Wave Life Sciences Ltd.

Good morning, and welcome to the Wave Life Sciences second quarter 2023 financial results conference call. At this time, all participants are in the listen-only mode. As a reminder, this call is being recorded and webcast. I'll now turn the call over to Kate Rausch, Vice President of Investor Relations in Corporate Affairs. Please go ahead.

Thank you, Haley. Good morning, and thank you for joining us today to discuss our recent business progress and review Wave's second quarter 2023 financial results. Joining me today are Dr. Paul Bono, President and Chief Executive Officer, Anne-Marie Lee-Kwai Chung, Chief Development Officer, Kyle Moran, Chief Financial Officer, and Dr. Chandra Varghese, Chief Technology 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 SFC filings, including our annual report on Form 10-K for the year ended December 31, 2022, and our quarterly report on Form 10-Q for the quarter ended June 30, 2023. We undertake no obligation to update or revise any forward-looking statements for any reason. I'd now like to turn the call over to Paul.

Thanks, Gabe. Good morning, and thank you all for joining us on today's call. Today, I'll share highlights on our progress during the second quarter and then turn the call to Kyle to review our financials. Then we'll open up the call for questions. Anne-Marie and Chandra are on the line today and will be available for Q&A. In the second quarter, we continue to execute on our vision of pioneering transformational RNA medicines using our multimodal platform. We remain on track to submit CTAs for our AATB program the first RNA editing medicine to enter human clinical trials. We're accelerating work on a number of compelling targets in our collaboration with GSK, and we continue to advance our clinical programs in DMV and HD. Today, I'll begin with AATD and RNA editing, then review our progress with GSK and building a sustainable pipeline. And finally, we'll end with an update on our clinical trials. As I speak with you today, we are preparing for the imminent submission of our first clinical trial applications, or CTAs, for WVE-006, the first RNA editing clinical candidate for the treatment of AATD. This milestone is important on multiple fronts. First, WVE-006 signifies an entirely new modality moving into the clinic. We are incredibly excited about this milestone, which is an important advancement for the nucleic acid field and for all patients who stand to benefit from RNA editing therapeutics. With AAPD, our ability to utilize validated biomarkers in the clinic is expected to enable rapid delivery of proof of concept data for OO6. This early clinical data set would increase the probability of success with ways future RNA editing programs in the liver and beyond. Second, our path from target to the clinic with OO6 reflects the translational speed of our platform. Upon first human dosing, we will demonstrate that we have expediently advanced this clinical candidate with a novel modality from the bench to patients at a remarkably fast pace. As we build our pipeline, we expect to drive further efficiencies with each new RNA editing clinical candidate. Importantly, OO6 is not only first of its kind, but it's also best in class in AATB as supported by our robust preclinical data package. We are able to achieve remarkable potency and durability of editing with convenient subcutaneous dosing because of our unique fully chemically modified oligonucleotides. OO6 is also compatible with GalNac conjugation, a highly specific and elegant delivery tool that is well validated through multiple approved silencing therapeutics on the market. For AATD, it is a significant advantage to have a stable and optimized candidate that can leverage GalNac and thereby avoid lipid nanoparticles, which require intravenous dosing. Among the AATD field, we continue to generate excitement for our RNA editing approach, which is a first-in-class therapy designed for restoration of both healthy hepatic and pulmonary function with a reversible, redosable therapeutic agent. Our team has heard the enthusiasm firsthand from the community at the Alpha-1 National Conference in Dallas, Texas in June. There is major unmet need in AATV with current therapies largely confined to treating either pulmonary or in the future, hepatic manifestations of the disease. Despite the limitations of current therapy, AATD already represents a substantial pharmaceutical market, with augmentation therapy alone currently accounting for about $1.3 billion in annual pharmaceutical revenue worldwide, and this market is expected to grow. Our collaboration with GSK puts us in a strong position to execute on bringing our novel therapeutic option to this market. GSK has a long history and clear leadership in respiratory medicine, development and commercialization, And under the terms of our deal, WAVE is eligible to receive substantial development, launch and sales milestone payments, including meaningful near-term clinical milestones, as well as significant loyalties. As with AETD, our internal discovery work on the next wave of RNA medicine is substantially focused on first-in-class RNA editing therapeutics designed to repair and restore proteins. With ADAR editing, we have a versatile modality that allows us to impact target biology in novel ways. As we look at the universe of genetic mutations driving disease, the majority of these mutations lead to a loss of protein function, meaning they can't be addressed with silencing tools such as siRNA or antisense. WAVE is best positioned to capitalize on these loss-of-function disease targets using our protein restoration and repair tools, including our leading RNA editing modality and validated pharmacological platforms. We are not constrained by therapeutic area and have previously shown robust editing in extrahepatic tissues, including CNS, kidney, and lungs. Beyond rare monogenic disorders, there's also a growing opportunity for RNA medicines for prevalent diseases. With genetic insights being unlocked from large genome-wide association studies, new druggable targets are rapidly becoming available. These targets have existing biological validation rooted in human genetics. GSK is at the forefront of investing in genetic discovery. Through our strategic collaboration, we are benefiting from their proprietary genetic insights, which augment our own internal data sets and are informing and accelerating our next wave of programs, including partnered and wholly owned programs. We are rapidly building momentum within our collaboration, and the WAVE and GSK teams are already actively working on multiple targets. Importantly, GSK pays 100% of the costs and expenses related to target validation for these partner programs. As a reminder, the GSK deal includes meaningful near-term milestone payment opportunities beyond the clinical development milestones related to WV006, which has the potential to add substantially to our balance sheet in 2023 and beyond. We are planning to hold a virtual R&D day on September 28, 2023, during which we will demonstrate how we are continuing to extend our leadership in RNA editing. We will also discuss how we are uniquely translating genetic insights into internal, fully-owned programs for both rare and more prevalent diseases. During the event, we will share new preclinical data for both hepatic and extrahepatic disease indications, highlighting the potential depth and breadth of our next wave of pipeline programs. Moving on to DMV, We are on track to initiate Part B, a potentially registrational Phase II study of WVN531, our exon 53 skipping candidate. This open-label study will evaluate doses of 10 mg per kg of N531 administered every other week, and we plan to assess dystrophin protein after 24 and 48 weeks of treatment. Since our last update, our clinical development team has filed the clinical trial protocol with regulatory authorities and identified additional trial studies. We expect to share clinical data inclusive of dystrophin proteins in 2024. If these data are supported, we intend to use them to file for accelerated approval in the U.S. As a reminder, our excitement for N531 is grounded in the proof-of-concept data from Part A of the study, which showed 53% exon skipping after just three biweekly doses, high muscle tissue concentration, and a favorable safety profile. We presented these results to the DMD community at the PPMD conference in June, where they were met with excitement and optimism. With the extended dosing period in the forthcoming trial, we expect these high levels of skip transcript to result in downstream accumulation of substantial fully functional dystrophin protein. We know the DMD community is waiting for additional and better therapeutic options. With N531, we aim to provide a treatment option that delivers convenient safe production of endogenous functional dystrophin and ultimately meaningful clinical benefit for all patients amenable to exon 53 skipping. We're also planning a broad strategy to expand the number of exons we can address, which we would accelerate rapidly following positive dystrophin data for N531 to build the wholly owned DMD franchise. Turning to WVE003, our first in class allele selective candidate for Huntington's disease or HD. HD patients have no disease-modifying therapies available to them today, and we believe OO3 is the most promising HD compound in development. OO3 takes advantage of broad delivery to the CNS, thereby reaching the variety of brain regions implicated in HD. We've now confirmed the ability of all of the nucleotides to distribute in the CNS in multiple NHP studies with our partner, including relevant concentrations in the cortex and striatum. Therefore, we are confident that OO3 is getting to the right part of the brain. It is also the most advanced approach designed to selectively knock down the toxic mutant Huntington protein while sparing the healthy wild-type HTT protein. Wild-type HTT is essential and plays several critical roles in the CNS, including regulation of the synaptic and protein transport, promoting neuronal survival, and formation and function of cilia, which are essential to regulate CSF flow and reabsorption. Dysfunction in any of these pathways could be expected to adversely impact response and could potentially cause declines. With only single doses of WV-003, we have already demonstrated positive initial mutant Huntington reductions of approximately 35% as compared to placebo in the CSS, with wild-type HTT levels appearing consistent with allele selectivity. The SelectHD trial has continued to progress. And in the second quarter of 2023, we initiated the multi-ascending dose phase of the trial, dosing at 30 milligrams every eight weeks. Given our robust and durable knockdown data observed in the multi-dose cohorts of the FOCUS-C9 clinical trial of WBE004, we believe the multi-dose data for 003 will be most important to informing our next phase of development. In the second half of 2023, We intend to share additional single-dose biomarker and safety data, along with any available multi-dose data. With that, I'll now turn the call over to Kyle Moran, our CFO, for our financial update. Thanks, Paul.