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What changed in Wave Life Sciences Ltd.'s 10-K — 2024 vs 2025

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Paragraph-level year-over-year comparison of Wave Life Sciences Ltd.'s 2024 and 2025 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2025 report.

+407 added−499 removedSource: 10-K (2026-02-26) vs 10-K (2025-03-04)

Top changes in Wave Life Sciences Ltd.'s 2025 10-K

407 paragraphs added · 499 removed · 288 edited across 7 sections

Item 1. Business

Business — how the company describes what it does

140 edited+84 added−160 removed301 unchanged
Biggest changeDiscovery Pipeline We are advancing new targets across multiple disease areas to expand our pipeline of wholly owned programs. Our compelling preclinical data indicates 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.
Biggest changeOur 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.
European Union Orphan Drug Designation In the EU, orphan drug designation by the European Commission (the “EC”) provides regulatory and financial incentives for companies to develop and market therapies that meet the following requirements: (1) the product is intended for the diagnosis, 39 prevention or treatment of life-threatening or chronically debilitating conditions; (2) either (a) such condition affects no more than five in 10,000 persons in the European Union when the application is made, or (b) the product, without the benefits derived from orphan status, would not generate sufficient return in the European Union to justify investment; and (3) there exists no satisfactory method of diagnosis, prevention or treatment of such condition authorized for marketing in the European Union, or if such a method exists, the product will be of significant benefit to those affected by the condition, as defined in Regulation (EC) 847/2000.
European Union Orphan Drug Designation In the EU, orphan drug designation by the European Commission (the “EC”) provides regulatory and financial incentives for companies to develop and market therapies that meet the following requirements: (1) the product is intended for the diagnosis, prevention or treatment of life-threatening or chronically debilitating conditions; (2) either (a) such condition affects no more than five in 10,000 persons in the European Union when the application is made, or (b) the product, without the benefits derived from orphan status, would not generate sufficient return in the European Union to justify investment; and (3) there exists no satisfactory method of diagnosis, prevention or treatment of such condition authorized for marketing in the European Union, or if such a method exists, the product will be of significant benefit to those affected by the condition, as defined in Regulation (EC) 847/2000.
However, the FDA may decide that it is appropriate to approve such a therapeutic product without an approved or cleared in vitro companion diagnostic device when the drug or therapeutic biologic is intended to treat a serious or life-threatening condition for which no satisfactory alternative treatment exists and the FDA determines that the benefits from the use of a product with an 41 unapproved or uncleared in vitro companion diagnostic device are so pronounced as to outweigh the risks from the lack of an approved or cleared in vitro companion diagnostic device.
However, the FDA may decide that it is appropriate to approve such a therapeutic product without an approved or cleared in vitro companion diagnostic device when the drug or therapeutic biologic is intended to treat a serious or life-threatening condition for which no satisfactory alternative treatment exists and the FDA determines that the benefits from the use of a product with an unapproved or uncleared in vitro companion diagnostic device are so pronounced as to outweigh the risks from the lack of an approved or cleared in vitro companion diagnostic device.
When Phase 2 evaluations demonstrate that a dose range of the product appears to be effective and has an acceptable safety profile, trials are undertaken in larger patient populations 34 to further evaluate dosage, to obtain substantial, statistical evidence of clinical efficacy and safety, generally at multiple, geographically-dispersed clinical trial sites, to establish the overall risk-benefit relationship of the product and to provide adequate information for approval of the product. • Phase 4.
When Phase 2 evaluations demonstrate that a dose range of the product appears to be effective and has an acceptable safety profile, trials are undertaken in larger patient populations to further evaluate dosage, to obtain substantial, statistical evidence of clinical efficacy and safety, generally at multiple, geographically-dispersed clinical trial sites, to establish the overall risk-benefit relationship of the product and to provide adequate information for approval of the product. • Phase 4.
With respect to the $50.0 million equity investment referred to above, simultaneously with our entry into the GSK Collaboration Agreement, we entered into a share purchase agreement with Glaxo Group Limited (“GGL”), an affiliate of GSK, pursuant to which 29 we agreed to sell to GGL 10,683,761 of our ordinary shares at a purchase price of $4.68 per share, for an aggregate purchase price of approximately $50.0 million (the “GSK Equity Investment”).
With respect to the $50.0 million equity investment referred to above, simultaneously with our entry into the GSK Collaboration Agreement, we entered into a share purchase agreement with Glaxo Group Limited (“GGL”), an affiliate of GSK, pursuant to which we agreed to sell to GGL 10,683,761 of our ordinary shares at a purchase price of $4.68 per share, for an aggregate purchase price of approximately $50.0 million (the “GSK Equity Investment”).
Through PRISM, our efforts continue to reveal structure-activity relationships among base modifications and sequence, chemistry and backbone stereochemistry that may allow us to further tune the activity of our oligonucleotides in a previously unexplored, modality-specific manner. 16 • Rapidly advance and sustainably grow our differentiated portfolio of RNA medicines.
Through PRISM, our efforts continue to reveal structure-activity relationships among base modifications and sequence, chemistry and backbone stereochemistry that may allow us to further tune the activity of our oligonucleotides in a previously unexplored, modality-specific manner. • Rapidly advance and sustainably grow our differentiated portfolio of RNA medicines.
The FDA is not bound by the recommendation of an advisory committee, but it considers such recommendations when making final decisions on approval. The FDA likely will re-analyze the clinical trial data, which could result 35 in extensive discussions between the FDA and the applicant during the NDA review process.
The FDA is not bound by the recommendation of an advisory committee, but it considers such recommendations when making final decisions on approval. The FDA likely will re-analyze the clinical trial data, which could result in extensive discussions between the FDA and the applicant during the NDA review process.
It is expected that the establishment of a separate United Kingdom authorization system, albeit with transitional recognition procedures in the United Kingdom, will lead to additional regulatory costs. 43 Rest of World Government Regulation The requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary from country to country.
It is expected that the establishment of a separate United Kingdom authorization system, albeit with transitional recognition procedures in the United Kingdom, will lead to additional regulatory costs. Rest of World Government Regulation The requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary from country to country.
Manufacturing To provide internal cGMP manufacturing capabilities and increase control and visibility of our drug product supply chain, we entered into a lease in September 2016 for a multi-use facility of approximately 90,000 square feet in Lexington, Massachusetts and initiated the build out of manufacturing space and related capabilities.
Manufacturing To provide internal cGMP manufacturing capabilities of drug substance and increase control and visibility of our drug product supply chain, we entered into a lease in September 2016 for a multi-use facility of approximately 90,000 square feet in Lexington, Massachusetts and initiated the build out of manufacturing space and related capabilities.
Beyond these approved therapies, there are investigational oral GLP-1 receptor agonists and other GLP-1 receptor agonist combinations (e.g., GLP-1/GIP/glucagon receptor agonists, GLP-1/glucagon receptor agonists, GLP-1/amylin receptor agonists, GLP-1/GLP-2 receptor agonists, etc.) in various stages of clinical development. Other FDA-approved therapies for obesity include Xenical (H2-Pharma), Qsymia (Vivus), and Contrave (Currax Pharmaceuticals).
Beyond these approved therapies, there are other investigational oral GLP-1 receptor agonists, other GLP-1 receptor agonist combinations (e.g., GLP-1/GIP/glucagon receptor agonists, GLP-1/glucagon receptor agonists, GLP-1/amylin receptor agonists, GLP-1/GLP-2 receptor agonists, etc.), and other mechanisms (e.g., amylin) in various stages of clinical development. Other FDA-approved therapies for obesity include Xenical (H2-Pharma), Qsymia (Vivus), and Contrave (Currax Pharmaceuticals).
The process required by the FDA before a new drug product may be marketed in the United States generally involves: • completion of preclinical testing in compliance with applicable FDA good laboratory practice regulations and other requirements (“GLP”); • submission to the FDA of an IND for human clinical testing which must become effective before human clinical trials may begin in the United States; • approval by an independent institutional review board (“IRB”) at each site where a clinical trial will be performed before the trial may be initiated at that site; • performance of adequate and well-controlled human clinical trials in accordance with good clinical practice (“GCP”), as well as other clinical research regulations, to establish safety and substantial evidence of effectiveness of the proposed product candidate for each intended use; • thorough characterization of the product candidate and establishment of acceptable standards to ensure suitable purity, identity, strength, quality and stability in compliance with cGMP; • satisfactory completion of an FDA pre-approval inspection of the facility or facilities at which the product is manufactured to assess compliance with cGMP; • satisfactory completion of an FDA pre-approval inspection of one or more clinical trial site(s) or the sponsor’s site and/or contract research organization responsible for conduct of key clinical trials in accordance with GCP; • submission to the FDA of a New Drug Application (“NDA”), which must be accepted for filing by the FDA; 33 • completion of an FDA advisory committee review, if applicable; • payment of user fees, if applicable; and • FDA review and approval of the NDA.
The process required by the FDA before a new drug product may be marketed in the United States generally involves: • completion of preclinical testing in compliance with applicable FDA good laboratory practice regulations and other requirements (“GLP”); • submission to the FDA of an IND for human clinical testing which must become effective before human clinical trials may begin in the United States; • approval by an independent institutional review board (“IRB”) at each site where a clinical trial will be performed before the trial may be initiated at that site; • performance of adequate and well-controlled human clinical trials in accordance with good clinical practice (“GCP”), as well as other clinical research regulations, to establish safety and substantial evidence of effectiveness of the proposed product candidate for each intended use; • thorough characterization of the product candidate and establishment of acceptable standards to ensure suitable purity, identity, strength, quality and stability in compliance with cGMP; • satisfactory completion of an FDA pre-approval inspection of the facility or facilities at which the product is manufactured to assess compliance with cGMP; • satisfactory completion of an FDA pre-approval inspection of one or more clinical trial site(s) or the sponsor’s site and/or contract research organization responsible for conduct of key clinical trials in accordance with GCP; • submission to the FDA of an NDA, which must be accepted for filing by the FDA; • completion of an FDA advisory committee review, if applicable; • payment of user fees, if applicable; and • FDA review and approval of the NDA.
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. 15 Following our positive clinical results, we initiated engagement with the FDA.
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. Following our positive clinical results, we initiated engagement with the FDA.
The cGMP requirements include requirements relating to, among other things, organization of personnel, buildings and facilities, equipment, control of components and drug product containers and closures, production and process controls, packaging and labeling controls, holding and distribution, 46 laboratory controls, records and reports, and returned or salvaged products.
The cGMP requirements include requirements relating to, among other things, organization of personnel, buildings and facilities, equipment, control of components and drug product containers and closures, production and process controls, packaging and labeling controls, holding and distribution, laboratory controls, records and reports, and returned or salvaged products.
Obesity There are two GLP-1 receptor agonists approved in the United States for the treatment of obesity: Saxenda (liraglutide, Novo Nordisk) and Wegovy (semaglutide, Novo Nordisk). Zepbound (tirzepatide, Eli Lilly), approved by the FDA in November 2023, is a GLP-1/GIP receptor agonist.
Obesity There are two GLP-1 receptor agonists approved in the United States for the treatment of obesity: Saxenda (liraglutide, Novo Nordisk) and Wegovy / Wegovy pill (semaglutide, Novo Nordisk). Zepbound (tirzepatide, Eli Lilly), approved by the FDA in November 2023, is a GLP-1/GIP receptor agonist.
Finally, the FDA may designate a product for priority review if it is a drug or biologic that treats a serious condition and, if approved, would provide a significant improvement in safety or effectiveness over existing therapy.
The FDA may designate a product for priority review if it is a drug or biologic that treats a serious condition and, if approved, would provide a significant improvement in safety or effectiveness over existing therapy.
The process for determining whether a payor will provide coverage for a product 44 may be separate from the process for setting the price or reimbursement rate that the payor will pay for the product once coverage is approved.
The process for determining whether a payor will provide coverage for a product may be separate from the process for setting the price or reimbursement rate that the payor will pay for the product once coverage is approved.
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 are in the early stages of the disease and carry SNP3 in association with their CAG expansion. Additional objectives included assessing PK and exploratory PD and clinical endpoints.
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 CAG expansion. Additional objectives included assessing PK and exploratory PD and clinical endpoints.
To date, no clinical benefit of Vyondys 53 or Viltepso has been established. Sarepta Therapeutics’ Elevidys, a microdystrophin gene therapy, is available in the United States and some ex-EU markets. Its current indication in the US is for ambulatory and non‑ambulatory DMD patients aged at least four years who have a confirmed mutation in the DMD gene.
To date, no clinical benefit of Vyondys 53 or Viltepso has been established. Sarepta Therapeutics’ Elevidys, a microdystrophin gene therapy, is available in the United States and some ex-EU markets. Its current indication in the US is for ambulatory patients with DMD aged at least four years who have a confirmed mutation in the DMD gene.
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 outcome.
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.
Several of our patent filings directed to stereopure compositions have entered national stage prosecution in multiple jurisdictions and some have issued in one or more jurisdictions; others are in the international stage. Certain filings offer 20-year protection terms that range from 2033 to at least 2044.
Several of our patent filings directed to stereopure compositions have entered national stage prosecution in multiple jurisdictions and some have issued in one or more jurisdictions; others are in the international stage. Certain filings offer 20-year protection terms that range from 2033 to at least 2045.
Current Treatments There are two GLP-1 receptor agonists approved in the United States and the European Union (“EU”) for the treatment of obesity: Saxenda (liraglutide, Novo Nordisk) and Wegovy (semaglutide, Novo Nordisk). Tirzepatide (Eli Lilly), approved as Zepbound by the U.S.
Current Treatments There are two GLP-1 receptor agonists (“GLP-1s”) approved in the United States and the European Union (“EU”) for the treatment of obesity: Saxenda (liraglutide, Novo Nordisk) and Wegovy (semaglutide, Novo Nordisk). Tirzepatide (Eli Lilly), approved as Zepbound by the U.S.
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.
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.
To our knowledge, we have the most advanced clinical stage program targeting allele-selective mHTT lowering. Several companies have ongoing discovery or preclinical programs for HD, including Atalanta Therapeutics, Ophidion, Roche, Sangamo Therapeutics and Takeda, Spark Therapeutics, and Voyager Therapeutics and Novartis, among others. Molecules to treat symptoms associated with HD are also in development.
To our knowledge, we have the most advanced clinical stage program targeting allele-selective mHTT lowering. Several companies have ongoing discovery or preclinical programs for HD, including Atalanta Therapeutics, Ophidion, Sangamo Therapeutics and Takeda, Sarepta Therapeutics, and Voyager Therapeutics and Novartis, among others. Molecules to treat symptoms associated with HD are also in development.
We also have applications pending in multiple jurisdictions around the world, including these major market jurisdictions. Synthetic Methodologies Our patent portfolio includes multiple families that protect synthetic methodologies and/or reagents for generating stereopure oligonucleotide compositions. 30 Certain such families have 20-year expiration dates that range from 2029 to at least 2043.
We also have applications pending in multiple jurisdictions around the world, including these major market jurisdictions. Synthetic Methodologies Our patent portfolio includes multiple families that protect synthetic methodologies and/or reagents for generating stereopure oligonucleotide compositions. Certain such families have 20-year expiration dates that range from 2029 to at least 2045.
Additionally, starting in payment year 2026, CMS will negotiate drug prices annually for a select number of single source Part D drugs without generic or biosimilar competition. CMS will also negotiate drug prices for a select number of Part B drugs starting for payment year 2028.
Additionally, CMS will negotiate drug prices annually for a select number of single source Part D drugs without generic or biosimilar competition. CMS will also negotiate drug prices for a select number of Part B drugs starting for payment year 2028.
F or example, in recent years, several states have formed prescription drug affordability boards (“PDABs”). Much like the IRA’s drug price negotiation program, these PDABs have attempted to implement upper payment limits (“UPLs”) on drugs sold in their respective states in both public and commercial health plans.
For example, in recent years, several states have formed prescription drug affordability boards (“PDABs”). Much like the IRA’s drug price negotiation program, these PDABs have attempted to implement upper payment limits (“UPLs”) on drugs sold in their respective states in both public and commercial health plans.
Other potential consequences include, among other things: • issuance of field alerts, restrictions on the marketing or manufacturing of the product, product recalls, or complete withdrawal of the product from the market; • mandated modification of promotional materials and labeling and the issuance of corrective information; • fines, warning letters or other enforcement-related letters or holds on clinical trials using the product or other products manufactured at the same facility; • refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of product approvals; • withdrawal of approval for any products approved through FDA’s accelerated approval pathway if required confirmatory trials are not completed on time, or at all; • product seizure or detention, or refusal to permit the import or export of products; • injunctions or the imposition of civil or criminal penalties; and • consent decrees, corporate integrity agreements, debarment, or exclusion from federal healthcare programs. 38 The FDA strictly regulates marketing, labeling, advertising and promotion of products that are placed on the market.
Other potential consequences include, among other things: • issuance of field alerts, restrictions on the marketing or manufacturing of the product, product recalls, or complete withdrawal of the product from the market; • mandated modification of promotional materials and labeling and the issuance of corrective information; • fines, warning letters or other enforcement-related letters or holds on clinical trials using the product or other products manufactured at the same facility; • refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of product approvals; • withdrawal of approval for any products approved through FDA’s accelerated approval pathway if required confirmatory trials are not completed on time, or at all; • product seizure or detention, or refusal to permit the import or export of products; • injunctions or the imposition of civil or criminal penalties; and • consent decrees, corporate integrity agreements, debarment, or exclusion from federal healthcare programs.
We believe that PRISM has the potential to set a new industry standard for the molecular characterization of complex oligonucleotide mixtures. Our rational process for designing stereopure oligonucleotides allows us to selectively optimize chemical modifications to a specific therapeutic modality in order to generate best-in-class oligonucleotides.
We believe that PRISM has the potential to set a new industry standard for the molecular characterization of therapeutic oligonucleotides. Our rational process for designing stereopure oligonucleotides allows us to selectively optimize chemical modifications to a specific therapeutic modality in order to generate best-in-class oligonucleotides.
Patients with HD still express some wtHTT protein, which is important for neuronal function, and which may be neuroprotective in an adult brain. Studies suggest a multifaceted mechanism by which gain of mHTT protein and a concurrent loss of wtHTT protein may drive the pathophysiology of HD.
Patients with HD still express some wtHTT protein, which is important for neuronal function, and which may be neuroprotective in an adult brain and specifically protective against HD. Studies suggest a multifaceted mechanism by which gain of mHTT protein and a concurrent loss of wtHTT protein may drive the pathophysiology of HD.
Reauthorization of the prescription drug user fee program would need to be finalized by Congress by the end of September 2027 in order to avoid a disruption in FDA’s review goals for NDAs and other activities supported by user fees assessed against industry.
Reauthorization of the prescription drug user fee program must be finalized by Congress by the end of September 2027 in order to avoid a disruption in FDA’s review goals for NDAs and other activities supported by user fees assessed against industry.
We believe that listening to, learning from, and partnering with individuals impacted by the diseases we hope to address , including families and caregivers, connects us more deeply to our mission, and enhances our ability to discover and develop meaningful therapies.
We believe that listening to, learning from, and partnering with individuals impacted by the diseases we are aiming to address, including families and caregivers, connects us more deeply to our mission and enhances our ability to discover and develop meaningful therapies.
This approach avoids the need, and certain limitations, for complex delivery vehicles such as lipid nanoparticles (“LNPs”) or adeno-associated viruses (“AAV”). 17 • Proprietary production of stereopure oligonucleotides and scalable manufacturing . Our scientists have developed expertise in the techniques required to produce adequate supplies of chemically modified stereopure oligonucleotide materials for our preclinical and clinical activities.
This approach avoids the need, and certain limitations, for complex delivery vehicles such as LNPs or adeno-associated viruses (“AAV”). • Proprietary production of stereopure oligonucleotides and scalable manufacturing . Our scientists have developed expertise in the techniques required to produce adequate supplies of chemically modified stereopure oligonucleotide materials for our preclinical and clinical activities.
The IVDR imposes additional requirements relating to post-market surveillance and submission of post-market performance follow-up reports. The EC has designated thirteen Notified Bodies to perform conformity assessments under the IVDR. MedTech Europe has issued guidance relating to the IVDR in several areas, e.g., clinical benefit, technical documentation, state of art, accessories, and EUDAMED.
The IVDR imposes additional requirements relating to post-market surveillance and submission of post-market performance follow-up reports. The EC has designated more than a dozen Notified Bodies to perform conformity assessments under the IVDR. MedTech Europe has issued guidance relating to the IVDR in several areas, e.g., clinical benefit, technical documentation, state of art, accessories, and EUDAMED.
The addition of PN chemistry drove a greater than 2-fold increase in cellular uptake and an over 4-fold increase in endosomal release compared with PS chemistry.
The addition of PN chemistry drove a greater than 2-fold increase in cellular uptake and an over 4-fold increase in endosomal release compared with AIMers lacking PN chemistry.
The CREATES Act aims to address the concern articulated by both the FDA and others in the industry that some brand manufacturers have improperly restricted the distribution of their products, including by invoking the existence of a REMS for certain products, to deny generic product developers access to samples of brand products.
The CREATES Act was enacted to address the concern articulated by both the FDA and others in the industry that some brand manufacturers had improperly restricted the distribution of their products, including by invoking the existence of a REMS for certain products, to deny generic product developers access to samples of brand products.
The key components of our strategy are as follows: • Extend our leadership in RNA medicines . We intend to establish a dominant position in the field of oligonucleotides, advancing basic research and pharmacology using stereochemistry and other novel modifications across multiple therapeutic modalities and target classes.
The key components of our strategy are as follows: • Extend our leadership in RNA medicines . We are establishing dominant position in the field of oligonucleotides, advancing basic research and pharmacology using stereochemistry and other novel modifications across multiple therapeutic modalities and target classes.
Patient Advocacy and Community Engagement : Our community engagement activities are focused on seeking to better understand the lived experience of people i mpacted by rare and prevalent diseases and identifying opportunities to support these communities .
Advocacy and Community Engagement: Our community engagement activities are focused on seeking to better understand the lived experience of people impacted by rare and prevalent diseases and identifying opportunities to support these communities.
We make these reports available through the “For Investors & Media – SEC Filings” section of our website as soon as reasonably practicable after we electronically file such reports with, or furnish such reports to, the SEC.
We make these reports available through the “Investors – SEC Filings” section of our website as soon as reasonably practicable after we electronically file such reports with, or furnish such reports to, the SEC.
In addition, assuming WVE-006 and GSK’s eight collaboration programs achieve initiation, development, launch, and commercialization milestones, we would be eligible to receive up to $3.3 billion in cash milestone payments, which are described in the following paragraphs.
In addition, assuming GSK’s eight collaboration programs achieve initiation, development, launch, and commercialization milestones, we would be eligible to receive up to $2.8 billion in cash milestone payments, which are described in the following paragraphs.
Under federal law, the fee for the submission of an NDA with clinical data is substantial (for example, for fiscal year 2025 this application fee exceeds $4.3 million), and the sponsor of an approved NDA is also subject to an annual program fee, currently more than $400,000 per program.
Under federal law, the fee for the submission of an NDA with clinical data is substantial (for example, for fiscal year 2026 this application fee exceeds $4.6 million), and the sponsor of an approved NDA is also subject to an annual program fee, currently more than $440,000 per program.
In preclinical experiments, we have demonstrated that judicious use of PN backbone chemistry modifications in stereopure oligonucleotides have generally increased potency, tissue exposure and durability of effect across our RNA editing, siRNA, splicing, and antisense modalities. 18 We have also investigated the impact of PN chemistry and performed experiments under gymnotic or free uptake conditions.
In preclinical experiments, we have demonstrated that judicious use of PN backbone chemistry modifications in stereopure oligonucleotides have generally increased potency, tissue exposure and durability of effect across our RNA editing, siRNA, splicing, and antisense modalities. We have also investigated the impact of PN chemistry on cellular uptake and trafficking using gymnotic or free uptake conditions.
We have built a hybrid internal / external manufacturing model that gives us the capability to produce stereopure oligonucleotides at scales from one micromole to potential commercial scale.
We have built a hybrid internal / external manufacturing model that enables us to produce stereopure oligonucleotides at scales from one micromole to potential commercial scale.
Compliance with applicable environmental laws and regulations is expensive, and current or future environmental regulations may impair our research, development and production efforts, which could negatively impact our business, operating results and financial condition. Human Capital As of December 31, 2024, we employed 288 employees, of which 287 were full-time employees.
Compliance with applicable environmental laws and regulations is expensive, and current or future environmental regulations may impair our research, development and production efforts, which could negatively impact our business, operating results and financial condition. Human Capital As of December 31, 2025, we employed 317 employees, all of whom were full-time employees.
Medium spiny neurons in a deep brain region called the striatum, which is composed of caudate and putamen, are particularly sensitive to death in HD.
Medium spiny neurons in a deep brain region called the striatum, which includes caudate and putamen, are particularly sensitive to death in HD.
(“Wave USA”), a Delaware corporation (formerly Ontorii, Inc.); Wave Life Sciences Japan, Inc. (“Wave Japan”), a company organized under the laws of Japan (formerly Chiralgen., Ltd.); Wave Life Sciences Ireland Limited (“Wave Ireland”), a company organized under the laws of Ireland; and Wave Life Sciences UK Limited (“Wave UK”), a company organized under the laws of the United Kingdom.
(“Wave Japan”), a company organized under the laws of Japan (formerly Chiralgen., Ltd.); Wave Life Sciences Ireland Limited (“Wave Ireland”), a company organized under the laws of Ireland; and Wave Life Sciences UK Limited (“Wave UK”), a company organized under the laws of the United Kingdom.
Additionally, in a separate ongoing study in DIO mice, 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 study. Left: 10nmol/kg in mouse is equivalent to therapeutic dose of GLP-1s in human.
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. Left: 10 nmol/kg in mouse is equivalent to therapeutic dose of GLP-1s in human.
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. WVE-003 incorporates our proprietary PN chemistry.
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.
Although GLP-1 receptor agonists induce weight loss, there remains a substantial unmet need in obesity, as GLP-1 receptors lead to weight loss at the expense of muscle mass.
Although GLP-1s induce weight loss, there remains a substantial unmet need in obesity, as GLP-1s lead to weight loss at the expense of muscle mass.
As with PS modifications, PN modifications are chiral, and we have the capacity to control PN backbone stereochemistry. Unlike PS modifications, PN modifications are neutral, meaning that the negative charge of the oligonucleotide is reduced with every PN modification added to the backbone.
We have incorporated these PN modifications – specifically phosphoryl guanidine – into oligonucleotide compounds. As with PS modifications, PN modifications are chiral, and we have the capacity to control PN backbone stereochemistry. Unlike PS modifications, PN modifications are neutral, meaning that the negative charge of the oligonucleotide is reduced with every PN modification added to the backbone.
PRISM has also enabled us to further innovate our chemistry, including the application of novel PN backbone chemistry modifications to our pipeline programs. • Broad applicability . PRISM is applicable to oligonucleotides acting via multiple therapeutic modalities, including RNA editing, splicing, and silencing (including siRNA and antisense).
PRISM has also enabled us to further innovate our chemistry, including the application of new chemistry modifications, to our pipeline programs. • Broad applicability . PRISM is applicable to oligonucleotides acting via multiple therapeutic modalities, including RNAi, RNA editing, splicing, antisense and bifunctional modalities.
We believe, based on publicly available information, that Alnylam (Phase 1), Annexon Biosciences (Phase 2 completed), Ionis Pharmaceuticals and Roche (Phase 2), Mitochon Pharmaceuticals (Phase 1/2), Prilenia Therapeutics (Preregistration with EMA), PTC Therapeutics (Phase 2), Skyhawk Therapeutics (Phase 1), uniQure (Phase 1/2), and Vico Therapeutics (Phase 1/2), among others, have investigational drugs aimed at slowing the progression of HD in clinical development.
We believe, based on publicly available information, that Alnylam (Phase 1), Annexon Biosciences (Phase 2 completed), Ionis Pharmaceuticals and Roche (allele-selective in Phase 1 and pan-silencing in Phase 2), Prilenia Therapeutics (Phase 3), PTC Therapeutics / Novartis (Phase 2), Roche (Phase 1/2), Skyhawk Therapeutics (Phase 2/3), uniQure (Phase 1/2), and Vico Therapeutics (Phase 1/2), among others, have investigational drugs aimed at slowing the progression of HD in clinical development.
After January 31, 2025, all clinical trials, including those that are ongoing, are now subject to the provisions of the Clinical Trials Regulation. Under the new centralized process, if the EU member state leading the CTA review approves or rejects the application, the decision will apply to all involved member states.
As of January 31, 2025, all clinical trials, including those initiated prior to such date, are subject to the provisions of the Clinical Trials Regulation. Under the new centralized process, if the EU member state leading the CTA review approves or rejects the application, the decision will apply to all involved member states.
There are also a number of companies with investigational drugs in clinical development for AATD lung disease: Kamada (Phase 3), Krystal Biotech (Phase 1), Mereo BioPharma (Phase 2 completed), and Sanofi (Phase 2), among others.
There are also a number of companies with investigational drugs in clinical development for AATD lung disease: Krystal Biotech (Phase 1), Mereo BioPharma (Phase 2 completed), and Sanofi (Phase 2), among others. Arrowhead Pharmaceuticals and Takeda have an investigational drug in Phase 3 clinical development for AATD liver disease.
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. 14 * p 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.
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.
In our 2024 Nucleic Acids Research paper (Lu et al., 2024 Nuc Acid Res; doi.org/10.1093/nar/gkae681 N), we described the development of new AIMer designs with base modifications and sequence, sugar and backbone modifications that improve RNA editing efficiency over our previous design. AIMers incorporating a novel pattern of backbone and 2′ sugar modifications support enhanced editing efficiency across multiple sequences.
In our 2024 Nucleic Acids Research paper (Lu et al., 2024 Nuc Acid Res; doi.org/10.1093/nar/gkae681 N), we described the development of new AIMer designs (AIMer-D) with base modifications and sequence, sugar and backbone modifications that improve RNA editing efficiency over our previous design (AIMer-S).
Our HD Program 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 HTT gene (Iwamoto et al., MTNA).
Our HD Program 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).
Sites where potential off-target editing occurred mapped predominantly to non-coding regions of the transcriptome and had either low read coverage in the analysis or occurred at low percentages of less than 10%, indicating that these are relatively rare events, as shown in the figure below on the right.
From this analysis, we observed nominal off-target editing across the transcriptome. Sites where potential off-target editing occurred mapped predominantly to non-coding regions of the transcriptome and had either low read coverage in the analysis or occurred at low percentages of less than 10%, indicating that these are relatively rare events.
The GSK Equity Investment closed on January 26, 2023. The shares purchased by GGL in the GSK Equity Investment are subject to lock-up and standstill restrictions and carry certain registration rights, customary for transactions of this kind.
The GSK Equity Investment closed on January 26, 2023. The shares purchased by GGL in the GSK Equity Investment carry certain registration rights, customary for transactions of this kind.
If a drug product is selected by CMS for negotiation, it is expected that the revenue generated from such drug will decrease. CMS has begun to implement these new authorities and entered into the first set of agreements with drug and biological product manufacturers for negotiated prices of 10 products, which will become applicable for payment year 2026.
If a drug product is selected by CMS for negotiation, it is expected that the revenue generated from such drug will decrease. CMS has begun to implement these new authorities, announcing the first round of negotiated prices for the first 10 drug products in August 2024, which will become applicable for payment year 2026.
On January 1, 2021, all existing European Union marketing authorizations were converted to United Kingdom marketing authorizations subject to a manufacturer opt-out. Since then, the United Kingdom has introduced separate, specific processes for regulatory submissions and medicinal product marketing authorization.
An MHRA authorization must be obtained for each medicine to be marketed in the regions that comprise the United Kingdom. On January 1, 2021, all existing European Union marketing authorizations were converted to United Kingdom marketing authorizations subject to a manufacturer opt-out. Since then, the United Kingdom has introduced separate, specific processes for regulatory submissions and medicinal product marketing authorization.
We were recently recognized by the Boston Business Journal and won the distinction of being one of the 2024 “Best Places to Work”, which underscores our employees’ recognition of our collective focus, resilience, and commitment to our mission.
We were previously recognized by the Boston Business Journal and won the distinction of being one of the 2024 “Best Places to Work”, which underscores our employees’ recognition of our collective focus, resilience, and commitment to our mission of unlocking the broad potential of RNA medicines to transform human health.
For example, the next FDA user fee reauthorization package is expected to enter stakeholder negotiations beginning in mid-2025, with any agreement sent to Congress in early 2027 for purposes of initiating the legislative process.
For example, negotiations on the next FDA user fee reauthorization package began in mid-2025, and the resulting agreement is expected to be sent to Congress in early 2027 for purposes of initiating the legislative process.
Our DMD Program 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.
In 2024, the FDA granted approval to Italfarmaco/ITF Therapeutics’ Duvyzat (givinostat), a histone deacetylase inhibitor. Our DMD Program 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.
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”).
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.
An intermediate clinical endpoint is a measurement of a therapeutic effect that is considered reasonably likely to predict the clinical benefit of a drug, such as an effect on IMM.
An intermediate clinical endpoint is a measurement of a therapeutic effect that is considered reasonably likely to predict the clinical benefit of a drug, such as an effect on IMM. There have been a limited number of Accelerated Approvals based on intermediate clinical endpoints.
To remedy this concern, the CREATES Act establishes a private cause of action that permits a generic product developer to sue the brand manufacturer to compel it to furnish the necessary samples on “commercially reasonable, market-based terms.” Although lawsuits have been filed under the CREATES Act since its enactment, those lawsuits have settled privately; therefore to date no federal court has reviewed or opined on the statutory language and there continues to be uncertainty regarding the scope and application of the law. 45 For a drug product to receive federal reimbursement under the Medicaid or Medicare Part B programs or to be sold directly to U.S. government agencies, the manufacturer must extend discounts to entities eligible to participate in the 340B Drug Pricing Program.
To remedy this concern, the CREATES Act establishes a private cause of action that permits a generic product developer to sue the brand manufacturer to compel it to furnish the necessary samples on “commercially reasonable, market-based terms.” Although lawsuits have been filed under the CREATES Act since its enactment, those lawsuits have settled privately; therefore to date no federal court has reviewed or opined on the statutory language and there continues to be uncertainty regarding the scope and application of the law.
From time to time, new legislation and regulations may be implemented that could significantly change the statutory provisions governing the approval, manufacturing and marketing of products regulated by the FDA.
The DSCSA mandates resource-intensive obligations for pharmaceutical manufacturers, wholesale distributors, and dispensers. From time to time, new legislation and regulations may be implemented that could significantly change the statutory provisions governing the approval, manufacturing and marketing of products regulated by the FDA.
The preclinical data demonstrated unprecedented Argonaute2 (“Ago2”) loading following administration of single subcutaneous GalNAc-siRNA doses, leading to improved potency and durability in vivo in mice versus comparator siRNA formats.
In April 2023, we announced the publication of preclinical data for our novel siRNA formats in the journal of Nucleic Acids Research . The preclinical data demonstrated unprecedented Argonaute2 (“Ago2”) loading following administration of single subcutaneous GalNAc-siRNA doses, leading to improved potency and durability in vivo in mice versus comparator siRNA formats.
The FDA has limited experience with accelerated approvals based on intermediate clinical endpoints, but has indicated that such endpoints generally may support accelerated approval when the therapeutic effect measured by the endpoint is not itself a clinical benefit and basis for traditional approval, if there is a basis for concluding that the therapeutic effect is reasonably likely to predict the ultimate long-term clinical benefit of a drug. 37 The accelerated approval pathway is most often used in settings in which the course of a disease is long and an extended period of time is required to measure the intended clinical benefit of a drug, even if the effect on the surrogate or intermediate clinical endpoint occurs rapidly.
The FDA has limited experience with accelerated approvals based on intermediate clinical endpoints, but has indicated that such endpoints generally may support accelerated approval when the therapeutic effect measured by the endpoint is not itself a clinical benefit and basis for traditional approval, if there is a basis for concluding that the therapeutic effect is reasonably likely to predict the ultimate long-term clinical benefit of a drug.
In June 2024, we announced positive clinical data from the Phase 1b/2a SELECT-HD study of WVE-003.
In June 2024, we announced positive clinical data from the SELECT-HD study.
The discovery collaboration has an initial four-year research term and combines our proprietary discovery and drug development platform, PRISM TM , with GSK’s novel genetic insights and its global development and commercial capabilities.
Pursuant to the GSK Collaboration Agreement, we and GSK have agreed to collaborate on the research, development, and commercialization of oligonucleotide therapeutics. The discovery collaboration has an initial four-year research term and combines our proprietary discovery and drug development platform, PRISM TM , with GSK’s novel genetic insights and its global development and commercial capabilities.
Approximately 200,000 people in the United States and Europe are homozygous for the Z allele, which is the most common form of severe disease. Current Treatments There are five treatments currently approved in the United States for chronic augmentation and maintenance therapy in adults with emphysema due to congenital deficiency of alpha1-proteinase inhibitor (“Alpha1-PI”).
Current Treatments There are five treatments currently approved in the United States for chronic augmentation and maintenance therapy in adults with emphysema due to congenital deficiency of alpha1-proteinase inhibitor (“Alpha1-PI”).
GSK collaboration programs will transfer to GSK for IND-enabling studies, clinical development, and commercialization.
We will lead all preclinical research for GSK and our collaboration programs up to IND-enabling studies. We will lead IND-enabling studies, clinical development and commercialization for our collaboration programs. GSK collaboration programs will transfer to GSK for IND-enabling studies, clinical development, and commercialization.
Basically, the MRP may be applied for all human drugs for which the centralized procedure is not obligatory. The MRP is applicable to the majority of conventional medicinal products and is based on the 42 principle of recognition of an already existing national marketing authorization by one or more member states.
The MRP is applicable to the majority of conventional medicinal products and is based on the principle of recognition of an already existing national marketing authorization by one or more member states.
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.
Through our collaboration with 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.
Our training programs provide training to our employees that is commensurate with their level of risk exposure and are designed to ensure that employees have the knowledge and equipment available to mitigate risk. Our cross-functional Safety Committee meets monthly to discuss any concerns and ways to improve our EH&S programs.
Our training programs provide training to our employees that is commensurate with their level of risk exposure and are designed to ensure that employees have the knowledge and equipment available to mitigate risk.
Austedo (Teva), tetrabenazine (generic), and, in 2023, Ingrezza (Neurocrine Biosciences) have been approved for the treatment of chorea associated with HD.
Huntington’s Disease (“HD”) There are no approved treatments available to slow the progression of HD. Austedo (Teva), tetrabenazine (generic), and, in 2023, Ingrezza (Neurocrine Biosciences) have been approved for the treatment of chorea associated with HD.
Other therapies available for DMD include Santhera Pharmaceuticals’ Agamree (vamorolone), an alternative steroid which was approved in the US and EU in 2023 and Italfarmaco/ITF Therapeutics’ Duvyzat (givinostat), a histone deacetylase inhibitor which was approved in the United States in 2024. 32 Several other companies have investigational drugs in clinical development targeting DMD more broadly, including patients amenable to exon 53 skipping.
This includes patients who have a DMD mutation amenable to exon 53 skipping. Other therapies available for DMD include Catalyst Pharmaceuticals’ Agamree (vamorolone), an alternative steroid which was approved in the US and EU in 2023, PTC Therapeutics’ Emflaza (steroid, now generic), and Italfarmaco/ITF Therapeutics’ Duvyzat (givinostat), a histone deacetylase inhibitor which was approved in the United States in 2024.
We are committed to transforming the care of devastating diseases where patients have limited treatment options. Our current and future portfolio is focused on novel therapeutic approaches that optimally address disease biology, that offer biomarkers for target engagement, and that inform on clinical effects early in development.
We are committed to transforming the care of individuals living with the burden of disease, including those with both rare and common diseases. Our current and future portfolio is focused on novel therapeutic approaches that optimally address disease biology, offer biomarkers for target engagement, inform on clinical effects early in development, and represent attractive commercial opportunities.
Al., 2022; doi.org/10.1038/s41587-022-01225-1), we demonstrated efficient RNA editing in vitro with our AIMers across a variety of cell lines, including non-human primate (“NHP”) and human primary hepatocytes, as shown in the figures below. We observed potent, dose-dependent RNA editing with three chemically distinct stereopure AIMers (ACTB 1, ACTB 2, ACTB 3) via GalNAc-mediated uptake.
In this manuscript, we demonstrated efficient RNA editing in vitro with our AIMers across a variety of cell lines, including non-human primate (“NHP”) and human primary hepatocytes. We observed potent, dose-dependent RNA editing with three chemically distinct stereopure AIMers (ACTB 1, ACTB 2, ACTB 3) via GalNAc-mediated uptake. We next evaluated these same GalNAc-conjugated ACTB-editing AIMers in vivo in NHPs.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeWe are required to comply with the Singapore Code on Take-Overs and Mergers (the “Singapore Takeover Code”), which specifies, among other things, certain circumstances in which a general offer is to be made upon a change in effective control, and further specifies the manner and price at which voluntary and mandatory general offers are to be made. 81 We are also subject to Section 34 of the Singapore Patents Act, which provides that a person residing in Singapore is required to obtain written authorization from the Singapore Registrar of Patents (the “Registrar”) before filing an application for a patent for an invention outside of Singapore, unless certain conditions have been satisfied.
Biggest changeWe are required to comply with the Singapore Code on Take-Overs and Mergers (the “Singapore Takeover Code”), which specifies, among other things, certain circumstances in which a general offer is to be made upon a change in effective control, and further specifies the manner and price at which voluntary and mandatory general offers are to be made.
We may incur substantial costs to comply with, and substantial fines or penalties if we violate any of, these laws or regulations. Risks Related to Our Dependence on Third Parties We depend on collaborations with third parties for the development and commercialization of certain of our product candidates.
We may incur substantial costs to comply with, and substantial fines or penalties if we violate any of, these laws or regulations. Risks Related to Our Dependence on Third Parties We may depend on collaborations with third parties for the development and commercialization of certain of our product candidates.
Collaborations involving our product candidates may pose the following risks to us: • collaborators may have significant discretion in determining the efforts and resources that they will apply to these collaborations; 68 • collaborators may not pursue development and commercialization of our product candidates or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in the collaborator’s strategic focus or available funding or external factors such as an acquisition that diverts resources or creates competing priorities; • collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing; • collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our products or product candidates if the collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours; • collaborators may require us to enter into collaboration agreements that contain exclusivity provisions and/or termination penalties; • a collaborator with marketing and distribution rights to one or more products may not commit sufficient resources to the marketing and distribution of such product or products; • collaborators may not properly maintain or defend our intellectual property rights or may use our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our proprietary information or expose us to potential litigation; • disputes may arise between the collaborators and us that result in the delay or termination of the research, development or commercialization of our products or product candidates or that result in costly litigation or arbitration that diverts management attention and resources; and • collaborations may be terminated and, if terminated, may result in a need for additional capital to pursue further development or commercialization of the applicable product candidates.
Collaborations involving our product candidates may pose the following risks to us: • collaborators may have significant discretion in determining the efforts and resources that they will apply to these collaborations; • collaborators may not pursue development and commercialization of our product candidates or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in the collaborator’s strategic focus or available funding or external factors such as an acquisition that diverts resources or creates competing priorities; • collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing; • collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our products or product candidates if the collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours; • collaborators may require us to enter into collaboration agreements that contain exclusivity provisions and/or termination penalties; • a collaborator with marketing and distribution rights to one or more products may not commit sufficient resources to the marketing and distribution of such product or products; • collaborators may not properly maintain or defend our intellectual property rights or may use our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our proprietary information or expose us to potential litigation; • disputes may arise between the collaborators and us that result in the delay or termination of the research, development or commercialization of our products or product candidates or that result in costly litigation or arbitration that diverts management attention and resources; and • collaborations may be terminated and, if terminated, may result in a need for additional capital to pursue further development or commercialization of the applicable product candidates.
Our success will depend on several factors, including the following: • successfully completing preclinical studies and clinical trials; • successfully conducting process development and manufacturing campaigns in accordance with cGMP; 54 • receiving regulatory approvals from applicable regulatory authorities to market our product candidates and, to the extent necessary, our companion diagnostic tests; • establishing commercial manufacturing capabilities or making arrangements with third party CMOs; • obtaining and maintaining patent and trade secret protection and regulatory exclusivity for our product candidates; • the degree to which we are successful in our current collaborations, and any additional collaborations we may establish; • launching commercial sales of the products, if and when approved, whether alone or in collaboration with others; • acceptance of the products, if and when approved, by patients, the medical community and third-party payors; • effectively competing with other therapies; • continuing to maintain an acceptable safety and efficacy profile of the products following regulatory approval; and • appropriately addressing the post-marketing requirements and/or commitments made upon regulatory approval.
Our success will depend on several factors, including the following: • successfully completing preclinical studies and clinical trials; • successfully conducting process development and manufacturing campaigns in accordance with cGMP; • receiving regulatory approvals from applicable regulatory authorities to market our product candidates and, to the extent necessary, our companion diagnostic tests; • establishing commercial manufacturing capabilities or making arrangements with third party CMOs; • obtaining and maintaining patent and trade secret protection and regulatory exclusivity for our product candidates; • the degree to which we are successful in our current collaborations, and any additional collaborations we may establish; • launching commercial sales of the products, if and when approved, whether alone or in collaboration with others; • acceptance of the products, if and when approved, by patients, the medical community and third-party payors; • effectively competing with other therapies; • continuing to maintain an acceptable safety and efficacy profile of the products following regulatory approval; and • appropriately addressing the post-marketing requirements and/or commitments made upon regulatory approval.
At our most recent annual general meeting of shareholders, our shareholders provided our directors with a general authority, subject to the 82 provisions of the Singapore Companies Act and our constitution, to allot and issue any number of new ordinary shares and/or make or grant offers, agreements, options or other instruments (including the grant of awards or options pursuant to our equity-based incentive plans and agreements in effect from time to time) that might or would require ordinary shares to be allotted and issued (collectively, the “Instruments”); and unless revoked or varied by us in a general meeting, such authority will continue in force until the earlier of (i) the conclusion of our next annual general meeting of shareholders, or (ii) the expiration of the period within which our next annual general meeting of shareholders is required by law to be held.
At our most recent annual general meeting of shareholders, our shareholders provided our directors with a general authority, subject to the provisions of the Singapore Companies Act and our constitution, to allot and issue any number of new ordinary shares and/or make or grant offers, agreements, options or other instruments (including the grant of awards or options pursuant to our equity-based incentive plans and agreements in effect from time to time) that might or would require ordinary shares to be allotted and issued (collectively, the “Instruments”); and unless revoked or varied by us in a general meeting, such authority will continue in force until the earlier of (i) the conclusion of our next annual general meeting of shareholders, or (ii) the expiration of the period within which our next annual general meeting of shareholders is required by law to be held.
Our competitors may develop or commercialize products with significant advantages over any products we are able to develop and commercialize based on many different factors, including: • the safety and effectiveness of our products relative to alternative therapies, if any; • the ease with which our products can be administered and the extent to which patients accept relatively new routes of administration; • the timing and scope of regulatory approvals for these products; • the availability and cost of manufacturing, marketing and sales capabilities; • price; 62 • more extensive coverage and higher levels of reimbursement; and • patent position.
Our competitors may develop or commercialize products with significant advantages over any products we are able to develop and commercialize based on many different factors, including: • the safety and effectiveness of our products relative to alternative therapies, if any; • the ease with which our products can be administered and the extent to which patients accept relatively new routes of administration; • the timing and scope of regulatory approvals for these products; • the availability and cost of manufacturing, marketing and sales capabilities; • price; • more extensive coverage and higher levels of reimbursement; and • patent position.
Failure to execute on our manufacturing requirements, either by us or by one of our third-party vendors, could adversely affect our business in a number of ways, including: • an inability to initiate or continue clinical trials of product candidates under development; • delays in submitting regulatory applications, or receiving regulatory approvals, for product candidates; • loss of the cooperation of a collaborator; • additional inspections by regulatory authorities; 71 • requirements to cease distribution or to recall batches of our product candidates; and • in the event of approval to market and commercialize a product candidate, an inability to meet commercial demands for our products.
Failure to execute on our manufacturing requirements, either by us or by one of our third-party vendors, could adversely affect our business in a number of ways, including: • an inability to initiate or continue clinical trials of product candidates under development; • delays in submitting regulatory applications, or receiving regulatory approvals, for product candidates; • loss of the cooperation of a collaborator; • additional inspections by regulatory authorities; • requirements to cease distribution or to recall batches of our product candidates; and • in the event of approval to market and commercialize a product candidate, an inability to meet commercial demands for our products.
Our manufacturing capabilities 56 could be affected by cost-overruns, unexpected delays, equipment failures, labor shortages, operator error, natural disasters, unavailability of qualified personnel, difficulties with logistics and shipping, problems regarding yields or stability of product, contamination or other quality control issues, power failures, and numerous other factors that could prevent us from realizing the intended benefits of our manufacturing strategy and have a material adverse effect on our business.
Our manufacturing capabilities could be affected by cost-overruns, unexpected delays, equipment failures, labor shortages, operator error, natural disasters, unavailability of qualified personnel, difficulties with logistics and shipping, problems regarding yields or stability of product, contamination or other quality control issues, power failures, and numerous other factors that could prevent us from realizing the intended benefits of our manufacturing strategy and have a material adverse effect on our business.
As a result, we might obtain regulatory approval for a product in a particular country, but then be 64 subject to price regulations that could delay our commercial launch of the product and negatively impact any potential revenues we may be able to generate from the sale of the product in that country and potentially in other countries due to reference pricing or other measures to reduce drug prices.
As a result, we might obtain regulatory approval for a product in a particular country, but then be subject to price regulations that could delay our commercial launch of the product and negatively impact any potential revenues we may be able to generate from the sale of the product in that country and potentially in other countries due to reference pricing or other measures to reduce drug prices.
Holders of stock that has experienced significant price and trading volatility have occasionally brought securities class action litigation against the companies that issued the stock. If any of our shareholders were to bring a lawsuit of this type against us, even if the 86 lawsuit is without merit, we could incur substantial costs defending the lawsuit.
Holders of stock that has experienced significant price and trading volatility have occasionally brought securities class action litigation against the companies that issued the stock. If any of our shareholders were to bring a lawsuit of this type against us, even if the lawsuit is without merit, we could incur substantial costs defending the lawsuit.
We are also subject to income, withholding or other taxes in certain jurisdictions by reason of our activities and operations, and it is also possible that tax authorities in any such jurisdictions could assert that we are subject to greater taxation than we currently anticipate. 83 Any such Singaporean and non-Singaporean tax liability could materially adversely affect our results of operations.
We are also subject to income, withholding or other taxes in certain jurisdictions by reason of our activities and operations, and it is also possible that tax authorities in any such jurisdictions could assert that we are subject to greater taxation than we currently anticipate. Any such Singaporean and non-Singaporean tax liability could materially adversely affect our results of operations.
However, initiation of such trials may be delayed if the FDA objects to our proposed diversity action plans for any future Phase 3 trial for our product candidates, and we may experience difficulties recruiting a diverse population of patients in attempting to fulfill the requirements of any approved diversity action plan.
Initiation of such trials may be delayed if the FDA objects to our proposed diversity action plans for any future Phase 3 trial for our product candidates, and we may experience difficulties recruiting a diverse population of patients in attempting to fulfill the requirements of any approved diversity action plan.
Even if we are successful in defending against these claims, litigation could result in substantial costs and be a distraction to management. 80 If our trademarks and trade names are not adequately protected, then we may not be able to build name recognition in our markets of interest and our business may be adversely affected.
Even if we are successful in defending against these claims, litigation could result in substantial costs and be a distraction to management. If our trademarks and trade names are not adequately protected, then we may not be able to build name recognition in our markets of interest and our business may be adversely affected.
If one or more of these analysts cease coverage of our company or fail to publish reports on us regularly, demand for our ordinary shares could decrease, which might cause our share price and trading volume to decline. 87 Item 1B. Unresolve d Staff Comments None.
If one or more of these analysts cease coverage of our company or fail to publish reports on us regularly, demand for our ordinary shares could decrease, which might cause our share price and trading volume to decline. Item 1B. Unresolve d Staff Comments None.
A severe or prolonged economic downturn could result in a variety of risks, including our ability to raise additional funding on a timely basis or on 52 acceptable terms. A weak or declining economy could also impact third parties upon whom we depend to run our business.
A severe or prolonged economic downturn could result in a variety of risks, including our ability to raise additional funding on a timely basis or on acceptable terms. A weak or declining economy could also impact third parties upon whom we depend to run our business.
Additional state and federal healthcare reform measures are expected to be adopted in the future, any of 65 which could limit the amounts that federal and state governments will pay for healthcare products and services, which could result in reduced demand for certain biopharmaceutical products or additional pricing pressures.
Additional state and federal healthcare reform measures are expected to be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, which could result in reduced demand for certain biopharmaceutical products or additional pricing pressures.
Any action against us for an alleged or suspected violation could cause us to incur significant legal expenses, could divert our management’s attention from 63 the operation of our business, and could harm our reputation, even if our defense is successful.
Any action against us for an alleged or suspected violation could cause us to incur significant legal expenses, could divert our management’s attention from the operation of our business, and could harm our reputation, even if our defense is successful.
Unauthorized access, loss or dissemination could also adversely 73 affect our business, damage our reputation, and disrupt our operations, including our ability to conduct research and development activities, process and prepare company financial information, and manage various general and administrative aspects of our business.
Unauthorized access, loss or dissemination could also adversely affect our business, damage our reputation, and disrupt our operations, including our ability to conduct research and development activities, process and prepare company financial information, and manage various general and administrative aspects of our business.
Section 404 of the Sarbanes-Oxley Act requires public companies to maintain effective internal control over financial reporting. In particular, we must perform system and process evaluation and testing of our internal control over financial reporting to allow management to report on the effectiveness of our 85 internal control over financial reporting.
Section 404 of the Sarbanes-Oxley Act requires public companies to maintain effective internal control over financial reporting. In particular, we must perform system and process evaluation and testing of our internal control over financial reporting to allow management to report on the effectiveness of our internal control over financial reporting.
If we or our licensors, collaborators or any future strategic partners are found to infringe a third-party patent or other intellectual property 78 rights, we could be required to pay damages, potentially including treble damages, if we are found to have willfully infringed.
If we or our licensors, collaborators or any future strategic partners are found to infringe a third-party patent or other intellectual property rights, we could be required to pay damages, potentially including treble damages, if we are found to have willfully infringed.
Congress also recently amended the FDCA to require sponsors of a Phase 3 clinical trial, or other “pivotal study” of a new drug to support marketing authorization, to design and submit a diversity action plan for such clinical trial.
Congress also amended the FDCA to require sponsors of a Phase 3 clinical trial, or other “pivotal study” of a new drug to support marketing authorization, to design and submit a diversity action plan for such clinical trial.
Furthermore, with 70 the increase of companies developing oligonucleotides, there may be increased competition for the supply of the raw materials that are necessary to make our oligonucleotides, which could severely impact the manufacturing of our product candidates.
Furthermore, with the increase of companies developing oligonucleotides, there may be increased competition for the supply of the raw materials that are necessary to make our oligonucleotides, which could severely impact the manufacturing of our product candidates.
To the extent the Pre-Funded Warrants above are exercised, additional ordinary shares will be issued and such issuance would dilute existing shareholders and increase the number of shares eligible for resale in the public market.
To the extent the Pre-Funded Warrants are exercised, additional ordinary shares will be issued and such issuance would dilute existing shareholders and increase the number of shares eligible for resale in the public market.
In the course of such proceedings, which may continue 76 for a protracted period of time, the patent owner may be compelled to limit the scope of the allowed or granted claims attacked or may lose the allowed or granted claims altogether.
In the course of such proceedings, which may continue for a protracted period of time, the patent owner may be compelled to limit the scope of the allowed or granted claims attacked or may lose the allowed or granted claims altogether.
Our goal is to develop and commercialize disease-modifying medicines for genetically defined diseases with a high degree of unmet medical need, and to become a fully integrated RNA 59 medicines company.
Our goal is to develop and commercialize disease-modifying medicines for genetically defined diseases with a high degree of unmet medical need, and to become a fully integrated RNA medicines company.
In addition, third parties may attempt to 77 invalidate our intellectual property rights. Even if our rights are not directly challenged, invalidated or circumvented, disputes could lead to the weakening of our intellectual property rights.
In addition, third parties may attempt to invalidate our intellectual property rights. Even if our rights are not directly challenged, invalidated or circumvented, disputes could lead to the weakening of our intellectual property rights.
Because the value of our assets for purposes of determining PFIC status will depend in part on the market price of our ordinary shares, which may fluctuate significantly, there can be no assurance that we will not be considered a PFIC for our current taxable year ending December 31, 2025 or for any future taxable year.
Because the value of our assets for purposes of determining PFIC status will depend in part on the market price of our ordinary shares, which may fluctuate significantly, there can be no assurance that we will not be considered a PFIC for our current taxable year ending December 31, 2026 or for any future taxable year.
For example, CMS promulgated a regulation permitting Medicare Advantage plans to use step therapy for Part B drugs 66 beginning January 1, 2020.
For example, CMS promulgated a regulation permitting Medicare Advantage plans to use step therapy for Part B drugs beginning January 1, 2020.
In addition, holders of book-entry interests in our shares will be required to be registered shareholders as reflected in our shareholder register in order to have standing to bring a shareholder action and, if successful, to enforce a foreign judgment against us, our directors or our executive officers in the Singapore courts.
In addition, holders of book-entry interests in our shares will be required to be registered shareholders as reflected in our shareholder register in order to have standing to bring a shareholder action in the United States and, if successful, to enforce a foreign judgment against us, our directors or our executive officers in the Singapore courts.
The rights of our shareholders and the responsibilities of the members of our Board under Singapore law are different from those applicable to a corporation incorporated in the United States. Principal shareholders of Singapore companies do not owe fiduciary duties to minority shareholders, as compared, for example, to controlling shareholders in corporations incorporated in Delaware.
The rights of our shareholders and the responsibilities of the members of our Board of Directors (“Board”) under Singapore law are different from those applicable to a corporation incorporated in the United States. Principal shareholders of Singapore companies do not owe fiduciary duties to minority shareholders, as compared, for example, to controlling shareholders in corporations incorporated in Delaware.
Our ability to effectively run our business could be adversely affected by general conditions in the global economy and in the financial services industry. Various macroeconomic factors could adversely affect our business, including fears concerning the banking sector, volatility in inflation, and interest rates and overall changes in economic conditions and uncertainties.
Our ability to effectively run our business could be adversely affected by general conditions in the global economy and in the financial services industry. Various macroeconomic factors could adversely affect our business, including fears concerning the banking sector, rising inflation, and interest rates and overall changes in economic conditions and uncertainties.
Based on our gross income, the average value of our assets, including goodwill and the nature of our active business, we do not expect to be treated as a PFIC for U.S. federal income tax purposes for the taxable year ended December 31, 2024.
Based on our gross income, the average value of our assets, including goodwill and the nature of our active business, we do not expect to be treated as a PFIC for U.S. federal income tax purposes for the taxable year ended December 31, 2025.
We may experience numerous unforeseen events during, or as a result of, preclinical studies and clinical trials that could delay or prevent regulatory approval or our ability to commercialize our product candidates, including: • our preclinical studies or clinical trials may produce negative or inconclusive results, including results that may not meet the level of significance or clinical benefit required by the FDA or other regulators, and we may decide, or regulators may require us, to conduct additional preclinical studies or clinical trials, or we may abandon projects that we had expected to be promising; • delays in filing INDs/CTAs or comparable foreign applications or delays or failure in obtaining the necessary approvals from regulators or IRBs in order to commence a clinical trial at a prospective trial site, or their suspension or termination of a clinical trial once commenced; • conditions imposed on us by the FDA or comparable foreign authorities regarding the scope or design of our clinical trials; • divergent views between FDA and other homologue regulatory authorities as to the objectives and/or design of the clinical trials required in support of marketing registration; • problems in obtaining or maintaining IRB approval of trials; • delays in enrolling patients or volunteers into clinical trials, and variability in the number and types of patients eligible for clinical trials; • delays in developing and receiving regulatory approval for companion diagnostic tests, to the extent such tests are needed, to identify patients for our clinical trials; • high drop-out rates for patients in clinical trials and substantial missing data; • an inability to open study sites, or enroll, treat, and monitor patients due to local restrictions implemented in response to local or global health epidemics; • negative or inconclusive results from our clinical trials or the clinical trials of others for product candidates similar to ours; • results from future clinical trials may not confirm positive results, if any, from earlier preclinical studies and clinical trials; • inability to consistently manufacture, inadequate supply, or unacceptable quality of product candidate materials or other materials necessary for the conduct of our clinical trials; • greater than anticipated clinical trial costs; • serious and unexpected side effects that may or may not be related to the product candidate being tested that are experienced by participants in our clinical trials or by individuals using drugs similar to our product candidates; • poor or disappointing effectiveness of our product candidates during clinical trials; • unfavorable outcome of FDA or other regulatory agency inspection and review of a manufacturing or clinical trial site or other records relating to the clinical investigation; • failure of our third-party contractors, investigators, or collaboration partners to comply with regulatory requirements or otherwise meet their contractual obligations in a timely manner, or at all; • governmental or regulatory delays and changes in regulatory requirements, policy and guidelines, including the imposition of additional regulatory oversight around manufacturing, preclinical, or clinical testing generally or with respect to the class, of any of our product candidates, in particular; or • varying interpretations of data by the FDA and similar foreign regulatory agencies. 58 If we do not successfully conduct clinical development, we will not be able to market and sell products derived from our product candidates and to generate product revenues.
We may experience numerous unforeseen events during, or as a result of, preclinical studies and clinical trials that could delay or prevent regulatory approval or our ability to commercialize our product candidates, including: • our preclinical studies or clinical trials may produce negative or inconclusive results, including results that may not meet the level of significance or clinical benefit required by the FDA or other regulators, and we may decide, or regulators may require us, to conduct additional preclinical studies or clinical trials, or we may abandon projects that we had expected to be promising; • delays in filing INDs/CTAs or comparable foreign applications or delays or failure in obtaining the necessary approvals from regulators or IRBs in order to commence a clinical trial at a prospective trial site, or their suspension or termination of a clinical trial once commenced; • conditions imposed on us by the FDA or comparable foreign authorities regarding the scope or design of our clinical trials; • divergent views between FDA and other homologue regulatory authorities as to the objectives and/or design of the clinical trials required in support of marketing registration; • problems in obtaining or maintaining IRB approval of trials; • delays in enrolling patients or volunteers into clinical trials, and variability in the number and types of patients eligible for clinical trials; • delays in developing and receiving regulatory approval for companion diagnostic tests, to the extent such tests are needed, to identify patients for our clinical trials; • high drop-out rates for patients in clinical trials and substantial missing data; • an inability to open study sites, or enroll, treat, and monitor patients due to local restrictions implemented in response to local or global health epidemics; • negative or inconclusive results from our clinical trials or the clinical trials of others for product candidates similar to ours; • results from future clinical trials may not confirm positive results, if any, from earlier preclinical studies and clinical trials; • inability to consistently manufacture, inadequate supply, or unacceptable quality of product candidate materials or other materials necessary for the conduct of our clinical trials; • greater than anticipated clinical trial costs; • serious and unexpected side effects that may or may not be related to the product candidate being tested that are experienced by participants in our clinical trials or by individuals using drugs similar to our product candidates; • poor or disappointing effectiveness of our product candidates during clinical trials; • unfavorable outcome of FDA or other regulatory agency inspection and review of a manufacturing or clinical trial site or other records relating to the clinical investigation; • failure of our third-party contractors, investigators, or collaboration partners to comply with regulatory requirements or otherwise meet their contractual obligations in a timely manner, or at all; • governmental or regulatory delays and changes in regulatory requirements, policy and guidelines, including the imposition of additional regulatory oversight around manufacturing, preclinical, or clinical testing generally or with respect to the class, of any of our product candidates, in particular; or • varying interpretations of data by the FDA and similar foreign regulatory agencies.
Although we determined that our internal controls over financing reporting were effective as of December 31, 2024, we may in the future identify internal control deficiencies that could rise to the level of a material weakness or uncover other errors in financial reporting.
Although we determined that our internal controls over financing reporting were effective as of December 31, 2025, we may in the future identify internal control deficiencies that could rise to the level of a material weakness or uncover other errors in financial reporting.
For the years ended December 31, 2024, 2023 and 2022, changes in foreign currency exchange rates did not have a material impact on our historical financial position, our business, our financial condition, the results of our operations or our cash flows.
For the years ended December 31, 2025, 2024 and 2023, changes in foreign currency exchange rates did not have a material impact on our historical financial position, our business, our financial condition, the results of our operations or our cash flows.
We or third parties upon whom we depend may be adversely affected by natural disasters and/or health epidemics, and our business, financial condition and results of operations could be adversely affected. Natural disasters could severely disrupt our operations and have a material adverse effect on our business operations.
We or third parties upon whom we depend may be adversely affected by natural disasters and/or local and global health epidemics, and our business, financial condition and results of operations could be adversely affected. Natural disasters or local and global health epidemics could severely disrupt our operations and have a material adverse effect on our business operations.
Based on information publicly available to us as of December 31, 2024, our executive officers, our directors and their respective affiliates, and our other significant shareholders beneficially own a significant portion of our outstanding ordinary shares.
Based on information publicly available to us as of December 31, 2025, our executive officers, our directors and their respective affiliates, and our other significant shareholders beneficially own a significant portion of our outstanding ordinary shares.
While we have taken steps to comply with all applicable privacy laws and regulations, including the GDPR, by taking measures including but not limited to enhancing our security procedures, updating our website, revising our clinical trial informed consents, adopting the standard contractual clauses for cross-border transfers of personal data, increasing our cyber insurance, and entering into data processing agreements with relevant CROs and third party partners, we cannot completely assure you that our efforts to remain in compliance will be fully successful.
While we have taken steps to comply with all applicable privacy laws and regulations, including the GDPR, by taking measures including but not limited to enhancing our security procedures, updating our website, revising our clinical trial informed consents, adopting the standard contractual clauses for cross-border transfers of personal data, increasing our cyber insurance, developing policies governing the use of AI, and entering into data processing agreements with relevant CROs and third party partners, we cannot completely assure you that our efforts to remain in compliance will be fully successful.
Disruptions at the FDA and other agencies may also extend the time necessary for new drugs to be reviewed and/or approved by necessary government agencies, which would adversely affect our business.
In addition, disruptions at the FDA and other agencies may also extend the time necessary for new drugs to be reviewed and/or approved by necessary government agencies, which would adversely affect our business.
Reauthorization of the prescription drug user fee program would need to be finalized by Congress by the end of September 2027 in order to avoid a disruption in FDA’s review goals for NDAs and other activities supported by user fees assessed against industry.
Reauthorization of the prescription drug user fee program must be finalized by Congress by the end of September 2027 in order to avoid a disruption in FDA’s review goals for NDAs and other activities supported by user fees assessed against industry.
Security breaches, cybersecurity threats, loss of data and other disruptions could compromise sensitive information related to our business, prevent us from accessing critical information or expose us to liability, which could adversely affect our business and our reputation.
Security breaches, cybersecurity threats, misuse of AI tools, loss of data and other disruptions could compromise sensitive information related to our business, prevent us from accessing critical information or expose us to liability, which could adversely affect our business and our reputation.
Our future capital requirements will depend on many factors, including, but not limited to, the following: • our monthly spending levels, based on new and ongoing development and corporate activities; • the scope, progress, results and costs of drug discovery, preclinical and clinical development for our product candidates; 51 • our ability to establish and maintain collaboration arrangements, and whether our collaboration partners decide to exercise option rights in connection with targets and development programs; • the costs, timing and outcome of regulatory review of our product candidates; • our ability to obtain marketing approval for our product candidates; • the impacts of any local or global health issues, the conflict involving Russia and Ukraine, the conflict in the Middle East, global economic uncertainty, volatility in inflation, volatility in interest rates or market disruptions on our business; • the achievement of milestones and other development targets that trigger payments under our agreements with our key collaboration partners, or any other strategic collaborations into which we may enter; • the costs and timing of future commercialization activities, including manufacturing, marketing, sales and distribution, for any of our product candidates for which we receive marketing approval; • market acceptance of our product candidates, to the extent any are approved for commercial sale, and the revenue, if any, received from commercial sales of our product candidates for which we receive marketing approval; • the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending any intellectual property-related claims; • the costs of securing manufacturing arrangements internally or with third parties for drug supply.
Our future capital requirements will depend on many factors, including, but not limited to, the following: • our monthly spending levels, based on new and ongoing development and corporate activities; • the scope, progress, results and costs of drug discovery, preclinical and clinical development for our product candidates; • our ability to establish and maintain collaboration arrangements, and whether our collaboration partners decide to exercise option rights in connection with targets and development programs; • the costs, timing and outcome of regulatory review of our product candidates; • our ability to obtain marketing approval for our product candidates; • the impacts of any local or global health epidemics, geopolitical conflicts, global economic uncertainty, tariffs, rising inflation, rising interest rates or market disruptions on our business; • the achievement of milestones and other development targets that trigger payments under our agreements with our key collaboration partners, or any other strategic collaborations into which we may enter; • the costs and timing of future commercialization activities, including manufacturing, marketing, sales and distribution, for any of our product candidates for which we receive marketing approval; • market acceptance of our product candidates, to the extent any are approved for commercial sale, and the revenue, if any, received from commercial sales of our product candidates for which we receive marketing approval; • the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending any intellectual property-related claims; • the costs of securing manufacturing arrangements internally or with third parties for drug supply.
While we have built up inventory to assist us through this uncertain operating environment, our suppliers may be disrupted now or in the future due to a local or global health epidemic, which could affect our ability to procure items that are essential for our research and development activities and could cause increases to our costs, inflation, and significant disruptions to our business.
While we have built up inventory to assist us through uncertain operating environments, our suppliers may be disrupted now or in the future due to a natural disaster and/or health epidemic, which could affect our ability to procure items that are essential for our research and development activities and could cause increases to our costs, inflation, and significant disruptions to our business.
Our operating history as a clinical-stage biotechnology company may make it difficult for shareholders to evaluate the success of our business to date and to assess our future viability. We are a clinical-stage biotechnology company focused on unlocking the broad potential of RNA medicines (also known as oligonucleotides), or those targeting RNA, to transform human health.
Our operating history as a clinical-stage biotechnology company may make it difficult for shareholders to evaluate the success of our business to date and to assess our future viability. We are a clinical-stage biotechnology company focused on unlocking the broad potential of RNA medicines to transform human health.
We rely upon third parties for many aspects of our business, including the raw materials used to make our product candidates and the conduct of our clinical trials and preclinical studies.
For example, w e rely upon third parties for many aspects of our business, including the raw materials used to make our product candidates and the conduct of our clinical trials and preclinical studies.
We have invested a significant portion of our efforts and financial resources in the identification and preclinical and clinical development of our oligonucleotides , the development of our RNA medicines platform, PRISM, including our RNA editing capability, and our novel chemistry modifications, and the continued growth of our manufacturing capabilities.
We have invested a significant portion of our efforts and financial resources in the identification and preclinical and clinical development of our oligonucleotides, the development of our RNA medicines platform, PRISM, including our toolkit of RNA-targeting modalities, and our novel chemistry modifications, and the continued growth of our manufacturing capabilities.
As a result, it may be more difficult for us to convince the medical community and third-party payors to accept and use our product, or to provide favorable reimbursement. 61 Other factors that we believe will materially affect market acceptance of our product candidates include: • the timing of our receipt of any regulatory approvals, the terms of any approvals and the countries in which approvals are obtained; • the ability to consistently manufacture our products within acceptable quality standards; • the safety and efficacy of our product candidates, as demonstrated in clinical trials and as compared with alternative treatments, if any; • the incidence, seriousness and severity of any side effects; • the relative convenience and ease of administration of our product candidates; • the willingness of patients to accept potentially new routes of administration and their risk tolerance as it relates to potentially serious side effects; • the success of our physician education programs; • the availability of government and third-party payer coverage and adequate reimbursement; • the pricing of our products, particularly as compared to alternative treatments; and • the availability of alternative effective treatments for the diseases that product candidates we develop are intended to treat and the relative risks, benefits and costs of those treatments.
Other factors that we believe will materially affect market acceptance of our product candidates include: • the timing of our receipt of any regulatory approvals, the terms of any approvals and the countries in which approvals are obtained; • the ability to consistently manufacture our products within acceptable quality standards; • the safety and efficacy of our product candidates, as demonstrated in clinical trials and as compared with alternative treatments, if any; • the incidence, seriousness and severity of any side effects; • the relative convenience and ease of administration of our product candidates; • the willingness of patients to accept potentially new routes of administration and their risk tolerance as it relates to potentially serious side effects; • the success of our physician education programs; • the availability of government and third-party payer coverage and adequate reimbursement; • the pricing of our products, particularly as compared to alternative treatments; and • the availability of alternative effective treatments for the diseases that product candidates we develop are intended to treat and the relative risks, benefits and costs of those treatments.
Our preclinical studies and clinical trials may not be successful. If we are unable to commercialize our product candidates or experience significant delays in doing so, our business may be materially harmed. We have a robust and diverse pipeline of first- or best-in-class RNA medicines using our RNA editing, splicing, silencing using siRNA and antisense silencing modalities.
Our preclinical studies and clinical trials may not be successful. If we are unable to commercialize our product candidates or experience significant delays in doing so, our business may be materially harmed. We have a robust and diverse pipeline of first- or best-in-class RNA medicines.
These broad and sector-specific market fluctuations can result in extreme fluctuations in the price of our ordinary shares, regardless of our operating performance, and can cause our shareholders to lose some or all of their investment in us. We issued pre-funded warrants as part of our June 2022 and September 2024 financings, which may cause additional dilution to our shareholders.
These broad and sector-specific market fluctuations can result in extreme fluctuations in the price of our ordinary shares, regardless of our operating performance, and can cause our shareholders to lose some or all of their investment in us. We have issued pre-funded warrants in certain of our financings, which may cause additional dilution to our shareholders.
Our ordinary shares are currently listed for trading on the Nasdaq Global Market. There is no assurance that the trading market for our shares will be or remain active. Our shareholders may not be able to sell their ordinary shares quickly or at the market price, or at all.
There is no assurance that the trading market for our shares will be or remain active. Our shareholders may not be able to sell their ordinary shares quickly or at the market price, or at all.
As the patchwork of U.S. privacy laws expands, state enforcement of data privacy and cybersecurity breaches has increased, along with the cost. In addition to state enforcement of privacy laws, the Federal Trade Commission has increased enforcement of cybersecurity and data privacy, and related fines in 2024.
As the patchwork of state and federal U.S. privacy laws expands, enforcement of data privacy and cybersecurity breaches has increased, along with the cost (for example, the Federal Trade Commission increased enforcement of cybersecurity and data privacy, and related fines in 2025).
Our net loss was $97.0 million, $57.5 million, and $161.8 million for the fiscal years ended December 31, 2024, 2023, and 2022, respectively. As of December 31, 2024, and 2023 we had an accumulated deficit of $1,121.9 million and $1,024.9 million, respectively. To date, we have not generated any product revenue.
Our net loss was $204.4 million, $97.0 million, and $57.5 million for the fiscal years ended December 31, 2025, 2024, and 2023, respectively. As of December 31, 2025, and 2024 we had an accumulated deficit of $1,326.2 million and $1,121.9 million, respectively. To date, we have not generated any product revenue.
The market price of our ordinary shares is likely to continue to be highly volatile, including in response to factors that are beyond our control. The stock market in general experiences extreme price and volume fluctuations.
The market price of our ordinary shares is likely to be highly volatile, and our shareholders may lose some or all of their investment. The market price of our ordinary shares is likely to continue to be highly volatile, including in response to factors that are beyond our control. The stock market in general experiences extreme price and volume fluctuations.
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 siRNA and antisense silencing, providing us with unique capabilities for designing and sustainably delivering candidates that optimally address disease biology.
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 silencing (SpiNA) and RNA editing (AIMers), provides us with unmatched capabilities for designing and sustainably delivering candidates that optimally address disease biology.
To the extent that any disruption or security breach were to result in a loss of or damage to our data or applications, or inappropriate disclosure of personal, confidential or proprietary information, we could incur liability and the further development of our product candidates could be delayed.
To the extent that any disruption or security breach were to result in a loss of or damage to our data or applications, or inappropriate disclosure of personal, confidential or proprietary information, we could incur liability and the further development of our product candidates could be delayed. Artificial Intelligence (“AI”) is increasingly being used within many different industries.
If third parties disclose or misappropriate our proprietary rights, it may materially and adversely impact our position in the market. 75 Legal issues related to the patentability of biopharmaceuticals, and methods of their manufacture and use, are complex and uncertain in some countries.
If third parties disclose or misappropriate our proprietary rights, it may materially and adversely impact our position in the market. Legal issues related to the patentability of biopharmaceuticals, and methods of their manufacture and use, are complex and uncertain in some countries. In some countries, applicants are not able to protect methods of treating human beings or medical treatment processes.
We depend on third-party collaborators for the development and commercialization of certain of our product candidates. Our potential future collaborators include large and mid-size pharmaceutical companies, regional and national pharmaceutical companies and biotechnology companies. In January 2023, we commenced a collaboration with GSK to research, develop, and commercialize oligonucleotide therapeutics, including WVE-006, our first-in-class A-to-I(G) RNA editing candidate for AATD.
We may depend on third-party collaborators for the development and commercialization of certain of our product candidates. Our potential future collaborators include large and mid-size pharmaceutical companies, regional and national pharmaceutical companies and biotechnology companies. For example, in January 2023, we commenced a collaboration with GSK to research, develop, and commercialize oligonucleotide therapeutics.
Through December 31, 2024, we have received an aggregate of approximately $1,578.4 million in net proceeds from these transactions, consisting of $977.8 million in net proceeds from public and other registered offerings of our ordinary shares, $511.3 million from our collaborations, exclusive of any potential future milestone and royalty payments, and $89.3 million in net proceeds from private placements of our debt and equity securities.
Through December 31, 2025, we have received an aggregate of approximately $2,076.7 million in net proceeds from these transactions, consisting of $1,450.5 million in net proceeds from public and other registered offerings of our ordinary shares, $536.9 million from our collaborations, exclusive of any potential future milestone and royalty payments, and $89.3 million in net proceeds from private placements of our debt and equity securities.
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.
Our pipeline is focused on our obesity, alpha-1 antitrypsin deficiency (“AATD”) and PNPLA3 I148M liver disease 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.
If we are unable to obtain or maintain sufficient insurance, a product liability claim against us could adversely affect our business. Our business exposes us to significant potential product liability risks that are inherent in the development, testing, manufacturing and marketing of human therapeutic products. Product liability claims could delay or prevent completion of our clinical development programs.
Our business exposes us to significant potential product liability risks that are inherent in the development, testing, manufacturing and marketing of human therapeutic products. Product liability claims could delay or prevent completion of our clinical development programs.
Approval by the FDA does not ensure approval by comparable regulatory authorities outside of the United States and vice versa. 60 If we are granted orphan drug designations in the United States for any of our product candidates, there can be no guarantee that we will maintain orphan status for these product candidates or receive approval for any product candidate with an orphan drug designation.
If we are granted orphan drug designations in the United States for any of our product candidates, there can be no guarantee that we will maintain orphan status for these product candidates or receive approval for any product candidate with an orphan drug designation.
This Annual Report on Form 10-K does not discuss any such tax legislation or changes to tax laws and legislation, or the 74 manner in which it might affect us or purchasers of our securities.
Any future changes may have an adverse effect on our business, financial condition and results of operations. This Annual Report on Form 10-K does not discuss any such tax legislation or changes to tax laws and legislation, or the manner in which it might affect us or purchasers of our securities.
In addition, government funding of the SEC and other government agencies on which our operations may rely, including those that fund research and development activities, is subject to the political process, which is inherently fluid and unpredictable.
In addition, government funding of the SEC and other government agencies on which our operations may rely, including those that fund research and development activities, is subject to the political process, which is inherently fluid and unpredictable. Future legislative and regulatory proposals may impact the ability of regulatory agencies to operate as they have historically operated.
The foreign regulatory approval process varies among countries and may include all of the risks associated with FDA approval described above, as well as risks attributable to the satisfaction of local regulations in foreign jurisdictions.
The foreign regulatory approval process varies among countries and may include all of the risks associated with FDA approval described above, as well as risks attributable to the satisfaction of local regulations in foreign jurisdictions. Approval by the FDA does not ensure approval by comparable regulatory authorities outside of the United States and vice versa.
While we have adapted our processes to lessen the impact of a potential local or global health epidemic may have on our business, any potential delays or long-term impacts on our business, our clinical trials, healthcare systems or the global economy could be highly uncertain.
While we have adapted our processes to lessen the potential impact that a natural disaster and/or health epidemic may have on our business, any potential delays or long-term impacts on our business, our clinical trials, healthcare systems or the global economy could be highly uncertain and the disaster recovery and business continuity plans we have in place may prove inadequate.
The next FDA user fee reauthorization package is expected to enter stakeholder negotiations beginning in mid-2025, with any agreement sent to Congress in early 2027 for purposes of initiating the legislative process.
The next FDA user fee reauthorization package entered the stakeholder negotiation phase in mid-2025, and the resulting agreement is expected to be sent to Congress in early 2027 for purposes of initiating the legislative process.
Further, the limited liquidity in our ordinary shares may also impair our ability to raise capital by conducting offerings of our ordinary shares and may impair our ability to enter into strategic partnerships or acquire companies or products by using our ordinary shares as consideration. 84 The market price of our ordinary shares is likely to be highly volatile, and our shareholders may lose some or all of their investment.
Further, the limited liquidity in our ordinary shares may also impair our ability to raise capital by conducting offerings of our ordinary shares and may impair our ability to enter into strategic partnerships or acquire companies or products by using our ordinary shares as consideration.
Furthermore, given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting such candidates, their manufacture or their use might expire before or shortly after those candidates receive regulatory approval and are commercialized.
Lack of patent protection in such cases may have a materially adverse effect on our business and financial condition. Furthermore, given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting such candidates, their manufacture or their use might expire before or shortly after those candidates receive regulatory approval and are commercialized.
We have concentrated our efforts and research and development activities on RNA medicines (also known as oligonucleotides) and enhancing PRISM, our proprietary discovery and drug development platform. PRISM enables us to target genetically defined diseases with stereopure oligonucleotides across multiple therapeutic modalities. Our future success depends on the successful development of our RNA medicines and the effectiveness of PRISM.
PRISM enables us to target genetically defined diseases with stereopure oligonucleotides across multiple therapeutic modalities. Our future success depends on the successful development of our RNA medicines and the effectiveness of PRISM.
We are currently evaluating the impact of the legislation on our future tax credit claims. Risks Related to Our Ordinary Shares The public market for our ordinary shares may not be liquid enough for our shareholders to sell their ordinary shares quickly or at market price, or at all.
Risks Related to Our Ordinary Shares The public market for our ordinary shares may not be liquid enough for our shareholders to sell their ordinary shares quickly or at market price, or at all. Our ordinary shares are currently listed for trading on the Nasdaq Global Market.
Key participants in pharmaceutical marketplaces, such as physicians, third-party payors and consumers, may not adopt a product intended to improve therapeutic results that is based on the technology employed by oligonucleotides.
Key participants in pharmaceutical marketplaces, such as physicians, third-party payors and consumers, may not adopt a product intended to improve therapeutic results that is based on the technology employed by oligonucleotides. As a result, it may be more difficult for us to convince the medical community and third-party payors to accept and use our product, or to provide favorable reimbursement.
Particularly given that some of our product candidates may represent stereopure versions of previously described oligonucleotides, it may be difficult or impossible to obtain patent protection for them in relevant jurisdictions. Thus, in some countries and jurisdictions, it may not be possible to patent some of our product candidates at all.
Further, many countries have enacted laws and regulatory regimes that do not allow patent protection for methods of use of known compounds. Particularly given that some of our product candidates may represent stereopure versions of previously described oligonucleotides, it may be difficult or impossible to obtain patent protection for them in relevant jurisdictions.
Further, drug development is a capital-intensive and highly speculative undertaking that involves a substantial degree of risk. You should consider our prospects in light of the costs, uncertainties, delays and difficulties frequently encountered by biotechnology companies in the early stages of clinical development, such as ours.
You should consider our prospects in light of the costs, uncertainties, delays and difficulties frequently encountered by biotechnology companies in the early stages of clinical development, such as ours.
Any of these events, even if we were ultimately to prevail, could require us to divert substantial financial and management resources that we would otherwise be able to devote to our business. 79 If we fail to comply with our obligations under any license, collaboration or other agreement, we may be required to pay damages and could lose intellectual property rights that are necessary for developing and protecting our product candidates, or we could lose certain rights to grant sublicenses.
If we fail to comply with our obligations under any license, collaboration or other agreement, we may be required to pay damages and could lose intellectual property rights that are necessary for developing and protecting our product candidates, or we could lose certain rights to grant sublicenses.
In some countries and jurisdictions, only composition claims may be obtained, and only when those compositions are or contain compounds that are new and/or novel. Also, patents issued with composition claims ( i.e., covering product candidates) cannot always be enforced to protect methods of using those compositions to treat or diagnose diseases or medical conditions.
Also, patents issued with composition claims ( i.e., covering product candidates) cannot always be enforced to protect methods of using those compositions to treat or diagnose diseases or medical conditions. In such countries or jurisdictions, enforcement of patents to protect our product candidates, or their uses, may be difficult or impossible.
Numerous federal, state and international laws address privacy, data protection and the collection, storing, sharing, use, disclosure and protection of personally identifiable information and other user data, including in the context of the development and deployment of artificial intelligence technologies.
Numerous federal, state and international laws address privacy, data protection and the collection, storing, sharing, use, disclosure and protection of personally identifiable information and other user data, including in the context of the development and deployment of AI technologies. In the United States, many states have already implemented state laws addressing privacy or are set to enact data protection legislation.
If a prolonged government shutdown or slowdown occurs, it could significantly impact the ability of the FDA to timely review and process our regulatory submissions, which could have a material adverse effect on our business.
Moreover, government shutdowns or slowdowns can increase the time needed for an agency to complete its review or make final approvals or other administrative decisions. If a prolonged government shutdown or slowdown occurs, it could significantly impact the ability of the FDA to timely review and process our regulatory submissions, which could have a material adverse effect on our business.
If we are not able to manage the clinical trial process successfully, our business plans could be delayed or be rendered unfeasible for us to execute within our planned or required time frames, or at all. 55 If we cannot successfully manufacture our product candidates for our research and development and preclinical activities, or manufacture sufficient amounts of our product candidates to meet our clinical requirements and timelines, our business may be materially harmed.
If we are not able to manage the clinical trial process successfully, our business plans could be delayed or be rendered unfeasible for us to execute within our planned or required time frames, or at all.
If we do not have sufficient funds to develop and bring our product candidates to market, we will not be able to generate sales revenues from these product candidates, and this will substantially harm our business. 69 We rely, and expect to continue to rely, on third parties to conduct some aspects of our compound formulation, research, preclinical studies and clinical trials, and those third parties may not perform satisfactorily, including failing to meet deadlines for the completion of such formulation, research or testing.
We rely, and expect to continue to rely, on third parties to conduct some aspects of our compound formulation, research, preclinical studies and clinical trials, and those third parties may not perform satisfactorily, including failing to meet deadlines for the completion of such formulation, research or testing.
Our diversified pipeline includes clinical programs in AATD, DMD, HD, and obesity, as well as several preclinical programs utilizing our broad RNA therapeutics toolkit. However, we currently have no products on the market.
Our pipeline is focused on our obesity, AATD and PNPLA3 I148M liver disease programs, and also includes clinical programs for DMD and HD, as well as several preclinical programs utilizing our versatile RNA medicines platform. However, we currently have no products on the market.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeOur Board delegates to the Audit Committee oversight of certain aspects of our risk management process, including risks related to information technology, data privacy and cybersecurity. 88 At least quarterly, our Audit Committee receives an update from management of our cybersecurity threat risk management and strategy processes, including recent cybersecurity incidents and related responses, cybersecurity testing, activities of third parties, and other similar matters.
Biggest changeAt least quarterly, our Audit Committee receives an update from management of our cybersecurity threat risk management and strategy processes, including recent cybersecurity incidents and related responses, cybersecurity testing, activities of third parties, and other similar matters. Our cybersecurity risk management and strategy processes are led by our Data Security Officer, Data Privacy Officer, Chief Financial Officer and General Counsel.
Our cybersecurity risk management and strategy processes are led by our Data Security Officer, Data Privacy Officer, Chief Financial Officer and General Counsel. Such individuals have collectively over 50 years of prior work experience in various roles involving managing information security, developing cybersecurity strategy , implementing effective information and cybersecurity programs, as well as several relevant degrees and certifications.
Such individuals have collectively over 50 years of prior work experience in various roles involving managing information security, developing cybersecurity strategy , implementing effective information and cybersecurity programs, as well as several relevant degrees and certifications.
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Our Board delegates to the Audit Committee oversight of certain aspects of our risk management process, including risks related to information technology, data privacy and cybersecurity.

Item 2. Properties

Properties — owned and leased real estate

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Biggest changeWe also occupy laboratory and office space in Japan. We believe our existing facilities are adequate to meet our current needs. Item 3. Legal Proceedings We are not currently a party to any material legal proceedings. Item 4. Mine Safety Disclosures Not applicable. 89 PART II
Biggest changeWe also occupy laboratory and office space in Japan. We believe our existing facilities are adequate to meet our current needs. Item 3. Legal Proceedings We are not currently a party to any material legal proceedings. Item 4. Mine Safety Disclosures Not applicable. PART II

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeItem 5. Market for Registrant’s Common Equity, Related Stoc kholder Matters and Issuer Purchases of Equity Securities Market Information Our ordinary shares are traded on the Nasdaq Global Market under the symbol “WVE”. Shareholders As of February 24, 2025, we had 153,486,021 ordinary shares outstanding and approximately nine shareholders of record of our ordinary shares.
Biggest changeItem 5. Market for Registrant’s Common Equity, Related Stoc kholder Matters and Issuer Purchases of Equity Securities Market Information Our ordinary shares are traded on the Nasdaq Global Market under the symbol “WVE”. Shareholders As of February 19, 2026, we had 188,254,954 ordinary shares outstanding and approximately seven shareholders of record of our ordinary shares.
In addition, the terms of any future debt agreements may preclude us from paying dividends. Unregistered Sales of Securities Not applicable. Issuer Purchases of Equity Securities None. Item 6. [ Reserved] 90
In addition, the terms of any future debt agreements may preclude us from paying dividends. Unregistered Sales of Securities Not applicable. Issuer Purchases of Equity Securities None. Item 6. [ Reserved]
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Share Performance Graph The following share performance graph compares our total share return with the total return for (i) the Nasdaq Composite Index and (ii) the Nasdaq Biotechnology Index for the period from December 31, 2020 through December 31, 2025.
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The figures represented below assume an investment of $100.00 in our ordinary shares at the closing price of $7.870 on December 31, 2020 and in the Nasdaq Composite Index and the Nasdaq Biotechnology Index on December 31, 2020 and the reinvestment of dividends, if any, into ordinary shares.
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The share return shown in the share performance graph below is not necessarily indicative of future performance, and we do not make or endorse any predictions as to future share return.
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This performance graph is not “soliciting material,” is not deemed filed with the SEC and is not to be incorporated by reference in any filing by us under the Securities Act or the Exchange Act whether made before or after the date hereof and irrespective of any general incorporation language in any such filing.

Item 7. Management's Discussion & Analysis

Management's Discussion & Analysis (MD&A) — revenue / margin commentary

45 edited+11 added−26 removed81 unchanged
Biggest changeThe increase of $14.1 million was due to the following: • an increase of $4.7 million in external expenses related to our AATD program, WVE-006 (RNA editing); • an increase of $5.2 million in external expenses related to our DMD programs, including WVE-N531 (splicing); • an increase of $5.1 million in external expenses related to our HD programs, including WVE-003 (silencing); • an increase of $1.6 million in other research and development expenses, including INHBE, 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 facilities-related expenses, partially offset by decreases in other external research and development expenses; and • a decrease of $2.5 million in external expenses related to our discontinued ALS and FTD program, WVE-004.
Biggest changeThe increase of $23.1 million was due to the following: • an increase of $6.4 million in external expenses related to our INHBE program, including WVE-007 (RNAi); • a decrease of $5.9 million in external expenses related to our AATD program, WVE-006 (RNA editing); • an increase of $3.9 million in external expenses related to our DMD program, including WVE-N531 (splicing); • a decrease of $9.1 million in external expenses related to our HD program, including WVE-003 (silencing); and • an increase of $27.8 million in other research and development expenses, including PNPLA3, additional preclinical programs, PRISM, and 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.
In addition, the Company considers whether the customer can benefit from a promise for its intended purpose without the receipt of the remaining promise, whether the value of the promise is dependent on the unsatisfied promise, whether there are other vendors that could provide the remaining promise, and whether it is separately identifiable from the remaining promise.
In addition, the Company considers whether the customer can benefit from a promise for its intended purpose without the receipt of the remaining promise, whether the value of the promise is dependent on the unsatisfied promise, whether there are other vendors that could provide the remaining promise, and whether it is separately identifiable from the remaining promise.
We evaluate our estimates and assumptions on an ongoing basis. Our actual results may differ from these estimates under different assumptions and conditions. 101 Revenue Recognition The Company recognizes revenue in accordance with Accounting Standards Codification (“ASC”) Topic 606, Revenue from Contracts with Customers (“ASC 606”).
We evaluate our estimates and assumptions on an ongoing basis. Our actual results may differ from these estimates under different assumptions and conditions. Revenue Recognition The Company recognizes revenue in accordance with Accounting Standards Codification (“ASC”) Topic 606, Revenue from Contracts with Customers (“ASC 606”).
In addition, we may elect to raise additional funds before we need them if the conditions for raising capital are 98 favorable due to market conditions or strategic considerations, even if we expect we have sufficient funds for our current or future operating plans.
In addition, we may elect to raise additional funds before we need them if the conditions for raising capital are favorable due to market conditions or strategic considerations, even if we expect we have sufficient funds for our current or future operating plans.
Additionally, there were $1.1 million in net proceeds from our "at-the-market" equity program. Funding Requirements We expect to continue to incur significant expenses in connection with our ongoing research and development activities and our internal cGMP manufacturing activities.
Additionally, there were $3.1 million in net proceeds from our "at-the-market" equity program. Funding Requirements We expect to continue to incur significant expenses in connection with our ongoing research and development activities and our internal cGMP manufacturing activities.
We base our estimates on communications with internal study managers, our knowledge of the ongoing and past work at the CROs and CMOs, and communications and reporting from our CROs and CMOs, where applicable. 103
We base our estimates on communications with internal study managers, our knowledge of the ongoing and past work at the CROs and CMOs, and communications and reporting from our CROs and CMOs, where applicable.
Research and Development Expenses Research and development expenses consist primarily of costs incurred for our research activities, including our discovery efforts, and the development of our product candidates, which include: • compensation-related expenses, including employee salaries, bonuses, share-based compensation expense and other related benefits expenses for personnel in our research and development organization; • expenses incurred under agreements with third parties, including CROs that conduct research, preclinical and clinical activities on our behalf, as well as CMOs that manufacture drug product for use in our preclinical studies and clinical trials; • expenses incurred related to our internal manufacturing of drug substance for use in our preclinical studies and clinical trials; • expenses related to compliance with regulatory requirements; • expenses related to third-party consultants; • research and development supplies and services expenses; and • facility-related expenses, including rent, maintenance and other general operating expenses.
Research and Development Expenses Research and development expenses consist primarily of costs incurred for our research activities, including development of our RNA medicines platform, our discovery efforts, and the development of our product candidates, which include: • compensation-related expenses, including employee salaries, bonuses, share-based compensation expense and other related benefits expenses for personnel in our research and development organization; • expenses incurred under agreements with third parties, including CROs that conduct research, preclinical and clinical activities on our behalf, as well as CMOs that manufacture drug product for use in our preclinical studies and clinical trials; • expenses incurred related to our internal manufacturing of drug substance for use in our preclinical studies and clinical trials; • expenses related to compliance with regulatory requirements; • expenses related to third-party consultants; • research and development supplies and services expenses; and • facility-related expenses, including rent, maintenance and other general operating expenses.
The 102 Company evaluates the measure of progress each reporting period and, if necessary, adjusts the measure of performance and related revenue recognition.
The Company evaluates the measure of progress each reporting period and, if necessary, adjusts the measure of performance and related revenue recognition.
As of December 31, 2024 and 2023, we have recorded a full valuation allowance against our net operating loss carryforwards and federal and state tax credits in all jurisdictions due to uncertainty regarding future taxable income.
As of December 31, 2025 and 2024, we have recorded a full valuation allowance against our net operating loss carryforwards and federal and state tax credits in all jurisdictions due to uncertainty regarding future taxable income.
We do not currently have any committed external source of funds, except for possible future payments from GSK under our collaborations with them.
We do not currently have any committed external source of funds, except for possible future payments from GSK under our collaboration with them.
Results of Operations In this section, we discuss the results of our operations for the year ended December 31, 2024 compared to the year ended December 31, 2023 and for the year ended December 31, 2023 compared to the year ended December 31, 2022 .
Results of Operations In this section, we discuss the results of our operations for the year ended December 31, 2025 compared to the year ended December 31, 2024 and for the year ended December 31, 2024 compared to the year ended December 31, 2023 .
Comparison of the Year Ended December 31, 2024 to the Year Ended December 31, 2023 The following table summarizes our results of operations for 2024 and 2023: For the Year Ended December 31, 2024 2023 Change (in thousands) Revenue $ 108,302 $ 113,305 $ (5,003 ) Operating expenses: Research and development 159,682 130,009 29,673 General and administrative 59,023 51,292 7,731 Total operating expenses 218,705 181,301 37,404 Loss from operations (110,403 ) (67,996 ) (42,407 ) Total other income, net 13,395 9,806 3,589 Loss before income taxes (97,008 ) (58,190 ) (38,818 ) Income tax benefit (provision) — 677 (677 ) Net loss $ (97,008 ) $ (57,513 ) $ (39,495 ) Revenue Revenue for the years ended December 31, 2024 and 2023, was $108.3 million and $113.3 million, respectively, and was earned under the GSK Collaboration Agreement and the Takeda Collaboration Agreement. 95 The $5.0 million decrease in revenue year over year was driven by the revenue recognized under the GSK Collaboration Agreement, partially offset by the increase in revenue recognized under the Takeda Collaboration Agreement.
Comparison of the Year Ended December 31, 2024 to the Year Ended December 31, 2023 The following table summarizes our results of operations for 2024 and 2023: For the Year Ended December 31, 2024 2023 Increase (Decrease) (in thousands) Revenue $ 108,302 $ 113,305 $ (5,003 ) Operating expenses: Research and development 159,682 130,009 29,673 General and administrative 59,023 51,292 7,731 Total operating expenses 218,705 181,301 37,404 Loss from operations (110,403 ) (67,996 ) 42,407 Total other income, net 13,395 9,806 3,589 Loss before income taxes (97,008 ) (58,190 ) 38,818 Income tax benefit — 677 (677 ) Net loss $ (97,008 ) $ (57,513 ) $ 39,495 Revenue Revenue for the years ended December 31, 2024 and 2023, was $108.3 million and $113.3 million, respectively, and was earned under the GSK Collaboration Agreement and the Takeda Collaboration Agreement.
Financing Activities During 2024, net cash provided by financing activities was $253.9 million, which was primarily due to the $215.8 million in net proceeds from the September 2024 Offering of ordinary shares and the 2024 Pre-Funded Warrants; as well as the $14.0 million in net proceeds from the January 2024 exercise of the underwriters’ option to purchase an additional 3,000,000 shares under the December 2023 Offering.
During 2024, net cash provided by financing activities was $253.9 million, primarily due to the $215.8 million in net proceeds from the September 2024 underwritten public offering of ordinary shares and the 2024 Pre-Funded Warrants (as defined below) (the "September 2024 Offering"); as well as the $14.0 million in net proceeds from the January 2024 exercise of the underwriters’ option to purchase an additional 3,000,000 shares under the December 2023 Offering.
Our future capital requirements for our therapeutic programs will depend on many factors, including: • the progress, results and costs of conducting research and continued preclinical and clinical development for our therapeutic programs and future potential pipeline candidates; • the number and characteristics of product candidates and programs that we pursue; • the cost of manufacturing clinical supplies of our product candidates; • whether and to what extent milestone events are achieved under our collaborations with Takeda and GSK or any potential future licensee or collaborator; • the costs, timing and outcome of regulatory review of our product candidates; • our ability to obtain marketing approval for our product candidates; 100 • the impacts of local and global health epidemics, the conflict involving Russia and Ukraine, the conflict in the Middle East, global economic uncertainty, volatility in inflation, volatility in interest rates or market disruptions on our business; • the costs and timing of future commercialization activities, including manufacturing, marketing, sales and distribution, for any of our product candidates for which we receive marketing approval; • market acceptance of our product candidates, to the extent any are approved for commercial sale, and the revenue, if any, received from commercial sales of our product candidates for which we receive marketing approval; • the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending any intellectual property-related claims; • the effect of competing technological and market developments; and • the extent to which we acquire or invest in businesses, products and technologies, including entering into licensing or collaboration arrangements for product candidates.
Our future capital requirements for our therapeutic programs will depend on many factors, including: • the progress, results and costs of conducting research and continued preclinical and clinical development for our therapeutic programs and future potential pipeline candidates; • the number and characteristics of product candidates and programs that we pursue; • the cost of manufacturing clinical supplies of our product candidates; • whether and to what extent milestone events are achieved under our collaboration with GSK or any potential future licensee or collaborator; • the costs, timing and outcome of regulatory review of our product candidates; • our ability to obtain marketing approval for our product candidates; • the impacts of local and global health epidemics, geopolitical conflicts, global economic uncertainty, tariffs, rising inflation, rising interest rates or market disruptions on our business; • the costs and timing of future commercialization activities, including manufacturing, marketing, sales and distribution, for any of our product candidates for which we receive marketing approval; • market acceptance of our product candidates, to the extent any are approved for commercial sale, and the revenue, if any, received from commercial sales of our product candidates for which we receive marketing approval; • the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending any intellectual property-related claims; • the effect of competing technological and market developments; and • the extent to which we acquire or invest in businesses, products and technologies, including entering into licensing or collaboration arrangements for product candidates.
Furthermore, we anticipate that our expenses will continue to vary if and as we: • continue to conduct our clinical trials evaluating our product candidates in patients; • conduct research and preclinical development of discovery targets and advance additional programs into clinical development; • file clinical trial applications with global regulatory agencies and conduct clinical trials for our programs; • make strategic investments in continuing to innovate our research and development platform, PRISM, and in optimizing our manufacturing processes and formulations; • maintain our manufacturing capabilities through our internal facility and our CMOs; • maintain our intellectual property portfolio and consider the acquisition of complementary intellectual property; • seek and obtain regulatory approvals for our product candidates; • respond to the impacts of local and global health epidemics, the conflict involving Russia and Ukraine, the conflict in the Middle East, global economic uncertainty, volatility in inflation, volatility in interest rates or market disruptions on our business; and • establish and build capabilities to market, distribute and sell our product candidates.
Furthermore, we anticipate that our expenses will continue to vary if and as we: • continue to conduct our clinical trials evaluating our product candidates in patients; • conduct research and preclinical development of discovery targets and advance additional programs into clinical development; • file clinical trial applications with global regulatory agencies and conduct clinical trials for our programs; • make strategic investments in continuing to innovate our research and development platform, PRISM, and in optimizing our manufacturing processes and formulations; • maintain our manufacturing capabilities through our internal facility and our CMOs; • maintain our intellectual property portfolio and consider the acquisition of complementary intellectual property; • seek and obtain regulatory approvals for our product candidates; • respond to the impacts of local and global health epidemics, geopolitical conflicts, global economic uncertainty, tariffs, rising inflation, rising interest rates or market disruptions on our business; and • establish and build capabilities to market, distribute and sell our product candidates.
Our operating lease commitments as of December 31, 2024 total $29.1 million, of which $9.6 million is related to payments in 2025 and approximately $19.5 million is related to payments beyond 2025.
Our operating lease commitments as of December 31, 2025 total $19.5 million, of which $9.6 million is related to payments in 2026 and approximately $9.9 million is related to payments beyond 2026.
Income Tax Benefit (Provision) During the years ended December 31, 2023 and 2022, we recorded an income tax benefit of $0.7 million and an income tax provision of $0.7 million, respectively.
Income Tax Benefit During the years ended December 31, 2024 and 2023, we recorded no income tax benefit or provision and an income tax benefit of $0.7 million, respectively.
For the three months ended December 31, 2024, we received $5.2 million in net proceeds from sales under our “at-the-market" equity program. Adequate additional financing may not be available to us on acceptable terms, or at all.
For the twelve months ended December 31, 2025, we received $94.6 million in net proceeds from sales under our “at-the-market" equity program. Adequate additional financing may not be available to us on acceptable terms, or at all.
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 94 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.
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.
Research and Development Expenses The following table summarizes our research and development expenses incurred for the years ended December 31, 2024 and 2023: For the Year Ended December 31, 2024 2023 Change (in thousands) AATD program $ 11,666 $ 8,453 $ 3,213 DMD programs 15,536 7,808 7,728 HD programs 11,790 13,086 (1,296 ) Other research and development expenses (1) , including INHBE, RNA editing, PRISM, others 119,976 91,617 28,359 ALS and FTD programs (discontinued) 714 9,045 (8,331 ) Total research and development expenses $ 159,682 $ 130,009 $ 29,673 (1) Includes expenses related to other research and development programs, identification of potential drug discovery candidates, compensation-related expenses, internal manufacturing expenses, equipment repairs and maintenance expense, facility-related expenses, and other operating expenses, which are not allocated to specific programs.
Research and Development Expenses The following table summarizes our research and development expenses incurred for the years ended December 31, 2024 and 2023: For the Year Ended December 31, 2024 2023 Increase (Decrease) (in thousands) INHBE program $ 9,294 $ 229 $ 9,065 AATD program 11,666 8,453 3,213 DMD program 15,536 7,808 7,728 HD program 11,790 13,086 (1,296 ) Other research and development expenses(1), including PNPLA3, additional preclinical programs, PRISM 111,396 100,433 10,963 Total research and development expenses $ 159,682 $ 130,009 $ 29,673 (1) Includes expenses related to other research and development programs, identification of potential drug discovery candidates, compensation-related expenses, internal manufacturing expenses, equipment repairs and maintenance expense, facility-related expenses, and other operating expenses, which are not allocated to specific programs.
The increase of $29.7 million was due to the following: • an increase of $3.2 million in external expenses related to our AATD program, WVE-006 (RNA editing); • an increase of $7.7 million in external expenses related to our DMD programs, including WVE-N531 (splicing); • a decrease of $1.3 million in external expenses related to our HD programs, including WVE-003 (silencing); • an increase of $28.4 million in other research and development expenses, including INHBE, 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 facilities-related expenses, partially offset by decreases in other external research and development expenses; and • a decrease of $8.3 million in external expenses related to our discontinued ALS and FTD program, WVE-004.
The increase of $29.7 million was due to the following: • an increase of $9.1 million in external expenses related to our INHBE program, including WVE-007 (RNAi); • an increase of $3.2 million in external expenses related to our AATD program, WVE-006 (RNA editing); • an increase of $7.7 million in external expenses related to our DMD program, including WVE-N531 (splicing); • a decrease of $1.3 million in external expenses related to our HD program, including WVE-003 (silencing); and • an increase of $11.0 million in other research and development expenses, including PNPLA3, additional preclinical programs, PRISM, and 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.
Through December 31, 2024, we have received an aggregate of approximately $1,578.4 million in net proceeds from these transactions, consisting of $977.8 million in net proceeds from public and other registered offerings of our ordinary shares and other securities, $511.3 million from our collaborations and $89.3 million in net proceeds from private placements of our debt and equity securities.
Through December 31, 2025, we have received an aggregate of approximately $2,076.7 million in net proceeds from these transactions, consisting of $1,450.5 million in net proceeds from public and other registered offerings of our ordinary shares and other securities, $536.9 million from our collaborations and $89.3 million in net proceeds from private placements of our debt and equity securities.
As of December 31, 2024, we had cash and cash equivalents of $302.1 million, restricted cash of $3.8 million and an accumulated deficit of $1,121.9 million. We expect that our existing cash and cash equivalents will be sufficient to fund our operations for at least the next twelve months.
As of December 31, 2025, we had cash and cash equivalents of $602.1 million, restricted cash of $3.8 million and an accumulated deficit of $1,326.2 million. We expect that our existing cash and cash equivalents will be sufficient to fund our operations for at least the next twelve months from the issuance date of these financial statements.
General and administrative expenses also include legal fees; expenses associated with being a public company; professional fees for accounting, auditing, tax and consulting services; insurance costs; travel expenses; other operating costs; and facility-related expenses.
General and administrative expenses also include legal fees; expenses associated with being a public company; professional fees for accounting, auditing, tax and consulting services; insurance costs; travel expenses; other operating costs; and facility-related expenses. Other Income, Net Other income, net is comprised primarily of interest income on cash and cash equivalents and refundable tax credits from tax authorities.
Cash Flows The following table summarizes our sources and uses of cash for each of the periods presented: For the Year Ended December 31, 2024 2023 2022 (in thousands) Net cash used in operating activities $ (151,026 ) $ (19,431 ) $ (127,781 ) Net cash used in investing activities (938 ) (1,115 ) (1,255 ) Net cash provided by financing activities 253,890 132,534 67,188 Effect of foreign exchange rates on cash (138 ) (95 ) (210 ) Net increase (decrease) in cash, cash equivalents and restricted cash $ 101,788 $ 111,893 $ (62,058 ) Operating Activities During 2024, operating activities used $151.0 million of cash, primarily due to our net loss of $97.0 million, partially offset by non-cash charges of $21.8 million and changes in our operating assets and liabilities of $75.8 million.
Cash Flows The following table summarizes our sources and uses of cash for each of the periods presented: For the Year Ended December 31, 2025 2024 2023 (in thousands) Net cash used in operating activities $ (187,493 ) $ (151,026 ) $ (19,431 ) Net cash used in investing activities (718 ) (938 ) (1,115 ) Net cash provided by financing activities 488,235 253,890 132,534 Effect of foreign exchange rates on cash 12 (138 ) (95 ) Net increase in cash, cash equivalents and restricted cash $ 300,036 $ 101,788 $ 111,893 Operating Activities During 2025, operating activities used $187.5 million of cash, primarily due to our net loss of $204.4 million and changes in our operating assets and liabilities of $16.9 million, partially offset by non-cash charges of $33.8 million The non-cash charges for 2025 related to share-based compensation expense of $25.0 million, amortization of right-of-use assets of $5.4 million, and depreciation expense of $3.4 million.
The increase of $3.6 million in other income, net was primarily driven by an increase in estimated refundable tax credits as well as an increase in dividend income during the year ended December 31, 2024. 96 Income Tax Benefit During the years ended December 31, 2024 and 2023, we recorded no income tax benefit or provision and an income tax benefit of $0.7 million, respectively.
The increase of $3.6 million in other income, net was primarily driven by an increase in estimated refundable tax credits as well as an increase in interest income during the year ended December 31, 2024.
Liquidity and Capital Resources Since our inception, we have not generated any product revenue and have incurred recurring net operating losses. To date, we have primarily funded our operations through public and other registered offerings of our ordinary shares and other securities, collaborations with third parties and private placements of debt and equity securities.
To date, we have primarily funded our operations through public and other registered offerings of our ordinary shares and other securities, collaborations with third parties and private placements of debt and equity securities.
The increase in revenue earned year over year related to the Takeda Collaboration is primarily due to the termination of the C9 and SCA3 programs in 2023 which led to the recognition of the remainder of the deferred revenue related to the research and development services, as well as the options related to the C9 and SCA3 programs.
The decrease in the Takeda Collaboration revenue earned year over year was primarily due to the termination of the collaboration agreement in October 2024, which led to the recognition of the remainder of the deferred revenue related to the research and development services, as well as the license related to the HD program.
General and Administrative Expenses General and administrative expenses were $59.0 million for the year ended December 31, 2024, compared to $51.3 million for the year ended December 31, 2023. The increase of $7.7 million is primarily driven by increases in compensation related expenses and administrative expenses.
This is mainly due to increases in compensation-related expenses and facilities-related expenses, partially offset by decreases in other external research and development expenses. General and Administrative Expenses General and administrative expenses were $59.0 million for the year ended December 31, 2024, compared to $51.3 million for the year ended December 31, 2023.
The income tax benefit for the year ended December 31, 2023 was due to a change in estimate in connection with U.S. tax guidance relating to the capitalization of research and development expenditures.
The income tax benefit for the year ended December 31, 2023 was due to a change in estimate in connection with U.S. tax guidance relating to the capitalization of research and development expenditures. Liquidity and Capital Resources Since our inception, we have not generated any product revenue and have incurred recurring net operating losses.
Other Income, Net Other income, net for the years ended December 31, 2024 and 2023 was $13.4 million and $9.8 million, respectively.
The increase of $7.7 million was primarily driven by increases in compensation related expenses and administrative expenses. Other Income, Net Other income, net for the years ended December 31, 2024 and 2023 was $13.4 million and $9.8 million, respectively.
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 toolkit of RNA-targeting modalities, including RNAi (SpiNA) and RNA editing (AIMers), provides us with unmatched capabilities for designing and sustainably delivering candidates that optimally address disease biology.
Revenue for year ended December 31, 2022 was $3.6 million and was earned primarily under the Takeda Collaboration Agreement, as the GSK Collaboration Agreement became effective in January 2023.
Revenue for the year ended December 31, 2024 was $108.3 million, and was earned under the GSK Collaboration Agreement ($37.0 million) and the Takeda Collaboration Agreement ($71.3 million).
We have more than a decade of experience challenging convention related to oligonucleotide design and pioneering novel chemistry modifications to optimize the pharmacological properties of our molecules. We have seen in clinical trials that these chemistry modifications enhance potency, distribution, and durability of effect of our molecules.
We were founded on the recognition that there was a significant, untapped opportunity to use chemistry innovation to tune the pharmacological properties of oligonucleotides. We have more than a decade of experience challenging convention related to oligonucleotide design and pioneering novel chemistry modifications to optimize the pharmacological properties of our molecules.
Our net loss was $97.0 million in 2024, $57.5 million in 2023, and $161.8 million in 2022. As of December 31, 2024 and 2023, we had an accumulated deficit of $1,121.9 million and $1,024.9 million, respectively. We expect to incur significant expenses and operating losses for the foreseeable future.
Financial Operations Overview We have never been profitable, and since our inception, we have incurred significant operating losses. Our net loss was $204.4 million in 2025, $97.0 million in 2024, and $57.5 million in 2023. As of December 31, 2025 and 2024, we had an accumulated deficit of $1,326.2 million and $1,121.9 million, respectively.
The $109.7 million increase in revenue year over year was driven by the revenue recognized under the new GSK Collaboration Agreement, after it became effective in January 2023, as well as the increase in revenue recognized under the Takeda Collaboration Agreement.
The $5.0 million decrease in revenue year over year was driven by the revenue recognized under the GSK Collaboration Agreement, partially offset by the increase in revenue recognized under the Takeda Collaboration Agreement.
During 2022, operating activities used $127.8 million of cash, primarily due to our net loss of $161.8 million, partially offset by non-cash charges of $27.3 million and changes in our operating assets and liabilities of $6.7 million. The non-cash charges for 2022 related mainly to share-based compensation expense of $17.2 million and depreciation expense of $6.6 million.
During 2024, operating activities used $151.0 million of cash, primarily due to our net loss of $97.0 million, partially offset by non-cash charges of $21.8 million and changes in our operating assets and liabilities of $75.8 million.
Other Income, Net Other income, net for the years ended December 31, 2023 and 2022 was $9.8 million and $1.6 million, respectively. The increase of $8.2 million in other income, net was primarily driven by an increase in dividend income as well as an increase in estimated refundable tax credits during the year ended December 31, 2023.
The decrease of $2.4 million in other income, net was primarily driven by a decrease in estimated refundable tax credits during the year ended December 31, 2025. Income Tax Benefit During the years ended December 31, 2025 and 2024, we recorded no income tax benefit or provision.
The largest change in operating assets and liabilities was a $9.3 million increase in accounts payable. Investing Activities During 2024, investing activities used $0.9 million of cash, primarily consisting of purchases of property and equipment.
Investing Activities During 2025, investing activities used $0.7 million of cash, primarily consisting of purchases of property and equipment. During 2024, investing activities used $0.9 million of cash, primarily consisting of purchases of property and equipment. During 2023, investing activities used $1.1 million of cash, primarily consisting of purchases of property and equipment.
The gross proceeds to us from the September 2024 Offering were $200.0 million before deducting underwriting discounts and commissions and other offering expenses. On October 1, 2024, the representatives of the underwriters exercised their option in full to purchase an additional 3,750,000 ordinary shares, for additional net proceeds to us of approximately $28.2 million.
The gross proceeds to us from the December 2025 Offering were approximately $402.5 million before deducting underwriting discounts and commissions and other offering expenses, and including gross proceeds from the exercise of the Underwriters' option to purchase the additional shares in full.
General and Administrative Expenses General and administrative expenses were $51.3 million for the year ended December 31, 2023, compared to $50.5 million for the year ended December 31, 2022. The increase of $0.8 million was primarily driven by increases in other general and administrative operating expenses, partially offset by a decrease in compensation-related expenses.
This is mainly due to increases in compensation-related expenses and facilities-related expenses, partially offset by decreases in other external research and development expenses. General and Administrative Expenses General and administrative expenses were $75.3 million for the year ended December 31, 2025, compared to $59.0 million for the year ended December 31, 2024.
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. We were founded on the recognition that there was a significant, untapped opportunity to use chemistry innovation to tune the pharmacological properties of oligonucleotides.
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.
Additionally, there were $3.1 million in net proceeds from our "at-the-market" equity program. During 2022, net cash provided by financing activities was $67.2 million, primarily due to the $65.5 million in net proceeds from the underwritten offering we completed in June 2022, which was comprised of sales of ordinary shares and the 2022 Pre-Funded Warrants.
Financing Activities During 2025, net cash provided by financing activities was $488.2 million, primarily due to the $377.8 million in net proceeds from the December 2025 Offering of ordinary shares and the 2025 Pre-Funded Warrants, $94.6 million in net proceeds from sales under our “at-the-market” equity program, as well as $14.9 million in proceeds from the exercise of stock options.
Research and Development Expenses The following table summarizes our research and development expenses incurred for the years ended December 31, 2023 and 2022: For the Year Ended December 31, 2023 2022 Change (in thousands) AATD program $ 8,453 $ 3,763 $ 4,690 DMD programs 7,808 2,610 5,198 HD programs 13,086 7,952 5,134 Other research and development expenses (1) , including INHBE, RNA editing, PRISM, others 91,617 89,992 1,625 ALS and FTD programs (discontinued) 9,045 11,539 (2,494 ) Total research and development expenses $ 130,009 $ 115,856 $ 14,153 (1) Includes expenses related to other research and development programs, identification of potential drug discovery candidates, compensation-related expenses, internal manufacturing expenses, equipment repairs and maintenance expense, facility-related expenses, and other operating expenses, which are not allocated to specific programs. 97 Research and development expenses were $130.0 million for the year ended December 31, 2023, compared to $115.9 million for the year ended December 31, 2022.
Research and Development Expenses The following table summarizes our research and development expenses incurred for the years ended December 31, 2025 and 2024: For the Year Ended December 31, 2025 2024 Increase (Decrease) (in thousands) INHBE program $ 15,715 $ 9,294 $ 6,421 AATD program 5,714 11,666 (5,952 ) DMD program 19,469 15,536 3,933 HD program 2,678 11,790 (9,112 ) Other research and development expenses(1), including PNPLA3, additional preclinical programs, PRISM 139,203 111,396 27,807 Total research and development expenses $ 182,779 $ 159,682 $ 23,097 (1) Includes expenses related to other research and development programs, identification of potential drug discovery candidates, compensation-related expenses, internal manufacturing expenses, equipment repairs and maintenance expense, facility-related expenses, and other operating expenses, which are not allocated to specific programs.
We received an additional $14.0 million in net proceeds from the December 2023 Offering in January 2024. On September 27, 2024, we closed the September 2024 Offering in which we issued and sold 23,125,001 of our ordinary shares and the 2024 Pre-Funded Warrants to purchase up to 1,875,023 of our ordinary shares.
On December 11, 2025, we closed an underwritten public offering (the "December 2025 Offering") in which we issued and sold 18,552,632 of our ordinary shares, including 2,763,157 ordinary shares issued and sold pursuant to the underwriter's exercise in full of their option to purchase additional shares, and pre-funded warrants to purchase up to 2,631,578 of our ordinary shares (the "2025 Pre-Funded Warrants").
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We are actively advancing programs using four distinct modalities, including novel A-to-I RNA editing oligonucleotides (“AIMers”). 91 These modalities include: • RNA editing, which uses AIMers that are designed to target single bases on an RNA transcript and recruit endogenous ADAR enzymes that naturally possess the ability to change an adenine (A) to an inosine (I), which cells read as guanine (G).
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We have seen in clinical trials that these chemistry modifications enhance potency, distribution, and durability of effect of our molecules.
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This approach enables both the correction of G-to-A point mutations and the modulation of RNA to either upregulate protein expression, modify protein-protein interactions, or alter RNA folding and processing.
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We are actively advancing programs across modalities, including RNA interference (“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.
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AIMers are short in length, fully chemically modified, and use our novel chemistry, which make them distinct from other ADAR-mediated editing approaches. • Antisense (silencing) , which uses our oligonucleotide designed to bind to a specific sequence in a target RNA strand that encodes a disease-associated protein or pathogenic RNA.
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We are currently prioritizing lead programs that use GalNAc delivery for hepatic and metabolic diseases, each of which have potential to translate powerful human genetic insights into potentially transformational RNA medicines: • WVE-007 is a GalNAc-conjugated siRNA (SpiNA design) targeting inhibin βE (“INHBE”) for obesity; • WVE-006 is a GalNAc-conjugated RNA editing oligonucleotide (AIMer) for AATD; • WVE-008 is a GalNAc-conjugated RNA editing oligonucleotide (AIMer) for PNPLA3 I148M liver disease.
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The resulting double-stranded molecule (“duplex”) is then recognized by a cellular enzyme called RNase H, which cleaves, or cuts, the target RNA in the duplex, thereby preventing the disease-associated protein from being made. • RNA interference (RNAi ) (silencing) , which uses our double-stranded RNAs called siRNAs to engage the RNAi machinery known as the RNA-induced silencing complex (“RISC”) and to silence a target RNA that is either pathogenic itself or encodes a disease-associated protein, thereby preventing the accumulation of the pathogenic species (RNA or protein). • Splicing / exon skipping , which is the processing of a nascent pre-mRNA transcript into mRNA by removing introns and joining exons together.
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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.
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Exon skipping uses our oligonucleotide designed to bind to a particular sequence within a target pre-mRNA and direct the cellular machinery to alter the final composition of exons in mature mRNA by deleting, or splicing out, certain specific regions of that RNA.
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We expect to incur significant expenses and operating losses for the foreseeable future.
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We have a robust and diverse pipeline of potential first-or best-in-class programs addressing both rare and common diseases: • GalNAc-conjugated oligonucleotides for hepatic and metabolic diseases including: • Obesity: WVE-007 is a GalNAc-conjugated siRNA targeting inhibin βE (“INHBE”); • Alpha-1 antitrypsin deficiency ("AATD"): WVE-006 is a GalNAc-conjugated SERPINA1 AIMer; • Liver disease: GalNAc-conjugated AIMer targeting PNPLA3 I148M for correction; and • 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. • Unconjugated oligonucleotides for muscle, CNS and other disease areas including: • Duchenne muscular dystrophy ("DMD"): WVE-N531 is an exon 53 splicing oligonucleotide; and 92 • Huntington’s disease ("HD"): WVE-003 is an allele-selective oligonucleotide designed to lower mutant huntingtin (“mHTT”) protein and preserve healthy, wild-type huntingtin (“wtHTT”) protein.
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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.
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Our RNA editing capability affords us the dexterity to address both rare and common diseases, as well as those diseases impacting large patient populations.
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Comparison of the Year Ended December 31, 2025 to the Year Ended December 31, 2024 The following table summarizes our results of operations for 2025 and 2024: For the Year Ended December 31, 2025 2024 Increase (Decrease) (in thousands) Revenue $ 42,727 $ 108,302 $ (65,575 ) Operating expenses: Research and development 182,779 159,682 23,097 General and administrative 75,331 59,023 16,308 Total operating expenses 258,110 218,705 39,405 Loss from operations (215,383 ) (110,403 ) 104,980 Total other income, net 11,005 13,395 (2,390 ) Loss before income taxes (204,378 ) (97,008 ) 107,370 Income tax benefit — — — Net loss $ (204,378 ) $ (97,008 ) $ 107,370 Revenue Revenue for the year ended December 31, 2025 was $42.7 million, and was earned under the GSK Collaboration Agreement.
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AIMers are designed to target single bases on an RNA transcript and recruit proteins that exist in the body, called ADAR enzymes, which naturally possess the ability to change an adenine (A) to an inosine (I), which cells read as guanine (G).
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The $65.6 million decrease in revenue year over year was driven by the revenue recognized under the Takeda Collaboration Agreement in 2024, partially offset by the increase in revenue recognized under the GSK Collaboration Agreement.
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This approach enables both the correction of G-to-A point mutations and the modulation of RNA to either upregulate protein expression, modify protein-protein interactions, or alter RNA folding and processing. AIMers enable simplified delivery and avoid the risk of permanent changes to the genome and irreversible off-target effects with DNA-targeting approaches.
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Research and development expenses were $182.8 million for the year ended December 31, 2025, compared to $159.7 million for the year ended December 31, 2024.
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AIMers are short in length, fully chemically modified, and use our novel chemistry, which make them distinct from other ADAR-mediated editing approaches. GSK Collaboration In December 2022, we announced a strategic collaboration with GlaxoSmithKline Intellectual Property (No. 3) (“GSK”) to advance transformative oligonucleotide therapeutics, including WVE-006.
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The increase of $16.3 million is primarily driven by increases in compensation related expenses and administrative expenses. Other Income, Net Other income, net for the years ended December 31, 2025 and 2024 was $11.0 million and $13.4 million, respectively.
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The collaboration combines GSK’s novel genetic insights, as well as its global development and commercial capabilities, with our PRISM platform and oligonucleotide expertise.
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The largest change in operating assets and liabilities was a $19.8 million decrease in deferred revenue, mainly driven by revenue recognized under the GSK Collaboration Agreement.
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The collaboration will enable us to continue building a pipeline of first-in-class oligonucleotide-based therapeutics and unlock new areas of disease biology, as well as realize the full value of WVE-006 as a potential best-in-class treatment for AATD that has the potential to simultaneously address both liver and lung manifestations of the disease.
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Our GSK collaboration has three components: (1) a discovery collaboration which enables us to advance up to three programs leveraging targets informed by GSK’s novel genetic insights; (2) a discovery collaboration which enables GSK to advance up to eight programs leveraging PRISM and our oligonucleotide expertise and discovery capabilities; and (3) an exclusive global license for GSK to WVE-006, our AATD program, that uses our proprietary AIMer technology.
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We will maintain development responsibilities for WVE-006 through completion of RestorAATion-2, at which point development and commercial responsibilities will transition to GSK.
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Takeda Collaboration (expired in October 2024) In February 2018, we entered into a global strategic collaboration with Takeda Pharmaceutical Company Limited (“Takeda”), pursuant to which we agreed to collaborate with Takeda on the research, development and commercialization of oligonucleotide therapeutics for disorders of the CNS.
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On October 11, 2024, we were notified by Takeda that Takeda did not intend to exercise and therefore elected to terminate its option for the HD target under the collaboration. As HD was the last active collaboration target under the collaboration, the collaboration expired with immediate effect.
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As a result of the option termination, we are now free to advance WVE-003, our clinical-stage Huntington’s disease program, as well as any other programs targeting HTT, independently or with other partners. 93 Financial Operations Overview We have never been profitable, and since our inception, we have incurred significant operating losses.
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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, splicing, RNAi, and antisense modalities.
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Other Income, Net Other income, net is comprised of refundable tax credits from tax authorities, dividend and interest income earned on cash and cash equivalents balances, gains and losses on foreign currency transactions, and real estate taxes.
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Comparison of the Year Ended December 31, 2023 to the Year Ended December 31, 2022 The following table summarizes our results of operations for 2023 and 2022: For the Year Ended December 31, 2023 2022 Change (in thousands) Revenue $ 113,305 $ 3,649 $ 109,656 Operating expenses: Research and development 130,009 115,856 14,153 General and administrative 51,292 50,513 779 Total operating expenses 181,301 166,369 14,932 Loss from operations (67,996 ) (162,720 ) 94,724 Total other income, net 9,806 1,578 8,228 Loss before income taxes (58,190 ) (161,142 ) 102,952 Income tax benefit (provision) 677 (681 ) 1,358 Net loss $ (57,513 ) $ (161,823 ) $ 104,310 Revenue Revenue for the year ended December 31, 2023 was $113.3 million and was earned under the GSK Collaboration Agreement and the Takeda Collaboration Agreement.
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The $113.3 million in revenue recognized during the year ended December 31, 2023 was comprised of $66.3 million in revenue recognized under the GSK Collaboration Agreement and $47.0 million of revenue recognized under the Takeda Collaboration Agreement.
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The $3.6 million in revenue recognized during the year ended December 31, 2022 was primarily related to the research and development services under the Takeda Collaboration Agreement related to the HD, C9, and SCA3 programs. During the year ended December 31, 2023, the Company recognized revenue of $47.0 million under the Takeda Collaboration.
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The income tax benefit for the year ended December 31, 2023 was due to a change in estimate in connection with recent U.S. tax guidance relating to the capitalization of research and development expenditures.
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The income tax provision for the year ended December 31, 2022 was primarily due to the requirement under the Tax Cuts and Jobs Act of 2017 for taxpayers to capitalize and amortize research and development expenditures over five or fifteen years pursuant to Section 174 of the Internal Revenue Code of 1986, as amended.

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Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

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Biggest changeFor the years ended December 31, 2024, 2023, and 2022, changes in foreign currency exchange rates did not have a material impact on our historical financial position, our business, our financial condition, our results of operations or our cash flows.
Biggest changeFor the years ended December 31, 2025, 2024, and 2023, changes in foreign currency exchange rates did not have a material impact on our historical financial position, our business, our financial condition, our results of operations or our cash flows.

Other WVE 10-K year-over-year comparisons