minzasolmin (UCB0599) / UCB, EVER Pharma, Novartis - LARVOL DELTA

An Extension Study to Evaluate the Long-Term Efficacy, Safety and Tolerability of Minzasolmin (UCB0599) in Study Participants With Parkinson's Disease (clinicaltrials.gov) - P2 | N=428 | Terminated | Sponsor: UCB Biopharma SRL | Active, not recruiting ➔ Terminated; Based on available data, the decision was made to stop development of UCB0599/minzasolmin as treatment of Parkinson's Disease.

Trial termination • 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

An Extension Study to Evaluate the Long-Term Efficacy, Safety and Tolerability of Minzasolmin (UCB0599) in Study Participants With Parkinson's Disease (clinicaltrials.gov) - P2 | N=428 | Active, not recruiting | Sponsor: UCB Biopharma SRL | Trial completion date: Oct 2029 ➔ Apr 2025 | Trial primary completion date: Oct 2029 ➔ Mar 2025

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

NPT100-18A rescues mitochondrial oxidative stress and neuronal degeneration in human iPSC-based Parkinson's model. (PubMed, BMC Neurosci) - "Our findings demonstrate that NPT100-18A limits neuronal degeneration in a human in vitro model of PD. In addition, we provide first mechanistic insights into how a compartment-specific antioxidant effect in mitochondria might contribute to the neuroprotective effects of NPT100-18A."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease • CASP3 • SNCA

An Extension Study to Evaluate the Long-Term Efficacy, Safety and Tolerability of Minzasolmin (UCB0599) in Study Participants With Parkinson's Disease (clinicaltrials.gov) - P2 | N=428 | Active, not recruiting | Sponsor: UCB Biopharma SRL | Trial completion date: Apr 2027 ➔ Oct 2029 | Trial primary completion date: Apr 2027 ➔ Oct 2029

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

Findings from minzasolmin proof-of-concept ORCHESTRA study shape next steps in UCB Parkinson’s research program (UCB Press Release) - P2a | N=496 | ORCHESTRA (NCT04658186) | Sponsor: UCB Biopharma SRL | "UCB today announced the ORCHESTRA proof-of-concept study of minzasolmin...developed in partnership with Novartis for early Parkinson’s disease, did not meet its primary and secondary clinical endpoints...Following the evaluation of the ORCHESTRA study results, UCB has initiated measures to terminate the extension phase of this program. This decision is based on the absence of evidence of clinical benefit in both primary and secondary endpoints. Disease biomarker data, in which there was a preliminary signal, is still being analyzed. The safety profile of minzasolmin was consistent with previous knowledge and no new safety concern has been identified."

P2a data • Trial termination • CNS Disorders • Parkinson's Disease

A Study to Assess the Bioavailability of a New Tablet Formulation of Minzasolmin and the Effect of Food in Healthy Participants (clinicaltrials.gov) - P1 | N=18 | Completed | Sponsor: UCB Biopharma SRL | Active, not recruiting ➔ Completed

Trial completion

A Study to Assess the Bioavailability of a New Tablet Formulation of Minzasolmin and the Effect of Food in Healthy Participants (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: UCB Biopharma SRL | Not yet recruiting ➔ Active, not recruiting

Enrollment closed

ORCHESTRA: A 18-month Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of Oral UCB0599 in Study Participants With Early-stage Parkinson's Disease (clinicaltrials.gov) - P2 | N=496 | Completed | Sponsor: UCB Biopharma SRL | Active, not recruiting ➔ Completed

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

An Extension Study to Evaluate the Long-Term Efficacy, Safety and Tolerability of Minzasolmin (UCB0599) in Study Participants With Parkinson's Disease (clinicaltrials.gov) - P2 | N=428 | Active, not recruiting | Sponsor: UCB Biopharma SRL | Enrolling by invitation ➔ Active, not recruiting

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

A Study to Assess the Bioavailability of a New Tablet Formulation of Minzasolmin and the Effect of Food in Healthy Participants (clinicaltrials.gov) - P1 | N=18 | Not yet recruiting | Sponsor: UCB Biopharma SRL

New P1 trial

An Extension Study to Evaluate the Long-Term Efficacy, Safety and Tolerability of Minzasolmin (UCB0599) in Study Participants With Parkinson's Disease (clinicaltrials.gov) - P2 | N=374 | Enrolling by invitation | Sponsor: UCB Biopharma SRL | Trial completion date: Dec 2029 ➔ Apr 2027 | Trial primary completion date: Dec 2029 ➔ Apr 2027

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

ORCHESTRA: A 18-month Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of Oral UCB0599 in Study Participants With Early-stage Parkinson's Disease (clinicaltrials.gov) - P2 | N=496 | Active, not recruiting | Sponsor: UCB Biopharma SRL | Trial primary completion date: Apr 2024 ➔ Oct 2024

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

A Study to Test Bioavailability of of 2 New Formulations of UCB0599 in Healthy Participants in Part A and to Test Safety, Tolerability, and Pharamacokinetic (PK) of UCB0599 in Healthy Japanese and Chinese Participants in Part B (clinicaltrials.gov) - P1 | N=73 | Completed | Sponsor: UCB Biopharma SRL | Recruiting ➔ Completed

Trial completion

Evaluation and Application of a PET Tracer in Preclinical and Phase 1 Studies to Determine the Brain Biodistribution of Minzasolmin (UCB0599). (PubMed, Mol Imaging Biol) - P1 | "Following positive preclinical results with the N-methyl labeled PET tracer, [C]minzasolmin was used in the phase 1 study, which demonstrated that minzasolmin readily crossed the blood-brain barrier and was well distributed throughout the brain. Safety and pharmacokinetic findings were consistent with previous early-phase studies (such as UP0077, NCT04875962)."

Journal • P1 data • Preclinical • CNS Disorders • Movement Disorders • Parkinson's Disease

A 18-month Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of Oral UCB0599 in Study Participants With Early-stage Parkinson's Disease (clinicaltrials.gov) - P2 | N=450 | Active, not recruiting | Sponsor: UCB Biopharma SRL | Phase classification: P2a ➔ P2

Phase classification • CNS Disorders • Movement Disorders • Parkinson's Disease

An Extension Study to Evaluate the Long-Term Efficacy, Safety and Tolerability of Minzasolmin (UCB0599) in Study Participants With Parkinson's Disease (clinicaltrials.gov) - P2 | N=374 | Enrolling by invitation | Sponsor: UCB Biopharma SRL | N=270 ➔ 374

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

Computational investigation on the effect of the peptidomimetic inhibitors (NPT100-18A and NPT200-11) on the α-synuclein and lipid membrane interactions. (PubMed, J Biomol Struct Dyn) - "The electron density profile analysis revealed the binding modes of NAC and C-terminal region of α-Syn (in the presence of NPT200-11 inhibitor) with lipid membrane are in the close vicinity from the lipid bilayer centre. Our findings in this study on α-Syn-membrane interactions may be useful for developing a new therapeutic approach for treating PD and other neurodegenerative disorders.Communicated by Ramaswamy H. Sarma."

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

In vivo effects of the alpha-synuclein misfolding inhibitor minzasolmin supports clinical development in Parkinson's disease. (PubMed, NPJ Parkinsons Dis) - P2a | "Minzasolmin (UCB0599) is an orally bioavailable and brain-penetrant small molecule ASYN misfolding inhibitor in clinical development as a disease-modifying therapeutic for Parkinson's disease...Reductions in ASYN pathology were correlated with improved aspects of gait and balance, reductions in CNS inflammation marker abundance, and normalized striatal DAT levels. These findings provide support for human dose determinations and have informed the translational strategy for clinical trial design and biomarker selection for the ongoing clinical studies of minzasolmin in patients living with early-stage Parkinson's disease (ClinicalTrials.gov ID: NCT04658186; EudraCT Number 2020-003265)."

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

A Study to Test Bioavailability of of 2 New Formulations of UCB0599 in Healthy Participants in Part A and to Test Safety, Tolerability, and Pharamacokinetic (PK) of UCB0599 in Healthy Japanese and Chinese Participants in Part B (clinicaltrials.gov) - P1 | N=72 | Recruiting | Sponsor: UCB Biopharma SRL | Not yet recruiting ➔ Recruiting

Enrollment open

A Study to Test Bioavailability of of 2 New Formulations of UCB0599 in Healthy Participants in Part A and to Test Safety, Tolerability, and Pharamacokinetic (PK) of UCB0599 in Healthy Japanese and Chinese Participants in Part B (clinicaltrials.gov) - P1 | N=72 | Not yet recruiting | Sponsor: UCB Biopharma SRL

New P1 trial

High-resolution structural information of membrane-bound α-synuclein provides insight into the MoA of the anti-Parkinson drug UCB0599. (PubMed, Proc Natl Acad Sci U S A) - "The explanatory power of the obtained high-resolution structural model is used to help determine the mode-of-actionof UCB0599. Here, it is shown that the ligand changes the ensemble of membrane-bound structures, which helps to explain the success this compound, currently being tested in Parkinson's disease patients in a phase 2 trial, has had in animal models of PD."

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

A 18-month Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of Oral UCB0599 in Study Participants With Early-stage Parkinson's Disease (clinicaltrials.gov) - P2a | N=450 | Active, not recruiting | Sponsor: UCB Biopharma SRL | Recruiting ➔ Active, not recruiting

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

A 18-month Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of Oral UCB0599 in Study Participants With Early-stage Parkinson's Disease (clinicaltrials.gov) - P2a | N=450 | Recruiting | Sponsor: UCB Biopharma SRL | Active, not recruiting ➔ Recruiting

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

A 18-month Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of Oral UCB0599 in Study Participants With Early-stage Parkinson's Disease (clinicaltrials.gov) - P2a | N=490 | Active, not recruiting | Sponsor: UCB Biopharma SRL | Recruiting ➔ Active, not recruiting

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