CVN293 / Cerevance - LARVOL DELTA

Cerevance Presents Positive Results from Phase 1 Study of CVN293 at American Academy of Neurology 2025 Annual Meeting (GlobeNewswire) - P1 | N=72 | "Results showed that CVN293 was generally well-tolerated following single and 14-day multiple dosing, with 100% of participants completing the trial. There were no severe or dose-limiting adverse events (AEs), treatment-related discontinuations or clinically meaningful changes in vital signs or laboratory parameters. All related AEs were considered mild. In the SAD and MAD parts of the study, CVN293 plasma exposure increased in a generally dose proportional manner. Cerebrospinal fluid (CSF) sampling demonstrated high levels of central nervous system (CNS) exposure with CVN293."

P1 data • CNS Disorders

A First-in-Human Phase 1 Study to Investigate the Safety, Tolerability, and Pharmacokinetics of CVN293, an Investigational Inhibitor of KCNK13 Targeting NLRP3-Mediated Neuroinflammation (P8-3.016). (PubMed, Neurology) - "Dr. Brice has received personal compensation for serving as an employee of Cerevance."

Clinical • Journal • P1 data • PK/PD data • CNS Disorders • Inflammation • NLRP3

New Data to Be Presented at Upcoming Congresses Showcase Cerevance's Advanced Clinical Program in Parkinson’s Disease and Deep Pipeline for CNS-based Disorders (GlobeNewswire) - "Cerevance...announced upcoming presentations at the International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders (AD/PD 2025) being held April 1-5 in Vienna, and the American Academy of Neurology (AAN) Annual Meeting being held April 5-9 in San Diego."

Clinical data • CNS Disorders • Parkinson's Disease

A First-in-Human Phase 1 Study to Investigate the Safety, Tolerability, and Pharmacokinetics of CVN293, an Investigational Inhibitor of KCNK13 Targeting NLRP3-Mediated Neuroinflammation (AAN 2025) - "This Phase 1 study demonstrates a favorable tolerability profile for CVN293 in healthy adults and supports the continued development of this novel KCNK13 inhibitor for neurodegenerative diseases driven by neuroinflammation."

Clinical • P1 data • PK/PD data • CNS Disorders • Inflammation • NLRP3

NETSseq Identifies Novel Therapeutic Targets for Neurodegenerative Diseases (AAN 2025) - "Based on the highly specific localisation and the biological function of GPR6 in models of PD, we developed solengepras (CVN424), which in a Phase 2 study was demonstrated to be generally well-tolerated and provided clinically meaningful activity in PD (Brice et al 2022/2024)...In conclusion, NETSseq has the potential to identify cell specific gene targets and biological insight into human brain disorders, which can be developed into novel therapies for neurodegenerative diseases."

Alzheimer's Disease • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • DRD2 • NLRP3

Cerevance’s CVN293 Demonstrated Positive Phase 1 Results in Healthy Volunteers (GlobeNewswire) - P1 | N=NA | "Cerevance...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 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."

P1 data • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Dementia

Identification and characterisation of CVN293, a brain permeable KCNK13 inhibitor (Neuroscience 2024) - "Functionally, CVN293 demonstrated a concentration-dependant inhibition of the NLRP3-inflammasome mediated production of IL-1β from LPS-primed murine microglia and good oral bioavailability in pharmacokinetic studies. These findings support the pharmacological mechanism that inhibiting KCNK13 K+ efflux could serve as a therapeutic option for neurodegenerative diseases thus supporting the advancement of CVN293 into clinical trials."

Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Parkinson's Disease • IL1B • NLRP3

Discovery of CVN293, a Brain Permeable KCNK13 (THIK-1) Inhibitor Suitable for Clinical Assessment. (PubMed, ACS Med Chem Lett) - "Cross-species pharmacokinetic data of CVN293 are also disclosed. These findings support the advancement of CVN293 in clinical trials."

Journal • Alzheimer's Disease • CNS Disorders • IL1B • NLRP3

Cerevance Presents at 35th Symposium on Medicinal Chemistry in Eastern England (GlobeNewswire) - "Cerevance...announced plans to deliver an oral presentation at the upcoming 35th Symposium on Medicinal Chemistry, taking place in Hatfield, United Kingdom April 25, 2024."

Clinical • Amyotrophic Lateral Sclerosis

Cerevance Announces Presentation at Alzheimer’s Research UK Conference (GlobeNewswire) - "Cerevance...announced plans to present a poster at the upcoming Alzheimer’s Research UK Conference, taking place in Liverpool, United Kingdom, March 20-21, 2024....Cerevance’s NETSseq platform enables the identification of novel targets, such as KCNK13 (THIK1), from specific cell types in the human brain. Following the discovery of KCNK13, Cerevance has developed CVN293, a novel compound that selectively inhibits KCNK13 and reduces the release of IL-1β from microglia dependent on NLRP3. CVN293 shows promise in potentially addressing CNS conditions characterized by neuroinflammation, such as frontotemporal dementia (FTD), Amyotrophic lateral sclerosis (ALS), and Alzheimer’s disease."

Clinical • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Dementia

Cerevance Announces Presentation at the 34th International Symposium on ALS/MND (GlobeNewswire) - "Cerevance will present CVN293...which effectively curbs the NLRP3-dependent release of IL-1β from microglia and notably decelerates the progression of disease in SOD1 (G39A) mice. The elevated levels of KCNK13 in ALS-affected tissue, alongside the favorable drug metabolism and pharmacokinetics profile of CVN293, underscore its promising potential for neurodegenerative diseases."

Preclinical • Amyotrophic Lateral Sclerosis

The two-pore potassium channel KCNK13 as a target to modulate neuroinflammation in Amyotrophic Lateral Sclerosis (ALS-MND 2023) - "Here we show the characterisation of the novel, selective KCNK13 inhibitor, CVN293, and demonstrate its utility as a potential therapeutic candidate molecule to slow the progression of ALS. dino.ossola@cerevance.com"

Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation • IL1B • NLRP3

Cerevance Doses First Subject in Phase 1 Clinical Study of CVN293, a Selective Inhibitor of KCNK13 Designed to Selectively Modulate Neuroinflammation, for the Treatment of ALS and Alzheimer’s Disease (GlobeNewswire) - "Cerevance...today announced that the first subject has been dosed in the Phase 1 clinical study evaluating the safety, tolerability, and pharmacokinetics of CVN293....The Phase 1 trial is a combined single ascending dose (SAD) and multiple ascending dose (MAD) study designed to investigate the safety, tolerability, and pharmacokinetics of orally administered CVN293 in healthy subjects"

Trial status • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders

Cerevance Announces Presentation at the Gordon Research Conference: Amyotrophic Lateral Sclerosis and Related Motor Neuron Diseases (GlobeNewswire) - "Cerevance...today announced plans to present a poster presentation at the upcoming Gordon Research Conference: Amyotrophic Lateral Sclerosis (ALS) and Related Motor Neuron Diseases, taking place in Les Diablerets, VD, Switzerland, July 2 – July 7, 2023....Cerevance’s compound, CVN293 is a novel, potent, and selective KCNK13 inhibitor that attenuates the NLRP3-dependent release of IL-1β from microglia and delays disease progression in SOD1(G39A) mice. The increase in KCNK13 in ALS tissue and the favorable drug metabolism and pharmacokinetics profile of CVN293 support its use in the treatment of ALS."

Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders

Cerevance Expands Series B Financing with Additional $51 Million (GlobeNewswire) - "Cerevance...today announced an expansion of its Series B funding round with an additional close of $51 million, bringing the total Series B financing to $116 million. The financing will support upcoming clinical trials focused on Parkinson’s disease....The company plans to initiate a Phase 2 proof of concept study assessing CVN424 as a monotherapy treatment in patients with newly diagnosed Parkinson’s disease not yet treated with levodopa in Q2 2023....CVN293, a blocker of KCNK13, a recently discovered novel target that is selectively expressed in brain microglia, dampens maladaptive central neuroinflammation associated with many neurodegenerative diseases such as ALS and Alzheimer’s disease. A Phase 1 study assessing CVN293 is planned for Q3 2023."

Financing • New P1 trial • New P2 trial • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Parkinson's Disease