s proprietary NETSseq platform, CVN293 aims to reduce the activation of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome specifically in the brain. This inflammasome plays a critical role in the activation of microglia, which are associated with neurodegenerative disorders such as Alzheimer’s disease and frontotemporal dementia. In contrast to other therapies that target NLRP3 which may suppress aspects of the peripheral immune system, we believe the selective inhibition of KCNK13 by CVN293 in microglia may provide better tolerability relative to other approaches targeting NLRP3 and has the potential to act as a disease-modifying treatment by specifically targeting neuroinflammation in the brain.

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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, Nuclear Enriched Transcript Sort sequencing (NETSseq), allows us to identify novel targets, even those 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.

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Contacts

Cerevance:

Johnna Simoes, [email protected]

Media

Andrew Mielach, [email protected], +1-646-876-5868