WVE-007 / Wave Life Sciences - LARVOL DELTA

Wave Life Sciences…announced the initiation of its Phase 2a clinical trial evaluating WVE-007, an investigational GalNAc-siRNA, in combination with tirzepatide in adults living with obesity (GlobeNewswire) - "The INLIGHT clinical program is evaluating WVE-007 as a monotherapy and in combination with tirzepatide as a treatment for obesity and other cardiometabolic indications, including MASH. The placebo-controlled (3:1) Phase 2a combination trial will evaluate 240 mg and 400 mg doses of WVE-007 in combination with weekly tirzepatide in individuals living with obesity (BMI 35-50 kg/m2) and type 2 diabetes....Wave also remains on track to initiate a clinical trial of WVE-007 as a maintenance therapy to preserve weight loss following discontinuation of incretin treatment in the second half of 2026."

New trial • Trial status • Obesity

Corporate Supported Symposium - Translating Human Genetics Into an Innovative Obesity Therapy: WVE-007, a Novel GalNAc-siRNA Targeting the INHBE Gene (OBESITY WEEK 2026) - "Description Details coming soon."

Genetic Disorders • Obesity

Interim results from INLIGHT: a Phase 1 clinical study of WVE-007, a GalNAc-siRNA targeting INHBE, for the treatment of overweight and obesity (EASD 2026) - P1/2 | "Durable Activin E reductions support the potential for once or twice-yearly dosing of WVE-007. These interim data suggest WVE-007 has the potential to promote fat loss and preserve lean mass. Overall, interim safety, tolerability, target engagement, and pharmacodynamic findings from the INLIGHT study support continued evaluation of WVE-007 for the treatment of people living with overweight and obesity."

Clinical • P1 data • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

WVE-007 is being evaluated in the ongoing placebo-controlled INLIGHT clinical trial. (GlobeNewswire) - "Phase 1 INLIGHT trial...Additional data from the INLIGHT trial, including data from the 600 mg Phase 1 SAD cohort, are expected in the second half of 2026...Phase 2a INLIGHT trial: Dosing is underway in the Phase 2a multidose portion of the INLIGHT trial of WVE-007 in individuals with higher BMI (35-50 kg/m2), with and without type 2 diabetes....Wave expects to initiate Phase 2 trials of WVE-007 in the combination and maintenance settings in the second half of 2026."

New P2 trial • P1 data • Obesity

Wave Life Sciences Announces Initiation of Phase 2a Portion of INLIGHT Trial of WVE-007 for Obesity and Cardiometabolic Diseases (Investing News Network (INN)) - "The Phase 2a portion of the INLIGHT trial is expected to demonstrate further body composition improvements, including greater fat loss with preserved muscle, weight loss, and improved biomarkers of cardiometabolic health...The Phase 2a portion of the INLIGHT trial is expected to enroll participants across the U.S. and Europe and includes multiple assessments over a 12-month period, including body weight, waist circumference, body composition (MRI and DEXA), liver fat (MRI-PDFF), HbA1c, and lipid levels....Wave also expects to initiate new clinical trials evaluating WVE-007 as an incretin add-on and as post-incretin maintenance in the second half of 2026."

New trial • Trial status • Obesity

Silencing Hepatokine Activin E Promotes a Healthy Body Composition and Metabolic Profile in Mice (ADA 2026) - "A single dose of INHBE-3 led to potent target engagement and impacted body weight, composition and adipose tissue remodeling in DIO mice. These preclinical data support INHBE-siRNA as a potential therapeutic for people living with obesity. Wave Life Sciences is evaluating WVE-007, an investigational INHBE GalNAc-siRNA, for the treatment of overweight or obesity in the Phase 1 INLIGHT clinical trial."

Preclinical • Metabolic Disorders • Obesity

Interim Results from INLIGHT, a Phase 1 Study of Investigational WVE-007, an INHBE Galnac siRNA for the Treatment of Overweight and Obesity (ADA 2026) - P1/2 | "Durable Activin E reductions support the potential for once or twice-yearly dosing of WVE-007. Interim safety, TE and body composition data support continued evaluation of WVE-007 for the treatment of overweight and obesity in the ongoing Phase 1 INLIGHT clinical trial."

P1 data • Metabolic Disorders • Obesity

INLIGHT: A Phase 1/2a Study of WVE-007 in Adults Living With Overweight or Obesity (clinicaltrials.gov) - P1/2 | N=296 | Recruiting | Sponsor: Wave Life Sciences USA, Inc. | Phase classification: P1 ➔ P1/2 | N=136 ➔ 296 | Trial completion date: Oct 2026 ➔ Dec 2027 | Trial primary completion date: Oct 2026 ➔ Dec 2027

Enrollment change • Phase classification • Trial completion date • Trial primary completion date • Genetic Disorders • Obesity

WVE-007 is being evaluated in the ongoing placebo-controlled INLIGHT clinical trial. (GlobeNewswire) - "Phase 1 INLIGHT...Additional data from INLIGHT, including data from the 600 mg Phase 1 SAD cohort, are expected in 2026...Wave is on track to initiate the Phase 2a portion of INLIGHT in the second quarter of 2026; Combination with incretin and post-incretin maintenance studies of WVE-007 are expected to initiate in 2026."

New P2a trial • P1 data • Obesity

Anticipated upcoming WVE-007 milestones (GlobeNewswire) - "...initiate new clinical trials evaluating WVE-007 as an incretin add-on and as post-incretin maintenance in 2026."

New trial • Obesity

Wave Life Sciences Announces Positive Interim Phase 1 Data from INLIGHT: Further Improvements in Body Composition, with Clinically Meaningful Reductions in Visceral Fat and Waist Circumference, at Six Months Following Single Dose of WVE-007 (GlobeNewswire) - "At 6-month follow-up, a single 240 mg dose of WVE-007 (INHBE GalNAc-siRNA) continued to drive significant placebo-adjusted reductions in visceral fat (-14%; p<0.05) and total fat (-5%), stabilization of lean mass (+2%), and reductions in waist circumference (-3%) and body weight (-1%); WVE-007 led to greater improvement in body composition (visceral fat-to-muscle ratio) at six months versus that seen with weekly GLP-1 in later-stage trial (BMI: ~37 kg/m2), even with participants in Phase 1 portion of INLIGHT having substantially lower BMI (~32 kg/m2) and lower levels of fat...Wave is on track to initiate the Phase 2a multidose portion of INLIGHT evaluating WVE-007 as monotherapy in individuals with higher BMI (35-50 kg/m2) and comorbidities in the second quarter of 2026...Additional data from INLIGHT, including data from the 600 mg Phase 1 SAD cohort, are expected in 2026."

P1 data • Trial status • Obesity

Wave Life Sciences Highlights Strategic Priorities for 2026 at the 44th Annual J.P. Morgan Healthcare Conference: Accelerating Development of WVE-007 (INHBE siRNA) for Obesity... (GlobeNewswire) - "Wave expects to initiate a Phase 2a multidose portion of WVE-007 INLIGHT clinical trial in individuals living with obesity with higher BMI and comorbidities in 1H 2026, and initiate new trials of WVE-007 as an add-on to incretin and as post-incretin maintenance in 2026...The 240 mg (n=32), 400 mg (n=32), and 600 mg (n=32) single dose cohorts of INLIGHT are fully dosed. In the first quarter of 2026, Wave expects to deliver six-month follow-up data from the 240 mg single-dose cohort, as well as three-month follow-up data from the 400 mg single dose cohort. In the second quarter of 2026, Wave expects to deliver six-month follow-up data from the 400 mg single dose cohort and three-month follow-up data from the 600 mg single dose cohort."

New trial • P1 data • Trial status • Obesity

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