Wave Life Sciences Ltd.

Good morning and welcome to the Wave Life Sciences fourth quarter and full year 2021 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, Head of Investor Relations at Wave Life Sciences. Please go ahead.

Thank you, operator. Good morning, and thank you for joining us today to discuss our recent business progress and review Wade's fourth quarter and full year 2021 financial results. Joining me today with prepared remarks are Dr. Paul Bono, Wade's President and Chief Executive Officer, Dr. Coloma Giangrande, VP Biology and Platform Development, Dr. Mike Panzera, Chief Medical Officer, Head of Therapeutics Discovery and Development, and Kyle Moran, Chief Financial Officer. This morning, we issued a news release detailing our fourth quarter and full year 2021 financial results and provided a business update. This news release and a slide presentation to accompany 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 filing, including our annual report on Form 10-K for the year ended December 31, 2021. 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. Paul?

Thanks, Kate. Good morning, and thank you all for joining us. Today, I will begin with opening remarks. Mike, our CMO and head of therapeutics discovery and development, and Paloma, VP of biology and platform discovery, will then provide an update on our clinical and preclinical therapeutic program. And lastly, WAVE CFO Kyle Moran will discuss our financials. At WAVE, we continue our journey building a leading genetic medicines company grounded in our innovative RNA therapeutics platform, PRISM. The platform today reflects nearly a decade of investment in entirely new chemistries including our PN backbone modification, which have the potential to disrupt the pharmacology of therapeutic oligonucleotides. Over the course of 2021, we made significant progress by bringing PN chemistry into the clinic with our three neurology candidates, as well as advancing PN chemistry within a new modality, our RNA editing AMERS. Today, we have a diversified portfolio that reflects the breadth of our platform, clinical data this year will inform next steps for our neurology program, and we are rapidly advancing our aimers using targeted delivery for hepatic diseases, starting with alpha-1 antitrypsin. Partnerships are an important component of our strategy to unlock value from our platform, pipeline, and other assets, such as our GMP manufacturing facility. In a growing number of preclinical studies, we have shown how PN chemistry benefits oligonucleotide therapeutics including modalities outside of our core focus, such as RNAi. We are seeing significant interest, and we expect 2022 to be an important year for executing on partnering opportunities. Just recently, we announced two peer-reviewed publications in nucleic acids research, which describe the incorporation of PN backbone modification in stereopure oligonucleotides to improve potency, tissue distribution, and durability effect for silencing in the CNS and for splicing in DMD. Our silencing paper was designated as a breakthrough article by the journal. Their acknowledgement of the strength of these data and the potential of our platform to impact the field is a significant milestone for WAVE. We continue to define the broad applicability of PN chemistry for the potential therapeutic use. As we first shared at our research day last year, PM modifications can be applied to siRNA and it results in meaningful improvements as compared to state-of-the-art advanced ESD chemistry. On slide seven, we show recent results that provide another compelling example, this time with HSD17B13 target. With a single dose of three milligrams per kilogram, we saw a remarkable 80% HSD silencing that persisted out 14 weeks. while the comparator lost activity in the same time point in the transgenic mouse model. We also saw significantly greater risk loading of PRISM siRNA at all time points as shown on the right. These results are dramatically improved from our earlier hepatic discovery efforts prior to the introduction of PN chemistry. Our current portfolio includes multiple stereopure PN-modified single-stranded oligonucleotides with and without targeted delivery conjugates. In the clinic, we are advancing WVE004, targeting C9ORC72 for ALS and FTD, and WVE003, an allele-selective mutant Huntington candidate for patients with HD and a CYP3 mutation. These candidates are dosed intrathecally and will give us insight into potency and duration of effect through biomarkers in the CNS. WVEN-531, our exon 53 splicing candidate for patients with BMD, is administered intravenously and will provide insight into how PN-modified compounds can improve muscle tissue concentration and hopefully the level and duration of exon skipping and dystrophin production. With AMERS, we are initially focused on hepatic indication and using targeted galnec-mediated delivery, which is expected to enable subcutaneous dosing in the clinics. We are unique in our RNA-based editing approach as our galnet conjugated AMRs are short, stabilized with chemical modifications, including PN, and designed to engage endogenous ADAR enzymes. Success with any of our ongoing programs unlocked a broad universe of targets in the CNS, muscle, and or liver. We expect to share clinical data in 2022 for WVE004, 003, and N531, to provide insight into clinical effects of PN chemistry and enable decision-making for each program. By using chemically modified guide strands to engage endogenous machinery, our RNA-based editing approach is distinct from others. We are very excited about the broad potential of AMERS. Our wholly-owned LEAD AATD program represents a significant commercial opportunity, with approximately 200,000 people carrying the homozygous disease mutations in the U.S. and Europe. Demonstrating clinical proof of concept in ATD would serve to de-risk additional monogenic diseases, as well as open opportunities to address large patient populations through modulation of proteins, such as disruption of protein-protein interactions. When we built WAVE, we recognized the growing momentum in RNA therapeutics and anticipated the value in having an internal GMP manufacturing facility. Our manufacturing team is made up of experts in oligonucleotide synthesis that have successfully delivered clinical supply for six global studies at wave to date. With this facility, we can support the supply of innovative oligonucleotide genetic medicines at all stages of product development with any chemistry. And we are now evaluating utilizing our additional capacity to support new partners. We plan to build on this capability throughout 2022. I'd now like to turn the call over to Mike Panzera for an update on our clinical pipeline. Mike.