VY-HTT01 / Voyager, Sanofi - LARVOL DELTA

"Disease-modifying Huntington Disease candidates in development include: Tominersen @roche HTT-lowering ASO WVE-120101, WVE-120102 AMT-130 @uniQure_NV VY-HTT01 @VoyagerTx PTC518 @PTCBio Branaplam @Novartis Pepinemab-semaphorin 4D-targeted antibody @Vaccinex https://t.co/wvw7UgWlzf" (@BRAINCURES)

Clinical • Genetic Disorders • Huntington's Disease • Movement Disorders

[VIRTUAL] Efficient and precise processing of the optimized priamiRNA in a Huntingtinlowering AAV gene therapy: from cultured cells to nonhuman primates (ESGCT 2021) - "Taken together, our results highlight the importance of optimizing not only target lowering, but also efficiency and precision of priamiRNA processing across cultured cells, rodent models and nonhuman primate systems. VYHTT01 was selected using this approach, resulting in a highly potent and selective AAV gene therapy that harnesses the endogenous miRNA biogenesis pathway for HTT lowering."

CNS Disorders • Gene Therapies • Huntington's Disease • Movement Disorders

Safety and Tolerability Study With VY-HTT01, in Adults With Early Manifesting Huntington's Disease (clinicaltrials.gov) - P1b; N=0; Withdrawn; Sponsor: Voyager Therapeutics; N=22 ➔ 0; Not yet recruiting ➔ Withdrawn

Clinical • Enrollment change • Trial withdrawal • Genetic Disorders • Huntington's Disease • Movement Disorders

Voyager Therapeutics Announces First Quarter 2021 Financial Results and Corporate Updates (GlobeNewswire) - “Preclinical data for VY-HTT01 have shown strong reduction in mutant HTT protein in transgenic animal models of Huntington’s disease, resulting in improvement in disease phenotype. Additional data in non-human primates have demonstrated widespread distribution of VY-HTT01 across the striatum and cortex, which are core areas of disease pathology, and robust and durable reduction of HTT mRNA and protein....The Company expects to initiate the planned VYTAL Phase 1/2 clinical trial by the end of 2021 and anticipates providing initial topline safety, tolerability and biomarker data in 2022.”

New P1/2 trial • P1/2 data • Preclinical • CNS Disorders • Huntington's Disease

Safety and Tolerability Study With VY-HTT01, in Adults With Early Manifesting Huntington's Disease (clinicaltrials.gov) - P1b; N=22; Not yet recruiting; Sponsor: Voyager Therapeutics

Clinical • New P1 trial • Genetic Disorders • Huntington's Disease • Movement Disorders

Voyager Therapeutics Receives FDA Clearance of IND Application for Gene Therapy Candidate VY-HTT01 for Treatment of Huntington’s Disease (GlobeNewswire) - “Voyager Therapeutics…announced the U.S. Food and Drug Administration (FDA) has removed its clinical hold on the company’s Investigational New Drug (IND) application for VY-HTT01, a gene therapy candidate for the treatment of Huntington’s disease (HD), and confirmed that the company may proceed with its planned Phase 1/2 clinical trial. The decision was made following a comprehensive review of the Chemistry, Manufacturing and Controls information previously submitted to the FDA. Voyager plans to initiate VYTAL, a Phase 1/2 clinical trial of VY-HTT01, this year.”

IND • New P1/2 trial • CNS Disorders • Huntington's Disease

Voyager Therapeutics Announces Fourth Quarter and Full Year 2020 Financial Results and Corporate Updates (Yahoo Finance) - “The Investigational New Drug (IND) application for VY-HTT01 for the treatment of Huntington’s disease remains on clinical hold by the U.S. Food and Drug Administration (FDA) pending the resolution of additional information requests regarding specific chemistry, manufacturing and controls (CMC) topics, including drug device compatibility and drug substance and product characterization. Voyager plans to provide its complete response to the FDA in the first half of 2021 and to initiate its clinical evaluation of VY-HTT01 subject to and upon resolution of the clinical hold and the clearance of the IND application.”

IND • CNS Disorders • Huntington's Disease

Voyager Therapeutics Announces Third Quarter 2020 Financial Results and Corporate Updates (GlobeNewswire) - “‘…For our Huntington’s disease program, the FDA has provided clarity regarding the additional information it is requesting pursuant to our IND filing. We plan to work with the FDA to respond to these requests to allow for an IND clearance and the start of VY-HTT01’s clinical evaluation’...Following clearance of the IND by the FDA, Voyager expects to begin a Phase 1b clinical trial of VY-HTT01 in Huntington’s disease patients.”

IND • New trial • CNS Disorders • Huntington's Disease

Voyager Therapeutics Provides Regulatory Update on VY-HTT01 Program (GlobeNewswire) - "Voyager Therapeutics...announced that it has received feedback from the U.S. Food and Drug Administration (FDA) on the Investigational New Drug (IND) submission for VY-HTT01 for the treatment of Huntington’s disease. Voyager submitted the IND for VY-HTT01 in September 2020 and has been notified that the IND was placed on clinical hold pending the resolution of certain chemistry, manufacturing and controls (CMC) matters."

IND • CNS Disorders • Huntington's Disease

"$VYGR ↓ 20% AH. IND for VY-HTT01 for the treatment of Huntington’s disease on hold." (@BioStocks)

Huntington's Disease • Movement Disorders

[VIRTUAL] Behavioral benefit in YAC128 and BACHD mouse models of Huntington's disease with reduced human HTT protein following intrastriatal administration of VY-HTT01 gene therapy (HSG 2020) - No abstract available

Preclinical • Gene Therapies • Huntington's Disease • Movement Disorders

Voyager Therapeutics Announces Second Quarter 2020 Financial Results and Corporate Updates (GlobeNewswire) - “Voyager recently completed IND-enabling preclinical studies and is finalizing an IND application for VY-HTT01 in Huntington’s disease, which it expects to file with the U.S. Food and Drug Administration (FDA) in the second half of 2020….The Company plans to present preclinical data from the IND-enabling studies at a future scientific congress in the first half of 2021. Following clearance of the IND by the FDA, the Company expects to begin the first-in-human clinical trial of VY-HTT01 in Huntington’s disease patients.”

IND • New trial • Preclinical • CNS Disorders • Huntington's Disease

Voyager Therapeutics announces first quarter 2020 financial results and corporate updates (GlobeNewswire) - “Voyager is currently engaged in the ongoing conduct and review of preclinical studies for its Huntington’s disease program, VY-HTT01. Pending this review, Voyager is planning for the potential initiation of both a first-in-human Phase 1 study of VY-HTT01 and a prospective observational study of patients with late prodromal and early manifest Huntington’s disease. Voyager anticipates providing an update on the program in mid-2020.”

New P1 trial • Preclinical • CNS Disorders • Genetic Disorders • Huntington's Disease

Voyager Therapeutics announces fourth quarter and full year 2019 financial results and corporate updates (Yahoo Finance) - “Voyager is currently engaged in the ongoing conduct and review of preclinical studies for its Huntington’s disease program, VY-HTT01, and expects to provide an update on the program in the second quarter of 2020, including plans to file an IND application. Voyager also plans to initiate a prospective observational study of patients with late prodromal and early manifest Huntington’s disease in mid-2020.”

IND • New trial • Preclinical

Voyager Therapeutics announces third quarter 2019 financial results and corporate highlights (GlobeNewswire, Voyager Therapeutics, Inc.) - "In October 2019, Voyager presented data on VY-HTT01 for the treatment of Huntington’s disease at the European Society of Gene and Cell Therapy (ESGCT) Annual Congress. The data showed widespread, dose-dependent and durable huntingtin protein (HTT) lowering in relevant brain regions affected in Huntington’s disease following intraparenchymal administration of VY-HTT01 to non-human primates. Leveraging its related clinical experience in Parkinson’s disease, Voyager still expects to screen and enroll the first patient in the planned clinical trial during 2020."

Clinical data • Enrollment open • Preclinical

Voyager Therapeutics Reports Second Quarter 2019 Financial Results and Corporate Highlights (GlobeNewswire, Voyager Therapeutics, Inc.) - "Gained worldwide rights to VY-HTT01 for Huntington’s disease, expanding wholly-owned pipeline. Presented additional Phase 1b results for VY-AADC in patients with Parkinson’s disease at the 2019 American Academy of Neurology (AAN) Annual Meeting.....Research and development (R&D) expenses of $28.6 million for the second quarter of 2019 compared to R&D expenses of $16.5 million for the second quarter of 2018. The increase in R&D expenses related primarily to an increase in costs associated with the advancement of the VY-AADC RESTORE-1 Phase 2 clinical program..."

Clinical • Clinical data • Commercial

Voyager Therapeutics Announces Restructured Gene Therapy Relationship with Sanofi Genzyme and Portfolio Update (GlobeNewswire, Voyager Therapeutics, Inc.) - Gains worldwide rights to VY-HTT01 for Huntington’s disease. Resources to be reallocated to VY-HTT01 and other programs.. rights to the VY-FXN01 Friedreich’s ataxia program. rights to VY-FXN01 are, in turn, transferred from Voyager to Neurocrine Biosciences under the terms of the collaboration agreement between Voyager and Neurocrine Biosciences announced in January 2019.

Commercial • Preclinical • Regulatory

Voyager Therapeutics Reports First Quarter 2019 Financial Results and Corporate Highlights (GlobeNewswire, Voyager Therapeutics, Inc.) - “…VY-HTT01 granted Orphan Drug Designation (ODD) by the U.S. Food and Drug Administration (FDA) for the treatment of Huntington’s disease.”

Orphan drug

Significant Reduction of Huntingtin Gene Expression in Cortex, Putamen and Caudate of Large Mammals with Combined Putamen and Thalamus Infusions of VY-HTT01, an AAV Gene Therapy Targeting Huntingtin for the Treatment of Huntington’s Disease (ASGCT 2019) - "Furthermore, good tolerability was supported by in-life observations, clinical pathology and histopathological analysis of the brain 5 weeks after dosing. Taken together, these results demonstrate the potential of VY-HTT01, an AAV gene therapy targeting HTT with RNAi, administered with combined infusions into the putamen and thalamus, for the treatment of Huntington’s disease."

Voyager Therapeutics reports fourth quarter and full year 2018 financial results and corporate highlights (GlobeNewswire) - “Presented preclinical data for VY-HTT01 for Huntington’s disease…One-time delivery of VY-HTT01 generated significant reduction of HTT gene expression in deeper tissues and outer layers of the brain of non-human primates…. Received 510(k) regulatory clearance of V-TAG™ from the Center for Devices and Radiological Health of the FDA…. V-TAG™ could also be used for Voyager’s Huntington’s disease and other programs….Advance VY-HTT01 for Huntington’s disease and VY-SOD102 for ALS-SOD1 towards clinical trials. Preclinical pharmacology and toxicology studies are underway to support potential filings of IND applications for both programs later this year.“

IND • Preclinical