Summary of Wave Life Sciences FY Conference Call Company Overview - **Company**: Wave Life Sciences (NasdaqGM: WVE) - **Industry**: RNA medicines, focusing on oligonucleotides, RNA editing, and genetic targets [3][4] Core Points and Arguments RNA Medicines and Pipeline - Wave Life Sciences is positioned at the forefront of RNA medicines, utilizing a proprietary chemistry engine to accelerate the development of oligonucleotides, including siRNA and RNA editing [3] - The company has successfully progressed from identifying genetic targets to generating meaningful human therapeutic data within 24 months, exemplified by their INHBE program for obesity [3] Alpha-1 Antitrypsin Program (WVE-006) - WVE-006 is the first RNA editing program to enter clinical trials, targeting alpha-1 antitrypsin deficiency [5] - The program achieved approximately 65% editing on protein levels, with a notable increase in protein response during acute exacerbations, demonstrating the potential for effective treatment [6][10] - The treatment paradigm is shifting from traditional IV protein replacement therapy to a more sustainable editing approach that can generate protein during acute events [9][10] - The FDA has not set a specific threshold for treatment efficacy, but the original approval for protein replacement therapy was based on an 11-micromolar threshold [19][20] Competitive Landscape - Wave Life Sciences is the only non-LNP derived therapy in the RNA editing space, differentiating itself through safety and durability by avoiding LNPs, which can cause liver injury [21][22] - The company emphasizes the specificity of its RNA editing approach, avoiding off-target effects and aberrant proteins, which are common in DNA editing [22][23] Obesity Program (INHBE - Program 007) - The INHBE program targets inhibin E, leveraging human clinical genetics to address obesity without inducing starvation or lean mass loss [28][29] - Wave has demonstrated significant reductions in activin E protein, correlating with weight loss similar to semaglutide, while maintaining lean muscle mass [30][31] - The potential for a once or twice yearly maintenance therapy is highlighted, with ongoing studies to assess fat loss and metabolic health [36][38] Future Studies and Market Strategy - Wave plans to conduct phase two studies on obese patients to evaluate fat reduction and sustainability of weight loss, with a focus on reducing reliance on GLP-1 therapies [42][43] - The company is exploring strategic collaborations while maintaining a wholly owned asset approach, aiming for clear registrational paths in the obesity landscape [42][43] Other Important Content - The company is optimistic about the potential for its therapies to transform patient outcomes in both alpha-1 antitrypsin deficiency and obesity [23][30] - Wave Life Sciences is focused on delivering data that demonstrates the efficacy and safety of its treatments, with upcoming data releases expected to provide further insights into their therapeutic potential [44][45]

Core Insights - Wave Life Sciences reported a quarterly loss of $0.32 per share, slightly worse than the Zacks Consensus Estimate of a loss of $0.30, but an improvement from a loss of $0.47 per share a year ago [1] - The company posted revenues of $7.61 million for the quarter ended September 2025, missing the Zacks Consensus Estimate by 41.25% [2] - Wave Life Sciences shares have declined approximately 36.5% year-to-date, contrasting with the S&P 500's gain of 14.4% [3] Financial Performance - The company has surpassed consensus EPS estimates only once in the last four quarters [2] - The current consensus EPS estimate for the upcoming quarter is -$0.27, with expected revenues of $17.32 million, and for the current fiscal year, the estimate is -$1.16 on revenues of $43.83 million [7] Market Outlook - The stock currently holds a Zacks Rank of 3 (Hold), indicating expected performance in line with the market in the near future [6] - The Medical - Biomedical and Genetics industry is ranked in the top 36% of over 250 Zacks industries, suggesting a favorable outlook compared to lower-ranked industries [8]

Financial Data and Key Metrics Changes - Revenue for Q3 2025 was $7.6 million compared to a net loss of $7.7 million in the prior year quarter, attributed to the timing of revenue recognized under the collaboration agreement with GSK [22] - Research and development expenses increased to $45.9 million from $41.2 million year-over-year, driven by advancements in the inhibin E and RNA editing programs [22] - General and administrative expenses rose to $18.1 million from $15 million in the prior year quarter, primarily due to share-based compensation [22] - Net loss for Q3 2025 was $53.9 million, an improvement from a net loss of $61.8 million in the prior year quarter [23] - Cash and cash equivalents at the end of Q3 2025 were $196.2 million, down from $302.1 million as of December 31, 2024, but extended cash runway into Q2 2027 with additional proceeds [24] Business Line Data and Key Metrics Changes - The company highlighted significant advancements in the WVE-007 program, showing dose-dependent reductions in activin E levels, with reductions of 56%, 75%, and 85% for different dosing cohorts [8][9] - WVE-006 demonstrated the potential to restore physiological AAT production, achieving AAT levels of up to 13 micromolar and a 60% decrease in mutant ZAAT protein [13] - The DMD program, WVEN531, showed a statistically significant improvement in time to rise, with a 3.8 seconds improvement compared to natural history [18] Market Data and Key Metrics Changes - The company is addressing a significant market need with an estimated 9 million homozygous individuals living with PNPLA3I148M liver disease in the US and Europe, who are at a nine-fold higher risk of dying from their liver disease compared to non-carriers [16] - The obesity market is highlighted as having over 1 billion individuals living with obesity, many of whom lack access to current GLP-1 therapies, presenting a unique opportunity for the company's treatments [55] Company Strategy and Development Direction - The company is focused on advancing its pipeline, particularly in RNAi and RNA editing, with a strategy to leverage proprietary chemistry and platform innovations [5] - There is a strong emphasis on developing non-incretin treatment approaches for obesity, with WVE-007 positioned as a potential maintenance therapy to prevent rebound weight gain [6][11] - The company aims to build on its momentum in the obesity space, with plans for further studies and potential partnerships to enhance development [43] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the progress made in clinical trials, particularly with WVE-007 and WVE-006, and the potential for these therapies to transform treatment paradigms [25] - The management team acknowledged the competitive landscape in the obesity market and the need for innovative solutions that provide durable results without the side effects associated with current therapies [55] - There is confidence in the ability to meet regulatory requirements and achieve clinical milestones, with ongoing discussions with the FDA regarding imaging endpoints for Huntington's disease [29][30] Other Important Information - The company is preparing for a global potentially registrational phase 2-3 study of WVE-003 in adults with Huntington's disease, using caudate volume as a primary endpoint [19] - The company has received positive feedback from key opinion leaders regarding the potential of its RNA editing programs to address unmet medical needs [14] Q&A Session Summary Question: Inquiry about cholesterol fat mobilization post-inhibin knockdown - Management confirmed no observed changes in increased lipids and deposits in the liver from preclinical studies, indicating positive findings regarding fat mobilization [26][27] Question: Pre-IND meeting with FDA regarding Huntington's imaging endpoints - Management confirmed alignment with the FDA on using MRI as an imaging endpoint, emphasizing the importance of well-designed clinical trials [29] Question: Changes in gene expression timing in obesity studies - Management noted that while gene expression changes occur over time, early engagement of targets and sustained suppression of proteins are observed [34] Question: Insights on acute phase response in AATD patient - Management indicated that the patient responded as expected, with no new insights beyond the initial findings [48] Question: Future studies beyond NYTE for obesity program - Management expressed interest in exploring further studies and potential strategic partnerships, while noting that the GSK collaboration would not hinder these opportunities [62]

Clinical Development - The company is focused on RNA medicines, utilizing its PRISM® platform to address both rare and common disorders, with a diversified pipeline including programs in obesity, AATD, DMD, and HD[72]. - WVE-007, targeting obesity, has shown a 70% reduction in Activin E levels in preclinical models, supporting potential for once or twice a year dosing in humans[83]. - In the INLIGHT clinical trial for WVE-007, significant dose-dependent Activin E reductions were observed, with an 85% reduction in the highest dose cohort at day 29[87]. - The AATD program, utilizing WVE-006, demonstrated a 7-fold increase in serum AAT protein levels (up to 30 µM) in preclinical models[90]. - In the RestorAATion-2 study, a single 200 mg dose of WVE-006 resulted in a mean wild-type M-AAT protein level of 6.9 µM at day 15, representing over 60% of total AAT[92]. - The company has initiated a Phase 1 clinical trial for WVE-007, assessing safety, tolerability, and pharmacokinetics in adults with obesity[85]. - The RestorAATion clinical program includes two parts, with RestorAATion-1 enrolling 29 healthy volunteers and RestorAATion-2 focusing on AATD patients[91]. - The ongoing clinical trials for WVE-006 have reported no serious adverse events, indicating a favorable safety profile[92]. - The company expects to deliver multiple clinical data updates from the INLIGHT trial in 2025 and 2026, including body composition and weight data[88]. - The AATD program aims to correct a single RNA base mutation affecting approximately 200,000 individuals in the US and Europe, addressing both lung and liver manifestations of the disease[89]. - WVE-N531 targets approximately 8-10% of DMD cases by skipping exon 53, with FDA granting Rare Pediatric Disease and Orphan Drug Designations in Q3 2024[96]. - Interim data from the FORWARD-53 study showed mean muscle content-adjusted dystrophin expression of 9.0% after 24 weeks of treatment with WVE-N531[99]. - WVE-006 demonstrated a total AAT level of 20.6 µM after a single 200 mg dose, with M-AAT levels reaching 64.4% of total AAT[101]. - The company plans to file a New Drug Application for WVE-N531 in 2026 to support accelerated approval with monthly dosing[103]. - WVE-008 is being developed for PNPLA3 I148M liver disease, with a clinical trial application expected in 2026[114]. - WVE-003 showed up to 46% reduction in cerebrospinal fluid mHTT in the SELECT-HD study, indicating potential benefits in slowing disease progression[108]. Financial Performance - The company reported a net loss of $53.9 million for Q3 2025, compared to a net loss of $61.8 million in Q3 2024, with an accumulated deficit of $1,273.1 million as of September 30, 2025[117]. - Collaboration revenue under the GSK agreement began in January 2023, but the company has not generated any product revenue since inception[118]. - Revenue for the three months ended September 30, 2025 was $7.6 million, compared to a loss of $7.7 million for the same period in 2024, reflecting a year-over-year change primarily due to an $8.0 million reduction in cumulative revenue recorded under the GSK Collaboration Agreement[130]. - Research and development expenses for the three months ended September 30, 2025 were $45.9 million, an increase of approximately $4.7 million from $41.2 million in the same period of 2024[132]. - General and administrative expenses for the three months ended September 30, 2025 were $18.1 million, up from approximately $15.0 million in 2024, driven by increases in compensation-related expenses[132]. - Total operating expenses for the three months ended September 30, 2025 were $63.9 million, compared to $56.2 million in 2024, resulting in a loss from operations of $56.4 million[129]. - For the nine months ended September 30, 2025, revenue was $25.5 million, an increase of $928,000 from $24.6 million in 2024, primarily due to increased revenue under the GSK Collaboration Agreement[137]. - Research and development expenses for the nine months ended September 30, 2025 totaled $130.0 million, compared to $115.0 million in 2024, reflecting an increase of approximately $14.9 million[139]. - General and administrative expenses for the nine months ended September 30, 2025 were $54.4 million, up from approximately $42.9 million in 2024, with an increase of approximately $11.6 million attributed to compensation-related expenses[140]. - As of September 30, 2025, the company had cash and cash equivalents totaling $196.2 million and an accumulated deficit of $1,273.1 million[144]. - The company expects existing cash and cash equivalents to be sufficient to fund operations for at least the next twelve months, although this is based on assumptions that may prove incorrect[145]. - The company filed a shelf registration statement for an indeterminate amount of securities, including up to $250.0 million in ordinary shares[147]. - For the nine months ended September 30, 2025, the company reported a net cash used in operating activities of $153.7 million, compared to $107.4 million for the same period in 2024[149][152]. - The net cash provided by financing activities for the nine months ended September 30, 2025, was $48.5 million, primarily from $42.6 million in net proceeds from sales under the "at-the-market" equity program[154]. - The company experienced a net loss of $151.2 million for the nine months ended September 30, 2025, compared to a net loss of $126.3 million for the same period in 2024[151][152]. - The company reported a net decrease in cash, cash equivalents, and restricted cash of $105.8 million for the nine months ended September 30, 2025[149]. - The company incurred $0.7 million in cash for investing activities during the nine months ended September 30, 2025, related to property and equipment purchases[153]. Operational Risks - The company has incurred significant operating losses since inception, with research and development expenses being the primary cost driver[119]. - The company anticipates significant expenses related to ongoing research and development activities, which may vary based on clinical trials and regulatory approvals[156][157]. - The company has no committed external source of funds, relying on potential future payments from collaborations and may face dilution of existing shareholders' interests if additional capital is raised[161][162]. - The company is exposed to market risks, including fluctuations in interest rates and foreign exchange rates, which could materially affect its financial condition[164][166]. - The company does not expect inflation to have a material effect on its business in the last two years, but anticipates increases in operating costs if global inflation trends continue[167].

Clinical Trials and Drug Development - WVE-007 achieved dose-dependent mean reductions of Activin E of up to 85% in the INLIGHT clinical trial, supporting its potential for obesity treatment with once or twice a year dosing[1] - WVE-006 demonstrated AAT protein levels exceeding 20 µM during acute phase response and basal AAT levels reaching 13 µM, with Z-AAT reduced by 60% in the RestorAATion-2 trial[3] - WVE-008, an investigational RNA editing oligonucleotide for PNPLA3 I148M liver disease, is expected to file a Clinical Trial Application in 2026[8] - Wave plans to file a New Drug Application for WVE-N531 in 2026 to support accelerated approval for Duchenne muscular dystrophy[13] - Wave expects to deliver multiple clinical data updates from the INLIGHT trial in the coming quarters, including body composition and weight data[4] - The company anticipates continued development and potential commercialization of its therapeutic programs, with a focus on achieving milestones in clinical trials[17] Financial Performance - Revenue recognized was $7.6 million for Q3 2025, compared to a net loss of $53.9 million, an improvement from a loss of $61.8 million in the prior year quarter[16] - Total revenue for the three months ended September 30, 2025, was $7.608 million, a decrease from $7.676 million in the same period of 2024[22] - Net loss for the three months ended September 30, 2025, was $53.852 million, an improvement from a net loss of $61.780 million in the same period of 2024[22] - The company reported a comprehensive loss of $53.881 million for the three months ended September 30, 2025, compared to a comprehensive loss of $61.660 million in 2024[22] Expenses and Cash Flow - Research and development expenses increased to $45.9 million in Q3 2025 from $41.2 million in the same period in 2024[16] - General and administrative expenses rose to $18.1 million in Q3 2025, compared to $15.0 million in the same period in 2024[16] - Research and development expenses increased to $45.874 million for the three months ended September 30, 2025, compared to $41.197 million in 2024, reflecting a growth of 9.8%[22] - Cash and cash equivalents were $196.2 million as of September 30, 2025, down from $302.1 million as of December 31, 2024[12] - Cash and cash equivalents decreased to $196.218 million as of September 30, 2025, down from $302.078 million at the end of 2024, representing a decline of 34.9%[20] - Subsequent to Q3 2025, an additional $72.1 million in ATM proceeds and committed GSK milestones extend the expected cash runway into Q2 2027[16] Assets and Liabilities - Total current liabilities decreased to $85.896 million as of September 30, 2025, from $110.953 million at the end of 2024, a reduction of 22.6%[20] - Total assets decreased to $241.378 million as of September 30, 2025, compared to $352.207 million at the end of 2024, indicating a decline of 31.5%[20] - The weighted-average ordinary shares used in computing net loss per share increased to 167,739,208 for the three months ended September 30, 2025, from 132,563,467 in 2024[22] Strategic Initiatives - The company is exploring strategic partnerships and collaborations to enhance its research capabilities and market reach[17]

Core Insights - Wave Life Sciences announced significant clinical progress with WVE-007 for obesity and WVE-006 for alpha-1 antitrypsin deficiency (AATD), highlighting the effectiveness of their proprietary RNA chemistry [2][3] - WVE-007 demonstrated up to 85% reduction in Activin E levels, indicating potential for fat loss while preserving muscle mass, with sustained effects observed for up to six months [1][7] - The company reported cash and cash equivalents of $196.2 million as of September 30, 2025, with additional funding expected to extend their cash runway into Q2 2027 [11][12] Obesity Treatment - WVE-007 is a GalNAc-siRNA designed to silence INHBE mRNA, showing promise as a treatment for obesity by improving cardiometabolic health without the side effects associated with GLP-1 therapies [3][4] - Preclinical data presented at ObesityWeek® supports WVE-007's potential as a monotherapy and in combination with existing treatments, demonstrating improvements in metabolic health markers [3][4] Alpha-1 Antitrypsin Deficiency (AATD) - WVE-006 achieved key treatment goals in the RestorAATion-2 trial, restoring AAT protein levels necessary to prevent lung damage during acute exacerbations [1][5] - Clinical data showed that WVE-006 reduced mutant Z-AAT by 60% and increased wild-type M-AAT protein to 64% of serum AAT levels [1][7] Pipeline and Future Developments - Wave Life Sciences is advancing multiple candidates, including WVE-008 for liver disease and WVE-N531 for Duchenne muscular dystrophy, with expected clinical data updates in the coming quarters [3][8][12] - The company is exploring a bifunctional single oligonucleotide construct that can silence one target while editing another, showcasing their innovative approach to RNA therapeutics [8] Financial Performance - The company reported a net loss of $53.9 million for Q3 2025, an improvement from a loss of $61.8 million in the prior year [16][22] - Research and development expenses increased to $45.9 million in Q3 2025, reflecting ongoing investment in clinical trials and product development [16][22]

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]

Core Insights - Wave Life Sciences Ltd. is set to host a live webcast and conference call on November 10, 2025, at 8:30 a.m. ET to discuss its third 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, obesity, Duchenne muscular dystrophy, and Huntington's disease, along with several preclinical programs [3] - The company is headquartered in Cambridge, MA, and emphasizes its mission to "Reimagine Possible" in the realm of human health [3]

Core Insights - Wave Life Sciences is hosting its 2025 Research Day, focusing on RNA editing and RNA interference (RNAi) technologies [2]. Group 1: Event Overview - The event is being recorded and is accessible for future reference [1]. - The presentation materials will be available on the company's website in the Investors section after the call [2]. Group 2: Management Statements - Management may provide forward-looking statements during the presentation, which are subject to various risks and uncertainties [3].