solengepras (CVN424) / Cerevance - LARVOL DELTA

Breakthrough: Results from ARISE: A phase 3 trial of solengepras in Parkinson’s patients with motor fluctuations (MDS Congress 2026) - No abstract available

Clinical • P3 data • CNS Disorders • Movement Disorders • Parkinson's Disease

Discovery of Small Molecule Ligands Targeting Orphan G Protein-Coupled Receptors GPR3, GPR6, and GPR12. (PubMed, J Med Chem) - "Notably, the GPR6 inverse agonist CVN424 is currently in Phase III clinical trials for the treatment of Parkinson's disease (PD)...Herein, we summarize the current understanding of the structural and functional characteristics of GPR3, GPR6, and GPR12. We further highlight recent progress in relevant ligand discovery and discuss the key challenges and opportunities in developing potent and selective modulators targeting these orphan receptors."

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

Talk #1 What’s new in PD motor symptom control - new advances and research pipeline (WPC 2026) - "Newer drugs awaiting FDA clearance that have shown promise to also improve on time without dyskinesias are tavapadon, a selective D1/D5 receptor partial agonist, and ND0612, a subcutaneous infusion of levodopa-carbidopa solution. Ongoing Phase 3 trials of Parkinson’s disease drugs designed to improve motor symptoms include CVNB424, a GPR6 receptor modulator, and P2B001, a combination of low doses of extended release rasagiline and pramipexole. While we await disease modifying therapies in Parkinson’s disease, pursuing scientific research of clinical treatments that minimize the impact of motor and non-motor symptoms on quality of life is imperative."

CNS Disorders • Movement Disorders • Parkinson's Disease

Topic #6: What’s New in PD motor symptom control - new advances and research pipel (WPC 2026) - "Newer drugs awaiting FDA clearance that have shown promise to also improve on time without dyskinesias are tavapadon, a selective D1/D5 receptor partial agonist, and ND0612, a subcutaneous infusion of levodopa-carbidopa solution. Ongoing Phase 3 trials of Parkinson’s disease drugs designed to improve motor symptoms include CVNB424, a GPR6 receptor modulator, and P2B001, a combination of low doses of extended release rasagiline and pramipexole. While we await disease modifying therapies in Parkinson’s disease, pursuing scientific research of clinical treatments that minimize the impact of motor and non-motor symptoms on quality of life is imperative."

CNS Disorders • Movement Disorders • Parkinson's Disease

Cerevance Completes Enrollment in Pivotal Phase 3 Parkinson’s Disease Trial and Closes Oversubscribed $20 Million Series C to Extend Runway into 2027 (GlobeNewswire) - "Phase 3 ARISE trial of solengepras, a potential first-in-class non-dopaminergic therapy, is fully enrolled and topline data is expected at the end of Q3 2026....The ARISE trial enrolled 341 patients across the United States, Europe, United Kingdom, and Australia, and is assessing solengepras as an adjunctive therapy to levodopa and other standard-of-care Parkinson’s medications in patients who experience motor fluctuations, including daily OFF periods."

Enrollment closed • Financing • P3 data: top line • 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 | "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

Characteristics of OFF-time Improvement in a Phase Two Study for Parkinson’s Disease (PD) with Solengepras, a Novel GPR6-inhibitor (AAN 2026) - P2 | "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

CVN-424: An Advanced GPR6 Inverse Agonist in Phase III Clinical Trials for Parkinson's Disease. (PubMed, J Med Chem) - No abstract available

Journal • P3 data • CNS Disorders • Movement Disorders • Parkinson's Disease

Cerevance to Present Positive Phase 2 Solengepras Data in Parkinson’s Disease at the American Academy of Neurology 2026 Annual Meeting (The Manila Times) - "Solengepras, a once-daily, oral, non-dopaminergic GPR6 inhibitor, demonstrated meaningful reductions in daily OFF time and improvements in sleep-related symptoms across two Phase 2 trials; Meeting presentations highlight the potential of a non-dopaminergic approach in addressing key areas of unmet need in Parkinson’s disease."

P2 data • Parkinson's Disease

To Evaluate the Efficacy of CVN424 in Parkinson's Disease Participants With Motor Complications (clinicaltrials.gov) - P3 | N=330 | Active, not recruiting | Sponsor: Cerevance | Recruiting ➔ Active, not recruiting | Trial completion date: Mar 2026 ➔ Aug 2026 | Trial primary completion date: Mar 2026 ➔ Aug 2026

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

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

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