Wave Life Sciences Ltd.

I will now turn the call over to Kate Roush, Vice President of Corporate Affairs and Investor Relations.

Thank you, Operator, and good morning to everyone on the call. Earlier this morning, we issued a press release outlining our third quarter 2025 earnings update. Joining me today with prepared remarks are Dr. Paul Bono, President and Chief Executive Officer, and Kyle Moran, Chief Financial Officer. Dr. Chris Wright, Chief Medical Officer. Dr. Eric Engelson, Chief Scientific Officer, and Dr. Chandra Varghese, Chief Technology Officer, will be available for questions following the prepared remarks. The press release issued this morning is available in the investor section of our website, www.wavelifesciences.com. Before we begin, I would like to remind you that discussions during this conference call will include forward-looking statements. These statements are subject to several risks and uncertainties that could cause their actual results to differ materially from those described in these forward-looking statements. The factors that could cause our actual results to differ are discussed in the press release issued today and in our SEC filings. We undertake no obligation to update or revise any forward-looking statement for any reason. I'd now like to turn the call over to Paul.

Thanks, Kate, and good morning to everyone joining us on today's call. I would like to first thank those of you who were able to join us for our 2025 Research Day on October 29th, where we shared the first-ever demonstration of activity reductions in a clinical trial. Notably, with a single dose of WVE-007, our inhibited GalNec siRNA, we were excited to show highly significant and durable human activity reductions that exceeded levels needed in preclinical models to drive meaningful weight loss and prevent rebound weight gain following cessation of a GLP-1. In addition, we provided an in-depth overview of our recent progress in RNAi and RNA editing and how we are building on the successful clinical translation of our WPE007 and 006 programs to advance our pipeline, including our new RNA editing clinical candidate, WPE008, for the treatment of the up to 9 million homozygous individuals living with PNPLA3I148M liver disease in the US and Europe. We also unveiled how we're harnessing the power of both siRNA and RNA editing to advance an innovative new bifunctional single oligonucleotide construct that is designed to silence one target while simultaneously editing or upregulating another distinct target. All of these clinical and preclinical advancements are made possible by our unique and proprietary chemistry and platform innovations. Just last week, we had the privilege of sharing data on 007 at Obesity Week. where we received significant attention from the patient community, key opinion leaders, and companies with deep understanding of and strategic interest in the obesity space. There was a clear recognition for the need for non-increasing treatment approaches and overwhelmingly positive engagement on 007's potential to induce fat loss, preserve lean mass, and improve cardiometabolic health, all without the negative GLP-1 class effects and with the convenience of once to twice a year dosing. There is particular excitement in 007's potential as a maintenance therapy, which would allow patients to transition off chronic incretin therapies while at the same time preventing reval weight gain, preserving lean mass, and sustaining cardiometabolic health. Reflecting on the rapid progress we've made advancing 007 in our in-light clinical trial, We have now enrolled over 70 participants and are well-positioned to deliver data on over 100 participants from the clinical trial sites in Europe and the U.S. in the first half of 2026. We began testing WVE007 and Enlight at our lowest subtherapeutic dose cohort of 75 milligrams in heat participants. Then, for the subsequent cohorts, 240 milligrams, 400 milligrams, and 600 milligrams, which are in the potential therapeutic range, we have expanded to 32 participants. WVE-007 was generally safe and well-tolerated, and our independent data monitoring committee has approved further escalation to a next higher dose in COVID-5. At Research Day, we shared highly significant dose-dependent and durable activity reductions one month post-single dose of the 007. In the first three cohorts of Enlight, including a 56% reduction for the 75 milligram cohort, 75% reduction for the 240 milligram cohort, and an 85% reduction for the 400 milligram cohort compared to baseline. In addition, we had the opportunity to evaluate our lowest dose cohort out to six months, and throughout the six-month follow-up period, we continued to see sustained reduction, supporting 007's potential for once or twice yearly dosing. The durability and potency we've observed thus far is particularly encouraging, as we expect consistent and robust activity reduction over time is necessary to achieve meaningful weight loss. As we shared at Research Day, WAVE's unique SPINA design and proprietary chemistry enabled the achievement of the potent and durable suppression needed for the inhibin E target. In our DIO mouse model, we demonstrated that weight loss in the same range as semaglutide occurred when active in E was durably reduced by greater than 70% from baseline. The knockdown we've observed in the 240 and 400 milligram cohorts already exceed these levels. In our preclinical studies, we have shown extensive data supporting OO7's unique mechanism of action to drive weight loss in monotherapy, as well as maintenance in combination settings. Specifically, we shared data that support OO7's ability to double weight loss when added to semaglutide and prevent rebound weight gain following cessation of GLP-1 in DIO mice. Furthermore, we've shown that inhibin E reduction led to adipocyte shrinkage, fewer pro-inflammatory macrophages, less fibrosis, and improved insulin sensitivity in adipose tissues, highlighting mechanisms that could explain the risk reduction for type 2 diabetes and coronary artery disease observed in human genetic data. With robust and durable target engagement in the clinic and comprehensive preclinical data that support both the mechanism of action and impact of our proprietary chemistry, we're incredibly excited to build on this positive momentum. We plan to deliver multiple near-term updates that assess blood-based biomarkers, metabolic health, body composition, and weight loss across multiple cohorts. Beginning this quarter, we'll have the first opportunity to assess the early impact of inhibity reduction at three months in the 240-milligram cohort. And importantly, in the first quarter of 2026, we'll be able to assess six-month follow-up data from the 240-milligram cohort, as well as three-month follow-up data from the 400-milligram cohort. In RNA editing, we continue to lead the field with WVE006, our GalNec RNA editing oligonucleotide for AATD. OO6 has the potential to be the first treatment for AETD that addresses the root cause of the disease with a convenient subcutaneously dose therapeutic. OO6 does not require IV-administered LMPs or complex delivery vehicles like other investigational treatments in development. This profile supports treating individuals living with AETD, including those living with lung or liver manifestations of the disease or both. Since the approval of weekly IV augmentation therapies to help manage lung disease, the field has focused on keeping serum AAT levels above a minimum threshold of 11 micromolar, in part because ZZ individuals do not produce any MAAT and have limited ability to increase serum AAT levels during an acute phase response or exacerbation. However, with RNA headings, Our goal is to restore the MZ phenotype by achieving three criteria, keeping basal protein levels at or above 11 micromolar, driving 50% or greater circulating MAAT with corresponding decreases in mutant ZAAT protein, and most importantly, restoring the physiological response serum AAT protein to acute inflammatory events. In September, we delivered data from a Restoration 2 trial demonstrating that we have already achieved these goals with O6. We observed AAT levels of up to almost 13 micromolar. We showed 64% of AAT was wild-type M-AAT with a corresponding 60% decrease in mutant Z-AAT protein. And these effects were highly consistent and durable across individuals, supporting infrequent dosing of monthly or less. Most notably, we were able to restore a ZZ participant's ability to respond to an acute inflammatory event with total AAT levels of greater than 20 micromolar, just two weeks after a single dose of O6. Encouragingly, the magnitude and four-week duration of this response were also proportional to the levels you'd anticipate in an MZ patient based on natural history. Following our September data, we've had multiple interactions with key opinion leaders in the field who have expressed their excitement about these data. In particular, the ability of WVEE006 to restore physiologic AAT production represents a major paradigm shift from weekly IV augmentation therapies. As we look ahead to the remainder of our restoration to trial, we are highly encouraged by our initial results, progressing rapidly and excited to advance a potentially transformational new medicine to individuals living with ATD. Dosing is ongoing in the 400 milligram multi-dose cohort, and we remain on track to deliver data in the first quarter of 2026. We've also initiated the single-dose portion of our third and final 600-milligram cohort, and we look forward to delivering single- and multi-dose data from the 600-milligram cohort in 2026. Building on our success with OO6, we are advancing WVE008, a Galnet-conjugated RNA editing program for PNPLA3I148N liver disease, as our next RNA editing clinical candidate. Like 006 and 007, PNPL-A3 is a compelling target with strong human genetic evidence and a clear translational path to early clinical proof of concept. There are an estimated 9 million homozygous I-148M carriers with liver disease across the US and Europe who are at a nine-fold higher risk of dying from their liver disease compared to non-carriers. The PMPLA3 I148M variant is a well-established driver of steatosis, inflammation, ballooning, and fibrosis, and yet there are no approved medicines that directly address this biology. Emerging preclinical and clinical data indicate that simply knocking down PMPLA3 is not the right solution, as loss of PMPLA3 function can worsen the very features we're trying to treat. By contrast, with 008, we aim to correct I148M using our leading RNA editing capability, which is expected to restore PNPLA3 activity and lipid mobilization, reverse steatosis, as well as improve inflammation, ballooning, and fibrosis. We share preclinical data that corroborate this approach. We've demonstrated that 008 restores functional PNPLA3 and decreases lipid accumulations. And importantly, we showed that we were able to achieve robust editing with no bystander edits or off-target signals and achieve high delivered tissue exposure, which support infrequent dosing. Clinical planning is underway for our first in-human study, where we will leverage previously genotype populations to efficiently identify homozygous I148M carriers, and we are on track for a CTA submission in 2026. Turning to DMD and HD clinical programs. Earlier this year, we shared data from BORD53 and DMD, which supported WBEN531 as a potentially best-in-class and important new therapeutic option for individuals with exon 53 amenable DMD. We observed a statistically significant and clinically meaningful improvement of 3.8 seconds in time to rise versus natural history, which is the largest effect observed relative to any approved dystrophin restoration therapy at 48 weeks. We also observed the first ever demonstration of substantial improvements in muscle health with exon skipping, including a statistically significant reduction in fibrosis and decreases in creatinine kinase and circulating inflammatory biomarkers. Moreover, we saw additional clinical evidence of myogenic stem cell or satellite cell uptake in N531 earlier in our trial, which supports the improvements in muscle health and muscle fiber maturation we observed at 48 weeks. WVN531 is also differentiated by supporting preclinical evidence, demonstrating even greater access to heart and diaphragms compared to skeletal muscles. We remain on track to submit an NDA in 2026 for accelerated approval of N531 with a monthly dosing regimen. In HD, we are continuing to prepare for a global potentially registrational phase 2-3 study of WVE003 in adults with SNP3 and HD using caudate volume as a primary endpoint, and we were actively engaged in discussions with prospective strategic partners. Developed using our platform's specificity of stereochemical control and best-in-class chemistry, we designed OO3 to be the first allele-selective approach in HD. By reducing mutant Huntington at the mRNA and protein level, OO3 addresses the underlying driver's nerd generation. And by sparing wild type Huntington protein, which is critical to central nervous system health, O3 is uniquely positioned to address the full spectrum of HD from early asymptomatic stage through the onset of symptoms and beyond. In SelectHD, we demonstrated potent and durable mutant Huntington reductions of up to an industry leading 46% and preservation of wild type Huntington with just three doses. Importantly, We observed a statistically significant correlation between allele-selective mutant Huntington reductions and slowing of caudate atrophy, marking the first time this correlation has been observed in HD. As a reminder, our own internal analysis of natural history data sets, including TRAQ and PREDICT-HD, show that an absolute reduction of just 1% in the rate of caudate atrophy is associated with a delay of onset of disability by more than seven and a half years. This is a staggering number with meaningful implications for health and economic outcomes and provides further evidence supporting the rate of caudate atrophy as a primary endpoint for an efficient clinical trial. These analyses along with the complete clinical results from our select HD trial were both part of our engagement with FDA that led to supportive feedback. We remain on track to submit an IMD application for this phase two, three study in the second half of this year. With that, I'd like to turn the call over to Kyle to provide an update on our financials. Kyle.