WVE-007 / Wave Life Sciences - LARVOL DELTA

Wave Life Sciences Announces Positive Interim Data from Phase 1 INLIGHT Trial of WVE-007 (INHBE) for Obesity; Single Dose Resulted in Improvement in Body Composition With Fat Loss Similar to GLP-1 at Three Months Without Muscle Loss (GlobeNewswire) - "In this interim assessment, a single 240 mg dose of WVE-007 led to an improvement in body composition characterized by reductions in total and visceral fat mass at three months and an increase in lean mass. There was also a favorable safety profile as well as durable reductions in serum Activin E that support potential once or twice-yearly dosing...From baseline, a single dose of WVE-007 improved body composition and led to a 9.4% reduction in visceral fat (p=0.02), a 4.5% reduction in total body fat (3.5 lbs; p=0.07), and a 3.2% increase in lean mass (4.0 lbs; p=0.01) as measured by DEXA scan at Day 85...Consistent and durable serum Activin E reductions continue to be observed across participants and support WVE-007’s potential for once or twice-yearly dosing....WVE-007 continues to be generally safe and well tolerated to date up to 600 mg."

First-in-human • P1 data • Obesity

Expected milestones (GlobeNewswire) - "Wave expects to deliver multiple clinical data updates from INLIGHT, including body composition and body weight. In the fourth quarter of 2025, Wave expects to deliver three-month follow-up data from Cohort 2 (240 mg), as well as data from Cohort 1 (75 mg). In the first quarter of 2026, Wave expects to deliver six-month follow-up data from Cohort 2 and three-month follow-up data from Cohort 3 (400 mg). In the second quarter of 2026, Wave expects to deliver six-month follow-up data from Cohort 3 and three-month follow-up data from Cohort 4 (600 mg)."

P1 data • Obesity

Targeting Adipose Lipolysis with INHBE Silencing Promotes a Healthy Weight Loss Profile in Mice (OBESITY WEEK 2025) - "Inhbe knockdown by INHBE-00003 was rapid, potent, and durable, and corresponded with body weight and composition changes that recapitulate human genetic findings for INHBE LoF, supporting the reduction of INHBE expression as means to induce healthy weight loss. These preclinical data support INHBE-siRNA treatment as a potential next-generation anti-obesity agent for patients living with obesity and other metabolic co-morbidities. INLIGHT is a clinical trial of WVE-007, an investigational INHBE GalNAc-siRNA for the treatment of adults living with overweight or obesity."

Preclinical • Cardiovascular • Coronary Artery Disease • Diabetes • Genetic Disorders • Inflammation • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus • CD68

Wave Life Sciences to Present Preclinical Data Supporting Therapeutic Potential of WVE-007 for Obesity at ObesityWeek 2025 (GlobeNewswire) - "Presentation will highlight preclinical data supporting the potential of WVE-007 (INHBE GalNAc-siRNA) as a unique approach for the treatment of obesity designed to drive fat loss while preserving muscle mass with once or twice annual dosing. In preclinical models, INHBE GalNAc-siRNA led to adipocyte shrinkage, fewer pro-inflammatory macrophages, less fibrosis, and improved insulin sensitivity in visceral adipose tissue, supporting potential for metabolic improvement."

Preclinical • Obesity

INLIGHT clinical study and target engagement update (GlobeNewswire) - "At day 29 (one month post single dose), mean Activin E reductions from baseline were all highly significant (p<0.0001 for all doses): Cohort 3 (400 mg): 85% reduction; Cohort 2 (240 mg): 75% reduction; Cohort 1 (75 mg): 56% reduction; The one-month reductions of Activin E observed in the 240 mg and 400 mg cohorts exceed levels that led to fat loss in preclinical models; In Cohort 1 (75 mg), Activin E reductions were durable throughout the 6-month follow-up, supporting WVE-007’s potential for once or twice yearly doing...Next steps...4Q 2025: anticipated three-month follow-up data from the expanded Cohort 2 (240 mg), as well as data from Cohort 1 (75 mg); 1Q 2026: anticipated six-month follow-up data from Cohort 2 and three-month follow-up data from Cohort 3; 2Q 2026: anticipated six-month follow-up data from Cohort 3 and three-month follow-up data from Cohort 4."

P1 data • Obesity

Recent Business Highlights and Expected Milestones (GlobeNewswire) - "INLIGHT is an ongoing, first-in-human clinical trial (3:1 active: placebo) evaluating WVE-007 in adults living with overweight or obesity and assesses safety, tolerability, pharmacokinetics, biomarkers for target engagement, body weight and composition, and metabolic health...Today, Wave announced dosing is complete for these additional participants in the expanded Cohort 2 and data from both Cohort 1 and Cohort 2 are expected in the fourth quarter of 2025; Dosing is also underway in Cohort 3 (400 mg) with data anticipated in the first quarter of 2026....Wave expects to submit an Investigational New Drug (IND) application for a potentially registrational Phase 2/3 study of WVE-003 in HD in the second half of 2025."

IND • New P2/3 trial • P1 data • Trial status • Huntington's Disease • Obesity

Silencing Hepatokine Activin E Production in Mice Recapitulates Human Genetic Data and Demonstrates Improved Healthy Weight Loss Profile (ENDO 2025) - "These preclinical data support reducing hepatokine Activin E levels through INHBE siRNA treatment as a potential next-generation anti-obesity agent for patients living with obesity and other metabolic co-morbidities. Wave Life Sciences expects to initiate dosing in the INLIGHT clinical trial for WVE-007, an investigational INHBE GalNAc-siRNA, for the treatment of people living with obesity, in Q1 2025."

Preclinical • Cardiovascular • Coronary Artery Disease • Diabetes • Genetic Disorders • Inflammation • Obesity • Type 2 Diabetes Mellitus

siRNA-INHBE Silencing in Mice Recapitulates Human Genetic Data and Demonstrates Improved Healthy Weight Loss Profile (ADA 2025) - "DIO mice treated with INHBE-00003 recapitulate human genetic findings for INHBE LoF, supporting the reduction of INHBE expression as means to support healthy weight loss. These preclinical data support INHBE-siRNA treatment as a potential next-generation anti-obesity agent for patients living with obesity and other metabolic co-morbidities. Wave Life Sciences expects to initiate a clinical trial for WVE-007, an investigational INHBE GalNAc-siRNA, for the treatment of people living with obesity, in 1Q 2025."

Preclinical • Metabolic Disorders • Obesity

Wave Life Sciences Announces Oral Presentation of Preclinical Data Supporting WVE-007’s Mechanism (INHBE) to Reduce Fat, Preserve Muscle, and Induce Healthy Weight Loss at ADA's Annual Scientific Sessions (GlobeNewswire) - "Wave Life Sciences... announced the presentation of preclinical data supporting WVE-007, its GalNAc-siRNA designed to silence INHBE mRNA, an obesity target with strong evidence from human genetics. The data demonstrate the ability of Wave’s long-acting GalNAc-siRNA to reduce INHBE mRNA and Activin E protein, induce weight loss mainly through reduction of fat mass, and reduce pro-inflammatory macrophage recruitment in a diet-induced obese (DIO) mouse model. The data were highlighted today in an oral presentation at the American Diabetes Association’s 85th Annual Scientific Sessions....'We are evaluating WVE-007 in our ongoing INLIGHT clinical trial in adults living with overweight or obesity, and we are on track to deliver the first clinical data in the second half of this year'."

P1 data • Preclinical • Obesity

siRNA-INHBE silencing in mice confirms human genetic data and supports the vision for next generation anti-obesity treatment (ECO 2025) - "DIO mice treated with INHBE-00003 recapitulate human genetic findings for INHBE LoF, supporting the reduction of INHBE expression as means to support healthy weight loss. We also observed synergy between INHBE lowering with INBHE-00003 and daily semaglu-tide treatment. These preclinical results support multiple options for an INHBE-lowering siRNA treatment: 1) as a monotherapy, 2) an add-on to GLP-1R to potentiate weight loss, and 3) to curtail weight regain upon cessation of GLP-1R."

Preclinical • Cardiovascular • Coronary Artery Disease • Diabetes • Genetic Disorders • Obesity • Type 2 Diabetes Mellitus

Recent Business Highlights and Expected Milestones (GlobeNewswire) - "Next week, in oral presentations at the 32nd European Congress on Obesity (ECO) and the American Society of Gene and Cell Therapies (ASGCT) 28th Annual Meeting, Wave will highlight its preclinical data supporting WVE-007’s potential in multiple treatment settings with potential for dosing once or twice a year, including: A single dose of Wave’s INHBE siRNA led to weight loss on par with semaglutide, but with no muscle loss; When administered as an add-on to semaglutide, a single dose of Wave’s INHBE siRNA doubled the amount of weight loss; Wave’s INHBE siRNA curtailed rebound weight gain when semaglutide treatment was discontinued, highlighting its potential as an off-ramp and maintenance treatment following GLP-1 treatment....Expected milestones: Wave expects to deliver clinical data from INLIGHT in the second half of 2025, including safety, tolerability and biomarkers reflective of healthy weight loss."

P1 data • Preclinical • Obesity

GalNAc-siRNA Programs (GlobeNewswire) - "INLIGHT is an ongoing, first-in-human, placebo-controlled, clinical trial evaluating WVE-007 in adults living with overweight or obesity and assesses safety, tolerability, pharmacokinetics, biomarkers for target engagement, body weight and composition, and metabolic health; Today, Wave announced that it has completed enrollment in the first single dose cohort of INLIGHT....Wave expects to deliver clinical data from INLIGHT in the second half of 2025, including safety, tolerability and biomarkers reflective of healthy weight loss."

Enrollment status • P1 data • Obesity

INLIGHT: A Phase 1 Study of WVE-007 in Adults Living with Overweight or Obesity (clinicaltrials.gov) - P1 | N=136 | Recruiting | Sponsor: Wave Life Sciences Ltd.

New P1 trial • Genetic Disorders • Obesity

Wave Life Sciences Announces Initiation of Phase 1 INLIGHT Clinical Trial of WVE-007 in Obesity (GlobeNewswire) - "Wave Life Sciences Ltd...today announced clinical trial application (CTA) approval and initiation of the Phase 1 INLIGHT clinical trial of WVE-007 in obesity. WVE-007 is a long-acting GalNAc-conjugated small interfering RNA (siRNA) that targets INHBE messenger RNA. INHBE is a genetically validated target that provides a novel approach for healthy weight loss. Wave expects to deliver proof-of-concept clinical data in 2025."

IND • New trial • P1 data • Obesity

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 Announces Submission of First Clinical Trial Application for WVE-007 (siRNA Targeting INHBE) in Obesity (GlobeNewswire) - "Wave Life Sciences Ltd...today announced the submission of its first clinical trial application (CTA) for WVE-007 in obesity. WVE-007 is an investigational GalNAc-conjugated small interfering RNA (siRNA) designed to silence Inhibin βE (INHBE) gene expression, which would induce fat burning (lipolysis) to decrease body weight without impacting muscle mass. Wave expects CTA approval and initiation of the first-in-human study of WVE-007 in the first quarter of 2025."

New P1 trial • Metabolic Disorders • Obesity

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