Wave Life Sciences Ltd.

Good morning and welcome to the Waves Life Sciences first quarter 2023 earnings call. At this time, all participants are in a listen-only mode. As a reminder, this call is being recorded and webcast. I'll turn the call over to Kate Roush, 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 first quarter 2023 financial results. Joining me today are Dr. Paul Bolno, 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 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 March 31st, 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, Kate. Good morning, and thank you all for joining us on today's call. Today, I'll share highlights on our progress during the first 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 also on the line today and will be available for Q&A. The first quarter marked a fundamental strategic change in how we at Wave are leveraging our leadership in oligonucleotide chemistry, including the formal beginning of our transformational collaboration with GSK, publicly announced in mid-December of last year. Let's take a moment to reflect on our evolution. More than 10 years ago, we started as a company focused on optimizing antisense oligonucleotide chemistry. We then leveraged relatively well-understood biological mechanisms of RNSH, directed silencing, and exon skipping. Gratifyingly, at this point in our evolution, we believe we are finally seeing the fruits of these chemistry efforts in our recent preclinical and clinical work. We see them in our positive BMD clinical data announced last December, to which I will return, and we are seeing them in our recent preclinical data with strong and durable RNAi-mediated silencing in liver and beyond. Over recent years, advances in chemistry combined with emerging genetic and genomic insights have enabled us to think more aggressively about engaging novel target biology, such as ADAR enzymes for editing, where we can use our validated chemistry to unlock high-value, first-in-class therapeutic franchises. Marrying novel biology with validated, best-in-class chemistry opens opportunities to make first-in-class medicine that can grow into class leaders. More, the sorts of targets we're interested in with biological validation rooted in human genetics when combined with validated pharmacology have improved the probability of success and development. Our demonstration at WAVE of best-in-class RNA editing, best-in-class exon skipping, and now also potentially best-in-class RNAi silencing allows us to be driven in a way we describe as multimodal in RNA medicine. This means we have a broad toolkit in RNA-directed pharmacology across multiple modalities, and we believe we can select the optimal tool for the job across the most attractive molecular targets and associated disease states. It is rare for a company to have both a validated pharmacologic platform and access to genetically validated targets, and a decade of work has uniquely positioned us to capitalize on this opportunity. Wave is leveraging our multimodal platform to pioneer first-in-class RNA medicine with a strategic focus on protein restoration and repair targets such as Alpha-1 Antitrypsin Deficiency, or AETD, that will provide life-changing medicines for patients and build major value for shareholders. Our unique capabilities enable us to quickly move beyond AETD to build value through pipeline expansion and de-risking. We intend to hold an investor event in the third quarter of this year, to highlight how we are translating our capabilities in protein restoration and repair into compelling new programs. Since we last gathered six weeks ago, we have made substantial progress in several aspects of our business, three of which I'd like to highlight today. First, our GSK collaboration with significant milestones that could be achieved in 2023 and beyond. dead-fast execution on driving WVE-006 to the clinic in alpha-1 antitrypsin deficiency, and rapidly generating data on the next set of RNA editing programs. And third, continued progress advancing WVE-N531 for DMD, a wholly-owned commercial opportunity for WAVE, into a study that would support potential accelerated approval. First, our transformational collaboration with GSK is off to a strong start. As a reminder, this partnership not only validates our leadership in RNA editing with our first-in-class 8R editing modality, it also acknowledges our best-in-class multimodal RNA medicine discovery and development platform. Through the collaboration, GSK provides WAVE with proprietary genetic insights to expand our pipeline both with partnered and wholly-owned WAVE programs. It has been an exciting and productive start to the collaboration, with both the WAVE and GSK teams working together to begin advancing the first set of targets. It's important to remind everyone that GSK has made significant investments in genetic discovery, as well as has a long history and clear current leadership in respiratory medicine development and commercialization. Both of these capabilities sets makes GSK the ideal partner for WAVE's pioneering AATD program. Importantly, The GSK deal bolstered our balance sheet with $170 million in upfront cash and equity to accelerate our existing pipeline and provide meaningful near-term milestone payment opportunities, including clinical development milestones related to WVE-006. These potential milestone payments, while confidential in their quantity and trigger events, have the potential to add substantially to our already strong balance sheet in the near term, including meaningful milestones anticipated in 2023, and beyond. Next, we continue to make steady progress advancing WVE-006 toward our first in-human trials. As a reminder, OO6 is our first-in-class galnet-conjugated RNA editing candidate for AATD. Since our last update, we have successfully completed the in-life portion of GLP toxicology studies as planned for OO6, and we are rapidly advancing towards CTA submissions this year. Among the fields, we continue to generate excitement for our novel treatment approach to AATD, which is a first-in-class therapy designed for restoration of both healthy hepatic and pulmonary function with a reversible and reducible therapeutic. There is major unmet need in AATD with current therapies largely confined to treating either pulmonary or in the future hepatic manifestations of the disease. Despite the limitations of current therapy, AADD 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. OO6 is on track to be the first RNA editing therapeutic taken into human clinical trials where we intend to utilize validated biomarkers to deliver proof of concept for OO6 and the field of RNA editing. Similar to the exponential growth of RNAi medicine following the de-risking of GalNec siRNA silencing in the liver, we believe early clinical data with OO6 would increase the probability of success of WAVE's future RNA editing program in the liver and beyond. We believe this would enable us to build substantial shareholder value in a way that is comparable to the early pioneers of RNA medicine. As we continue to expand our wholly-owned pipeline, we are focused on investing in first-in-class RNA editing therapeutics designed to repair and restore protein, such as with our AATD program. Our discovery team is intensely working on the next wave of RNA medicines to sustain our pipeline. We plan to hold an investor event in the third quarter of this year, during which we will demonstrate how we are continuing to extend our leadership in RNA editing and we also expect to share preclinical data on new programs. In DMV, we are laser focused on initiating our potentially registrational phase two study of WVEN531, our exon 53 skipping candidate, following our positive data in December. Our proof of concept data continues to be met with excitement by neuromuscular clinicians and the DMV community. As a reminder, These results included the impressive 53% exon skipping observed after just three consecutive biweekly doses, high muscle tissue concentration, and a favorable safety profile. With longer dosing, we expect these high levels of skip transcripts to result in downstream accumulation of substantial, fully functional dystrophin protein, as has been the case with other exon skipping strategies observed across the industry to date. A key distinction of exon skipping approaches such as N531 from gene therapy is the intent to generate functional Becker-like dystrophin protein, not mini or micro truncated dystrophin. Functional dystrophin protein has been established by the FDA as a surrogate endpoint for accelerated approval in DMD, something that is still in question for micro dystrophin. More, our hope for the DMD community is that options for patients continue to expand, and we believe that convenient, safe production of endogenous functional dystrophin can be a highly valuable and attractive option for patients as an alternative to or in combination with gene therapy approaches should they become available. Our team is quickly moving to initiate dosing in Part B of our study, a Phase II open-label study with doses of 10 milligrams per kilogram administered every other week. and plans to assess dystrophin proteins after 24 and 48 weeks of treatment. We will continue to share updates as we progress with Part B of the study, and we expect to share data in 2024. If the data are supportive, we intend to use them to file for accelerated approval. Importantly, our vision extends beyond Exxon 53, and we are planning a broad multi-exxon strategy which we would accelerate following positive distress and data for N5G1 to build a wholly owned DMD franchise. Turning to WV004 and 003, our CNS silencing programs are advancing in adaptive clinical trials. And as a reminder, these programs are part of an active collaboration with CICADA. WV004, our candidate for C9 ORF72-associated ALS and FTD, is being evaluated in the FOCUS C9 clinical trial. We remain on track to deliver a substantial data set consisting of several single and multi-dose cohorts in the first half of this year. This will enable discussions with our partner and inform next steps for this program. WVE003 is the first-in-class allele selective candidate for Huntington's disease, which is being evaluated in patients with a SNP3 polymorphism in the SelectHG clinical trial. Last year, we adapted the SelectHD study to expand the single-dose cohorts based on initial positive clinical mutant and wild-type Huntington biomarker data. Recently, the vendor of our mutant Huntington assay announced that they were subject to a cybersecurity attack, and we remain in close contact with them as they work to address this issue. Our patient samples were not impacted, and we will ensure that our vendor's relevant computer systems are fully operational and validated before processing. With this shift in timing, we now expect to deliver additional single-dose biomarker and safety data, along with some multi-dose data, in the second half of 2023. Like with 004, these clinical data will also enable us to discuss next steps for the program with our partners. As a multimodal RNA medicines company, we are able to leverage our collaborations to explore our best-in-class potential in RNAi silencing. RNAi is one of multiple modalities being advanced in our strategic collaboration with GSK. Just a few weeks ago, we announced the first publication of our siRNA design in nucleic acid research, and we have since received highly positive feedback from our peers, recognizing the transformational impact these findings have for the field of RNAi. The published data demonstrated unprecedented AGO2 loading following administration of a single subcutaneous dose leading to improved potency and durability in vivo as compared to a comparator from a commercial company with a clinically proven track record in RNAi. We believe these data are critical and highly enabling as the translatability of RNAi-based approaches from preclinical observation to clinical proof of concept have been well established. there remain many high-value RNAi targets in attractive accessible tissues, and more novel targets continue to flow from leading work in human genetics, including work by our collaborator, GSK. In sum, we are building a leading multimodal RNA medicines company with significant opportunity to expand our foundational work in the field of RNA editing. We are working with urgency to bring a novel RNA editing medicine to people living with AATD and important new treatment options for boys with DMD. We will deliver two important data sets this year to inform our CNS silencing programs for the ALS, FTD, and HD communities, and we're also excited to share more on our work with GSK and our emerging RNA editing portfolio beyond the ATDs later this year. It is a uniquely busy time at WAVE, and we believe we are well-positioned to capitalize on now years of hard work to enable rapid pipeline development. With that, we'll now turn the call over to Kyle Moran, our CFO, for our financial update.