Wave Life Sciences Ltd
For the period ended Sep 30, 2024. Filed Nov 12, 2024.
View on SEC.govAbout this filing
A company's report for each of its first three quarters. The financial statements are not audited. It shows how the business has moved since the last annual report, and what management says changed.
Sep 30, 2024 · Filed Nov 12, 2024
WVE$3.37+4.5%Stored close · as of Nov 6, 2026
What changed in Management’s Discussion and Analysis?
Read the current filingPrevious report: 10-Q
Period ended 2024-06-30; filed 2024-08-08.
0000950170-24-093341
Item 2. Management’s Discussion and Analysis of Financial Condition and Results of OperationsCurrent report: 10-Q
Period ended 2024-09-30; filed 2024-11-12.
0000950170-24-124595
Item 2. Management’s Discussion and Analysis of Financial Condition and Results of OperationsThe baseline is this issuer’s latest earlier reporting period of the same form that was filed before the current report. A previous 10-Q is a different quarter, not a year-over-year comparison. Amendments are excluded.
Compared 162 previous paragraphs and 173 current paragraphs.
115 unchanged; 41 reworded; 15 added; 5 removed; 1 previous and 2 current paragraphs rearranged.
Tables are not compared: 5 previous and 5 current tables excluded. Dates, whitespace, punctuation and numbering changes are ignored; changes to financial figures remain significant.
A changed paragraph is not evidence that risk increased or decreased. An unchanged paragraph does not establish that risk stayed the same.
Added paragraphs (15)
Current report
Liver disease: GalNAc-conjugated RNA editing oligonucleotide targeting PNPLA3 I148M for correction; and
Current report
Heterozygous Familial Hypercholesterolemia (“HeFH”): GalNAc-conjugated RNA editing oligonucleotide targeting low-density lipoprotein receptor (“LDLR”) for upregulation and GalNAc-conjugated RNA editing oligonucleotide targeting apolipoprotein B (“APOB”) for correction.
Current report
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Current report
o
Current report
In the fourth quarter of 2024, we announced positive proof-of-mechanism data from the ongoing Phase 1b/2a RestorAATion-2 study, which provided the first-ever clinical demonstration of RNA editing in humans. Following a single subcutaneous dose of 200 mg of WVE-006 in the study’s first two patients, circulating wild-type M-AAT protein in plasma reached a mean of 6.9 micromolar at day 15, representing more than 60% of total AAT. Increases in neutrophil elastase inhibition from baseline were consistent with production of functional M-AAT. Mean total AAT protein increased from below the level of quantification at baseline to 10.8 micromolar at day 15, meeting the level that has historically been the basis for regulatory approval for AAT augmentation therapies. Increases in total AAT from baseline and M-AAT protein were observed as early as day 3 and through day 57. WVE-006 has been well-tolerated with a favorable safety profile. All adverse events in RestorAATion-2, as well as in the ongoing RestorAATion-1 trial of healthy volunteers, were mild to moderate, with no Serious Adverse Events reported. The RestorAATion-2 trial is ongoing and we expect to share multidose data in 2025.
Current report
In September 2024, we announced positive interim data from the ongoing Phase 2 FORWARD-53 study. Eleven boys amenable to exon 53 skipping (age 5-11; 10 ambulatory and 1 non-ambulatory) are enrolled. The interim analysis was conducted after 24 weeks of 10 mg/kg dosing Q2W. WVE-N531 appeared safe and well tolerated. We observed mean muscle content-adjusted dystrophin expression of 9.0% and unadjusted dystrophin of 5.5%, with high consistency across participants, in a prespecified analysis. Dystrophin expression was quantified from two isoforms consistent with those observed in Becker muscular dystrophy patients who display milder disease. In addition, we observed meaningful improvements in serum biomarkers for muscle health, with localization of WVE-N531 present in myogenic stem cells and regeneration of myofibers. Skeletal muscle concentrations of ~41,000 ng/g and 61-day tissue half-life observed support monthly dosing going forward.
Current report
Following our positive clinical results, we initiated engagement with the U.S. Food and Drug Administration (“FDA”). In November 2024, we received supportive initial feedback from FDA, who recognize the severity of HD and are receptive to and engaged with us regarding a potential pathway to accelerated approval. FDA is open to our plan to evaluate biomarkers, including caudate atrophy, as an endpoint to assess HD progression with the potential to predict clinical outcome. Also in November 2024, FDA granted Orphan Drug Designation to WVE-003.
Current report
Planning is underway for a global, potentially registrational Phase 2/3 study, including finalization of key aspects of design. We expect to submit an Investigational New Drug (“IND”) application for WVE-003 in the second half of 2025.
Current report
In October 2024, we announced three new, wholly owned RNA editing programs that are on track for candidate selection in 2025. These programs build on the achievement of proof-of-mechanism for RNA editing with WVE-006. As with WVE-006, these programs leverage GalNAc conjugates and have efficient clinical paths to proof-of-concept. These new programs include PNPLA3, which aims to use mRNA correction to restore the heterozygous phenotype for those at high risk for a variety of liver diseases, and LDLR and APOB which utilize first-in-class mRNA upregulation and mRNA correction treatment approaches to achieve target low-density lipoprotein cholesterol (LDL-c) levels in heterozygous familial hypercholesterolemia patients.
Current report
In 2026, we expect to have five GalNAc-conjugated clinical programs, including WVE-006, our WVE-007 siRNA program, and three new RNA editing programs.
Current report
Recent Developments
Current report
As previously disclosed, on September 27, 2024, we closed an underwritten public offering (the “September 2024 Offering”) of 26,875,001 of our ordinary shares at a price of $8.00 per ordinary share and pre-funded warrants (the “2024 Pre-Funded Warrants”) to purchase 1,875,023 ordinary shares at a price of $7.9999 per 2024 Pre-Funded Warrant, for gross proceeds of $200.0 million. On October 1, 2024, the representatives of the underwriters in the September 2024 Offering exercised their option to purchase an additional 3,750,000 ordinary shares, for additional gross proceeds of $30.0 million to us.
Current report
Revenue recognized for the three months ended September 30, 2024 and 2023 was $(7.7) million and $49.2 million, respectively, and is comprised of revenue recognized under the GSK Collaboration Agreement and the Takeda Collaboration Agreement. The year-over-year change in revenue was primarily driven by the decrease in revenue recognized under the Takeda Collaboration Agreement as we recognized $28.0 million of revenue related to the termination of the C9 program, as well as $7.0 million of revenue related to the achievement of a development milestone under the Takeda Collaboration Agreement in the three months ended September 30, 2023. Additionally, revenue recognized under the GSK Collaboration Agreement also declined year-over-year; $14.3 million was recognized for the three months ended September 30, 2023, and for the same period in 2024, an $8.0 million reduction to cumulative revenue was recorded due to a change in the estimate to fulfill the GSK Collaboration Agreement performance obligations in accordance with the revenue recognition standard.
Current report
Comparison of the nine months ended September 30, 2024 and 2023
Current report
On September 27, 2024, the Company closed the September 2024 Offering in which the Company issued and sold 23,125,001 of the Company’s ordinary shares and the 2024 Pre-Funded Warrants to purchase up to 1,875,023 of the Company’s ordinary shares. The gross proceeds to the Company from the September 2024 Offering were $200.0 million before deducting underwriting discounts and commissions and other offering expenses.
Removed paragraphs (5)
Previous report
If we are successful in the clinic with WVE-006, this would validate our clinical approach to AATD and demonstrate the feasibility of RNA editing as a therapeutic modality in humans.
Previous report
We have submitted an opt-in package to our partner, Takeda, and initiated engagement with regulators on a clinical development path to accelerated approval. We expect to receive a decision from Takeda on their option right, as well as feedback from regulators by year-end.
Previous report
We expect to select five new clinical candidates by the end of 2025, including WVE-007, our INHBE candidate for obesity.
Previous report
Comparison of the six months ended June 30, 2024 and 2023
Previous report
Revenue for the six months ended June 30, 2024 and 2023 was $32.2 million and $35.0 million, respectively, and is comprised of revenue earned under the GSK Collaboration Agreement and the Takeda Collaboration Agreement. There was a slight decrease in the revenue earned under both the GSK Collaboration Agreement and the Takeda Collaboration Agreement year-over-year.
Reworded paragraphs (41)
Previous wording
AATD: WVE-006 is a GalNAc-conjugated SERPINA1 RNA editing oligonucleotide; and
Current wording
AATD: WVE-006 is a GalNAc-conjugated SERPINA1 RNA editing oligonucleotide;
Previous wording
WVE-006 is first-in-class in AATD and is the most advanced program currently in development using an oligonucleotide to harness an endogenous enzyme for RNA editing. In the fourth quarter of 2023, we initiated our RestorAATion clinical program investigating WVE-006 as a treatment for AATD. The RestorAATion clinical program includes both healthy volunteers (“RestorAATion-1”), as well as patients with AATD who have the homozygous PiZZ mutation (“RestorAATion-2”) and is designed to provide an efficient path to proof-of-mechanism as measured by restoration of wild-type alpha-1 antitrypsin (“M-AAT”) protein in serum. RestorAATion-2 is a Phase 1b/2a open label study designed to evaluate the safety, tolerability, pharmacodynamics (“PD”) and pharmacokinetics (“PK”) of WVE-006 in individuals with AATD who have the homozygous PiZZ mutation. The trial includes both single ascending dose (“SAD”) and multiple ascending dose (“MAD”) portions. In the third quarter of 2024, we initiated dosing in the single dose portion of the first dose cohort of RestorAATion-2. We expect to deliver proof-of-mechanism data in patients with AATD in the fourth quarter of 2024.
Current wording
WVE-006 is first-in-class in AATD and is the most advanced program currently in development using an oligonucleotide to harness an endogenous enzyme for RNA editing. Our RestorAATion clinical program investigating WVE-006 as a treatment for AATD is ongoing. The RestorAATion clinical program includes both healthy volunteers (“RestorAATion-1”), as well as patients with AATD who have the homozygous PiZZ mutation (“RestorAATion-2”) and is designed to provide an efficient path to proof-of-mechanism as measured by restoration of wild-type alpha-1 antitrypsin (“M-AAT”) protein in serum. RestorAATion-2 is a Phase 1b/2a open label study designed to evaluate the safety, tolerability, pharmacodynamics (“PD”) and pharmacokinetics (“PK”) of WVE-006 in individuals with AATD who have the homozygous PiZZ mutation. The trial includes both single ascending dose (“SAD”) and multiple ascending dose (“MAD”) portions. In the third quarter of 2024, we initiated dosing in the single dose portion of the first dose cohort of RestorAATion-2.
Previous wording
Under our GSK collaboration, GSK received an exclusive global license for WVE-006, with clinical development and commercial responsibilities transitioning to GSK after we complete the RestorAATion-2 trial. Under the terms of the collaboration, we are eligible to receive up to $525 million in development, launch, and commercial milestone payments, as well as double-digit tiered royalties up to the high teens, as a percentage of net sales for WVE-006. In December 2023, we announced that we achieved the first WVE-006 milestone in our collaboration with GSK, resulting in a $20 million payment.
Current wording
Under our GSK collaboration, GSK received an exclusive global license for WVE-006, with clinical development and commercial responsibilities transitioning to GSK after we complete the RestorAATion-2 trial. Under the terms of the collaboration, we are eligible to receive up to $525 million in development, launch, and commercial milestone payments, as well as double-digit tiered royalties up to the high teens, as a percentage of net sales for WVE-006. In December 2023, we announced that we achieved the first WVE-006 milestone in our collaboration with GSK, resulting in a $20.0 million payment.
Previous wording
Our first wholly owned program to emerge from our collaboration with GSK is WVE-007, a GalNAc-small interfering RNA (“siRNA”) that is designed to silence the Inhibin βE gene (“INHBE”) to induce lipolysis (fat-burning) while preserving muscle mass to restore and maintain a healthy metabolic profile. There are approximately 174 million people in the United States and Europe with obesity, and therapeutic options beyond GLP-1 receptor agonists are needed. GLP-1 receptor agonists lead to weight loss at the expense of muscle, suppress the general reward system, and are associated with a poor tolerability profile and 68% drop-off after one year. 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. In connection with our 2023 Research and Development Day, we sharedin 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. These are the first data to demonstrate INHBE silencingin vivo in an animal model is consistent with the phenotypes of heterozygous loss-of-function carriers.
Current wording
Our first wholly owned program to emerge from our collaboration with GSK is WVE-007, a GalNAc-small interfering RNA (“siRNA”) that is designed to silence the Inhibin βE gene (“INHBE”) to induce lipolysis (fat-burning) while preserving muscle mass to restore and maintain a healthy metabolic profile. There are approximately 174 million people in the United States and Europe living with obesity, and therapeutic options beyond GLP-1 receptor agonists are needed. GLP-1 receptor agonists lead to weight loss at the expense of muscle, suppress the general reward system, and are associated with a poor tolerability profile and 68% drop-off after one year. 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. In connection with our 2023 Research and Development Day, we sharedin 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. These are the first data to demonstrate INHBE silencingin vivo in an animal model is consistent with the phenotypes of heterozygous loss-of-function carriers.
Previous wording
WVE-007 utilizes our next generation GalNAc-siRNA format. In preclinical diet-induced obesity (“DIO”) mouse models, our INHBE GalNAc-siRNA has demonstrated highly potent INHBE silencing (ED50 < 1 mg/kg), durable silencing following one, low-single digit dose supporting every-six-month or annual subcutaneous dosing in humans, weight loss with no loss of muscle mass and reduction in fat mass, with preferential effect to the visceral fat, consistent with the profile of INHBE LoF in human genetics. In a head-to-head study in DIO mice, we have observed a weight loss effect from a single dose of our INHBE GalNAc-siRNA similar to semaglutide. In addition, treatment with our INHBE GalNAc-siRNA upon cessation of semaglutide treatment curtailed expected rebound weight gain. Additionally, in a separate ongoing study in DIO mice, when administered in combination with semaglutide, a single dose of our INHBE GalNAc-siRNA doubled the weight loss observed with semaglutide alone and this effect was sustained throughout the duration of the study. We plan to share additional preclinical data later this year and expect to initiate a clinical trial for WVE-007 in the first quarter of 2025.
Current wording
WVE-007 utilizes our next generation GalNAc-siRNA format. In preclinical diet-induced obesity (“DIO”) mouse models, our INHBE GalNAc-siRNA has demonstrated highly potent INHBE silencing (ED50 < 1 mg/kg), durable silencing following one, low-single digit dose supporting every-six-month or annual subcutaneous dosing in humans, weight loss with no loss of muscle mass and reduction in fat mass, with preferential effect to the visceral fat, consistent with the profile of INHBE LoF in human genetics. In a head-to-head study in DIO mice, we have observed a weight loss effect from a single dose of our INHBE GalNAc-siRNA similar to semaglutide. In addition, treatment with our INHBE GalNAc-siRNA upon cessation of semaglutide treatment curtailed expected rebound weight gain. Additionally, in a separate ongoing study in DIO mice, when administered as an add-on to semaglutide, a single dose of our INHBE GalNAc-siRNA doubled the weight loss observed with semaglutide alone and this effect was sustained throughout the duration of the study. We are on track to initiate a Phase 1 clinical trial for WVE-007 in adults living with overweight or obesity in the first quarter of 2025. The trial is planned to assess safety, tolerability, pharmacokinetics, and Activin E lowering (a biomarker for target engagement), as well as body composition.
Previous wording
In DMD, we are advancing WVE-N531, which is designed to skip exon 53 within the dystrophin gene – a therapeutic approach that would address approximately 8-10% of DMD cases. WVE-N531 is designed to cause the cellular splicing machinery to skip over exon 53 during pre-mRNA processing, which restores the dystrophin mRNA reading frame and enables production of a truncated, but functional, dystrophin protein. Exon skipping produces dystrophin from the endogenous dystrophin gene (not micro or mini dystrophin expressed from a foreign vector), under the control of native gene-regulatory elements, resulting in normal expression. WVE-N531 is our first splicing candidate incorporating PN backbone (“PN”) chemistry to be assessed in the clinic.
Current wording
In DMD, we are advancing WVE-N531, which is designed to skip exon 53 within the dystrophin gene – a therapeutic approach that would address approximately 8-10% of DMD cases. WVE-N531 is designed to cause the cellular splicing machinery to skip over exon 53 during pre-mRNA processing, which restores the dystrophin mRNA reading frame and enables production of a truncated, but functional, dystrophin protein. Exon skipping produces dystrophin from the endogenous dystrophin gene (not micro or mini dystrophin expressed from a foreign vector), under the control of native gene-regulatory elements, resulting in normal expression. WVE-N531 is our first splicing candidate incorporating PN backbone (“PN”) chemistry to be assessed in the clinic. In the third quarter of 2024, the FDA granted Rare Pediatric Disease Designation and Orphan Drug Designation to WVE-N531.
Previous wording
In December 2022 (data cut-off: December 6, 2022), we announced a positive update from Part A of the Phase 1b/2a proof-of-concept, open label trial of WVE-N531 in three boys with DMD amenable to exon 53 skipping. High muscle concentrations of WVE-N531 and exon skipping were observed six weeks after initiating multi-dosing at 10 mg/kg every other week, achieving proof-of-concept in the trial. WVE-N531 also appeared safe and well-tolerated.
Current wording
In December 2022, we announced a positive update from Part A of the Phase 1b/2a proof-of-concept, open label trial of WVE-N531 in three boys with DMD amenable to exon 53 skipping. High muscle concentrations of WVE-N531 and exon skipping were observed six weeks after initiating multi-dosing at 10 mg/kg every other week, achieving proof-of-concept in the trial. WVE-N531 also appeared safe and well-tolerated.
Previous wording
In December 2023, we initiated dosing of WVE-N531 in FORWARD-53, the Phase 2 portion of the open-label trial (“Part B”). In Part B, boys are being dosed at 10 mg/kg every other week, and we plan to assess dystrophin protein after 24 and 48 weeks of dosing. The primary endpoint will be dystrophin protein levels, and the trial will also evaluate pharmacokinetics, digital and functional endpoints, and safety and tolerability. We expect to deliver data from FORWARD-53, including dystrophin protein expression from muscle biopsies taken after 24 weeks of treatment, in the third quarter of 2024. Pending positive results from this trial, we are planning to advance a broader DMD pipeline with PN-modified splicing oligonucleotides designed to skip other exons, with the goal of providing new treatment options for a larger population of boys with DMD.
Current wording
In December 2023, we initiated dosing of WVE-N531 in FORWARD-53, the Phase 2 portion of the open-label trial (“Part B”). The study is designed to administer 10 mg/kg infusions of WVE-N531 every two weeks (“Q2W”) and muscle biopsies are taken after 24 and 48 weeks of dosing. The primary endpoint will be dystrophin protein levels, and the trial will also evaluate pharmacokinetics, digital and functional endpoints, and safety and tolerability.
Previous wording
In HD, we are currently advancing WVE-003, a stereopure allele-selective oligonucleotide designed to selectively target an undisclosed single nucleotide polymorphism (“SNP”), “mHTT SNP3”, associated with the disease-causing mHTT mRNA transcript within the Huntingtin (“HTT”) gene. Approximately 40% of the HD population carries SNP3 according to published literature (Carroll et al., Molecular Therapy, 2011), and up to 80% of HD may be addressed in the future with other SNP-targeted candidates.
Current wording
In HD, we are currently advancing WVE-003, a stereopure allele-selective oligonucleotide designed to selectively target an undisclosed single nucleotide polymorphism (“SNP”), “mHTT SNP3”, associated with the disease-causing mHTT mRNA transcript within the Huntingtin (“HTT”) gene. Approximately 40% of the HD population carries SNP3 according to published literature (Carroll et al., Molecular Therapy, 2011), and up to 80% of HD may be addressed in the future with other SNP-targeted candidates. There are currently no disease modifying therapies for HD, which affects over 200,000 individuals across all disease stages in the United States and Europe alone.
Previous wording
In June 2024, we announced positive clinical data from the Phase 1b/2a SELECT-HD study of WVE-003. Results from the multi-dose portion of the trial, which evaluated three doses of 30mg WVE-003 administered every eight weeks, showed clear translation of target engagement to clinic with statistically significant, potent, durable and allele-selective reductions in cerebrospinal fluid (“CSF”) mHTT of up to 46% and preservation of healthy protein. This cohort also revealed a statistically significant correlation between mHTT reductions and slowing of caudate atrophy, indicating a potential benefit of allele-selective mHTT reductions. Structural brain magnetic resonance imaging (“MRI”) changes such as caudate atrophy are well-characterized measures of disease progression and neurodegeneration in HD. WVE-003 was generally safe and well-tolerated, with mild-to-moderate adverse events (“AEs”) and no Serious AEs.
Current wording
In June 2024, we announced positive clinical data from the Phase 1b/2a SELECT-HD study of WVE-003. Results from the multi-dose portion of the trial, which evaluated three doses of 30mg WVE-003 administered every eight weeks, showed clear translation of target engagement to clinic with statistically significant, potent, durable and allele-selective reductions in cerebrospinal fluid (“CSF”) mHTT of up to 46% and preservation of healthy protein. This cohort also revealed a statistically significant correlation between mHTT reductions and slowing of caudate atrophy, indicating a potential benefit of allele-selective mHTT reductions. Structural brain magnetic resonance imaging (“MRI”) changes such as caudate atrophy are well-characterized measures of disease progression and neurodegeneration in HD. WVE-003 was generally safe and well-tolerated, with mild-to-moderate adverse events (“AEs”) and no Serious AEs (“SAEs”). In November 2024, five months after a patient completed their final safety visit, an SAE was reported that we assessed to be not-related to WVE-003.
Previous wording
Through our collaboration with GSK, we are leveraging GSK’s novel genetics insights to expand our wholly owned pipeline, with the first being our INHBE program. In addition, we and GSK are actively working on multiple target validation programs for our GSK-partnered programs, for which all of our costs and expenses are prepaid by GSK. In April 2024, GSK selected its first two programs to advance to development candidates following achievement of target validation, triggering an aggregate initiation payment of $12 million from GSK. These programs utilize our next generation GalNAc-siRNA format and are in hepatology.
Current wording
Through our collaboration with GSK, we are also leveraging GSK’s novel genetics insights to expand our wholly owned pipeline, with the first being our INHBE program. In addition, we and GSK are actively working on multiple target validation programs for our GSK-partnered programs, for which all of our costs and expenses are prepaid by GSK. In April 2024, GSK selected its first two programs to advance to development candidates following achievement of target validation, triggering an aggregate initiation payment of $12.0 million from GSK. These programs utilize our next generation GalNAc-siRNA format and are in hepatology.
Previous wording
We have never been profitable, and since our inception, we have incurred significant operating losses. Our net loss for the three months ended June 30, 2024 and 2023 was $32.9 million and $21.1 million, respectively. Our net loss for the six months ended June 30, 2024 and 2023 was $64.5 million and $48.5 million, respectively. As of June 30, 2024 and December 31, 2023, we had an accumulated deficit of $1,089.3 million and $1,024.9 million, respectively. We expect to continue to incur significant expenses and operating losses for the foreseeable future.
Current wording
We have never been profitable, and since our inception, we have incurred significant operating losses. Our net loss for the three months ended September 30, 2024 was $61.8 million and our net income for the three months ended September 30, 2023 was $7.3 million. Our net loss for the nine months ended September 30, 2024 and 2023 was $126.3 million and $41.3 million, respectively. As of September 30, 2024 and December 31, 2023, we had an accumulated deficit of $1,151.1 million and $1,024.9 million, respectively. We expect to continue to incur significant expenses and operating losses for the foreseeable future.
Previous wording
Research and development expenses were $40.4 million for the three months ended June 30, 2024, compared to $33.3 million for the three months ended June 30, 2023. The increase of approximately $7.1 million was due to the following:
Current wording
Research and development expenses were $41.2 million for the three months ended September 30, 2024, compared to $31.6 million for the three months ended September 30, 2023. The increase of approximately $9.6 million was due to the following:
Previous wording
an increase of $1.0 million in external expenses related to our AATD program, WVE-006 (RNA editing);
Current wording
an increase of $0.5 million in external expenses related to our AATD program, WVE-006 (RNA editing);
Previous wording
an increase of $1.8 million in external expenses related to our DMD programs, including WVE-N531 (splicing);
Current wording
an increase of approximately $1.8 million in external expenses related to our DMD programs, including WVE-N531 (splicing);
Previous wording
a decrease of $1.4 million in external expenses related to our HD programs, including WVE-003 (silencing);
Current wording
an increase of $0.9 million in external expenses related to our HD programs, including WVE-003 (silencing);
Previous wording
an increase of $8.0 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
Current wording
an increase of $9.0 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 in other external research and development expenses; and
Previous wording
a decrease of $3.3 million in external expenses related to our discontinued ALS and FTD program, WVE-004.
Current wording
a decrease of $2.6 million in external expenses related to our discontinued ALS and FTD program, WVE-004.
Previous wording
General and administrative expenses were $14.3 million for the three months ended June 30, 2024, as compared to $12.3 million for the three months ended June 30, 2023. The increase is primarily driven by increases in compensation related expenses and administrative expenses.
Current wording
General and administrative expenses were $15.0 million for the three months ended September 30, 2024, as compared to $13.1 million for the three months ended September 30, 2023. The increase is primarily driven by increases in compensation related expenses and administrative expenses.
Previous wording
Other income, net for the three months ended June 30, 2024 and 2023 was $2.1 million and $2.4 million, respectively, and consisted primarily of dividend income.
Current wording
Other income, net for the three months ended September 30, 2024 and 2023 was $2.1 million and $2.1 million, respectively, and consisted primarily of dividend income.
Previous wording
During the three months ended June 30, 2024 and 2023, we recorded no income tax provision. We maintained a full valuation allowance for the three months ended June 30, 2024 and 2023 in all jurisdictions due to uncertainty regarding future taxable income.
Current wording
During the three months ended September 30, 2024, we recorded no income tax benefit or provision. During the three months ended September 30, 2023, we recorded an income tax benefit of $0.7 million due to a provision to return adjustment in connection with the U.S. tax guidance relating to the capitalization of research and development expenditures. We maintained a full valuation allowance for the three months ended September 30, 2024 and 2023 in all jurisdictions due to uncertainty regarding future taxable income.
Previous wording
Revenue for the three months ended June 30, 2024 and 2023 was $19.7 million and $22.1 million, respectively, and is comprised of revenue earned under the GSK Collaboration Agreement and the Takeda Collaboration Agreement. There was a slight decrease in the revenue earned under both the GSK Collaboration Agreement and the Takeda Collaboration Agreement year-over-year.
Current wording
Revenue for the nine months ended September 30, 2024 and 2023 was $24.6 million and $84.2 million, respectively, and is comprised of revenue earned under the GSK Collaboration Agreement and the Takeda Collaboration Agreement. The year-over-year change in revenue was primarily driven by the decrease in revenue recognized under the Takeda Collaboration Agreement, as we recognized $28.0 million of revenue in the nine months ended September 30, 2023 related to the termination of the C9 program, as well as $7.0 million of revenue related to the achievement of a development milestone under the Takeda Collaboration Agreement. Additionally, there was a decrease in revenue recognized under the GSK Collaboration Agreement, as in the nine months ended September 30, 2023, we recognized $47.4 million under the GSK Collaboration Agreement and in the nine months ended September 30, 2024, we recognized $23.4 million under the GSK Collaboration Agreement. As previously discussed, during the three months ended September 30, 2024, an $8.0 million reduction to cumulative revenue was recorded due to a change in the estimate to fulfill the GSK Collaboration Agreement performance obligations in accordance with the revenue recognition standard.
Previous wording
Research and development expenses were $73.8 million for the six months ended June 30, 2024, compared to $64.3 million for the six months ended June 30, 2023. The increase of approximately $9.5 million was due to the following:
Current wording
Research and development expenses were $115.0 million for the nine months ended September 30, 2024, compared to $95.9 million for the nine months ended September 30, 2023. The increase of approximately $19.1 million was due to the following:
Previous wording
an increase of $2.6 million in external expenses related to our AATD program, WVE-006 (RNA editing);
Current wording
an increase of $3.1 million in external expenses related to our AATD program, WVE-006 (RNA editing);
Previous wording
an increase of $4.5 million in external expenses related to our DMD programs, including WVE-N531 (splicing);
Current wording
an increase of $6.4 million in external expenses related to our DMD programs, including WVE-N531 (splicing);
Previous wording
an increase of $9.7 million in other research and development expenses(1), including INHBE, RNA editing, PRISM, and other internal and external research and development expenses that are no 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
Current wording
an increase of approximately $18.6 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 in other external research and development expenses; and
Previous wording
a decrease of $5.9 million in external expenses related to our discontinued ALS and FTD program, WVE-004.
Current wording
a decrease of $8.5 million in external expenses related to our discontinued ALS and FTD program, WVE-004.
Previous wording
General and administrative expenses were $27.8 million for the six months ended June 30, 2024, as compared to approximately $24.5 million for the six months ended June 30, 2023. The increase of $3.3 million was primarily driven by increases in compensation related expenses and professional fees.
Current wording
General and administrative expenses were $42.9 million for the nine months ended September 30, 2024, as compared to approximately $37.6 million for the nine months ended September 30, 2023. The increase of $5.3 million was primarily driven by increases in compensation related expenses and professional fees.
Previous wording
Other income, net for the six months ended June 30, 2024 and 2023 was $5.0 million and $5.2 million, respectively, and consisted primarily of dividend income, as well as estimated refundable tax credits.
Current wording
Other income, net for the nine months ended September 30, 2024 and 2023 was $7.1 million and $7.4 million, respectively, and consisted primarily of dividend income, as well as estimated refundable tax credits.
Previous wording
During the six months ended June 30, 2024 and 2023, we recorded no income tax provision. We maintained a full valuation allowance for the six months ended June 30, 2024 and 2023 in all jurisdictions due to uncertainty regarding future taxable income.
Current wording
During the nine months ended September 30, 2024, we recorded no income tax benefit or provision. During the nine months ended September 30, 2023, we recorded an income tax benefit of $0.7 million due to a provision to return adjustment in connection with the U.S. tax guidance relating to the capitalization of research and development expenditures. We maintained a full valuation allowance for the nine months ended September 30, 2024 and 2023 in all jurisdictions due to uncertainty regarding future taxable income.
Previous wording
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. Through June 30, 2024, we have received an aggregate of approximately $1,342.7 million in net proceeds from these transactions, consisting of $742.1 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.
Current wording
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. Through September 30, 2024, we have received an aggregate of approximately $1,544.9 million in net proceeds from these transactions, consisting of $944.3 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.
Previous wording
As of June 30, 2024, we had cash and cash equivalents totaling $154.0 million, restricted cash of $3.7 million and an accumulated deficit of $1,089.3 million. Subsequent to June 30, 2024, we received $12.7 million in net proceeds under our at-the-market equity program.
Current wording
As of September 30, 2024, we had cash and cash equivalents totaling $310.9 million, restricted cash of $3.7 million and an accumulated deficit of $1,151.1 million. On October 1, 2024, the representatives of the underwriters in connection with the previously disclosed underwritten public offering 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.
Previous wording
Our operating lease commitments as of June 30, 2024 total approximately $33.7 million, of which approximately $4.6 million is related to payments in 2024 and approximately $29.1 million is related to payments beyond 2024.
Current wording
Our operating lease commitments as of September 30, 2024 total approximately $31.4 million, of which approximately $2.3 million is related to payments in 2024 and approximately $29.1 million is related to payments beyond 2024.
Previous wording
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. 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. 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. 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. 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.
Current wording
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. 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. 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. Since we no longer qualified as a “well-known seasoned issuer” (“WKSI”) 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. 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.
Previous wording
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. As of August 7, 2024, we have $298.2 million in securities available for issuance under the 2022 Form S-3, including approximately $115.2 million in ordinary shares available for issuance under our at-the-market equity program.
Current wording
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 included 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. In connection with and to access capacity for the September 2024 Offering, we reduced the amount of ordinary shares that may be sold pursuant to our “at-the-market” equity offering program with Jefferies to $0.
Previous wording
During the six months ended June 30, 2024, operating activities used $60.9 million of cash, due to our net loss of $64.5 million and changes in operating assets and liabilities of $7.1 million, offset by non-cash charges of $10.7 million.
Current wording
During the nine months ended September 30, 2024, operating activities used $107.4 million of cash, due to our net loss of $126.3 million and offset by changes in operating assets and liabilities of $2.5 million and by non-cash charges of $16.4 million.
Previous wording
During the six months ended June 30, 2023, operating activities provided $48.3 million of cash, due to our net loss of $48.5 million, offset by non-cash charges of $9.9 million and changes in operating assets and liabilities of $86.9 million. The largest change in operating assets and liabilities was a $104.3 million increase in deferred revenue, mainly driven by our GSK Collaboration Agreement, which became effective in January 2023.
Current wording
During the nine months ended September 30, 2023, operating activities provided $13.8 million of cash, due to our net loss of $41.3 million, offset by non-cash charges of $14.5 million and changes in operating assets and liabilities of $40.6 million. The largest non-cash charge was the $7.4 million of share-based compensation. The largest change in operating assets and liabilities was a $62.3 million increase in deferred revenue, mainly driven by our GSK Collaboration Agreement, which became effective in January 2023, which was offset by the second largest change in operating assets and liabilities, the $7.0 million increase in accounts receivable related to the achievement of a milestone under the Takeda Collaboration Agreement.
Previous wording
During the six months ended June 30, 2024, investing activities used $0.5 million of cash, related to purchases of property and equipment.
Current wording
During the nine months ended September 30, 2024, investing activities used $0.9 million of cash, related to purchases of property and equipment.
Previous wording
During the six months ended June 30, 2023, investing activities used $0.6 million of cash, related to purchases of property and equipment.
Current wording
During the nine months ended September 30, 2023, investing activities used $0.8 million of cash, related to purchases of property and equipment.
Previous wording
During the six months ended June 30, 2024, net cash provided by financing activities was $15.2 million, which was primarily due to the $14.0 million in net proceeds from the January 2024 exercise of the underwriters’ option to purchase an additional 3,000,000 shares under the December 2023 Offering. Additionally, we received $0.5 million in net proceeds from sales under our at-the-market equity program.
Current wording
During the nine months ended September 30, 2024, net cash provided by financing activities was $218.9 million, which was primarily due to the $188.0 million in net proceeds from the September 2024 Offering of ordinary shares and the 2024 Pre-Funded Warrants; as well as the $14.0 million in net proceeds from the January 2024 exercise of the underwriters’ option to purchase an additional 3,000,000 shares under the December 2023 Offering. Additionally, we received $15.3 million in net proceeds from sales under our “at-the-market” equity program.
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Rearranged current paragraphs (2)
Current report — wording carried from elsewhere
In the first quarter of 2025, we expect to deliver the complete 48-week FORWARD-53 data, and receive feedback from regulators on a pathway to accelerated approval. Pending positive results from this trial, we are planning to advance a broader DMD pipeline with PN-modified splicing oligonucleotides designed to skip other exons, with the goal of providing new treatment options for a larger population of boys with DMD.
Current report — wording carried from elsewhere
On November 12, 2024, we plan to file a WKSI shelf registration statement on Form S-3ASR with the SEC pursuant to which we expect to register 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”. Our 2024 WKSI Shelf is expected to include 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 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 (as defined below) (collectively, the “Sales Agreement”), for our “at-the-market” equity program. As of the filing and automatic effectiveness of our 2024 WKSI Shelf, the 2022 Form S-3 will be deemed terminated.
Rearranged previous paragraphs (1)
Previous report — wording carried elsewhere
There are currently no disease modifying therapies for HD, which affects over 200,000 individuals across all disease stages in the United States and Europe.