Summary of Wave Life Sciences Conference Call Company Overview - **Company**: Wave Life Sciences (NasdaqGM: WVE) - **Focus**: Building a fully integrated RNA medicines company capable of unlocking the potential of genetic medicines, particularly in RNA editing and siRNA technologies [3][4][39] Key Programs and Developments 1. Inhibin E (WVE-007) - **Target**: Obesity, focusing on fat loss without impacting lean mass - **Mechanism**: Utilizes siRNA to knock down inhibin E, leading to significant fat loss while preserving muscle mass - **Preclinical Results**: Demonstrated a 70% reduction in activin E levels in DIO mice, translating to fat loss equivalent to GLP-1s without affecting lean mass [10][12][13] - **Clinical Data**: - 75 mg cohort showed a 55% reduction in activin E sustained over six months - 240 mg cohort achieved a 75% reduction at day 29, with ongoing decline [13][14] - **Future Outlook**: Q4 will provide three-month data on the 240 mg cohort, with further insights expected in Q1 2026 [14][20] 2. Alpha-1 Antitrypsin Deficiency (AATD) - **Mechanism**: RNA editing to convert Z protein to M protein, enhancing protein levels in patients - **Clinical Results**: At the lowest dose, patients showed a return to near-normal levels of total protein, with significant increases in M protein [32][34] - **Upcoming Data**: Focus on the 400 mg dose cohort to assess durability and editing efficiency [32][37] 3. PNPLA3 Program (WVE-008) - **Target**: Liver disease associated with homozygous mutations - **Potential Impact**: Could address a large patient population (approximately 9 million) at risk of liver diseases, with a unique mechanism that siRNAs cannot treat [39][40] Industry Context and Market Opportunity - **Obesity Treatment Landscape**: The company aims to shift the paradigm in obesity treatment from frequent dosing (weekly/monthly) to potentially once or twice a year with their siRNA therapies, addressing a significant global health issue [27][28] - **Market Size**: The global obesity market presents a substantial opportunity, with the potential to treat a billion patients worldwide [27] Important Considerations - **Kinetics of Fat Loss**: The company emphasizes the importance of understanding the kinetics of fat loss versus total weight loss, particularly in the context of preserving muscle mass [18][19][21] - **Regulatory Perspective**: The FDA's framing of healthy weight loss has influenced the company's approach to defining success in their clinical trials [17][18] Conclusion - Wave Life Sciences is positioned to make significant advancements in genetic medicine, particularly in obesity and liver disease, with promising data expected in the near future. The focus on innovative RNA technologies and the potential for long-term treatment regimens could disrupt current treatment paradigms in these areas [39][40]

WVE-007, an INHBE GalNAc-siRNA for obesity designed to drive fat loss while preserving muscle mass, achieved dose-dependent, mean reductions of Activin E of up to 85% in INLIGHT clinical trial, exceeding levels that led to weight loss and prevention of rebound weight gain following cessation of GLP-1 in preclinical models Activin E reduction in lowest single dose cohort of INLIGHT was sustained through six months, supporting once or twice a year dosing Achieved key AATD treatment goals to recapitulate the ...

Core Insights - Wave Life Sciences Ltd. is a clinical-stage biotechnology company focused on RNA medicines aimed at transforming human health [1][3] - The company will participate in two investor conferences in November 2025, showcasing its leadership and ongoing projects [2] Conference Participation - At the Guggenheim Annual Healthcare Innovation Conference on November 11, 2025, Paul Bolno, MD, MBA, President and CEO, will engage in an analyst-led fireside chat at 10:00 a.m. ET [2] - At the Jefferies London Healthcare Conference on November 20, 2025, Dr. Bolno will participate in an analyst-led fireside chat at 8:30 a.m. GMT / 3:30 a.m. ET and in the "Anti-Obesity Panel" at 9:00 a.m. GMT / 4:00 a.m. ET [2] Company Overview - Wave Life Sciences utilizes its RNA medicines platform, PRISM, which integrates various modalities and innovations in chemistry to address both rare and common disorders [3] - The company's pipeline includes clinical programs targeting obesity, alpha-1 antitrypsin deficiency, Duchenne muscular dystrophy, and Huntington's disease, along with several preclinical programs [3] - Wave Life Sciences is headquartered in Cambridge, MA, and is committed to advancing human health by overcoming disease burdens [3]

Core Insights - Wave Life Sciences Ltd. presented preclinical data for WVE-007, a GalNAc-siRNA therapeutic aimed at treating obesity by promoting fat loss while preserving muscle mass with infrequent dosing [1][3][12] - The investigational therapy demonstrated significant reductions in Activin E levels, leading to weight loss and improved metabolic health in preclinical models and ongoing clinical trials [1][7][14] Group 1: Preclinical Data and Mechanism - WVE-007 targets INHBE mRNA, which is linked to lower levels of unhealthy visceral fat and reduced risk of type 2 diabetes and cardiovascular disease [2][3] - In preclinical studies, WVE-007 resulted in adipocyte shrinkage, decreased pro-inflammatory macrophages, reduced fibrosis, and enhanced insulin sensitivity in visceral adipose tissue [1][14] - The treatment showed a significant weight loss effect in mice, with no loss of skeletal muscle mass, indicating a healthy weight loss profile [5][14] Group 2: Clinical Trial Progress - The ongoing INLIGHT clinical trial is evaluating WVE-007 in adults with overweight or obesity, focusing on safety, tolerability, and metabolic health [11] - Recent data from the trial showed dose-dependent reductions in Activin E levels, with reductions of up to 85% observed one month after a single dose [7][11] - The treatment was reported to be safe and well-tolerated, leading to the expansion of dosing cohorts in the trial [8][11] Group 3: Future Expectations - Wave Life Sciences anticipates multiple clinical data updates from the INLIGHT trial, including body composition and weight data, starting in Q4 2025 [9] - The company aims to demonstrate the potential for WVE-007 to provide effective obesity treatment with infrequent dosing, potentially only once or twice a year [3][9]

CAMBRIDGE, Mass., Nov. 04, 2025 (GLOBE NEWSWIRE) -- Wave Life Sciences Ltd. (Nasdaq: WVE), a clinical-stage biotechnology company focused on unlocking the broad potential of RNA medicines to transform human health, will host a live webcast and conference call at 8:30 a.m. ET on Monday, November 10, 2025, to review the company’s third quarter 2025 financial results and provide business updates. The webcast and conference call may be accessed by visiting “Investor Events” on the investors section of the Wave ...

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]