Wave Life Sciences Ltd.

Good morning and welcome to the Wave Live Sciences fourth quarter and full year 2020 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. I'll now turn the call over to Kate Rauch, Head of Investor Relations at Wave Live Sciences. Please go ahead.

Thank you, operator. Good morning, and thank you for joining us today to discuss our recent business progress and review wave fourth quarter and full year 2020 operating results. On the call with me today are Dr. Paul Bono, our president and CEO, Dr. Mike Panzera, our chief medical officer, head of therapeutics discovery and development, and Kyle Moran, our CFO. Dr. Ken Rhodes, our senior vice president, therapeutics discovery, and Dr. Chandra Varghese, our chief technology officer, We'll also be available for questions following the prepared remarks portion of the call. This morning, we issued a news release detailing our fourth quarter and full year results. Please note that this news release and the slide presentation that accompanies this webcast are 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 a number of 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 31, 2020. 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 Bono, President and CEO of Wave Life Sciences. Paul?

Thanks, Kate. Good morning to everyone on the call, and thank you for joining us. During the call today, I will provide opening remarks, after which Mike Panzera will give an update on our new clinical trials kicking off this year, and Kyle will briefly discuss our financial results. After our prepared remarks, Ken Rhodes and Chandra Varghese will be available for Q&A. 2020 was a productive year for WAVES, resulting from focused and deliberate execution that was driven by our commitment to developing transformative medicines for our patients. As we start 2021, I would like to reflect on the progress we made, which has positioned us to have five programs in the clinic this year. In our neurology pipeline, we progressed our precision HD programs amidst the backdrop of a global pandemic, and we are on track for a data readout at the end of the month. We are delivering on our guidance to advance three new programs into the clinic this year, our SNP3 program in HD, our C9-ORF72 program in ALS and FTD, and our exon 53 program in Duchenne, all of which incorporates our new PN chemistry. We also achieved several milestones for the CNS programs we're advancing with Takeda, including the first demonstration of substantial and widespread target engagement in NHPs. We continue to expand our PRISM platform into new modalities and made significant progress last year on advancing our novel ADAR-mediated RNA editing modality, culminating with the announcement of our first ADAR editing program for Alpha-1 antitrypsin deficiency. Highlighting the progress of both our pipeline and platform, we published five papers within the past 12 months, and we expect to continue to publish more. From a capital position, we raised over $150 million in 2020, ensuring WAVE is well-resourced to advance our pipeline and deliver proof-of-concept results to support growth in 2021 and beyond. Turning to 2021, we anticipate a very busy year of updates on our programs, starting with the upcoming readout of our Precision HD programs in Huntington's disease. These programs consist of core Phase 1b-2a studies and open-label extension studies for both WVE 120-101 and WVE 120-102, targeting SNP 1 and 2, respectively. On slide six, we provide an overview of the data we expect to report from the Precision HD programs at the end of this month. These include biomarker and safety data from all cohorts of precision HD2 core trial, including the 32 milligram cohort, along with all complete cohorts up to and including the 16 milligram cohort from the precision HD1 core trial. We will also share data from the patients who have received multiple doses of 8 or 16 milligrams from the WVE-120-101 or WVE-120-102 in the open-label extension trials. We anticipate sharing data on multiple biomarkers, including mutant Huntington, neurofilament light chain, and wild-type Huntington. This will clearly be a robust data set, which we expect will enable us to make a decision regarding potential Phase III development for either candidate. Before turning to our next pipeline program, I will touch on our novel PN chemistry backbone modification, which augments the first-generation chemistry used in the programs just discussed. As we first highlighted during our research webcast last year, these PN backbone chemistry modifications are an advancement from our PRISM platform and have generally been shown to increase potency, exposure, and durability in preclinical studies across silencing, splicing, and ADAR editing applications. Essentially, our PN chemistry has the potential to lead to compounds with favorable profiles independent of sequence, tissue type, and modality. Importantly, we've already submitted multiple clinical trial applications for candidates using PN Chemistry and anticipate initiating three trials this year. Turning to slide eight, our three upcoming clinical programs targeting SNP3, C9R72, and Exon 53 reflect several advances resulting from the evolution of our platform and our experiences over the past eight years. Enabled by stereo pure design, each candidate has been optimized with PN Chemistry, We've also prioritized the use of in vivo models during preclinical development, and each of these programs has incorporated learnings in translational pharmacology and clinical trial design from our first-generation programs. Mike will speak further to these learnings and provide an update on our planned clinical trials later on this call. Slide 9 provides an overview of our neurology-focused pipeline, which includes silencing, splicing, and editing programs. All of our current discovery and preclinical stage programs utilize this PN backbone chemistry modification. Among our discovery and preclinical CNS programs that we're advancing with our partner Takeda, we continue to produce compelling in vivo data and progress multiple discovery programs towards portfolio entry and candidate nomination. In 2020, we also made significant progress on our ADAR editing modality, which we believe has many advantages in the editing space and positions us at the forefront of RNA editing. Our approach to RNA editing employs short, fully chemically modified oligonucleotides to recruit endogenous RNA editing enzymes called ADAR. Our ADAR editing compounds are optimized using our proprietary stereochemistry and PN backbone chemistry modifications, which enables us to avoid delivery vehicles such as AAV vectors or nanoparticles and allows us to leverage established manufacturing processes. ADAR editing opens the door to a number of therapeutic applications, including restoring or modifying protein function and upregulation of protein expression, which greatly expands the landscape of disease variants that we can potentially address. In 2020, we generated exciting proof-of-concept data in non-human primates that resulted in successful and durable RNA editing of up to 50% in vivo. We are excited about the potential to apply ADAR editing in neurology, and last year we demonstrated successful RNA editing in vitro in neurons and in vivo in the CNS of mice. This year, we anticipate sharing additional non-human primate ADAR editing data, and we are actively evaluating potential neurology programs to address with this modality. Our first ADAR editing program addresses alpha-1 antitrypsin deficiency, or AATD, by correcting a single-point mutation on the mRNA coded by the Z allele of the serpent A1 gene This mutation leads to misfolding and aggregation of alpha-1 antitrypsin protein, or AAT, in hepatocytes and a lack of functional protein in the lungs where it would protect lung tissues from neutrophil elastase. Patients with AATD typically exhibit progressive lung damage, liver damage, or both, leading to frequent hospitalizations of potentially terminal lung or liver disease. Unlike a silencing approach, We believe that our novel ADAR editing modality has the potential to address both the lung and liver manifestations of AETD. By editing at the RNA level, we avoid the risk of off-target genome editing and are able to titrate our dose, thereby avoiding potential challenges with overexpressing an aggregation-prone protein. In the fourth quarter of 2020, we successfully demonstrated editing of the SERPEN A1Z allele transcript to wild-type in vitro in hepatocytes from a transgenic model with upwards of 60% correction of the Z allele transcripts. This level of editing resulted in a threefold increase in AAT protein. Since our last update, we have further validated these secreted proteins to be functional wild-type AAT proteins. These in vitro results are what gives us excitement to generate preclinical in vivo data. We continue to optimize our proprietary in vivo model, which contains both humanized serpent A1 and humanized ADAR, and we are on track to share additional data in the first half of 2021. I'd now like to turn the call over to Mike Panzera for an update on our Huntington's franchise and our three clinical trials planned for this year. Mike?