CPL'36 / Celon Pharma - LARVOL DELTA

The U.S. Food and Drug Administration (FDA) provided positive feedback clearing the path for Phase 3 testing of CPL’36, the company’s novel second-generation PDE10A inhibitor for schizophrenia. (GlobeNewswire) - "Regulatory alignment confirms preclinical data sufficient for pivotal initiation; Phase 3 to include two 28-day trials and a 12-month safety extension....Celon Pharma plans to finalize its Phase 3 protocols incorporating FDA feedback and expects to initiate pivotal studies in 2026."

FDA event • New P3 trial • Schizophrenia

Recent and on-going trials for the treatment of levodopa-induced dyskinesia: a review of the clinical trial databases. (PubMed, Neurodegener Dis Manag) - "Promising results were obtained in Phase II trials with the serotonin type 1A (5-HT1A) agonist befiradol, the dopamine D3 receptor antagonist mesdopetam and the phosphodiesterase inhibitor CPL500036. In contrast, the metabotropic glutamate 4 (mGlu4) receptor negative allosteric modulator foliglurax and JM-010 (a combination of the 5-HT1A partial agonist buspirone and the and the 5-HT type 1B and 1D [5-HT1B/1D] agonist zolmitriptan) did not meet their endpoints in Phase II studies. Lastly, robot-assisted Repetitive Transcranial Magnetic Stimulation (rTMS) of the pre-supplementary motor area may be a promising non-pharmacological approach to alleviate dyskinesia."

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

Safety Assessment of CPL'36 (PDE10A Inhibitor) in Patients With Acute Exacerbation of Schizophrenia – Results From a Phase 2 Clinical Trial (APA 2025) - "Administration of CPL500036 was generally safe and well tolerated by patients with acute exacerbation of schizophrenia within 28-day treatment phase. Mostly mild and moderate adverse events were observed. AEs reported in active group were mostly characterized as not related to the investigational product."

Clinical • P2 data • CNS Disorders • Dystonia • Epilepsy • Insomnia • Mood Disorders • Movement Disorders • Ophthalmology • Psychiatry • Schizophrenia • Sleep Disorder

Strong Proof-of-Concept Data from Phase 2 Trial of PDE10A Inhibitor (CPL’36), a Novel Once-Daily Treatment of Levodopa-Induced Dyskinesia in Parkinson’s Disease (GlobeNewswire) - P2 | N=105 | NCT05297201 | Sponsor: Celon Pharma SA | "The study met its primary endpoint and many of its secondary endpoints. CPL’36 demonstrated robust and consistent efficacy across all utilized scales measuring improvement in treatment of LID in Parkinson’s disease. The effect size was large and clinically meaningful....At Week 4, the improvement in UDysRS total score (primary endpoint) for the 20 mg dose was 12.30 units (LS Mean difference from placebo, p<0.001, Cohen’s d: 0.90) and improvement for the 40 mg dose was 13.58 units (LS Mean difference from placebo, p<0.001, Cohen’s d: 1.00). CPL’36 treatment was associated with improvement in most secondary endpoints, including the UDysRS objective subscale, in which the improvement in both active groups was statistically significant from Day 7 of the treatment phase."

Movement Disorders • Parkinson's Disease

Efficacy, Safety and Pharmacokinetic Study of CPL500036 in Patients with Levodopa Induced Dyskinesia (clinicaltrials.gov) - P2 | N=104 | Completed | Sponsor: Celon Pharma SA | Recruiting ➔ Completed

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

Efficacy, Safety and Pharmacokinetics Study of CPL500036 (PDE10A Inhibitor) in Patients With Schizophrenia (clinicaltrials.gov) - P2 | N=189 | Completed | Sponsor: Celon Pharma SA | Recruiting ➔ Completed

Trial completion • CNS Disorders • Psychiatry • Schizophrenia

Efficacy, Safety and Pharmacokinetic Study of CPL500036 in Patients With Levodopa Induced Dyskinesia (clinicaltrials.gov) - P2 | N=108 | Recruiting | Sponsor: Celon Pharma SA | Trial completion date: Jul 2024 ➔ Dec 2024 | Trial primary completion date: Jun 2024 ➔ Nov 2024

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

Efficacy, Safety and Pharmacokinetics Study of CPL500036 (PDE10A Inhibitor) in Patients With Schizophrenia (clinicaltrials.gov) - P2 | N=165 | Recruiting | Sponsor: Celon Pharma SA | Trial completion date: Nov 2023 ➔ Apr 2024 | Trial primary completion date: Oct 2023 ➔ Mar 2024

Trial completion date • Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

Efficacy, Safety and Pharmacokinetic Study of CPL500036 in Patients With Levodopa Induced Dyskinesia (clinicaltrials.gov) - P2 | N=108 | Recruiting | Sponsor: Celon Pharma SA | Trial completion date: Dec 2023 ➔ Jul 2024 | Trial primary completion date: Nov 2023 ➔ Jun 2024

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

Levodopa-induced dyskinesia: do current clinical trials hold hope for future treatment? (PubMed, Expert Opin Pharmacother) - No abstract available

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

Repeated, 4-week dosing of CPL500036, a novel phosphodiesterase 10A inhibitor, does not induce tolerance to its antipsychotic-like action (ECNP 2023) - "The development of tolerance to antipsychotics is a challenge influencing dosing and compliance of patients. Here, we report that a chronic, 4 week dosing of CPL500036, a novel PDE10A inhibitor, in a rat model of psychosis does not decrease the antipsychotic action of the compound. The molecular assessments confirms behavioral observations."

CNS Disorders • Parkinson's Disease • Psychiatry • Schizophrenia • B2M

Efficacy, Safety and Pharmacokinetic Study of CPL500036 in Patients With Levodopa Induced Dyskinesia (clinicaltrials.gov) - P2 | N=108 | Recruiting | Sponsor: Celon Pharma SA | Trial completion date: Mar 2023 ➔ Dec 2023 | Trial primary completion date: Feb 2023 ➔ Nov 2023

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

Efficacy, Safety and Pharmacokinetics Study of CPL500036 (PDE10A Inhibitor) in Patients With Schizophrenia (clinicaltrials.gov) - P2 | N=165 | Recruiting | Sponsor: Celon Pharma SA | Trial completion date: Sep 2022 ➔ Nov 2023 | Trial primary completion date: Aug 2022 ➔ Oct 2023

Trial completion date • Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

A PDE10A inhibitor CPL500036 is a novel agent modulating striatal function devoid of most neuroleptic side-effects. (PubMed, Front Pharmacol) - " CPL500036 is a potent, selective and orally bioavailable PDE10A inhibitor with a good safety profile distinct from marketed antipsychotics. CPL500036 may be a compelling drug candidate."

Adverse events • Journal • Cardiovascular • CNS Disorders • Diabetes • LINC00473

CPL500036 – a novel inhibitor of phosphodiesterase 10A – attenuates the development of L-DOPA-induced dyskinesias in 6-OHDA lesioned rats (ECNP 2022) - "Sedation was observed only after acute treatment with all doses of CPL500036 but disappeared at day 16. The level of cAMP increased significantly in striatum treated with the highest dose of CPL500036 in both hemispheres and for a dose of 0.03 mg/kg in the lesioned site. Conclusion : CPL500036 attenuates the development of L-DOPA-induced dyskinesias with regards to both their frequencies and amplitudes supporting further clinical development of the compound in the treatment of LID."

Preclinical • CNS Disorders • Parkinson's Disease

Efficacy, Safety and Pharmacokinetic Study of CPL500036 in Patients With Levodopa Induced Dyskinesia (clinicaltrials.gov) - P2 | N=108 | Recruiting | Sponsor: Celon Pharma SA | Trial completion date: Jan 2024 ➔ Mar 2023 | Trial primary completion date: Dec 2023 ➔ Feb 2023

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

Efficacy, Safety and Pharmacokinetics Study of CPL500036 (PDE10A Inhibitor) in Patients With Schizophrenia (clinicaltrials.gov) - P2 | N=165 | Recruiting | Sponsor: Celon Pharma SA | Trial completion date: May 2022 ➔ Sep 2022 | Trial primary completion date: Apr 2022 ➔ Aug 2022

Trial completion date • Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

Efficacy, Safety and Pharmacokinetic Study of CPL500036 in Patients With Levodopa Induced Dyskinesia (clinicaltrials.gov) - P2 | N=108 | Recruiting | Sponsor: Celon Pharma SA

New P2 trial • CNS Disorders • Movement Disorders • Parkinson's Disease

Efficacy, Safety and Pharmacokinetics Study of CPL500036 (PDE10A Inhibitor) in Patients With Schizophrenia (clinicaltrials.gov) - P2 | N=165 | Recruiting | Sponsor: Celon Pharma SA

New P2 trial • CNS Disorders • Psychiatry • Schizophrenia

CPL500036 - a novel inhibitor of phosphodiesterase 10A - attenuates parkinsonian-like and L-DOPA induced dyskinetic effects in 6-OHDA lesioned rats (Neuroscience 2021) - "CPL036 attenuated effectively L-DOPA induced dyskinesias in combination therapy with L-DOPA, without negative impact on the therapeutic antiparkinsonian efficacy of the latter drug, in a rat model of PD.; Grant Support: POIR.01.01.01-00-0617/20-00 (National Centre for Research and Development, Poland); statutory funds of the Maj Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland; Celon Pharma S.A."

Preclinical • CNS Disorders • Parkinson's Disease

Antiparkinsonian-like effects of CPL500036, a novel selective inhibitor of phosphodiesterase 10A, in the unilateral rat model of Parkinson's disease. (PubMed, Eur J Pharmacol) - "Moreover, CPL500036 did not diminish the therapeutic effects produced by acute and chronic treatment with L-DOPA in these tests. The present study suggests a potential use of CPL50036 as a co-treatment to L-DOPA in PD therapy."

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

Safety and Pharmacokinetics Study of CPL500036 Compound in Healthy Volunteers (clinicaltrials.gov) - P1; N=56; Completed; Sponsor: Celon Pharma SA; Recruiting ➔ Completed

Clinical • Trial completion

Brief- Celon Pharma completes administration of drug candidate in phase I clinical test (Reuters) - "Celon Pharma SA: * SAID ON THURSDAY THAT IT HAS COMPLETED ADMINISTRATION OF DRUG CANDIDATE IN PHASE I OF CLINICAL TEST OF A DRUG BASED ON PDE10A INHIBITOR, DEVELOPED IN THE TREATMENT OF PSYCHOTIC AND NEUROMOTOR DISORDERS - CPL500036 * SAID DURING THE TEST THE DRUG WAS WELL TOLERATED AND SHOWED DESIRED PHARMACOKINETICS BOTH AFTER SINGLE AND REPEATED ADMINISTRATION"

PK/PD data • Trial status

Safety and pharmacokinetic study of phosphodiesterase 10A inhibitor (CPL500036) after a single dose in healthy volunteers (Neuroscience 2019) - "CPL500036 administration in all doses was safe and well tolerated by volunteers and resulted in few AE with mild to moderate severity. Pharmacokinetics of CPL500036 supports once daily dosing regimen. The obtain results justify further clinical development."

Clinical • PK/PD data