Wave Life Sciences Ltd.

Good morning and welcome to the WAVE Life Sciences Third Quarter 2024 Financial Results Conference Call. At this time, all participants are in a listen-only mode. As a reminder, this call is being recorded in webcast. I'll now turn the call over to Kate Rausch, Vice President, Investor Relations and Corporate Affairs. Please go ahead.

Thank you, Operator. Good morning, and thank you for joining us to discuss our recent business progress and review WAVE's Third Quarter 2024 Financial Results. Joining me today with prepared remarks are Dr. Paul Bono, President and Chief Executive Officer, Anne Marie Lee Kwai Chung, Chief Development Officer, and Kyle Moran, Chief Financial Officer. The press release issued this morning is available on 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 our actual results to differ materially from those described in these forward-looking statements. The factors that could cause 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.

Good morning, and thank you all for joining us on today's call. It's an exciting time for WAVES. This year, we have executed ahead of plan, delivered three positive clinical data sets, received supportive initial feedback from FDA on HD, rapidly advanced our obesity program towards the clinic, and strengthened our balance sheet to support our maturing and growing pipeline. Our best-in-class RNA platform is consistently translating in the clinic and demonstrating how we can uniquely design and advance first and best-in-class RNA medicines that's reimagining what's possible for patients. Our achievements have set us up for another potentially transformative year in 2025 as we aim to build on our strong momentum and deliver on key milestones from four clinical programs. We are advancing WVEN 531 and DMD, and WVE003 and HD on their respective paths towards potential accelerated approval, and WV006 and ATD towards multi-dose RNA editing data, and WVE007 and obesity toward initiation of dosing in the next clinical quarter, as well as advancing our wholly-owned pipeline. Our upcoming milestones offer the potential to unlock a high-impact and high-value portfolio in both rare and common diseases. Starting with AATD, in October, we delivered a breakthrough in RNA medicine with the first-ever clinical demonstration of RNA editing in humans using our GalNec AMER WVE006. These proof-of-mechanism data from the ongoing Restoration II study in AATD patients represent a significant milestone for WAVE and in the development of therapeutic oligonucleotides as a whole. We are pleased to observe 6.9 micromolar of MAAT just two weeks post-single dose an impressive durability of effect that we believe could support extended dosing. These initial data, alongside 006's safety profile, durability, and convenient subcutaneous administration, all support a best-in-class approach to address significant unmet needs for both liver and lung manifestations of AATD, and we look forward to delivering multi-dose data from Restoration 2 in 2025. Our RNA editing approach differs greatly from others in the field. Our chemistry was built from the ground up for our RNA editing aimers. It is novel, best-in-class, and supported by deep and broad IP. We do not require IV-administered LMPs or complex delivery vehicles. Our aimers are compatible with GalNec, enabling convenient subcutaneous dosing. Our RNA editing approach also differs from DNA editing technologies, which rely on hyperactive, exogenously delivered artificial enzymes that can result in irreversible collateral bystander edits and indels. PRUPA mechanism with WVE-006 has broadly validated our GalNec conjugated RNA editing capability. In our recent research day, we unveiled our next GalNec RNA editing programs, which aims to address significant unmet needs in the cardiometabolic space. These targets include PNPLA-3, where we are using an mRNA correction approach for those at high risk for a variety of liver diseases, as well as two targets that enable best-in-class LDL-C lowering in heterozygous familial hypocholesterolemia patients, LDLR, which utilizes first-in-class mRNA upregulation, and APOB, which utilizes mRNA correction. Each program is strongly supported by human genetics, has well-defined patient populations, and offers a completely novel treatment approach to collectively address upwards of 10 million patients. They also feature readily accessible biomarkers and approaches to assess pharmacodynamics along with established regulatory paths. We expect to select candidates for all three programs in 2025. In obesity, we are advancing WVE007, our GalNec siRNA-targeted inhibite that is a completely novel approach for healthy and sustainable weight loss. Enabled by our best-in-class siRNA technology, we believe this molecule has the potential to unlock the next frontier in obesity treatment and address the millions impacted by the disease. While GLP-1s have become current standard of care for weight loss, their impact is limited by frequent dosing, loss of muscle mass, poor tolerability, and high discontinuation rates. At Research Day, we shared preclinical data supporting 007's potential to address these unmet needs across three treatment settings. First, as a monotherapy. where a single dose delivered weight loss similar to semaglutide. These data showed no loss of muscle mass and a reduction in fat mass favoring visceral fat, all without suppressing food intake. Second, as an add-on to GLPs for further improvement of weight loss or to reduce the doses of GLP-1s. In DIO mites, we saw a synergistic effect with GLP-1s due to OO7's unique mechanism of action. When administered as an add-on with semaglutide, A single dose of WAVES inhibin E-galnec S-IRNA doubled the weight loss observed with semaglutide alone. And thirdly, as a maintenance therapy following cessation of GLP-1s to prevent rebound weight gain. Weight cycling is known to lead to the return of metabolic comorbidities. In DIO mice, we showed that inhibin E-galnec S-IRNA treatment prevented any significant weight rebound after stopping galisemaglutide. We remain on track to file a CTA for 07 by the end of this year and initiate a clinical trial in the first quarter of next year. Turning to DMD, in the third quarter, we delivered interim results from our Forward53 trial of WVN531 in boys with DMD amenable to exon 53 skipping, supporting N531 as a potential best-in-class treatment approach. Recall, this is a devastating disease and there is an urgent need to deliver safe and more effective therapeutic options to patients. We hear frequently from caregivers about the burden of weekly IV dosing and the need for therapies that can distribute to the heart and diaphragm and reach stem cells, which would enhance functional benefit and ultimately extend survival. In September, We share 24-week dystrophin data from our 453 trial, which included highly consistent mean muscle content-adjusted dystrophin of 9%, evidence of improved muscle health, muscle concentrations that enable monthly dosing intervals, and a safe and well-tolerated profile. In light of the recent PPMO discontinuations, the benefit-risk profile for our approach, which relies on novel chemistry to improve tissue and cellular uptake instead of conjugates, is even more compelling. With upcoming 48-week dystrophin data from Forward 53 expected in the first quarter of 2025, we look to build on our interim results as we aim to deliver a much-needed therapeutic option for the up to 10% of patients who are amenable to exon 53 skipping. Pending positive data and regulatory feedback with N531, we intend to advance a potentially best-in-class DMD pipeline of oligonucleotides for up to 40% of boys with DMD. Finally, Turning to WVE003, our first-in-class allele selective oligonucleotide for the treatment of HD. In June, we shared results of our SelectHD study that demonstrated potent mutant Huntington silencing of close to 50% and preservation of wild-type HDT. As a reminder, This unique ability to precisely silence only mutant HDT is enabled by our novel platform and opens up the possibility to treat pre-symptomatic patients with HD in addition to those with symptoms. HD is a devastating disease affecting more than 200,000 patients across all stages of the disease in the US and Europe, and patients are faced with extremely limited treatment options with no disease-modifying therapies currently available. With our compelling clinical results, we continue to receive substantial engagement on HD, including from potential strategic partners. Additionally, following supportive initial feedback from FDA, we believe there is potential for an accelerated approval path forward for WVE003 using caudate atrophy, and we expect to submit an IND application in the second half of 2025. I'll now turn the call over to Anne-Marie to discuss this update further, as well as share some more details on the progress of our clinical trials.