Wave Life Sciences Ltd.

Previous wording

The following discussion and analysis of our financial condition and results of operations should be read in conjunction with our financial statements and related notes appearing elsewhere in this Quarterly Report on Form 10-Q and in our Annual Report on Form 10-K for the year ended December 31, 2024, filed with the Securities and Exchange Commission (“SEC”) on March 4, 2025, as amended (the “2024 Annual Report on Form 10-K”). Some of the information contained in this discussion and analysis or set forth elsewhere in this Quarterly Report on Form 10-Q, including information with respect to our plans and strategy for our business, includes forward-looking statements that involve risks and uncertainties. As a result of many factors, including those factors set forth in the “Risk Factors” section of this Quarterly Report on Form 10-Q and the “Risk Factor” section of our 2024 Annual Report on Form 10-K, our actual results could differ materially from the results described in, or implied by, these forward-looking statements.

Current wording

The following discussion and analysis of our financial condition and results of operations should be read in conjunction with our financial statements and related notes appearing elsewhere in this Quarterly Report on Form 10-Q and in our Annual Report on Form 10-K for the year ended December 31, 2025, filed with the Securities and Exchange Commission (“SEC”) on February 26, 2026 (the “2025 Annual Report on Form 10-K”). Some of the information contained in this discussion and analysis or set forth elsewhere in this Quarterly Report on Form 10-Q, including information with respect to our plans and strategy for our business, includes forward-looking statements that involve risks and uncertainties. As a result of many factors, including those factors set forth in the “Risk Factors” section of this Quarterly Report on Form 10-Q and the “Risk Factors” section of our 2025 Annual Report on Form 10-K, our actual results could differ materially from the results described in, or implied by, these forward-looking statements.

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 (“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.

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, including RNAi interference (“RNAi”) (SpiNA) and RNA editing (AIMers), provides us with unmatched capabilities for designing and sustainably delivering candidates that optimally address disease biology. Our pipeline is focused on our obesity (WVE-007), alpha-1 antitrypsin deficiency (“AATD”) (WVE-006) and PNPLA3 I148M liver disease (WVE-008) programs, and also includes clinical programs for Duchenne muscular dystrophy (“DMD”) and Huntington’s disease (“HD”), as well as several preclinical programs utilizing our versatile RNA medicines platform.

Previous wording

The inspiration for our multimodal platform is based on the recognition that the biological machinery(i.e., enzymes) needed to address human disease already exists within our cells and can be harnessed for therapeutic purposes with the right tools. We believe that we have built the most versatile toolkit of RNA-targeting modalities in the industry, with multiple means of repairing, restoring, or reducing proteins and designing best-fit solutions based on the unique biology of a given disease target. We are actively advancing programs using four distinct modalities, including novel A-to-I RNA editing oligonucleotides (“AIMers”).

Current wording

The inspiration for our multimodal platform is based on the recognition that the biological machinery(i.e., enzymes) needed to address human disease already exists within our cells and can be harnessed for therapeutic purposes with the right tools. We believe that we have built the most versatile toolkit of RNA-targeting modalities in the industry, with multiple means of repairing, restoring, or reducing proteins and designing best-fit solutions based on the unique biology of a given disease target. We are actively advancing programs across modalities, including RNAi (silencing), RNA editing, which uses novel A-to-I RNA editing oligonucleotides (“AIMers”), antisense silencing, and splicing. We have also advanced novel bifunctional modalities designed to silence multiple targets or silence one target while simultaneously editing or upregulating another unique target.

Previous wording

Leverage diversity of expression across cell types by modulating the many regulatory pathways that impact gene expression, including transcription, endogenous RNA interference (“RNAi”) pathways, splicing, and translation;

Current wording

Leverage diversity of expression across cell types by modulating the many regulatory pathways that impact gene expression, including transcription, endogenous RNAi pathways, splicing, and translation;

Previous wording

GalNAc-conjugated oligonucleotides for hepatic and metabolic diseases including:

Current wording

We are currently prioritizing lead programs that use GalNAc delivery for hepatic and metabolic diseases, each of which has potential to translate powerful human genetic insights into potentially transformational RNA medicines:

Previous wording

Obesity: WVE-007 is a GalNAc-conjugated siRNA targeting inhibin βE (“INHBE”);

Current wording

WVE-007 is a GalNAc-conjugated siRNA (SpiNA design) targeting inhibin βE (“INHBE”) for obesity;

Previous wording

AATD: WVE-006 is a GalNAc-conjugated SERPINA1 AIMer;

Current wording

WVE-006 is a GalNAc-conjugated RNA editing oligonucleotide (AIMer) for AATD;

Previous wording

Liver disease: WVE-008 is a GalNAc-conjugated AIMer targeting PNPLA3 I148M; and

Current wording

WVE-008 is a GalNAc-conjugated RNA editing oligonucleotide (AIMer) for PNPLA3 I148M liver disease.

Previous wording

DMD: WVE-N531 is an exon 53 splicing oligonucleotide;

Current wording

Our clinical-stage portfolio also includes WVE-N531, an exon 53 splicing oligonucleotide for DMD, and WVE-003, an allele-selective oligonucleotide designed to lower mutant huntingtin (“mHTT”) protein and preserve healthy, wild-type huntingtin (“wtHTT”) protein. We are also advancing several emerging siRNA and RNA editing programs targeting both hepatic and extra-hepatic tissues.

Previous 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.

Current wording

WVE-007 is a GalNAc-siRNA, that utilizes Wave’s proprietary design (“SpiNA”). 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 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.

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. Weight loss was driven by visceral fat loss, and muscle mass was preserved in the mice, which is consistent with the profile of human INHBE LoF carriers. In DIO mice studies, a single dose of our INHBE GalNAc-siRNA led to a weight loss effect 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 a head-to-head study in DIO mice, 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.

Previous wording

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 wording

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, RNA sequencing data from subcutaneous adipose tissue indicates that INHBE GalNAc-siRNA leads to the upregulation of genes promoting insulin sensitivity, fatty acid utilization and beiging of white adipose, while downregulating adipose inflammation and fibrosis pathways. RNA sequencing data from visceral adipose tissue demonstrate that our INHBE GalNAc-siRNA increased glucose and fatty acid utilization, and reduced inflammation and fibrosis in adipose tissue.

Previous wording

Our AATD program uses our novel GalNAc-conjugated AIMers (RNA editing oligonucleotides) and endogenous ADAR enzymes to correct a single base in the mutant SERPINA1 mRNA. By correcting the single RNA base mutation that causes a majority of AATD cases with the Pi*ZZ genotype (approximately 200,000 in the United States and Europe), RNA editing may provide an ideal approach for increasing circulating levels of wild-type AAT protein and reducing mutant protein aggregation in the liver, thus simultaneously addressing both the lung and liver manifestations of the disease.

Current wording

Our AATD program uses our novel GalNAc-conjugated AIMers (RNA editing oligonucleotides) and endogenous ADAR enzymes to correct a single base in the mutant SERPINA1 mRNA. By correcting the single RNA base mutation that causes a majority of AATD cases with the Pi*ZZ genotype (approximately 200,000 in the United States and Europe), RNA editing may provide an ideal approach for increasing circulating levels of wild-type AAT protein and reducing mutant protein aggregation in the liver, thus simultaneously addressing both the lung and liver manifestations of the disease. WVE-006 does not require lipid nanoparticle (“LNP”) delivery, which may be associated with systemic and liver toxicities, and comes without the risk of irreversible, collateral bystander edits and indels, which are associated with DNA base editing.

Previous 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.

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 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 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 wording

In September 2025, we announced positive data from the 200 mg single and multidose (n=8), and 400 mg single dose (n=8) cohorts of the ongoing RestorAATion-2 study. Key highlights included:

Previous wording

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.

Current wording

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 serious adverse events (“SAEs”).

Previous wording

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 wording

To effectively address the manifestations of PNPLA3 I148M liver disease, we use our novel RNA editing approach and have advanced WVE-008, a GalNAc-conjugated AIMer, as our clinical candidate.

Previous wording

In DMD, we are advancing WVE-N531, which is designed to skip exon 53 within the dystrophin gene – a therapeutic approach that would address approximately 8-10% of DMD cases. WVE-N531 is designed to cause the cellular splicing machinery to skip over exon 53 during pre-mRNA processing, which restores the dystrophin mRNA reading frame and enables production of a truncated, but functional, dystrophin protein. Exon skipping produces dystrophin from the endogenous dystrophin gene (not micro or mini dystrophin expressed from a foreign vector), under the control of native gene-regulatory elements, resulting in physiological control over its expression. WVE-N531 is our first splicing candidate incorporating PN backbone (“PN”) chemistry to be assessed in the clinic. In the third quarter of 2024, the U.S. Food and Drug Administration (“FDA”) granted Rare Pediatric Disease Designation and Orphan Drug Designation to WVE-N531.

Current wording

In DMD, we are advancing WVE-N531, which is designed to skip exon 53 within the dystrophin gene – a therapeutic approach that would address approximately 8-10% of DMD cases. WVE-N531 is designed to cause the cellular splicing machinery to skip over exon 53 during pre-mRNA processing, which restores the dystrophin mRNA reading frame and enables production of a truncated, but functional, dystrophin protein. Exon skipping produces dystrophin from the endogenous dystrophin gene (not micro or mini dystrophin expressed from a foreign vector), under the control of native gene-regulatory elements, resulting in physiological control over its expression. WVE-N531 is our first splicing candidate incorporating PN backbone (“PN”) chemistry to be assessed in the clinic. In the third quarter of 2024, the FDA granted Rare Pediatric Disease Designation and Orphan Drug Designation to WVE-N531.

Previous wording

In March 2025, we announced positive data from the FORWARD-53 trial of WVE-N531, including biopsy data from eight boys with available biopsies at 24 and 48 weeks, as well as safety and functional outcome assessments for all participants. The results were analyzed after 48 weeks of 10 mg/kg of WVE-N531 dosed every two weeks and key highlights included:

Current wording

FORWARD-53, the Phase 1b/2a proof-of-concept, open label trial of WVE-N531 included “Part A,” in which 3 boys received 3 doses of WVE-N531 at 10 mg/kg every two weeks and “Part B,” in which 11 boys initially received 10 mg/kg every two weeks for 48 weeks. In “Part B”, biopsy data was gathered from eight boys after 24 and 48 weeks, as well as safety and functional outcome assessments for all participants. Key results from the study included:

Previous wording

In September 2023, we shared an analysis of muscle biopsy data from the Part A proof-of-concept trial indicating that WVE-N531 was present in myogenic stem cells, which are integral to muscle regeneration. This is the first demonstration of uptake in myogenic stem cells in a clinical study and supports the potential differentiation of WVE-N531 from other therapeutics, including gene therapies.

Current wording

WVE-N531 uptake in myogenic stem cells, which are integral to muscle regeneration, and in myofibers;

Previous wording

Dystrophin expression was quantified from two isoforms consistent with those observed in Becker muscular dystrophy patients who display milder disease. In addition, we observed meaningful improvements in serum biomarkers for muscle health, with localization of WVE-N531 in myogenic stem cells and in myofibers. Mean skeletal muscle concentrations of ~41,000 ng/g and a 61-day tissue half-life support monthly dosing going forward.

Current wording

Mean WVE-N531 skeletal muscle concentrations of ~41,000 ng/g and a 61-day tissue half-life support monthly dosing;

Previous wording

Statistically significant and clinically meaningful improvement of 3.8 seconds in Time-to-Rise vs. natural history with largest effect observed relative to any approved dystrophin restoration therapy at 48 weeks; additional functional benefits observed in other outcome measures including NSAA.

Current wording

Statistically significant and clinically meaningful improvement of 3.8 seconds in Time-to-Rise vs. natural history with largest effect observed relative to any approved dystrophin restoration therapy at 48 weeks; additional functional benefits observed in other outcome measures including North Star Ambulatory Assessment (“NSAA”);

Previous wording

Dystrophin expression stabilized between 24 and 48 weeks and averaged 7.8%, with 88% of boys above 5% average dystrophin.

Current wording

Dystrophin expression stabilized between 24 and 48 weeks and averaged 7.8% with 88% of boys above 5% average dystrophin; and

Previous wording

WVE-N531 remains generally safe and well-tolerated with no SAEs observed.

Current wording

WVE-N531 was generally safe and well-tolerated with no SAEs observed.

Previous 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.

Current 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 expanded FORWARD-53 to include additional boys on a monthly dosing regimen. We plan to file a New Drug Application in 2026 to support accelerated approval of WVE-N531 with monthly dosing.

Previous wording

In HD, we are currently advancing WVE-003, a stereopure allele-selective oligonucleotide designed to selectively target rs362273, a variant of the single nucleotide polymorphism (“SNP”), “mHTT SNP3”, associated with the disease-causing mHTT mRNA transcript within the Huntingtin (“HTT”) gene. Approximately 40% of the HD population carries SNP3 according to published literature (Carroll et al., Molecular Therapy, 2011), and up to 80% of HD may be addressed in the future with other SNP-targeted candidates. There are currently no disease modifying therapies for HD, which affects over 200,000 individuals across all disease stages in the United States and Europe alone.

Current wording

WVE-003 is our stereopure allele-selective oligonucleotide that incorporates our proprietary PN chemistry and is designed to selectively target rs362273, a variant of the single nucleotide polymorphism (“SNP”), “mHTT SNP3”, associated with the disease-causing mHTT mRNA transcript within the HTT gene (Iwamoto et al., MTNA). Targeting mRNA through SNP3 allows us to lower expression of transcript from the mutant allele, while leaving the healthy transcript relatively intact, thereby preserving wild-type (healthy) huntingtin (“wtHTT”) protein, which is important for neuronal function. Approximately 40% of the HD population carries SNP3 according to published literature (Carroll et al., Molecular Therapy, 2011), and up to 80% of HD may be addressed in the future with other SNP-targeted candidates.

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 pharmacodynamics and clinical endpoints.

Current wording

SELECT-HD 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 were in the early stages of the disease and carry SNP3 in association with their cytosine adenine guanine (“CAG”) expansion. Additional objectives included assessing PK 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 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.

Current wording

In June 2024, we announced positive clinical data from the SELECT-HD study. Results from the multi-dose portion of the trial, which evaluated three doses of 30 mg 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 a mean 46%, with preservation of wtHTT protein. The multi-dose cohort also revealed a statistically significant correlation between mHTT reduction and slowing of caudate atrophy, indicating a potential benefit of allele-selective mHTT reductions. Caudate atrophy, as measured by MRI, is a well-characterized measure of disease progression in HD. In the multi-dose cohort, WVE-003 was generally safe and well-tolerated, with mild-to-moderate adverse events (“AEs”) 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 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.

Current wording

Following our positive clinical results, we initiated engagement with the FDA. In November 2024, we received supportive initial feedback from the FDA, who recognize the severity of HD and are receptive to and engaged with us regarding a potential pathway to accelerated approval. The 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 outcomes. Also in November 2024, the FDA granted Orphan Drug Designation to WVE-003.

Previous 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.

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 correcting the disease-causing mutation, as evidenced by restoration of healthy protein function for the treatment of AATD. Beyond correction, we have preclinical data demonstrating our ability to increase the stability of the mRNA transcript to upregulate protein levels. Within RNAi, we have shared preclinical data which show 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, our preclinical data demonstrate we can silence targets in extra-hepatic tissues including adipose, skeletal muscle, heart, central nervous system (“CNS”), and kidney. We are utilizing a combination of human genetics and artificial intelligence (“AI”) for target discovery and oligonucleotide design, and we have initiated a number of preclinical RNA editing and RNAi programs supported by evidence from human genetics, that leverage easily accessible biomarkers, offer efficient paths to proof-of-concept in humans, and represent meaningful commercial opportunities.

Previous wording

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 wording

We have applied learnings from across our platform and chemistry optimization to investigate new bifunctional modalities which combine RNAi and RNA editing or dual RNAi silencing into a single oligonucleotide construct. These constructs are designed to silence multiple targets or silence one target while simultaneously editing or upregulating another distinct target. We demonstrated the ability of a single bifunctional oligonucleotide to engage in silencing and editingin vivo in mice 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 low-density lipoprotein receptor and silence PCSK9 using a single construct in primary human hepatocytes.

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. 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.

Current wording

Through our collaboration with GlaxoSmithKline Intellectual Property (No. 3) (“GSK”), we 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 four programs, across multiple modalities in both 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 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.

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 March 31, 2026 and 2025 was $26.1 million and $46.9 million, respectively. As of March 31, 2026 and December 31, 2025, we had an accumulated deficit of $1,352.3 million and $1,326.2 million, respectively. We expect to continue to incur significant expenses and operating losses for the foreseeable future.

Previous wording

Our primary research and development focus has been the development of our RNA medicines platform, PRISM. We are using PRISM, which includes our novel chemistry modifications, to design, develop and commercialize a broad pipeline of first- or best-in-class RNA medicines using our editing, RNAi, splicing, and antisense modalities.

Current wording

Our primary research and development focus has been the development of our RNA medicines platform, PRISM. We are using PRISM, which combines multiple modalities, chemistry innovation and deep insights in human genetics, to deliver scientific breakthroughs that treat both rare and common disorders, and advance our pipeline of RNA medicines.

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 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 expenses, 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 PNPLA3, additional preclinical programs, PRISM” 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 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.

Current wording

Revenue for the three months ended March 31, 2026 and 2025 was $38.2 million and $9.2 million, respectively, and is comprised of revenue earned under the GSK Collaboration Agreement. The year-over-year change in revenue was primarily driven by the recognition of the remaining deferred revenue related to the AATD performance obligation ($35.9 million), which was fully satisfied upon the termination of the AATD license, in the three months ended March 31, 2026.

Previous 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:

Current wording

Research and development expenses were $47.4 million for the three months ended March 31, 2026, compared to $40.6 million for the three months ended March 31, 2025. The increase of approximately $6.8 million was due to the following:

Previous wording

an increase of $2.0 million in external expenses related to our INHBE program, including WVE-007 (siRNA);

Current wording

an increase of $2.3 million in external expenses related to our INHBE program, including WVE-007 (RNAi);

Previous wording

a decrease of $1.7 million in external expenses related to our AATD program, WVE-006 (RNA editing);

Current wording

an increase of $0.3 million in external expenses related to our AATD program, WVE-006 (RNA editing);

Previous wording

an increase of $1.6 million in external expenses related to our DMD program, including WVE-N531 (splicing);

Current wording

an increase of $1.1 million in external expenses related to our DMD program, including WVE-N531 (splicing);