Financial Data and Key Metrics Changes - Revenue for Q4 2024 was $83.7 million, compared to $29.1 million in Q4 2023, while full-year revenue was $108.3 million, down from $113.3 million in 2023 [35] - R&D expenses increased to $44.6 million in Q4 2024 from $34.1 million in Q4 2023, and for the full year, R&D expenses rose to $159.7 million from $130.0 million [35] - Net income for Q4 2024 was $29 million, compared to a net loss of $16.3 million in Q4 2023, while the full-year net loss was $96.7 million, up from $57.5 million in 2023 [35][36] - Cash and cash equivalents at year-end 2024 were $302.1 million, compared to $200.4 million at the end of 2023, primarily due to financing proceeds and milestone payments [36] Business Line Data and Key Metrics Changes - The company advanced its pipeline with WVE-007 for obesity, which is expected to provide a unique mechanism of action with dosing just once or twice a year [7][10] - WVE-006 for AATD demonstrated a mean 6.9% micromolar circulating AAT and 10.8% micromolar total AAT two weeks post single dose in the first patient study, indicating a favorable safety profile [12] - In DMD, WVE-531 showed a mean muscle content adjusted dystrophin of 9%, with a well-tolerated profile, and the company is on track to deliver 48-week data by the end of the month [15][17] Market Data and Key Metrics Changes - The obesity treatment market is highlighted as having over 1 billion people affected globally, with WVE-007 positioned to address limitations of current GLP-1 therapies [9][10] - Huntington's disease impacts more than 200,000 people in the US and Europe, with the company emphasizing the need for early intervention therapies [18][64] Company Strategy and Development Direction - The company is focused on RNA medicines, with a commitment to advancing its pipeline and addressing high unmet needs in various therapeutic areas [6][14] - WVE-007 is positioned as an alternative to GLP-1 therapies, focusing on peripheral action to avoid disadvantages associated with centrally acting drugs [29] - The company plans to initiate clinical development of additional RNA editing programs in 2026, expanding its therapeutic offerings [14][32] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the progress made in 2024 and the potential for multiple value-accretive milestones in 2025 across all clinical programs [38] - The management highlighted the importance of engaging with the obesity community and clinicians to combat disease stigma and improve treatment outcomes [8] - The company anticipates that its current cash reserves will fund operations into 2027, excluding potential future milestone payments [36] Other Important Information - The company has seen a surge in enrollment and demand for its clinical studies, particularly for WVE-006, indicating strong interest from both clinicians and patients [13] - The management emphasized the unique aspects of their RNA editing technology compared to traditional DNA editing, highlighting the safety and efficacy of their approach [12][85] Q&A Session Summary Question: Can you provide more information on WVE-006's baseline protein levels? - Management noted that the baseline was below the lower limit of detection, and emphasized tracking M-protein levels as a key indicator of therapeutic impact [40][42] Question: Regarding WVE-007, how will DEXA scanning be utilized in the study? - Management confirmed that DEXA scans will be used to assess fat loss versus muscle mass changes, with the goal of demonstrating healthy weight loss [47][48] Question: What are the expectations for the upcoming DMD data readout? - Management indicated that discussions with regulators are ongoing, and they expect to provide updates on both the 24-week and 48-week data [52][56] Question: How does the company view the potential for mutant huntingtin lowering as a surrogate endpoint in Huntington's disease? - Management expressed that if the FDA accepts this as a clinical surrogate, they would be positioned to file based on existing data showing significant mutant huntingtin reductions [61][62] Question: What has changed regarding the prevalence of Huntington's disease? - Management explained that recent research has shown that the disease begins before symptom onset, leading to a higher estimated prevalence than previously thought [64][66]

Financial Performance - The company reported net losses of $97.0 million, $57.5 million, and $161.8 million for the fiscal years ended December 31, 2024, 2023, and 2022, respectively, with an accumulated deficit of $1,121.9 million as of December 31, 2024[275]. - The company has not generated any product revenue to date and does not expect to do so in the foreseeable future, leading to continued significant operating losses[276]. - The company has received approximately $1,578.4 million in net proceeds from sales of securities and collaborations through December 31, 2024, including $977.8 million from public offerings and $511.3 million from collaborations[280]. - The company anticipates that its existing cash and cash equivalents will be sufficient to fund operations for at least the next 12 months[277]. - The company has never declared or paid cash dividends on its ordinary shares and does not anticipate doing so in the foreseeable future[460]. Capital Requirements and Funding - The company filed a shelf registration statement for the sale of up to $250.0 million in ordinary shares, allowing for potential future capital raising[281]. - The company’s future capital requirements are uncertain and will depend on various factors, including monthly spending levels and the progress of drug discovery and clinical development[279]. - The company relies on third parties for raw materials and clinical trials, which may be disrupted by local or global health epidemics, affecting research and development activities[289]. - The company faces risks related to macroeconomic conditions, including inflation and volatility in interest rates, which could impact its ability to raise additional funding[284]. Research and Development Challenges - The company has not yet demonstrated the ability to successfully complete pivotal clinical trials or obtain marketing approvals necessary for product commercialization[287]. - The company’s RNA medicines platform, PRISM, aims to target genetically defined diseases but has not yet completed successful clinical development of an oligonucleotide therapeutic[291]. - The company has invested significantly in the development of its RNA medicines platform, PRISM, and has no products currently on the market, with revenue generation expected to be many years away[295]. - The company has a diverse pipeline including clinical programs in AATD, DMD, HD, and obesity, but the success of these programs is uncertain[294]. - The company experienced a discontinuation of the WVE-004 program after Phase 1b/2a study results showed no clinical benefit, highlighting the high failure rate in drug development[312]. Regulatory and Compliance Risks - Regulatory approval processes for product candidates are extensive and costly, with unpredictable timelines that can materially impair revenue generation[319]. - The company must submit a diversity action plan for future Phase 3 trials, which may affect planning and recruitment of diverse patient populations[315]. - Regulatory authorities may suspend clinical trials if unacceptable health risks are identified, impacting the approval process for product candidates[307]. - The company is subject to ongoing regulatory oversight for marketed drugs, which includes compliance with U.S. and foreign requirements, and failure to comply could result in penalties or withdrawal of approvals[325]. Manufacturing and Supply Chain Issues - Manufacturing capabilities are being developed at a 90,000 square foot facility in Lexington, Massachusetts, which began cGMP manufacturing in early 2018[299]. - The company faces risks related to the complexity of oligonucleotide manufacturing, including potential delays and quality control issues[301]. - The company’s ability to manufacture product candidates may be hindered by supply chain disruptions, particularly for raw materials sourced from international suppliers[300]. - Increased competition for raw materials necessary for oligonucleotide production could severely impact manufacturing capabilities[376]. Market and Competitive Landscape - The pharmaceutical industry is highly competitive, with many large companies and research organizations targeting the same diseases, which could affect the company's ability to commercialize its drugs successfully[330]. - Competitors may have advantages such as greater financial resources, more extensive experience, and established products, which could adversely affect the company's competitive position[333]. - Market acceptance of the company's product candidates may be hindered, as key participants in the pharmaceutical marketplace may not adopt new technologies based on oligonucleotides[328]. Intellectual Property and Legal Risks - The company faces risks related to obtaining and enforcing market exclusivity for its technologies and product candidates, which is critical for maintaining commercial value[400]. - Legal issues regarding the patentability of biopharmaceuticals may create uncertainty and affect the company's ability to protect its intellectual property rights[401]. - The company may face challenges from third parties regarding its patent rights, which could adversely affect its ability to develop and commercialize its products[407]. - The company relies on trade secrets and confidential information for competitive advantage, but breaches of confidentiality agreements could harm its position[422]. International Operations and Taxation - The company faces risks associated with international operations, including regulatory changes and geopolitical instability, which could adversely affect its business[360]. - The company is subject to income and other taxes in the United States and foreign jurisdictions, and future changes in tax laws may adversely affect its business and financial condition[395]. - The company may be classified as a passive foreign investment company (PFIC), potentially resulting in adverse U.S. federal income tax consequences for U.S. holders[437]. Collaboration and Dependency Risks - The company commenced a collaboration with GSK in January 2023 to research, develop, and commercialize oligonucleotide therapeutics, including WVE-006, its first-in-class A-to-I(G) RNA editing candidate for AATD[365]. - Future revenues may heavily depend on the success of third-party collaborators, such as GSK, which is responsible for later clinical development and commercialization of the AATD program[369]. - The company relies on third-party collaborators for the development and commercialization of certain product candidates, which may limit control over resources and timelines[366].

Exhibit 99.1 Wave Life Sciences Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Update Dosing underway in INLIGHT trial of WVE-007 in obesity with clinical data expected in 2H 2025; enrollment complete in first single dose cohort Multi-dosing ongoing in 200 mg cohort of RestorAATion-2 clinical trial of WVE-006 in AATD with data expected in 2025; second single dose cohort initiated at 400 mg Recent Business Highlights and Expected Milestones GalNAc-siRNA Programs Obesity • W ...

Core Insights - Wave Life Sciences Ltd. has initiated dosing in the INLIGHT trial for WVE-007, targeting obesity, with clinical data expected in the second half of 2025 [2][3] - The company is advancing its clinical studies for WVE-006 in Alpha-1 antitrypsin deficiency (AATD) and WVE-N531 in Duchenne muscular dystrophy (DMD), with significant data anticipated in 2025 [2][3][6] - Financially, Wave reported cash and cash equivalents of $302.1 million as of December 31, 2024, providing a runway into 2027 [8][11] GalNAc-siRNA Programs - WVE-007 is designed to silence INHBE mRNA, showing potential for significant weight loss comparable to semaglutide, with a single dose leading to weight loss without muscle loss [3] - The INLIGHT trial is a first-in-human, placebo-controlled study assessing safety, tolerability, and metabolic health in adults with obesity, with enrollment in the first single dose cohort completed [3] - Expected clinical data from INLIGHT will include safety and biomarkers reflective of healthy weight loss, anticipated in the second half of 2025 [3] AATD and RNA Editing Programs - WVE-006 is a GalNAc-conjugated oligonucleotide targeting AATD, with ongoing multi-dosing in the RestorAATion-2 clinical trial [6] - Initial proof-of-mechanism data from WVE-006 demonstrated a mean circulating wild-type M-AAT protein level of 6.9 micromolar, representing over 60% of total AAT [6] - Multi-dose data for WVE-006 is expected to be shared in 2025, with the potential for extended dosing intervals [6] DMD Programs - WVE-N531 is an exon skipping oligonucleotide for DMD, with ongoing trials showing positive interim results, including a mean dystrophin expression of 9.0% [6] - The FORWARD-53 trial is evaluating the safety and efficacy of WVE-N531, with 48-week data and regulatory feedback expected in the first quarter of 2025 [6] Financial Highlights - Revenue for the fourth quarter of 2024 was $83.7 million, up from $29.1 million in the prior year quarter, while total revenue for 2024 was $108.3 million compared to $113.3 million in 2023 [11] - Research and development expenses increased to $44.6 million in Q4 2024 from $34.1 million in Q4 2023, with full-year expenses at $159.7 million compared to $130.0 million in 2023 [11] - The net income for Q4 2024 was $29.3 million, a significant improvement from a net loss of $16.3 million in the same quarter of the previous year [11]

Core Viewpoint - Wave Life Sciences Ltd. is set to host a live webcast and conference call on March 4, 2025, to discuss its fourth quarter and full year 2024 financial results and provide business updates [1]. Company Overview - Wave Life Sciences is a clinical-stage biotechnology company focused on RNA medicines aimed at transforming human health [4]. - The company's RNA medicines platform, PRISM, integrates various modalities, chemistry innovations, and insights from human genetics to achieve scientific breakthroughs for treating both rare and common disorders [4]. - Wave's RNA-targeting modalities include editing, splicing, RNA interference, and antisense silencing, which enhance its capabilities in designing and delivering therapeutic candidates [4]. - The company's diversified pipeline includes clinical programs targeting Alpha-1 antitrypsin deficiency, Duchenne muscular dystrophy, Huntington's disease, and obesity, along with several preclinical programs [4]. - Wave Life Sciences is driven by the mission to "Reimagine Possible," aiming to alleviate the burden of disease on human potential [4].

Core Insights - Wave Life Sciences Ltd. has initiated the Phase 1 INLIGHT clinical trial for WVE-007, a novel GalNAc-siRNA targeting INHBE mRNA, aimed at treating obesity with a focus on healthy weight loss and muscle preservation [1][2] - The company anticipates proof-of-concept clinical data from the INLIGHT trial to be available in 2025, which will include safety, tolerability, and biomarkers for healthy weight loss [2][3] Company Overview - Wave Life Sciences is a clinical-stage biotechnology company focused on RNA medicines, utilizing its PRISM® platform to develop treatments for both rare and common disorders [4] - The company's pipeline includes clinical programs targeting Alpha-1 antitrypsin deficiency, Duchenne muscular dystrophy, Huntington's disease, and obesity, showcasing its diverse approach to RNA therapeutics [4] Product Details - WVE-007 is designed to directly impact fat cells, promoting weight reduction while maintaining muscle mass and improving cardiometabolic health outcomes [2][3] - The mechanism of WVE-007 involves silencing INHBE mRNA, which encodes a protein that inhibits fat burning, thereby potentially inducing a healthier metabolic profile [3] Market Potential - WVE-007 is positioned to address the global obesity epidemic, with over 1 billion individuals affected worldwide, and offers the potential for infrequent dosing (once or twice a year) [2][3]

Core Insights - Wave Life Sciences Ltd. is advancing its RNA medicines platform with significant milestones expected in 2025, focusing on clinical programs for Duchenne Muscular Dystrophy (DMD), Huntington's Disease (HD), Alpha-1 Antitrypsin Deficiency (AATD), and obesity treatments [1][2][11] Clinical Programs - The company has submitted Clinical Trial Applications (CTAs) for the Phase 1 INLIGHT clinical trial of WVE-007, targeting obesity through a novel GalNAc-siRNA approach, with proof-of-concept data anticipated in 2025 [1][3] - WVE-006 has shown promising proof-of-mechanism data in AATD, with a mean total AAT protein increase to 10.8 micromolar, meeting regulatory approval levels for AAT augmentation therapies [7][8] - The FORWARD-53 trial for WVE-N531 in DMD is ongoing, with interim results showing a mean muscle content-adjusted dystrophin expression of 9.0%, and 48-week data expected in Q1 2025 [7][8] - WVE-003, an allele-selective treatment for HD, has demonstrated a reduction in mutant huntingtin protein and preservation of healthy huntingtin, with plans for a registrational Phase 2/3 study [8][13] Pipeline and Future Plans - The company is expanding its GalNAc-AIMer pipeline and plans to share multidose data for WVE-006 in 2025, along with new preclinical data from hepatic and extra-hepatic RNA editing programs [4][7] - Wave expects to initiate clinical development of additional RNA editing programs, including PNPLA3, LDLR, and APOB, in 2026 [7] - The company is well-capitalized, with a cash runway expected to last into 2027, allowing for continued investment in its clinical programs [9] Upcoming Events - The CEO of Wave Life Sciences is scheduled to present at the 43rd Annual J.P. Morgan Healthcare Conference on January 13, 2025, highlighting the company's advancements and future strategies [10]

Company Overview - Wave Life Sciences Ltd. (NASDAQ: WVE) specializes in developing stereopure oligonucleotides through its PRISM platform, aimed at targeting disease-causing genetic mutations [1] - Stereopure molecules are characterized by precise control over stereochemistry at each chiral center, enhancing both efficacy and safety of the molecules [1] Services Offered - The Total Pharma Tracker provides tools for DIY investors, including a software that allows users to enter any ticker for extensive curated research material [2] - For investors seeking hands-on support, in-house experts analyze tools to identify the best investable stocks, along with buy/sell strategies and alerts [2]

Core Insights - Wave Life Sciences Ltd. has submitted its first clinical trial application (CTA) for WVE-007, an investigational GalNAc-conjugated small interfering RNA (siRNA) aimed at treating obesity by silencing the INHBE gene [4] - The company anticipates approval of the CTA and initiation of the first-in-human study in the first quarter of 2025 [4][8] - WVE-007 is designed to promote fat burning while preserving muscle mass, with the potential for once or twice-annual dosing [5][8] Company Overview - Wave Life Sciences is a clinical-stage biotechnology company focused on RNA medicines, utilizing its PRISM® platform to develop treatments for various disorders [7] - The company’s pipeline includes clinical programs targeting Duchenne muscular dystrophy, Alpha-1 antitrypsin deficiency, and Huntington's disease, alongside a preclinical program in obesity [7] Product Details - WVE-007 aims to induce a healthy metabolic profile by silencing the INHBE gene, which has shown promising results in preclinical studies, including weight loss comparable to semaglutide without muscle loss [5][6] - In preclinical trials, a single dose of WVE-007 led to significant weight loss and prevented weight regain when combined with semaglutide [5] Clinical Trial Information - The first-in-human study of WVE-007 will be a Phase 1 clinical trial focusing on safety, tolerability, pharmacokinetics, and metabolic health in adults with overweight or obesity [6]

Company Overview - Wave Life Sciences Ltd. is a clinical-stage biotechnology company focused on RNA medicines aimed at transforming human health [1][3] - The company utilizes its RNA medicines platform, PRISM®, which integrates various modalities and innovations in chemistry to address both rare and prevalent disorders [3] Upcoming Event - Paul Bolno, MD, MBA, President and CEO of Wave Life Sciences, is scheduled to present at the 43rd Annual J.P. Morgan Healthcare Conference on January 13, 2025, at 9:45 a.m. PT / 12:45 p.m. ET [1] Pipeline and Research Focus - Wave Life Sciences has a diversified pipeline that includes clinical programs targeting Duchenne muscular dystrophy, Alpha-1 antitrypsin deficiency, and Huntington’s disease, along with a preclinical program in obesity [3] - The company aims to leverage its RNA-targeting modalities, which include editing, splicing, RNA interference, and antisense silencing, to develop effective treatments [3]