Wave Life Sciences Ltd.

Good morning and welcome to the Wavelife Sciences second quarter 2021 earnings call. My name is Brandon and I'll be your operator for today. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session during which you may dial star 1 if you have a question. Please note this conference is being recorded. I will now turn the call over to Kate Roush, Head of Investor Relations at Wavelife Sciences. And Kate, you may begin. Thank you.

Thank you, operator. Good morning, and thank you for joining us today to discuss our recent business progress and review WAVE's second quarter 2021 operating results. On the call with me today are Paul Polno, WAVE's President and Chief Executive Officer, Mike Panzera, Chief Medical Officer, Head of Therapeutics Discovery and Development, Paloma Giangrande, Vice President of Platform and Discovery Sciences and Biology, and Kyle Moran, Chief Financial Officer. This morning, we issued a news release detailing our second quarter financial results and provided a business update. This news release and the 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 filings, including our annual report on Form 10-K for the year ended December 31, 2020, and our quarterly report on Form 10-Q for the quarter ended June 30, 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, Gabe. Good morning, everyone on the call, and thank you for joining us. During the call today, I will provide opening remarks, after which Mike will give an update on our three ongoing clinical programs. We'll then turn the call over to Paloma Gironde to provide an update on our Discovery Stage Alpha-1 Antitrypsin program, which provides ongoing proof of concept for our ADAR editing capability. Paloma joined WAVE for Moderna at the start of this year as VP Platform Discovery Sciences and Biology. Finally, Kyle will briefly review our financials. Since the start of the second quarter, we achieved several important milestones. Most significantly, we started dosing in our focus C9 clinical trial of WVE004, our C9 ORF72 candidate in amyotrophic lateral sclerosis and frontal temporal dementia. This marked the first human dosing with an oligonucleotide containing our next generation PN chemistry, which is a critical and very exciting milestone for the company. Right behind C9, we're advancing two additional clinical trials, the SelectHD trial of WBE003, our SNP3 candidate in HD, and a clinical trial of WBEN531, our Exxon 53 candidate in DMD. Each of these innovative, adaptive clinical trials is designed to quickly establish a dose level and frequency, and ultimately clinical effects to enable decision-making on next steps for these programs. Data generated over the next 18 months We'll also provide insight into the clinical effects of PN chemistry, both with intrathecal and systemic administration, as well as provide the opportunity to confirm the promised same in vivo preclinical results. RNA editing is the most recent therapeutic approach to emerge from our PRISM platform, which also utilizes oligonucleotides with our novel PN backbone modifications. For this new modality, we designed the oligonucleotides to engage the endogenous ADAR to achieve RNA editing During the second quarter, we share proof-of-concept data that demonstrates restoration of functional alpha-1 antitrypsin protein with in vivo 8R editing, an important achievement for both the platform and for this exciting program. Palumbo will review these data later on in the call. These recent accomplishments are direct results of our investment in our PRISM platform and our swift execution advancing PN chemistry from concept to discovery into therapeutic molecules. Since the founding of WAVE, we have been innovating on oligonucleotide chemistry to optimize our therapeutic candidates using the resolution of stereopure design. Our novel PN chemistry is the first significant new modification that we've advanced, which has demonstrated a step change in pharmacology across many in vitro and in vivo studies. These studies show that the addition of even just a few properly placed PN backbone chemistry modifications to oligonucleotides consistently enhances potency, distribution, and durability of effect. These improvements appear to be independent of sequence, tissue type, or modality, enabling us to expand the use of these chemistry modifications to build our next-generation oligonucleotide pipeline. Less than a year after first unveiling this new chemistry, we have ongoing clinical studies for three PN-modified candidates that are now dosing in the first of these clinical trials with others soon to follow in the coming weeks. Given the complexities of many nucleic acid therapeutics today, it's important to note this novel chemistry is scalable. We are manufacturing the supply for all three clinical trials and multiple preclinical therapeutic programs within our GMP manufacturing facility. We have a robust portfolio of oligonucleotides led by our clinical programs, WVE004 in ALS and FTD, WVE003 in HD, and WVE-N531 in DMD. These ongoing clinical trials all include biomarker assessments and clinical data which will enable potential paths to registration and unlock value for our additional pipeline programs, including those in collaboration with ACADA and our wholly-owned targets. Our chemistry experience with optimizing silencing and exon-skipping compounds enables us to rapidly apply our PRISM platform to develop RNA-editing oligonucleotides and accelerate this capability, such that we are now among the leaders advancing AR editing towards the clinic. Our stereopure editing oligonucleotides are fully chemically modified and incorporate PN backbone modifications. They're also single-stranded and short in length. Altogether, these features enable simplified delivery, avoiding the need for AEB or nanoparticles such as LNPs. As you can see on the lower left of slide 8, Once our oligonucleotides reach the target RNA, they engage endogenous ADAR, a ubiquitously expressed enzyme across tissue types, to correct or modify single RNA bases. Our approach is highly specific, and by staying focused at the RNA level, we avoid potentially permanent off-target DNA base edits. The target landscape for this modality is vast, enabling therapeutic applications such as restoration of protein function, modification of protein function, and upregulation of protein expression. We intend to show the versatility of editing we can achieve at an upcoming research day on September 28th. I'd now like to turn the call over to Mike Panzera for an update on our clinical trials. Mike.