Ladies and gentlemen, thank you for standing by. Welcome to the Wave Life Sciences PRECISION-HD2 Top Line Results Call. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question-and-answer session. To ask a question during this session, you will need to press star one on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star zero. I would now like to hand the conference over to your speaker today, Kate Roush, Head of Investor Relations at Wave Life Sciences. Please go ahead.
Thank you, operator. Good morning, and thank you for joining us. With me here today is Dr. Paul Bolno, President and CEO of Wave Life Sciences, and Dr. Mike Panzara, Wave's Chief Medical Officer. This morning, we issued a news release announcing top-line data from our PRECISION-HD2 trial. Please note that this news release is available on the investor section of our website, www.wavelifesciences.com. The slide presentation that accompanies this webcast will also be available on our website following this call. 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, 2018. We undertake no obligation to update or revise any forward-looking statements for any reason. I'd now like to turn the call over to Paul Bolno, President and CEO of Wave Life Sciences.
Thank you, Kate. Good morning, and thank you for joining us. This morning, we issued a press release announcing top-line data from our ongoing PRECISION-HD2 trial in Huntington's disease, as well as addition of a higher dose cohort to this trial. These data are preliminary as the trial is still ongoing, but we are pleased to share that treatment with WVE-120102 resulted in a statistically significant reduction in mutant huntingtin compared to placebo in a pooled analysis across all those cohorts, with a safety profile that clearly supports exploration of higher doses. In addition, as Mike will discuss in more detail, an analysis of the data suggests a dose response that gives us confidence we may potentially achieve greater knockdown of mutant huntingtin with a higher dose. Briefly, I'll provide some opening remarks on Huntington's disease and our unique allele-selective approach.
Next, Mike will discuss top-line results in more detail and provide an update on our PRECISION-HD clinical programs. Finally, I'll conclude with remarks on our broader strategy in Huntington's and upcoming milestones. Huntington's disease, or HD, is an autosomal dominant disease with no approved disease-modifying therapies. HD patients harbor an expanded CAG triplet repeat in their huntingtin gene, which results in production of a mutant huntingtin protein in addition to healthy wild-type huntingtin protein. Accumulation of mutant huntingtin causes progressive loss of neurons in the brain. Wild-type huntingtin protein is critical for neuronal function, and suppression may have detrimental long-term consequences. Evidence suggests Huntington's disease may involve both a dominant gain of function in mutant huntingtin and a corresponding loss of function of wild-type huntingtin protein.
Therefore, we believe an ideal therapy would be one that could uniquely silence the mutant huntingtin transcripts while leaving wild-type levels relatively intact. Approximately 30,000 people are living with Huntington's disease in the U.S., and a significantly larger population are at risk of developing the condition based on their genetics. There is a similar incidence in Europe. Wave's approach is unique. We are the first company to advance multiple investigational compounds into clinical development that are designed to selectively silence the mutant huntingtin transcripts while leaving a patient's healthy wild-type transcripts relatively intact. Specifically, these compounds are designed to target single nucleotide polymorphisms, or SNPs, which are associated with the expanded long CAG repeats on the mutant huntingtin allele. This is achieved through precise targeting enabled by our stereochemistry, which is an element of Prism, our proprietary drug discovery and development platform.
Our compounds recruit RNase H, which cleaves the mutant huntingtin transcript, leading to its degradation and preventing the production of mutant protein. With the advancement of compounds to target three SNPs, SNP1, SNP2, and SNP3, we have the opportunity to potentially provide treatment for up to 80% of the HD population. I will now turn the call over to Dr. Mike Panzara, our Chief Medical Officer, who will review today's announcement around the PRECISION-HD2 trial. Mike?
Thanks, Paul, and thanks to all of you for joining the call today. PRECISION-HD2 is an ongoing phase I-B/II-A multi-center randomized double-blind placebo-controlled trial which is evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of WVE-120102 in adult patients with early manifest HD who carry a targeted SNP, rs362331, termed SNP2. The trial includes both single and multi-dose portions where patients are randomized to either WVE-120102 or a placebo and received a maximum of four total intrathecal doses. After receiving a single dose of treatment, patients had to undergo a washout period of at least eight weeks before entering the multi-dose portion of the trial. There are 4 multi-dose cohorts, 2 milligram, 4 milligram, 8 milligram, and 16 milligrams.
As we announced this morning, we expect to initiate a 32 mg cohort in January, which I'll discuss more later in the presentation. At the time of the data cutoff, a total of 44 patients had participated in the multi-dose portion of the study, 31 patients in the active treatment arm and 13 patients on placebo. Out of these 39, 27 on active and 12 on placebo were available for the mutant huntingtin assessment. Patients had received a maximum of four doses over this time period. Ten patients had not reached day 140 by the time of data cutoff. The primary objective of the trial is the assessment of safety and tolerability of WVE-120102 in early manifest Huntington's disease patients. Additional objectives in the study include measurement of mutant huntingtin and total huntingtin, exploratory pharmacokinetic, pharmacodynamic, clinical, and MRI endpoints.
Patients were eligible for the trial if they were between 25 and 65, had Stage 1 or 2 Huntington's disease, and screened positive for the presence of SNP2. Top line results included safety and tolerability and CSF measurements of mutant huntingtin, total huntingtin, and neurofilament light chain. CSF samples were taken at baseline and approximately four weeks post each dose. The study also includes longer-term follow-up beyond the last on-treatment CSF collection, but these data will be included as part of a full data presentation when the study is complete. Further, patients outside of the U.S. who participated in PRECISION-HD2 are eligible to enroll in an ongoing open-label extension study, or OLE, which we initiated in October of 2019.
Regarding safety, you may recall that this is a global study that includes patients outside of the U.S. receiving multiple doses of WVE-120102 as part of the PRECISION-HD2 study, but also patients in the U.S. receiving single doses as part of the single ascending dose portion of the study. At the time of data cutoff, 71 patients had received at least one dose of WVE-120102 and were included in the overall safety assessment, along with the multi-dose patients. Within this group, 72% of those who received WVE-120102 experienced an adverse event, or AE, as compared with 83% on placebo. These events were mostly mild to moderate in intensity. The most common AEs occurring in at least 10% of the patients on WVE-120102 were headache, procedural pain, falls, and viral upper respiratory infection. There were no serious adverse events, or SAEs, related to treatment, and no stopping rules were met.
Recall that inclusion of study stopping rules is typical for first-in-human studies and consistent with regulatory guidance. Finally, there were no notable changes in laboratory tests, including liver or renal function tests, platelets, or biological markers of immune activation. Together with the mutant huntingtin results, this favorable safety profile supports continued dose escalation in the PRECISION-HD2 study. The top-line biomarker results from our ongoing study are shown on this slide. A nonparametric test was used for the primary statistical analysis, as this was the most appropriate given the distribution of data. Walking you through the table, the left-hand column indicates which values are shown in each row. Moving to the right, placebo values are shown in the second column, and values from the pooled active group in the third.
While the analysis included the median change from baseline for a given group, the main analysis was the comparison between the pooled active group and placebo, assessing the size of the reduction as well as the statistical significance. The table also includes the associated 95% confidence intervals. As shown, 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. This reduction was statistically significant, with a P value of less than 0.05. We also looked across treatment groups using all of the available data from each cohort to determine whether there was a dose response across groups. This analysis suggested that there was a significant dose response at the highest doses tested with a P value of 0.03, providing confirmation of dose-related target engagement.
These data are very encouraging and provide the supportive information we needed to proceed to higher doses. The next cohort is set to initiate in January now that regulatory approvals have been received to begin dosing at 32 milligrams monthly. WVE-120102 was developed as an allele-selective molecule designed to preferentially lower mutant huntingtin protein by targeting SNP2 in order to keep the level of healthy wild-type huntingtin protein relatively intact. As you know, wild-type huntingtin protein is important for neuronal function and may be neuroprotective in adult brain, particularly in times of neuronal stress. Data suggest that transport of key neurotrophic factors such as brain-derived neurotrophic factor, or BDNF, are regulated by wild-type huntingtin levels and the pathophysiology of HD may involve the dominant gain of function of mutant HTT as well as a loss of function of wild-type huntingtin protein.
There is currently no assay available to directly measure wild-type huntingtin in the CSF. As a result, Wave is using an assay developed by CHDI Foundation to measure total huntingtin protein to indirectly assess the effects of WVE-120102 on wild-type huntingtin. These total huntingtin assay results are the first ever reported from a clinical trial. With this assay, a non-selective pan-silencing approach would be expected to lead to a commensurate reduction in total huntingtin relative to mutant huntingtin. While there was a statistically significant reduction in mutant huntingtin compared to placebo in the PRECISION-HD top line analysis, there was no difference in total huntingtin compared to placebo, suggesting a potentially differential effect on huntingtin as measured by the mutant huntingtin and total huntingtin assays.
This observation will continue to be followed with higher doses, where larger reductions of mutant huntingtin are expected and where a more discernible impact on total huntingtin may be observed. Moving on to neurofilament light chain. Neurofilament light chain, or NfL, is an indicator of axonal damage and is elevated in many neurological disorders, including HD. In PRECISION-HD2, there was no change in CSF NfL observed between WVE-120102 and the placebo-treated groups in the top-line results, using the same statistical testing used across other analysis. In summary, we are excited about these top-line results that demonstrate WVE-120102 treatment leads to a significant reduction compared to placebo in mutant huntingtin in treated patients. Further, there is a favorable safety profile that allows us to advance to higher dose cohorts with the goal of maximizing mutant huntingtin knockdown.
We expect to initiate the 32 milligram dose cohort in January and plan to share these data in the second half of 2020. I'll turn to our other HD clinical development candidate, WVE-120101, which is being investigated in the PRECISION-HD1 trial. This trial also enrolled early manifest HD patients and required patients to screen positive for SNP1 or rs362307. In light of the PRECISION-HD2 results, PRECISION-HD1 will remain blinded. Unblinding the SNP2 study, PRECISION-HD2, clearly demonstrated target engagement with the need to dose higher to maximize the effect. Similar to PRECISION-HD2, PRECISION-HD1 includes four cohorts of 2 milligrams, 4 milligrams, 8 milligrams, and 16 milligrams. There is no reason to believe that these doses of WVE-120101 in the SNP1 study would be substantially more effective than the same doses of WVE-120102.
There's no reason to unblind the SNP1 study before it is complete, including the addition of the 32 milligram cohort. Leaving the placebo control study blinded assures the clearest assessment of efficacy and safety of this allele-specific molecule. Top-line results for PRECISION-HD1, including those from the 32 milligram cohort, are now anticipated in the second half of 2020. With that, I'll turn the call back over to Paul.
Thanks, Mike. As Mike described, we are encouraged by these preliminary results from the ongoing PRECISION-HD2 study and look forward to sharing data from the next cohort in the second half of next year, along with top-line data from our PRECISION-HD1 trial of WVE-120101. I would like to thank all the patients and their families for their participation in our PRECISION-HD studies thus far. We are grateful for their continued support as we move forward. Further expanding our commitment to and research in HD, we continue to advance our SNP3 programs. Approximately 40% of the HD population have a SNP3 mutation. With an overlap of SNP3, this would address an incremental 10% of patients versus SNP1 and 2 alone. We are particularly excited about this program as we have in vivo models available for us for preclinical development.
I'd like to take a few moments to review the key preclinical data. As we first described during our research day this fall, our SNP3 compounds demonstrated potent mutant huntingtin knockdown in patient-derived neurons that are homozygous for SNP3. In these cells, our compounds are sevenfold more potent than the analog of a clinical stage pan-selective agent. On the right of the slide, we demonstrated the selectivity of our SNP3 compounds in patient-derived neurons that are heterozygous for SNP3. Both of our SNP3 compounds lead to the selective silencing of the mutant transcripts while largely sparing the wild-type transcripts. By comparison, the pan-silencing analog potently silences both the mutant and wild-type transcripts. In the BACHD mouse model, which is homozygous for SNP3, we were able to assess target engagement in vivo.
In this model, most, but not all of these transgenes contain SNP3, so a pan-silencing approach would be expected to have an advantage. By eight weeks, the expression of huntingtin in mice treated with our SNP3 compound is significantly lower than those in mice treated with a pan-silencing agent. This suppression of huntingtin transcript persists even at 12 weeks in both the cortex and striatum. Given the high hurdle rate for our SNP3 compounds in this model, these results were particularly exciting. We are integrating the learnings from our SNP1 and two development programs into our SNP3 program, and we expect to initiate clinical development of our SNP3 candidate in the second half of next year. Since the beginning of Wave, we have been focused on advancing our innovative antisense oligonucleotide work in the central nervous system.
As we look at the year ahead, we intend to continue building on this foundation. In the second half of 2020, we anticipate several key milestones for our CNS programs. We expect to report data from the 32 milligram cohort of PRECISION-HD2, and top line data from our PRECISION-HD1 trial, including data from a planned 32 milligram cohort. As I just discussed, we are advancing our SNP3 program as well as our C9orf72 program for the treatment of ALS and frontotemporal dementia. We have multiple preclinical models, including in vivo models, to help guide the development of both of these programs, which are expected to begin clinical development in the second half of 2020. In addition, we continue to advance multiple preclinical programs with our partner, Takeda, targeting Parkinson's, Alzheimer's, and other CNS diseases.
This is an exciting time for the application of RNA therapeutics in the central nervous system, and we are proud to be contributing to advancing this science. With that, we'll open up the call for questions. Operator?
Thank you. As a reminder, to ask a question, you will need to press star one on your telephone. To withdraw your question, press the pound key. In the interest of time, we ask that you limit yourself to one question. Any additional questions, please reenter the queue. Please stand by while we compile a Q&A roster. Our first question comes from Salim Syed of Mizuho. Your line is now open. Again, our first question comes from Salim Syed.
Hello. Yep, hello. Sorry, I was on mute. Hey, guys. Thanks for taking the question, and thanks for all the color this morning on the data, Paul and Mike. Paul or Mike, I guess one question just on the breakout of the mutant huntingtin knockdown. I know you probably want to reserve it for a conference, but is my math right here that if we were to look at the way you worded the press release, that 12.4% was at a P value of less than .05.
Assuming that something less than 12.4, you wouldn't have met statistical significance, that if we were to do simple math here and say that slightly less than 12.4% at the lower three doses, and then see what that would imply for the 60 milligram dose, we could get something at 20%, something like 20% of the 60 milligram dose, which would be actually comparable to the Roche- Ionis data on an apples for apples dose basis. Is that generally correct ballpark thinking, or am I way off? Thanks.
Well, hi, Salim. Yeah, I don't think I would think about it that way. You have here that the 12.4% obviously involves looking at all the data of the active cohort, and within that data, you have a certain distribution of effect, which is going to be as shown in the confidence interval that I showed you. We had people that had greater than 25% knockdown and people who had less. I wouldn't say anything about that if we had a lower effect, we would not see it. I think what you're seeing is that we did have an overall effect with some people getting that 25% plus effect, and then as we go higher, we would therefore expect to see more. I wouldn't look at it any other way except that.
Okay, thanks so much.
Thank you. Our next question comes from Whitney Ijem with Guggenheim. Your line is now open.
Hey, guys. Thanks for taking the question. I guess, curiously, can you, I guess, discuss the relative potency of your drug for SNP1 and 2 versus Ionis? I guess the rationale for the doses you initially chose versus what they saw, both in terms of serum drug concentration in the CSF and then knockdown.
This is Mike. The relative potency is hard to compare, it's a very different approach. We're targeting the SNP versus a non-selective approach. Looking at the relative potency is kind of hard to do. What I would say is that based on the preclinical data that we had, and based on the goal of dosing in a range that we thought would get us target engagement in the brain, this is how we selected the doses. What we're seeing is that we at least at, in a dose-related way, engaged target. We also have to think about the situation that the trial design is quite different, where you have a single dose followed by a washout and then multi-dose. That also makes it a bit different to actually do a direct comparison.
What I can say is that, again, the study was designed using the doses based on preclinical as well as, of course, the usual regulatory conversations that enabled us to dose in a range we thought would engage target, and that's what we're seeing. It's also safe, and that allows us to go higher.
Okay, just one quick follow-up. How high did you test in animals, and I guess why not add dose up even further, again, in the context of the broader data generated in the space? Thanks.
We don't get into specifics of the different dosing range of the animals. What I can say is that we have a wide range now to dose higher, both from our toxicology coverage as well as these human data give us a nice wide range to dose even beyond the 32 if we choose to do so.
Thank you. Our next question comes from Mani Foroohar of SVB Leerink. Your line is now open.
Hey, good morning, everyone. This is Rick on the line for Mani. My question has to do with the levels of wild-type huntingtin protein. I just need some help interpreting this. In my mind, if you assume that wild-type huntingtin protein makes up approximately 50% of the protein you would see, you'd expect to see some sort of change in wild-type huntingtin protein if you're knocking down the mutant protein. Could you maybe just help me interpret this? Was there any difference in the sensitivity of the assays that were used for the mutant and the wild-type huntingtin protein? Do you think this could be an artifact of those assays, or is this some real underlying biology here?
Yeah. Hi, this is Mike again. The sensitivity assays are quite similar, so it's not an assay sensitivity issue. I think the thing to remember is these are two separate assays using two different antibodies, and the relative contributions of mutant and wild-type, as well as the fragments associated with those, are going to be different in that total huntingtin assay versus the mutant assay. When you think about the total assay, you can't say, well, 50% of that has to be mutant because of simply how the assay is designed, the epitopes used for the various reagents, it doesn't break down to a 50/50. As we're approaching this, we would anticipate that with higher doses of mutant knockdown, we would potentially start to see some changes in that total, but less than one might expect with a non-selective approach.
What we're going to be looking at going forward is as we get higher levels of mutant knockdown, do we still see this lack of change in total, which would be indicative of the allele-selective approach.
Got it. Thanks. I have one quick follow-up just about the readout we're expecting for HD1 in the second half of the year. Is the change in that readout, is that driven mostly by the pace of enrollment, or is that just due to the addition of the 32-mg dose cohort?
Yeah. Hi, this is Mike again. It's basically because of the addition of 32-milligram cohort. We're essentially now aligning the two studies within the same timeframe in the second half of the year.
Great. Thanks for taking my questions. I'll hop back in the queue.
Thank you.
Thank you. Our next question comes from Yun Zhong at Jefferies. Your line is now open.
Thank you. Question is that, the absolute reduction on the drug was about 6% in placebo, mutant huntingtin protein went up about 9%. Question to you is that for the placebo, mutant huntingtin protein increase is what you expect during that period?
Yeah. Hi, Yun. This is Mike again. I think what we saw in this time period is that we did indeed see an increase in mutant huntingtin. I'd say that's not unexpected, in that these patients are progressing, you're going to get a slight increase in mutant huntingtin. It was pretty consistent across the patients, and basically, we did not see that with the treated patients. That is exactly you're getting a reduction overall because you saw an increase in mutant and a decrease in the treated patients. I think they behaved like we would have expected.
When you measure mutant huntingtin protein reduction with a specific antibody, do you know what % of a reduction is in the full length mutant huntingtin protein versus a fragmented protein?
In the mutant assay, I'm not going to get into the very detailed discussion of the different antibodies because I would be speaking basically beyond my level of expertise. I would say that what we're detecting in the mutant assays, essentially all of the total amount of mutant protein, just like it's a standard assay developed by CHDI, same one everybody else uses. It's basically detecting the mutant that everybody else is detecting.
Okay. Thank you very much.
Thank you. Our next question comes from Debjit Chatterjee of H.C. Wainwright. Your line is now open.
Hi, guys. Good morning. Thanks for the data update. This is Aaron on for Debjit. My question is about the half-life of WVE-120101 and WVE-120102. I was wondering if you guys had checked that out and if there was any potential for less frequent dosing based on your analyses.
Yeah. Hi, Aaron. It's Mike. We actually do have pharmacokinetic analyses that were done on these dose groups, and we're able now, based on those, to do a bit of modeling to try and understand a bit more about what frequency might be necessary. I think that what we're going to do is as we get to 32 milligram dose, as we get the data beyond the four doses administered in this study with the OLE, we'll be able to do a pretty good assessment of how frequent we need to be. That's obviously going to be governed by the degree of knockdown we eventually achieve, as well as the profile in the CSF and blood of the drug. We are looking at that, and our intent is to try and optimize the frequency along with the dose and the degree of knockdown.
We should have the potential to do such thing.
Okay, great. Thank you.
Thank you. Our next question comes from Paul Matteis of Stifel. Your line is now open.
Great. Thanks for taking my questions. Since the hope here is that higher doses will lead to greater mutant huntingtin knockdown, I was wondering if you could quantify the magnitude of knockdown you saw at the 16 milligram dose and whether or not that was materially better than all the lower dose cohorts. Then secondarily, just a follow-up, is there any reason, be it preclinical, why you're unable right now to dose up to, say, 90 or 120 milligrams, as has been done by the Roche Ionis program? Thanks so much.
Yeah. Hi, Paul. It's Mike. Regarding your first question about the 16, we're pleased that what we did was we looked across the dose groups, and we saw that the higher doses did have a dose effect. We're not breaking out the individual groups. What we can say is that the way we looked at this is that we looked across the groups using an approach that is qualified by FDA, and there is regulatory acceptance to look at dose effects. When you look across the groups, you do see this dose response at the highest doses. That was statistically significant. What I can also then say, you asked then about the level of dosing, whether we could ever get to that 90-120, I guess, or those higher levels. It's like any other drug.
The pharmacologies here are likely to be very different, and I don't know if we'll ever need to get to those levels. We're seeing a very nice reduction at these lower doses. We're going up with a broad range of ability to go higher. We'll dose as high as we need to be able to give the maximal degree of knockdown while minimizing any effect on the total. Our safety looks quite clean. We have a bit of room here, but I think to say, can you ever get to 120 really is not a question that I think is something we would be striving for. It's to get whatever gets the best knockdown.
Right. Maybe if I could just follow up. Mike, is it reasonable to think that your goal for mutant huntingtin knockdown is to get to that 40% level? Or do you not think that is necessary?
Oh, I think that we're fortunate in that the degree of knockdown there, that 40% threshold, may not be the ceiling for us. We may be able to go even greater knockdown because we don't have this issue of having to balance the wild-type and the mutant knockdown piece, right? I don't see why we wouldn't be able to achieve that level of knockdown. We're already seeing knockdown at the low dose. As we go higher, the allele-selective approach here is going to really free us up a little bit from needing to worry about how low we could go.
Right. Thanks for the color. Appreciate it.
Thank you. Our next question comes from Yaron Werber of Cowen. Your line is now open.
Hey, this is Leo on for Yaron Werber. Thanks for taking our questions. My question is just the sustainability of the mutant HTT knockdown. Can you give some colors on the specific sustainability for different dose levels?
I actually didn't understand the question. It was hard to understand.
Hey. How sustainable was the mutant HTT knockdown at different dose levels?
Oh, how sustainable? Is that what? At the different dose levels?
Yes.
As I mentioned, the statistical methods we use show that when you look across the dose level and you use all different dose levels and use those doses, you get a statistically significant dose effect. All of that suggests that it encourages us to go higher and that we're seeing this effect that is influenced by dose. Once we are in the OLE, once we are dosing more consistently at the 16 and now 32, if we can get to that level, we are going to be able to look for the durability of that knockdown and using, again, some of the modeling I mentioned earlier, be able to see how infrequent we can dose.
I see. I have one follow-up question. For the 32-milligram dose cohort, what was the dosing frequency, and can you please remind us about the animal data for that dose regimen?
The dose frequency for this study was patients got a single dose, had an eight-week washout, and then had three additional monthly doses. This was designed in a way that allowed us to have the monthly multi-dose cohort. We could evaluate the change in mutant huntingtin during that time period. That was based upon some of the monkey data that we had that shows how much we could get in the brain, and also influenced by how frequent you might want to do a lumbar puncture. It was set up again to try and maximize the exposure. Once we are further with additional multi-dose data, and we have, again, some of the modeling I mentioned, we'll determine if we can reduce that, because the literature does suggest that once you knock down mutant huntingtin, it may actually be quite durable, and we wouldn't have to dose this frequently.
We dosed it this way to maximize as much knockdown as we can see in the shortest period of time.
Thank you.
Thank you very much.
Thank you.
Thank you. Our next question comes from Jason Zemansky of Bank of America. Your line is now open.
Hey, good morning. Thanks for taking my questions. Just a couple. Just on the neurofilament light chain commentary, just trying to understand how to compare versus some of the competitor data that we've seen. I believe that they saw the elevation really start at month five. I think your data analysis stops at month five, so it seemed like that would be a difficult comparison to make. I think that they didn't see NfL increases unless mutant HTT reduction was exceeding 30%. Just trying to understand if you can contextualize how to maybe think about what you've seen versus the competitor data.
I think you're asking very reasonable questions. This is something that we're going to have to continue to follow. We see what we see with this period of time, which is that we saw no change. We're going to continue to follow this with the continued dosing, both longer dosing as well as higher dosing. One of the things you've mentioned is looking at those with the greatest degree of knockdown and whether that influences the direction of NfL, are all on the list of things we need to do now once we get beyond this top-line assessment. Those are excellent questions, and they are things we're going to be looking at.
Just one follow-up, just to confirm, you guys, I assume, won't be presenting any detailed data at AAN and presumably are going to wait till you have the 32 milligram data generated before you have a detailed presentation of PRECISION-HD?
That's correct. That's our intention is to, once we have the finished PRECISION-HD2 study, including the 32, that would be the timeframe where we'd be talking about, which is, we said in the second half of this year.
Got it. Thank you.
Thank you.
Thank you. We do have a follow-up question from Yun Zhong of Jefferies. Your line is now open.
Thank you. I know that it's a small number of patient data, but when you look at inter-individual variability, did you see any difference in terms of mutant huntingtin protein reduction between patients with SNP2 only versus SNP1 and SNP2 both?
Hi, Yun. It's Mike again. We did not specifically do assessments like that as part of this top-line analysis. That's, again, one of those ones that as we collect additional data, as we get larger numbers of patients, those are the types of analyses that we're going to be considering trying to understand. Luckily, we're in a situation where because we're really specifically targeting patient groups, you can do these types of analyses to determine are there cohorts of patients who are those high responders? That's a really important question. That's something that we're going to try and sort out as the dataset gets larger.
Thank you.
Thank you.
Thank you. Ladies and gentlemen, this does conclude our question- and- answer session. I would now like to turn the call back over to Paul Bolno for President and CEO of Wave Life Sciences with any further remarks.
Thank you again, everyone, for your time today. Looking forward to an exciting 2020. Thank you.
Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.