Financial Data and Key Metrics Changes - Revenue for Q1 2025 was $9.2 million, down from $12.5 million in the prior year quarter, attributed to the timing of revenue recognition under the collaboration agreement with GSK [35] - Research and development expenses increased to $40.6 million from $33.4 million year-over-year, driven by spending on the Inhibin E program and RNA editing programs [35] - General and administrative expenses rose to $18.4 million from $13.5 million, primarily due to share-based compensation and professional fees [35] - Net loss for Q1 2025 was $46.9 million, compared to a net loss of $31.6 million in the prior year quarter [35] - Cash and cash equivalents at the end of Q1 2025 were $243.1 million, down from $302.1 million as of December 31, 2024, expected to fund operations into 2027 [35] Business Line Data and Key Metrics Changes - The company is advancing its clinical pipeline, including obesity, AATD, DMD, and HD programs, with significant progress reported in the last twelve months [6][7] - WVE-007 for obesity is designed to provide sustainable weight loss with infrequent dosing, showing promising preclinical data [8][10] - WVE-006 for AATD is positioned as a first treatment addressing the root cause of the disease, with ongoing clinical trials demonstrating durability of effect [12][13] - WVE-N531 for DMD has shown statistically significant improvements in muscle health and function, with plans for NDA submission in 2026 [15][20] Market Data and Key Metrics Changes - The obesity treatment market is evolving with the introduction of WVE-007, which aims to overcome limitations of current GLP-1 therapies [8][10] - The DMD market has a significant unmet need, with approximately 20,000 new cases annually, and current exon skipping therapies generating about $1.1 billion in sales in 2024 [19] - The Huntington's disease market is also underserved, with no disease-modifying therapies available, affecting over 200,000 people in the US and Europe [21] Company Strategy and Development Direction - The company is focused on unlocking the potential of RNA medicines, with a unique platform enabling a multimodal pipeline and pioneering RNA editing [6][7] - Plans include submitting NDAs for multiple candidates in 2026 and advancing a wholly owned discovery pipeline targeting both hepatic and extrahepatic diseases [14][30] - The company aims to differentiate its therapies through unique mechanisms of action and improved patient outcomes compared to existing treatments [8][19] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ongoing clinical trials and the potential for significant data disclosures throughout 2025 [38] - The company is committed to engaging with regulatory agencies to ensure alignment on accelerated approval pathways for its therapies [45][86] - Management highlighted the importance of comprehensive data to support filings and the potential for transformative impacts on patient health [20][90] Other Important Information - The company is actively engaged in discussions with prospective strategic partners for its Huntington's disease program [23] - Upcoming data releases are expected to provide insights into the efficacy and safety of the company's pipeline candidates [28][34] Q&A Session Summary Question: What triggers data disclosure for the inhibit E program? - The company will look at time points such as one month, three months, and six months for data disclosure, with an internal cutoff for target engagement, weight loss, and biomarkers [41][43] Question: Are all drugs slated for accelerated approval under CDER? - Yes, the company confirmed that all drugs are under CDER, and discussions with the agency have remained consistent regarding the accelerated approval pathway [44][45] Question: What are the major pros and cons of RNA editing versus DNA editing? - RNA editing avoids bystander edits and potential irreversible collateral effects seen in DNA editing, making it a safer option for patients [58][61] Question: Why divide the dataset for AATD into two separate announcements? - The company believes that the 200 mg multidose data will be highly informative and does not plan to hold back data for the 400 mg cohort [71][72] Question: Will monthly dosing data be included in the NDA submission for DMD? - Yes, the plan is to include monthly dosing in the label, with ongoing discussions with the agency to support this [75][84]

Pipeline and Programs - Wave Life Sciences is developing WVE-007, a GalNAc-siRNA targeting INHBE for obesity treatment, addressing a market of approximately 175 million adults in the US and Europe[11, 14] - WVE-006, an RNA editing treatment for Alpha-1 antitrypsin deficiency (AATD), aims to address both liver and lung manifestations, targeting ~200,000 people in the US and Europe homozygous for the Z allele[37, 36] - WVE-N531, a splicing oligonucleotide for Duchenne muscular dystrophy (DMD) amenable to exon 53 skipping, showed 78% average dystrophin expression between 24 and 48 weeks in clinical trials, with 88% of boys above 5% dystrophin[52, 54, 56] - WVE-003, an allele-selective oligonucleotide for Huntington's Disease (HD), achieved up to a 46% reduction in mutant HTT protein in CSF[97, 101] Clinical and Regulatory Milestones - Clinical data for WVE-007 (INHBE) in obesity is expected in the second half of 2025[31] - Data from the complete 200 mg multidose and single dose cohorts of WVE-006 (AATD) is expected in 3Q 2025, with 400 mg single dose cohort data expected in the fall of 2025[43] - Wave Life Sciences plans to submit an NDA in 2026 to support accelerated approval of WVE-N531 with monthly dosing[53, 86] - An IND application for a potentially registrational Phase 2/3 study of WVE-003 in Huntington's Disease is expected to be submitted in the second half of 2025[104] Platform and Technology - Wave Life Sciences' RNA medicines platform (PRISM®) utilizes multiple modalities including RNA editing, RNAi, splicing, and allele-selective silencing[7] - The company is developing GalNAc-AIMer programs for liver disease (PNPLA3) targeting ~9 million patients, HeFH (LDLR) targeting ~900,000 patients with expansion to ~30 million, and HeFH (APOB) targeting ~70,000 patients[45]

PART I - FINANCIAL INFORMATION [Financial Statements](index=5&type=section&id=Item%201.%20Financial%20Statements) This section presents the unaudited consolidated financial statements for Q1 2025, detailing financial position, operations, equity, and cash flows with accompanying notes [Unaudited Consolidated Balance Sheets](index=5&type=section&id=Unaudited%20Consolidated%20Balance%20Sheets) As of March 31, 2025, total assets decreased to **$288.3 million** from **$352.2 million** at year-end 2024, primarily due to reduced cash and cash equivalents Consolidated Balance Sheet Highlights (in thousands) | Account | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $243,075 | $302,078 | | Total current assets | $257,976 | $320,394 | | Total assets | $288,343 | $352,207 | | **Liabilities & Equity** | | | | Total current liabilities | $87,367 | $110,953 | | Total liabilities | $108,666 | $134,818 | | Total shareholders' equity | $171,803 | $209,515 | [Unaudited Consolidated Statements of Operations and Comprehensive Loss](index=6&type=section&id=Unaudited%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) For Q1 2025, the company reported revenue of **$9.2 million** and a net loss of **$46.9 million**, an increase from the **$31.6 million** net loss in Q1 2024 Statement of Operations Summary (in thousands, except per share data) | Metric | Q1 2025 | Q1 2024 | | :--- | :--- | :--- | | Revenue | $9,175 | $12,538 | | Research and development | $40,622 | $33,447 | | General and administrative | $18,357 | $13,549 | | Loss from operations | $(49,804) | $(34,458) | | Net loss | $(46,878) | $(31,558) | | Net loss per share | $(0.29) | $(0.24) | [Unaudited Consolidated Statements of Series A Preferred Shares and Shareholders' Equity](index=7&type=section&id=Unaudited%20Consolidated%20Statements%20of%20Series%20A%20Preferred%20Shares%20and%20Shareholders%27%20Equity) Total shareholders' equity decreased to **$171.8 million** by March 31, 2025, primarily due to the quarterly net loss, partially offset by capital inflows - Total shareholders' equity decreased by **$37.7 million** during Q1 2025, from **$209.5 million** to **$171.8 million**, mainly due to the quarterly net loss of **$46.9 million**[21](index=21&type=chunk) [Unaudited Consolidated Statements of Cash Flows](index=8&type=section&id=Unaudited%20Consolidated%20Statements%20of%20Cash%20Flows) The company used **$63.0 million** in cash for operating activities during Q1 2025, resulting in a net decrease in cash, cash equivalents, and restricted cash of **$59.0 million** Cash Flow Summary (in thousands) | Activity | Q1 2025 | Q1 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(63,039) | $(33,432) | | Net cash used in investing activities | $(165) | $(417) | | Net cash provided by financing activities | $4,155 | $14,510 | | **Net decrease in cash** | **$(58,991)** | **$(19,413)** | [Notes to Unaudited Consolidated Financial Statements](index=9&type=section&id=Notes%20to%20Unaudited%20Consolidated%20Financial%20Statements) The notes detail the company's business, liquidity, collaboration agreements, and a breakdown of research and development expenses by program - The company expects its existing cash and cash equivalents of **$243.1 million** as of March 31, 2025, to be sufficient to fund operations for at least the next twelve months[30](index=30&type=chunk) - Under the GSK Collaboration Agreement, the company recognized **$9.2 million** in revenue for Q1 2025. As of March 31, 2025, the total unsatisfied transaction price allocated to performance obligations is **$74.45 million**[53](index=53&type=chunk)[57](index=57&type=chunk) - The Takeda collaboration expired in October 2024. Consequently, no revenue was recognized under this agreement in Q1 2025, compared to **$0.3 million** in Q1 2024[59](index=59&type=chunk)[60](index=60&type=chunk) Research and Development Expenses by Program (Q1 2025, in thousands) | Program | Expense | | :--- | :--- | | AATD program | $1,446 | | INHBE program (Obesity) | $2,539 | | DMD program | $3,038 | | HD program | $1,167 | | Other R&D expenses | $32,432 | | **Total R&D Expenses** | **$40,622** | [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=21&type=section&id=Item%202.%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses the company's RNA medicines platform, clinical pipeline progress, and financial performance, including revenue, net loss, and liquidity - The company is advancing a diversified pipeline of RNA medicines, with clinical programs in obesity, alpha-1 antitrypsin deficiency (AATD), Duchenne muscular dystrophy (DMD), and Huntington's disease (HD)[71](index=71&type=chunk) - Key clinical updates include: - **Obesity (WVE-007):** Phase 1 trial initiated, with clinical data expected in the second half of 2025 - **AATD (WVE-006):** Positive proof-of-mechanism data demonstrated; further data from multidose and single dose cohorts expected in Q3 2025 and fall 2025 - **DMD (WVE-N531):** Positive 48-week data showed significant functional improvement; plan to file for accelerated approval in 2026 - **HD (WVE-003):** Positive Phase 1b/2a data showed potent mHTT reduction; preparing for a global Phase 2/3 study with an IND submission planned for the second half of 2025[82](index=82&type=chunk)[86](index=86&type=chunk)[94](index=94&type=chunk)[102](index=102&type=chunk)[104](index=104&type=chunk) Comparison of Operations (Q1 2025 vs Q1 2024, in thousands) | Item | Q1 2025 | Q1 2024 | Change | | :--- | :--- | :--- | :--- | | Revenue | $9,175 | $12,538 | $(3,363) | | Research and development | $40,622 | $33,447 | $7,175 | | General and administrative | $18,357 | $13,549 | $4,808 | | **Net loss** | **$(46,878)** | **$(31,558)** | **$(15,320)** | - As of March 31, 2025, the company had cash and cash equivalents of **$243.1 million**, which is expected to be sufficient to fund operations for at least the next twelve months[130](index=130&type=chunk)[131](index=131&type=chunk) [Quantitative and Qualitative Disclosures About Market Risk](index=35&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company identifies primary market risks including interest rate, foreign currency, inflation, and capital market risks, impacting operations and future funding - The company's main market risks are identified as interest rate risk on cash holdings, foreign currency risk from international operations, inflation risk on operating costs, and capital market risk related to future funding needs[149](index=149&type=chunk) - The company does not currently hedge its foreign currency exposure and acknowledges that continued global inflation could lead to appreciable increases in clinical trial and labor costs[151](index=151&type=chunk)[152](index=152&type=chunk) [Controls and Procedures](index=36&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that the company's disclosure controls and procedures were effective as of March 31, 2025, with no material changes to internal control over financial reporting - Based on an evaluation as of March 31, 2025, the principal executive officer and principal financial officer concluded that the company's disclosure controls and procedures were effective at the reasonable assurance level[155](index=155&type=chunk) - There were no changes in internal control over financial reporting during the first quarter of 2025 that have materially affected, or are reasonably likely to materially affect, these controls[156](index=156&type=chunk) PART II - OTHER INFORMATION [Legal Proceedings](index=37&type=section&id=Item%201.%20Legal%20Proceedings) The company reports that it is not currently a party to any material legal proceedings - As of the filing date, the company is not involved in any material legal proceedings[158](index=158&type=chunk) [Risk Factors](index=37&type=section&id=Item%201A.%20Risk%20Factors) This section refers readers to the 'Risk Factors' section of the company's Annual Report on Form 10-K for a comprehensive discussion of potential risks and uncertainties - For a detailed discussion of risk factors, the report refers to Item 1A of the company's 2024 Annual Report on Form 10-K[159](index=159&type=chunk) [Unregistered Sales of Equity Securities and Use of Proceeds](index=37&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) The company reports that there were no unregistered sales of its equity securities and no repurchases during the first quarter of 2025 - The company made no unregistered sales of equity securities and did not repurchase any of its equity securities during the three months ended March 31, 2025[160](index=160&type=chunk)[161](index=161&type=chunk) [Defaults Upon Senior Securities](index=37&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) The company reports that there have been no defaults upon its senior securities - No defaults upon senior securities were reported[162](index=162&type=chunk) [Mine Safety Disclosures](index=37&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This item is not applicable to the company's business - This section is not applicable[163](index=163&type=chunk) [Other Information](index=37&type=section&id=Item%205.%20Other%20Information) This section discloses that several officers and directors adopted Rule 10b5-1 trading plans in March 2025 for the pre-planned sale of company shares - During Q1 2025, certain officers and directors adopted Rule 10b5-1 trading plans for the sale of company securities[164](index=164&type=chunk) - On March 13, 2025, CFO Kyle Moran adopted a plan for the sale of up to **296,000 shares**, and three board members adopted plans for the sale of an aggregate of **313,845 shares**[165](index=165&type=chunk)[166](index=166&type=chunk)[167](index=167&type=chunk)[168](index=168&type=chunk) [Exhibits](index=40&type=section&id=Item%206.%20Exhibits) This section lists the exhibits filed with the Form 10-Q, including certifications by the Principal Executive Officer and Principal Financial Officer, and Inline XBRL documents - The report includes certifications from the Principal Executive Officer and Principal Financial Officer (Exhibits 31.1, 31.2, and 32) and Inline XBRL data files[170](index=170&type=chunk)

Executive Summary [First Quarter 2025 Overview](index=1&type=section&id=First%20Quarter%202025%20Overview) Wave Life Sciences reported Q1 2025 results, highlighting clinical progress and a cash runway into 2027 - Dosing completed in the first two cohorts of the INLIGHT trial for WVE-007 in obesity, with clinical data on track for **2H 2025**[1](index=1&type=chunk) - Dosing is underway in the RestorAATion-2 trial for WVE-006 in AATD, with data expected in **3Q 2025** and **Fall 2025**[1](index=1&type=chunk) - Positive data from the FORWARD-53 trial for WVE-N531 in DMD showed significant functional improvement, with an **NDA submission planned for 2026**[1](index=1&type=chunk) - An **IND submission is expected in 2H 2025** for the potentially registrational WVE-003 Phase 2/3 study in HD[1](index=1&type=chunk) - Cash and cash equivalents of **$243.1 million** as of March 31, 2025, provide a financial runway expected into **2027**[1](index=1&type=chunk) [CEO Commentary](index=1&type=section&id=CEO%20Commentary) The CEO highlighted consistent execution, leadership in RNA medicines, and upcoming clinical data across key programs - Wave Life Sciences is on track to deliver multiple clinical datasets in **2025**, demonstrating broad capabilities in RNA medicines[2](index=2&type=chunk) - WVE-007 in obesity has the potential to transform treatment with **healthy weight loss** and infrequent dosing[2](index=2&type=chunk) - WVE-N531 in DMD delivered the first-ever substantial improvements in **muscle health** with an exon skipping therapy[2](index=2&type=chunk) - WVE-003 in HD has industry-leading CSF mutant lowering and is the only program to demonstrate **allele-selective knockdown** in the clinic[2](index=2&type=chunk) Recent Business Highlights and Expected Milestones [Obesity (WVE-007)](index=2&type=section&id=Obesity) WVE-007 shows preclinical potential for healthy weight loss, with clinical data from the INLIGHT trial expected in 2H 2025 - WVE-007 is a GalNAc-siRNA designed to silence **INHBE mRNA**, an obesity target with strong human genetics evidence[4](index=4&type=chunk) - Dosing has been completed in the first and second single dose cohorts of the **INLIGHT clinical trial**[4](index=4&type=chunk) - Preclinical data showed a single dose of WVE-007 led to weight loss on par with semaglutide but with **no muscle loss**[4](index=4&type=chunk) - Clinical data from INLIGHT, including safety, tolerability, and biomarkers, is expected in the **second half of 2025**[4](index=4&type=chunk) [Alpha-1 Antitrypsin Deficiency (AATD) (WVE-006)](index=2&type=section&id=AATD%20(Alpha-1%20antitrypsin%20deficiency)) WVE-006 demonstrated the first-ever clinical RNA editing in humans, with further data from the RestorAATion-2 trial expected in 2025 - WVE-006 is a subcutaneously delivered RNA editing oligonucleotide (AIMer) designed to address **AATD-related lung and/or liver disease**[4](index=4&type=chunk) - Multi-dosing is ongoing in the first cohort of **RestorAATion-2** (200 mg) and dosing is underway in the second single dose cohort (400 mg)[4](index=4&type=chunk) - Proof-of-mechanism data showed mean circulating wild-type M-AAT protein reached **6.9 micromolar**, with total AAT increasing to **10.8 micromolar**[7](index=7&type=chunk) - Data from complete 200 mg multidose and single dose cohorts is expected in **Q3 2025**, with 400 mg single dose data expected in **Fall 2025**[7](index=7&type=chunk) [Emerging Wholly Owned siRNA and RNA Editing Pipeline](index=3&type=section&id=Emerging%20wholly%20owned%20siRNA%20and%20RNA%20editing%20pipeline) Wave is expanding its pipeline with new siRNA and RNA editing targets, with clinical development for additional programs planned for 2026 - Wave is advancing new targets to expand its pipeline of wholly owned programs in both **rare and common diseases**[7](index=7&type=chunk) - The wholly owned RNA editing pipeline includes programs for **PNPLA3** (liver diseases) and **LDLR/APOB** (familial hypercholesterolemia)[7](index=7&type=chunk) - Preclinical data for AIMers in lung indications showed increased CFTR mRNA expression **3-fold** and restored up to **50%** of functional protein levels[7](index=7&type=chunk) - New preclinical data is expected in **2025**, with initiation of clinical development for PNPLA3, LDLR, and APOB planned for **2026**[7](index=7&type=chunk) [Duchenne Muscular Dystrophy (DMD) (WVE-N531)](index=3&type=section&id=DMD%20(Duchenne%20muscular%20dystrophy)) Positive 48-week data for WVE-N531 showed significant functional and muscle health improvements, supporting a planned 2026 NDA submission - WVE-N531 is an exon skipping oligonucleotide for Duchenne muscular dystrophy amenable to **exon 53 skipping**[7](index=7&type=chunk) - Positive 48-week data from the FORWARD-53 trial included a statistically significant improvement of **3.8 seconds in Time-to-Rise** vs natural history[7](index=7&type=chunk) - The trial demonstrated substantial improvements in muscle health, including a statistically significant **reduction in fibrosis**[10](index=10&type=chunk) - Dystrophin expression stabilized, averaging **7.8%**, with **88%** of boys above 5% average dystrophin[10](index=10&type=chunk) - The U.S. FDA confirmed the **accelerated approval pathway** using dystrophin expression as a surrogate endpoint remains open[10](index=10&type=chunk) - An **NDA submission for accelerated approval** of WVE-N531 with monthly dosing is planned for **2026**[10](index=10&type=chunk) [Huntington's Disease (HD) (WVE-003)](index=4&type=section&id=HD%20(Huntington's%20disease)) WVE-003 demonstrated allele-selective mHTT reduction correlated with slowing caudate atrophy, with an IND for a Phase 2/3 study expected in 2H 2025 - WVE-003 is a first-in-class, **allele-selective oligonucleotide** for the treatment of Huntington's disease[10](index=10&type=chunk) - SELECT-HD trial data showed the first-ever allele-selective reduction in CSF mHTT protein and a significant correlation with **slowing of caudate atrophy**[10](index=10&type=chunk) - Wave has received supportive initial feedback from the FDA regarding a potential pathway to **accelerated approval**[10](index=10&type=chunk) - An **IND application** for a potentially registrational Phase 2/3 study of WVE-003 in HD is expected in the **second half of 2025**[10](index=10&type=chunk) Financial Highlights [First Quarter 2025 Financial Performance](index=4&type=section&id=First%20Quarter%202025%20Financial%20Performance) The company reported a net loss of $46.9 million for Q1 2025, with a cash runway projected into 2027 First Quarter 2025 Financial Summary (in thousands) | Metric | Q1 2025 | Q1 2024 | Change (YoY) | | :------------------------ | :------ | :------ | :----------- | | Revenue | $9,175 | $12,538 | -26.8% | | Research and development | $40,622 | $33,447 | +21.4% | | General and administrative| $18,357 | $13,549 | +35.5% | | Total operating expenses | $58,979 | $46,996 | +25.5% | | Loss from operations | $(49,804)| $(34,458)| -44.5% | | Net loss | $(46,878)| $(31,558)| -48.5% | | Net loss per share (basic & diluted) | $(0.29) | $(0.24) | -20.8% | - Cash and cash equivalents were **$243.1 million** as of March 31, 2025, which is expected to fund operations into **2027**[10](index=10&type=chunk)[18](index=18&type=chunk) Company Information [Investor Conference Call and Webcast](index=5&type=section&id=Investor%20Conference%20Call%20and%20Webcast) Wave Life Sciences hosted an investor call on May 8, 2025, to review its Q1 2025 financial results and pipeline updates - An investor conference call and webcast was held on **May 8, 2025**, at 8:30 a.m. ET[11](index=11&type=chunk) - The purpose was to review **first quarter 2025 financial results** and pipeline updates[11](index=11&type=chunk) [About Wave Life Sciences](index=5&type=section&id=About%20Wave%20Life%20Sciences) Wave Life Sciences is a clinical-stage biotechnology company developing RNA medicines using its proprietary PRISM® platform - Wave Life Sciences is a clinical-stage biotechnology company focused on unlocking the broad potential of **RNA medicines**[12](index=12&type=chunk) - The company's **PRISM® platform** combines multiple modalities, chemistry innovation, and deep insights in human genetics[12](index=12&type=chunk) - Wave's diversified pipeline includes clinical programs in **AATD, DMD, HD, and Obesity**[12](index=12&type=chunk) [Forward-Looking Statements](index=5&type=section&id=Forward-Looking%20Statements) This report contains forward-looking statements regarding future goals and financial outlook, which are subject to various risks and uncertainties - The press release contains forward-looking statements concerning goals, clinical trial data, regulatory submissions, and **financial runway**[13](index=13&type=chunk) - Actual results may differ materially due to factors such as financing ability, clinical trial outcomes, regulatory actions, and **market competition**[15](index=15&type=chunk) [Contact Information](index=6&type=section&id=Contact) Contact information is provided for investor relations and media inquiries - Contact for investors: **InvestorRelations@wavelifesci.com**[16](index=16&type=chunk) - Contact for media: **MediaRelations@wavelifesci.com**[16](index=16&type=chunk) Unaudited Consolidated Financial Statements [Consolidated Balance Sheets](index=7&type=section&id=WAVE%20LIFE%20SCIENCES%20LTD.%20UNAUDITED%20CONSOLIDATED%20BALANCE%20SHEETS) Total assets decreased to $288.3 million as of March 31, 2025, primarily due to a reduction in cash and cash equivalents Consolidated Balance Sheet Highlights (in thousands) | Metric | March 31, 2025 | December 31, 2024 | Change | | :-------------------------- | :------------- | :---------------- | :----- | | Cash and cash equivalents | $243,075 | $302,078 | $(59,003) | | Total current assets | $257,976 | $320,394 | $(62,418) | | Total assets | $288,343 | $352,207 | $(63,864) | | Total current liabilities | $87,367 | $110,953 | $(23,586) | | Total liabilities | $108,666 | $134,818 | $(26,152) | | Total shareholders' equity | $171,803 | $209,515 | $(37,712) | [Consolidated Statements of Operations and Comprehensive Loss](index=8&type=section&id=WAVE%20LIFE%20SCIENCES%20LTD.%20UNAUDITED%20CONSOLIDATED%20STATEMENTS%20OF%20OPERATIONS%20AND%20COMPREHENSIVE%20LOSS) The company reported a net loss of $46.9 million for Q1 2025, an increase from $31.6 million in the prior year quarter Consolidated Statements of Operations Highlights (in thousands) | Metric | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :---------------------------------- | :-------------------------------- | :-------------------------------- | | Revenue | $9,175 | $12,538 | | Research and development | $40,622 | $33,447 | | General and administrative | $18,357 | $13,549 | | Total operating expenses | $58,979 | $46,996 | | Loss from operations | $(49,804) | $(34,458) | | Net loss | $(46,878) | $(31,558) | | Net loss per share (basic and diluted) | $(0.29) | $(0.24) |

Core Insights - Wave Life Sciences Ltd. has made significant progress in its clinical trials, including the completion of dosing in the INLIGHT trial for obesity and positive data from the FORWARD-53 trial for Duchenne muscular dystrophy (DMD) [1][2][3] - The company is on track to deliver multiple clinical datasets in 2025, which will showcase its capabilities in RNA medicines [2] - Financial results for Q1 2025 indicate a net loss of $46.9 million, with cash and cash equivalents of $243.1 million, expected to fund operations into 2027 [6][7][14] Obesity - WVE-007, a GalNAc-conjugated siRNA, aims to induce healthy weight loss by silencing INHBE mRNA, with dosing completed in the first two cohorts of the INLIGHT trial [3][4] - The trial assesses safety, tolerability, pharmacokinetics, and metabolic health, with clinical data expected in the second half of 2025 [3][4] - WVE-007 has shown potential for significant weight loss without muscle loss, and when combined with semaglutide, it doubled weight loss [4] Alpha-1 Antitrypsin Deficiency (AATD) - WVE-006 is being evaluated in the RestorAATion-2 trial, with ongoing dosing in both single and multiple cohorts [1][3] - Data from the 200 mg multidose and single dose cohorts are expected in Q3 2025, while data from the 400 mg cohort is anticipated in fall 2025 [1][4] - The trial aims to demonstrate the safety and efficacy of WVE-006 in individuals with the PiZZ mutation [4] Duchenne Muscular Dystrophy (DMD) - WVE-N531 has shown statistically significant improvements in muscle health and function in the FORWARD-53 trial, with a 3.8-second improvement in Time-to-Rise [7] - The drug has received Orphan Drug Designation and is expected to file for accelerated approval in 2026 [7] - All participants in the trial have opted to continue into the extension phase, receiving monthly doses [7] Huntington's Disease (HD) - WVE-003 is positioned as a first-in-class treatment for HD, demonstrating allele-selective reduction of mutant HTT protein while preserving wild-type HTT [7] - The company is preparing for a potentially registrational Phase 2/3 study, with an IND submission expected in the second half of 2025 [7][5] Financial Overview - Revenue for Q1 2025 was $9.2 million, down from $12.5 million in the same quarter of the previous year [6][14] - Research and development expenses increased to $40.6 million from $33.4 million year-over-year, while general and administrative expenses rose to $18.4 million from $13.5 million [6][14] - The net loss for the quarter was $46.9 million, compared to a loss of $31.6 million in the prior year [6][14]

Core Viewpoint - Wave Life Sciences (WVE) is anticipated to report a year-over-year decline in earnings despite an increase in revenues for the quarter ended March 2025, which could significantly influence its stock price based on actual results compared to estimates [1][2]. Company Summary - The consensus estimate indicates a quarterly loss of $0.27 per share for Wave Life Sciences, reflecting a year-over-year change of -12.5%. Revenues are projected to be $13.97 million, representing an 11.4% increase from the previous year [3]. - Over the last 30 days, the consensus EPS estimate has been revised 0.43% lower, indicating a reassessment by analysts regarding the company's earnings prospects [4]. - The Most Accurate Estimate for Wave Life Sciences is lower than the Zacks Consensus Estimate, resulting in an Earnings ESP of -1.89%. The company currently holds a Zacks Rank of 3, making it challenging to predict an earnings beat [10][11]. Earnings Surprise History - In the last reported quarter, Wave Life Sciences was expected to post a loss of $0.17 per share but instead reported earnings of $0.17, resulting in a surprise of +200%. However, the company has only beaten consensus EPS estimates once in the last four quarters [12][13]. Industry Context - Rhythm Pharmaceuticals, another company in the Zacks Medical - Biomedical and Genetics industry, is expected to report a loss of $0.69 per share for the same quarter, indicating a year-over-year change of +70.6%. Its revenues are expected to be $40.18 million, up 54.7% from the previous year [17]. - The consensus EPS estimate for Rhythm Pharmaceuticals has been revised 0.7% lower in the last 30 days, leading to an Earnings ESP of -12.84% and a Zacks Rank of 3, complicating predictions for an earnings beat [18].

Company Overview - Wave Life Sciences Ltd. is a clinical-stage biotechnology company focused on RNA medicines to transform human health [3] - The company utilizes its RNA medicines platform, PRISM®, which integrates various modalities and chemistry innovations to address both rare and common disorders [3] - Wave's pipeline includes clinical programs targeting Alpha-1 antitrypsin deficiency, Duchenne muscular dystrophy, Huntington's disease, and obesity, along with several preclinical programs [3] Upcoming Events - Wave Life Sciences will host a live webcast and conference call on May 8, 2025, at 8:30 a.m. ET to review Q1 2025 financial results and provide business updates [1] - The event can be accessed via the "Investor Events" section on the company's website [2] - An archived version of the webcast will be available on the company's website following the live event [2]

Group 1 - The article discusses Wave Life Sciences Ltd. (NASDAQ: WVE) and its recent positive data for WVE-006 related to Alpha-1 Antitrypsin Deficiency (AATD), which is expected to lead to a catalyst in 2025 [2] - The author operates the Biotech Analysis Central service, which provides in-depth analysis of various pharmaceutical companies and includes a model portfolio of small and mid-cap stocks [2] - The service offers a subscription model with a promotional two-week free trial and a discounted annual plan [1] Group 2 - The article does not provide any specific financial data or performance metrics related to Wave Life Sciences or the broader biotech industry [3][4]

Company Overview - Wave Life Sciences (WVE) shares increased by 6.1% to $10.02, following a significant trading volume, contrasting with an 8.9% decline over the past four weeks [1] - The company is focused on developing treatments for Duchenne muscular dystrophy (DMD) [2] Clinical Study Results - The stock's rally was driven by positive results from the phase II FORWARD-53 study, which assessed WVE-N531 for DMD treatment [2] - The study met all objectives, showing sustained exon skipping, muscle concentrations, and dystrophin restoration over 48 weeks, with a 61-day tissue half-life supporting monthly dosing [2] - Treatment with WVE-N531 was reported to be safe and well-tolerated [2] Financial Expectations - The upcoming quarterly report is expected to show a loss of $0.26 per share, reflecting an 8.3% year-over-year decline, while revenues are projected at $13.26 million, a 5.8% increase from the previous year [3] - The consensus EPS estimate for the quarter has been revised 9.8% higher in the last 30 days, indicating potential price appreciation [4] Industry Context - Wave Life Sciences operates within the Zacks Medical - Biomedical and Genetics industry, where another company, Agios Pharmaceuticals (AGIO), has seen a 12.6% decline over the past month [4] - Agios Pharmaceuticals' EPS estimate has decreased by 5.4% over the past month, indicating a challenging outlook compared to the previous year [5]

Core Insights - Wave Life Sciences announced positive results from the Phase 2 FORWARD-53 trial of WVE-N531, demonstrating significant improvements in muscle health and function in boys with Duchenne muscular dystrophy (DMD) [1][4][10] Group 1: Trial Results - The FORWARD-53 trial achieved all goals, showing a statistically significant and clinically meaningful improvement of 3.8 seconds in Time-to-Rise (TTR) compared to natural history, the largest effect observed relative to any approved dystrophin restoration therapy at 48 weeks [1][3][12] - A 28.6% reduction in muscle fibrosis was observed between weeks 24 and 48 (p<0.01), alongside a 50% decrease in serum creatine kinase (CK) levels (p<0.001) [3][12] - Dystrophin expression stabilized between 24 and 48 weeks, averaging 7.8%, with 88% of boys achieving over 5% average dystrophin [1][8] Group 2: Safety and Tolerability - WVE-N531 was reported to be safe and well-tolerated, with no serious adverse events and all treatment-related adverse events being mild to moderate [1][8] - The trial included 11 boys, all of whom advanced to the extension portion of the study receiving monthly doses of WVE-N531 [7][8] Group 3: Regulatory and Future Plans - Following feedback from the FDA, Wave plans to file a New Drug Application (NDA) in 2026 for accelerated approval of WVE-N531, supported by data for monthly dosing [1][5][6] - Wave expects to submit multiple clinical trial applications (CTAs) for other DMD candidates targeting different exons in 2026, aiming to establish a best-in-class exon skipping franchise [1][6][10] Group 4: Market Opportunity - WVE-N531 and other exon skipping programs could address approximately 40% of the DMD population, representing a market opportunity exceeding $2.4 billion in the United States alone [6][10]