ezaladcigene resoparvovec (VY-AADC) / Voyager - LARVOL DELTA

VY-AADC02 for Parkinson's Disease With Motor Fluctuations (RESTORE-1) (clinicaltrials.gov) - P1 | N=14 | Completed | Sponsor: Neurocrine Biosciences | Active, not recruiting ➔ Completed

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

Observational, Long-term Extension Study for Participants of Prior VY-AADC01 Studies (clinicaltrials.gov) - P=N/A | N=14 | Completed | Sponsor: Neurocrine Biosciences | Active, not recruiting ➔ Completed | Trial completion date: May 2026 ➔ Jul 2023 | Trial primary completion date: Apr 2026 ➔ Jul 2023

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

VY-AADC02 for Parkinson's Disease With Motor Fluctuations (RESTORE-1) (clinicaltrials.gov) - P1 | N=14 | Active, not recruiting | Sponsor: Neurocrine Biosciences | Phase classification: P2 ➔ P1 | N=85 ➔ 14 | Trial completion date: Dec 2023 ➔ Nov 2024 | Trial primary completion date: Dec 2023 ➔ Nov 2024

Enrollment change • Metastases • Phase classification • Surgery • Trial completion date • Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

Observational, Long-term Extension Study for Participants of Prior VY-AADC01 Studies (clinicaltrials.gov) - P=N/A | N=14 | Active, not recruiting | Sponsor: Neurocrine Biosciences | Enrolling by invitation ➔ Active, not recruiting | N=23 ➔ 14

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

Safety and Efficacy Study of VY-AADC01 for Advanced Parkinson's Disease (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: Neurocrine Biosciences | Active, not recruiting ➔ Completed | Trial completion date: Dec 2021 ➔ Aug 2021 | Trial primary completion date: Dec 2021 ➔ Aug 2021

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

VY-AADC02 for Parkinson's Disease With Motor Fluctuations (RESTORE-1) (clinicaltrials.gov) - P2 | N=85 | Active, not recruiting | Sponsor: Neurocrine Biosciences | Trial completion date: Dec 2022 ➔ Dec 2023 | Trial primary completion date: Dec 2022 ➔ Dec 2023

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

Voyager Therapeutics Reports Third Quarter 2021 Financial and Operating Results (GlobeNewswire) - “R&D Expenses: Research and development expenses were $17.9 million for the third quarter of 2021, compared to $25.0 million for the same period in 2020. The decrease in R&D expenses was primarily related to lower research and development employee-related expenses as well as manufacturing and clinical expenses for the VY-AADC program for Parkinson’s disease.”

Commercial • CNS Disorders • Parkinson's Disease

VY-AADC01 Gene Therapy Demonstrates Safety, Improved Motor Function in Phase 1 Trial (NeurologyLive) - "Lead author Chadwick Christine, MD...assessed safety and tolerability of VY-AADC01, an experimental AAV2 gene therapy encoding the human aromatic L-amino acid decarboxylase (AADC) enzyme in 15 patients aged 40 to 70 years with moderately advanced PD. The treatment was delivered via bilateral, intraoperative MRI-guided putaminal infusions to 3 cohorts, with 5 participants each."

P1 data

Safety of AADC Gene Therapy for Moderately Advanced Parkinson Disease: Three-Year Outcomes From the PD-1101 Trial. (PubMed, Neurology) - P1 | "VY-AADC01 and the surgical administration procedure were well-tolerated and resulted in stable or improved motor function and quality of life across cohorts, as well as reduced PD medication requirements in cohorts 2 and 3 over 3 years.Clinicaltrials.gov identifier: NCT01973543 CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that, in patients with moderately advanced PD and motor fluctuations, putaminal infusion of VY-AADC01 is well tolerated and may improve motor function."

Clinical • Journal • Atrial Fibrillation • Cardiovascular • CNS Disorders • Gene Therapies • Movement Disorders • Parkinson's Disease • Pulmonary Embolism • Respiratory Diseases • MRI

[VIRTUAL] The PD-1102 trial in advanced Parkinson’s disease: safety and clinical outcomes from a 3-year phase 1b study of AADC gene therapy administered via a posterior approach (MDS Congress 2021) - "Administration of VY-AADC01 to the putamen delivered via a posterior approach was well tolerated. Relative to baseline, 3-year data show a reduction in daily PD medication, stable or improved motor function, and improved quality of life. These results are consistent with data from the 2 higher-dose cohorts of the PD-1101 trial [1]."

Clinical • Clinical data • P1 data • Cerebral Hemorrhage • CNS Disorders • Dystonia • Parkinson's Disease • MRI

Voyager Therapeutics Provides Update on NBIb-1817 (VY-AADC) Gene Therapy Program (GlobeNewswire) - "Voyager Therapeutics...announced that Neurocrine Biosciences...provided notice of termination of the Parkinson’s disease portion of the collaboration agreement, effective August 2, 2021...Neurocrine’s decision to terminate the NBIb-1817 (VY-AADC) program was based on a portfolio review and prioritization of its current pipeline assets. Voyager plans to support Neurocrine, the IND holder and sponsor of the RESTORE-1 Phase 2 clinical trial..."

Licensing / partnership • CNS Disorders • Gene Therapies • Parkinson's Disease

Neurocrine Biosciences Provides Preliminary Fourth Quarter and Full-Year 2020 Net Product Sales Results and 2021 Program Milestones (PRNewswire) - "NBI-827104...Rare Pediatric Epilepsy, Epileptic Encephalopathy with Continuous Spike and Wave During Sleep, Neurological Indication: Continue Phase II Enrollment. NBI-921352: Focal Onset Seizure in Adults, Rare Pediatric Epilepsy: SCN8A-DEE: Initiate Phase II, Ongoing Dialogue with FDA. NBIb-1817: Gene Therapy for Parkinson's Disease: Determine Regulatory Path with FDA."

Enrollment status • FDA event • New P2 trial • CNS Disorders • Epilepsy • Parkinson's Disease

Voyager Therapeutics Provides Update on NBIb-1817 (VY-AADC) Gene Therapy Program (GlobeNewswire) - "Voyager Therapeutics, Inc....today announced that the U.S. Food and Drug Administration (FDA) has notified Neurocrine Biosciences...that it has placed a clinical hold on the RESTORE-1 clinical trial of NBIb-1817 (VY-AADC)....The DSMB has requested additional patient level data from the trial and now plans to review these data in early 2021. The clinical hold follows the submission by Neurocrine Biosciences of an IND Safety Report related to the observation of MRI abnormalities in some RESTORE-1 study participants. The clinical implications of this observation are currently unknown and are being evaluated."

DSMB • Trial suspension • CNS Disorders • Parkinson's Disease

Voyager Therapeutics Announces Third Quarter 2020 Financial Results and Corporate Updates (GlobeNewswire) - "In November 2020, the Data Safety Monitoring Board (DSMB) for the RESTORE-1 Phase 2 clinical trial reviewed certain patient imaging data from the ongoing trial and recommended a pause in the dosing of patients in RESTORE-1 pending review by the DSMB of additional data....In response to the DSMB’s recommendation, Voyager and Neurocrine have decided to delay the planned resumption of patient screening in the RESTORE-1 trial until the DSMB is able to complete its evaluation. The DSMB is expected to consider additional patient data before year-end. Neurocrine is preparing an expedited safety report that will be submitted to the FDA within the 15-day reporting window."

DSMB • Trial suspension • CNS Disorders • Parkinson's Disease

Observational, Long-term Extension Study for Participants of Prior VY-AADC01 Studies (clinicaltrials.gov) - P=N/A; N=23; Enrolling by invitation; Sponsor: Neurocrine Biosciences; N=50 ➔ 23; Trial completion date: Aug 2026 ➔ Apr 2026; Trial primary completion date: Aug 2026 ➔ Apr 2026

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

[VIRTUAL] AADC gene therapy administered via a posterior approach: 18-month results from the PD-1102 trial in advanced Parkinson’s disease (MDS Congress 2020) - "VY-AADC01 administered using a single posterior trajectory per putamen was well tolerated. Average daily PD medication doses were substantially reduced, and study participants showed stable or improved motor function 18 months following VY-AADC01 administration. These findings were consistent with those observed in the 2 higher-dose cohorts of the PD-1101 trial.1"

Cerebral Hemorrhage • CNS Disorders • Dystonia • Parkinson's Disease

[VIRTUAL] Three-year safety and clinical outcomes from the PD-1101 trial of AADC gene therapy for advanced Parkinson’s disease (MDS Congress 2020) - "Three years after VY-AADC01 administration, participants in cohorts 2 and 3 of the PD-1101 trial for advanced PD continued to require substantially less antiparkinsonian medications and showed stable or improved motor function and quality of life."

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

Neurocrine Biosciences and Voyager Therapeutics Present New Long-Term Three-Year Data Demonstrating that One-Time Treatment with an Investigational Gene Therapy Showed Sustained Improvement in Motor Function in Patients with Parkinson's Disease (PRNewswire) - P1, N=15; PD-1101 (NCT01973543); P1, N=16; PD-1102 (NCT03065192); Sponsor: Neurocrine Biosciences; "Neurocrine Biosciences, Inc....and Voyager Therapeutics, Inc....today announced data from PD-1101, a Phase Ib...demonstrating...NBIb-1817 (VY-AADC), showed sustained improvement in motor function including greater 'On' time without troublesome dyskinesia...in patients with Parkinson's disease....14 out of 15 patients treated with NBIb-1817 continued to show an improvement in disease staging after three years...These new data, along with two-year data from another open-label Phase Ib trial, PD-1102, were presented today at the MDS Virtual Congress 2020, September 12–16, 2020....'We plan to re-initiate enrollment in our registrational RESTORE-1 clinical trial with NBIb-1817 this year and look forward to further evaluating NBIb-1817 in patients with Parkinson's disease.'"

Enrollment status • P1 data • CNS Disorders • Parkinson's Disease

Neurocrine Biosciences to Present New Data from its Movement Disorder Programs for Tardive Dyskinesia and Parkinson's Disease at Upcoming Scientific Meetings (PRNewswire) - "Neurocrine Biosciences, Inc....today announced it will present new data as part of 30 abstracts...for tardive dyskinesia and Parkinson's disease at...2020 Psych Congress on September 10–13 and the MDS Virtual Congress 2020 on September 12–16....New Phase III data analyses of ONGENTYS® (opicapone) capsules as an add-on therapy to levodopa/carbidopa in patients with Parkinson's disease experiencing motor 'off' episodes, and new Phase Ib data of an investigational gene therapy, NBIb-1817 (VY-AADC), evaluating the three-year safety and clinical outcomes of patients with advanced Parkinson's disease."

P1 data • P3 data • Retrospective data • CNS Disorders • Parkinson's Disease

Voyager Therapeutics Announces Second Quarter 2020 Financial Results and Corporate Updates (GlobeNewswire) - "Voyager and Neurocrine Biosciences plan to present the final three-year data on all three cohorts of the PD-1101 Phase 1b trial, as well as two-year data from the PD-1102 Phase 1 trial, at the MDS Virtual Congress 2020 being held in September....Voyager and Neurocrine Biosciences expect patient screening and enrollment to resume at clinical sites in the RESTORE-1 Phase 2 clinical trial during the second half of 2020....Voyager and Neurocrine Biosciences plan to initiate the RESTORE-2 Phase 3 global registrational clinical study of VY-AADC (NBIb-1817) in Parkinson’s disease during the first half of 2021."

Enrollment status • P1 data • Trial initiation date • CNS Disorders • Parkinson's Disease

Voyager Therapeutics announces positive longer-term data for VY-AADC for Parkinson’s disease (GlobeNewswire) - P1b, N=15; "Voyager Therapeutics...today announced positive longer-term results from the open-label, dose-escalating Phase 1b trial of VY-AADC demonstrating sustained improvements in patients’ motor function. Patients in the two highest dose cohorts (Cohorts 3 and 2) experienced mean improvements in diary on-time without troublesome dyskinesia (good ON time) of 1.7 hours per day at 18 months and 2.7 hours per day at two years, respectively."

P1 data • CNS Disorders • Parkinson's Disease

VY-AADC01 in Medically Refractory Parkinson’s Disease: Safety and Efficacy of a Phase 1b Dose-Ranging Study 12 Months and Beyond (ANA 2018) - "VY-AADC01 was well tolerated in this ongoing Phase 1b study, with evidence for dose-dependent responses that are both clinically important and durable."

Clinical • P1 data • CNS Disorders • Parkinson's Disease

Safety and Efficacy Study of VY-AADC01 for Advanced Parkinson's Disease (clinicaltrials.gov) - P1; N=16; Active, not recruiting; Sponsor: Voyager Therapeutics; Recruiting ➔ Active, not recruiting

Enrollment closed • Alzheimer's Disease • Biosimilar • CNS Disorders • Gene Therapies • Genetic Disorders • Parkinson's Disease

Voyager Therapeutics announces longer-term data from ongoing Phase 1b trial of VY-AADC for advanced Parkinson’s disease (GlobeNewswire) - P1b, N=15; "Voyager Therapeutics...today announced longer-term data from its ongoing dose-ranging Phase 1b trial of VY-AADC in advanced Parkinson’s disease. The results continue to demonstrate durable, dose-dependent and time-dependent improvements across multiple measures of patients’ motor function after a one-time administration of the gene therapy....Voyager plans to meet with the Food and Drug Administration (FDA) during a Type C meeting to discuss the current Phase 1b data and designs for the pivotal program. Voyager expects...Phase 2-3 pivotal program, which remains on track to dose the first patient during mid-2018."

FDA event • New P2/3 trial • P1 data • CNS Disorders • Parkinson's Disease

Efficacy and safety of AAV2 gene therapy in children with aromatic L-amino acid decarboxylase deficiency: an open-label, phase 1/2 trial. (PubMed, Lancet Child Adolesc Health) - P1/2; "Our findings suggest that intraputaminal injection of AAV2-hAADC is well tolerated and might improve motor development in children with AADC deficiency."

Clinical • Journal • P1/2 data • Biosimilar • Immunology • Ophthalmology