Core Viewpoint - Wave Life Sciences Ltd. presents promising preclinical data for its candidate drug WVE-007, which targets INHBE mRNA to reduce fat mass without compromising muscle quality, potentially lowering the risk of metabolic diseases such as type 2 diabetes and coronary artery disease [1][7]. Group 1: Mechanism and Efficacy - WVE-007 is a GalNAc-modified siRNA that significantly downregulates INHBE mRNA and its product Activin E protein, which inhibits fat breakdown in obesity [2]. - A single administration of WVE-007 results in weight loss comparable to the widely used GLP-1 receptor agonist semaglutide [3]. - The drug effectively reduces visceral fat, decreases adipocyte size, and preserves muscle mass, supporting weight loss through the restoration of adipose tissue function [4]. Group 2: Inflammatory Response - WVE-007 significantly inhibits the recruitment of pro-inflammatory M1 macrophages while maintaining levels of anti-inflammatory M2 macrophages, demonstrating strong anti-inflammatory potential [5]. Group 3: Combination and Maintenance Therapy - When used in conjunction with semaglutide, INHBE-siRNA can double the weight loss effect, indicating a synergistic therapeutic potential [6]. - After discontinuation of semaglutide, INHBE-siRNA significantly slows weight regain, suggesting it could serve as a maintenance or transitional therapy for GLP-1 treatments [7]. Group 4: Genetic Insights and Future Prospects - Individuals carrying INHBE gene loss-of-function variants often exhibit healthier metabolic profiles, including reduced abdominal fat, lower triglyceride levels, and decreased risks of type 2 diabetes and cardiovascular diseases [7]. - The Chief Scientific Officer of Wave emphasizes that if clinical trials confirm these mechanisms, WVE-007 could revolutionize obesity treatment by offering a new pathway that requires only one to two injections per year for healthy weight loss while preserving muscle mass [7].

Core Insights - Wave Life Sciences Ltd. presented preclinical data supporting WVE-007, a GalNAc-siRNA targeting INHBE mRNA, as a potential novel treatment for obesity, demonstrating significant weight loss and muscle preservation [1][2][3] - The data indicate that WVE-007 can reduce inflammation in adipose tissue and lower pro-inflammatory M1 macrophages, suggesting a mechanism for reducing risks associated with type 2 diabetes (T2D) and coronary artery disease (CAD) [1][2] Group 1: Preclinical Data and Mechanism - A single dose of INHBE siRNA resulted in a robust reduction of INHBE mRNA and Activin E protein, leading to weight loss primarily through fat mass reduction [3] - The treatment showed a decrease in visceral adipose mass and preserved muscle mass, indicating a restoration of healthy adipose tissue [3] - INHBE siRNA significantly reduced the infiltration of activated macrophages in visceral adipose tissue, shifting the inflammatory state towards a less pro-inflammatory profile [3] Group 2: Clinical Implications and Future Trials - WVE-007 is being evaluated in the ongoing INLIGHT clinical trial for adults with overweight or obesity, with initial clinical data expected in the second half of the year [2] - The therapeutic profile of WVE-007 is differentiated from existing treatments like GLP-1s, as it operates through a unique mechanism that does not impact appetite directly [2] - The potential for infrequent dosing of WVE-007, possibly once or twice a year, could transform the obesity treatment landscape [2] Group 3: Genetic Evidence and Therapeutic Target - Human genetics strongly supports INHBE as a therapeutic target, with individuals carrying a protective loss-of-function variant showing a healthier cardiometabolic profile [2] - These carriers exhibit lower abdominal fat, triglycerides, and reduced risk of T2D and cardiovascular disease, reinforcing the relevance of targeting INHBE [2] Group 4: Company Overview - Wave Life Sciences is focused on RNA medicines, utilizing its PRISM platform to develop treatments for various disorders, including obesity [5] - The company aims to deliver scientific breakthroughs through its diverse pipeline, which includes clinical programs targeting multiple diseases [5]

Summary of Wave Life Sciences Conference Call Company Overview - **Company**: Wave Life Sciences (WVE) - **Event**: 2025 Jefferies Global Healthcare Conference - **Date**: June 04, 2025 Key Points Industry and Pipeline - Wave Life Sciences is focused on RNA editing, aiming to establish a new category of medicine with its unique chemistry [5][6] - The company has multiple pipeline programs, with a lead program targeting alpha-one antitrypsin deficiency (ATD) [3][4] Alpha-One Antitrypsin Program - Upcoming data sets include a 200 mg cohort in Q2 and a 400 mg cohort later in the year [4][8] - Initial data showed therapeutic levels of alpha-one antitrypsin protein, with 11 micromolar total protein and 7 micromolar of the edited M protein [5][6] - The program aims to demonstrate the potential for monthly dosing based on the observed protein production [6][8] - The collaboration with GSK includes over $520 million in milestones and $2.3 billion in total milestones related to the RNA editing pipeline [18][19] Obesity Program - The obesity program (HIBE) is in Phase 1, with data expected later this year [21][22] - The study includes subtherapeutic and therapeutic cohorts, with a focus on weight loss mechanisms and safety [22][26] - Inhibin E is highlighted for its potential to drive fat loss without muscle loss, showing a favorable metabolic profile in heterozygous patients [25][26][28] DMD and Huntington's Disease Programs - For Duchenne Muscular Dystrophy (DMD), discussions with the FDA are ongoing regarding accelerated approval based on dystrophin expression and muscle health data [39][40] - The company is also preparing for a pivotal trial for Huntington's disease, utilizing natural history data to measure patient progression [42][43] Regulatory Environment - The regulatory landscape for Huntington's disease is evolving, with potential changes in endpoints that could benefit Wave Life Sciences [43][44] - The company is positioned to adapt to changes in regulatory expectations, particularly regarding mutant huntingtin as a clinical surrogate endpoint [44] Additional Insights - The focus on RNA editing and the unique delivery mechanisms may differentiate Wave Life Sciences from other companies in the siRNA space [31][32] - The potential for once or twice a year dosing in obesity treatment could significantly expand market opportunities [36][37] - The emphasis on safety, tolerability, and target engagement in clinical trials is critical for advancing the pipeline [28][30]

Core Insights - Wave Life Sciences Ltd. is a clinical-stage biotechnology company focused on RNA medicines aimed at transforming human health [3] - The company will participate in the 2025 Jefferies Global Healthcare Conference on June 4, 2025, with CEO Paul Bolno leading an analyst-led fireside chat [1] Company Overview - Wave Life Sciences utilizes its RNA medicines platform, PRISM, which integrates various modalities and chemistry innovations to address both rare and common disorders [3] - The company's pipeline includes clinical programs targeting Alpha-1 antitrypsin deficiency, Duchenne muscular dystrophy, Huntington's disease, and obesity, along with several preclinical programs [3] - Wave Life Sciences is headquartered in Cambridge, MA, and aims to "Reimagine Possible" by alleviating the burden of disease on human potential [3]

Core Insights - Wave Life Sciences Ltd. has appointed Dr. Christopher Wright as Chief Medical Officer to lead the clinical development of its RNA medicines pipeline [1][2] - Dr. Wright brings extensive experience in global development, having worked with regulatory agencies in both the US and EU, and has a strong track record in drug development for various diseases [2][3] - The company has a robust therapeutic pipeline and has delivered positive clinical datasets over the past year, indicating the potential of its RNA medicines [4] Company Overview - Wave Life Sciences is a biotechnology company focused on RNA medicines, utilizing its PRISM platform to address both rare and common disorders [5] - The company's RNA-targeting modalities include editing, splicing, RNA interference, and antisense silencing, providing a comprehensive toolkit for disease treatment [5] - Wave's pipeline includes clinical programs for Alpha-1 antitrypsin deficiency, Duchenne muscular dystrophy, Huntington's disease, and obesity, along with several preclinical programs [5] Leadership Background - Dr. Wright has held significant roles in various biotechnology companies, including CMO at Ring Therapeutics and AavantiBio, and has experience in leading global development functions [2][3] - He has a strong academic background, having served as a board-certified neurologist and Associate Professor of Neurology at Harvard Medical School [3] Equity Grant - In connection with his appointment, Dr. Wright received a share option to purchase 300,000 ordinary shares of Wave, with an exercise price of $5.94 per share, vesting over four years [4]

分组1 - Wave Life Sciences reported a quarterly loss of $0.29 per share, which was worse than the Zacks Consensus Estimate of a loss of $0.27, and compared to a loss of $0.24 per share a year ago, indicating an earnings surprise of -7.41% [1] - The company posted revenues of $9.18 million for the quarter ended March 2025, missing the Zacks Consensus Estimate by 34.33%, and down from $12.54 million in the same quarter last year [2] - Wave Life Sciences shares have declined approximately 47.5% since the beginning of the year, contrasting with the S&P 500's decline of -4.3% [3] 分组2 - The current consensus EPS estimate for the upcoming quarter is -$0.25 on revenues of $18.12 million, and for the current fiscal year, it is -$1.01 on revenues of $66.47 million [7] - The Zacks Industry Rank for Medical - Biomedical and Genetics is in the top 33% of over 250 Zacks industries, suggesting that the industry outlook can significantly impact stock performance [8]

Financial Data and Key Metrics Changes - Revenue for Q1 2025 was $9.2 million, down from $12.5 million in the same quarter last year, attributed to the timing of revenue recognition under the collaboration agreement with GSK [34] - 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 [34] - General and administrative expenses rose to $18.4 million from $13.5 million, primarily due to share-based compensation and professional fees [35] - The 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, with expectations to fund operations into 2027 [36] Business Line Data and Key Metrics Changes - The company is advancing its clinical pipeline, particularly in obesity and AATD (Alpha-1 Antitrypsin Deficiency) programs, with significant progress reported in clinical trials [7][9] - WVE-007 for obesity is designed to provide sustainable weight loss with infrequent dosing, showing promising preclinical data [10][28] - WVE-006 for AATD aims to be the first treatment addressing the root cause of the disease, with ongoing trials demonstrating well-tolerated results and potential for extended dosing intervals [12][14] Market Data and Key Metrics Changes - The obesity treatment market is seeing rapid advancements, with WVE-007 positioned to compete against GLP-1s, which have limitations such as frequent dosing and side effects [10][29] - The DMD (Duchenne Muscular Dystrophy) market has an urgent need for effective therapies, with approximately 20,000 new cases annually and a significant portion of patients remaining untreated [19][20] - The company reported that sales of exon skipping therapies reached approximately $1.1 billion in 2024, highlighting the market potential for its DMD treatment [20] Company Strategy and Development Direction - The company is focused on unlocking the potential of RNA medicines, with a multimodal pipeline that includes programs for obesity, AATD, DMD, and Huntington's disease [7][8] - Plans to submit an NDA for WVE-531 in 2026 for accelerated approval, emphasizing the importance of dystrophin expression as a surrogate endpoint [21][84] - The company aims to differentiate its therapies by demonstrating comprehensive clinical benefits, including muscle health improvements and reduced fibrosis [75] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ongoing clinical trials and the potential for significant milestones throughout 2025, including data on healthy weight loss and RNA editing [38] - The company is actively engaging with the FDA regarding its accelerated approval pathways and is committed to providing comprehensive data to support its filings [44][86] - There is a recognition of the evolving landscape in gene therapy and the need for effective communication with clinicians regarding treatment options for DMD [93] Other Important Information - The company is advancing a wholly owned discovery pipeline addressing both hepatic and extrahepatic targets, with plans to initiate clinical development of new programs in 2026 [30][33] - Upcoming data presentations at medical meetings are expected to provide insights into the efficacy and safety of the company's RNA editing programs [16][32] Q&A Session Summary Question: What triggers data disclosure for the Inhibin 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 data analysis [40][42] Question: Are all drugs slated for accelerated approval under CDER? - Yes, the company confirmed that its drugs are under CDER, and discussions with the agency have remained consistent regarding the accelerated approval pathway [43][84] Question: What are the benefits of RNA editing versus DNA editing for AATD? - RNA editing avoids bystander edits and potential irreversible collateral effects associated with DNA editing, making it a safer option for patients [57][60] Question: How many additional DMD patients are needed for the monthly dosing regimen? - The company is currently enrolling patients and expects to provide updates on the number needed for the monthly dosing regimen [91][92] Question: Is the plan for using dystrophin expression for accelerated approval locked in? - The agency has indicated that dystrophin is a clinical surrogate endpoint for accelerated approval, but there is always a risk of changes with new leadership at the agency [84][86]

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)