solengepras (CVN424) / Cerevance - LARVOL DELTA

Solengepras is being evaluated in the global, Phase 3 ARISE trial as a once-daily, oral treatment for use as an adjunctive therapy to levodopa and other anti-Parkinsonian medications. (GlobeNewswire) - "Topline data are expected in 2026."

P3 data: top line • Parkinson's Disease

Cerevance Showcases Positive Phase 2 Results Demonstrating Significant Reduction in OFF Time with Solengepras as an Adjunctive Treatment in Parkinson’s Disease (GlobeNewswire) - "The findings demonstrated that four weeks of once-daily treatment with solengepras significantly reduced OFF time (periods of symptomatic worsening) by decreasing both the number and duration of OFF episodes, including morning OFF time...Primary efficacy endpoint: Solengepras 150mg achieved a statistically significant 1.3-hour reduction in average daily OFF time versus placebo after 27 days of treatment (p=0.02)."

P2 data • Parkinson's Disease

Cerevance to Highlight Potential of Solengepras in Parkinson’s Disease at the 2025 Parkinson Study Group Annual Meeting (GlobeNewswire) - "New findings from Phase 2 adjunctive study evaluating the characteristics of OFF time improvement with solengepras, a novel, non-dopaminergic GPR6 inhibitor; poster selected as one of 10 featured selections for the Poster Tour; Results from Phase 2 ASCEND trial of solengepras as a monotherapy treatment for patients with early-stage Parkinson’s disease to be presented....In addition to the poster presentations, Cerevance CEO Craig Thompson will present updates on the company’s latest progress in Parkinson’s disease research during the PSG Industry Forum on Friday, December 5, 2025."

Clinical data • Parkinson's Disease

To Evaluate the Efficacy of CVN424 in Parkinson's Disease Participants With Motor Complications (clinicaltrials.gov) - P3 | N=330 | Recruiting | Sponsor: Cerevance | Trial primary completion date: Oct 2025 ➔ Mar 2026

Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

Solengepras: An Investigational Therapy with Potential Benefits on Functional and Non-Motor Measures in Parkinson's Disease (PD) (MDS Congress 2025) - P2 | "Solengepras is an investigational GPR6-inhibitor with a novel non-dopaminergic mechanism-of-action and a favorable safety profile that may have potential benefits in functional and non-motor symptoms in both early and later stage PD."

CNS Disorders • Movement Disorders • Parkinson's Disease

Cerevance to Present Phase 2 Data on Solengepras in Parkinson’s Disease at the 2025 International Congress of Parkinson's Disease and Movement Disorders (GlobeNewswire) - "Solengepras was generally well-tolerated during the 12-week study and a low rate of dopaminergic side effects were observed....The presentation will share findings from the Phase 2 ASCEND study of solengepras, an investigational, non-dopaminergic GPR6 inhibitor being evaluated in patients with early-stage Parkinson’s disease. Results from the trial include analyses of functional and non-motor measures, together with safety observations."

P2 data • Parkinson's Disease

Motor fluctuations in Parkinson disease - a mini-review of emerging drugs. (PubMed, Expert Opin Emerg Drugs) - "Preliminary results of a phase III study of dopamine D1/D5 agonist tavapadon and phase II of CVN424, a GRP6 inverse agonist suggest improved ON time. Negative studies were reported with foliglurax (MGluR4 inverse agonist) and the repurposed drugs naftazone and bumetanide. Several novel targets are in early-stage development with results awaited. Overall, it is unclear whether the field is significantly further ahead, as the benefit of these emerging drugs in comparison with currently available agents for motor fluctuations needs to be clarified."

Journal • Review • CNS Disorders • Movement Disorders • Parkinson's Disease

HOW THE THERAPEUTIC APPROACH TO EARLY PARKINSON'S DISEASE WILL CHANGE IN THE NEXT FUTURE (ADPD 2025) - "Levodopa remains the most efficacious drug, a better preparation of levodopa like IPX 203 can ensure more stable plasma levels of Levodopa...Tavapadon is a new dopamine agonist stimulating D1-D5 receptors which concluded the phase III. Other compounds such as CVN424 (Cerevance) orally active and selective GPR6 inverse agonist, piperamat (IRLAB 752) a cortical enhancer to improve balance, Clenbuterol/Nadolol for cognition, mesdopetam a D3 antagonist are under investigation...These include the monoclonal antibody prasinezumab, UCB0599 and buntanetap small-molecules α-synuclein aggregation inhibitor, the vaccine ACI-7104.056 by AC immune...The LRKK2 kinase inhibitor BIIB122/DNL151 is in phase IIb in PD. BIAL BIA 28-6156 activator of the GCase enzyme is under investigation in patients with GBA mutation. The combination of symptomatic and disease modifying therapy, the use of accurate biomarkers and more precise treatment will be the future in the treatment of PD."

CNS Disorders • Movement Disorders • Parkinson's Disease • GBA

RESULTS OF ASCEND: A PHASE 2 TRIAL OF SOLENGEPRAS (CVN424) AS AN INVESTIGATIONAL MONOTHERAPY FOR TREATMENT OF EARLY PARKINSON'S DISEASE (ADPD 2025) - P2 | "The trial is expected to be completed in February 2025 and the unblinded efficacy and safety Results are planned to be presented at the conference. Conclusions The Results of the ASCEND trial will help evaluate the potential of solengepras as a monotherapy and may further support GPR6-inhibition as a novel non-dopaminergic treatment strategy for PD."

Monotherapy • P2 data • CNS Disorders • Movement Disorders • Parkinson's Disease

Cerevance Presents Topline Results from Phase 2 ASCEND Trial of Solengepras as Monotherapy Treatment for Early-Stage Parkinson’s Disease at AD/PD 2025 (GlobeNewswire) - P2 | N=62 | ASCEND (NCT06006247) | Sponsor: Cerevance Beta, Inc. | "Solengepras showed evidence of potential benefit in functional and non-motor symptoms versus placebo as measured by MDS-UPRDS Parts I, II, NMSS, and ESS, consistent with its novel non-dopaminergic mechanism of action; This investigational treatment was generally well tolerated with no serious adverse events; fewer adverse events related to non-motor symptoms were reported in the solengepras arm; Pivotal Phase 3 ARISE trial evaluating solengepras as adjunctive therapy in Parkinson’s disease is ongoing with topline data expected in first half of 2026."

P2 data • P3 data: top line • Parkinson's Disease

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

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

Solengepras (CVN424): A Novel GPR6 Inhibitor in Clinical Development as an Investigational Therapy for Parkinson's Disease (AAN 2025) - "Solengepras is a novel investigational agent that targets the indirect pathway through GPR6 and is being studied for PD in the ASCEND and ARISE clinical trials."

Clinical • CNS Disorders • Movement Disorders • Parkinson's Disease

Early Parkinson's Disease Monotherapy With CVN424 (clinicaltrials.gov) - P2 | N=62 | Completed | Sponsor: Cerevance Beta, Inc. | Active, not recruiting ➔ Completed | Trial primary completion date: Oct 2024 ➔ Jan 2025

Monotherapy • Trial completion • Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

Structural insights into the high basal activity and inverse agonism of the orphan receptor GPR6 implicated in Parkinson's disease. (PubMed, Sci Signal) - "Here, we solved crystal structures of GPR6 without the addition of a ligand (a pseudo-apo state) and in complex with two inverse agonists, including CVN424, which improved motor symptoms in patients with Parkinson's disease in clinical trials...A combination of site-directed mutagenesis, native mass spectrometry, and computer modeling suggested potential mechanisms for high constitutive activity and inverse agonism in GPR6 and identified a series of lipids and ions bound to the receptor. The structures and results obtained in this study could guide the rational design of drugs that modulate GPR6 signaling."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

Cerevance Doses First Patient in Pivotal Phase 3 ARISE Trial of Solengepras for Treatment of Parkinson’s Disease (GlobeNewswire) - "ARISE is a global, randomized, double-blind, placebo-controlled Phase 3 clinical trial, with a plan to enroll approximately 330 patients with three or more hours of 'OFF' time per day. The primary endpoint is the change from baseline in the total daily 'OFF' time at Week 12....The trial will also evaluate the safety and tolerability of solengepras."

Trial status • Parkinson's Disease

Early Parkinson's Disease Monotherapy With CVN424 (clinicaltrials.gov) - P2 | N=62 | Active, not recruiting | Sponsor: Cerevance Beta, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Monotherapy • CNS Disorders • Movement Disorders • Parkinson's Disease

CVN424, a GPR6 inverse agonist, for Parkinson's disease and motor fluctuations: a double-blind, randomized, phase 2 trial. (PubMed, EClinicalMedicine) - P2 | "This study supports the development of CVN424 for the treatment of PD. Cerevance."

Journal • P2 data • CNS Disorders • Movement Disorders • Pain • Parkinson's Disease

To Evaluate the Efficacy of CVN424 in Parkinson's Disease Participants With Motor Complications (clinicaltrials.gov) - P3 | N=330 | Recruiting | Sponsor: Cerevance | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Movement Disorders • Parkinson's Disease

Cerevance Announces Publication of Positive Phase 2 Results of Solengepras for the Treatment of Parkinson’s Disease in eClinicalMedicine (GlobeNewswire) - P2 | N=136 | NCT04191577 | Sponsor: Cerevance Beta, Inc. | "On Day 27, the change from baseline in daily OFF time was -1.6 hours (p <0.0001) in the solengepras 150 mg group, -1.3 hours (p <0.01) in the solengepras 50 mg group, and -0.5 hours in the placebo group. The placebo-adjusted least squares mean treatment difference was statistically significant for the solengepras 150 mg dose at -1.3 hours (p=0.0225). Decreases in OFF time were accompanied by trends towards increased total daily ON time without troublesome dyskinesia (Good ON time). The placebo-adjusted least squares mean treatment difference for good ON time was +0.67 (p=0.27) with the solengepras 150 mg dose...In the supplementary post-hoc analysis, treatment with solengepras 150 mg group reduced OFF time by -1.78 hours (p= 0.0045) compared to placebo and increased good ON time by +1.3 hours (p=0.04)...Solengepras was generally well tolerated, and no serious treatment-related adverse events were reported."

P2 data • CNS Disorders • Parkinson's Disease

Phase 3 Study of CVN424 (clinicaltrials.gov) - P3 | N=330 | Not yet recruiting | Sponsor: Cerevance

New P3 trial • CNS Disorders • Movement Disorders • Parkinson's Disease

Cerevance Presents at IAPRD XXIX World Congress on Parkinson’s Disease and Related Disorders (GlobeNewswire) - P2 | N=141 | NCT04191577 | Sponor: Cerevance Beta, Inc. | "Cerevance...will present an oral presentation at the upcoming International Association of Parkinsonism and Related Disorders (IAPRD) XXIX World Congress on Parkinson’s Disease and Related Disorders, taking place in Lisbon, Portugal from May 19-22, 2024....In a Phase 2 clinical trial, CVN424...demonstrated a significant reduction in OFF time and was safe and well tolerated with low rates of mostly mild and moderate adverse events. Patients also reported enhanced motor functionality in daily activities, as assessed by the UPDRS Part II."

P2 data • CNS Disorders • Parkinson's Disease

Cerevance Adds $47 Million in Series B-1 Extension to Advance Robust Clinical Pipeline (GlobeNewswire) - "Cerevance...today announced an initial closing of its Series B-1 Extension financing round that will add $47 million to the $51 million previously raised bringing the total Series B-1 raise to $98 million....Proceeds from this financing will support the upcoming Phase 3 clinical trial for CVN424, a first-in-class non-dopamine therapy for patients with Parkinson’s disease, as well as the advancement of a pipeline of novel treatments for other CNS disorders, including Alzheimer’s disease, Amyotrophic lateral sclerosis, and frontotemporal dementia."

Financing • CNS Disorders • Parkinson's Disease

Early Parkinson's Disease Monotherapy With CVN424 (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Cerevance Beta, Inc.

Monotherapy • Trial completion date • Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

Early Parkinson's Disease Monotherapy With CVN424 (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Cerevance Beta, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • CNS Disorders • Movement Disorders • Parkinson's Disease