Wave Life Sciences Ltd.

Previous wording

WVE-007 is a GalNAc-siRNA that is designed to silence the INHBE gene to induce lipolysis (fat-burning) while preserving muscle mass to restore and maintain a healthy metabolic profile. There are approximately 175 million people in the United States and Europe living with obesity, and therapeutic options beyond GLP-1 receptor agonists are needed. GLP-1 receptor agonists lead to weight loss at the expense of muscle, suppress the general reward system, and are associated with a poor tolerability profile and 68% drop-off after one year. Heterozygous INHBE loss-of-function (“LoF”) human carriers exhibit a healthy metabolic profile, including reduced waist-to-hip ratio and reduced odds of developing type 2 diabetes or coronary artery disease, and reduction of INHBE by 50% or more is expected to restore a healthy metabolic profile. In connection with our 2023 Research and Development Day, we sharedin vivo proof-of-concept data in diet-induced obesity (“DIO”) mice demonstrating INHBE silencing well beyond the anticipated 50% therapeutic threshold, which led to substantially lower body weight and reduction of visceral fat as compared to controls. These are the first data to demonstrate INHBE silencingin vivo in an animal model is consistent with the phenotypes of heterozygous loss-of-function carriers.

Current wording

WVE-007 is a GalNAc-siRNA that is designed to silence the INHBE gene to induce fat loss by stimulating lipolysis (fat breakdown) while preserving muscle mass to restore and maintain a healthy metabolic profile. There are approximately 175 million people in the United States and Europe living with obesity, and therapeutic options beyond GLP-1 receptor agonists are needed. GLP-1 receptor agonists lead to weight loss at the expense of muscle, suppress the general reward system, and are associated with a poor tolerability profile and high discontinuation rates. Heterozygous INHBE loss-of-function (“LoF”) human carriers exhibit a healthy metabolic profile, including reduced waist-to-hip ratio and reduced odds of developing type 2 diabetes or coronary artery disease, and reduction of INHBE by 50% or more is expected to restore a healthy metabolic profile. In connection with our 2023 Research and Development Day, we sharedin vivo proof-of-concept data in diet-induced obesity (“DIO”) mice demonstrating INHBE silencing well beyond the anticipated 50% therapeutic threshold, which led to substantially lower body weight and reduction of visceral fat as compared to controls. These are the first data to demonstrate INHBE silencingin vivo in an animal model is consistent with the phenotypes of heterozygous loss-of-function carriers.

Previous wording

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 prior to 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.

Current wording

In DIO mice studies, we observed a weight loss effect from a single dose of our INHBE GalNAc-siRNA similar to daily subcutaneous injection of semaglutide for 28 days. We also observed a decrease in high fat diet-induced expansion of visceral adipose mass. This reduction of visceral fat mass was associated with significant shrinkage of adipocyte enlargement induced by high fat diet compared with phosphate-buffered saline (“PBS”) treatment. Collectively, these results support the restoration of healthy adipose tissue with this mechanism of action, while muscle mass was preserved. Additionally, a single dose of INHBE GalNAc-siRNA led to robust target engagement, including reduction of liver INHBE mRNA and its protein product Activin E in serum, a lipolysis suppressor that is upregulated in obesity and insulin resistance. Liver INHBE mRNA was strongly correlated with serum Activin E levels following INHBE-siRNA treatment. Infiltration of macrophages into visceral adipose was shown to be significantly decreased by a single dose of INHBE GalNAc-siRNA compared with PBS controls. INHBE GalNAc-siRNA also significantly reduced proinflammatory M1 macrophage (CD11c positive) while sustaining levels of anti-inflammatory M2 macrophages in visceral fat, indicating an overall shift away from a pro-inflammatory state. In addition, treatment with our INHBE GalNAc-siRNA prior to cessation of semaglutide treatment curtailed expected rebound weight gain. When administered as an add-on to semaglutide, a single dose of our INHBE GalNAc-siRNA doubled the weight loss observed with semaglutide alone, and this effect was sustained throughout the duration of the preclinical study.

Previous wording

In February 2025, we announced that we had initiated INLIGHT, the first-in-human Phase 1 clinical trial of WVE-007 in obesity. INLIGHT is enrolling adults living with overweight or obesity to assess safety, tolerability, pharmacokinetics (“PK”), biomarkers for target engagement, body weight and composition, and metabolic health. In May 2025, we announced that we completed dosing in the first and second single dose cohorts of INLIGHT. We expect to deliver clinical data from INLIGHT in the second half of 2025, including safety, tolerability and biomarkers reflective of healthy weight loss.

Current wording

In February 2025, we announced that we had initiated INLIGHT, the first-in-human Phase 1 clinical trial of WVE-007 (3:1 active:placebo) in obesity. INLIGHT is enrolling adults living with overweight or obesity to assess safety, tolerability, pharmacokinetics (“PK”), biomarkers for target engagement, body weight and composition, and metabolic health.

Previous wording

Multi-dosing is ongoing in the first cohort of RestorAATion-2, where patients with AATD who have the homozygous Pi*ZZ mutation are receiving 200 mg subcutaneous doses of WVE-006 every other week. Dosing is underway in the second single dose cohort of RestorAATion-2 at 400 mg. We expect to share data from the complete 200 mg multidose and single dose cohorts in the third quarter of 2025, and data from the complete 400 mg single dose cohort in the fall of 2025.

Current wording

Multi-dosing is complete in the first cohort of RestorAATion-2, where patients with AATD who have the homozygous Pi*ZZ mutation are receiving 200 mg subcutaneous doses of WVE-006 every other week. Dosing is complete in the second single dose cohort of RestorAATion-2 at 400 mg. We expect to share data from the complete 200 mg single and multidose cohorts of RestorAATion-2 in the third quarter of 2025, and data from the complete 400 mg single dose cohort in the fall of 2025.

Previous wording

We have never been profitable, and since our inception, we have incurred significant operating losses. Our net loss for the three months ended March 31, 2025 and 2024 was $46.9 million and $31.6 million, respectively. As of March 31, 2025 and December 31, 2024, we had an accumulated deficit of $1,168.7 million and $1,121.9 million, respectively. We expect to continue to incur significant expenses and operating losses for the foreseeable future.

Current wording

We have never been profitable, and since our inception, we have incurred significant operating losses. Our net loss for the three months ended June 30, 2025 and 2024 was $50.5 million and $32.9 million, respectively. Our net loss for the six months ended June 30, 2025 and 2024 was $ 97.3 million and $64.5 million, respectively. As of June 30, 2025 and December 31, 2024, we had an accumulated deficit of $1,219.2 million and $1,121.9 million, respectively. We expect to continue to incur significant expenses and operating losses for the foreseeable future.

Previous wording

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 our consolidated financial statements appearing elsewhere in this Quarterly Report on Form 10-Q). We have not generated any product revenue since our inception and do not expect to generate any revenue from the sale of products for the foreseeable future.

Current wording

We recognize collaboration revenue under the GSK Collaboration Agreement (as defined in Note 5 in the notes to our unaudited consolidated financial statements appearing elsewhere in this Quarterly Report on Form 10-Q), which became effective in January 2023. We have not generated any product revenue since our inception and do not expect to generate any revenue from the sale of products for the foreseeable future.

Previous wording

Revenue for the three months ended March 31, 2025 was $9.2 million and is comprised of revenue earned under the GSK Collaboration Agreement. Revenue for the three months ended March 31, 2024 was $12.5 million and is comprised of revenue earned under the GSK Collaboration Agreement and the Takeda Collaboration Agreement. The year-over-year change in revenue was primarily driven by the decrease in revenue recognized under the GSK Collaboration Agreement with a slight decrease in revenue under the Takeda Collaboration Agreement.

Current wording

Revenue for the three months ended June 30, 2025 was $8.7 million and is comprised of revenue earned under the GSK Collaboration Agreement. Revenue for the three months ended June 30, 2024 was $19.7 million and is comprised of revenue earned under the GSK Collaboration Agreement and the Takeda Collaboration Agreement. The year-over-year change in revenue was primarily driven by the decrease in revenue recognized under the GSK Collaboration Agreement with a slight decrease in revenue under the Takeda Collaboration Agreement.

Previous wording

Includes expenses related to discovery 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.

Current wording

(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.

Previous wording

Research and development expenses were $40.6 million for the three months ended March 31, 2025, compared to $33.4 million for the three months ended March 31, 2024. The increase of approximately $7.2 million was due to the following:

Current wording

Research and development expenses were $43.5 million for the three months ended June 30, 2025, compared to $40.4 million for the three months ended June 30, 2024. The increase of approximately $3.1 million was due to the following:

Previous wording

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

Current wording

a decrease of $1.3 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 INHBE program, including WVE-007 (siRNA); and

Current wording

an increase of $1.9 million in external expenses related to our INHBE program, including WVE-007 (siRNA);

Previous wording

a decrease in external expenses related to our DMD program, including WVE-N531 (splicing);

Current wording

a decrease of $1.4 million in external expenses related to our DMD program, including WVE-N531 (splicing);

Previous wording

a decrease of $1.2 million in external expenses related to our HD program, including WVE-003 (silencing);

Current wording

a decrease of $2.8 million in external expenses related to our HD program, including WVE-003 (silencing); and

Previous wording

an increase of approximately $8.3 million in other research and development expenses(1), including RNA editing, PRISM, and other internal and external research and development expenses that are not allocated on a program-by-program basis or are related to other discovery and development programs, and the identification of potential drug discovery candidates, mainly due to increases in compensation-related expenses and in other external research and development expenses.

Current wording

an increase of approximately $6.8 million in other research and development expenses(1), including RNA editing, PRISM, and other internal and external research and development expenses that are not allocated on a program-by-program basis or are related to other discovery and development programs, and the identification of potential drug discovery candidates, mainly due to increases in compensation-related expenses and in other external research and development expenses.

Previous wording

General and administrative expenses were $18.4 million for the three months ended March 31, 2025, as compared to approximately $13.5 million for the three months ended March 31, 2024. The increase of approximately $4.9 million was primarily driven by increases in compensation related expenses and other external expenses.

Current wording

General and administrative expenses were $18.0 million for the three months ended June 30, 2025, as compared to approximately $14.3 million for the three months ended June 30, 2024. The increase of approximately $3.7 million was primarily driven by increases in compensation related expenses and other external expenses.

Previous wording

Other income, net for each of the three months ended March 31, 2025 and 2024 was $2.9 million, and consisted primarily of interest income on cash and cash equivalents.

Current wording

Other income, net for the three months ended June 30, 2025 and 2024 was $2.3 million and $2.1 million, respectively, and consisted primarily of interest income on cash and cash equivalents.

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 March 31, 2025, we have received an aggregate of approximately $1,582.4 million in net proceeds from these transactions, consisting of $979.1 million in net proceeds from public and other registered offerings of our ordinary shares and other securities, $514.0 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 June 30, 2025, we have received an aggregate of approximately $1,593.6 million in net proceeds from these transactions, consisting of $990.3 million in net proceeds from public and other registered offerings of our ordinary shares and other securities, $514.0 million from our collaborations and $89.3 million in net proceeds from private placements of our debt and equity securities.

Previous wording

As of March 31, 2025, we had cash and cash equivalents totaling $243.1 million, restricted cash of $3.8 million and an accumulated deficit of $1,168.7 million.

Current wording

As of June 30, 2025, we had cash and cash equivalents totaling $208.5 million, restricted cash of $3.8 million and an accumulated deficit of $1,219.2 million. Subsequent to June 30, 2025, we received $24.9 million in net proceeds under our “at-the-market” equity program.

Previous wording

Our operating lease commitments as of March 31, 2025 total approximately $26.7 million, of which approximately $7.2 million is related to payments in 2025 and approximately $19.5 million is related to payments beyond 2025.

Current wording

Our operating lease commitments as of June 30, 2025 total approximately $24.3 million, of which approximately $4.8 million is related to payments in 2025 and approximately $19.5 million is related to payments beyond 2025.

Previous wording

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”. 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 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, for our “at-the-market” equity program. For the three months ended March 31, 2025, we received $1.3 million in net proceeds from sales of ordinary shares under our “at-the-market" equity program.

Current wording

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”. 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 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, for our “at-the-market” equity program. For the six months ended June 30, 2025, we received $12.4 million in net proceeds from sales of ordinary shares under our “at-the-market" equity program.

Previous wording

During the three months ended March 31, 2025, operating activities used $63.0 million of cash, due to our net loss of $46.9 million and by changes in operating assets and liabilities of $23.3 million, offset by non-cash charges of $7.1 million. The largest changes in operating assets and liabilities were the $13.3 million decrease in accrued expenses and other current liabilities and the $9.2 million decrease in deferred revenue.

Current wording

During the six months ended June 30, 2025, operating activities used $109.1 million of cash, due to our net loss of $97.3 million and by changes in operating assets and liabilities of $27.2 million, offset by non-cash charges of $15.5 million. The largest changes in operating assets and liabilities were the $16.3 million decrease in deferred revenue and the $8.1 million decrease in accrued expenses and other current liabilities.

Previous wording

During the three months ended March 31, 2024, operating activities used $33.4 million of cash, due to our net loss of $31.6 million and changes in operating assets and liabilities of $6.9 million, offset by non-cash charges of $5.1 million. The largest changes in operating assets and liabilities were the $21.1 million decrease in accounts receivable related to collection of accounts receivable under the GSK Collaboration Agreement, the $12.5 million decrease in deferred revenue, and the $10.2 million decrease in accrued expenses and other current liabilities.

Current 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.

Previous wording

During the three months ended March 31, 2025, investing activities used $0.2 million of cash, related to purchases of property and equipment.

Current wording

During the six months ended June 30, 2025 and 2024, investing activities used $0.5 million of cash, related to purchases of property and equipment.

Previous wording

During the three months ended March 31, 2025, net cash provided by financing activities was $4.2 million, which was primarily due to $2.5 million in proceeds from the exercise of share options and $1.3 million in net proceeds from sales under our “at-the-market” equity program.

Current wording

During the six months ended June 30, 2025, net cash provided by financing activities was $15.8 million, which was primarily due to $12.4 million in net proceeds from sales under our “at-the-market” equity program and $3.0 million in proceeds from the exercise of share options.

Previous wording

During the three months ended March 31, 2024, net cash provided by financing activities was $14.5 million, 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 our underwritten offering completed in December 2023.

Current 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 our underwritten offering completed in December 2023.

Previous wording

Adequate additional funds may not be available to us on acceptable terms when we need them, or at all. 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. To the extent that we raise additional capital through the sale of equity or convertible debt securities, the ownership interest of our existing shareholders will be diluted, and the terms may include liquidation or other preferences that adversely affect the rights of our shareholders. Additional debt financing and preferred equity financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends and may require the issuance of warrants, which could potentially dilute our shareholders’ ownership interests.

Current wording

Adequate additional funds may not be available to us on acceptable terms when we need them, or at all. We do not currently have any committed external source of funds, except for possible future payments from GSK under our collaboration with them. To the extent that we raise additional capital through the sale of equity or convertible debt securities, the ownership interest of our existing shareholders will be diluted, and the terms may include liquidation or other preferences that adversely affect the rights of our shareholders. Additional debt financing and preferred equity financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends and may require the issuance of warrants, which could potentially dilute our shareholders’ ownership interests.