GSK5462688 / Wave Life Sciences, GSK - LARVOL DELTA

A Phase 1 Research Study to Evaluate Safety, Tolerability, and Pharmacokinetics of WVE-006 in Healthy Participants With Wild-type AAT Expression (RestorAATion-1) (clinicaltrials.gov) - P1 | N=47 | Completed | Sponsor: Wave Life Sciences Ltd. | Recruiting ➔ Completed

Trial completion • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases

GalNAc-RNA Editing Programs (GlobeNewswire) - "RestorAATion-2 is a Phase 1b/2a open-label study with both single and multiple ascending dose portions, which is evaluating the safety, tolerability, pharmacodynamics and pharmacokinetics of WVE-006 in individuals with AATD who have the homozygous Pi*ZZ mutation....Wave expects to share multi-dose data for WVE-006 from RestorAATion-2 in 2025."

P1/2 data • Alpha-1 Antitrypsin Deficiency

RNA EDITING FOR THE TREATMENT OF ALPHA-1 ANTITRYPSIN DEFICIENCY (AASLD 2024) - "These findings highlight the potential of WVE-006 to address both liver and lung manifestations of AATD. Wave Life Sciences is evaluating WVE-006 into clinical trials. The clinical program (RestorAATion) is designed to provide proof of concept for the first RNA editing therapy in humans."

Alpha-1 Antitrypsin Deficiency • Chronic Obstructive Pulmonary Disease • Genetic Disorders • Hepatology • Immunology • Inflammation • Liver Failure • Pulmonary Disease • Respiratory Diseases • ADAR • SERPINA1

An RNA Editing Approach for the Treatment of Alpha-1 Antitrypsin Deficiency (AATD) (ERS 2024) - "WVE-006 directed editing of SERPINA1 RNA in the mouse liver, which led to the production of functional M-AAT protein, with total AAT in serum reaching levels higher than the 11µM threshold believed to lower risk for COPD."

Alpha-1 Antitrypsin Deficiency • Chronic Obstructive Pulmonary Disease • Genetic Disorders • Hepatology • Immunology • Pulmonary Disease • Respiratory Diseases • ELANE • SERPINA1

RestorAATion-2: A Phase 1b/2a, Open-label Single Ascending Doses and Multiple Ascending Doses Study in Participants With Pi*ZZ AATD (clinicaltrials.gov) - P1/2 | N=24 | Recruiting | Sponsor: Wave Life Sciences Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases

RNA editing for the treatment of Alpha-1 antitrypsin deficiency (EASL-ILC 2024) - "These findings highlight the potential of GalNAc-AIMers to address both liver and lung manifestations of AATD. Wave Life Sciences is advancing WVE-006, an investigational GalNAc-AIMer, into clinical trials for the treatment of AATD. This clinical program (RestorAATion) is designed to provide proof of concept for the first RNA editing therapy in humans."

Alpha-1 Antitrypsin Deficiency • Chronic Obstructive Pulmonary Disease • Genetic Disorders • Hepatology • Immunology • Inflammation • Liver Failure • Pulmonary Disease • Respiratory Diseases • ADAR • SERPINA1

RNA editing for the treatment of Alpha-1 antitrypsin deficiency (EASL-ILC 2024) - "These findings highlight the potential of GalNAc-AIMers to address both liver and lung manifestations of AATD. Wave Life Sciences is advancing WVE-006, an investigational GalNAc-AIMer, into clinical trials for the treatment of AATD. This clinical program (RestorAATion) is designed to provide proof of concept for the first RNA editing therapy in humans."

Alpha-1 Antitrypsin Deficiency • Chronic Obstructive Pulmonary Disease • Genetic Disorders • Hepatology • Immunology • Inflammation • Liver Failure • Pulmonary Disease • Respiratory Diseases • ADAR • SERPINA1

An RNA Editing Approach for the Treatment of Alpha-1 Antitrypsin Deficiency (AATD) (ATS 2024) - "These data indicate that WVE-006 directed substantial editing of the SERPINA1 Z transcript in the mouse liver, which led to the production of functional M-AAT protein, with total AAT in serum reaching levels higher than the 11 μM threshold believed to lower risk for COPD. Together, these data support a biweekly dosing regimen for WVE-006 in clinical studies."

Alpha-1 Antitrypsin Deficiency • Chronic Obstructive Pulmonary Disease • Genetic Disorders • Hepatology • Immunology • Pulmonary Disease • Respiratory Diseases • ELANE • SERPINA1

RestorAATion-2: A Phase 1b/2a, Open-label Single Ascending Doses and Multiple Ascending Doses Study in Participants With Pi*ZZ AATD (clinicaltrials.gov) - P1/2 | N=24 | Not yet recruiting | Sponsor: Wave Life Sciences Ltd.

New P1/2 trial • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases

A Phase 1 Research Study to Evaluate Safety, Tolerability, and Pharmacokinetics of WVE-006 in Healthy Participants With Wild-type AAT Expression (RestorAATion-1) (clinicaltrials.gov) - P1 | N=56 | Recruiting | Sponsor: Wave Life Sciences Ltd.

New P1 trial • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases

"$MREO how much is Alvelestat phase 3 ready in #AATD worth ? @VertexPharma should acquire Alvelestat for $1Bn $WVE landed $3.3Bn partnership deal with $GSK for WVE-006 preclinical asset $XBI $IBB $VRTX" (@ej23ny)

Licensing / partnership • P3 data

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

Wave Life Sciences to Highlight Leading RNA Editing Capability and Multimodal Discovery and Development Platform at ASGCT 26th Annual Meeting (GlobeNewswire) - "Wave Life Sciences...today announced it will highlight its leading RNA editing capability and its multimodal discovery and development platform at the American Society of Gene & Cell Therapy (ASGCT) Annual Meeting, taking place May 16-20, 2023...New preclinical data for WVE-006, Wave’s investigational, GalNAc-conjugated RNA editing candidate for the treatment of alpha-1 antitrypsin deficiency (AATD), will be presented in an oral abstract session....WVE-006 is uniquely designed to address both liver and lung disease related to AATD and is poised to be the industry’s first RNA editing candidate to enter clinical trials, with CTA submissions by Wave expected in the second half of 2023."

New trial • Preclinical • Alpha-1 Antitrypsin Deficiency • Genetic Disorders

[VIRTUAL] A versatile platform for ADARmediated RNA editing in vivo in preclinical models (ESGCT 2021) - "Finally, we will illustrate our application of this technology to AATD (a1 antitrypsin deficiency), a genetic disorder with lung and liver manifestations that has potential to be corrected with an ADAR editing therapeutic. Stereopure oligonucleotides support dosedependent increases in SERPINA1 RNA editing in vitro and in vivo , resulting in a 3fold increase in serum AAT levels, and restoration of AAT protein function. These preclinical investigations lay the foundation for development of RNAediting therapeutics with potential to treat human genetic disease."

Preclinical • Genetic Disorders • Hepatology • Respiratory Diseases • ADAR • SERPINA1

Wave Life Sciences Reports Third Quarter 2020 Financial Results and Provides Business Update (GlobeNewswire) - "Wave announced today that it is applying its ADAR editing platform capability to develop a potential novel treatment for AATD....By correcting the single RNA base mutation, ADAR editing may provide an ideal approach for increasing circulating levels of wild-type AAT protein....Wave is developing a proprietary in vivo model system, which uses human ADAR and human target transcript, to support the ongoing development of its ADAR editing platform. Data from its humanized SERPINA1/ADAR model are expected in the first half of 2021."

Preclinical • Alpha-1 Antitrypsin Deficiency • CNS Disorders • Frontotemporal Lobar Degeneration