Wave Life Sciences Ltd.

Good morning and welcome to the Wave Life Sciences first quarter 2022 financial results 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 Roush, VP of Investor Relations and Corporate Affairs at Wave Life Sciences. Please go ahead.

Good morning, and thank you for joining us today to discuss our recent business progress and review WAVE's first quarter 2022 financial results. Joining me today with prepared remarks are Dr. Paul Bolno, WAVE's president and chief executive officer, Dr. Mike Panzera, chief medical officer, head of therapeutics discovery and development, and Kyle Moran, chief financial officer. The press release issued this morning 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 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, 2021, and our quarterly report on Form 10-Q for the quarter ended March 31, 2022. 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. Paul?

Thanks, Kate. Good morning, and thank you all for joining us. Today, I will start by highlighting our achievements so far this year and provide a business update. Mike will discuss our therapeutic pipeline, and finally, Kyle will discuss our first quarter of financials. This has been an exciting first half of 2022 for WAVE. We are executing on multiple pillars to drive value for both our shareholders and the patients and families we serve. We remain on track to deliver data from our three clinical programs to rapidly inform their next stages of development. This was exemplified by our recent positive data announcement on our C9 program. Rapidly advance our first RNA editing AMER alpha-1 antitrypsin or AETD program into IND-enabling toxicology studies a key step on the path to the clinic, and leverage partnerships to unlock value from our platform, pipeline, and manufacturing. Starting with our clinical programs, WAVE has been at the forefront of accelerating innovation in oligonucleotides, and our recent clinical data is a first glimpse of how our preclinical data are translating in patients. As we announced in April, WVE-004 demonstrated successful target engagement in the central nervous system, in the ongoing FOCUS-C9 study for patients with C9 ORF72-associated ALS or STD. We were able to rapidly identify this positive signal with single low doses of 004 due to the innovative and adaptive design of the trial. As Mike will highlight today, the clinical trial is advancing to optimize dose and frequency for the next phase of development. As you are all aware, ALS and STD are devastating diseases with extremely high unmet needs. For those with C9 mutations, these illnesses are also marked by faster rates of progression, and we are moving with urgency to advance this program. This year, we also expect to deliver data from our ongoing select HD clinical trials, studying WVE-003 in Huntington's disease, and our ongoing clinical trial in DMD, studying WVE-N531. These data will help us further elucidate the broad potential of PN chemistry for CNS and muscle diseases. Beyond our current clinical portfolio, we are advancing our AACD program using GalNec-targeted delivery. Not only does our RNA editing modality have the potential to transform the way patients are treated for this disease, but initial clinical proof of concepts will substantially de-risk additional RNA editing disease targets. Finally, we remain active in our business development efforts. there is widespread recognition of the potential for oligonucleotide therapeutics. With several key publications on our novel PN chemistry earlier this year and our recent positive clinical data, discussions with potential partners are accelerated. RNA editing in particular is ripe for collaboration and vastly expands the landscape of addressable genetic targets. Waves AMERS are enabled by our unique chemistry modification, as well as the creativity and expertise of our scientists. In the first quarter, we announced the publication of our foundational preclinical proof-of-concept editing data in Nature Biotechnology, which showed that a simplified oligonucleotide approach can be used for robust, durable, and highly specific RNA-based editing without exogenous enzymes or delivery vehicles. This paper served to further distinguish our aimers from others pursuing editing applications at both the RNA and DNA levels. We expect 2022 to continue to be an important year for partnering, including leveraging our manufacturing capability. We see vast potential to expand the reach of our platform with AMERS. There are tens of thousands of single nucleotide disease variants that are potentially amenable to ADAR editing correction. Demonstrating clinical proof of concept in AETD would serve to de-risk additional monogenic diseases, as well as open opportunities to address large patient population through modulation of proteins, such as disruption of protein-protein interactions. Our positive ALS-FE clinical data ox the potential to leverage our preclinical data demonstrating potent and durable editing in the central nervous system. Our PRISM platform enables us to capture learnings with each new target, and we expect to shorten our cycle times from target identification to preclinical proof of concept to clinical candidate over time. Today, in tandem with this earnings call, Dr. Paloma Giagrande is presenting our preclinical AMER data at the TIDES USA conference. As a reminder, we observed clinically relevant levels of AAT restoration with AMER treatments in a transgenic mouse model following multiple doses of Galnex Serpin A1 AMERS. Specifically, in week 19, we observed RNA editing of approximately 60% in liver. This level of editing resulted in total AAT serum protein levels of 18.5 micromolar, or five-fold higher than control. The majority of the circulating AAT protein, approximately 70%, was confirmed healthy wild-type MAAT protein. While there are multiple approaches being developed to address AATD, The advantages of AMERS is the ability to address both lung and liver manifestations of the disease with a single subcutaneous administered compound. Today, Paloma is also sharing new data at TIDE demonstrating the functionality of the restored AAT protein at week 19 as measured by neutrophil elastase inhibition, as shown on slide 8 on the left. Histological analysis of liver biopsies indicate treatment with AMERS reduces accumulation of liver Z AAT aggregates over time, as assessed by path D staining, as shown on the right. We will be highlighting our AETD program data again in an oral presentation at the ASG team meeting next week. I'll now turn the call over to Mike to give an update on our clinical program, as well as the progress advancing AETD towards the clinical development.