WVE-003 / Wave Life Sciences, Takeda - LARVOL DELTA

Huntington's Disease Clinical Trials Update: September 2024. (PubMed, J Huntingtons Dis) - "In this edition of the Huntington's Disease Clinical Trials Update, we expand on the ongoing extension study of PTC518 from PTC Therapeutics, including 12-month interim results from the parent study. We also discuss 24-month interim results from uniQure's AMT-130 program and 28-week follow-up results from Wave Life Sciences' SELECT-HD clinical trial of WVE-003. Additionally, we provide a comprehensive listing of all currently registered and ongoing clinical trials in Huntington's disease."

Journal • Review • Huntington's Disease • Movement Disorders

Wave Life Sciences Highlights Strategic Priorities and Expected 2025 Milestones Ahead of J.P. Morgan Presentation (GlobeNewswire) - "Wave expects to initiate dosing in the INLIGHT clinical trial for WVE-007 in the first quarter of 2025 and to deliver proof-of-concept clinical data in 2025. Proof-of-concept data are expected to include safety, tolerability, and biomarkers reflective of healthy weight loss....Planning is underway for a global, potentially registrational Phase 2/3 study of WVE-003, including finalization of key aspects of design. Wave expects to submit an Investigational New Drug ('IND') application for WVE-003 in the second half of 2025."

Clinical data • IND • New P2/3 trial • New trial • CNS Disorders • Huntington's Disease • Metabolic Disorders • Obesity

Wave Life Sciences Reports Third Quarter 2024 Financial Results and Provides Business Update (GlobeNewswire) - "Expected upcoming milestone: Wave expects to submit an Investigational New Drug ('IND') application for WVE-003 in the second half of 2025."

IND • CNS Disorders • Huntington's Disease

Goodbye Wave: Takeda axes Huntington’s pact, freeing partner to pursue fresh interest (FierceBiotech) - "Takeda is walking away from the last target in a collaboration with Wave Life Sciences into which the Japanese pharma has already sunk $260 million over the past six years. The decision leaves Wave holding a Huntington’s disease program that it says has caught the attention of other drug developers....Takeda reached its decision late last week. In a notice published Tuesday, Wave said Takeda was turning down its option. As WVE-003 was the last program standing in a once-wider collaboration, the decision brought the curtain down on the alliance."

Licensing / partnership • CNS Disorders • Huntington's Disease

Preclinical evaluation of stereopure antisense oligonucleotides for allele-selective lowering of mutant HTT. (PubMed, Mol Ther Nucleic Acids) - P1/2 | "Through comparisons with a surrogate for the nonselective investigational compound tominersen, we also demonstrate that allele-selective molecules display equivalent potency toward mHTT with improved durability while sparing wtHTT. Our preclinical findings support the advancement of WVE-003, an investigational allele-selective compound currently in clinical testing (NCT05032196) for the treatment of patients with HD."

Journal • Preclinical • Huntington's Disease • Movement Disorders

Study of WVE-003 in Patients With Huntington's Disease (clinicaltrials.gov) - P1/2 | N=47 | Completed | Sponsor: Wave Life Sciences Ltd. | Recruiting ➔ Completed | Trial completion date: Dec 2024 ➔ May 2024 | Trial primary completion date: Dec 2024 ➔ May 2024

Trial completion • Trial completion date • Trial primary completion date • Genetic Disorders • Huntington's Disease • Movement Disorders

Wave Life Sciences Announces Positive Results from Phase 1b/2a SELECT-HD Trial with First Clinical Demonstration of Allele-Selective Mutant Huntingtin Lowering in Huntington’s Disease (GlobeNewswire) - P1b/2a | N=54 | SELECT-HD (NCT05032196) | Sponsor: Wave Life Sciences Ltd. | "Wave Life Sciences Ltd...today announced positive results from its Phase 1b/2a SELECT-HD clinical trial of WVE-003...WVE-003 was generally safe and well-tolerated, with no Serious Adverse Events (SAEs) reported; ventricular volume was in line with natural history. Significant mHTT protein lowering was observed throughout the 28-week assessment period...'We are very proud to have demonstrated mHTT lowering of 46%, with preservation of wtHTT, and are encouraged to see these reductions in mHTT significantly correlating with a slowing in caudate atrophy after just 28 weeks.'...Wave remains on track...to initiate a clinical trial for its INHBE GalNAc siRNA (WVE-007) for obesity in 1Q 2025..."

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

Understanding Pharmacy Costs and the Changing Treatment Landscape in Huntington's Disease (HD) in the US: A Systematic Literature Review (SLR) and Database Review for Disease-Modifying Therapies (DMT) in Development (ISPOR 2024) - "Motor symptoms incur the greatest annual drug cost, with high median costs per patient (2019) for tetrabenazine ($24,996), deutetrabenazine ($69,972), and valbenazine ($76,908). Ten clinical trials are investigating potential future DMTs: two-antisense oligonucleotides (n=5; Tominersen [RO7234292, ISIS 443139], WVE-003), two-RNA-targeting small molecules (n=2; PTC518, Branaplam), monoclonal antibodies (n=2; ANX005, VX15/2503), and gene therapy (n=1; rAAV5-miHTT). Pharmacy costs for symptomatic treatment are substantial in HD, with these costs increasing as HD progresses and symptom severity increases. This significant burden illustrates the importance of developing new DMTs that can prevent or slow disease progression for patients with HD."

Review • CNS Disorders • Depression • Gene Therapies • Huntington's Disease • Mood Disorders • Movement Disorders • Psychiatry

Wave Life Sciences Highlights Recent Achievements and Upcoming 2024 Milestones (GlobeNewswire) - "WVE-003....Wave expects to report data from the 30 mg multi-dose cohort with extended follow-up, along with all single-dose data, in the second quarter of 2024. These data are expected to enable decision-making on the program and support the opt-in package for Takeda."

P1/2 data • CNS Disorders • Huntington's Disease

Study of WVE-003 in Patients With Huntington's Disease (clinicaltrials.gov) - P1/2 | N=54 | Recruiting | Sponsor: Wave Life Sciences Ltd.

Trial completion date • Trial primary completion date • Genetic Disorders • Huntington's Disease • Movement Disorders

Study of WVE-003 in Patients With Huntington's Disease (clinicaltrials.gov) - P1/2 | N=54 | Recruiting | Sponsor: Wave Life Sciences Ltd. | Phase classification: P1b/2a ➔ P1/2 | N=36 ➔ 54

Enrollment change • Phase classification • Genetic Disorders • Huntington's Disease • Movement Disorders

Wave Life Sciences Highlights Growth Strategy for Building the Leading RNA Medicines Company in Annual R&D Day (GlobeNewswire) - "The multidose portion of the SELECT-HD clinical trial is ongoing and has been enrolling with high demand. Wave expects to deliver complete data from the first multidose cohort with extended follow-up in the second quarter of 2024 to enable decision-making, in addition to the update on single dose and available multidose data in the second half of this year."

P1/2 data • CNS Disorders • Huntington's Disease

Wave Life Sciences Announces Topline Results from Phase 1b/2a FOCUS-C9 Study of WVE-004 for C9orf72-associated Amyotrophic Lateral Sclerosis and Frontotemporal Dementia (GlobeNewswire) - P1b/2a | N=35 | FOCUS-C9 (NCT04931862) | Sponsor: Wave Life Sciences Ltd. | "Wave Life Sciences...today announced topline results from the Phase 1b/2a FOCUS-C9 study evaluating WVE-004 as an investigational treatment for C9orf72-associated amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9-ALS/FTD). The results include data from a planned analysis of the study, where participants received multiple 10 mg doses of WVE-004 or placebo every 12 weeks (Q12W) or every 4 weeks (Q4W), as well as an additional 20 mg single dose cohort....Wave remains on track to share data from its Phase 1b/2a SELECT-HD study in Huntington’s disease investigating WVE-003 in the second half of 2023....WVE-006, into a clinical trial in Alpha-1 antitrypsin deficiency in the second half of 2023. In addition, the company continues to advance preclinical research with its modalities that restore or repair endogenous proteins, including additional RNA editing programs."

New trial • P1/2 data • Preclinical • Alpha-1 Antitrypsin Deficiency • Amyotrophic Lateral Sclerosis • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Genetic Disorders • Huntington's Disease

Study of WVE-003 in Patients With Huntington's Disease (clinicaltrials.gov) - P1b/2a | N=36 | Recruiting | Sponsor: Wave Life Sciences Ltd. | Trial completion date: Dec 2022 ➔ Jun 2023 | Trial primary completion date: Dec 2022 ➔ Jun 2023

Trial completion date • Trial primary completion date • Genetic Disorders • Huntington's Disease • Movement Disorders

Wave Life Sciences Reports Third Quarter 2022 Financial Results and Provides Business Update (GlobeNewswire) - “Key Anticipated Upcoming Milestones: WVE-003 for HD: Additional single-dose biomarker and safety clinical data expected in 1H 2023; WVE-004 for C9-ALS and C9-FTD: Clinical data from all cohorts in the FOCUS-C9 trial expected in 1H 2023….Research and development expenses were $27.6 million in the third quarter of 2022 as compared to $31.1 million in the same period in 2021. The decrease in research and development expenses in the third quarter was primarily due to decreased external expenses related to our HD programs...”

Biomarker • Commercial • P1/2 data • Amyotrophic Lateral Sclerosis • CNS Disorders • Frontotemporal Lobar Degeneration • Huntington's Disease

Wave Life Sciences Announces Positive Update from Phase 1b/2a SELECT-HD Trial with Initial Results Indicating Allele-Selective Target Engagement with WVE-003 in Huntington’s Disease (GlobeNewswire) - P1b/2a | N= 36 | SELECT-HD (NCT05032196) | Sponsor: Wave Life Sciences Ltd. | “observations include: Single doses of WVE-003 up to 90 mg appeared generally safe and well-tolerated….Among participants in the 30 and 60 mg WVE-003 cohorts, the mean reduction in CSF mHTT from baseline was 22% (median reduction 30%) at 85 days following a single dose….Increases in neurofilament light chain (NfL) from baseline were observed in some participants. Wave will continue to monitor trends in NfL as SELECT-HD advances….Based on these data, Wave is adapting the SELECT-HD clinical trial to expand the single dose cohorts and will also continue advancing the 90 mg cohort for biomarker analysis at day 85. Additional single dose biomarker and safety data are expected in the first half of 2023.”

Biomarker • P1/2 data • CNS Disorders • Huntington's Disease

Wave Life Sciences Reports Second Quarter 2022 Financial Results and Provides Business Update (GlobeNewswire) - “Key Anticipated Upcoming Milestones: WVE-004 for C9-ALS and C9-FTD: Additional single and multidose clinical data for WVE-004 expected in 2H 2022. Planning underway to initiate an open-label extension (OLE) clinical trial in 2H 2022. WVE-003 for HD: Clinical data expected in 2H 2022 for WVE-003 to provide further insight into the clinical effects of PN chemistry and enable decision-making for this program….Research and development expenses were $29.7 million in the second quarter of 2022 as compared to $31.6 million in the same period in 2021. The decrease in research and development expenses in the second quarter was primarily due to decreased external expenses related to our previously disclosed discontinued PRECISION-HD programs…”

Commercial • New trial • P1/2 data • Amyotrophic Lateral Sclerosis • CNS Disorders • Frontotemporal Lobar Degeneration • Huntington's Disease

Wave Life Sciences Reports First Quarter 2022 Financial Results and Provides Business Update (GlobeNewswire) - “Wave plans to share…clinical data in an oral presentation at the upcoming European Network to Cure ALS (ENCALS) Meeting in Edinburgh, Scotland, which is taking place June 1 – 3, 2022….Key Anticipated 2022 Milestones: WVE-004 for C9-ALS and C9-FTD: Additional single and multidose clinical data for WVE-004 expected throughout 2022. Wave expects to use these data to optimize WVE-004 dose level and frequency, as well as to enable discussions with regulatory authorities regarding the next phase of development later in 2022. Planning underway to initiate an open-label extension (OLE) clinical trial in mid-2022….Research and development expenses were $27.5 million in the first quarter of 2022…The decrease in research and development expenses in the first quarter was primarily due to decreased external expenses related to our previously disclosed discontinued PRECISION-HD programs…”

Commercial • New trial • P1/2 data • Regulatory • Amyotrophic Lateral Sclerosis • CNS Disorders • Frontotemporal Lobar Degeneration • Huntington's Disease

Wave Life Sciences Reports Fourth Quarter and Full Year 2021 Financial Results and Provides Business Update (GlobeNewswire) - “WVE-004 for C9orf72-associated amyotrophic lateral sclerosis (C9-ALS) and frontotemporal dementia (C9-FTD): FOCUS-C9 is an ongoing, double-blind, adaptive, Phase 1b/2a clinical trial of WVE-004. WVE-003 targeting SNP3 for Huntington’s disease (HD): SELECT-HD is an ongoing, double-blind, adaptive, Phase 1b/2a clinical trial of WVE-003. Upcoming clinical milestones: Wave expects to share clinical data in 2022 for WVE-004, WVE-003…to provide insight into the clinical effects of PN chemistry and enable decision-making for each program.”

P1/2 data • Amyotrophic Lateral Sclerosis • CNS Disorders • Frontotemporal Lobar Degeneration • Huntington's Disease

SELECT-HD: An Adaptive Randomized Controlled Phase 1B/2A Trial of WVE-003 in Participants with Early Manifest Huntington’s Disease (HSG 2021) - "This first-in-human study will provide proof of concept for pharmacodynamic effects, as well as PK, safety, and tolerability of WVE-003 in early manifest Huntington’s disease."

Clinical • P1/2 data • CNS Disorders • Huntington's Disease • Movement Disorders

Dosing Starts in SELECT-HD Trial That Seeks to Lower mHTT Levels (Huntington’s Disease News) - “A Phase 1/2 trial evaluating Wave Life Science’s investigational therapy WVE-003 for Huntington’s disease has started dosing patients, the company has announced. The SELECT-HD trial (NCT05032196), underway in clinical sites in Australia, Germany, Poland, and the U.K., is currently looking to enroll 36 Huntington’s patients, ages 25 to 60, at the early stages of the disease and with a specific single nucleotide polymorphism (SNP), called SNP3, in the mutated HTT gene. An SNP is a change in a single nucleotide, the building blocks of DNA….The trial is scheduled to end in December 2022.”

Trial completion date • Trial status • CNS Disorders • Huntington's Disease

A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 1b/2a Study of WVE-003 Administered Intrathecally in Patients With Huntington’s Disease (clinicaltrialsregister.eu) - P1/2; N=24; Ongoing; Sponsor: Wave Life Sciences UK Limited

Clinical • New P1/2 trial • Huntington's Disease • Movement Disorders • MRI

Wave Life Sciences Highlights Pipeline Progress and Expansion Leveraging New PN Backbone Chemistry Modifications (GlobeNewswire) - “‘We also plan to deliver comprehensive data results from the ongoing PRECISION-HD trials late in the first quarter to enable a decision regarding potential Phase 3 development for WVE-120101 and WVE-120102...' Wave expects to initiate dosing in three proof-of-concept studies in 2021, which will assess target engagement, impact on key disease biomarkers, and initial safety for WVE-003 in Huntington’s disease (HD), WVE-004 in amyotrophic lateral sclerosis (ALS)…In December 2020, Wave submitted a CTA for WVE-004. Wave expects to initiate dosing in ALS and FTD patients with G4C2 expansions in 2021.”

New trial • P3 data • Amyotrophic Lateral Sclerosis • CNS Disorders • Frontotemporal Lobar Degeneration • Huntington's Disease

Wave Life Sciences Reports Third Quarter 2020 Financial Results and Provides Business Update (GlobeNewswire) - “‘…on track to file clinical trial applications for WVE-003 for Huntington’s disease and WVE-004 for amyotrophic lateral sclerosis and frontotemporal dementia this quarter.’…Wave is developing a third allele-selective HD candidate, WVE-003, which is designed to selectively target an undisclosed SNP on the mHTT mRNA transcript (SNP3), while leaving wtHTT protein relatively intact….Wave expects to initiate clinical development of WVE-004 with the submission of a CTA in the fourth quarter of 2020….Wave expects to initiate clinical development of WVE-003 with the submission of a clinical trial application (CTA) in the fourth quarter of 2020.”

New trial • Amyotrophic Lateral Sclerosis • CNS Disorders • Huntington's Disease

Wave Life Sciences to Highlight Preclinical ADAR Editing Data and Neurology Programs at TIDES and OTS Annual Meetings (GlobeNewswire) - “Wave Life Sciences…announced today that it will highlight its ADAR (adenosine deaminases acting on RNA)-mediated RNA editing technology ('ADAR editing') and its neurology programs in Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) at upcoming conferences, including the TIDES…presentation at TIDES will highlight Wave’s neurology pipeline, including its C9orf72 variant-selective silencing program for ALS and FTD, as well as its SNP3 program for HD, both of which are expected to initiate clinical development with the submission of clinical trial applications in the fourth quarter of 2020.”

Clinical • Amyotrophic Lateral Sclerosis • CNS Disorders • Huntington's Disease