Wave Life Sciences Ltd.
For the period ended Sep 30, 2025. Filed Nov 10, 2025.
View on SEC.govAbout this filing
A company's report for each of its first three quarters. The financial statements are not audited. It shows how the business has moved since the last annual report, and what management says changed.
Sep 30, 2025 · Filed Nov 10, 2025
WVE$3.37+4.5%Stored close · as of Nov 6, 2026
What changed in Management’s Discussion and Analysis?
Read the current filingPrevious report: 10-Q
Period ended 2025-06-30; filed 2025-07-30.
0000950170-25-099884
Item 2. Management’s Discussion and Analysis of Financial Condition and Results of OperationsCurrent report: 10-Q
Period ended 2025-09-30; filed 2025-11-10.
0001193125-25-273288
Item 2. Management’s Discussion and Analysis of Financial Condition and Results of OperationsThe baseline is this issuer’s latest earlier reporting period of the same form that was filed before the current report. A previous 10-Q is a different quarter, not a year-over-year comparison. Amendments are excluded.
Compared 174 previous paragraphs and 173 current paragraphs.
104 unchanged; 57 reworded; 11 added; 9 removed; 4 previous and 1 current paragraphs rearranged.
Tables are not compared: 5 previous and 5 current tables excluded. Dates, whitespace, punctuation and numbering changes are ignored; changes to financial figures remain significant.
A changed paragraph is not evidence that risk increased or decreased. An unchanged paragraph does not establish that risk stayed the same.
Added paragraphs (11)
Current report
Emerging siRNA and RNA editing programs targeting both hepatic and extra-hepatic tissues.
Current report
In preclinical studies, we have also observed that infiltration of macrophages into visceral adipose was significantly decreased by a single dose of INHBE GalNAc-siRNA compared with PBS controls. INHBE GalNAc-siRNA also significantly reduced proinflammatory M1 macrophage (CD11c positive) while sustaining levels of anti-inflammatory M2 macrophages in visceral fat, indicating an overall shift away from a pro-inflammatory state. Further, we have shared RNA sequencing data from subcutaneous adipose tissue which support that INHBE GalNAc-siRNA leads to the upregulation of genes supporting better insulin sensitivity, fatty acid utilization and beiging of white adipose, while downregulating adipose inflammation and fibrosis pathways. We have also shared RNA sequencing data from visceral adipose tissue which support INHBE GalNAc-siRNA increased glucose and fatty acid utilization, reduced inflammation and fibrosis in adipose tissue.
Current report
In October 2025 at our annual analyst and investor Research Day, we announced that highly significant, dose-dependent Activin E reductions were observed in Cohorts 1, 2, and 3 of our INLIGHT clinical trial. At day 29 (one month post-single dose), mean Activin E reductions from baseline were all highly significant (p<0.0001 for all doses) including: 85% reduction in Cohort 3, 75% reduction in Cohort 2, and 56% reduction in Cohort 1. The one-month reductions of Activin E observed in Cohort 2 and Cohort 3 exceed levels that led to fat loss and prevention of rebound weight gain following cessation of semaglutide in our preclinical models. In Cohort 1, Activin E reductions were durable throughout the six-month follow-up, supporting WVE-007’s potential for once or twice a year dosing. We also reported that WVE-007 was generally safe and well tolerated to date.
Current report
In September 2025, we announced positive data from the 200 mg single and multidose, and 400 mg single dose cohorts of the ongoing RestorAATion-2 study. Key highlights included:
Current report
Following a single 200 mg dose of WVE-006, a total AAT level of 20.6 µM, including a M-AAT level of 10.3 µM, was observed in one individual during an acute phase response due to a kidney stone. These data demonstrate that treatment with WVE-006 enables endogenous regulation and dynamic increased secretion of AAT protein during an acute phase response as indicated by a concurrent C-reactive protein elevation.
Current report
In the 200 mg multidose cohort, we observed 11.9 µM of total AAT and M-AAT of 7.2 µM, which was significantly increased from levels achieved during the single dose portion of the cohort. M-AAT levels reached 64.4% of total AAT, and mutant Z-AAT protein declined from baseline by 60.3%.
Current report
In the 400 mg single dose cohort, we observed total AAT of 12.8 µM and M-AAT of 5.3 µM.
Current report
Dosing is ongoing in the 400 mg multidose cohort with a monthly dosing regimen. Dosing is ongoing in the 600 mg single dose cohort. We expect to deliver data from the 400 mg multidose cohort in the first quarter of 2026. We expect to deliver single and multidose data from the third and final cohort (600 mg) in 2026.
Current report
We have advanced WVE-008, a GalNAc-conjugated AIMer, as our clinical candidate for PNPLA3 I148M liver disease. There are an estimated nine million homozygous PNPLA3 I148M individuals with liver disease in the United States and Europe. These homozygous carriers have a significantly higher risk of liver-related death compared to heterozygous carriers. The PNPLA3 I148M variant is a well-established driver of steatosis, inflammation, ballooning and fibrosis; however, there are no approved medicines that directly address this biology. Emerging preclinical and clinical data indicate that knocking down PNPLA3 is not an optimal approach as loss of PNPLA3 function inadequately addresses steatosis and fibrosis. To effectively address these manifestations of the disease, we use our novel RNA editing approach. In preclinical studies, we have demonstrated that our PNPLA3 GalNAc-AIMer restores functional PNPLA3 protein and decreases lipid accumulation. We expect to file a clinical trial application for WVE-008 in 2026.
Current report
In October 2025 at our annual analyst and investor Research Day, we shared that we have applied learnings from across our platform and chemistry optimization to investigate a new modality which is designed to combine RNA editing and silencing into a single bifunctional oligonucleotide construct. This construct is designed to silence one target while simultaneously editing or upregulating another distinct target. We confirmed the ability of this single bifunctional oligonucleotide construct to engage in silencing and editingin vivo using a GalNAc conjugated oligonucleotide that is designed to edit UGP2 and silence TTR. In a separate preclinical study, we also demonstrated that we were able to upregulate LDLR and silence PCSK9 using this construct.
Current report
Comparison of the nine months ended September 30, 2025 and 2024
Removed paragraphs (9)
Previous report
Heterozygous Familial Hypercholesterolemia (“HeFH”): GalNAc-conjugated AIMer targeting low-density lipoprotein receptor (“LDLR”) for upregulation and GalNAc-conjugated AIMer targeting apolipoprotein B (“APOB”) for correction.
Previous report
o
Previous report
WVE-007 utilizes our next generation GalNAc-siRNA format. In preclinical DIO mouse models, our INHBE GalNAc-siRNA has demonstrated highly potent INHBE silencing (ED50 < 1 mg/kg), durable silencing following one, low-single digit dose supporting every-six-month or annual subcutaneous dosing in humans, weight loss with no loss of muscle mass and reduction in fat mass, with preferential effect to the visceral fat, consistent with the profile of INHBE LoF in human genetics.
Previous report
Multi-dosing is complete in the first cohort of RestorAATion-2, where patients with AATD who have the homozygous Pi*ZZ mutation are receiving 200 mg subcutaneous doses of WVE-006 every other week. Dosing is complete in the second single dose cohort of RestorAATion-2 at 400 mg. We expect to share data from the complete 200 mg single and multidose cohorts of RestorAATion-2 in the third quarter of 2025, and data from the complete 400 mg single dose cohort in the fall of 2025.
Previous report
Our wholly owned discovery-stage pipeline includes hepatic and extra hepatic targets, including three RNA editing programs in liver that leverage GalNAc conjugates and have efficient clinical paths to proof-of-concept.
Previous report
PNPLA3, which uses mRNA correction to restore the heterozygous phenotype for those at high risk for genetically defined liver disease. Homozygous PNPLA3-I148M carriers are at high risk for a variety of liver diseases and there are more than nine million impacted individuals in the United States and Europe.
Previous report
LDLR and APOB, which utilize first-in-class mRNA upregulation and mRNA correction approaches, respectively, to achieve target low-density lipoprotein cholesterol (LDL-c) levels in people with heterozygous familial hypercholesterolemia. Combined, LDLR and APOB AIMers could address approximately one million people living with HeFH in the United States and Europe. LDLR upregulation also offers significant expansion opportunities in people with statin intolerance or prior cardiovascular events which represent approximately 30 million individuals in the United States and Europe.
Previous report
We plan to share new preclinical data from our wholly owned hepatic and extra-hepatic RNA editing programs in 2025. In 2026, we expect to initiate clinical development of additional RNA editing programs, including PNPLA3, LDLR, and APOB.
Previous report
Comparison of the six months ended June 30, 2025 and 2024
Reworded paragraphs (57)
Previous wording
We are a clinical-stage biotechnology company focused on unlocking the broad potential of ribonucleic acid (“RNA”) medicines (also known as oligonucleotides), or those targeting RNA, to transform human health. Our RNA medicines platform, PRISM®, combines multiple modalities, chemistry innovation and deep insights into human genetics to deliver scientific breakthroughs that treat both rare and common disorders. Our toolkit of RNA-targeting modalities includes RNA editing, splicing, silencing using RNA interference (“siRNA") and antisense silencing, providing us with unique capabilities for designing and sustainably delivering candidates that optimally address disease biology. Our diversified pipeline includes clinical programs in obesity, alpha-1 antitrypsin deficiency (“AATD”), Duchenne muscular dystrophy (“DMD”), and Huntington’s disease (“HD”), as well as several preclinical programs utilizing our versatile RNA medicines platform.
Current wording
We are a clinical-stage biotechnology company focused on unlocking the broad potential of ribonucleic acid (“RNA”) medicines (also known as oligonucleotides), or those targeting RNA, to transform human health. Our RNA medicines platform, PRISM®, combines multiple modalities, chemistry innovation and deep insights into human genetics to deliver scientific breakthroughs that treat both rare and common disorders. Our toolkit of RNA-targeting modalities includes RNA editing, splicing, silencing using RNA interference (“RNAi") and antisense, providing us with unique capabilities for designing and sustainably delivering candidates that optimally address disease biology. Our diversified pipeline includes clinical programs in obesity, alpha-1 antitrypsin deficiency (“AATD”), Duchenne muscular dystrophy (“DMD”), and Huntington’s disease (“HD”), as well as several preclinical programs utilizing our versatile RNA medicines platform.
Previous wording
Liver disease: GalNAc-conjugated AIMer targeting PNPLA3 I148M for correction; and
Current wording
Liver disease: WVE-008 is a GalNAc-conjugated AIMer targeting PNPLA3 I148M; and
Previous wording
DMD: WVE-N531 is an exon 53 splicing oligonucleotide; and
Current wording
DMD: WVE-N531 is an exon 53 splicing oligonucleotide;
Previous wording
HD: WVE-003 is an allele-selective oligonucleotide designed to lower mutant huntingtin (“mHTT”) protein and preserve healthy, wild-type huntingtin (“wtHTT”) protein.
Current wording
HD: WVE-003 is an allele-selective oligonucleotide designed to lower mutant huntingtin (“mHTT”) protein and preserve healthy, wild-type huntingtin (“wtHTT”) protein; and
Previous wording
WVE-007 is a GalNAc-siRNA that is designed to silence the INHBE gene to induce fat loss by stimulating lipolysis (fat breakdown) while preserving muscle mass to restore and maintain a healthy metabolic profile. There are approximately 175 million people in the United States and Europe living with obesity, and therapeutic options beyond GLP-1 receptor agonists are needed. GLP-1 receptor agonists lead to weight loss at the expense of muscle, suppress the general reward system, and are associated with a poor tolerability profile and high discontinuation rates. Heterozygous INHBE loss-of-function (“LoF”) human carriers exhibit a healthy metabolic profile, including reduced waist-to-hip ratio and reduced odds of developing type 2 diabetes or coronary artery disease, and reduction of INHBE by 50% or more is expected to restore a healthy metabolic profile. In connection with our 2023 Research and Development Day, we sharedin vivo proof-of-concept data in diet-induced obesity (“DIO”) mice demonstrating INHBE silencing well beyond the anticipated 50% therapeutic threshold, which led to substantially lower body weight and reduction of visceral fat as compared to controls. These are the first data to demonstrate INHBE silencingin vivo in an animal model is consistent with the phenotypes of heterozygous loss-of-function carriers.
Current wording
WVE-007 is a GalNAc-siRNA, that utilizes Stereopure interfering Nucleic Acid (“SpiNA”), our next generation siRNA format. WVE-007 is designed to silence INHBE mRNA to induce fat loss by stimulating lipolysis (fat breakdown) while preserving muscle mass to promote and maintain a healthy metabolic profile. There are approximately 175 million people in the United States and Europe, and over one billion people globally, living with obesity, and therapeutic options beyond GLP-1 receptor agonists are needed. GLP-1 receptor agonists lead to weight loss at the expense of muscle, suppress the general reward system, and are associated with a poor tolerability profile and high discontinuation rates. Heterozygous INHBE loss-of-function (“LoF”) human carriers exhibit a healthy metabolic profile, including reduced waist-to-hip ratio and reduced odds of developing type 2 diabetes or coronary artery disease, and reduction of INHBE by 50% or more is expected to promote a healthy metabolic profile.
Previous wording
In DIO mice studies, we observed a weight loss effect from a single dose of our INHBE GalNAc-siRNA similar to daily subcutaneous injection of semaglutide for 28 days. We also observed a decrease in high fat diet-induced expansion of visceral adipose mass. This reduction of visceral fat mass was associated with significant shrinkage of adipocyte enlargement induced by high fat diet compared with phosphate-buffered saline (“PBS”) treatment. Collectively, these results support the restoration of healthy adipose tissue with this mechanism of action, while muscle mass was preserved. Additionally, a single dose of INHBE GalNAc-siRNA led to robust target engagement, including reduction of liver INHBE mRNA and its protein product Activin E in serum, a lipolysis suppressor that is upregulated in obesity and insulin resistance. Liver INHBE mRNA was strongly correlated with serum Activin E levels following INHBE-siRNA treatment. Infiltration of macrophages into visceral adipose was shown to be significantly decreased by a single dose of INHBE GalNAc-siRNA compared with PBS controls. INHBE GalNAc-siRNA also significantly reduced proinflammatory M1 macrophage (CD11c positive) while sustaining levels of anti-inflammatory M2 macrophages in visceral fat, indicating an overall shift away from a pro-inflammatory state. In addition, treatment with our INHBE GalNAc-siRNA prior to cessation of semaglutide treatment curtailed expected rebound weight gain. When administered as an add-on to semaglutide, a single dose of our INHBE GalNAc-siRNA doubled the weight loss observed with semaglutide alone, and this effect was sustained throughout the duration of the preclinical study.
Current wording
In preclinical diet-induced obesity (“DIO”) mouse models, a single dose of our INHBE GalNAc-siRNA has demonstrated highly potent and durable INHBE silencing (and >70% Activin E reductions), supporting once or twice a year subcutaneous dosing in humans, and weight loss driven by visceral fat loss while preserving muscle mass, consistent with the profile of INHBE LoF carriers based on human genetics. In DIO mice studies, we observed a weight loss effect from a single dose of our INHBE GalNAc-siRNA that was similar to daily subcutaneous injections of semaglutide for 28 days. We also observed a decrease in high fat diet-induced expansion of visceral adipose mass. This reduction of visceral fat mass was associated with significant shrinkage of adipocyte enlargement induced by a high fat diet compared with phosphate-buffered saline (“PBS”) treatment. Collectively, these results support the promotion of healthy adipose tissue with this mechanism of action, while muscle mass was preserved. In addition, treatment with our INHBE GalNAc-siRNA prior to cessation of semaglutide treatment prevented rebound weight gain. When administered as an add-on to semaglutide, a single dose of our INHBE GalNAc-siRNA doubled the weight loss observed with semaglutide alone, and this effect was sustained throughout the duration of the preclinical study.
Previous wording
In February 2025, we announced that we had initiated INLIGHT, the first-in-human Phase 1 clinical trial of WVE-007 (3:1 active:placebo) in obesity. INLIGHT is enrolling adults living with overweight or obesity to assess safety, tolerability, pharmacokinetics (“PK”), biomarkers for target engagement, body weight and composition, and metabolic health.
Current wording
In February 2025, we announced that we had initiated INLIGHT, our first-in-human Phase 1 clinical trial of WVE-007 (3:1 active:placebo) in obesity. INLIGHT is enrolling adults living with overweight or obesity to assess safety, tolerability, pharmacokinetics (“PK”), and Activin E levels for target engagement. In addition, the trial has exploratory endpoints of body weight, body composition, and biomarkers of metabolic health. Key inclusion criteria include A1c of less than 5.9 and BMI between 28 and 35.
Previous wording
In the second quarter of 2025, we expanded Cohort 2 of INLIGHT, which is evaluating single 240 mg doses of WVE-007, from eight to 32 individuals. This expansion was triggered by favorable safety and tolerability, as well as robust Activin E reduction observed in Cohort 1 (75 mg; n=8), the lowest single dose cohort. The 240 mg dose level is predicted to be therapeutically active based on our preclinical DIO mice data, where a single dose of INHBE GalNAc-siRNA led to potent and durable reductions of both INHBE mRNA and Activin E protein and drove weight loss.
Current wording
In May 2025, we announced that we completed dosing in the first and second single dose cohorts of INLIGHT. In the second quarter of 2025, we expanded Cohort 2 of INLIGHT, which is evaluating single 240 mg doses of WVE-007, from eight to 32 individuals. This expansion was triggered by favorable safety and tolerability, as well as robust Activin E reduction observed in Cohort 1 (75 mg; n=8), the lowest single dose cohort. The 240 mg dose level is predicted to be therapeutically active based on our preclinical DIO mice data, where a single dose of INHBE GalNAc-siRNA led to potent and durable reductions of both INHBE mRNA and Activin E protein and drove weight loss. In July 2025, we announced that dosing is complete in the expanded Cohort 2 (240 mg) and that dosing was underway in Cohort 3 (400 mg) of INLIGHT.
Previous wording
We expect to deliver data from the expanded Cohort 2 (240 mg) as well as data from Cohort 1 (75mg) of INLIGHT in the fourth quarter of 2025, including safety, tolerability and measurements reflective of healthy weight loss. Data from Cohort 3 (400 mg) of INLIGHT are anticipated in the first quarter of 2026.
Current wording
INLIGHT is currently ongoing at multiple trial sites including in the US, following clearance of an Investigational New Drug (“IND”) application. We have expanded Cohort 2, Cohort 3, and Cohort 4 to 32 individuals and the independent data monitoring committee approved escalation to a higher dose in Cohort 5. We expect to deliver multiple clinical data updates from INLIGHT, including body composition and body weight. In the fourth quarter of 2025, we expect 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, we expect 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, we expect to deliver six-month follow-up data from Cohort 3 and three-month follow-up data from Cohort 4 (600 mg).
Previous wording
Preclinical data show that treatment with WVE-006 resulted in serum AAT protein levels of up to 30 micromolar in an established AATD mouse model (NSG-PiZ). WVE-006 also led to restoration of approximately 50% wild-type M-AAT protein in serum and a 3-fold increase in neutrophil elastase inhibition activity, indicating that the restored M-AAT protein was functional. Our AATD AIMers are highly specific to SERPINA1 RNAin vitro andin vivo based on transcriptome-wide analyses.
Current wording
WVE-006 is first-in-class in AATD and is the most advanced program currently in clinical development using an oligonucleotide to harness an endogenous enzyme for RNA editing. Preclinical data show that treatment with WVE-006 resulted in serum AAT protein levels of up to 30 µM (7-fold increase) in an established AATD mouse model (NSG-PiZ). WVE-006 also led to restoration of approximately 50% wild-type M-AAT protein in serum and a 3-fold increase in neutrophil elastase inhibition activity, indicating that the restored M-AAT protein was functional. Our AATD AIMers are highly specific to SERPINA1 RNAin vitro andin vivo based on transcriptome-wide analyses.
Previous wording
WVE-006 is first-in-class in AATD and is the most advanced program currently in clinical development using an oligonucleotide to harness an endogenous enzyme for RNA editing. Our RestorAATion clinical program investigating WVE-006 as a treatment for AATD is comprised of two parts: RestorAATion-1, a study of healthy volunteers; and RestorAATion-2, a study in individuals with AATD who have the homozygous Pi*ZZ mutation. We have completed multi-dosing in healthy volunteers in RestorAATion-1 at a dose level greater than those planned for any cohort in RestorAATion-2. RestorAATion-2 is a Phase 1b/2a open label study designed to evaluate the safety, tolerability, pharmacodynamics (“PD”) and PK of WVE-006 in patients with AATD. The trial includes both single ascending dose (“SAD”) and multiple ascending dose (“MAD”) portions.
Current wording
Our RestorAATion clinical program investigating WVE-006 as a treatment for AATD is comprised of two parts: RestorAATion-1, a study of healthy volunteers, and RestorAATion-2, a study in individuals with AATD who have the homozygous Pi*ZZ mutation. RestorAATion-1 enrolled 29 individuals on active drug, with participants receiving up to three, 600 mg doses of WVE-006 every other week in the highest dose cohort. WVE-006 was generally safe and well tolerated, with the related treatment emergent adverse event being mild in intensity. RestorAATion-2 is a Phase 1b/2a open label study designed to evaluate the safety, tolerability, pharmacodynamics and pharmacokinetics of WVE-006 in patients with AATD. The trial includes both single ascending dose and multiple ascending dose portions.
Previous wording
In October 2024, we announced positive proof-of-mechanism data from the ongoing Phase 1b/2a RestorAATion-2 study: Following a single subcutaneous dose of 200 mg of WVE-006 in the study’s first two participants, circulating wild-type M-AAT protein in plasma reached a mean of 6.9 micromolar at day 15, representing more than 60% of total AAT. Increases in neutrophil elastase inhibition from baseline were consistent with production of functional M-AAT. Mean total AAT protein increased from below the level of quantification at baseline to 10.8 micromolar at day 15, meeting the level that has historically been the basis for regulatory approval for AAT augmentation therapies. Increases in total AAT from baseline and M-AAT protein were observed as early as day 3 and through day 57. WVE-006 was well-tolerated with a favorable safety profile. All adverse events in RestorAATion-2, as well as in the RestorAATion-1 trial of healthy volunteers, were mild to moderate, with no serious adverse events (“SAEs”) reported. These data were the first-ever clinical demonstration of RNA editing in humans.
Current wording
In October 2024, we announced positive proof-of-mechanism data from the ongoing Phase 1b/2a RestorAATion-2 study: following a single subcutaneous dose of 200 mg of WVE-006 in the study’s first two participants, circulating wild-type M-AAT protein in plasma reached a mean of 6.9 µM at day 15, representing more than 60% of total AAT. Increases in neutrophil elastase inhibition from baseline were consistent with production of functional M-AAT. Mean total AAT protein increased from below the level of quantification at baseline to 10.8 µM at day 15, achieving the level that has historically been the basis for regulatory approval for AAT augmentation therapies. Increases in total AAT from baseline and M-AAT protein were observed as early as day 3 and through day 57. WVE-006 was generally safe and well-tolerated with a favorable safety profile. All adverse events in RestorAATion-2 were mild to moderate, with no serious adverse events (“SAEs”) reported. These data were the first-ever clinical demonstration of RNA editing in humans.
Previous wording
GlaxoSmithKline Intellectual Property (No. 3) (“GSK”) has an exclusive global license for WVE-006, with clinical development and commercial responsibilities transitioning to GSK after we complete the RestorAATion trial. Under the terms of the collaboration, we are eligible to receive up to $525 million in development, launch, and commercial milestone payments, as well as double-digit tiered royalties up to the high teens, as a percentage of net sales for WVE-006. In December 2023, we announced that we achieved the first WVE-006 milestone in our collaboration with GSK, resulting in a $20 million payment.
Current wording
GlaxoSmithKline Intellectual Property (No. 3) (“GSK”) has an exclusive global license for WVE-006, with clinical development and commercial responsibilities transitioning to GSK after we complete the RestorAATion trial. Under the terms of the collaboration, we are eligible to receive up to $525 million in development, launch, and commercial milestone payments, as well as double-digit tiered royalties up to the high teens, as a percentage of net sales for WVE-006. We have achieved multiple milestones for WVE-006 to date in our collaboration with GSK.
Previous wording
In December 2022, we announced a positive update from Part A of the Phase 1b/2a proof-of-concept, open label trial of WVE-N531 in three boys with DMD amenable to exon 53 skipping. High muscle concentrations of WVE-N531 and exon skipping were observed six weeks after initiating multi-dosing at 10 mg/kg every other week, achieving proof-of-concept in the trial. WVE-N531 also appeared safe and well-tolerated.
Current wording
In December 2022, we announced a positive update from Part A of the Phase 1b/2a proof-of-concept, open label trial of WVE-N531 in three boys with DMD amenable to exon 53 skipping. High muscle concentrations of WVE-N531 and exon skipping were observed six weeks after initiating multi-dosing at 10 mg/kg every other week, achieving proof-of-concept in the trial. WVE-N531 also appeared generally safe and well-tolerated.
Previous wording
In September 2024, we announced positive interim data from our Phase 2 FORWARD-53 open-label study (“Part B”) of eleven boys amenable to exon 53 skipping (age 5-11; 10 ambulatory and 1 non-ambulatory). The interim analysis was conducted after 24 weeks of 10 mg/kg of WVE-N531 dosed every two weeks. WVE-N531 appeared safe and well tolerated. We observed mean muscle content-adjusted dystrophin expression of 9.0% and unadjusted dystrophin of 5.5%, with high consistency across participants, in a prespecified analysis of ambulatory participants.
Current wording
In September 2024, we announced positive interim data from our Phase 2 FORWARD-53 open-label study (“Part B”) of eleven boys amenable to exon 53 skipping (age 5-11; 10 ambulatory and 1 non-ambulatory). The interim analysis was conducted after 24 weeks of 10 mg/kg of WVE-N531 dosed every two weeks. WVE-N531 appeared generally safe and well-tolerated. We observed mean muscle content-adjusted dystrophin expression of 9.0% and unadjusted dystrophin of 5.5%, with high consistency across participants, in a prespecified analysis of ambulatory participants.
Previous wording
WVE-N531 remains safe and well-tolerated with no SAEs observed.
Current wording
WVE-N531 remains generally safe and well-tolerated with no SAEs observed.
Previous wording
All participants in FORWARD-53 elected to advance to the extension portion of the clinical trial, which is currently ongoing with boys receiving monthly doses of WVE-N531. To augment monthly data and ensure a monthly regimen at a potential launch, we are also expanding FORWARD-53 to include additional boys who will be dosed monthly.
Current wording
Also in March 2025, we announced that we met with the FDA on WVE-N531 to discuss our interim 24-week data and initial plans for the confirmatory trial, where the FDA confirmed that the accelerated approval pathway using dystrophin expression as a surrogate endpoint remains open. All participants in FORWARD-53 elected to advance to the extension portion of the clinical trial, which is currently ongoing with boys receiving monthly doses of WVE-N531. To augment monthly data and ensure a monthly regimen at a potential launch, we are also expanding FORWARD-53 to include additional boys who will be dosed monthly. We plan to file a New Drug Application in 2026 to support accelerated approval of WVE-N531 with monthly dosing. We also expect to submit clinical trial applications for other exon skipping programs.
Previous wording
In the third quarter of 2023, we achieved a milestone in our collaboration with Takeda Pharmaceutical Company Limited (“Takeda”), which pertained to the positive results from a non-clinical study of WVE-003 in non-human primates and resulted in a payment of $7.0 million to us. This study showed significant tissue exposure levels of WVE-003 in the deep brain regions, including striatum and bolstered our existing datasets that confirm the ability of our oligonucleotides to distribute to the areas of the CNS important for HD.
Current wording
In the third quarter of 2023, we achieved a milestone in our collaboration with Takeda Pharmaceutical Company Limited, which pertained to the positive results from a non-clinical study of WVE-003 in non-human primates and resulted in a payment of $7.0 million to us. This study showed significant tissue exposure levels of WVE-003 in the deep brain regions, including striatum and bolstered our existing datasets that confirm the ability of our oligonucleotides to distribute to the areas of the CNS important for HD.
Previous wording
The SELECT-HD trial was a global, multicenter, randomized, double-blind, placebo-controlled Phase 1b/2a clinical trial to assess the safety and tolerability of WVE-003 in people with a confirmed diagnosis of HD who are in the early stages of the disease and carry SNP3 in association with their cytosine-adenine-guanine expansion. Additional objectives included assessing pharmacokinetics and exploratory PD and clinical endpoints.
Current wording
The SELECT-HD trial was a global, multicenter, randomized, double-blind, placebo-controlled Phase 1b/2a clinical trial to assess the safety and tolerability of WVE-003 in people with a confirmed diagnosis of HD who are in the early stages of the disease and carry SNP3 in association with their cytosine-adenine-guanine expansion. Additional objectives included assessing pharmacokinetics and exploratory pharmacodynamics and clinical endpoints.
Previous wording
In June 2024, we announced positive clinical data from the Phase 1b/2a SELECT-HD study of WVE-003. Results from the multi-dose portion of the trial, which evaluated three doses of 30mg WVE-003 administered every eight weeks, showed clear translation of target engagement to clinic with statistically significant, potent, durable and allele-selective reductions in cerebrospinal fluid (“CSF”) mHTT of up to 46% and preservation of healthy protein. This cohort also revealed a statistically significant correlation between mHTT reductions and slowing of caudate atrophy, indicating a potential benefit of allele-selective mHTT reductions. Structural brain magnetic resonance imaging (“MRI”) changes such as caudate atrophy are well-characterized measures of disease progression and neurodegeneration in HD. WVE-003 was generally safe and well-tolerated, with mild-to-moderate adverse events and no SAEs. In November 2024, five months after a patient completed their final safety visit, an SAE was reported that we assessed to be not-related to WVE-003.
Current wording
In June 2024, we announced positive clinical data from the Phase 1b/2a SELECT-HD study of WVE-003. Results from the multi-dose portion of the trial, which evaluated three doses of 30mg WVE-003 administered every eight weeks, showed clear translation of target engagement to clinic with statistically significant, potent, durable and allele-selective reductions in cerebrospinal fluid mHTT of up to 46% and preservation of healthy protein. This cohort also revealed a statistically significant correlation between mHTT reductions and slowing of caudate atrophy, indicating a potential benefit of allele-selective mHTT reductions. Structural brain magnetic resonance imaging changes such as caudate atrophy are well-characterized measures of disease progression and neurodegeneration in HD. WVE-003 was generally safe and well-tolerated, with mild-to-moderate adverse events and no SAEs. In November 2024, five months after a patient completed their final safety visit, an SAE was reported that we assessed to be not-related to WVE-003.
Previous wording
Following our positive clinical results, we initiated engagement with the FDA. In November 2024, we received supportive initial feedback from FDA, who recognize the severity of HD and are receptive to and engaged with us regarding a potential pathway to accelerated approval. FDA is open to our plan to evaluate biomarkers, including caudate atrophy, as an endpoint to assess HD progression with the potential to predict clinical outcome. Also in November 2024, FDA granted Orphan Drug Designation to WVE-003.
Current wording
Following our positive clinical results, we have engaged with the FDA and received supportive feedback. FDA recognizes the severity of HD and is receptive to and engaged with us regarding a potential pathway to accelerated approval. FDA is open to our plan to evaluate biomarkers, including caudate atrophy, as an endpoint to assess HD progression with the potential to predict clinical outcome. In November 2024, FDA granted Orphan Drug Designation to WVE-003.
Previous wording
Preparation is ongoing for a global, potentially registrational Phase 2/3 study of WVE-003 with caudate atrophy as a primary endpoint. We expect to submit an Investigational New Drug (“IND”) application for WVE-003 in the second half of 2025.
Current wording
Preparation is ongoing for a global, potentially registrational Phase 2/3 study of WVE-003 with caudate atrophy as a primary endpoint. We expect to submit an IND application for WVE-003 in the second half of 2025.
Previous wording
We are advancing new targets across multiple disease areas to expand our pipeline of wholly owned programs. Our compelling preclinical data indicate our oligonucleotides can distribute to various tissues and cells without complex delivery vehicles, enabling us to address a wide variety of diseases, including pulmonary and renal diseases. Within RNA editing, we have demonstrated clinically that we can address monogenic diseases by restoring healthy protein function for the treatment of AATD. Building on our work in AATD, we have shown our ability to correct single variants to restore wild-type protein function or to increase the stability of the mRNA transcript to upregulate protein levels. Utilizing our proprietary “edit-verse,” which is powered by genetic datasets and deep learning models, we have identified several RNA editing targets in indications that leverage easily accessible biomarkers, offer efficient paths to proof-of-concept in humans, and represent meaningful commercial opportunities.
Current wording
We are advancing new targets across multiple disease areas to expand our pipeline of wholly owned programs. Our compelling preclinical data demonstrate that our oligonucleotides can distribute to various tissues and cells without complex delivery vehicles, enabling us to address a wide variety of diseases. Within RNA editing, we have demonstrated clinically that we can address monogenic diseases by restoring healthy protein function for the treatment of AATD. Building on our work in AATD, we have shown our ability to correct single variants to restore wild-type protein function or to increase the stability of the mRNA transcript to upregulate protein levels. Building on our proprietary “edit-verse,” we are continuing to utilize a combination of human genetics and AI for drug discovery and development, and have identified several RNA editing and RNAi targets in indications that leverage easily accessible biomarkers, offer efficient paths to proof-of-concept in humans, and represent meaningful commercial opportunities. Within RNAi, we have shared preclinical data which support that our SpiNA designs enable RNAi-mediated silencing by further improving Ago2 loading and pharmacokinetics, leading to increased potency and durability compared to industry benchmarks. With our SpiNA designs, we have shared preclinical data demonstrating our ability to access extra-hepatic tissues including: adipose, heart, skeletal muscle, CNS, and kidney.
Previous wording
Through our collaboration with GSK, we are also leveraging GSK’s novel genetic insights to expand our wholly owned pipeline. In addition, we and GSK are actively working on multiple target validation programs as GSK-partnered programs, for which all of our costs and expenses are prepaid by GSK. In April 2024, GSK selected its first two programs to advance to development candidates following achievement of target validation, triggering an aggregate initiation payment to us of $12.0 million from GSK. These programs utilize our next generation GalNAc-siRNA format and are in hepatology.
Current wording
Through our collaboration with GSK, we are also leveraging GSK’s novel genetic insights to expand our wholly owned pipeline. In addition, we and GSK are actively working on multiple target validation programs as GSK-partnered programs, for which all of our costs and expenses are prepaid by GSK. GSK has selected three programs, across multiple modalities and hepatic and extra-hepatic tissues, to advance to development candidates following achievement of target validation, which have resulted in additional payments to us under the collaboration.
Previous wording
We have never been profitable, and since our inception, we have incurred significant operating losses. Our net loss for the three months ended June 30, 2025 and 2024 was $50.5 million and $32.9 million, respectively. Our net loss for the six months ended June 30, 2025 and 2024 was $ 97.3 million and $64.5 million, respectively. As of June 30, 2025 and December 31, 2024, we had an accumulated deficit of $1,219.2 million and $1,121.9 million, respectively. We expect to continue to incur significant expenses and operating losses for the foreseeable future.
Current wording
We have never been profitable, and since our inception, we have incurred significant operating losses. Our net loss for the three months ended September 30, 2025 and 2024 was $53.9 million and $61.8 million, respectively. Our net loss for the nine months ended September 30, 2025 and 2024 was $151.2 million and $126.3 million, respectively. As of September 30, 2025 and December 31, 2024, we had an accumulated deficit of $1,273.1 million and $1,121.9 million, respectively. We expect to continue to incur significant expenses and operating losses for the foreseeable future.
Previous wording
Our research and development expenses consist primarily of expenses related to our CROs, CMOs, consultants, other external vendors and fees paid to global regulatory agencies to conduct our clinical trials, in addition to compensation-related expenses, internal manufacturing expenses, facility-related expenses and other general operating expenses. These expenses are incurred in connection with research and development efforts and our preclinical studies and clinical trials. We track certain external expenses on a program-by-program basis. However, we do not allocate compensation-related expenses, internal manufacturing expenses, equipment repairs and maintenance expense, facility-related expenses or other operating expenses to specific programs. These expenses, which are not allocated on a program-by-program basis, are included in the “Other research and development expenses(1), including INHBE, RNA editing, PRISM, others” category along with other external expenses related to our discovery and development programs, as well as platform development and identification of potential drug discovery candidates.
Current wording
Our research and development expenses consist primarily of expenses related to our CROs, CMOs, consultants, other external vendors and fees paid to global regulatory agencies to conduct our clinical trials, in addition to compensation-related expenses, internal manufacturing expenses, facility-related expenses and other general operating expenses. These expenses are incurred in connection with research and development efforts and our preclinical studies and clinical trials. We track certain external expenses on a program-by-program basis. However, we do not allocate compensation-related expenses, internal manufacturing expenses, equipment repairs and maintenance expense, facility-related expenses or other operating expenses to specific programs. These expenses, which are not allocated on a program-by-program basis, are included in the “Other research and development expenses(1), including RNA editing, PRISM, others” category along with other external expenses related to our discovery and development programs, as well as platform development and identification of potential drug discovery candidates.
Previous wording
Revenue for the six months ended June 30, 2025 was $17.9 million and is comprised of revenue earned under the GSK Collaboration Agreement. Revenue for the six months ended June 30, 2024 was $32.2 million and is comprised of revenue earned under the GSK Collaboration Agreement and the Takeda Collaboration Agreement. The year-over-year change in revenue was primarily driven by the decrease in revenue recognized under the GSK Collaboration Agreement with a slight decrease in revenue under the Takeda Collaboration Agreement.
Current wording
Revenue for the three months ended September 30, 2025 was $7.6 million and is comprised of revenue earned under the GSK Collaboration Agreement. Revenue for the three months ended September 30, 2024 was $(7.7) million and is comprised of revenue under the GSK Collaboration Agreement and the Takeda Collaboration Agreement. The year-over-year change in revenue was primarily driven by an $8.0 million reduction to cumulative revenue recorded due to a change in the estimate to fulfill the GSK Collaboration Agreement performance obligations in accordance with the revenue recognition standard in three months ended September 30, 2024.
Previous wording
Research and development expenses were $43.5 million for the three months ended June 30, 2025, compared to $40.4 million for the three months ended June 30, 2024. The increase of approximately $3.1 million was due to the following:
Current wording
Research and development expenses were $45.9 million for the three months ended September 30, 2025, compared to $41.2 million for the three months ended September 30, 2024. The increase of approximately $4.7 million was due to the following:
Previous wording
a decrease of $1.3 million in external expenses related to our AATD program, WVE-006 (RNA editing);
Current wording
a decrease of $1.7 million in external expenses related to our AATD program, WVE-006 (RNA editing);
Previous wording
an increase of $1.9 million in external expenses related to our INHBE program, including WVE-007 (siRNA);
Current wording
an increase of $2.0 million in external expenses related to our INHBE program, including WVE-007 (siRNA);
Previous wording
a decrease of $1.4 million in external expenses related to our DMD program, including WVE-N531 (splicing);
Current wording
an increase of $1.6 million in external expenses related to our DMD program, including WVE-N531 (splicing);
Previous wording
a decrease of $2.8 million in external expenses related to our HD program, including WVE-003 (silencing); and
Current wording
a decrease of $3.3 million in external expenses related to our HD program, including WVE-003 (silencing); and
Previous wording
an increase of approximately $6.8 million in other research and development expenses(1), including RNA editing, PRISM, and other internal and external research and development expenses that are not allocated on a program-by-program basis or are related to other discovery and development programs, and the identification of potential drug discovery candidates, mainly due to increases in compensation-related expenses and in other external research and development expenses.
Current wording
an increase of approximately $6.1 million in other research and development expenses(1), including RNA editing, PRISM, and other internal and external research and development expenses that are not allocated on a program-by-program basis or are related to other discovery and development programs, and the identification of potential drug discovery candidates, mainly due to increases in compensation-related expenses and in other external research and development expenses.
Previous wording
General and administrative expenses were $18.0 million for the three months ended June 30, 2025, as compared to approximately $14.3 million for the three months ended June 30, 2024. The increase of approximately $3.7 million was primarily driven by increases in compensation related expenses and other external expenses.
Current wording
General and administrative expenses were $18.1 million for the three months ended September 30, 2025, as compared to approximately $15.0 million for the three months ended September 30, 2024. The increase of approximately $3.1 million was primarily driven by increases in compensation related expenses and other external expenses.
Previous wording
Other income, net for the three months ended June 30, 2025 and 2024 was $2.3 million and $2.1 million, respectively, and consisted primarily of interest income on cash and cash equivalents.
Current wording
Other income, net for the three months ended September 30, 2025 and 2024 was $2.5 million and $2.1 million, respectively, and consisted primarily of interest income on cash and cash equivalents.
Previous wording
Revenue for the three months ended June 30, 2025 was $8.7 million and is comprised of revenue earned under the GSK Collaboration Agreement. Revenue for the three months ended June 30, 2024 was $19.7 million and is comprised of revenue earned under the GSK Collaboration Agreement and the Takeda Collaboration Agreement. The year-over-year change in revenue was primarily driven by the decrease in revenue recognized under the GSK Collaboration Agreement with a slight decrease in revenue under the Takeda Collaboration Agreement.
Current wording
Revenue for the nine months ended September 30, 2025 was $25.5 million and is comprised of revenue earned under the GSK Collaboration Agreement. Revenue for the nine months ended September 30, 2024 was $24.6 million and is comprised of revenue earned under the GSK Collaboration Agreement and the Takeda Collaboration Agreement. The year-over-year change in revenue was primarily driven by an increase in revenue recognized under the GSK Collaboration Agreement, partially offset by a decrease in revenue recognized under the Takeda Collaboration Agreement.
Previous wording
Research and development expenses were $84.1 million for the six months ended June 30, 2025, compared to $73.8 million for the six months ended June 30, 2024. The increase of approximately $10.3 million was due to the following:
Current wording
Research and development expenses were $130.0 million for the nine months ended September 30, 2025, compared to $115.0 million for the nine months ended September 30, 2024. The increase of approximately $14.9 million was due to the following:
Previous wording
a decrease of $3.1 million in external expenses related to our AATD program, WVE-006 (RNA editing);
Current wording
a decrease of $4.8 million in external expenses related to our AATD program, WVE-006 (RNA editing);
Previous wording
an increase of $3.7 million in external expenses related to our INHBE program, including WVE-007 (siRNA);
Current wording
an increase of $5.7 million in external expenses related to our INHBE program, including WVE-007 (siRNA);
Previous wording
a decrease of $1.4 million in external expenses related to our DMD program, including WVE-N531 (splicing);
Current wording
an increase of $0.2 million in external expenses related to our DMD program, including WVE-N531 (splicing);
Showing the first 40 of 57 pairs. Open the source sections for the rest.
Rearranged current paragraphs (1)
Current report — wording carried from elsewhere
WVE-006 was generally safe and well tolerated with a favorable safety profile. All adverse events were mild to moderate in intensity, and there were no SAEs.
Rearranged previous paragraphs (4)
Previous report — wording carried elsewhere
In May 2025, we announced that we completed dosing in the first and second single dose cohorts of INLIGHT.
Previous report — wording carried elsewhere
In July of 2025, we announced that dosing is complete in the expanded Cohort 2 (240 mg) and that dosing is underway in Cohort 3 (400 mg) of INLIGHT.
Previous report — wording carried elsewhere
Also in March 2025, we announced that we met with the FDA on WVE-N531 to discuss our interim 24-week data and initial plans for the confirmatory trial, where the FDA confirmed that the accelerated approval pathway using dystrophin expression as a surrogate endpoint remains open.
Previous report — wording carried elsewhere
We plan to file a New Drug Application in 2026 to support accelerated approval of WVE-N531 with monthly dosing. We also expect to submit clinical trial applications for other exon skipping programs in 2026.