Good morning, and welcome to the Wave Life Sciences Fourth Quarter and Full Year 2022 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 [Kia Telepore] (ph), Wave's IR Consultant. 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 fourth quarter and full year 2022 financial results. Joining me today are Dr. Paul Bolno, President and Chief Executive Officer; Anne-Marie Li-Kwai-Cheung, Chief Development Officer; Kyle Moran, Chief Financial Officer; and Dr. Chandra Vargeese, Chief Technology Officer. The press release issued this morning and the slide presentation to accompany this webcast are available in the Investors Section of our website at 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. We undertake no obligation to update or revise any forward-looking statements for any reason. Now, I'd like to turn the call over to Paul.

Thanks, Kia. Good morning and thank you all for joining us. I'm excited to begin today's call with a review of recent business highlights and how they position Wave in 2023 and beyond. I'll then turn the call over to Anne-Marie to discuss our clinical development update with a focus on DMD. Kyle will discuss our financial results and I will end with a summary of upcoming catalysts expected in 2023. We'll then proceed to the Q&A portion of the call where Chandra will also be available. At Wave, we believe the power of our PRISM platform and the potential of our current and future pipeline has positioned us to become the leading RNA medicines company. PRISM is the most versatile discovery and drug development platform in the industry. It offers three distinct RNA targeting modalities: editing, slicing and silencing, so that we can design built for purpose molecules that optimally address disease biology. Our platform reflects nearly a decade of investment in proprietary chemistry which are disrupting the existing dogma of oligonucleotides, and are opening up new capabilities. Our chemistry advancements have also enabled us to push into new areas of disease biology that were not accessible or were inadequately addressed with other modalities. And we continue to build a pipeline of innovative first or best-in-class candidates. Importantly, every data point generated by Wave is incorporated into PRISM to accelerate learnings about oligonucleotide structure and optimization, and improve our probability of success with each new target. Today, we have all the pieces in place to achieve our vision of delivering life changing RNA medicines so that patients and families can realize a brighter future. 2022 was a transformational year for Wave, resulting from focused and deliberate execution. Entering 2023, we have clinical validation of our PRISM platform, a leading…

Thanks, Paul. In 2022, we delivered key data sets for each of our lead programs, including positive clinical data from our DMD, HD, and ALS/FTD trials. I will review each of these programs today beginning with WVE-N531 for DMD and the next steps we are taking to evaluate dystrophin. Next, WVE-006 shown here in green is rapidly approaching the clinic. We believe 006 may also be best-in-class in the treatment of AATD and our partner GSK is well positioned to maximize the opportunity of 006 around the world. Finally, we continue to advance our CNS silencing program shown on the right of this slide in dark blue under our Takeda collaboration. WVE-003, which is the first allele selective candidate for Huntington’s disease and WVE-004 for C9orf72 associated ALS/FTD. In 2022, we demonstrated target engagement in the CNS for both programs after patients receive a single dose of 003 or 004 and we're working towards the next stage [indiscernible]. Starting with WVE-N531, in December 2022, we achieved proof-of-concept for N531 [indiscernible]with DMD amenable to exon 53 skipping. This study was designed to rapidly evaluate whether N531 as a pharmacological profile, but also comes the limitations of our first generation DMD candidate dystrophin with muscle concentration and safety and tolerability as primary endpoint. Three ambulatory boys participated in this open-label, intra-patient dose escalation clinical trial. The boys received single escalating doses of one, three, six and 10 mg/kg of N531. In the multidose portion of studies, the same boys received three doses of 10 mg/kg every other week. A biopsy was taken after three bi weekly doses of treatment. We were excited to observe the high muscle concentration of N531, which exceeded our expectations and even more excited to see 53 exon skipping at this time point. It's particularly notable that all…

Thanks, Anne-Marie. Turning to the financial. Our net loss for the three months ended December 31, 2022 was $43.7 million as compared to $34.8 million in the same period in 2021. The increase in net loss year-over-year was primarily driven by increased spend on our clinical program, as well as increased compensation-related expenses. We recognized approximately $1.2 million in revenue from our Takeda collaboration for the fourth quarter of 2022 as compared to $1.8 million in the same period in 2021. R&D expenses increased $5.3 million to $31.1 million in the fourth quarter of 2022 as compared to $25.8 million in the same period in 2021. This increase was primarily due to increased external expenses related to our AATD, C9 and DMD program and compensation related expenses, partially offset by a decrease in spending in our HD program. General and administrative expenses increased $1.6 million to $13.7 million for the fourth quarter of 2022 as compared to $12.1 million last year, primarily due to increases in professional and service fee expenses. We ended the fourth quarter with $88.5 million in cash and cash equivalents as compared to $150.6 million as of December 31, 2021. Additionally, in Q1 2023 where strategic collaboration with GSK became effective and provided upfront cash of $170 million to Wave. Accordingly, we expect our cash and cash equivalents will be sufficient to fund operations since 2025. As a reminder, we do not include future milestones or opt in payments under our GSK or Takeda collaboration in our cash runway. I'll now turn the call back over to Paul.

Thanks, Kyle. I am proud of how the team continues to execute with resolute focus on unlocking program value through our ability to align the right target with the best oligonucleotide approach, be that editing, slicing or silencing with antisense or RNAi. In the year ahead, we expect to deliver on multiple pipeline and platform candidates. With our clinical silencing programs, we're advancing two candidates for which we expect additional data in the first half of this year. WVE-003 and HD is the only clinical stage mutant Huntington lowering wild Huntington sparing approach, while WVE-004 offers a variant selective approach to C9orf72 associated ALS/FTD. We'll have substantial data sets to determine the next step for these programs and if successful would initiate discussions with our partner Takeda. With slicing, WVE-N531 is demonstrating the potential to be a best-in-class approach in the DMD space. We plan to initiate dosing in Part B in 2023 and announce data in 2024. If successful, these data would unlock high value DMD franchise. In addition to DMD, we see future expansion opportunities for slicing in other muscle diseases as well as CNS. With editing, WVE-006 is the most advanced candidate and potentially a best-in-class approach for AATD. We expect transition of this program to the clinic in the second half of this year, if successful, WVE-006will unlock the broad potential of AIMers. With RNAi, our preclinical data suggests that we have best-in-class potential with this modality and is shaping up to be a powerful silencing component our RNA medicines platform with applicability in the liver, CNS and beyond. We are rapidly advancing discovery activities in RNA editing and beyond and expect to announce new programs and share preclinical data this year. Finally, we are already advancing collaboration activities with GSK with potential for additional cash inflows over the course of this year and beyond. 2023 promises to be another great year of PRISM innovation and progress towards bringing medicines to patients. With that, I'll now turn it over to the operator for Q&A.

[Operator Instructions] The first question comes from Salim Syed with Mizuho. Your line is now open.

Hi, good morning. This is Mike Linden on for Salim. Thanks so much for taking our question. I guess just on WVE-N531. So for Part A, we saw this three patients at the six weeks starting after the 10 milligram dose. What are the plans to follow-up on these patients? Is there any update you can provide maybe on the protocol going forward here for the first three patients? And then I guess to follow-up with that on Part B, maybe how should we be thinking about the regulatory pathway going forward and potential timeline for that?

Thanks. So the Part B that we announced today looking at up to 10 boys includes boys who were originally enrolled in our Part A, so they have the opportunity to also enroll in this Part B extension. With regards to regulatory pathways, as you're alluding to, there are well trodden regulatory paths for accelerated approval on the basis of dystrophin. And obviously, when we have our data, we will be assessing and discussing with the regulators what the best pathway is for us.

Got it. Thanks.

Please stand by for our next question. Our next question comes from Joon Lee with Truist. Your line is now open.

Hi, thanks for the updates and for taking our questions. The FDA is hosting a couple of Adcoms that directly impacted programs. One is happening today to discuss the neurofilament light chain as a potential surrogate endpoint. And the other is sometime next month to discuss dystrophin as a biomarker for DMD. How likely do you think the Adcom will be supportive of these biomarkers? And how would these decisions impact your clinical development strategy for your programs? And I have a quick follow-up.

Sure. So obviously, we'll be watching the outcome of these Adcoms very closely. And I can't of course state what the outcome will be, but I would say that any indications that the FDA is still supporting the use of biomarkers to aid the approval of new therapies, the rare diseases is highly encouraging and supported, of course, by us. And when we see the outcome of those ADcoms we will be assessing how it impacts our own therapy.

I think the added nuance to, Joon, your second point on the direct the Adcom on micro dystrophin. I mean, I think it will be an interesting discussion, one on the continued support of dystrophin as a regulatory endpoint potentially for accelerated approval. But I think what we think consistently in the exon skipping field is, approvals based on dystrophin level. So I think, again, it's encouraging to see the agency continue to leverage these clinical biomarkers as potential registration info.

Great. And regarding the Huntington's program, are you looking to -- what exactly are you looking to achieve with the additional SAD study before you feel confident enough to advance to MAD study? Correct me if I'm wrong, but the 30, 60 and 90 milligrams were already studied in the prior SAD study? Thank you.

Yes. I think that's the follow-up of the expansion cohorts are going to help with them read that I think establish the dosing regimen for multi dose in the progress?

Yes. So that original cost that we reported was underpowered and so we wanted to further explore those doses before we move into the multi dose cohort. Obviously, when you move into the multi dose, you want to be sure that you are selecting the right dose for a continued study. So it's the logical and normal way to follow the drug development.

Thank you.

Please stand by for our next question. The next question comes from Paul Matteis with Stifel. Your line is now open.

Hi. This is Julian on for Paul. Thanks so much for taking our question. On the AATD program, is there anything specific or out of the ordinary that may be required for the CTA? Just given it's a first of its kind technology entering the clinic? So if there's any specific ask from the regulatory agency or any other requirements, it would be great to hear. Thanks so much.

No. There are no specific or unusual requests for our filing CTAs. They'll just follow the normal route for a CTA filing.

And I think stepping back, I mean, this is an important reason of our unique approach of using oligonucleotide to engage with endogenous RNA editing. So again, I think the question obviously refers to a whole bunch of other approaches predominantly based on the DNA editing space, the base editing space. But I think our approach has been to use endogenous enzymes as we've said very similar to what's used against Ago2 for RNAi with acceptable for [indiscernible]. And so we're following a well driving path of RNA therapeutics.

Great. Thanks so much.

Please stand by for our next question. The next question comes from Luca Issi with RBC. Your line is now open.

Perfect. Thanks for taking our questions. This is Lisa on for Luca. Just on the APP program. I have a three part question here. It looks like your mouse data is Intracerebroventricular delivery. But is it fair to assume that if you were to move this program into humans, you would use [intrasaccular] (ph) delivery like [Nylem] (ph) is using for their program? Also on the chemistry, we know a Nylem is using C16 ligand. So just wondering if you can remind us about the chemistry that you're using for your program for CNS delivery here? And finally, just maybe a bigger picture question. How are you planning to differentiate your siRNA platform? Is there any technological differentiation that we should be aware of? Or is it more of an indication selection type of play here? Any color would be much appreciated. Thank you.

That's great. And look, I appreciate the question, because a lot of this is building on work that we began last year and, obviously, we're continuing to build on. So I think to your question, starting with the first on mouse data and ICV delivery, that's pretty standard for mice. But obviously, we have a long history of looking at CNS translation from IVB data in mice to [indiscernible] nonhuman primates and ultimately into patient. And again, in that case, using the [indiscernible] dose. We do recognize the translational value and we've seen that data from others in the space. I think what was impressive to us is, it doses better our own par, if not, more effective potentially than others have shown. We've seen target engagement across all regions of the brain with ICV administration. I think that's important because I think there's always a question of where do these drugs distribute in CNS. I know these questions come up a lot as we think about potential target implications. But I think it's encouraging again with the first CNS experiment to be able to see broad potent. And most importantly, I think relative to what we've seen with others, it's durable. We know that's an important function even when we think about ICV – sorry, IC injection is that the durability effect is critical because, obviously, it means reduce dosing administration frequency. So we're encouraged by again the initial data, exciting to continue to see more work and it's obviously something that we’ve has interest in from a number of parties. Additionally, to that, you asked a question about chemistry and I think that was the piece that was, I think, unique to what we've been developing all along around PN chemistry distribution. So again, utilizing our unique chemistry,…

Please standby for our next question. Next question comes from Mani Foroohar with SVB. Your line is now open.

Hi. [indiscernible] on for Mani. Thank you for taking our question. Regarding GSK collaboration, so for 006 first, given that this first in human study could potentially derisk RNA editing, how quickly could we expect the expansion of clinical development in other follow on indication? And more broadly, in regard to the collaboration, should we expect to see simultaneous program moving on to the clinic alongside GSK? Or is there a limitation in terms of the number of programs that could be pushed through development every year?

Thank you for your question. And again, I'll pause between them in case it was unclear. So, yes, as you know, the first in human study we announced this year will begin with that translation to the clinic. And I think this is an exciting meaningful inflection for our relationship with GSK. And most importantly for the AATD patients with whom we're going to accelerate, Wave developing this medicine for initially. I think to your point, the other substantial portion of this collaboration is the research and discovery portion of the collaboration. And I said in the beginning, this is underway. And so, we did say that this has those targets that get selected. There's a research period where as we said we announced the deal, we could be working on more, what are called, target validation, more programs than they have the ability to select and nominate. And so, I think what's exciting for us is, we are working together, we are initiating some of these programs to begin to start working together to understand the target. And I expect over the course of this year, more opportunities to keep you all updated on our progress with that relationship. Both on the targets that GSK is working on, although we may not be able to disclose the targets per se, but at least the momentum on that side of the collaboration. But importantly, on the other side of the collaboration where our access to unique genetic insights enable Wave distillate programs. And those programs, we will be able to share our progress on. So it really is a multi [indiscernible] collaboration. I think it's off to a great start. And obviously, all of that gets driven on the productive translation of the first potential clinical program, [indiscernible] excited about our progress. I'll pause just because I've lost the tail end of your last question just to make sure we answered your question.

Thank you. I guess just as a follow on regarding those, would there be a pathway to potential foster approval in a subset of population for AATD?

So I think that's something that we and importantly GSKs are interested in exploring, obviously, off of the biomarker. Again, it's an important factor of how we think about -- thinking about programs that we select as we're developing our programs within our pipeline, which is, if you have a clinically validated biomarker and that biomarker is actually the treatment for disease on the case of Alpha-1 antitrypsin deficiency, it's the deficiency of Alpha-1 antitrypsin deficiency protein. If you can restore that protein back to functional levels and that creates the potential for registration. So I think both we and GSK are interested in utilizing that biomarker as a potential strategy, but thinking then more broadly about how to continue to build that to optimize the commercial. So I think there's a lot of opportunity for AATD and we're excited to work with our partners to maximize that opportunity.

Thank you.

[Operator Instructions] Our next question comes from Joon Lee with Truist. Your line is now open.

Hey, thanks for taking our follow-up. Regarding the sRNA program, angiotensolivos can just about do many of the same things that sRNA's can do. So how are you thinking about diseases for which ASL may be more appropriate versus sRNA? And it's a bit of a loaded question, but in your opinion, do you think the valuation discrepancy between [indiscernible] differences in the size of the adjustable targets or some perceived superiority of one versus the other platform? Just would appreciate your thoughts there. Thank you.

I'll take your last question first and say that you all are much better than I am around assessing the differential valuation between [indiscernible]. I think they're both companies that have been in the space for a long time and are both trying to address unmet need as best possible utilizing their platform. I think to your first question, I think what this technology capability inside Wave does by having what we believe through the best in class RNAi approach, is really do what we set up from the beginning to do, which is not to be restricted by a particular modality. I think if you're a hammer everything looks like it now and the opportunity for us to say, well, what's the best way to address the given target with the right tool? I think this establishes for silencing the ability for us to think creatively really about what is the best opportunity for different indications and separate tissues, not because that's the technology we have, but we have the optionality of thinking about qualitative. I think that's the real opportunity set. I think that was one of the real drivers for why we were excited usually to work with GSK is really to think about a target universe. Where we're unrestricted on RNA medicines and can really think about the flexibility of again, right target right indication. Again, a great example is, we could have used RNAi to silence AATD as others are doing. We thought for the biology, the best approach was to correct it, fix it and restore the protein function, not just by giving it like protein ingredient, but actually fixing it and generating more of it and that comes through RNA editing. And so, I think having these tools on our hand, to really say best approach to deal with really important meaningful diseases, I think does set us up for future success.

When do you think we'll see first update on sRNA?

As we said, I think we're going to give a broader update, historically, as you know, we have done R&D days with big updates both on platform. And then importantly, programs as we shared earlier, when we typically share updates on programs, it's not just a list of target that usually is substantiated by data. So excited to share progress later this year.

Thank you.

I show no further questions at this time. I would now like to turn the conference back to Dr. Paul Bolno for closing remark.

Well, thank you everyone for joining the call this morning. This is an exciting time for our organization and we are grateful to every Wave employee for their dedication and unrelenting commitment to our mission and to the patients and families we serve. Have a great day. Thank you.

This concludes today's conference call. Thank you for participating. You may now disconnect.