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What changed in Wave Life Sciences Ltd.'s 10-K — 2023 vs 2024

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Paragraph-level year-over-year comparison of Wave Life Sciences Ltd.'s 2023 and 2024 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 2024 report.

+551 added−600 removedSource: 10-K (2025-03-04) vs 10-K (2024-03-06)

Top changes in Wave Life Sciences Ltd.'s 2024 10-K

551 paragraphs added · 600 removed · 424 edited across 7 sections

Item 1. Business

Business — how the company describes what it does

219 edited+79 added−147 removed303 unchanged
Biggest changeWe have a robust and diverse pipeline of potential first-or best-in-class programs, including: • GalNAc-conjugated oligonucleotides for hepatic and metabolic diseases including: o AATD: WVE-006 is a GalNAc-conjugated SERPINA1 RNA editing oligonucleotide. o Obesity: Lead clinical candidate is a GalNAc-conjugated RNAi oligonucleotide targeting inhibin βE (“INHBE”). • Unconjugated oligonucleotides for muscle, CNS and other disease areas including: o DMD: WVE-N531 is an exon 53 splicing oligonucleotide. o HD: WVE-003 is a selective mutant huntingtin (“mHTT”)-lowering SNP3 antisense silencing oligonucleotide.
Biggest changeWe 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 • 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. 7 Our Current Programs Additional details regarding our lead therapeutic programs are set forth below.
Item 1. Business Overview We are a clinical-stage biotechnology company focused on unlocking the broad potential of RNA medicines (also known as oligonucleotides), or those targeting ribonucleic acid (“RNA”), to transform human health.
Item 1. Business Overview We are a clinical-stage biotechnology company focused on unlocking the broad potential of ribonucleic acid (“RNA”) medicines (also known as oligonucleotides), or those targeting RNA, to transform human health.
The 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 program for AATD that uses our proprietary AIMer technology.
The 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.
Most such applications are meant to be reviewed within ten months from the date it is accepted for filing (i.e., 12 months from submission), and most applications for “priority review” products are meant to be reviewed within six months from the date the application is accepted for filing (i.e., eight months from submission).
Most such applications are meant to be reviewed within ten months from the date it is accepted for filing (i.e., within 12 months from submission), and most applications for “priority review” products are meant to be reviewed within six months from the date the application is accepted for filing (i.e., within eight months from submission).
This calculation is made on a drug product by drug product basis and the amount of the rebate owed to the federal government is directly dependent on the volume of a drug product that is paid for by Medicare Parts B or D.
This calculation is made on a product-by-product basis and the amount of the rebate owed to the federal government is directly dependent on the volume of a drug product that is paid for by Medicare Parts B or D.
We also have a supplier diversity program that identifies and classifies the diversity of our suppliers, encouraging the use of a more diversified supply base.
We also have a supplier diversity program that identifies and classifies our suppliers, encouraging the use of a more diversified supply base.
If an orphan drug-designated product subsequently receives FDA approval for the disease for which it was designed, the product will be entitled to seven years of product exclusivity, which means that the FDA may not approve any other applications to market the same drug for the same indication, except in very limited circumstances (such as a showing of clinical superiority to the product with 49 orphan exclusivity by means of greater effectiveness, greater safety or providing a major contribution to patient care or in instances of drug supply issues), for seven years.
If an orphan drug-designated product subsequently receives FDA approval for the disease for which it was designed, the product will be entitled to seven years of product exclusivity, which means that the FDA may not approve any other applications to market the same drug for the same indication, except in very limited circumstances (such as a showing of clinical superiority to the product with orphan exclusivity by means of greater effectiveness, greater safety or providing a major contribution to patient care or in instances of drug supply issues), for seven years.
With regard to biopharmaceutical products, the ACA, among other things, addressed a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected, increased the minimum Medicaid rebates owed by manufacturers under the Medicaid Drug Rebate Program and extended the rebate program to individuals enrolled in Medicaid managed care organizations, established annual fees on manufacturers of certain branded prescription drugs, and created a new Medicare Part D coverage gap discount program.
With regard to biopharmaceutical products, the ACA, among other things, addressed a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected, increased the minimum Medicaid rebates owed by such manufacturers under the rebate program and extended the program to individuals enrolled in Medicaid managed care organizations; established annual fees on manufacturers of certain branded prescription drugs; and created a new Medicare Part D coverage gap discount program.
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.
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.
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.
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.
Accelerated Approval Pathway In addition, products studied for their safety and effectiveness in treating serious or life-threatening illnesses and that provide meaningful therapeutic benefit over existing treatments may receive accelerated approval from the FDA and may be approved on the 47 basis of adequate and well-controlled clinical trials establishing that the drug product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit.
Accelerated Approval Pathway In addition, products studied for their safety and effectiveness in treating serious or life-threatening illnesses and that provide meaningful therapeutic benefit over existing treatments may receive accelerated approval from the FDA and may be approved on the basis of adequate and well-controlled clinical trials establishing that the drug product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit.
Discovery of previously unknown problems with a product, including adverse events of unlisted severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements such as noncompliance with cGMP or failure to correct previously identified inspection findings, may result in mandatory revisions to the approved labeling to add new safety information; imposition of post-market or clinical trials to assess new 48 safety risks; or imposition of distribution or other restrictions under a REMS program.
Discovery of previously unknown problems with a product, including adverse events of unlisted severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements such as noncompliance with cGMP or failure to correct previously identified inspection findings, may result in mandatory revisions to the approved labeling to add new safety information; imposition of post-market or clinical trials to assess new safety risks; or imposition of distribution or other restrictions under a REMS program.
We believe that our scalable synthesis processes will allow us to meet demand for current good manufacturing practices (“cGMP”)-qualified clinical trial supply, as well as the potential for commercial manufacturing at a cost of goods and potential cost-per-patient that are comparable to stereorandom oligonucleotides. 12 Our Proprietary Chemistry Backbone Stereochemistry In our foundational Nature Biotechnology paper (Iwamoto N, et al.
We believe that our scalable synthesis processes will allow us to meet demand for current good manufacturing practices (“cGMP”)-qualified clinical trial supply, as well as the potential for commercial manufacturing at a cost of goods and potential cost-per-patient that are comparable to stereorandom oligonucleotides. Our Proprietary Chemistry Backbone Stereochemistry In our foundational Nature Biotechnology paper (Iwamoto N, et al.
Together, these studies provide evidence that wtHTT is both neural protective during stress and is specifically protective against HD; thus, we believe an allele-selective therapeutic, one that can diminish the production of mHTT while sparing wtHTT, may be ideal. 34 Symptoms of HD typically appear between the ages of 30 and 50 and worsen over the next 10 to 20 years.
Together, these studies provide evidence that wtHTT is both neural protective during stress and is specifically protective against HD; thus, we believe an allele-selective therapeutic, one that can diminish the production of mHTT while sparing wtHTT, may be ideal. Symptoms of HD typically appear between the ages of 30 and 50 and worsen over the next 10 to 20 years.
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”).
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”).
This approach avoids the need, and certain limitations, for complex delivery vehicles such as lipid nanoparticles (“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.
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.
Control treatment did not increase expression of any of the NRF2-dependent genes, indicating that AIMer treatment did not lead to NRF2-dependent gene expression changes through non-specific mechanisms such as increased cellular stress. To exemplify our ability to upregulate protein expression levels using ADAR, we evaluated AIMers designed to modify regulatory elements in RNA that mediate protein-RNA or RNA-RNA interactions.
Control treatment did not increase expression of any of the NRF2-dependent genes, indicating that AIMer treatment did not lead to NRF2-dependent gene expression changes through non-specific mechanisms such as increased cellular stress. 23 To exemplify our ability to upregulate protein expression levels using ADAR, we evaluated AIMers designed to modify regulatory elements in RNA that mediate protein-RNA or RNA-RNA interactions.
RNAi : We have applied our stereopure PS and PN modifications to the RNAi modality using double-stranded siRNAs and demonstrated potent and durable silencing in vivo in transgenic mice, leveraging GalNAc to enhance delivery to liver hepatocytes. In April 2023, we announced the publication of preclinical data for our novel siRNA formats in the journal of Nucleic Acids Research .
RNAi : We have applied our stereopure PS and PN modifications to the siRNA modality using double-stranded siRNAs and demonstrated potent and durable silencing in vivo in transgenic mice, leveraging GalNAc to enhance delivery to liver hepatocytes. 24 In April 2023, we announced the publication of preclinical data for our novel siRNA formats in the journal of Nucleic Acids Research .
The data, shown below, illustrate a GalNAc-siRNA, with controlled stereochemistry and PN backbone chemistry, that led to remarkably durable transcript silencing in mice three months after a single dose, compared with mice treated with a siRNA based on 19 state-of-the-art designs, where expression levels had recovered to control levels (left).
The data, shown below, illustrate a GalNAc-siRNA, with controlled stereochemistry and PN backbone chemistry, that led to remarkably durable transcript silencing in mice three months after a single dose, compared with mice treated with a siRNA based on state-of-the-art designs, where expression levels had recovered to control levels (left).
Asuragen has leveraged its AmplideX® PCR technology to develop companion diagnostic tests designed to size and phase HTT CAG repeats with the SNPs targeted by our previous investigational therapeutic programs in HD, as well as WVE-003, our current HD program being investigated in the ongoing SELECT-HD clinical trial.
Asuragen has leveraged its AmplideX® PCR technology to develop companion diagnostic tests designed to size and phase HTT CAG repeats with the SNPs targeted by WVE-003, our current HD program being investigated in the ongoing SELECT-HD clinical trial as well as those SNPs targeted by our previous investigational therapeutic programs.
We cannot assure you that the Registrar will offer to compound any such violations of Section 34, or that any offer to compound will be for an amount similar to previous compound offers. 41 Competition The biotechnology and pharmaceutical marketplace is characterized by rapidly advancing technologies, intense competition and a strong emphasis on proprietary products.
We cannot assure you that the Registrar will offer to compound any such violations of Section 34, or that any offer to compound will be for an amount similar to previous compound offers. Competition The biotechnology and pharmaceutical marketplace is characterized by rapidly advancing technologies, intense competition and a strong emphasis on proprietary products.
We also are subject to, or 54 may in the future become subject to, U.S. federal and state, and foreign laws and regulations imposing obligations on how we collect, use, disclose, store and process personal information. Our actual or perceived failure to comply with such obligations could result in liability or reputational harm and could harm our business.
We also are subject to, or may in the future become subject to, U.S. federal and state, and foreign laws and regulations imposing obligations on how we collect, use, disclose, store and process personal information. Our actual or perceived failure to comply with such obligations could result in liability or reputational harm and could harm our business.
We expect that additional state and federal healthcare reform measures will be 56 adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, including any future drug products for which we secure marketing approval. Manufacturing Requirements We and our third-party manufacturers must comply with applicable cGMP requirements.
We expect that additional state and federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, including any future drug products for which we secure marketing approval. Manufacturing Requirements We and our third-party manufacturers must comply with applicable cGMP requirements.
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.
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.
Utilizing our proprietary “edit-verse,” which is powered by genetic datasets and deep learning models, we have identified several RNA editing targets that leverage easily accessible biomarkers, offer efficient paths to proof-of-concept in humans, and represent meaningful commercial opportunities.
Utilizing our proprietary “edit-verse,” which is powered by genetic datasets and deep learning models, we have identified several RNA editing targets in indications that leverage easily accessible biomarkers, offer efficient paths to proof-of-concept in humans, and represent meaningful commercial opportunities.
IVDs are regulated by the FDA as medical devices, and since 2014 the agency has issued final and draft guidance documents that are intended to assist companies developing in vitro companion diagnostic devices and companies 51 developing therapeutic products that depend on the use of a specific in vitro companion diagnostic for the safe and effective use of the therapeutic product.
IVDs are regulated by the FDA as medical devices, and since 2014 the agency has issued final and draft guidance documents that are intended to assist companies developing in vitro companion diagnostic devices and companies developing therapeutic products that depend on the use of a specific in vitro companion diagnostic for the safe and effective use of the therapeutic product.
The manufacturers of such devices remaining on the market must comply with specific requirements in the IVDR, but ultimately, such products, as with all new IVDs, will have to undergo the IVDR’s conformity assessment procedures. In addition, 53 IVDs in the highest risk class will have to be tested by a Designated Reference Laboratory.
The manufacturers of such devices remaining on the market must comply with specific requirements in the IVDR, but ultimately, such products, as with all new IVDs, will have to undergo the IVDR’s conformity assessment procedures. In addition, IVDs in the highest risk class will have to be tested by a Designated Reference Laboratory.
Professional Development Programs and Opportunities : Employees are our most valuable resource, and we focus on providing them with opportunities so that they can continue to grow and excel in their functions and our company. Professional development of our employees drives engagement and allows us to leverage opportunities to grow and promote key talent from within our organization.
Professional Development Programs and Opportunities : Employees are our most valuable resource, and we focus on providing them with opportunities so that they can continue to grow and excel in their functions and our company. Professional development of our 47 employees drives engagement and allows us to leverage opportunities to grow and promote key talent from within our organization.
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 principle of recognition of an already existing national marketing authorization by one or more member states.
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.
To date, we have achieved in vivo proof-of-concept modulating protein-protein interactions and upregulating protein expression. 17 To exemplify our ability to modulate protein-protein interactions using ADAR, we evaluated the well characterized KEAP1/NRF2 system. Through direct protein-protein interactions, KEAP1 negatively regulates the activity of NRF2 as an inducer of antioxidant gene expression.
To date, we have achieved in vivo proof-of-concept modulating protein-protein interactions and upregulating protein expression. To exemplify our ability to modulate protein-protein interactions using ADAR, we evaluated the well characterized KEAP1/NRF2 system. Through direct protein-protein interactions, KEAP1 negatively regulates the activity of NRF2 as an inducer of antioxidant gene expression.
The navy dots represent the impact of a few stereopure PN modifications in compounds with otherwise identical sequences and 2’-ribose 21 chemical modifications. There is an overall shift upwards in activity among the PS / PO / PN compounds, representing a substantial potency gain in most cases.
The navy dots represent the impact of a few stereopure PN modifications in compounds with otherwise identical sequences and 2’-ribose chemical modifications. There is an overall shift upwards in activity among the PS / PO / PN compounds, representing a substantial potency gain in most cases.
Under the Prescription Drug User Fee Act (“PDUFA”), for original NDAs, the FDA has ten months from the filing date in which to complete its initial review of a standard application and respond to the applicant, and six months from the filing date for an application 45 with priority review.
Under the Prescription Drug User Fee Act (“PDUFA”), for original NDAs, the FDA has ten months from the filing date in which to complete its initial review of a standard application and respond to the applicant, and six months from the filing date for an application with priority review.
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.
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.
Heterozygous INHBE loss-of-function 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 restore a healthy metabolic profile.
A significant number of our management and professional employees have had prior experience with pharmaceutical, biotechnology or medical product companies. None of our employees are represented by a labor union or covered under a collective bargaining agreement. Management considers relations with our employees to be good.
A significant number of our management and employees have had prior experience with pharmaceutical, biotechnology or medical product companies. None of our employees are represented by a labor union or covered under a collective bargaining agreement. Management considers relations with our employees to be good.
The GSK Equity Investment closed on January 26, 2023. The shares purchased by GGL 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 are subject to lock-up and standstill restrictions and carry certain registration rights, customary for transactions of this kind.
The manufacturing development, preclinical and clinical testing, and review process requires substantial time, effort and financial resources. Manufacturing development includes laboratory evaluation of product chemistry, formulation, development of manufacturing and control procedures, evaluation of stability, and the establishment of procedures to ensure continued product quality.
The manufacturing development, preclinical and clinical testing, and regulatory review process requires substantial time, effort and financial resources. Manufacturing development includes laboratory evaluation of product chemistry, formulation, development of manufacturing and control procedures, evaluation of stability, and the establishment of procedures to ensure continued product quality.
The FDA may request additional information rather than accept an NDA for review. Any resubmitted application, following a refusal to file action, is also subject to 60-day review before the FDA accepts it for review.
The FDA may request additional information rather than accept an NDA for review. Any resubmitted application, following a refusal to file action, is also subject to 60-day review before the FDA accepts it for filing.
European Union Orphan Drug Designation In the European Union (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.
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.
Although sponsors are also obligated to disclose the results of their clinical trials after completion, disclosure of the results can be delayed in some cases for up to two years after the date of completion of the trial.
Although sponsors are also obligated to disclose the results of their clinical trials after completion, such disclosure can be delayed in some cases for up to two years after the date of completion of the trial.
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 and human primary hepatocytes, as shown 14 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.
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.
The GSK 38 Collaboration Agreement contains customary termination provisions, including certain termination rights for convenience, breach, and others, including on a target/program basis or of the Collaboration Agreement in its entirety.
The GSK Collaboration Agreement contains customary termination provisions, including certain termination rights for convenience, breach, and others, including on a target/program basis or of the GSK Collaboration Agreement in its entirety.
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.
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.
We have demonstrated potent (up to 65%) and durable (out to at least four months) editing of UGP2 mRNA in vivo in multiple regions of the CNS following a single unconjugated AIMer dose in a mouse model with human ADAR, as shown in the figure below. 15 We have also demonstrated that RNA editing observed in mice translates when moving to non-human primates.
We have demonstrated potent (up to 65%) and durable (out to at least four months) editing of UGP2 mRNA in vivo in multiple regions of the CNS following a single unconjugated AIMer dose in a mouse model with human ADAR, as shown in the figure below. 21 We have also demonstrated that RNA editing observed in mice translates when moving to non-human primates.
We provide an Employee Assistance Program (“EAP”), as a cost-free benefit, which is available to help employees and their household members to confidentially manage everyday life, work challenges, stress, and other personal issues, by providing consultation, referrals, and resources, along with ongoing webinars on various work-life, mental health, and wellness topics for employees.
We provide an Employee Assistance Program as a cost-free benefit, which is available to help employees and their household members to confidentially manage everyday life, arising work challenges, stress, and other personal issues, by providing consultation, referrals, and resources, along with ongoing webinars on various work-life, mental health, and wellness topics for employees.
We will continue to evolve and strengthen our strategies relating to talent, while furthering our investment in our employees, culture, community partnerships and outreach, and other human capital measures. 59 Corporate Information We were incorporated under the name Wave Life Sciences Pte. Ltd. (Registration No.: 201218209G) under the laws of Singapore on July 23, 2012.
We will continue to evolve and strengthen our strategies relating to talent, while furthering our investment in our employees, culture, community partnerships and outreach, and other human capital measures . 49 Corporate Information We were incorporated under the name Wave Life Sciences Pte. Ltd. (Registration No.: 201218209G) under the laws of Singapore on July 23, 2012.
The pharmacokinetic data, shown in the figure below on the left, confirmed that a significant amount of AIMer was still detectable in the liver at that time. To assess off-target editing for the whole transcriptome, a mutation-calling software was used to call edit sites. From this analysis, we observed nominal off-target editing across the transcriptome.
The PK data, shown in the figure below on the left, confirmed that a significant amount of AIMer was still detectable in the liver at that time. To assess off-target editing for the whole transcriptome, a mutation-calling software was used to call edit sites. From this analysis, we observed nominal off-target editing across the transcriptome.
The IVDR imposes additional requirements relating to post-market surveillance and submission of post-market performance follow-up reports. The EC has designated twelve 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 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.
We believe that providing employees with an ownership interest in Wave through grants of equity awards further strengthens the level of employee engagement. In addition, we have an Employee Share Purchase Plan, as amended (“ESPP”), which provides our U.S. employees with an opportunity to purchase our ordinary shares at a 15% discount to the market price.
We believe that providing employees with an ownership interest in Wave through grants of equity awards further strengthens the level of employee engagement. In addition, our Employee Share Purchase Plan, as amended (“ESPP”), provides our U.S. employees with an opportunity to purchase our ordinary shares at a 15% discount to the market price.
These additional tissues in mice include heart, kidney, lung, and spleen, as well as liver cells beyond hepatocytes. The application of PRISM to RNA editing opens the door to therapeutic applications extending beyond precise correction of genetic mutations, including upregulation of expression, modification of protein function, or alteration of protein stability.
These additional tissues in mice include heart, kidney, lung, pancreas and spleen, as well as liver cells beyond hepatocytes. 22 The application of PRISM to RNA editing opens the door to therapeutic applications extending beyond precise correction of genetic mutations, including upregulation of expression, modification of protein function, or alteration of protein stability.
The CRL may require additional clinical or other data, additional pivotal Phase 3 clinical trial(s) and/or other significant and time-consuming requirements related to clinical trials, preclinical studies or manufacturing. If a CRL is issued, the applicant may choose to either resubmit the NDA addressing all of the deficiencies identified in the letter or withdraw the application.
The CRL may require additional clinical or other data, additional pivotal Phase 3 clinical trial(s) and/or other significant and time-consuming requirements related to clinical trials, nonclinical studies or manufacturing. If a CRL is issued, the applicant may choose to either resubmit the NDA addressing all of the deficiencies identified in the letter or withdraw the application.
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”); 43 • submission to the FDA of an Investigational New Drug application (“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”) 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; • 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 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.
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 2043.
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.
After January 31, 2025, all clinical trials, including those that are ongoing, will become 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.
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.
This focus enables us to: 6 • Leverage diversity of expression across cell types by modulating the many regulatory pathways that impact gene expression, including transcription, endogenous RNA interference pathways, splicing, and translation; • Address diseases that have historically been difficult to treat with small molecules or biologics; • Access a variety of tissue types or cell types throughout the body and modulate the frequency of dosing for broad distribution in tissues over time; • Avoid the risk of permanent off-target genetic changes and other challenges associated with DNA editing or gene therapy approaches; and • Leverage well-established industry manufacturing processes and regulatory, access, and reimbursement pathways.
This focus enables us to: • Leverage diversity of expression across cell types by modulating the many regulatory pathways that impact gene expression, including transcription, endogenous RNAi pathways, splicing, and translation; • Address diseases that have historically been difficult to treat with small molecules or biologics; • Access a variety of tissue types or cell types throughout the body and modulate the frequency of dosing for broad distribution in tissues over time; • Avoid the risk of permanent off-target genetic changes and other challenges associated with DNA editing or gene therapy approaches; and • Leverage well-established industry manufacturing processes and regulatory, access, and reimbursement pathways.
Today, 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 preclinically and in clinical trials that these chemistry modifications enhance potency, distribution, and durability of effect of our molecules.
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.
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 RNAi and antisense).
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).
The prescribing information for each notes that the effect of augmentation therapy with any alpha1-proteinase inhibitor on pulmonary exacerbations and on the progression of emphysema in Alpha1-PI deficiency has not been demonstrated in randomized, controlled clinical trials.
The prescribing information for each states that the effect of augmentation therapy with any alpha1-proteinase inhibitor on pulmonary exacerbations and on the progression of emphysema in Alpha1-PI deficiency has not been demonstrated in randomized, controlled clinical trials.
If a sponsor or the FDA believes that a diagnostic test is essential for the safe and effective use of a corresponding therapeutic product, a sponsor will typically work with a collaborator to develop an in vitro diagnostic (“IVD”).
If a sponsor or the FDA believes that a diagnostic test is essential for the safe and effective use of a corresponding therapeutic product, a sponsor will typically work with a collaborator to develop an appropriate in vitro diagnostic product (“IVD”) for such use.
The three types of marketing pathways for medical devices are clearance of a premarket notification under Section 510(k) of the FDCA (“510(k)”), approval of a premarket approval application (“PMA”) or authorization of a de novo classification request, or de novo .
The three types of marketing pathways for medical devices, including IVDs, are clearance of a premarket notification under Section 510(k) of the FDCA (“510(k)”), approval of a premarket approval application (“PMA”) or authorization of a De Novo classification request (“ De Novo ”).
Our Strategy We are building a leading RNA medicines company by leveraging PRISM to design, develop and commercialize optimized disease-modifying medicines for indications with a high degree of unmet medical need. We have a robust and diverse pipeline of first- or best-in-class RNA medicines using our RNA editing, RNAi, splicing, and antisense modalities.
Our Strategy We are building a leading RNA medicines company by leveraging PRISM to design, develop and commercialize optimized disease-modifying medicines for indications with a high degree of unmet medical need. 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.
Under Singapore law, the Registrar has discretion to offer a compound of such offences against payment of a sum of money of up to S$2,000, or to prosecute the offence subject to the other penalties noted above.
Under Singapore law, the Registrar has discretion to offer a compound of such offences against payment of a sum of money of up to S$2,500, or to prosecute the offence subject to the other penalties noted above.
In addition, we regularly use our website to post information regarding our business and governance, and we encourage investors to use our website, particularly the information in the section entitled “For Investors & Media,” as a source of information about us. 60
In addition, we regularly use our website to post information regarding our business and governance, and we encourage investors to use our website, particularly the information in the section entitled “For Investors & Media,” as a source of information about us. 50
Clinical trials for which an application was submitted prior to January 31, 2022 under the Clinical Trials Directive, or between January 31, 2022 and January 31, 2023 and for which the sponsor has opted for the application of the Clinical Trials Directive, remain governed by the Directive until January 31, 2025.
Clinical trials for which an application was submitted prior to January 31, 2022 under the Clinical Trials Directive, or between January 31, 2022 and January 31, 2023 and for which the sponsor has opted for the application of the Clinical Trials Directive, remained governed by the Directive until January 31, 2025.
We partner with advocacy and service organizations to provide opportunities for employees to contribute directly to our local communities, including through our Wave Service Day and holiday giving drives. By participating in a broad range of volunteer activities, our employees donate time and resources to support individuals and families in the rare disease community and beyond.
We partner with advocacy and service organizations to provide opportunities for employees to contribute directly to our local communities, including through our Wave Service Day and holiday giving drives. By participating in a broad range of volunteer activities, our employees donate time and resources to support individuals and families in our community and beyond.
Nonclinical tests may include in vitro and in vivo (animal model) studies to assess the toxicity and other safety characteristics of the product candidate, as well as important aspects of drug pharmacology and pharmacodynamics.
Nonclinical tests may include in vitro and in vivo (animal model) studies to assess the toxicity and other safety characteristics of the product candidate, as well as important aspects of drug pharmacology and PD.
Through PRISM, our efforts continue to reveal structure-activity relationships among 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.
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.
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.
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.
In our splicing programs, as with our other modalities, the sequence, chemistry and backbone stereochemistry of oligonucleotides impact their activity. In our Nucleic Acids Research paper (Kandasamy et al., 2022; doi: 10.1093/nar/gkac018), we highlight the impact of PN chemistry on exon skipping.
In our splicing programs, as with our other modalities, the base modifications and sequence, chemistry and backbone stereochemistry of oligonucleotides impact their activity. 26 In our Nucleic Acids Research paper (Kandasamy et al., 2022; doi: 10.1093/nar/gkac018), we highlight the impact of PN chemistry on exon skipping.
In this circumstance, EMA ensures that the evaluation for the opinion of the CHMP is completed within 150 days and the opinion issued thereafter. The mutual recognition procedure (“MRP”) for the approval of human drugs is an alternative approach to facilitate individual national marketing authorizations within the European Union.
In this circumstance, EMA ensures that the evaluation for the opinion of the CHMP is completed within 150 days (excluding clock stops) and the opinion issued thereafter. The mutual recognition procedure (“MRP”) for the approval of human drugs is an alternative approach to facilitate individual national marketing authorizations within the European Union.
Under the terms of the collaboration, we are eligible to receive up to $505 million in additional development, launch, and commercial milestone payments, as well as double-digit tiered royalties up to the high teens, as a percentage of net sales for WVE-006.
Under the terms of the collaboration, we are eligible to receive up to $525 million in development, launch, and commercial milestone payments, as well as double-digit tiered royalties up to the high teens, as a percentage of net sales for WVE-006.
In connection with our 2023 Research and Development Day (“R&D Day”), we shared in vivo proof of concept data in diet-induced obesity mice demonstrating INHBE silencing well beyond the anticipated 50% therapeutic threshold, which led to substantially lower body weight and reduction of visceral fat as compared to controls.
In connection with our 2023 Research and Development Day, we shared in vivo proof-of-concept data in diet-induced obesity (“DIO”) mice demonstrating INHBE silencing well beyond the anticipated 50% therapeutic threshold, which led to substantially lower body weight and reduction of visceral fat as compared to controls.
Exon skipping produces dystrophin from the endogenous dystrophin gene (not micro or mini dystrophin expressed from a foreign vector), under the control of native gene-regulatory elements, resulting in normal expression. WVE-N531 is our first splicing candidate incorporating PN backbone (“PN”) chemistry to be assessed in the clinic.
Exon skipping produces dystrophin from the endogenous dystrophin gene (not micro or mini dystrophin expressed from a foreign vector), under the control of native gene-regulatory elements, resulting in physiological control over its expression. WVE-N531 is our first splicing candidate incorporating PN backbone (“PN”) chemistry to be assessed in the clinic.
By correcting the single RNA base mutation that causes a majority of AATD cases with the Pi*ZZ genotype (approximately 200,000 in the United States and Europe), RNA editing may provide an ideal approach for increasing circulating levels of wild-type Alpha-1 antitrypsin (“AAT”) protein and reducing mutant protein aggregation in the liver, thus simultaneously addressing both the lung and liver manifestations of the disease.
By correcting the single RNA base mutation that causes a majority of AATD cases with the Pi*ZZ genotype (approximately 200,000 in the United States and Europe), RNA editing may provide an ideal approach for increasing circulating levels of wild-type AAT protein and reducing mutant protein aggregation in the liver, thus simultaneously addressing both the lung and liver manifestations of the disease.
For instance, in a Phase 3 study of semaglutide, 36% of total weight loss was from loss of lean mass (Wilding 2021), and in a Phase 3 study of tirzepatide, treatment led to an approximately 34% loss in fat mass and an approximately 11% loss in lean mass (Jastreboff 2022).
For instance, in a Phase 3 study of semaglutide, 34% of total weight loss was from loss of lean mass (King 2021), and in a Phase 3 study of tirzepatide, treatment led to an approximately 34% loss in fat mass and an approximately 11% loss in lean mass (Jastreboff 2022).
As part of this strategy, we have entered into, and may enter into new partnership and collaboration agreements as a means of advancing our own therapeutic programs, investing in third-party technologies to further strengthen PRISM and leveraging external partnerships to extend the reach of PRISM into therapeutic areas where our platform demonstrates a competitive advantage.
As part of this strategy, we have entered into, and may enter into new partnership and collaboration agreements as a means of advancing our own therapeutic programs and maximizing their potential for patients, investing in third-party technologies to further strengthen PRISM and leveraging external partnerships to extend the reach of PRISM into therapeutic areas where our platform demonstrates a competitive advantage.
A CRL indicates that the review cycle for an application is complete and that the application will not be approved in its present form. CRLs outline the deficiencies in the submission and may require substantial additional testing or 46 information in order for the FDA to reconsider the application.
A CRL indicates that the review cycle for an application is complete and that the application will not be approved in its present form. A CRL outlines the deficiencies in the submission and may require substantial additional testing or information in order for the FDA to reconsider the application.
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 and which offer biomarkers for target engagement and to provide insights into clinical effects early in development.
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.
Progress reports detailing progress and safety data gathered from clinical trials must be submitted at least annually to the FDA. Safety reports are submitted more frequently if certain serious adverse effects (“SAEs”) occur. Phase 1, Phase 2 and Phase 3 clinical trials may not be completed successfully within any specified period, or at all.
Progress reports detailing progress and safety data gathered from clinical trials must be submitted at least annually to the FDA. Safety reports are submitted more frequently if certain SAEs occur. Phase 1, Phase 2 and Phase 3 clinical trials may not be completed successfully within any specified period, or at all.
These AIMers are GalNAc conjugated to increase uptake in hepatocytes. The addition of PN chemistry substantially improves both potency and editing efficiency. In our Nature Biotechnology paper (Monian P, et.
These AIMers are GalNAc conjugated to increase uptake in hepatocytes. The addition of PN chemistry substantially improves both potency and editing efficiency. 20 In our foundational RNA editing paper published in Nature Biotechnology (Monian P, et.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeOn March 3, 2022, we filed a new universal shelf registration on Form S-3 with the SEC, which was declared effective by the SEC on May 4, 2022, pursuant to which we registered for sale up to $500.0 million of any combination of our ordinary shares, debt securities, warrants, rights and/or units from time to time and at prices and on terms that we may determine, which we refer to as the “2022 Form S-3.” The 2022 Form S-3 includes a prospectus covering up to approximately $132.0 million in ordinary shares that had not yet been issued or sold under our Sales Agreement with Jefferies LLC (“Jefferies”) for our “at-the-market” equity program.
Biggest changeOn November 12, 2024, we filed an automatic shelf registration statement on Form S-3ASR with the SEC for which we registered for sale an indeterminate amount of any combination of our ordinary shares, debt securities, warrants, rights and/or units from time to time and at prices and on terms that we may determine, which we refer to as the “2024 WKSI Shelf”.
Holder” is a beneficial owner of ordinary shares that is for U.S. federal income tax purposes: (i) an individual who is a citizen or resident of the United States; (ii) a corporation (or other entity taxable as a corporation for U.S. federal income tax purposes) created or organized in or under the laws of the United States, any state thereof or the District of Columbia; (iii) an estate the income of which is subject to U.S. federal income taxation regardless of its source; or (iv) a trust (a) if a court within the U.S. can exercise primary supervision over its administration, and one or more U.S. persons have the authority to control all of the substantial decisions of that trust, or (b) that was in existence on August 20, 1996, and validly elected under applicable Treasury Regulations to continue to be treated as a domestic trust.
Holder” is a beneficial owner of ordinary shares that is for U.S. federal income tax purposes: (i) an individual who is a citizen or resident of the United States; (ii) a corporation (or other entity taxable as a corporation for U.S. federal income tax purposes) created or organized in or under the laws of the United States, any state thereof or the District of Columbia; (iii) an estate the income of which is subject to U.S. federal income taxation regardless of its source; or (iv) a trust (a) if a court within the United States can exercise primary supervision over its administration, and one or more U.S. persons have the authority to control all of the substantial decisions of that trust, or (b) that was in existence on August 20, 1996, and validly elected under applicable Treasury Regulations to continue to be treated as a domestic trust.
The successful initiation and completion of any of our clinical trials, within timeframes consistent with our business plans, is dependent on various factors, which include, but are not limited to, our ability to: • retain and recruit employees, contractors or consultants with the required level of knowledge and experience; • retain and recruit in a timely manner a sufficient number of patients necessary to conduct a clinical trial, which is a function of many factors, including the proximity of participants to clinical sites, the size of the relevant population, the eligibility criteria for the trial, possible adverse effects from treatments, the existence of competing clinical trials, the involvement of patient advocacy groups, the availability of new or alternative treatments, lack of efficacy, personnel issues and ease of participation in our clinical trials; • open study sites, and enroll, treat, and monitor patients due to local restrictions implemented in response to local or global health issues; • develop companion diagnostic tests for use with certain of our product candidates or identify partners with such expertise; • manufacture and maintain a sufficient amount of clinical material, internally or through third parties; 65 • ensure adherence to trial designs and protocols agreed upon and approved by regulatory authorities and applicable regulatory and legal guidelines; • apply the appropriate pharmacovigilance measures in case of adverse effects emerging during a clinical trial; • execute clinical trial designs and protocols approved by regulatory authorities without deficiencies; • timely and effectively contract with (under reasonable terms), manage and work with investigators, institutions, hospitals and contract research organizations (“CROs”) involved in the clinical trial; • negotiate contracts and other related documents with clinical trial parties and IRBs, CRO agreements and site agreements, which can be subject to extensive negotiations that could cause significant delays in the clinical trial process, with terms possibly varying significantly among different trial sites and CROs and possibly subjecting us to various risks; and • conduct clinical trials in a cost-effective manner, including management of foreign currency risk in clinical trials conducted in foreign jurisdictions and cost increases due to unforeseen or unexpected complications such as enrollment delays, or needing to outsource certain functions during the clinical trial.
The successful initiation and completion of any of our clinical trials, within timeframes consistent with our business plans, is dependent on various factors, which include, but are not limited to, our ability to: • retain and recruit employees, contractors or consultants with the required level of knowledge and experience; • retain and recruit in a timely manner a sufficient number of patients necessary to conduct a clinical trial, which is a function of many factors, including the proximity of participants to clinical sites, the size of the relevant population, the eligibility criteria for the trial, possible adverse effects from treatments, the existence of competing clinical trials, the involvement of patient advocacy groups, the availability of new or alternative treatments, lack of efficacy, personnel issues and ease of participation in our clinical trials; • open study sites, and enroll, treat, and monitor patients due to local restrictions implemented in response to local or global health issues; • develop companion diagnostic tests for use with certain of our product candidates or identify partners with such expertise; • manufacture and maintain a sufficient amount of clinical material, internally or through third parties; • ensure adherence to trial designs and protocols agreed upon and approved by regulatory authorities and applicable regulatory and legal guidelines; • apply the appropriate pharmacovigilance measures in case of adverse effects emerging during a clinical trial; • execute clinical trial designs and protocols approved by regulatory authorities without deficiencies; • timely and effectively contract with (under reasonable terms), manage and work with investigators, institutions, hospitals and contract research organizations (“CROs”) involved in the clinical trial; • negotiate contracts and other related documents with clinical trial parties and IRBs, CRO agreements and site agreements, which can be subject to extensive negotiations that could cause significant delays in the clinical trial process, with terms possibly varying significantly among different trial sites and CROs and possibly subjecting us to various risks; and • conduct clinical trials in a cost-effective manner, including management of foreign currency risk in clinical trials conducted in foreign jurisdictions and cost increases due to unforeseen or unexpected complications such as enrollment delays, or needing to outsource certain functions during the clinical trial.
In addition, there can be no assurance that: • Others will not or may not be able to make, use or sell compounds that are the same as or similar to our product candidates but that are not covered by the claims of the patents that we own or license. • We or our licensors, collaborators or any future collaborators are the first to make the inventions covered by each of our issued patents and pending patent applications that we own or license. • We or our licensors, collaborators or any future collaborators are the first to file patent applications covering certain aspects of our inventions. • Others will not independently develop similar or alternative technologies or duplicate any of our technologies without infringing our intellectual property rights. • A third party may not challenge, invalidate, circumvent or weaken our patents, or that, if any of these events should occur, that a court would hold that our patents are valid, enforceable and infringed. • Any issued patents that we own or have licensed will provide us with any competitive advantages, or will not be challenged, invalidated, circumvented or weakened by third parties. • We may develop additional proprietary technologies that are patentable. • The patents of others will not have an adverse effect on our business. 87 • Our competitors do not conduct research and development activities in countries where we do not have enforceable patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets.
In addition, there can be no assurance that: • Others will not or may not be able to make, use or sell compounds that are the same as or similar to our product candidates but that are not covered by the claims of the patents that we own or license. • We or our licensors, collaborators or any future collaborators are the first to make the inventions covered by each of our issued patents and pending patent applications that we own or license. • We or our licensors, collaborators or any future collaborators are the first to file patent applications covering certain aspects of our inventions. • Others will not independently develop similar or alternative technologies or duplicate any of our technologies without infringing our intellectual property rights. • A third party may not challenge, invalidate, circumvent or weaken our patents, or that, if any of these events should occur, that a court would hold that our patents are valid, enforceable and infringed. • Any issued patents that we own or have licensed will provide us with any competitive advantages, or will not be challenged, invalidated, circumvented or weakened by third parties. • We may develop additional proprietary technologies that are patentable. • The patents of others will not have an adverse effect on our business. • Our competitors do not conduct research and development activities in countries where we do not have enforceable patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets.
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.
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.
Disclosure of such information is made by CMS on a publicly available website; and 73 • state and foreign laws comparable to each of the above federal laws, such as, for example: state anti-kickback and false claims laws applicable to commercial insurers and other non-federal payors; state laws that require pharmaceutical manufacturers to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government; state laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures; and state and foreign laws governing the privacy and security of health information, some which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.
Disclosure of such information is made by CMS on a publicly available website; and • state and foreign laws comparable to each of the above federal laws, such as, for example: state anti-kickback and false claims laws applicable to commercial insurers and other non-federal payors; state laws that require pharmaceutical manufacturers to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government; state laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures; and state and foreign laws governing the privacy and security of health information, some which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.
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.
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.
These enforcement actions include, among others: • adverse regulatory inspection findings; • warning and/or untitled letters; • voluntary or mandatory product recalls or public notification or medical product safety alerts to healthcare professionals; • restrictions on, or prohibitions against, marketing our products; • restrictions on, or prohibitions against, importation or exportation of our products; • restrictions on the labeling, use or distribution of our products; • suspension of review or refusal to approve pending applications or supplements to approved applications; • exclusion from participation in government-funded healthcare programs; • exclusion from eligibility for the award of government contracts for our products; • suspension or withdrawal of product approvals; • product seizures; • injunctions; 74 • consent decrees; and • civil and criminal penalties, up to and including criminal prosecution resulting in fines, exclusion from healthcare reimbursement programs and imprisonment.
These enforcement actions include, among others: • adverse regulatory inspection findings; • warning and/or untitled letters; • voluntary or mandatory product recalls or public notification or medical product safety alerts to healthcare professionals; • restrictions on, or prohibitions against, marketing our products; • restrictions on, or prohibitions against, importation or exportation of our products; • restrictions on the labeling, use or distribution of our products; • suspension of review or refusal to approve pending applications or supplements to approved applications; • exclusion from participation in government-funded healthcare programs; • exclusion from eligibility for the award of government contracts for our products; • suspension or withdrawal of product approvals; • product seizures; • injunctions; • consent decrees; and • civil and criminal penalties, up to and including criminal prosecution resulting in fines, exclusion from healthcare reimbursement programs and imprisonment.
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.
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.
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.
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.
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.
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.
Any interruption of the development or operation of the manufacturing of our product candidates, such as order delays for equipment or materials, equipment malfunction, quality control and quality assurance issues, regulatory delays and possible negative effects of such delays on supply chains and expected timelines for product availability, production yield issues, shortages of qualified personnel, discontinuation of a facility or business or failure or damage to a facility resulting from natural disasters, could result in the cancellation of shipments, loss of product in the manufacturing process or a shortfall in available product candidates or materials.
Any interruption of the development or manufacturing of our product candidates, such as order delays for equipment or materials, equipment malfunction, quality control and quality assurance issues, regulatory delays and possible negative effects of such delays on supply chains and expected timelines for product availability, production yield issues, shortages of qualified personnel, discontinuation of a facility or business or failure or damage to a facility resulting from natural disasters, could result in the cancellation of shipments, loss of product in the manufacturing process or a shortfall in available product candidates or materials.
The rights of our shareholders and the obligations of our directors and officers under Singapore law (including under the Companies Act 1967 of Singapore (the “Singapore Companies Act”) are different from those applicable to a company incorporated in the State of Delaware in material respects, and our shareholders may have more difficulty and less clarity in protecting their interests in connection with actions taken by our 92 management, members of our board of directors or our affiliated shareholders than would otherwise apply to a company incorporated in the State of Delaware.
The rights of our shareholders and the obligations of our directors and officers under Singapore law (including under the Companies Act 1967 of Singapore (the “Singapore Companies Act”) are different from those applicable to a company incorporated in the State of Delaware in material respects, and our shareholders may have more difficulty and less clarity in protecting their interests in connection with actions taken by our management, members of our Board or our affiliated shareholders than would otherwise apply to a company incorporated in the State of Delaware.
Substantially all of our losses have resulted from expenses incurred in connection with our research and development programs and from general and administrative costs associated with our operations. We are a clinical-stage biotechnology company focused on unlocking the broad potential of RNA medicines (also known as oligonucleotides), or those targeting ribonucleic acid (RNA), to transform human health.
Substantially all of our losses have resulted from expenses incurred in connection with our research and development programs and from general and administrative costs associated with our operations. We are a clinical-stage biotechnology company focused on unlocking the broad potential of ribonucleic acid (“RNA”) medicines (also known as oligonucleotides), or those targeting RNA, to transform human health.
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.
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.
Subject to receiving approval from the FDA of an NDA or Biologics License Application (“BLA”), products granted orphan drug designation are provided with seven years of orphan marketing exclusivity in the United States, meaning the FDA generally will not approve applications for other product candidates for the same orphan indication that contain the same active ingredient.
Subject to receiving approval from the FDA of an NDA or Biologics License Application, products granted orphan drug designation are provided with seven years of orphan marketing exclusivity in the United States, meaning the FDA generally will not approve applications for other product candidates for the same orphan indication that contain the same active ingredient.
As a result of these factors, any such potential litigation could have a material adverse effect on our financial results, harm our business, and cause our share price to decline. 96 We do not anticipate paying any cash dividends on our ordinary shares in the foreseeable future. We have never declared or paid cash dividends on our ordinary shares.
As a result of these factors, any such potential litigation could have a material adverse effect on our financial results, harm our business, and cause our share price to decline. We do not anticipate paying any cash dividends on our ordinary shares in the foreseeable future. We have never declared or paid cash dividends on our ordinary shares.
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.
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.
We may be required to perform additional or unanticipated clinical trials to obtain regulatory approval or be subject to additional post-marketing 64 studies or other requirements to maintain such approval. As a result, we may never succeed in developing a marketable product, we may not become profitable and the value of our ordinary shares could decline.
We may be required to perform additional or unanticipated clinical trials to obtain regulatory approval or be subject to additional post-marketing studies or other requirements to maintain such approval. As a result, we may never succeed in developing a marketable product, we may not become profitable and the value of our ordinary shares could decline.
Among policy makers and payors in the United States and elsewhere, there is significant interest in promoting changes in healthcare systems with the stated goals of containing healthcare costs, improving quality and/or expanding access. In the United States, the 76 pharmaceutical industry has been a focus of these efforts and has been significantly affected by major legislative initiatives.
Among policy makers and payors in the United States and elsewhere, there is significant interest in promoting changes in healthcare systems with the stated goals of containing healthcare costs, improving quality and/or expanding access. In the United States, the pharmaceutical industry has been a focus of these efforts and has been significantly affected by major legislative initiatives.
Because we rely on third parties and do not have the ability to conduct preclinical studies or clinical trials independently, we have less control over the timing, quality and other aspects 80 of preclinical studies and clinical trials than we would if we conducted them on our own, including our inability to control whether sufficient resources are applied to our programs.
Because we rely on third parties and do not have the ability to conduct preclinical studies or clinical trials independently, we have less control over the timing, quality and other aspects of preclinical studies and clinical trials than we would if we conducted them on our own, including our inability to control whether sufficient resources are applied to our programs.
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.
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.
However, initiation of such trials may be delayed if the FDA objects to our proposed diversity action plans for any future Phase 69 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.
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.
In particular, sales, marketing and business arrangements in the healthcare industry are subject to extensive laws and regulations intended to prevent fraud, kickbacks, 83 self-dealing and other abusive practices. These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive programs and other business arrangements.
In particular, sales, marketing and business arrangements in the healthcare industry are subject to extensive laws and regulations intended to prevent fraud, kickbacks, self-dealing and other abusive practices. These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive programs and other business arrangements.
Regional and/or national patent applications may be pursued 88 outside of the United States, either based on a PCT application or as a direct filing, in some cases claiming priority to a prior U.S. or PCT filing. Some of our cases have been filed in multiple jurisdictions, including major market jurisdictions.
Regional and/or national patent applications may be pursued outside of the United States, either based on a PCT application or as a direct filing, in some cases claiming priority to a prior U.S. or PCT filing. Some of our cases have been filed in multiple jurisdictions, including major market jurisdictions.
Net prices for drugs may be reduced by mandatory discounts or rebates required by government healthcare programs or private payors and by any future relaxation of laws that presently restrict imports of drugs from countries 75 where they may be sold at lower prices than in the United States.
Net prices for drugs may be reduced by mandatory discounts or rebates required by government healthcare programs or private payors and by any future relaxation of laws that presently restrict imports of drugs from countries where they may be sold at lower prices than in the United States.
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.
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.
These limitations and restrictions may limit the size of the market for the product and affect reimbursement by third-party payors. 70 We are also subject to numerous foreign regulatory requirements governing, among other things, the conduct of clinical trials, manufacturing and marketing authorization, pricing and payment.
These limitations and restrictions may limit the size of the market for the product and affect reimbursement by third-party payors. We are also subject to numerous foreign regulatory requirements governing, among other things, the conduct of clinical trials, manufacturing and marketing authorization, pricing and payment.
In entering into third-party marketing or distribution arrangements, any revenue we may receive will depend upon the efforts of the third parties and there can be no assurance that such third parties will establish adequate sales and distribution capabilities or be successful in gaining market acceptance of any approved 82 product.
In entering into third-party marketing or distribution arrangements, any revenue we may receive will depend upon the efforts of the third parties and there can be no assurance that such third parties will establish adequate sales and distribution capabilities or be successful in gaining market acceptance of any approved product.
The rights of our shareholders and the responsibilities of the members of our board of directors 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 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.
If we are unable to obtain access to a sufficient supply of these non-human primates in a timely manner or at all, 67 our timelines and our ability to complete preclinical testing and submit IND/CTA or equivalent foreign applications may be adversely affected.
If we are unable to obtain access to a sufficient supply of these non-human primates in a timely manner or at all, our timelines and our ability to complete preclinical testing and submit IND/CTA or equivalent foreign applications may be adversely affected.
To the extent that we have existing, or enter into future, manufacturing arrangements with third parties, we will depend on these third parties to perform their 81 obligations in a timely manner consistent with contractual and regulatory requirements, including those related to quality control and assurance.
To the extent that we have existing, or enter into future, manufacturing arrangements with third parties, we will depend on these third parties to perform their obligations in a timely manner consistent with contractual and regulatory requirements, including those related to quality control and assurance.
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, changes in inflation, interest rates and overall 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, volatility in inflation, and interest rates and overall changes in economic conditions and uncertainties.
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.
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.
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.
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.
The outcome following legal allegations 89 of invalidity and unenforceability during patent litigation is unpredictable. With respect to the validity question, for example, we cannot be certain that there is no invalidating prior art, of which we and the patent examiner were unaware during prosecution.
The outcome following legal allegations of invalidity and unenforceability during patent litigation is unpredictable. With respect to the validity question, for example, we cannot be certain that there is no invalidating prior art, of which we and the patent examiner were unaware during prosecution.
The fair 93 market value of our assets is expected to relate, in part, to (a) the market price of our ordinary shares and (b) the composition of our income and assets, which will be affected by how, and how quickly, we spend any cash that is raised in any financing transaction.
The fair market value of our assets is expected to relate, in part, to (a) the market price of our ordinary shares and (b) the composition of our income and assets, which will be affected by how, and how quickly, we spend any cash that is raised in any financing transaction.
We cannot predict the timing or content of such potential changes, and such changes could increase our overall tax liability, which could adversely affect our financial condition, results of operations and cash flows. 94 Our financial results reflect the effect of certain tax credits and the operation of certain tax regimes within the United Kingdom.
We cannot predict the timing or content of such potential changes, and such changes could increase our overall tax liability, which could adversely affect our financial condition, results of operations and cash flows. Our financial results reflect the effect of certain tax credits and the operation of certain tax regimes within the United Kingdom.
Such changes carry the risk that they will not achieve their intended objectives, and any of these changes could cause our product candidates to perform differently and affect the results of current or future clinical trials, or 66 the performance of the product, once commercialized.
Such changes carry the risk that they will not achieve their intended objectives, and any of these changes could cause our product candidates to perform differently and affect the results of current or future clinical trials, or the performance of the product, once commercialized.
We may incur substantial costs to comply with, and substantial fines or penalties if we violate any of, these laws or regulations. 78 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 depend on collaborations with third parties for the development and commercialization of certain of our product candidates.
Moreover, our licensors may own or control intellectual property that has not been licensed to us and, as a result, we may be subject to 90 claims, regardless of their merit, that we are infringing or otherwise violating the licensor’s rights.
Moreover, our licensors may own or control intellectual property that has not been licensed to us and, as a result, we may be subject to claims, regardless of their merit, that we are infringing or otherwise violating the licensor’s rights.
We are currently evaluating the impact of the draft 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.
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.
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.
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.
Although our agreements with third-party manufacturers require them to perform according to certain cGMP requirements such as those relating to quality control, quality assurance and qualified personnel, we cannot control the conduct of our third-party manufacturers to implement and maintain these standards.
Although our agreements with third-party manufacturers require them to perform according to certain cGMP requirements such as those relating to quality control, quality assurance and qualified personnel, we cannot otherwise control the conduct of our third-party manufacturers to implement and maintain these standards.
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.
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.
For the years ended December 31, 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, 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.
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.
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.
We may incur substantial expenses as a result of the limited nature of our disaster recovery and business continuity plans, which could have a material adverse effect on our business. There is a substantial risk of product liability claims in our business.
We may incur substantial expenses as a result of the limited nature of our disaster recovery and business continuity plans, which could have a material adverse effect on our business. 67 There is a substantial risk of product liability claims in our business.
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.
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.
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; 61 • 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, 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.
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 public shareholders may have more difficulty in protecting their interests in connection with actions taken by our management, members of our board of directors or our principal shareholders than they would as shareholders of a corporation incorporated in the United States.
Our public shareholders may have more difficulty in protecting their interests in connection with actions taken by our management, members of our Board or our principal shareholders than they would as shareholders of a corporation incorporated in the United States.
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.
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.
For example, over the last several years, the U.S. 85 government has shut down several times and certain regulatory agencies, such as the FDA and the SEC, have had to furlough critical FDA, SEC and other government employees and stop critical activities.
For example, over the last several years, the U.S. government has shut down several times and certain regulatory agencies, such as the FDA and the SEC, have had to furlough critical FDA, SEC and other government employees and stop critical activities.
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.
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.
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.
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.
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.
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.
Department of the 77 Treasury), and other trade barriers; global instability from an outbreak of pandemic or contagious disease, difficulties in attracting and retaining qualified personnel; and cultural differences in the conduct of business.
Department of the Treasury), and other trade barriers; global instability from an outbreak of pandemic or contagious disease, difficulties in attracting and retaining qualified personnel; and cultural differences in the conduct of business.
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.
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.
There is uncertainty as to whether judgments of courts in the United States based upon the civil liability 91 provisions of the federal securities laws of the United States would be recognized or enforceable in Singapore.
There is uncertainty as to whether judgments of courts in the United States based upon the civil liability provisions of the federal securities laws of the United States would be recognized or enforceable in Singapore.
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, antisense silencing and RNA interference 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 using our RNA editing, splicing, silencing using siRNA and antisense silencing modalities.
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 ribonucleic acid (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 (also known as oligonucleotides), or those targeting RNA, to transform human health.
In addition, while our collaboration with Takeda and GSK will provide us with know-how and experience related to commercialization, we have limited experience of our own.
In addition, while our collaboration with GSK will provide us with know-how and experience related to commercialization, we have limited experience of our own.
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, 2024 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, 2025 or for any future taxable year.
Foreign data protection, privacy, information security, user protection and other laws 84 and regulations are often more restrictive than those in the United States.
Foreign data protection, privacy, information security, user protection and other laws and regulations are often more restrictive than those in the United States.
Bribery Act; changes in the political or economic condition of a specific country or region, including Russia’s invasion of Ukraine, the conflict in the Middle East, and the potential for a wider European or global conflict; fluctuations in the value of foreign currency versus the U.S. dollar; inflation and interest rate changes; our ability to deploy overseas funds in an efficient manner; tariffs, trade protection measures, import or export licensing requirements, trade embargoes, and sanctions (including those administered by the Office of Foreign Assets Control of the U.S.
Bribery Act; changes in the political or economic condition of a specific country or region, including Russia’s invasion of Ukraine, the conflict in the Middle East, and the potential for a wider European or global conflict; fluctuations in the value of foreign currency versus the U.S. dollar; volatility in inflation and interest rates; our ability to deploy overseas funds in an efficient manner; tariffs, trade protection measures, import or export licensing requirements, trade embargoes, and sanctions (including those administered by the Office of Foreign Assets Control of the U.S.
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. 97 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. 87 Item 1B. Unresolve d Staff Comments None.
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, 2023.
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.
Collaborations involving our product candidates may pose the following risks to us: • collaborators 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. 79 Collaboration agreements may not lead to development or commercialization of product candidates in the most efficient manner, or at all.
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.
Under Singapore law, the Registrar has discretion to offer a compound of such offences against payment of a sum of money of up to S$2,000, or to prosecute the offence subject to the other penalties noted above.
Under Singapore law, the Registrar has discretion to offer a compound of such offences against payment of a sum of money of up to S$2,500, or to prosecute the offence subject to the other penalties noted above.
Based on information publicly available to us as of December 31, 2023, 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, 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.
Moreover, eligibility for coverage does not imply that any drug will be paid for in all cases or at a rate that covers our costs, including research, development, manufacture, sale and distribution. Interim payments for new drugs, if applicable, may also not be sufficient to cover our costs and may not be made permanent.
Moreover, eligibility for coverage does not imply that any of our drug products, if approved, will be paid for in all cases or at a rate that covers our costs, including research, development, manufacture, sale and distribution. Interim payments for new drugs, if applicable, may also not be sufficient to cover our costs and may not be made permanent.
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 2023.
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.
In June 2022, we closed an underwritten offering in which we issued and sold 25,464,483 ordinary shares and, to RA Capital Management, L.P. in lieu of additional ordinary shares, pre-funded warrants (“Pre-Funded Warrants”) to purchase up to 7,093,656 ordinary shares at an exercise price of $0.0001 per share.
In June 2022, we closed an underwritten offering in which we issued and sold 25,464,483 ordinary shares and, to RA Capital Management, L.P. in lieu of additional ordinary shares, pre-funded warrants (the “2022 Pre-Funded Warrants”) to purchase up to 7,093,656 ordinary shares at an exercise price of $0.0001 per share.
As we advance product candidates through preclinical studies and clinical trials, we will need to expand our development, regulatory and manufacturing capabilities or contract with other organizations to provide these capabilities for us. In addition, we must manage our relationships with collaborators or partners, suppliers and other organizations, including our collaborations with GSK and Takeda.
As we advance product candidates through preclinical studies and clinical trials, we will need to expand our development, regulatory and manufacturing capabilities or contract with other organizations to provide these capabilities for us. In addition, we must manage our relationships with collaborators or partners, suppliers and other organizations, including our collaboration with GSK.
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, including emerging or future variants of COVID-19; • 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; 68 • 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 our product candidates class, in particular; or • varying interpretations of data by the FDA and similar foreign regulatory agencies.
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 are a clinical-stage biotechnology company focused on unlocking the broad potential of RNA medicines (also known as oligonucleotides), or those targeting ribonucleic acid (RNA), to transform human health. Our RNA medicines platform, PRISM, combines multiple modalities, chemistry innovation and deep insights into human genetics to deliver scientific breakthroughs that treat both rare and prevalent disorders.
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 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.
We are a clinical-stage biotechnology company focused on unlocking the broad potential of RNA medicines (also known as oligonucleotides), or those targeting ribonucleic acid (RNA), to transform human health. Our RNA medicines platform, PRISM, combines multiple modalities, chemistry innovation and deep insights into human genetics to deliver scientific breakthroughs that treat both rare and prevalent disorders.
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 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.
Further, we may not be able to continue to claim a U.K. tax credit for research and development tax credits under the small and medium-sized companies regime in the future if our revenue or turnover exceeds €100 million for a second consecutive year. In such an event, we will no longer qualify as a small or medium-sized enterpri se .
Further, we may not be able to continue to claim a U.K. tax credit for research and development tax credits under the small and medium-sized companies regime in the future if our revenue or turnover exceeds €100 million for two consecutive years. In such an event, we will no longer qualify as a small or medium-sized enterpri se .
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 financing, 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 issued pre-funded warrants as part of our June 2022 and September 2024 financings, which may cause additional dilution to our shareholders.
As of February 2024, the CMS Innovation Center continues to test the proposed models and has started to roll out plans for access model testing of certain product types (e.g., cell and gene therapies) by states and manufacturers.
The CMS Innovation Center continues to test the proposed models and has started to roll out plans for access model testing of certain product types (e.g., cell and gene therapies) by states and manufacturers.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeRisk Factors, which disclosures are incorporated by reference herein. Cybersecurity Governance Our Board of Directors (our “Board”) is actively involved in oversight of our risk management activities, and cybersecurity represents an important element of our overall approach to risk management.
Biggest changeRisk Factors, which disclosures are incorporated by reference herein. Cybersecurity Governance Our Board is actively involved in oversight of our risk management activities, and cybersecurity represents an important element of our overall approach to risk management.
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. 98 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.
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. 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.
As part of the above processes, we regularly engage with consultants and other third parties, including a bi-annual review of our cybersecurity program by an independent Qualified Security Assessor. In the last three fiscal years, we have not experienced any material cybersecurity incidents and the expenses we have incurred from cybersecurity incidents were immaterial.
As part of the above processes, we regularly engage with consultants and other third parties, including a bi-annual review of our cybersecurity program by an independent Qualified Security Assessor. In the last three fiscal years, we have no t experienced any material cybersecurity incidents and the expenses we have incurred from cybersecurity incidents were immaterial.

Item 2. Properties

Properties — owned and leased real estate

1 edited+0 added−0 removed1 unchanged
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. 99 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. 89 PART II

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

2 edited+0 added−0 removed1 unchanged
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 28, 2024, we had 122,284,139 ordinary shares outstanding and approximately 10 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 24, 2025, we had 153,486,021 ordinary shares outstanding and approximately nine 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] 100
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

Item 7. Management's Discussion & Analysis

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

51 edited+28 added−7 removed73 unchanged
Biggest changeWe have a robust and diverse pipeline of potential first-or best-in-class programs, including: • GalNAc-conjugated oligonucleotides for hepatic and metabolic diseases including: o AATD: WVE-006 is a GalNAc-conjugated SERPINA1 RNA editing oligonucleotide. o Obesity: Lead clinical candidate is a GalNAc-conjugated RNAi oligonucleotide targeting inhibin βE (“INHBE”). • Unconjugated oligonucleotides for muscle, CNS and other disease areas including: o DMD: WVE-N531 is an exon 53 splicing oligonucleotide. o HD: WVE-003 is a selective mutant huntingtin (“mHTT”)-lowering SNP3 antisense silencing oligonucleotide.
Biggest changeWe 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.
We are using PRISM, which includes our novel chemistry modifications, to design, develop and commercialize a broad pipeline of first- or best- in class RNA medicines using our editing, RNAi, splicing, and antisense modalities.
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.
The 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 (1) , 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.
The 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.
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.
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, rising inflation, rising 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, 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.
AIMers are short in length, fully chemically modified, and use our novel chemistry, which make them distinct from other ADAR-mediated editing approaches. In December 2022, we announced a strategic collaboration with GlaxoSmithKline Intellectual Property (No. 3) (“GSK”) to advance transformative oligonucleotide therapeutics, including WVE-006.
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.
Our product revenue, if any, will be derived from sales of products that we do not expect to be commercially available for many years, if ever. Accordingly, we will need to obtain substantial additional funds to achieve our business objectives. 108 Adequate additional funds may not be available to us on acceptable terms when we need them, or at all.
Our product revenue, if any, will be derived from sales of products that we do not expect to be commercially available for many years, if ever. Accordingly, we will need to obtain substantial additional funds to achieve our business objectives. Adequate additional funds may not be available to us on acceptable terms when we need them, or at all.
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; • the impacts of local and global health epidemics, the conflict involving Russia and Ukraine, the conflict in the Middle East, global economic uncertainty, 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.
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.
Liquidity and Capital Resources Since our inception, we have not generated any product revenue and have incurred recurring net 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.
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.
As part of the accounting for these arrangements, the Company must use significant judgment to determine: (a) the number of performance obligations based on the determination under step (ii) above; (b) the transaction 109 price under step (iii) above; and (c) the timing of satisfaction of performance obligations as a measure of progress in step (v) above.
As part of the accounting for these arrangements, the Company must use significant judgment to determine: (a) the number of performance obligations based on the determination under step (ii) above; (b) the transaction price under step (iii) above; and (c) the timing of satisfaction of performance obligations as a measure of progress in step (v) above.
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”).
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”).
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.
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.
Additionally, there were $1.1 million in net proceeds from our at-the-market equity program. 107 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 $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.
General and Administrative Expenses General and administrative expenses consist primarily of compensation-related expenses, including salaries, bonuses, share-based compensation and other related benefits costs for personnel in our executive, finance, corporate, legal and administrative functions, as well as compensation-related expenses for our board of directors.
General and Administrative Expenses General and administrative expenses consist primarily of compensation-related expenses, including salaries, bonuses, share-based compensation and other related benefits costs for personnel in our executive, finance, corporate, legal and administrative functions, as well as compensation-related expenses for our Board.
This focus enables us to: • Leverage diversity of expression across cell types by modulating the many regulatory pathways that impact gene expression, including transcription, endogenous RNA interference pathways, splicing, and translation; • Address diseases that have historically been difficult to treat with small molecules or biologics; • Access a variety of tissue types or cell types throughout the body and modulate the frequency of dosing for broad distribution in tissues over time; • Avoid the risk of permanent off-target genetic changes and other challenges associated with DNA editing or gene therapy approaches; and • Leverage well-established industry manufacturing processes and regulatory, access, and reimbursement pathways.
This focus enables us to: • Leverage diversity of expression across cell types by modulating the many regulatory pathways that impact gene expression, including transcription, endogenous RNAi pathways, splicing, and translation; • Address diseases that have historically been difficult to treat with small molecules or biologics; • Access a variety of tissue types or cell types throughout the body and modulate the frequency of dosing for broad distribution in tissues over time; • Avoid the risk of permanent off-target genetic changes and other challenges associated with DNA editing or gene therapy approaches; and • Leverage well-established industry manufacturing processes and regulatory, access, and reimbursement pathways.
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.
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
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.
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.
Overview We are a clinical-stage biotechnology company focused on unlocking the broad potential of RNA medicines (also known as oligonucleotides), or those targeting ribonucleic acid (“RNA”), to transform human health. Our RNA medicines platform, PRISM TM , combines multiple modalities, chemistry innovation and deep insights into human genetics to deliver scientific breakthroughs that treat both rare and prevalent disorders.
Overview We are a clinical-stage biotechnology company focused on unlocking the broad potential of ribonucleic acid (“RNA”) medicines (also known as oligonucleotides), or those targeting RNA, to transform human health. Our RNA medicines platform, PRISM ® , combines multiple modalities, chemistry innovation and deep insights into human genetics to deliver scientific breakthroughs that treat both rare and common disorders.
The Company evaluates the measure of progress each reporting period and, if necessary, adjusts the measure of performance and related revenue recognition.
The 102 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, 2023 and 2022, 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, 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.
We do not currently have any committed external source of funds, except for possible future payments from Takeda or 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 collaborations with them.
Revenue We recognize collaboration revenue under the GSK Collaboration Agreement, which became effective in January 2023, and the Takeda Collaboration Agreement, which became effective in April 2018, (both of which are defined in Note 5 in the notes to the consolidated financial statements appearing elsewhere in this Annual Report on Form 10-K).
Revenue We recognize collaboration revenue under the GSK Collaboration Agreement, which became effective in January 2023, and the Takeda Collaboration Agreement, which became effective in April 2018 and expired in the fourth quarter of 2024, (both of which are defined in Note 5 in the notes to the consolidated financial statements appearing elsewhere in this Annual Report on Form 10-K).
Results of Operations In this section, we discuss the results of our operations 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, 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 .
Our net loss was $57.5 million in 2023 and $161.8 million in 2022. As of December 31, 2023 and 2022, we had an accumulated deficit of $1,024.9 million and $967.3 million, respectively. We expect to incur significant expenses and operating losses for the foreseeable future.
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.
In January 2024, the representatives of the underwriters in connection with the previously disclosed underwritten public offering (the “December 2023 Offering”) exercised their option to purchase an additional 3,000,000 ordinary shares at a price of $5.00 per ordinary share as a part of the December 2023 Offering, for additional net proceeds of approximately $14.0 million.
In January 2024, the representatives of the underwriters in connection with the previously disclosed underwritten public offering (the “December 2023 Offering”) exercised their option to purchase an additional 3,000,000 ordinary shares at a price of $5.00 per ordinary share as a part of the December 2023 Offering.
The largest change in operating assets and liabilities was a $9.3 million increase in accounts payable. Investing Activities During 2023, investing activities used $1.1 million of cash, primarily consisting of purchases of property and equipment. During 2022, investing activities used $1.3 million of cash, primarily consisting of purchases of property and equipment.
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.
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 insights, the first of which is our INHBE program for obesity and other metabolic disorders; (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.
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.
As a practical expedient, the Company recognizes the incremental costs of obtaining a contract as an expense when incurred if the amortization period of the asset that it otherwise would have recognized is one year or less.
As a practical expedient, the Company recognizes the incremental costs of obtaining a contract as an expense when incurred if the amortization period of the asset that it otherwise would have recognized is one year or less. To date, the Company has not incurred any incremental costs of obtaining a contract with a customer.
In May 2019, we filed a shelf registration statement on Form S-3ASR with the SEC pursuant to which we registered for sale an indeterminate amount of any combination of our ordinary shares, debt securities, warrants, rights and/or units from time to time and at prices and on terms that we may determine.
On November 12, 2024, we filed a shelf registration statement on Form S-3ASR with the SEC for which we registered for sale an indeterminate amount of any combination of our ordinary shares, debt securities, warrants, rights and/or units from time to time and at prices and on terms that we may determine, which we refer to as the “2024 WKSI Shelf”.
As of December 31, 2023, we had cash and cash equivalents of $200.4 million, restricted cash of $3.7 million and an accumulated deficit of $1,024.9 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, 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.
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 pre-funded warrants.
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.
Critical Accounting Policies and Significant Judgments and Estimates Our consolidated financial statements are prepared in accordance with generally accepted accounting principles in the United States of America (“U.S. GAAP”). The preparation of our financial statements and related disclosures requires us to make estimates and assumptions that affect the reported amount of assets, liabilities, revenue, costs and expenses and related disclosures.
Critical Accounting Policies and Significant Judgments and Estimates Our consolidated financial statements are prepared in accordance with U.S. GAAP. The preparation of our financial statements and related disclosures requires us to make estimates and assumptions that affect the reported amount of assets, liabilities, revenue, costs and expenses and related disclosures.
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. 105 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.
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.
Financing Activities During 2023, net cash provided by financing activities was $132.5 million, primarily due to the $93.6 million in net proceeds from the December 2023 Offering, which comprised of sales of ordinary shares, as well as $34.6 million in net proceeds from the GSK Equity Investment. Additionally, there were $3.1 million in net proceeds from our at-the-market equity program.
Additionally, we received $20.4 million in net proceeds from sales under our “at-the-market” equity program. During 2023, net cash provided by financing activities was $132.5 million, primarily due to the $93.6 million in net proceeds from the December 2023 Offering, which comprised of sales of ordinary shares, as well as $34.6 million in net proceeds from the GSK Equity Investment.
Through December 31, 2023, we have received an aggregate of approximately $1,295.1 million in net proceeds from these transactions, consisting of $727.6 million in net proceeds from public and other registered offerings of our ordinary shares and other securities, $478.2 million from our collaborations and $89.3 million in net proceeds from private placements of our debt and equity securities.
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.
Our operating lease commitments as of December 31, 2023 total $38.4 million, of which $9.3 million is related to payments in 2024 and approximately $29.1 million is related to payments beyond 2024.
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.
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 were $159.7 million for the year ended December 31, 2024, compared to $130.0 million for the year ended December 31, 2023.
Other Income, Net Other income, net for the years ended December 31, 2023 and 2022 was $9.8 million and $1.6 million, respectively.
Other Income, Net Other income, net for the years ended December 31, 2024 and 2023 was $13.4 million and $9.8 million, respectively.
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. 104 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 $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.
We will need to generate significant revenue to achieve profitability, and we may never do so. 106 Cash Flows The following table summarizes our sources and uses of cash for each of the periods presented: For the Year Ended December 31, 2023 2022 (in thousands) Net cash used in operating activities $ (19,431 ) $ (127,781 ) Net cash used in investing activities (1,115 ) (1,255 ) Net cash provided by financing activities 132,534 67,188 Effect of foreign exchange rates on cash (95 ) (210 ) Net increase (decrease) in cash, cash equivalents and restricted cash $ 111,893 $ (62,058 ) Operating Activities During 2023, operating activities used $19.4 million of cash, primarily due to our net loss of $57.5 million, partially offset by non-cash charges of $19.0 million and changes in our operating assets and liabilities of $19.1 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, 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.
We are actively advancing programs in all of our modalities. 101 We intentionally focus on targeting the transcriptome using oligonucleotides rather than other nucleic acid modalities such as gene therapy and DNA editing.
We intentionally focus on targeting the transcriptome using oligonucleotides rather than other nucleic acid modalities such as gene therapy and DNA editing.
These expenses, which are not allocated on a program-by-program basis, are included in the “Other research and development expenses (1) , including INHBE, RNA editing, PRISM, others” category along with other external expenses related to our discovery and development programs, as well as platform development and identification of potential drug discovery candidates. 103 Product candidates in later stages of clinical development generally have higher development costs than those in earlier stages of clinical development, primarily due to the increased size and duration of later-stage clinical trials.
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.
To date, the Company has not incurred any incremental costs of obtaining a contract with a customer. 110 For additional discussion of accounting for collaboration revenues, see Note 5 of our consolidated financial statements. Prepaid and Accrued Research and Development Expenses As we prepare our consolidated financial statements, we are required to estimate our prepaid and accrued expenses.
For additional discussion of accounting for collaboration revenues, see Note 5 of our consolidated financial statements. Prepaid and Accrued Research and Development Expenses As we prepare our consolidated financial statements, we are required to estimate our prepaid and accrued expenses.
Our shelf registration statement on Form S-3ASR also included a prospectus covering up to an aggregate of $250.0 million in ordinary shares that we could issue and sell from time to time, through Jefferies LLC (“Jefferies”) acting as our sales agent, pursuant to the open market sales agreement that we entered into with Jefferies in May 2019, as amended in March 2020 and March 2022 (the “Sales Agreement”), for our “at-the-market” equity program.
Our 2024 WKSI Shelf includes a prospectus covering up to an aggregate of $250.0 million in ordinary shares that we are able to issue and sell from time to time, through Jefferies LLC (“Jefferies”) acting as our sales agent, pursuant to the Open Market Sale Agreement, dated May 10, 2019, as amended by Amendment No. 1, dated as of March 2, 2020, Amendment No. 2, dated as of March 3, 2022, and Amendment No. 3, dated November 12, 2024, (collectively, the “Sales Agreement”), for our “at-the-market” equity program.
We are also building a pipeline of novel A-to-I RNA editing oligonucleotides (“AIMers”). Our RNA editing capability affords us the dexterity to address both rare diseases, as well as those diseases impacting large patient populations.
Our RNA editing capability affords us the dexterity to address both rare and common diseases, as well as those diseases impacting large patient populations.
N -acetylgalactosamine or (“GalNAc”)) or free uptake for delivery to a variety of cell and tissue types. We maintain strong and broad intellectual property, including for our novel chemistry modifications.
Our novel chemistry also allows us to avoid using complex delivery vehicles, such as lipid nanoparticles and viruses, and instead use clinically proven conjugates ( e.g., N -acetylgalactosamine or (“GalNAc”)) or free uptake for delivery to a variety of cell and tissue types. We maintain strong and broad intellectual property, including for our novel chemistry modifications.
Our toolkit of RNA-targeting modalities includes RNA editing, splicing, antisense silencing and RNA interference (“RNAi"), providing us with unique capabilities for designing and sustainably delivering candidates that optimally address disease biology. Our lead programs are in rare and prevalent diseases, including alpha-1 antitrypsin deficiency (“AATD”), obesity, Duchenne muscular dystrophy (“DMD”), and Huntington’s disease (“HD”).
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.
Additionally, we purchased $75.0 million of short-term investments during 2022, all of which matured in 2022.
During 2023, investing activities used $1.1 million of cash, primarily consisting of purchases of property and equipment. 99 During 2022, investing activities used $1.3 million of cash, primarily consisting of purchases of property and equipment. Additionally, we purchased $75.0 million of short-term investments during 2022, all of which matured in 2022.
We were founded on the recognition that there was a significant, untapped opportunity to use chemistry innovation to tune the pharmacological properties of oligonucleotides. Today, 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 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.
Adequate additional financing may not be available to us on acceptable terms, or at all. Our inability to raise capital as and when needed would have a negative impact on our financial condition and our ability to pursue our business strategy.
Our inability to raise capital as and when needed would have a negative impact on our financial condition and our ability to pursue our business strategy. We will need to generate significant revenue to achieve profitability, and we may never do so.
In January 102 2024, the representatives of the underwriters in the December 2023 Offering exercised their option to purchase an additional 3,000,000 ordinary shares, for additional gross proceeds of $15.0 million. Financial Operations Overview We have never been profitable, and since our inception, we have incurred significant operating losses.
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.
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We have seen preclinically and in clinical trials that these chemistry modifications enhance potency, distribution, and durability of effect of our molecules. Our novel chemistry also allows us to avoid using complex delivery vehicles, such as lipid nanoparticles and viruses, and instead use clinically proven conjugates (e.g.
Added
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.
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Recent Developments As previously disclosed, on December 11, 2023, we closed an underwritten public offering (the “December 2023 Offering”) of 20,000,000 of our ordinary shares at a price to the public of $5.00 per ordinary share for gross proceeds of $100.0 million.
Added
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).
Removed
Until we can generate significant revenue from product sales, if ever, we expect to continue to finance our operations through a combination of public or private equity or debt financings or other sources, which may include collaborations with third parties.
Added
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.
Removed
Since we no longer qualified as a “well-known seasoned issuer” at the time of the filing of our Annual Report on Form 10-K for the year ended December 31, 2019, we previously amended the shelf registration statement to register for sale up to $500.0 million of any combination of our ordinary shares, debt securities, warrants, rights and/or units from time to time and at prices and on terms that we may determine, including the $250.0 million in ordinary shares that we may issue and sell from time to time pursuant to our “at-the-market” equity program.
Added
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.
Removed
This registration statement, which we refer to as the “2019 Form S-3,” remained effective until our 2022 Form S-3 (as defined below) was declared effective on May 4, 2022, after which time we may no longer offer or sell any securities under the 2019 Form S-3.
Added
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.
Removed
On March 3, 2022, we filed a new universal shelf registration on Form S-3 with the SEC, which was declared effective by the SEC on May 4, 2022, pursuant to which we registered for sale up to $500.0 million of any combination of our ordinary shares, debt securities, warrants, rights and/or units from time to time and at prices and on terms that we may determine, which we refer to as the “2022 Form S-3.” The 2022 Form S-3 includes a prospectus covering up to approximately $132.0 million in ordinary shares that had not yet been issued or sold under our Sales Agreement with Jefferies at the time the 2022 Form S-3 was declared effective.
Added
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.
Removed
During the year ended December 31, 2023, we sold 751,688 ordinary shares under our at-the-market equity program for aggregate gross proceeds of $3.3 million. As of March 1, 2024 we have $311.7 million in securities available for issuance under the 2022 Form S-3, including approximately $128.7 million in ordinary shares available for issuance under our at-the-market equity program.
Added
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.
Added
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.
Added
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.
Added
Product candidates in later stages of clinical development generally have higher development costs than those in earlier stages of clinical development, primarily due to the increased size and duration of later-stage clinical trials.
Added
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.
Added
The $108.3 million in revenue recognized during the year ended December 31, 2024 was comprised of $37.0 million in revenue recognized under the GSK Collaboration Agreement and $71.3 million of revenue recognized under the Takeda Collaboration Agreement.
Added
The increase in the Takeda Collaboration revenue earned year over year was primarily due to the termination of the collaboration 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.
Added
This was offset by the decrease in the GSK revenue earned year over year primarily related to the AATD program.
Added
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.
Added
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.
Added
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.
Added
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.
Added
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.
Added
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.
Added
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.
Added
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.

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Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

3 edited+0 added−3 removed5 unchanged
Biggest changeForeign Currency Risk Due to our operations outside of the United States, we are exposed to market risk related to changes in foreign currency exchange rates. Historically, we have not hedged our foreign currency exposure.
Biggest changeOur cash and cash equivalents are comprised of funds held in checking accounts and money market accounts. Foreign Currency Risk Due to our operations outside of the United States, we are exposed to market risk related to changes in foreign currency exchange rates. Historically, we have not hedged our foreign currency exposure.
Financial Stateme nts and Supplementary Data The information required by this Item 8 is included at the end of this Annual Report on Form 10-K beginning on page F-1. Item 9. Changes in and Disagreements with Accou ntants on Accounting and Financial Disclosure Not applicable. 111
Financial Stateme nts and Supplementary Data The information required by this Item 8 is included at the end of this Annual Report on Form 10-K beginning on page F-1. Item 9. Changes in and Disagreements with Accou ntants on Accounting and Financial Disclosure Not applicable.
For the years ended December 31, 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.
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, our results of operations or our cash flows.
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Our cash and cash equivalents are comprised of funds held in checking accounts and money market accounts. Our short-term investments were comprised of term deposits which had fixed interest rates.
Removed
There were no short-term investments as of December 31, 2023 or 2022, as the $75.0 million of term deposits that constitute the Company’s short-term investments were purchased and all matured during the twelve months ended December 31, 2022.
Removed
A hypothetical 10% change in foreign currency rates would not have a material impact on our historical financial position or results of operations. However, there can be no assurance that changes in foreign currency exchange rates will not have a material adverse impact on us in the future.

Other WVE 10-K year-over-year comparisons