solengepras (CVN424) / Cerevance - LARVOL DELTA

SPEECH AND VIDEO BASED DIGITAL BIOMARKERS' RELATIONSHIP TO MDS-UPDRS SCORES IN EARLY PARKINSON'S DISEASE: BASELINE DATA FROM A PLACEBO-CONTROLLED TRIAL (ADPD 2026) - "Aims: To assess relationships between remote digital audiovisual measures and MDS-UPDRS scores in assessing early Parkinson's Disease (PD). We analyzed baseline data from ASCEND, a Phase 2 clinical trial of Solengepras (CVN424) in 64 early, untreated PD participants... Remote digital speech and video measures have potential to capture disease state in early PD along multiple domains. Correlations with video measures highlight how early-stage facial and limb bradykinesia can be assessed remotely using digital assessments. Unstructured self reports of problems also capture some aspects in parallel with standard rating scores."

Biomarker • Clinical • Video • CNS Disorders • Movement Disorders • Myelodysplastic Syndrome • Parkinson's Disease

A NOVEL METHOD ASSESSING REM SLEEP WITHOUT ATONIA IN PARKINSON'S DISEASE USING THE WAVEBAND, AN AT-HOME EEG SLEEP MONITORING DEVICE (ADPD 2026) - P2 | "A cross-sectional analysis was performed on baseline recordings in early PD patients enrolled in CVN424-203 (NCT06006247)... This study provides preliminary evidence that RSWA, while generally undetectable through clinical assessment, can be measured at home using the Beacon Waveband. RSWA-negative participants had lower MDS-UPDRS scores at baseline, suggesting RSWA correlated with disease severity. As RSWA is an early clinical feature of PD, these results provide support for using the at-home Waveband as an objective tool for diagnosis, patient stratification, and assessing disease severity."

Behavior Disorders • CNS Disorders • Mental Retardation • Movement Disorders • Parkinson's Disease • Sleep Disorder

SOLENGEPRAS, A NOVEL GPR6-INHIBITOR, SHOWS POTENTIAL TO IMPROVE SLEEP DISTURBANCE IN PARKINSON'S DISEASE: RESULTS FROM THE ASCEND PHASE 2 TRIAL (ADPD 2026) - P2 | "In this Phase 2 study in early PD, solengepras showed potential benefits in reducing non-motor symptoms, particularly in sleep-related disturbances. At-home sleep monitoring demonstrated no overall worsening of sleep architecture and suggested a potential benefit on sleep quality. These findings support further investigation of solengepras in addressing sleep dysfunction in PD."

P2 data • CNS Disorders • Movement Disorders • Parkinson's Disease • Sleep Disorder • DRD2

CHARACTERISTICS OF OFF-TIME IMPROVEMENT IN A PHASE 2 STUDY FOR PARKINSON'S DISEASE (PD) WITH SOLENGEPRAS, A NOVEL GPR6-INHIBITOR (ADPD 2026) - P2 | "In this Phase 2 post-hoc analysis of patient motor diaries, solengepras reduced daily OFF-time in PD patients with ≥3 hours of OFF-time at baseline and reduced the mean number of OFF periods per day. A non-significant reduction was also observed in the duration of OFF periods and morning OFF. These results help describe the potential of solengepras to reduce patient burden and disability in PD."

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

Cerevance to Present Phase 2 Trial Results on OFF Time and Sleep‑Related Outcomes with Solengepras in Parkinson’s Disease at AD/PD 2026 (GlobeNewswire) - "Post hoc analyses of two Phase 2 trials examine the potential benefits of solengepras, a once-daily, oral, non-dopaminergic GPR6 inhibitor, across Parkinson’s disease populations. Phase 2 adjunctive trial data showed a significant reduction in the frequency and duration of OFF time in individuals with Parkinson’s disease experiencing motor fluctuations, largely translating into increased good ON time. New Phase 2 ASCEND monotherapy trial demonstrated potential benefit in non-motor symptoms versus placebo, with the largest standardized improvement observed in sleep-related symptoms."

P2 data • Parkinson's Disease

Characteristics of OFF-time Improvement in a Phase Two Study for Parkinson's Disease (PD) with Solengepras, a Novel GPR6-inhibitor (AAN 2026) - P2 | "In this Phase 2 post-hoc analysis of patient motor diaries, solengepras reduced daily OFF-time in PD patients with ≥3 hours of OFF-time at baseline and reduced the mean number of OFF periods per day. A non-significant reduction was also observed in the duration of OFF periods and morning OFF. These results help describe the potential of solengepras to reduce patient burden and disability in PD."

CNS Disorders • Movement Disorders • Parkinson's Disease

Solengepras, A Novel GPR6-inhibitor, Shows Potential to Improve Sleep Disturbance in Parkinson's Disease: Results from the ASCEND Phase Two Trial (AAN 2026) - P2 | "In this Phase 2 study in early PD, solengepras showed potential benefits in reducing non-motor symptoms, particularly in sleep-related disturbances. At-home sleep monitoring demonstrated no overall worsening of sleep architecture and suggested a potential benefit on sleep quality. These findings support further investigation of solengepras in addressing sleep disturbance in PD."

CNS Disorders • Movement Disorders • Parkinson's Disease • Sleep Disorder • DRD2

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