Wave Life Sciences Ltd. Q2 FY2020 Earnings Call

- : Mani Foroohar - SVB Leerink Salim Syed - Mizuho Suji Jeong - Jefferies Aaron Welch - H.C. Wainwright

Good morning, and welcome to Wave Life Sciences Second Quarter 2020 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 Rausch, Head of Investor Relations at Wave Life Sciences. Please go ahead.

Thank you, operator. Good morning, and thank you for joining us today to discuss our recent business progress and review Wave's second quarter 2020 operating results. On the call with me today are Dr. Paul Bolno, our President and CEO; Dr. Mike Panzara, our Chief Medical Officer, Head of Therapeutics Discovery and Development; David Gaiero, Interim CFO; Dr. Chandra Vargeese, Chief Technology Officer; and Dr. Ken Rhodes, SVP Therapeutics Discovery. Paul and Mike will provide opening remarks, after which Dave will discuss our second quarter financial results. This morning, we issued a news release detailing our second quarter results. 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-K for the year ended December 31, 2019 and our quarterly report on Form 10-Q for the quarter ended June 30, 2020. 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. Paul?

Thanks, Kate. Good morning to everyone on the call and thank you for joining us today. I hope you and your families are staying healthy and safe during these challenging times. While we have been impacted by the global COVID-19 pandemic, we have continued to advance our clinical and preclinical neurology pipeline. Since the declaration of the pandemic in the United States back in March, we like others have been navigating a fluid and unprecedented environment and recent outbreaks around the world remind us of the uncertainty that is likely to persist well into the second half of this year. Built from our PRISM platform, our pipeline addresses a wide range of neurology targets, and includes 11 programs that span discovery through clinical stage development. Since our last update, both our PRECISION-HD clinical trials for patients with Huntington's disease have continued, with patients advancing through the 32-milligram dose cohorts. We now expect to report data from these trials in the first quarter of 2021. We have also continued to successfully advance the work required to submit the clinical trial applications for our SNP3 program for Huntington's disease in the fourth quarter of this year. This third, allele-selective program incorporates all of our learnings from our SNP1 and SNP2 programs, as well as the advancements in our platform including new chemistry. Importantly, targeting SNP3 increases the number of Huntington's disease patients who could potentially benefit from a new allele-selective HD therapeutic. In addition, we are all excited about the progress that we are making to advance our C9orf72 program for ALS and frontotemporal dementia (FTD). These are two devastating diseases with high unmet need and our approach has the potential to target one mutation within both diseases. Like SNP3 this program is designed with new chemistry off the platform and the variant-selective strategy was optimized with our PRISM technology. We remain on track to submit a clinical trial application for our C9 program in the fourth quarter of this year. Lastly, our collaboration with Takeda for multiple CNS indications including Alzheimer's disease and Parkinson's disease continues to yield new compounds with target validation for a third program expected to be achieved by the end of this year. With regards to our PRISM platform, we have a lot of exciting work ongoing much of which will be discussed during our upcoming Analyst & Investor Research Webcast at the end of this month. We continue to generate promising data with our new ADAR-mediated RNA editing capability and we expect to present additional in vivo editing data during this upcoming webcast, as well as discuss the opportunity to apply this modality to neurology targets. The ability to edit RNA transcripts significantly expands our targetable landscape and adds to our existing toolbox and modalities for the design of novel RNA therapeutics. We also expect to present ADAR editing data at multiple scientific meetings this fall including the Oligonucleotide Therapeutics Society (OTS) annual meeting and the Keystone Symposia on RNA editing and modifications as well as announce our first RNA ADAR editing program later this year. More broadly, we have implemented novel chemistry enhancements across our pipeline. Our next wave of neurology programs including C9orf72, SNP3 and our RNA-editing oligonucleotide are all designed with this new chemistry. We will discuss more details on our new PRISM chemistry platform for the first time during our research webcast. So I would like to provide a brief update on our operations amidst the ongoing pandemic. In the second quarter, we shifted from responding to the COVID-19 restrictions to developing and implementing a robust business continuity plan enabling us to resume many of our critical on-site activities. We expanded a number of on-site laboratory and manufacturing staff over the past couple of months, while maintaining strict protective measures to ensure their health and safety. To date, more than 60% of our employees are now trained on these protective measures and eligible to work on site. The remainder of our team has adapted well to working from home. Overall, everyone at Wave has embraced and excelled in new ways of working and their flexibility and ingenuity also mirrors what we are seeing among the broad network of researchers and patients who are participating in our studies. Our supply chain has remained intact, ensuring we have sufficient material to drive our preclinical and clinical pipeline forward. In the month of May, Dr. Ken Rhodes joined our team as Senior Vice President, Therapeutics Discovery and I'm very excited to have him on board. Ken comes to Wave with decades of experience discovering and advancing therapeutic candidates in the neurology space. He will help build our pipeline by identifying new targets in therapeutic areas of focus and guiding the research needed to advance candidates to the clinic. You will hear from Ken at our upcoming Analyst & Investor Research Webcast. I'd now like to turn the call over to Dr. Michael Panzara for an update on our clinical and preclinical neurology programs. Mike?

Thanks, Paul. Today, I will begin with an update on our PRECISION-HD1 and PRECISION-HD2 clinical trials for the treatment of Huntington's disease. During the COVID-19 pandemic, we have remained keenly focused on ensuring the safety of our study teams, patients and investigators. While both clinical trials have continued to advance, clinical trial sites, patients and investigators are facing new or continued restrictions. Progress has continued and we have been successful at identifying the patients needed to complete the 32-milligram cohorts for both studies. While we are working to enroll these patients as safely and efficiently as possible, we now anticipate being able to share data from all treatment cohorts for both SNP1 and SNP2 studies, as well as data from our open-label extension trials in the first quarter of 2021. At the beginning of the pandemic and at the time of our last update, we were hopeful that we could keep our studies on track because of the prioritization of disease-modifying studies by health authorities, the infrequent dosing regimen of the PRECISION-HD trials and based on the locations of our clinical trial sites. While this has certainly been helpful the ongoing impact of the coronavirus has been unavoidable. We believe that selectively lowering mutant huntingtin will be critical to achieving a long-term clinical benefit with any therapeutic in HD, which is why we are expanding our commitment to HD patients with the development of our third allele-selective program SNP3. Preparations continue toward beginning clinical development, with the submission of a clinical trial application, or CTA, for SNP3, which is expected to occur in the fourth quarter of 2020. We have leveraged the learnings from both our first HD clinical programs in terms of candidate screening, identification and in vivo target validation, as well as advancements in our platform when designing our SNP3 compound, which incorporates a novel chemistry advancement from our PRISM platform. Beyond the advances in developing our lead SNP3 compound, over the past several years we have significantly evolved our methods to identify patients eligible for SNP3 targeting and measurement of fluid biomarkers. When we started this journey, we were told that identifying patients with relevant SNPs through a process called SNP phasing was not possible, or too burdensome to be practical for therapeutic development. Since then we have clearly proved SNP phasing can be accomplished successfully and efficiently. We not only confirm the feasibility of phasing in a prospective observational study, which was recently published in Neurology Genetics, but we have successfully phased and identified more than enough patients appropriate for our studies in a timeline to enable enrollment. Taking this approach to the next level, last year we entered into a collaboration with Asuragen for the development and commercialization of a potential companion diagnostic for each of our SNP1 and SNP2 programs. Just recently, we expanded this agreement to enable us to use their scalable technology for patient selection in our upcoming clinical trial for SNP3. Our SNP3 program has the potential to also broaden our reach into the HD population. This program addresses a significant portion of the Huntington's disease population on its own, as approximately 40% of the HD population has SNP3, an observation we have confirmed using patient samples from our observational study. Today, together with our SNP1 and SNP2 programs, we have the potential to address up to 80% of the HD population. To remind you why we believe allele selectivity matters, patients with Huntington's disease have approximately half the level of wild-type huntingtin protein as healthy patients and there is a growing understanding around the importance of minimizing any effects on wild-type huntingtin, given the role it plays in so many critical biological functions, both in the central nervous system and systemically. The supporting data not only continues to grow, as does the recognition of this fact and conversations with the HD community. I'm sure those of you who listened in on the virtual Huntington’s Disease Society of America (HDSA) congress in June noticed this. We have also been told that it would never be possible to measure wild-type huntingtin in the CSF of HD patients. We have turned our focus to this scientific challenge and have made progress. We believe that it is critical to understand the impact of potential treatments on wild-type huntingtin and look forward to keeping you updated as we strive to complete this work in time for our data readouts. Now turning the focus to our C9orf72 program, targeting the most frequent genetic cause of the familial forms of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two neurodegenerative diseases that are both devastating and fatal. C9orf72 genetic mutations are also a strong genetic risk factor for sporadic forms of these diseases. Our C9orf72-targeting compound is designed to selectively and potently silence the hexanucleotide repeat-containing transcripts, which drives the formation of toxic RNA and proteins in the central nervous system. Our clinical candidate had striking effects in transgenic animal models with potent and durable knockdown of both the repeat-containing transcripts and associated peptides, while leaving C9orf72 protein levels relatively intact. The ability to measure dipeptide repeats in the CSF of ALS and FTD patients is a critical biomarker of target engagement and other biomarkers in neurodegeneration will afford us the opportunity to rapidly assess for signs of efficacy in the clinic. We plan to include both ALS and FTD patients in our clinical trial with the intention to advance developments in both indications. We hope to share more details on this clinical trial design later this year once the details are agreed upon with key stakeholders including the regulatory authorities. We continue to expect to submit this CTA in the fourth quarter of this year. Similar to our SNP3 program, our C9 program takes advantage of innovations from our PRISM platform that have led to a compound with the potential to be highly differentiated from other therapeutic approaches. Dr. Ken Rhodes will discuss this program in more detail during our upcoming research webcast. So with that I'll turn it over to David Gaiero for a review of our financials.

Thanks, Mike. For the second quarter of 2020, Wave reported a net loss of $40.5 million compared to $41.9 million for the same period in 2019. Research and development expenses were $31.5 million in the second quarter of 2020 compared to $41.6 million for the same period in the prior year. The decrease in research and development expenses in the second quarter was primarily due to decreased external expenses related to suvodirsen, due to our December 2019 decision to discontinue the program, partially offset by increased external expenses related to our clinical and preclinical activities including our HD programs and our C9orf72 program for ALS and FTD. General and administrative expenses were $10.2 million for the second quarter of 2020 compared to $11.6 million for the same period in the prior year. The decrease in general and administrative expenses in the second quarter of 2020 was mainly driven by decreased headcount resulting from the workforce reduction implemented in February 2020. Wave ended the second quarter of 2020 with approximately $94 million in cash and cash equivalents. We expect that our existing cash and cash equivalents together with expected and committed cash from our existing collaboration will enable us to fund our operating and capital expenditure requirements into the fourth quarter of 2021. As a reminder, we do not include potential milestone payments and other uncommitted payments related to our Takeda collaboration in our cash runway. I will now turn the call back over to Paul for closing remarks. Paul?

Thanks, Dave. We have made significant progress this year despite challenges posed by the global pandemic. We continue to advance our neurology pipeline with two CTA submissions expected in the fourth quarter and data readouts from our PRECISION-HD trials expected in the first quarter next year. In the near term, we have several updates planned to be included in our upcoming research webcast presentation, including C9orf72 preclinical data, in vivo data on our ADAR editing modality and data highlighting our new chemistry enhancements from our platform. The research webcast will be held August 25 and we hope you can tune in. With that we'll open up the call for questions. Operator?

Operator instructions. Our first question comes from the line of Eun Yang from Jefferies. Your line is open. Please go ahead.

This is Suji dialing for Eun. Thanks for taking the question. So I have a question about this SNP phasing that Paul mentioned. You mentioned that SNP phasing was burdensome earlier. Does it mean that the SNP3 clinical trial will use different protocols for SNP3 compared to the earlier HD1 and HD2 programs? And then could you please give a quick enrollment update for the PRECISION-HD1 program please? Thank you.

I'll pass the call to Mike, but just to begin, I think it was clear what Mike was saying was that it was presented to us that this would be a challenge. We have been able to do that from the beginning and have continued to provide enhancements to that. I'll let Mike continue to comment on the SNP phasing aspect.

Yeah, hi. It's exactly what Paul said. What I had said is that when we started this process of identifying patients to have this allele-specific approach we were told there would be a lot of burden and it wouldn't be feasible to do it in a practical way for clinical trials, but from the beginning we've managed to do that. We've managed to do the study that I mentioned we published. We managed to do it in the trials. The new approach will be working with our partner Asuragen to develop the next-generation phasing approach that makes it more amenable to a companion diagnostic. So we've moved it along. We've managed to use it efficiently and we're looking forward to continuing to do that. And I think the second part of your question was about enrollment. We don't give specifics about enrollment. But what I can say is luckily we've been able to identify patients for the filling of the cohorts including their SNP phasing and we're just working to get them into the studies.

Okay, great. Thank you.

We have our next question. It comes from the line of Mani Foroohar from SVB Leerink. Your line is open. Please go ahead.

Hey, guys, thanks for taking the question. A couple of quick ones. We'll start with the finance question. I'm looking at how you guys have fairly rapidly reduced your cash burn in the follow-on to the suvodirsen data. Can you give us a sense of how much of your spend this quarter to last quarter was separation costs regarding that? And how much incremental cost is there to come? It's proving a little bit challenging to reconcile your fourth quarter 2021 cash runway guidance, and I think we aren't going to overmodel it. Moving to clinical trial operations, you guys have seen a series of delays in your Huntington's enrollments. Taking your own published data versus what we know about the epidemiology of Huntington's, you should have been able to enroll assuming you are all somewhere near the speeds that Roche and Ionis have reported. Given the epidemiological data you've given us regarding the prevalence of SNPs, it seems like the entire study could be filled from one or two large sites. So what do you think the reasons are that patients are avoiding your study? Are there changes you can make to your R&D leadership or to your R&D strategy and execution to avoid future underperformance in enrollment speed and clinical development? Thanks.

Thank you. So we’ll take the first question first and I will let Dave follow up with some of the financial guidance. But yes as you pointed out there was a substantial reduction related to suvodirsen costs as well as operating costs related to that program. Dave do you want to speak to the finances?

Sure Paul. So as you saw we did have reduced cash burn from Q1 to Q2. In addition as we reported in our 10-Q this morning we've also raised approximately $20 million on our ATM since March of this year and so that's also adding to our extended cash runway.

And the second part of the question, Mike, do you want to talk about the speed of enrollment?

Yeah. I mean, I think that there are patients out there. We've managed to identify them. We've actually started to be able to work with the sites to get through this pandemic but let's just remember we have this pandemic going on. I'll give you a concrete example: we have many of our sites in Australia. We had a whole group of patients scheduled to come into the study beginning last Wednesday. Then Monday, Melbourne announced a sudden lockdown that essentially wiped out a whole group of patients that could have gone into the study at that point because of the lockdown in Melbourne and so we had to redirect efforts then to other places. This is a very complex and fluid environment. The issues of this year are certainly very different than the issues of last year. We have adapted — we made changes last year to improve upon our recruitment this year but it's not a patient interest issue. There's a lot of interest in the community and I think we are just trying to navigate a very complex situation.

That makes a lot of sense to me. Given the severity and the relentless decline associated with Huntington's disease there is understandably a lot of patient interest in any potential therapy. But again what are the structural changes, Paul, that you are thinking of making in your research leadership and headcount to avoid delays like this? For example, one could have chosen for an APAC enrollment site in New Zealand, which has much less COVID impact, or other places where you would have exposed yourself to less of this risk. Given the study has been going on for a couple of years, I would have thought you would have considered that.

Yes. I think the key is that earlier in the process, to your point on New Zealand, we only knew about New Zealand being less impacted more recently. Getting sites up and running during a pandemic and shifting sites wasn't straightforward. We had the diversity of clinical trial sites that earlier this year had things on a positive trajectory. To Mike's point, we made changes in our operating relationships internally with our global CRO network, and we enhanced our clinical development team adding additional physicians more recently to continue to focus on delivering and executing on the study. As Mike said, the patients are identified so this is now an issue of closing enrollment out and hence that shift.

Okay. Thanks for taking the question guys.

We have our next question. It comes from the line of Salim Syed from Mizuho. Your line is open. Please go ahead.

Hey, Paul. Hey, Mike, Hey, Dave. Thanks for all the color guys. Just a few from me if that's okay, all in the Huntington's program. So Paul or Mike, could you maybe just give us some color on how you guys are thinking about the benchmark here? Given Roche and Ionis reported roughly 60% knockdown on both mutant and wild-type, what do you think you need to have — and if you are just knocking down the mutant — in order to be clinically successful in the upcoming dataset? Number two: when we looked at the pooled data that you disclosed in December, which included the 16-milligram cohort, on the 95% confidence interval you went up as high as 25% knockdown on mutant huntingtin. Is there anything to suggest that the 16-milligram cohort is actually hitting closer to 25% rather than something lower? And then lastly, do you have access to any blinded aggregated biomarker data such as NfL or anything you're looking at in the blinded aggregate data? Thank you.

I'll pass the call on to Mike to answer specifically, but it's an interesting transition over because we are excited to have continued OLE data in that first quarter as well to review at the time we have the 32-milligram data. So in aggregate there will be a lot of data to evaluate. Mike, do you want to speak to the numbers?

Yes. In terms of what is a meaningful reduction in mutant huntingtin, that has not been firmly established. The 40% to 60% knockdown number that's often quoted relates to non-allele-selective approaches; at recent HD meetings the target of 20% to 25% was being discussed by some as a minimum meaningful reduction in the context of non-specific knockdown. We would think that if a non-specific knockdown at that level is meaningful, then a selective knockdown of mutant huntingtin at similar levels would also be meaningful. But ultimately the true answer requires clinical effect data to see how it translates. We've said many times that we were dissatisfied with the interim analysis that we saw and wanted to go higher. We have gone higher and now we are looking forward to seeing the data. Regarding ongoing assessments of biomarkers, those assays and related data are very tightly held and restricted. We share safety data with our safety monitoring committee that is unblinded, where they review data after each cohort as we've talked about and discuss dose escalation. We review blinded clinical information, but we do not review blinded biomarker information as part of our standard process.

Got it. Thanks, Mike. On the 16-milligram cohort, can you opine a little bit whether it's closer to the upper bound?

We've been clear that we shared the interim pooled analysis of active cohorts versus pooled placebo cohorts. We've not broken out the individual knockdown for each cohort separately. Those details will be part of the data readout in the first quarter.

Okay. Thanks very much, guys.

We have our next question. It comes from the line of Paul Matteis from Stifel. Your line is open. Please go ahead.

Hey. Thanks for taking the question. This is Alex on for Paul. Just a couple from us. For your next clinical programs SNP3 and the C9orf72 programs, you mentioned the CTA filing in 4Q. When do you think you could start dosing, and will that be ex-U.S. only or do you expect to file an IND in the U.S. as well? And then, on your AD and PD programs with Takeda, curious if you can give more color on the source of targets you are looking at? Thanks.

That's great. As it relates to C9orf72 and SNP3 CTA updates, Mike do you want to comment?

Typically, once you submit a CTA, and depending on regulatory timelines and site activation, dosing often begins roughly a quarter after CTA acceptance. Of course, that's in a non-COVID environment, so we'll have to see how things go. We will target countries where we can run the trial despite COVID. Our plan is to take this globally and our intention is to get this off the ground both inside and outside of the U.S.

As it relates to the AD and PD targets in our Takeda collaboration, we are not at liberty to disclose the confidential targets as part of the collaboration, but as they make progress, we are working with Takeda to share more around those programs. The team continues to push forward and we've been able to implement our new chemistry across programs similar to those we are using for SNP3 and C9. We are excited to provide research updates during our upcoming research webcast.

Thanks. And a quick follow-up, could you give a quick update on the ophthalmology programs? I didn't see that in the press release.

Regarding ophthalmology, we have done work looking at target engagement in the retina around USH2A and RhoP23H. We haven't provided additional updates related to those programs as we look at the collaborative path forward to advance them.

We have our next question. It comes from the line of Yaron Werber from Cowen. Your line is open. Please go ahead.

Hi, guys. This is Brendan on for Yaron. Thanks for taking the question. A couple quick ones on HD and dosing cohorts. You mentioned the Q1 readout will include data through the 32 mg. Have you considered higher additional doses? What can we expect from the readout in Q1 in terms of follow-up timing after treatment — namely how far out after dosing will the readout include? And how should we think about the timeline to pivotal — would you potentially wait to proceed to a pivotal until additional higher-dose cohorts are fully enrolled and read out? Thanks.

Mike, would you like to take the HD question?

At the time of the first-quarter readout you will get the full dataset including the 32-milligram cohorts and the lower dose cohorts. It will include key biomarkers — we have talked about mutant huntingtin — and we are striving to include assessment of wild-type huntingtin as well. You will have clinical and safety data. After the 32-milligram data are reviewed we will determine whether to escalate to a higher dose. You will also have open-label extension data for SNP1 and SNP2, which will provide longer-term dosing information for some patients. It's a fairly large dataset to be shared in that first quarter, and based on those data we will discuss next steps toward a pivotal. The decision to move toward pivotal will be driven by the degree of knockdown observed across cohorts. Remember the interim analysis was only partial and not everybody had reached day 140 at that time. Once we look at the full dataset and the OLE and the 32-milligram knockdown that will put us in a better position to determine the next steps toward a pivotal study.

Okay, great. Thanks. And one follow-up: you mentioned optimizing the wild-type detection assay. Can you give more color on where that stands and what's left to optimize? Will it be implemented differently than before?

I'll hand that to Mike. It's an important area of work for the research team and for the field.

As we discussed at the interim analysis, the mutant assay is similar to what others use for mutant measurement and at that time we also looked at total huntingtin in CSF samples. We noted limitations in measuring wild-type indirectly from total. We are now focused on specifically measuring the wild-type portion of that total pool. This has required substantial work and we are implementing a new approach. Our intention is that when we reveal the data in the first quarter we will include an assessment using this new approach that will clarify what portion of the total assay is wild-type versus mutant. We aim to work with the community to make this approach more widely available should we be successful because we believe it is an important measurement that should be broadly accessible. The partners we are working with are quite excited about the approach.

Moving away from dynamic ratios to more concrete numbers is the direction we've pursued and the team has been working very hard to advance it. We're excited to keep pushing that forward.

Okay. Great. Thanks, guys.

Your last question comes from the line of Eun Yang from Jefferies. Your line is open. Please go ahead.

Hi. This is Suji again. I have a quick question on the OLE data expected in the first quarter of next year. Are the patients in the OLE currently receiving drug right now? What do you expect to show? And the second question: for the SNP3 Phase 1 trial that you are going to start, will the design be similar to the SNP1 and SNP2 programs, or do you expect to start that study in healthy volunteers first? Thank you.

I'll pass the question to Mike, but the Phase 1/2 study for SNP3 will be in patients. Mike?

In the open-label extension study, all patients receive active drug. The study is designed so that once a cohort is shown to be safe in PRECISION-HD, patients migrate up to the highest safe dose tested in PRECISION-HD. What we'll see in the first quarter are the safety and biomarker results of those patients over the duration they have been exposed. Regarding SNP3, the study will have many similarities to SNP1 and SNP2 but will incorporate learnings from those studies. For phasing, we will use the new technology through our partnership with Asuragen.

Thank you.

We have another question from the line of Debjit Chattopadhyay from H.C. Wainwright. Please go ahead.

Hi, guys. Good morning. Thanks for the updates. This is Aaron on for Debjit. I wanted to ask: are the newly identified patients for the PRECISION studies all at the same site or are they geographically diverse? Do you have more patients identified than needed to fill out the cohorts or exactly the number required? And if a patient misses an injection or a follow-up visit are they excluded or is there flexibility?

Mike, would you like to take those?

We have multiple sites with patients and backups across geographies. We have more phased patients than needed to ensure we can fill cohorts and account for contingencies. Regarding missed visits or injections, the study has procedures to manage those situations; there is some flexibility depending on timing, but the specifics are handled on a case-by-case basis with clinical site teams and the study protocol in mind.

Okay, great. Thank you. Quick follow-up: would dose escalation beyond 32 mg be dependent on a full dataset at 32 mg out to the full timepoint, or can decisions be made with partial data?

We haven't waited for the full 196 days to make dose-escalation decisions in the past. Escalations from 8 to 16 and 16 to 32 mg were made before we had complete biomarker data, based on the safety of the single-dose cohort and review of the independent safety committee. Decisions are informed by safety and independent review, not necessarily waiting for full biomarker timepoints.

Okay, great. Thanks guys.

There are no questions at this time. I'll now turn the call back over to Dr. Paul Bolno.

Thanks everyone for joining the call this morning to review our second quarter update and thanks to our employees for their hard work and commitment to patients. We look forward to speaking to you again soon in our upcoming research webcast. Have a nice day. Thank you.

Ladies and gentlemen that does conclude our conference for today. Thank you all for participating and you may now disconnect. Have a great day.