Financial Data and Key Metrics Changes - Revenue for Q2 2025 was $8.7 million, a decrease from $19.7 million in the prior year quarter, attributed to the timing of revenue recognized under the collaboration agreement with GSK [28] - Research and development expenses increased to $43.5 million from $40.4 million in the same period in 2024, driven by spending in the inhibin E program and RNA editing programs [28] - General and administrative expenses rose to $18 million from $14.3 million in the prior year quarter, primarily due to share-based compensation and other external expenses [28] - The net loss for Q2 2025 was $50.5 million, compared to a net loss of $32.9 million in the prior year quarter [28] - Cash and cash equivalents at the end of Q2 2025 were $208.5 million, down from $302.1 million as of December 31, 2024, with expectations to fund operations into 2027 [29] Business Line Data and Key Metrics Changes - The AATD clinical program is advancing with promising data from the RESTORATION trials, showing significant increases in circulating AAT levels [7][9] - The Enlight clinical program for obesity has expanded its second cohort from 8 to 32 participants due to favorable safety and tolerability results [10][11] - FORWARD 53 clinical results for DMD demonstrated a statistically significant improvement in time to rise, marking it as a best-in-class therapeutic option [13][14] Market Data and Key Metrics Changes - The company is actively engaging with the DMD community, highlighting the importance of their FORWARD 53 clinical results [12][13] - The obesity market is being targeted with the Enlight program, which is positioned to offer a differentiated approach compared to current standard care [22][24] Company Strategy and Development Direction - The company aims to unlock the potential of RNA medicines through proprietary oligonucleotide chemistry, focusing on both rare and common diseases [4][5] - Plans to initiate clinical development of new programs in 2026, with a focus on expanding their wholly owned discovery pipeline [12][25] - The strategy includes preparing for regulatory filings and engaging with the FDA for accelerated approval pathways [15][16] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the ongoing clinical programs and the potential for upcoming data readouts to inform the therapeutic pipeline [31] - The company is encouraged by the engagement from the community and clinicians regarding their AATD program, indicating a strong need for effective therapies [6][9] - Future data from the RESTORATION and Enlight trials are expected to serve as key inflection points for the company [12][25] Other Important Information - The company welcomed Dr. Chris Wright as Chief Medical Officer, bringing extensive experience in drug development [5] - The company is focused on addressing both hepatic and extrahepatic targets with their RNA editing and siRNA programs [25][26] Q&A Session Summary Question: Can you elaborate on your reasons for expanding cohort two over advancing to cohort three sooner? - The decision to expand cohort two was based on safety data indicating the ability to dose escalate, and cohort two was modeled to align with weight loss similar to semaglutide [34][36] Question: Should we expect a linear dose response, or does the preservation of lean mass offset the weight loss aspect? - The expectation is that weight loss will be driven by fat without impacting muscle, but human data will clarify the translation of these effects [38] Question: What is your guidance on the different expectations from the two data readouts for the AATD program? - The focus will be on the multidose data, which is expected to show larger liver exposure and higher protein levels compared to single doses [44][46] Question: What is the desirable knockdown level for inhibin E? - The goal is to replicate preclinical data, aiming for a knockdown that aligns with therapeutic weight loss, and the company is open to continuing dose escalation beyond cohort three [51][52] Question: Can you provide specifics on the dosing completion for the two hundred milligram multidose? - All patients in the cohort have received their seven doses, and the study remains on track for data readout in the third quarter [58][59] Question: Is there anything qualitatively about the consistency of effect for the AATD program? - The company is encouraged by the consistency observed in preclinical models and early clinical data, indicating substantial protein production [65][66]

Core Insights - Wave Life Sciences is advancing its clinical programs, particularly WVE-006 for Alpha-1 Antitrypsin Deficiency (AATD) and WVE-007 for obesity, with significant milestones expected in the coming years [1][2][3] AATD Program (WVE-006) - WVE-006 is designed to correct AAT protein and address lung and liver manifestations of AATD, with multi-dosing complete in the first cohort (200 mg) and single dosing complete in the second cohort (400 mg) [1][3] - Data from the complete 200 mg cohorts are expected in Q3 2025, while data from the 400 mg cohort are anticipated in fall 2025 [1][7] - Positive proof-of-mechanism data from a single dose of WVE-006 showed a mean total AAT protein level that met regulatory approval standards for AAT augmentation therapies [2][4] Obesity Program (WVE-007) - WVE-007 is an INHBE GalNAc-siRNA aimed at inducing fat loss while preserving muscle, with dosing complete in an expanded cohort of the INLIGHT trial [1][3] - The expansion of Cohort 2 was based on favorable safety and tolerability data, with results from both Cohort 1 and Cohort 2 expected in Q4 2025 [3][7] - Preclinical data indicated that a single dose of WVE-007 led to significant reductions in INHBE mRNA and Activin E protein, driving weight loss comparable to semaglutide [3][7] Financial Overview - As of June 30, 2025, the company reported cash and cash equivalents of $208.5 million, sufficient to fund operations into 2027 [1][9] - Revenue for Q2 2025 was $8.7 million, a decrease from $19.7 million in the same quarter of the previous year [9][20] - The net loss for Q2 2025 was $50.5 million, compared to a net loss of $32.9 million in Q2 2024 [9][20] Corporate Developments - In May 2025, the company appointed Christopher Wright, MD, PhD, as Chief Medical Officer, enhancing its leadership in global development [10] - Wave Life Sciences plans to host a Research Day in fall 2025 to share updates on its clinical and preclinical pipeline [3][7]

Core Viewpoint - Wave Life Sciences Ltd. is set to host a live webcast and conference call on July 30, 2025, to discuss its second quarter 2025 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 [3]. - The company's RNA medicines platform, PRISM®, 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]. - The company is headquartered in Cambridge, MA, and emphasizes its mission to "Reimagine Possible" in the context of human health [3]. Event Details - The webcast and conference call will be accessible via the "Investor Events" section on the Wave Life Sciences website [2]. - An archived version of the webcast will be available after the live event [2].

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]

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]

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]

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]

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]

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]