Good morning. Welcome to the Wave Life Sciences fourth quarter and full year 2019 conference call. At this time, all participants are in a listen-only mode. As a reminder, this call is being recorded and webcast. I will now turn the call over to Kate Roush, Head of Investor Relations at Wave Life Sciences. Please go ahead.
Thank you, operator. Good morning. 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. Michael 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 31st, 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 Chief Executive Officer 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 Michael 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 modifications, allele-selective designs, and novel modalities like RNA editing. 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 three 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, pre-clinical work, and clinical development, and provide us with increased control and visibility of our drug substance supply chains. Using PRISM, we leverage the ability to control stereochemistry of each backbone position of an 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 bound 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 and 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 two clinical programs for Huntington's disease, our CNS-focused pipeline of stereopure oligonucleotides, 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 a safety profile that supported advancing to higher doses. Michael 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 SNP 3 mutation, and with overlap, up to 80% of the HD population carries at least one of SNP 1, 2, and/or 3. Last week, we presented our SNP 3 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 solely and potently silence the transcripts that contain the hexanucleotide repeat, which drives the formation of toxic RNA and abnormal proteins in brain tissue. Like our SNP 3 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 transcripts 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. 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 two 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 16 times more potent than a stereorandom reference compound. In vivo, we've seen similar potent target knockdown with good durability out to eight weeks of treatment. Beyond CNS, in 2019, we continued to work on two ophthalmology programs, USH2A for Usher syndrome type 2A and RHO P23H 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 RHO P23H program, which is designed to selectively silence RHO P23H transcripts. We continue to explore opportunities to advance our work in ophthalmology. We've also continued to evolve our PRISM platform in 2019. Through PRISM, we can design and optimize diverse sets of stereopure oligonucleotides, which allows us to characterize and compare the behavior of various stereoisomers.
With each target and a growing body of in vitro and vivo and clinical data from our programs, we gain insight into how the interplay between sequence, chemistry, including 2'-prime 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 off 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 will 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 two approaching the clinic, which positions Wave to potentially have four 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 31st, 2019, compared to $146.7 million for the year ended December 31st, 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 programs, 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 collaborations, 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. Michael?
Thanks, Dave. 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 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 a 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's loss of function as a likely driver of HD pathogenesis.
Specifically, one 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. 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 to 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-to-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. In a 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 I-B/II-A multi-center, randomized, double-blind, placebo-controlled trial, which is evaluating safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of 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 four 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 was a 12.4% reduction in mutant huntingtin protein in the CSF when comparing all patients treated with multiple doses of WVE-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 the 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, 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, Michael. Our latest modality, RNA editing, which we initially announced at our research day last year, continues to advance. We've developed this program over a relatively short period of time, 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 oligonucleotides, 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 nanoparticles for viral delivery. Second, our oligonucleotides are based on PRISM, so they are fully chemically modified and stereo pure.
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 transcripts, 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 programs. Importantly, we believe these will be the first in vivo RNA editing data using endogenous ADAR with GalNAc conjugates. In summary, 2020 is a year of execution.
In the first months of this year, we've initiated the 32-milligram cohort for our PRECISION-HD2 study and right-sized 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 two 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 two 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 four 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 filings 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. With that, we'll open up the call for questions. Operator?
At this time, I would like to inform everyone if you would like to ask a question, please press star, then the number 1 on your telephone keypad. We'll pause for just a moment to compile the Q&A roster. Your first question comes from the line of Debjit Chowdhury with H.C. Wainwright.
Morning. Thanks for taking the call. 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? How many patients in that cohort might we expect an update on in the second half?
Hi, this is Michael. 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. On the first part how many would you need to dose? Do you need to dose everyone in the cohort to escalate, I assume?
Our intention is to dose the complete cohort. We're not going to be dosing less than what we intended to.
Okay. All right. That's great. Thank you. I'll get back in this queue.
Your next question comes from the line of Whitney Eigen with Guggenheim Securities.
This is Evan for Whitney. Just again 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?
You broke up there in your call. This is Michael 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. One follow-up. On the SNP-3 trial, can you provide more details around trial design there? How do you plan to design this trial versus PRECISION-HD studies?
Yeah, this is Michael again. 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. More to come later in the year on that.
Got it. Thank you.
Your next question comes from the line of Mani Foroohar with SVB Leerink.
Hey, guys. Thanks for taking my question. I got two quick ones. Does the oligo for SNP 3 use a similar or identical backbone chemistry as the first two SNPs? Have there been many modifications that you've made as you continue to extract some learnings from that program? 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 six targets? Are there sort of stage-gating studies you have to do? I'm just trying to think about the timeline of those getting into the clinic and the scale of any potential milestone cash flows as those become early clinical assets.
To answer your first question relating to the design of SNP 3, as we said on the call, we've leveraged what we've learned around the PRISM platform with new two-prime modification backbone designs and the interplay with stereochemistry. SNP 3 has a different design than SNP 1 and 2, and that gives a different profile pharmacologically. To Michael's point, we want to understand that.
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. We're very excited about the implementation, not just in how we're using that in SNP-3, 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 six programs in the collaboration. Those are moving forward.
We are generating data sets. As data gets generated, we provide guidance as we just did around the transition of those programs. Starting with the first program that we identified, we'll have, as we said, expect two more this year. We haven't guided beyond that. That's the best way to think about it. If you think about this Category 2 structure, we have the potential for $1 billion in milestones pre-commercially and about another post-commercial with a 15% loyalty. Pretty substantial in terms of the activities. We're excited about the progress of the collaboration. We will keep things moving.
Great. Thanks for taking my question, guys.
Your next question comes from the line of Yun Yang with Canaccord Genuity.
Thank you. Based on the SNP 2 data last December, as you up the dose to 32 mg in SNP-1 and SNP 2 and starting SNP-3 program second half of this year, how do you think your patient enrollment would be based on the data?
Hi, Yun. This is Michael. Well, I have to say for the SNP 2. Let's start with SNP 2. The release of the data at the end of last year actually helped our recruitment a fair amount simply because target engagement and good tolerability tend to pique interest in physicians and patients. We're not having any issues with identifying patients, and that'll drive this cohort and any additional cohorts that are required. The interesting thing about SNP 3 is that when you have the screening for SNP 1 and SNP 2 complete, you also have samples that allow you to assess for SNP 3. It's the same type of technology. 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 SNP 1 or SNP 2 to be potentially eligible for SNP 3.
That's how we're going to start, and then we're going to go from there. We'll see where it goes. I have no concern about identification of patients in the group.
Thank you. For SNP-1 and SNP 2 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.
Thank you. My last question is on financials. Based on the cash guidance, is it reasonable to think that potential collaboration milestone payments from partners would be around $30 million in 2020?
We have not broken out the individual cash payments from the R&D expenses, we do expect those R&D expenses being the contributing factors to the continuation of the .
Thank you.
Your next question comes from the line of Salim Syed with Mizuho Securities.
Hi, good morning. This is Bennett from Salim's team at Mizuho. Thanks for taking our questions. 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? Then from the preclinical studies, did you find any off-target genes silenced? Thanks.
I think I'll take the first part of the question.
The level, the threshold.
That threshold level.
Correct.
There are two things we are looking at in thresholds. We think they're both important in treatments. One is potency. Obviously that's the level of knockdown. We want to see as much knockdown as possible. We haven't guided to a specific threshold. 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. Reducing the frequency of those injections. As we saw, out at eight weeks, we still saw durable knockdown of targets. Again, the potential, not just for potent knockdown, but durability as both being equivalent. Thirdly, again, being variant specific. Again, leaving the non-hexanucleotide repeat-containing transcripts intact.
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 three critical thresholds of the program. Again, why we're excited about the program that's currently advancing into the clinic.
Yeah. This is Michael. Just to round that out, in addition to those criteria, obviously we are very sensitive during the design process and the preclinical process to any sorts of off-target effects there might be, because that would manifest as either specific or non-specific tolerability. Obviously, balancing all those criteria are important for the molecule that we eventually take forward.
As we demonstrated, just to follow up on that, in the slide where we showed the crystal structure and kind of our first crystal structure, we were able to look at that engagement. That degree of specificity is a key criteria in our designs and we think a core advantage of the program going forward.
Okay. Thank you very much. That was helpful.
Your next question comes from Paul Matteis with Stifel.
Hey, thanks so much for taking my questions. I think when the original SNP 1, SNP 2 data came out, there were a couple 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? Secondarily, is there any more granularity you can give us on what you saw at that 16 mg dose? I feel like that's kind of the main question I get as it relates to how can we be confident that 32 mgs will look better. Thanks so much.
Yeah. Hi, Paul. Michael. 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 and wild type. It could be something that as we increase the dose, we'd see clearer. Those questions still remain, so there's no update to provide on that. In terms of the dose response, as we said also all along that, what we did see was this, when you looked at pooled active versus placebo, we saw an effect, and we saw, based on analyses, suggestion of a dose effect.
It was that suggestion of a dose effect that led us to the plan that we're now executing to increase the dose. 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 numerically, was 16 better than eight, better than four, or?
What we said is that 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. 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.
All right. Thanks, Michael. I appreciate it.
As we get to the end of the year, we'll be breaking all of that out for you.
I think as we-
Yeah. 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 SNP three stuff at CHDI. It seemed like that would have been a great opportunity to show more color here. What are your thoughts on that? You've got AAN as another opportunity as well, where Roche had some data last year.
Yeah. We have all intention, just like with suvodirsen, of presenting this at a medical meeting, but we also don't want to present partial datasets at a medical meeting. The suvorexant dataset will be a complete assessment of what we have. That is the approach we'd like to take with HD. There are medical meetings that we're thinking about where we would present these data. The intention is to show the complete dataset, not an interim analysis from the ongoing study.
I think, Paul, that was some of the discussion, as you said, maybe there was some context. This was an interim update on an ongoing study. To that end, we provided that interim update because we wanted to be transparent, share that the study was progressing. We will present the full data when the full data is complete.
Fair enough. Thanks so much.
Your next question comes from the line of Yaron Werber with Cowen.
Hi, guys. This is Brendan on for Yaron. Thanks very much for taking the question. Just two quick ones from us. Let's pile on the 32 mg dose, but I was actually just wondering how you came to actually decide on that 32 milligrams, if there was any preclinical work you felt correlated well with that dose, and why maybe you didn't think to go even higher. To that effect, would you consider adding another dose cohort if safety looks good down the line, and you think you can get better knockdown? One other question just on the C9orf72. Obviously a pretty exciting target. Just in terms of timing for the year, are you looking at the SNIP3 program and C9orf moving roughly in parallel at this point?
Are you maybe thinking to focus on either ALS or FTD first as you move that one into the clinic? Thanks very much.
Hi, this is Michael. First of all, starting off with the 32 milligrams. As you'll recall, for our preclinical work, we had in vitro evidence in fibroblasts of differentiation between mutant and wild type, and that was what we had when we started. As we've gone along now, we've collected human data, which 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. We thought a doubling from 16 to 32 was reasonable and probably the most that an ethics committee and a regulatory authority would want. Doubling is a pretty big increase. That was sort of what guided the 32.
Whether we go to double that from there, that's going to be dependent upon what we see with the 32. 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. That's where we'll go. That's our intention, assuming that's supported by the 32. That's the intention for HD. In terms of C9orf72 versus SNP 3, 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.
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.
Got it. Thanks very much.
Thank you.
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.