Core Insights - Wave Life Sciences announced significant progress in its clinical trial for WVE-007, demonstrating dose-dependent mean reductions of Activin E by up to 85% one month post single dose, indicating potential for effective obesity treatment [1][6] - The company is expanding its RNA editing pipeline with WVE-008, targeting PNPLA3 RNA editing for liver disease, with a Clinical Trial Application (CTA) submission anticipated in 2026 [1][5] Clinical Trial Updates - The INLIGHT clinical trial for WVE-007 showed highly significant Activin E reductions: 85% in the 400 mg cohort, 75% in the 240 mg cohort, and 56% in the 75 mg cohort, with reductions exceeding preclinical models [6] - WVE-007 is reported to be safe and well tolerated, with an independent data monitoring committee supporting dose expansion to 600 mg [6] - Future clinical data updates from the INLIGHT trial are expected, including body composition and weight data starting in Q4 2025 [6] Pipeline Developments - WVE-006 is being evaluated for alpha-1 antitrypsin deficiency (AATD), with promising results in restoring protein levels associated with lower risk of liver and lung diseases [7] - WVE-008 has been selected as a clinical candidate for PNPLA3-I148M liver disease, targeting a significant patient population in the U.S. and Europe [7] - Wave's RNA medicines platform, PRISM®, combines various modalities and innovations to address both rare and common disorders [10] Future Directions - The company plans to file a CTA for WVE-008 in 2026, aiming to achieve at least 50% correction in liver disease risk for homozygous PNPLA3-I148M individuals [7] - Wave is pioneering a new modality that combines editing and silencing in a single oligonucleotide construct, enhancing its therapeutic capabilities [12]

Core Insights - Wave Life Sciences announced significant reductions in Activin E levels of up to 85% one month after a single dose of WVE-007 in the INLIGHT clinical trial, indicating potential for effective obesity treatment [1][3][7] - The company is advancing its RNA editing pipeline with WVE-008, targeting PNPLA3-I148M liver disease, with a Clinical Trial Application (CTA) submission expected in 2026 [1][5][8] - Wave's innovative approach combines RNA editing and silencing in a single oligonucleotide construct, enhancing its therapeutic capabilities [9] Clinical Trial Updates - INLIGHT trial results showed dose-dependent Activin E reductions: 85% in Cohort 3 (400 mg), 75% in Cohort 2 (240 mg), and 56% in Cohort 1 (75 mg), all statistically significant (p<0.0001) [3][7] - The reductions in Activin E levels in the trial exceeded those observed in preclinical models, supporting the potential for WVE-007 to achieve fat loss comparable to semaglutide [7] - Follow-up data from the INLIGHT trial is expected in multiple phases, with updates on body composition and weight anticipated starting in Q4 2025 [1][7] Pipeline and Future Developments - WVE-006, an RNA editing candidate for alpha-1 antitrypsin deficiency (AATD), has shown promising results, with key treatment goals achieved and further data expected in early 2026 [8] - The company is expanding its RNA medicines pipeline, focusing on both hepatic and extra-hepatic delivery systems, which include treatments for various conditions such as obesity and liver diseases [6][10] - Wave's proprietary PRISM platform integrates multiple RNA-targeting modalities, positioning the company to address a wide range of diseases effectively [10]

Core Insights - Wave Life Sciences Ltd. is hosting a virtual Research Day on October 29, 2025, at 10:00 a.m. ET to discuss its advancements in RNA medicines [1][3] - The company will also participate in several investor conferences, including the Bernstein 2nd Annual Healthcare Forum and the Stifel Virtual Cardiometabolic Forum [2] Company Overview - Wave Life Sciences is a biotechnology company focused on RNA medicines, utilizing its PRISM® platform to address both rare and common disorders [4] - The company's RNA-targeting modalities include editing, splicing, RNA interference, and antisense silencing, which enhance its capabilities in developing therapeutic candidates [4] - Wave's pipeline includes clinical programs targeting alpha-1 antitrypsin deficiency, obesity, Duchenne muscular dystrophy, and Huntington's disease, along with several preclinical programs [4]

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]