WAVE Life Sciences Ltd (WVE) 2019 Q4 法說會逐字稿

Good morning, and welcome to the Wave Life Sciences Fourth Quarter and Full Year 2019 Conference Call. (Operator Instructions) As a reminder, this call is being recorded and webcast.

I will 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 Wave's fourth quarter and full year 2019 operating results. With me here today is Dr. Paul Bolno, our President and CEO; Dave Gaiero, Interim CFO; and Dr. Mike Panzara, Wave's Chief Medical Officer.

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 Investors 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, 2019. 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 Bolno, President and CEO of Wave Life Sciences. Paul?

Thank you, Kate. Good morning, and thank you for joining us today. I'll start today's call with a few introductory remarks and a company update. Next, Dave Gaiero will discuss our financial results and then Mike Panzara will provide an update on our PRECISION-HD development programs. I'll conclude with an update on our ADAR-mediated RNA editing program and an outlook for 2020.

Wave is a genetic medicines company that was founded to design and develop novel oligonucleotide therapeutics using our proprietary PRISM platform. This unique platform enables us to design therapies in a rational way through a deep understanding of how the interplay among sequence, chemistry and stereochemistry impact key pharmacologic properties. Over the past decade, our chemistry has progressed and evolved, enabling us to build a broad pipeline that includes different modalities, a range of disease targets and innovative properties such as unique backbone modification of Allele-selective designs and novel modalities like RNA editing.

Going forward, we will continue to innovate and expand our pipeline. The foundation of this pipeline is our work in CNS, including Huntington's disease, ALS and FTD and several programs in collaboration with our partner, Takeda. Over the course of our relatively short history, we've moved 3 programs into clinical development and have embraced and been humbled by the learnings that have come out of these and other programs along the way. Our dedicated and experienced team is actively preparing to advance 2 additional programs into clinical development in the second half of this year.

Finally, we have established internal manufacturing capabilities that enable us to produce oligonucleotides to support our platform, preclinical work and clinical development and provide us with increased control and visibility of our drug substance supply chain. Using PRISM, we leveraged the ability to control stereochemistry of each backbone position of oligonucleotide to rationally design potential therapeutics. Validating the importance of backbone structure to controlling RNase H activity, we have demonstrated the x-ray crystal structure, which we initially presented at our research day last October. As seen on the slide, the image depicts RNase H balanced to a heteroduplex containing a C9orf72 mRNA target in red and a stereopure oligonucleotide in blue. Controlling the activity of RNase H is paramount to Allele-selectivity, the core differentiating feature in our Huntington's disease programs, where we have designed compounds, including WVE-120101, WVE-120102 to target single nucleotide polymorphisms, or SNPs, to selectively lower mutant huntingtin. Similarly, we have designed stereopure oligonucleotides with a transcript selective approach for our C9orf72 program aimed at treating ALS and FTD.

During the fourth quarter and recent months, we have made important progress in advancing our 2 clinical programs for Huntington's disease. Our CNS focused pipeline of stereopure oligonucleotide and our proprietary PRISM platform. First, our Huntington's disease programs, PRECISION-HD1 and PRECISION-HD2 are the first and only in clinical development that are designed to selectively lower mutant huntingtin protein, while leaving wild-type huntingtin relatively intact. Wild-type huntingtin is important for neuronal function, and there is increasing evidence that wild-type huntingtin is an essential protein for basic health, both in the central nervous system and systemically. At the end of last year, we reported the first results from our ongoing PRECISION-HD2 clinical trial in Huntington's disease, which demonstrated mutant huntingtin reduction and no change in total huntingtin as compared to placebo as well as the safety profile that supported advancing to higher doses. Mike Panzara will provide further updates on these programs later in the call.

Rounding out our HD portfolio is our SNP3 program, which is on track to initiate clinical development in the second half of the year. Approximately 40% of the HD population have a SNP3 mutation and with overlap up to 80% of the HD population carries at least one of SNP1, 2 and/or 3. Last week, we presented our SNP3 preclinical in vitro and in vivo preclinical data at the CHDI conference, and we are excited to introduce this program into our portfolio of clinical programs for the potential treatment of Huntington's disease. Our next program also approaching the clinic aims to address Amyotrophic Lateral Sclerosis and Frontotemporal Dementia caused by mutation in the C9orf72 gene. Our C9 program is designed to durably and potently silence the transcripts that contain the hexanucleotide repeats, which drives the formation of toxic RNA and abnormal proteins in brain tissue.

Like our SNP3 program, we have used transgenic mouse models to help guide our preclinical development. In these in vivo studies, we've shown potent knockdown of both the repeat containing transcript and dipeptide, while the C9orf72 protein is preserved. We continue to advance our C9orf72 program and are on track to initiate clinical development in the second half of the year.

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We continue to develop multiple preclinical CNS programs with our partner, Takeda, targeting CNS diseases, such as Parkinson's and Alzheimer's. As a reminder, our agreement with Takeda included $230 million in committed capital, which includes at least $60 million in research support to advance multiple preclinical targets over the term of the collaboration.

Last year, we achieved target validation in vivo with a lead compound for one of the programs and expect 2 more in 2020. As shown on the slide, we highlight in vitro and in vivo results from an undisclosed target that we are working on in the collaboration. In vitro, we've demonstrated that our compound is 16x more potent than a stereorandom reference compounds. In vivo, we've seen similar potent target knockdown with good durability out to 8 weeks achievement.

Beyond CNS, in 2019, we continued to work on 2 ophthalmology program, USH2A for Usher Syndrome Type 2A and RhoP23H for retinitis pigmentosa. In October 2019, we presented in vitro and ex vivo preclinical data on our USH2A program, which is designed to promote USH2A exon 13 skipping. And in vitro data on our RhoP23H program, which is designed to selectively silence RhoP23H transcripts. We continue to explore opportunities to advance our work in ophthalmology. We have also continued to evolve our PRISM platform in 2019.

Through PRISM, we can design and optimize diverse set of stereopure oligonucleotide, which allows us to characterize and compare the behavior of various stereoisomers. With each target and a growing body of in vitro and in vivo and clinical data from our programs, we gain insight into how the interplay between sequence, chemistry, including 2-point modifications in backbone chemistry and stereochemistry impacts activity. Most importantly, we build these learnings into future programs. For example, our SNP3 and C9orf72 programs are both designed with optimized chemistry of our platform. One of the exciting new developments to come off of our PRISM platform is our ADAR RNA editing modality, which I'll touch on more later in the call.

While Wave had many accomplishments in 2019. We also had an unexpected and disappointing setback in the fourth quarter with our DMD program. We are committed to better understanding the suvodirsen clinical data and incorporating any learnings into future programs. We are also committed to sharing these clinical data with the Duchenne community and others, and we'll have additional results analyzed in time for presentation at the Muscular Dystrophy Association conference at the end of this month.

In summary, Wave has an innovative and differentiated pipeline, led by our CNS development programs, including 2 approaching the clinic, which positions Wave to potentially have 4 clinical programs in 2021.

With that, I'll turn the call over to Dave Gaiero to review our fourth quarter and full year financial results. Dave?

Thanks, Paul. For the fourth quarter of 2019, we reported a net loss of $56.8 million compared to $37.9 million for the same period in 2018. We reported a net loss of $193.6 million for the year ended December 31, 2019, compared to $146.7 million for the year ended December 31, 2018. The increase in net loss in the fourth quarter and full year was largely driven by increased research and development efforts and continued organizational growth, both of which included costs and efforts, including manufacturing, in preparation for the potential commercialization of suvodirsen.

Research and development expenses were $49.1 million in the fourth quarter of 2019 compared to $39.8 million for the same period in 2018. Research and development expenses for the full year were $175.4 million compared to $134.4 million for the prior year. The increase in research and development expenses in the fourth quarter and full year was primarily due to increased external expenses related to our clinical activities, including our HD programs and our now discontinued DMD program as well as increased investments in PRISM and other research and development expenses.

General and administrative expenses were $13.8 million for the fourth quarter of 2019 compared to $12.8 million for the same period in the prior year. General and administrative expenses were $48.9 million in 2019 compared to $39.5 million in 2018. The increase in general and administrative expenses in the fourth quarter and full year was mainly driven by our continued organizational growth to support Wave's 2019 corporate goals. We ended 2019 with approximately $147 million in cash and cash equivalents.

While our cash utilization rate in the first quarter of 2020 will benefit from some wind down of DMD spend, there will also be costs associated with the termination of this program in the first quarter of 2020. We expect to begin to realize the results of our overall cost reduction efforts, including our workforce reduction, in the second quarter of 2020. We expect that our existing cash and cash equivalents, together with expected and committed cash from existing collaboration, will enable us to fund our operating and capital expenditure requirements into the third quarter of 2021.

I will now turn the call over to Dr. Michael Panzara, our Chief Medical Officer, who will provide an update on our clinical development programs. Mike?

Thanks, Dave, and thanks to all of you for joining the call today. From the start, we set out to develop an Allele-selective approach to treat Huntington's disease. Because we felt that preserving wild-type huntingtin was going to be essential to impacting clinical outcomes of the disease. As you know, patients with Huntington's disease have an expanded CAG triplet repeat in their huntingtin gene, which results in the production of mutant huntingtin protein. However, Huntington's patients still possess wild-type or healthy protein as well, which is important for neuronal function and some components of Huntington's disease are likely caused by the wild-type loss of function.

Two recent publications over the past few months are worth highlighting today as they support wild-type huntingtin loss of function as a likely driver of HD pathogenesis. Specifically, 1 publication concluded that a Striatum-specific defect in synaptic vesicle endocytosis was corrected by overexpression of wild-type huntingtin, but not by lowering total huntingtin. A second publication concluded that striatal projection neurons require huntingtin for motor regulation, synaptic development, cell health and survival during aging. Loss of huntingtin function could, therefore, play a critical role in Huntington's disease. Both of these publications support previous literature that we've discussed around the importance of wild-type huntingtin.

Also, just last week, I attended the 15th annual CHDI Conference, where I was privileged to have the opportunity to meet with many of the world's experts in HD. And I hear about much of the cutting-edge research underway in this disease area. During the meeting, an entire session was dedicated to understanding the importance of wild-type huntingtin in the normal and diseased states and the effects of modulation in vitro and in vivo.

From this session, and the Wave team's other discussions at the meeting, we gathered several critical takeaways. First, there were multiple presentations supporting that wild-type huntingtin has numerous critical functions throughout life, such as intracellular trafficking, cell-cell adhesion and BDNF transport. Next, near elimination of wild-type huntingtin in mice was detrimental regardless of when suppression began, suggesting a critical role for the protein throughout life, in addition to its well-known importance in embryonic and early development. Finally, in the study of non-HD patients, huntingtin protein loss of function mutations are highly constrained, which suggests evolutionary pressure against such loss of function mutations, again, speaking to the importance of the healthy huntingtin protein. While we and the community continue to learn more about the many various roles of this essential protein, there is no doubt as to its importance.

Turning to an update on our clinical studies, beginning with the PRECISION-HD2 study of WVE-120102, as a reminder, PRECISION-HD2 is our Phase Ib/IIa multicenter, randomized, double-blind, placebo-controlled trial, which is evaluating safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple doses at WVE-120102, in adult patients with early manifest HD, who carry a targeted single nucleotide polymorphism rs362331 that we refer to as SNP2. The trial includes both single and multi-dose portions where patients are randomized to either WVE-120102 or placebo and receive a maximum of 4 total intrathecal doses. After a single dose of treatment, patients undergo a washout period before entering the multi-dose portion of the trial.

In December of last year, we announced initial data from this trial, which clearly demonstrated target engagement with an ability to dose higher to maximize the effect. Specifically, there's a 12.4% reduction in mutant huntingtin protein in the CSF when comparing all patients treated with multiple doses of 120102 to those treated with placebo. These mutant huntingtin reduction results, coupled with the favorable safety profile observed, supported continued dose escalation in the PRECISION-HD2 study. In January, we initiated the 32-milligram cohort of the precision HD2 trial, and we look forward to sharing the results from this cohort, which is on track to be available in the second half of this year. The ability to go beyond this dose level will be determined by the single dose safety results of 32-milligram cohort as well as our existing preclinical data package.

An open-label extension trial, or OLE, for the patients that participated in the precision HD2 study is ongoing. Based on the preliminary clinical data announced last year, we are working to amend the OLE to enable all patients to receive the highest doses tested in our PRECISION-HD2 study. The PRECISION-HD1 study comes next, turning to 120101, which is being investigated in the ongoing precision HD1 trial. This trial also enrolled early manifest HD patients who carry a different SNP, rs362307 or SNP1. Based on the precision HD2 initial results, PRECISION-HD1 has remained blinded. And we are working diligently to initiate a 32-milligram cohort. We remain on track to deliver top line results for PRECISION-HD1, including those from the 32-milligram cohort in the second half of 2020.

An OLE for patients who participated in the precision HD1 trial was just initiated in February for patients that persist -- similar -- for patients, as I mentioned, who participated in this trial. Similar to the PRECISION-HD2 OLE, our goal is to enable patients in the PRECISION-HD1 OLE to be treated with the highest possible doses tested in the PRECISION-HD1 study.

With that, I'll hand the call back over to Paul. Paul?

Thanks, Mike. Our latest modality, RNA editing, which we initially announced at our research day last year continues to advance. We developed this program over a relatively short period of time. And while it's still early, we believe our technology confers several advantages over other players in the emerging RNA editing field. In 2019, our team evaluated more than 1,000 oligonucleotide, assessing a variety of sugar or base modifications, backbone chemistry and stereochemistry, as well as other parameters to gain insight into the relationship between an oligonucleotide structure and its ADAR activity.

Wave's approach to RNA editing has several advantages over others. First, our oligonucleotides freely enter cells and do not require lipid nano particles for viral delivery. Second, our oligonucleotides are based on PRISM, so they are fully chemically modified and stereopure. And finally, our oligonucleotides recruit endogenous RNA editing enzyme, ADAR, so no exogenous proteins such as CAS9 or chimeric ADAR are needed.

Most recently, our team presented a poster at the inaugural International Conference on base editing enzymes and applications. These results have demonstrated that we can achieve editing efficiencies of up to 70% across primary human cell lines in vitro. Additionally, as seen on the right side of the slide, we've achieved editing across several distinct RNA transcript, validating the technology across multiple sequences in vitro. We will begin in vivo studies in the near future for this program and look forward to sharing results this year, which will guide our initial therapeutic program. Importantly, we believe these will be the first in vivo RNA editing data using endogenous ADAR with GalNAc conjugates.

In summary, 2020 is the year of execution. In the first months of this year, we've initiated a 32-milligram cohort for our PRECISION-HD2 study and rightsized our organization, ensuring that we have the right team in place to continue and expand clinical development, advance our preclinical portfolio and sustain a leading nucleic acid discovery engine. In this first half, our team is focused on completing the preclinical and manufacturing activities required to submit 2 clinical trial applications in the second half of the year. As I just discussed, we'll have data to share from our first in vivo studies for our ADAR RNA editing programs this year.

Moving to the second half of the year, we'll have data readouts from the 32-milligram cohorts of our PRECISION-HD1 and PRECISION-HD2 trials. We continue to explore opportunities to advance our 2 ophthalmology programs and look forward to sharing our progress with you. We'll also continue to advance multiple preclinical CNS programs in collaboration with Takeda.

Looking to 2021, we anticipate having 4 clinical programs ongoing, including the potential for pivotal trials within our HD portfolio. In 2022 and beyond, we and our partner, Takeda will be positioned to deliver multiple potential CTA filing each year. We'll also have the first clinical data from our SNP3 and C9orf72 programs, both of which have been optimized with our PRISM chemistry. In addition, we expect to transition ADAR RNA editing from a platform capability to delivering multiple programs by that time.

Finally, we are capitalized to accomplish this exciting and innovative work in front of us. And with that, we'll open up the call for questions. Operator?

(Operator Instructions) Your first question comes from the line of Debjit Chattopadhyay with H.C. Wainwright.

This is Aaron on for Debjit. I just wanted to ask how many patients would you need to dose at the 32-milligram dose cohort to escalate. And how many patients in that cohort, might we expect an update on in the second half?

So this is Mike. From -- as you know, each cohort has 12 patients planned to be dosed, and we would expect that in the second half of this year, we would present the full data set from all cohorts.

Okay. And on the first part, how many would you need to dose? Do you need to dose everyone in the cohort to escalate?

Our intention is to dose the complete cohort. We're not going to be dosing less than what we intended to.

Your next question comes from the line of Whitney Ijem with Guggenheim Securities.

This is Evan for Whitney. Just to get on the PRECISION-HD trials. Will you be providing more information on if you guys dose higher than 32-mg dose? And as you dose up, will you provide safety updates through the year?

I -- you broke up there in your call. This is Mike again. I believe you were asking if we'd be providing interim updates throughout the year in the 32 or if we go higher. Our intention, as I said, is to second half of this year, provide you with an update on the progress of the study.

Got it. And then one follow-up. On the SNP3 trial. Can you provide more details around trial design there? I guess how do you plan to design this trial versus PRECISION-HD studies?

This is Mike again. I mean what we're doing now is obviously the design of that trial will be based upon the final profile that we evaluate with the preclinical work, which is ongoing. So more to come later in the year on that.

Your next question comes from the line of Mani Foroohar with SVB Leerink.

I got 2 quick ones. So does the oligo for SNP3 uses similar or identical backbone chemistry as the first 2 SNPs. Are there any -- been any modifications that you've made that you -- as you continue to extract some learnings from that program? And then the second question, how should we think about the tempo of preclinical assets in the Takeda partnership, moving into the clinic, do you anticipate advancing all 6 targets. Are there sort of like stage gating studies you have to do? And just trying to think about the time line of those getting into the clinic. And the scale of any potential milestone cash flows as those become early clinical assets.

So to answer your first question relating to the design of SNP3. I mean as we said on the call, we've leveraged what we've learned around the PRISM platform with new 2-point modifications backbone designs and the interplay with stereochemistry. And so SNP3 has a different design than SNP1 and 2, and that gives a different profile pharmacologically. To Mike's point, we want to understand that. And with the in vivo data sets that we're able to run in transgenic models we have much better visibility into helping to design that study. So we're very excited about the implementation, not just in how we're using that in SNP3, but in C9 and, to your next question, with Takeda across the multiple programs.

What's interesting in the Takeda collaboration, as we've said, and you alluded to it, there's up to 6 programs in the collaboration. Those are moving forward. We are generating data sets. And as data gets generated, we provide guidance, as we just did around the transition of those programs. So starting with the first program that we identified, and we'll have, as we said, expect 2 more this year. We haven't guided beyond that, and that's the best way to think about it.

If you think about this category to structure, we have the potential for over $2 billion in milestones precommercially and another -- sorry, $1 billion precommercially and about another post commercial with a 15% royalty -- royalty. So pretty substantial in terms of the activities. We're excited about the progress of the collaboration and we will keep things going.

Your next question comes from the line of Eun Yang with Jefferies.

Based on the SNP2 data last December. As you up the dose to 32-milligram in SNP1 and SNP2 and starting in SNP3 program in the second half of this year, how do you think your patient enrollment would be based on the data?

Yes. Eun, this is Mike. Well, I have to say for SNP2 -- let's start with SNP2. The release of the data at the end of last year actually helped our recruitment of their amount simply because target engagement and good tolerability tend to peak interest in physicians and patients. So we're not having any issues with identifying patients, and that will drive this cohort and any additional cohorts that are required.

Now the interesting thing about SNP3 is that when you have the screening for SNP1 and SNP2 complete, you also have samples that allow you to assess for SNP3. It's the same type of technology. So we're starting in a very good place with the sites who are already involved. And the ability for those patients who might not have qualified for SNP1 or SNP2 to be potentially eligible for SNP3. So that's how we're going to start and then we're going to go from there and we'll see where it goes. But we have no -- I have no concern about identification of patients in the group.

For SNP1 and SNP2 data in second half of this year, are those data coming out at the same time or they are coming out as they become available?

We haven't really provided guidance about the timing of that. We've just said the second half of this year that we will be actually providing both study results.

My last question is on financials. So based on the cash guidance, is it reasonable to think that potential collaboration milestone payments from partners will be around $30 million in 2020?

So we have not broken out the individual cash payments from the R&D expenses, but we do expect those R&D expenses being a contributing factors to the extension of the [run rate].

Your next question comes from the line of Salim Syed with Mizuho Securities.

This is [Bennett] for Salim Syed at Mizuho. Just a couple of quick ones for us. Regarding the C9orf72 program, is there any threshold that you are planning to achieve in terms of silencing? And then from the preclinical studies, did you find any off-target genes silence it?

So I think I'll take the first part of the question. The first part of the question in terms of level of threshold.

Correct.

There are 2 things we are looking at a threshold because there's -- and we think they're both important in treatments. One is potency and obviously, that's the level of knockdown and we want to see as much knockdown as possible. We haven't guided to a specific threshold, but we see substantial knockdown as demonstrated on the slides we showed earlier.

I think the second piece that we think is important beyond potency is durability. So reducing the frequency of those injections. As we saw, out of 8 weeks, we still saw durable knockdown of target. So again, the potential, not just for potent knockdown, but durability is both being equivalent. And thirdly -- again, being very unspecific. So again, take or leaving the non-hexanucleotide repeat containing transcripts intact.

So when we think about building the program and have run our in vivo models to demonstrate that, we look at potency, durability and selectivity as kind of the 3 critical thresholds of the program. And again, why we're excited about the program that's currently advancing into the clinic.

Yes, this is Mike. Just to round that out. I mean in addition to those criteria, obviously, we are very sensitive during the design process and in the preclinical process, any sorts of off-target effects there might be because that would manifest as either specific or nonspecific tolerability. So obviously, balancing all those criteria are important for the molecule that we eventually take forward.

I mean as we demonstrated -- and just a follow-up on that, in the slide where we showed the crystal structure and kind of our first crystal structure, we're able to look at that engagement. That degree of specificity is the key criteria in our designs, and we think a core advantage of our program going forward.

Your next question comes from Paul Matteis with Stifel.

So I think when the original SNP1, SNP2 data came out, there were a couple of controversies on the Wall Street side related to dose response and also related to the data from the mutant versus total huntingtin assays. I guess on the latter point, do you have any updated thoughts on why you saw a mutant change, but no change in total huntingtin? And secondarily, is there any more granularity you can give us on what you saw at that 16-mg dose? Because I feel like that's kind of the main question I get as it relates to how can we be confident that 32-mg will look better.

Paul, it's Mike. Regarding the first question about total and how to assess the total versus the mutant. As we said at the time, which was only a couple of months ago, we did see this reduction in mutant. We didn't see a big change in the total assay, meaning no change from placebo. We're trying to understand what that means. As we've said, that could be related to, again, a differential effect between mutant wild-type. It could be something that as we increase the dose, we see it clearer. Those questions still remain. So there's no update to provide on that.

And in terms of the dose response, as we've said also all along that, what we did see was this -- when you look at full active versus placebo, we saw an effect. And we saw, based on analysis suggestion of a dose effect. And that suggestion of a dose effect that led us to the plan that we're now executing to increase the dose. I mean we had statistical evidence of a dose effect. That's what guided us and that's why we're comfortable that increasing the dose is going to give us a greater effect.

Okay. I guess was -- numerically, was 16 better than 8, better than 4 or?

So what we said is that I think when you -- it is safe to assume that when you look at some of the individual comparisons, they're not going to each be statistically significant. We've said that previously. But what we did say is by looking across all the dose cohorts, pooling all of the data, what you do when you have a small data set that's variable, you look across the cohorts and at the highest doses tested we see a statistically significant effect. That's what we said, and that's why we're comfortable increasing the dose. As we get to the end of the year, we'll be breaking all that out for you.

I mean I think...

Yes, sir. And then just maybe one more question. Are there any plans to present this at a medical meeting. I think it's great you guys are presenting the suvodirsen data. I know you presented SNP3 stuff at CHDI. It seems like that would have been a great opportunity to show more color here. What are your thoughts on that? I mean you've got AAM as another opportunity as well, where Roche had some data last year.

Yes. I mean we have all intention, just like with suvodirsen of presenting us at a medical meeting, but we also don't want to present partial data set at a medical meeting. That suvodirsen data set will be a complete assessment of what we have. So that is the approach we'd like to take with HD. And there are medical meetings that we're thinking about that would -- where we would present these data. But the intention is to show the complete data set, not an interim analysis from the ongoing study.

And I think, Paul, that was some of the discussion, as you said, maybe there was some counter argument. I mean this was an interim update on an ongoing study. So to that end, we provided that interim update because we wanted to be transparent and share that the study was progressing. But we will present the full data when the full data is complete.

Your next question comes from the line of Yaron Werber with Cowen.

This is Brendan on for Yaron. Just 2 quick ones from -- about the pilot on the 32-mg dose. But I was actually just wondering of how you came to actually decide on that 32 milligrams? If there was any preclinical work you all correlated well with that dose. And why maybe you didn't think to go even higher when I guess, would you -- to that effect, would you consider adding another dose cohort? Is safety looks good on the line, do you think you can get better knockdown? And then one other question just on the C9orf72. Obviously, a pretty exciting target. Just in terms of timing for the year, are you kind of looking at SNP3 program and C9orf72 moving roughly in parallel at this point? And are you maybe thinking to focus on either ALS or FTD first as you move that one just a little quick?

Yes, this is Mike. So first of all, starting off with the 32-milligram. As you'll recall, our preclinical work, we had in vitro evidence in fibers of differentiation between mutant and wild-type, and that was what we had when we started. And as we've gone along now, we've collected human data, which then has guided us in terms of the dose escalation, as I've described. The jump from 16 to 32 was after seeing that the 16-milligram cohort was safe at a single dose. And that started the process of going up to 32, purely based upon safety. And we thought a doubling from 16 to 32 was reasonable and probably the most that an ethics committee and the regulatory authority would want, doubling is a pretty big increase. So that was sort of what guided the 32.

Whether we go to -- whatever, double that from there, whatever. I mean that's going to be dependent upon what we see with the 32. And in this case, we'll have more human data, human safety data, human pharmacokinetics, pharmacodynamic data that will then guide what that next dose level should be so that's where we'll go. And that's our intention, assuming that's supported by the 32. So that's the intention for HD.

In terms of C9orf72 versus SNP3, as it is now, teams are working diligently to move those along in parallel. Obviously, that's all guided upon the data that you generate. We look forward to engaging regulatory authorities and the community on the best ways to develop those in light of the data that we're generating from our preclinical studies. And as of now, our intention is to approach FTD and ALS in a similar way and to figure out, again, the best way to develop them as close to parallel as possible.

And at this time, there are no further questions, I would like to turn the call back over to Dr. Paul Bolno.

Great. Thank you again, everyone, for your time today and for your interest in Wave Life Sciences. Have a great day. Take care.

This concludes today's conference. You may now disconnect. Goodbye.