Ladies and gentlemen, thank you for standing by, and 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's presentation, there will be a question and answer session. Please be advised that today's conference is being recorded. 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 Doctor. Paul Bono, President and CEO of Wave Life Sciences and Doctor. Mike Panzera, 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 Investors 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 ks for the year ended December 31, 2018. 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 Bono, 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 so ongoing, but we are pleased to share that treatment with WVE-one hundred and twenty-one hundred and two resulted in a statistically significant reduction in mutant Huntington 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 in mutant Huntington 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 triple 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. However, 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 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 transcript 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 1st company to advance multiple investigational compounds into clinical development that are designed to selectively silence the mutant or SNPs, which are associated with the expanded long CAG repeat on the mutant Huntington allele.
This is achieved through precise targeting enabled by our which cleaves the mutant Huntington transcript, leading to its degradation and preventing the production of mutant protein. With the advancement of compounds to target 3 SNPs, CYP1, CYP2 and CYP3, we have the opportunity to potentially provide treatment for up to 80% of the HD population. I will now turn the call over to Doctor. Michael Panzera, 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 IbIIa multicenter, randomized, double blind, placebo controlled trial, which is evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple doses of WAVE-one hundred and twenty-one hundred and two in adult patients with early manifest HD who carry a targeted SNP, RS362 331, termed SNP 2. The trial includes both single and multi dose portions where patients are randomized to either wave 12102 or placebo and received a maximum of 4 total intrathecal doses. After receiving a single dose of treatment, patients had to undergo a washout period of at least 8 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 milligram 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 Huntington assessment. Patients had received a maximum of 4 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 WAVE-twelve thousand one hundred and two in early manifest Huntington's disease patients. Additional objectives in the study include measurement of mutant Huntington and total Huntington, exploratory pharmacokinetic, pharmacodynamic, clinical and MRI endpoints. Patients were eligible for the trial if they were between 2565, 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 Huntington, total Huntington and neurofilament light chain. CSF samples were taken at baseline and approximately 4 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 WAVE-twelve thousand one hundred and two 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 WAVE-twelve thousand one hundred and two and were included in the overall safety assessment along with the multi dose patients.
Within this group, 72% of those who received WAVE-twelve thousand one hundred and two 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 waveonetwo102 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 1st in immuno 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 Huntington 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 the 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 3rd. 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 wave-twelve thousand one hundred and two 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 is 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. WAVE-twelve thousand one hundred and two 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 maybe neuroprotective in adult brain, particularly in times of neuronal stress. Also, data suggests that transport of key neurotrophic factors such as brain derived neurotrophic factor or BDNF are regulated by wild type Huntington levels and the pathophysiology of HD may involve the dominant gated function of mutant HGT as well as a loss of function of wild type Huntington protein. There is currently no assay available to directly measure wild type Huntington in the CSF. As a result, WAVE is using an assay developed by CHGI Foundation to measure total huntingtin protein to indirectly assess the effects of wave-twelve thousand one hundred and two on wild type Huntington. These total Huntington 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 commensurate reduction in total Huntington relative to mutant Huntington. While there was a statistically significant reduction in mutant Huntington compared to placebo in the Precision HD top line analysis, there was no difference in total Huntington compared to placebo, suggesting a potentially differential effect on Huntington as measured by the mutant Huntington and total Huntington assets. This observation will continue to be followed with higher doses where larger reductions of mutant Huntington are expected and where a more discernible impact on total Huntington 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 wave 12,102 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 WAVE-twelve thousand one hundred and two treatment leads to a significant reduction compared to placebo in mutant Huntington in treated patients. Further, there is a favorable safety profile that allows us to advance to higher dose cohorts with a goal of maximizing mutant Huntington knockdown. We expect to initiate the 32 milligram dose cohort in January and plan to share these data in the second half of twenty twenty. Now I'll turn to our other HD clinical development candidate, WAVE-twelve thousand one hundred and one, which is being investigated in the PRECISION HD-one trial.
This trial also enrolled early manifest HD patients and required patients to screen positive for SNP-one or RS-three sixty two-three zero seven. In light of the precision HD-two results, PRECISION HD1 will remain blinded. Unblinding the SNP2 study PRECISION HD2 clearly demonstrated the target engagement demonstrated target engagement with the need to dose higher to maximize the effect. Similar to PRECISION HD2, PRECISION HD1 includes 4 cohorts of 2 milligrams, 4 milligrams, 8 milligrams and 16 milligrams. There is no reason to believe that these doses of WVE-twelve thousand one hundred and one in the SNP-one study would be substantially more effective than the same doses of wave-twenty one-two.
Therefore, there's no reason to unblind the SNP-one study before it is complete, including the addition of the 32 milligram cohort. Leaving the placebo controlled study blinded assures the clearest assessment of efficacy and safety of this allele specific molecule. Top line results for PRECISION HT1, including those from the 32 milligram cohort, are now anticipated in the second half of twenty twenty. Now 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 HD-one trial of WBE-one hundred and twenty-one hundred and one. 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 program.
Approximately 40% of the HD population have a SNP3 mutation. With and with an overlap of SNP3, this would address an incremental 10% of patients versus SNP1 and two 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 data this fall, our SNP3 compound demonstrated potent mutant huntingtin knockdown in patient derived neurons that are homozygous for SNP3.
In these cells, our compounds are 7 fold 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 compound in patient derived neurons that are heterozygous for SNP3. Both of our SNP3 compounds lead to the selective silencing of the mutant transcript, while largely sparing the wild type transcript. By comparison, the pan silencing analog potently silences both the mutant and wild type transcripts. In the back HD 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 8 weeks, the expression of Huntington in mice treated with our SNP3 compound is significantly lower than those in mice treated with a pan silencing agent. This suppression of Huntington's 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 SNP-three candidate in the second half of next year. Since the beginning 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 twenty twenty, 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're advancing our SNP3 program as well as our C9orf72 program for the treatment of ALS and frontal temporal 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 twenty twenty. 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 And our first question comes from Salim Syed of Mizuho. Your line is now open. And again, our first question comes from Salim Syed.
Hello. Yes. 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, I have one question just on the breakout of the Mutant and Huntington 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 0.05%. So 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 lower three doses and then see what that would imply for the 16 milligram dose, we could get something to 20% something like 20% of the 16 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, Celine. Yes, I don't think I would think about it that way. I mean, you have here that the 12.4% obviously involves looking at all the data of the active cohort. And within that data, you have 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 25% knockdown and people who had less. So 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. So I wouldn't look at it any other way except that.
Okay.
Thanks so much.
Thank you. And our next question comes from Whitney Ijem with Guggenheim. Your line is now open.
Hey guys. Thanks for taking the question. So
I guess, curious, can you I guess discuss the relative potency of your drug for CYP-one and CYP-two versus Ionis? And 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?
Yes. So, this is Mike. So, I mean, the relative potency is hard to compare. It's a very different approach. I mean we're targeting the SNP versus a non selective approach.
So 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 and what we're seeing is that we at least have 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. And just one quick follow-up. How high did you test in animals if you and I guess why not add kind of dose up even further again in the context of the broader data generated in the space? Thanks.
So 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. And our next question comes from Manny Forrester of SVB Leerink. Your line is now open.
Hey, good morning, everyone. This is Rick on the line for Manny. So my question has to do with the levels of wild type Huntington's protein. I just need some help interpreting this. So in my mind, if you assume that wild type Huntington's protein makes up approximately 50% of the protein you would see, you'd expect to see some sort of change in wild type Huntington protein if you're knocking down the mutant protein.
So 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?
Yes. Hi. This is Mike again. These the assays sensitivity assays are quite similar. So it's not an assay sensitivity issue.
I think the thing to remember is these are 2 separate assays using 2 different antibodies and the relative contributions of mutants and wild type as well as the fragments associated with those are going to be different in that total Huntington assay versus the mutant assay. So you can't really 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 fifty-fifty. So when 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. And 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. And I have one quick follow-up. Just about the readout we're expecting for HD-one 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 second dose or the 32 mg dose cohort?
Yes. Hi, this is Mike again. It's basically because of the addition of 32 mg cohort, we're essentially now aligning the 2 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. And the next question comes from Ying Zheng with Jefferies. Your line is now open.
Thank you. So question is that, so the absolute reduction on the drug was about 6 percent and placebo, mutant huntingtin protein went up about 9%. So question to you is that for the placebo, mutant Huntington protein increase is what you expect during that period?
Hi, Eun. This is Mike again. So I mean, I think what we saw in this time period is that we did indeed see an increase in mutant Huntington. And I'd say that's not unexpected. I mean that these patients are progressing, you're going to get a slight increase in mutant Huntington.
It was pretty consistent across the patients and basically, we did not see that for the treated patients. So that is exactly you're getting a reduction overall because you saw an increase in mutant and a decrease in the treated patients. So I think they behave like we
would have expected.
So with your major mutant Huntington protein reduction with a specific antibody, do you know what percent of a reduction is in the full length mutant huntingtin protein versus a fragmented protein?
In the mutant assay, I mean, we I can't I'm not going to get into the very detailed discussion of like the different antibodies because I would be speaking basically beyond my level of expertise. But I would say that what we're detecting in the mutant assay is essentially all of the mutant the total amount of mutant protein, just like, it's a standard assay developed by CHDI, same one everybody else uses. So we're actually pulling, it's basically, detecting, the mutant, that
Okay. Thank you very much.
Thank you. And our next question comes from Debjit Choudhary of H. C. Wainwright. Your line is now open.
Hi, guys. Good morning. Thanks for the data update. This is Aaron on for Debjit. So my question is about the half life of wave 1, 2,102.
I was wondering if you guys had checked that out and if there was any potential for less frequent dosing based on your analyses?
Yes. Hi, this is 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 the 32 milligram dose, as we get the data beyond the 4 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. But 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 things.
Okay, great. Thank you.
Thank you. And our next question comes from Paul Matteis with 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? And 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 milligrams or 120 milligrams as has been done by the Roti Ionis program? Thanks so much.
Yes. Hi, Paul. It's Mike. Regarding your first question about the 16, what we are not 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. So we're not breaking out the individual groups.
But 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 those effects. And 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 92, 120, I guess, are those higher levels. It's like any other drug. The pharmacologies here are likely to be very, very different.
And I don't know if we'll ever need to get to those levels. I mean, 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, to be able to give the maximal degree of knockdown while minimizing the while minimizing any effect on the total. And also our safety looks quite clean.
So 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 Huntington knockdown is to get to that 40% level? Or do you not think that that is necessary?
I mean, I think that we're fortunate in that the degree of knockdown there as 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? So I don't see why we wouldn't be able to achieve that level of knockdown. We're already seeing knockdown of the low dose. As we go higher, the allele specific approach
here is going
to really free us up a little bit for needing to worry about how low we could go.
All right. Thanks for the color. Appreciate it.
Thank you. And 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. So my question is just the sustainability of the mutant STT knockdown. Can you give some of the colors on the specific stability for different dose levels?
I actually didn't understand the question. It was hard to understand.
Hey, how sustainable was the mutant STT knockdown at different dose levels?
How sustainable? Is that what you that's a different dose level? Yes. I mean, 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. So all of that suggests that it encourages us to go higher and that we're seeing this effect that is influenced by dose.
So we're 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 the again some of the modeling I mentioned earlier, be able to see how infrequent we can dose.
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?
So, the dose frequency for this study was patients got a single dose, had an 8 week washout and then had 3 additional monthly doses. And this was designed in a way that allowed us to have the monthly multi dose cohort. We could evaluate the change in mutant Huntington 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 Huntington, it may actually be quite durable and we wouldn't have to dose this frequently. But 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. And our next question comes from Jason Gerberry of Bank of America. Your line is now open.
Hey, good morning. Thanks for taking my questions. Just a couple. So just on the neuro filament light chain commentary, just trying to understand how to compare versus some of the competitor data that we've seen. I believe that they're based on the elevation really start at month 5.
I think your data analysis stops at month 5. It seems like that would be a difficult comparison to make. And I think that they're they didn't see NFL increases unless mutant HTT reduction was exceeding 30%. So 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. I mean, 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 continued dosing, both longer dosing as well as higher dosing. And we 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 that once we get beyond the type this top line assessment.
So these are excellent questions and there are things we're going to be looking at.
And just one follow-up, just
to confirm, you guys, I assume, won't be presenting any detailed data at AAN and presumably you're 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 HD 2 study, including the 32, that would be the timeframe we would be talking about, which is we said in the second half of this year.
Got it.
Thank you.
Thank you.
Thank you. And we do have a follow-up question from Ying Yang 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 interindigial variability, did you see any difference in terms of a mutant items and protein reduction between patients with a SNIT-two only versus a SNIT-one and SNIT-two both?
Hi, Eun. It's Mike again. We did not specifically do assessments like that as part of this top line analysis, but 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 data set gets larger.
Thank you. Thank you.
Thank you. And ladies and gentlemen, this does conclude our question and answer session. I would now like to turn the call back over to Paul Boulno, 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.