Wave Life Sciences Ltd.

Good morning, and welcome to WAVE Life Sciences' third quarter 2023 financial results conference call. At this time, all participants are in a listen-only mode. As a reminder, this call is being recorded and webcast. Now, I'll 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 today to discuss our recent business progress and review WAVE's third quarter 2023 financial results. Joining me today are Dr. Paul Bono, President and Chief Executive Officer, Kyle Moran, Chief Financial Officer, Anne-Marie Lee-Kwai Chung, Chief Development Officer, Dr. Ginny Yang, SDP Translational Medicine, and Dr. Chandra Varghese, Chief Technology Officer. 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 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, including our annual report on Form 10-K for the year ended December 31st, 2022, and our quarterly report on Form 10-Q for the quarter ended September 30th, 2023. 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. I will begin with opening remarks. Next, Anne-Marie will provide an update on our clinical trials, and finally, Kyle will review our financials. We will then open up the call for questions. Chandra and Janique will also be available for questions. In the third quarter, our team made tremendous progress advancing our pipeline of novel RNA medicine. Since our last update, we have brought our first-in-class RNA editing therapeutic program, WVE-006 for AATD, into the clinic. We outlined our strategy for growth at our annual R&D day, including announcing a new, wholly-owned siRNA program targeting inhibity for metabolic disorders, including obesity, and we continue to advance our clinical trials in BMD and HD. Looking ahead to 2024, we are approaching a transformative year for WAVE. where we will deliver key data sets for all three of our clinical programs and select an inhibitory clinical candidate. Starting with WVE-006, today we are announcing the approval of multiple clinical trial applications, or CTAs, and the initiation of our restoration program, which will investigate WVE-006, the industry's first ever clinical RNA editing candidate for alpha-1 antichrypsin deficiency, or AATD. This is another significant milestone for ways patients, and the field of nucleic acids. We remain on track to begin dosing healthy volunteers this quarter, and as Anne-Marie will describe in more detail later, the restoration program is designed to enable a highly efficient path to prove the mechanism. Our excitement for WVE-006 is grounded in the strong preclinical profile we have observed to date. We have achieved remarkable potency and durability of editing with convenient subcutaneous dosing in our preclinical studies. because of our unique, fully chemically modified oligonucleotides and their ability to effectively recruit ADAR enzymes. WVE-006 precisely corrects the PIZ mutation on the transcript with no bystander editing. In contrast, genome editing technologies rely on hyperactive, exogenously delivered artificial enzymes that can result in significant and irreversible collateral bystander editing of DNA, yielding not only the potential for permanent off-target edits to DNA, but isoforms of protein with differential function. O6 contains a galnet conjugate, 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 galnet and avoid lipid nanoparticles, which have their own challenges and require intravenous dosing. With current therapies largely confined to treating either pulmonary or in the future hepatic manifestations of the disease, the unmet need in AETD remains high. Even with the limitations of available therapies, the pharmaceutical market for AETD is substantial, with augmentation therapy alone accounting for over a billion dollars in sales per year. Our partner, GSK, has a long history and clear leadership in respiratory medicine development and commercialization, And together with 006's differentiated profile, we believe this program is in a strong position, and we look forward to delivering proof-of-mechanism data next year. As a reminder, under the terms of our collaboration, WAVE is also eligible to receive meaningful near-term clinical milestones starting this year, which have the potential to add substantially to our balance sheet. Clinical proof-of-mechanism with 006 would serve to meaningfully de-risk this novel modality. and will continue to unlock value for our emerging pipeline of RNA editing programs. As we shared at our R&D day, we are actively building a pipeline of wholly-owned therapeutic candidates designed to either correct or upregulate mRNA across a range of high-impact targets. We presented both in vivo and in vitro data on several of these targets, which all offer efficient paths to clinical proof of concept and represent meaningful commercial opportunities for both rare and common disease indications. We look forward to continuing to share data on these exciting programs over the course of 2024. Beyond WVE-006, our strategic collaboration with GSK continues to make meaningful progress. The WAVE and GSK teams continue to work to advance multiple targets, and as our partners shared during our R&D day, this work spans multiple modalities beyond RNA editing, including silencing using siRNA. As a reminder, GSK pays 100% of the costs related to target validation of these partner programs, and WAVE is eligible for up to $2.8 billion in milestone non-inclusive OO6 and additional tier royalty payments. At R&D Day, we also announced our first fully-owned program to emerge from the collaboration, a Galnet-conjugated siRNA program targeting an IV and E to treat metabolic disorders, including obesity. Inhibit E is a particularly exciting target, given its strong supporting genetic evidence. Inhibit E loss-of-function heterozygous carriers exhibit a healthy metabolic profile, including reduced hip-to-weight ratio, improved lipid profile, reduced odds of coronary artery disease, and type 2 diabetes. GLP-1 therapeutics have established a substantial market opportunity for weight loss therapeutics. We estimate there are more than 47 million people in the United States and Europe with metabolic disorders, including obesity. While GLP-1s are becoming standard of care for weight loss, they come with several drawbacks, including loss of muscle mass, depression of the general reward system, and poor tolerability. With discontinuation rates as high as 70%, there is a need for more therapeutic options, including long-term maintenance. We believe a therapeutic approach for obesity that improves metabolism increases fat loss while maintaining muscle mass, offers the potential for infrequent dosing, and does not affect the general reward system would be ideal. This is what we aim to achieve with our Inhibit E program. At R&D Days, we presented the first in vivo data supporting preclinical proof of concepts for this target. We achieved Inhibit E silencing well beyond the 50% therapeutic threshold, which led to substantially lower body weight and substantial reduction of visceral fat in BIO mice as compared to control. These are the first in vivo data to demonstrate inhibin E silencing is consistent with the phenotype of heterozygous loss of function carriers. Since R&D deck, we have identified potent and highly specific leads using our new chemistry format and are rapidly advancing towards our goal of selecting an inhibin E clinical candidate by the fourth quarter of 2024. Notably, because the levels of inhibin E protein and other relevant clinical biomarkers can be readily measured in serums, we believe the path to assessing target engagement and clinical efficacy can be straightforward and achieved in a relatively short period of time. As a reminder, our collaboration allows WAVE to leverage GSK's genetically validated targets to advance at least three programs, meaning we have an additional two slots open for new wholly-owned programs beyond infinity. Turning to WVN531 and WVE003, we continue to advance our clinical DMD and HD programs and are on track to deliver key data from both programs in 2024. For DMD with WVE-N531, we aim to provide a treatment option that delivers convenient, safe production of endogenous functional or Becker-like dystrophins and ultimately meaningful clinical benefit for all patients amenable to exon 53 skip it. There remain significant questions around the functional benefit of micro or mini dystrophin, and we recognize the urgency to deliver more therapeutic options to these patients. We look forward to evaluating the translation of our best-in-class exon skipping to functional dystrophin protein in 2024. In Huntington's disease, we believe WVE003 is the most promising asset in the field. To date, we have demonstrated successful translation of our compelling preclinical data to the clinic with reduction of mutant Huntington and preservation of wild type Huntington after a single dose in humans. We have robust evidence from multiple preclinical studies, including NHP studies, that support the ability of our oligonucleotides to achieve significant exposure levels throughout the CNS. As we look ahead to the first multi-dose data from our SelectHG clinical trial next year, we anticipate potent and durable knockdown of mutant Huntington while sparing wild-type protein, similar to what we observed in poly-GP reduction in our WVE-004 program when we transitioned from single to multi-dose. Anne-Marie will speak more on SelectHD and our other clinical development programs, and I'd now like to turn the call over to her. Anne-Marie.