WAVE Life Sciences Ltd (WVE) 2020 Q1 法說會逐字稿

Good morning and welcome to the Wave Life Sciences First Quarter 2020 Conference Call. (Operator Instructions) As a reminder, this call is being recorded and webcast.

I will now turn the call over to Kate Rausch, Head of Investor Relations at Wave Life Sciences. Please go ahead.

Thank you, operator. Good morning and thank you for joining us today to discuss our recent business progress and review Wave's first quarter 2020 operating results. On the call with me here today are Dr. Paul Bolno, our President and CEO; David Gaiero, Interim CFO; Dr. Mike Panzara, our Chief Medical Officer; and Dr. Chandra Vargeese, Senior Vice President, Drug Discovery.

This morning, we issued a news release detailing our first quarter results. Please note that this news release is available in 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 March 31, 2020. 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 Dr. Paul Bolno, President and CEO of Wave Life Sciences. Paul?

Thanks, Kate. Good morning and thank you for joining us today. I'll start today's call with a few introductory remarks. Next, Dave Gaiero will discuss our financial results. Mike Panzara will provide an update on the progress of our neurology pipeline. And finally, Chandra Vargeese will provide an exciting update on our emerging RNA-editing platform capability.

During the first quarter, I am proud that our team's commitment, along with the close partnership and support of our clinical trial sites, has allowed both PRECISION-HD clinical trials to continue despite the challenges presented by the COVID-19 global pandemic. We have also continued to progress work that will allow us to submit clinical trial applications for 2 additional neurology programs in the second half of this year: our SNP3 for Huntington's disease and our C9orf72 program for ALS and frontotemporal dementia. And today, we are announcing our first in vivo RNA-editing data, delivering on one of our key corporate goals for 2020.

Like everyone else, we are operating in the midst of the COVID-19 pandemic, an evolving and dynamic situation. While the unknown duration of the pandemic makes it difficult to predict or plan for potential longer-term impact to our business, we have leaned into the challenge and maintained a consistently proactive approach. We quickly established an internal COVID-19 response team that includes expertise from across all areas of our organization. This team meets on a regular basis and has facilitated our ongoing operations by focusing on 3 priorities.

First, we are safeguarding the health and well-being of our employees as well as patient caregivers and clinicians. The majority of our team has been working from home since mid-March, and we have implemented strict protective measures for the small number of employees whose work requires them on site in our lab and manufacturing facility.

Second, we are focused on advancing our programs while adapting to new challenges in the current environment. Importantly, even before the pandemic, we had been actively investing in our manufacturing facility, managing our supply chain, vendors and inventory levels to limit the potential for disruption. As a result, we have sufficient materials stored locally to enable us to continue to manufacture our products for at least 12 months. Mike Panzara will share more details on how we've been able to maintain momentum with our 2 global clinical trials.

Finally, we are working to create opportunities in this new environment. For example, we have found ways to creatively engage with our stakeholders, including virtual meetings with researchers, clinicians, advocates and broader patient communities, all while maintaining social distancing.

Additionally, we are working to get ahead of future opportunities and challenges, including planning for an expansion of on-site activities in our labs and manufacturing suites as well as remaining prepared for a second wave of coronavirus outbreak. For patients and families with devastating neurodegenerative diseases, progress cannot come fast enough. Knowing that they are counting on us has kept us going and continues to motivate everyone at Wave.

Our innovative pipeline is focused on neurology. Notably, we continue to make excellent progress on the multiple preclinical CNS programs we are advancing with our partner, Takeda. In the first quarter, we achieved target validation in vivo with a lead compound for a second program, and we expect to achieve target validation for a third program later in 2020. Takeda is excited about the progress we are making, and we look forward to sharing further updates on these programs.

Beyond neurology, our platform capabilities offer the opportunities for us to help more patients, including those living with genetically defined diseases of the liver and eye. To that end, we continue exploring opportunities to advance our 2 preclinical ophthalmology programs, USH2A for Usher Syndrome Type 2A and RhoP23H for retinitis pigmentosa, both of which have demonstrated positive preclinical data.

Within hepatic diseases, while the collaboration with Pfizer concluded earlier this month, we are today announcing our initial ADAR-mediated RNA-editing data in the liver of nonhuman primates, and we expect our initial disease target for ADAR to be focused in hepatic disease. We are building our RNA-editing technology as a platform capability and see opportunity to apply this to other therapeutic areas over time or in collaboration with potential partners.

I will now turn this call over to Dave Gaiero for a review of our financial. Dave?

Thanks, Paul. For the first quarter of 2020, we reported a net loss of $47.5 million compared to $44.2 million for the same period in 2019. Research and development expenses were $41.2 million in the first quarter of 2020 compared to $40.1 million for the same period in the prior year. The increase in research and development expenses in the first quarter was primarily due to increased external expenses related to our clinical and preclinical activities, including our HD programs and our C9orf72 program for ALS and FTD and separation costs associated with the workforce reduction implemented in February 2020, partially offset by decreased external expenses related to our DMD programs due to our December 2019 decision to discontinue the suvodirsen program and to cease development of our other DMD programs.

General and administrative expenses were $13 million for the first quarter of 2020 compared to $10.9 million for the same period in the prior year. The increase in general and administrative expenses in the first quarter was mainly driven by separation costs associated with the workforce reduction implemented in February 2020.

We ended the first quarter of 2020 with approximately $121 million in cash and cash equivalents, including $20 million in research support funding received from Takeda in the first quarter under our collaboration. As a reminder, we expect to begin to realize the results of our overall cost reduction efforts, including our February 2020 workforce reduction, in the second quarter of 2020.

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 third quarter of 2021.

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

Thanks, Dave. Today, I will be giving an update on where things stand with our clinical development programs. However, I'd like to begin with yet another publication that highlights the importance of what we are doing in Huntington's disease by working to develop allele-selective treatments.

This recent publication by Poplawski et al in Nature adds to a growing body of evidence that preserving wild-type Huntington will be essential to impacting clinical outcomes of this disease, demonstrating that Huntington is at the center of the regeneration transcriptome, playing an essential role in neuroplasticity after injury.

Turning to an update on our PRECISION-HD clinical trials. Since the start of the pandemic in the first quarter, we have been keenly focused on ensuring the safety of our study teams, patients and investigators while continuing to advance our trials and mitigate future potential risks. As you know, this is a dynamic situation that we have been monitoring vigilantly and proactively, doing what we can to enable our patients to continue treatment while ensuring the data quality required to enable definitive results.

As a reminder, PRECISION-HD1 and PRECISION-HD2 are evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple doses of WVE-120101 and WVE-120102 in adult patients with early manifest HD who carries SNP1 or SNP2, respectively. WVE-120101 and WVE-120102 are the first and only compounds in clinical development designed to selectively target the mutant allele of the Huntington gene transcript while leaving the wild-type Huntington relatively intact.

Both studies have continued to progress. We have benefited from the prioritization of disease-modifying studies by health authorities, the infrequent dosing regimen and the global distribution of our clinical trial sites. Most importantly, the commitment of our patients and investigators has remained steadfast, speaking to the importance of the work we are doing and the high unmet needs of those suffering from Huntington's disease.

As all health care systems are currently under significant stress, some PRECISION-HD trial sites have been impacted by the pandemic. However, I'm pleased to report that we currently remain on track to deliver data from both the PRECISION-HD trials in the second half of the year. Specifically, for PRECISION-HD2, we expect to report data from the 32-milligram cohort, which was initiated in January as well as data from each of the previous individual cohorts.

Similarly, for PRECISION-HD1 trial, which remains blinded, we initiated the 32-milligram cohort in March as planned, and we expect to report results from the individual cohorts in this trial, including 32 milligram in the second half also. Of course, should global restrictions continue or worsen, the ability to evaluate patients as planned in each of these studies has the potential to be impacted. For both PRECISION-HD trials, we continue to assess the ability to advance to a next higher dose, which will be determined by single-dose safety results of the 32-milligram cohorts and available pharmacokinetic data as well as our preexisting preclinical packages.

Our third allele-selective HD program, our SNP3 program, continues to advance towards clinical development. As a quick reminder, approximately 40% of the HD population has SNP3, and with overlap, up to 80% of the HD population contains at least one of SNP1, SNP2 and/or SNP3. Our SNP3 program is designed with a novel chemistry advancement from our PRISM platform, and we are particularly excited by the in vivo data we have seen to date in preclinical models. We expect to initiate clinical development, meaning submission of a clinical trial application, or CTA, for SNP3 in the second half of this year.

Turning now to our C9orf72 program, which is also approaching the clinic. This program aims to address amyotrophic lateral sclerosis and frontotemporal dementia caused by mutations in the C9orf72 gene. This is the most common cause of familial ALS and FTD and a strong genetic risk factor for the sporadic forms of the disease. This program is designed to selectively and potently silence the transcripts that contain the hexanucleotide repeat, which drives the formation of toxic RNA and abnormal proteins in brain tissue.

Similar to our SNP 3 program, our C9 program also uses new chemistry off of our platform, and we have demonstrated proof of principal in transgenic animal models. In these in vivo studies, we've shown potent knockdown of both the repeat-containing transcripts and the associated dipeptides while avoiding a reduction in wild-type protein. We expect to submit a CTA for our C9orf72 program also in the second half of the year.

And with that, I'll hand over the call to Chandra Vargeese.

Thank you, Mike. Good morning, everyone. Today, I'll provide an exciting update on our RNA-editing platform. RNA editing is the newest modality to come off of our PRISM platform, adding significant capabilities to the advancement that we have made in RNA splicing and silencing.

As with our other modalities, by focusing on RNA, we feel that this approach offers several distinct benefits over gene editing, including the ability to use endogenous proteins, ease of delivery, titratable dosing and reversible effects. The endogenous protein we harness, ADAR, or adenosine deaminases acting on RNA, leads to effective A-to-G editing providing ample opportunity across a wide variety of diseases.

As you see on the right, the landscape of genetic variants amenable to A-to-G editing is very large, in the tens of thousands, which represents a rich source for discovery and identification of potential clinical target. In an analysis of pathogenic human SNPs, it has been published that nearly half could be corrected with A-to-G editing.

Beyond offering advantages over gene editing, this technology is unique among other players in RNA editing. Endogenous ADAR-mediated editing technology has emerged relatively recently, and we are at the forefront of developing this technology for potential therapeutic use. We use endogenous proteins, which avoids risk of immunogenicity from exogenous proteins such as Cas13 or chimeric ADARs and the related potential off-target effects of these proteins.

Our oligonucleotides are fully chemically modified, which increases stability and duration of activity. And typically, their 30 bases are fewer. Importantly, our ability to precisely control chirally in the backbone enables us to maximize the endogenous ADAR activity.

Lastly, we use a simplified delivery strategy, meaning no AAV vectors or no nanoparticles. In our initial therapeutic investigations, we are using simple GalNAc-conjugated oligonucleotides for hepatic targets. However, we also continued to build the RNA-editing capability of our PRISM platform and expect this RNA technology to be used across various therapeutic indications.

As we have previously described, we have achieved very efficient RNA editing in vitro with our oligonucleotides across a variety of cell lines, including nonhuman primate and human primary hepatocytes. As shown here in this slide, we have observed potent and durable dose-dependent RNA editing with 3 chemically distinct stereopure oligonucleotides via GalNAc-mediated uptake. Having achieved this in vitro, our next task was to determine whether these in vitro results translate to in vivo system, which they did. For the first time, we are sharing in vivo RNA-editing results in nonhuman primates.

For this study, we dosed 6 nonhuman primates in 3 groups subcutaneously once a day for 5 days with 3 chemically distinct RNA-editing oligonucleotides. We took liver biopsy samples at baseline and 2 days post last dose and evaluated sequence of the targeted site. As you can see on the chart on the left, we detected up to 50% editing as compared to baseline in vivo. On the right, you can see a Sanger sequencing plug for the targeted oligonucleotides, showing clear editing at the target site.

While this is an ongoing proof-of-concept study, we are very excited by these results. And to our knowledge, these are the first successful RNA editing in nonhuman primates. Importantly, we have achieved these results using our endogenous ADAR technology, which we believe makes them more compelling.

I would like to add that I'm proud of our team for delivering these results amidst a very challenging environment as we continue to adapt our work streams as a result of the ongoing pandemic. Now looking ahead, we have previously demonstrated successful RNA editing in vitro across multiple transcripts, which supports the potential of this technology to be applied across a variety of disease targets.

Our in vitro data will also be presented in a poster tomorrow at the American Society of Gene & Cell Therapy Annual Meeting, which is being held virtually. Later this year, we expect to add or share additional in vivo ADAR-mediated RNA-editing data, and we also expect to announce our first RNA-editing program in a hepatic indication.

Now with that, I'll turn the call back to Paul for closing remarks.

Thanks, Chandra. In closing, we've had a solid start to the year. We have already delivered on our first milestone and are on track to achieve several more this year, including multiple CTA submissions and data from both our PRECISION-HD clinical trials.

I want to close by taking the time to thank the entire Wave team as well as our partners in these endeavors, namely our investigators and patients, without whose steadfast commitment, we could never be where we are today. The Wave team has worked tirelessly to keep our clinical trials ongoing, our preclinical programs and our discovery work on track, all while supporting each other and our communities in this difficult time.

Whether working from home or working in our labs and manufacturing suites, the entire organization has come together to adapt to our new reality. I am grateful our team has risen to this challenge and for their dedication to bring potential new therapeutics to patients living with devastating diseases.

With that, we'll open up the line for questions. Operator?

(Operator Instructions) And our first question comes from Debjit Chattopadhyay with H.C. Wainwright.

Aaron on for Debjit. I just have a couple of questions. So the Phase I study of Tominersen was halted due to infections from the device that was used to collect some CSFs. So I was wondering if you guys can tell us if you're using a similar device or how you might be mitigating that risk.

Yes. This is Mike. Yes. So that study that was halted was a frequent PK study, to our knowledge, where they had a device in to take frequent lumbar puncture CSF samples. We are not using that device in the studies. These are monthly lumbar punctures for CSF collection and for administration of drug.

Okay. Great. And so the RNA-editing platform looks interesting. But my concern would be that systemic administration could induce immunogenic responses, similar to what we saw from suvodirsen. So could you tell us about any steps you guys have taken to mitigate that risk, especially if there are differences from the precautions that you took with suvodirsen?

Yes. I'll take the first part of this and then hand this to Mike to talk about -- and Chandra. I think the first steps were really in understanding now utilization of subcutaneous administration of GalNAc and lower doses in non-IV administration. In addition, I think as we've learned from suvodirsen, continuing to characterize those drugs preclinically is important. And I think as Mike can share, with repeat administration even systemically of suvodirsen, the study was inconclusive not because of safety, but ultimately because of efficacy. Mike, I don't know if you have anything you want to add to that.

No. I mean I'd just add that as we learn more and more about administration and distribution in getting the oligonucleotides to the target, it is about -- suvodirsen was about getting enough oligonucleotide to target with the profile that enabled us to do that. And I think right now where we are here, you've heard that this is using GalNAc. And I think also, we're in the very early stages here that as we learn more about this approach and optimize the oligonucleotide, certainly, immune activation is one of the criteria we're going to use in our screening of future candidates.

And our next question comes from Salim Syed with Mizuho.

A couple of questions on the COVID-related impacts, maybe Paul or Mike. One is, how are you guys collecting these CSF samples? Are you seeing patients still coming into the sites? Or what's been the impact there? Have you -- second is, have you seen -- do you define impact differently between site activation and enrollment versus the already enrolled patient population? And then lastly, for any sites that have been particularly hit hard during the COVID-19 crisis, have you seen the enrollment tick back up at all in the last couple of weeks as some of your peers who've noted it for their trials as well, not necessarily HD related, but in general?

Thanks, Salim. I'll turn it over to Mike. Mike?

Yes. Salim, well, I would say that this situation, I think that -- well, first of all, your first question about CSF samples and the patients coming in. One of the things that we were most worried about, but we have been very encouraged by, is that patients are wanting to come in. They're wanting to come in for their visits. They're wanting to come in for their CSF collections and their administration.

So we've been fortunate, the monthly visits allow the flexibility to schedule around what's happening at the site. So we've been fortunate in that situation. And I think we having a very dedicated patient population has mitigated much of what could -- the potential there of patients just saying, "No, I'm just going to stay home, I'm a little worried." So that's been our experience thus far.

I think with your other questions about what's essentially happening at different -- in terms of timing and different visits and how we look at some of the site activation versus enrollment, I think, basically, all of these are factors as we're looking at different sites around the world. Different sites have different challenges, different health authorities have different rules. As you know, the different countries have been impacted and handled it quite differently.

We have approached each one of the sites individually. And whatever plan is best for them in terms of recruitment and monitoring of patients, we've done that. But we've done that in a way that's consistent with our protocols that allows us to ensure the data quality. And we've been fortunate. I think it just happens to be where we've chosen the sites and the disease indication we've chosen.

And to your last point over the last several weeks, obviously, things have been loosening up around the world, and we have -- are optimistic about where that's heading, and that's been -- that optimism certainly is being conveyed from our sites.

Our next question comes from Mani Foroohar with SVB Leerink.

Aravinda in for Mani. Just a quick question on our end. Just following up on the COVID impact on the HD program, have you had any problems with enrollment, treatment from -- enrollment from 32-milligram cohort for the PRECISION-HD1, HD2 programs? Meaning like can you guide how many patients have been treated at this point? And can we anticipate data from all 12 patients in each cohort from the HD1 program moving forward?

Mike, do you want to take that?

Yes, I'll take that. So I think that our guidance is that, as we've said, that we anticipate that when we present these data in the second half and then release these data in the second half, it will include all patients in the cohort. In terms of the individual, we never comment on the individual enrollment. But again, our diversity of sites are -- the disease indication itself, the infrequent dosing, the monitoring that's required has allowed us to -- if a given site might reduce their enrollment or reduce their activity, we can always pivot to another site. So our intention is to share complete cohort data in the second half.

And our next question comes from Eun Yang with Jefferies.

For PRECISION-HD1 and 2 study, your selection of higher dose from 32 milligram, are you going to be announcing that before the data that we are going to be expecting second half of this year or at the same time?

This is Paul. Mike, you can comment after. I mean at this point, we're guiding to the clinical trials and that we're assessing moving to the higher dose. We haven't yet announced when we would be announcing next cohorts and that publicly. Obviously, as we continue to progress and assess, we will give updates. Mike?

Right. And just to stay with that, the data that will be -- second half will be that 32-milligram cohort that you're asking about.

Okay. And then RNA-editing therapeutics, so in nonhuman primates, you showed up to 50% editing efficiency. I don't know, maybe it's too early to ask, but for clinical benefit, what kind of editing efficiency do you think you would need to achieve?

I think Eun -- and then if Chandra had to add, I'm happy to bring Chandra in. I mean I think a lot of it depends on target selection. And again, the beginning part is these are the unoptimized starting point, so this is not yet the preclinical data around clinical programs, which continue to be progressed. But I think our target selection, when one looks at heterozygous diseases, where 50% correction could restore a normal phenotype, there are diseases where restoration of 50% and even less than 50% could actually change diseases. So the goal doesn't necessarily have to be 100% editing, not that we wouldn't achieve, try to achieve as much as possible.

So I think the hurdle of achieving what we would need to, to be able to go into any number of diseases, we feel like we can cross that on this initial exploratory program. I think the exciting part is, and we'll give more updates as we move through the year, is really on what targets are coming and one can see where our data will deliver on a potential program. Chandra, I don't know if you have anything you want to add to that.

No, this is correct. What you said is correct. In some diseases with the heterozygous patient population, 50% editing will restore a full phenotype.

I see. And the last question is, and if I misheard you, Paul, I apologize, but the partner to programs with Pfizer, are you also utilizing RNA-editing technology?

No. The RNA-editing technology came outside of Pfizer. Pfizer was only using the very early chemistry out of Wave, not even [to be] applying to our more recent programs. RNA editing is outside the scope of the Pfizer collaboration.

And our next question comes from Whitney Ijem with Guggenheim Securities.

On the PRECISION-HD trials, are you guys in any ways limited on the ability to dose higher based on previous data or preclinical data?

Mike, would you like to, Mike?

Yes. So no, we -- based on our preclinical data, we definitely have clearance to go higher. We have the -- I should say, the window to go higher. So that's part of the -- what we're looking at when we will be looking at all the clinical data in terms of safety PK and then that safety window. So -- but we have -- the preclinical data does support a dose escalation.

And then in terms of the data we'll see in the second half, can you kind of go over what we can expect to see? Will it be similar to the kind of special top line we got in December?

Yes. So it will -- yes, it will be similar to what you've seen there, except that what you'll be seeing is the individual cohorts because we now rather than -- that was an interim analysis of an ongoing study. What you'll be seeing at the end of this year will be the complete data sets of the individual cohorts.

And I just had one last question. Do you expect to receive any more cash payments or upfronts from collaborations this year as we think about cash runway?

I think we always contemplate doing business development, potential opportunities. Those all have the potential to bring in additional capital, both through pipeline programs as well as through the platform. So I think there are opportunities. In addition, our cash runway statements don't take into account models, those from existing collaborations with the committed payments. So I think as we think long term, I think there are opportunities for additional capital inflows.

And our next question comes from Paul Matteis with Stifel.

Just a couple of questions from us today. Just curious if thinking about the SNP3 program, whether or not that initiation is going to be gated at all by the top line from the HD1, HD2 readouts? And along with that, if you expect to start at higher doses, pending that -- those data? And then additionally, just curious if you had any updates on the presentation of the full suvodirsen data?

Thanks. I'll take the beginning, and then Mike the follow-up. But I think what was important to us is in advancing SNP3, it's a different scenario than advancing in -- within DMD, our exon 53 program on the back of suvodirsen, our exon 51 program. Our commitment to Huntington's disease remains steadfast. SNP3, for us, represents a different opportunity, a different data set is generated. We had a preclinical in vivo model that we could develop it off of, and I'll let Mike speak to that subsequently. But I think we remain committed to advancing SNP3 outside of it independently from the data that we got from PRECISION-HD1 and 2.

Mike, I don't know if you want to continue.

Yes. Sure. As Paul said, I mean, we have a data set on SNP3 using new chemistry from the platform in vivo that makes us see this as a totally different molecule as we -- as each of our molecules are, they're optimized and specifically designed. So SNP1 and SNP2 data will not influence our interest in moving forward here, given our commitment to HD and the fact that these data stand on their own.

In terms of dosing, again, we're in a very different place than we were with SNP1 and SNP2, where we did not have models to look at target engagement in the in vivo setting. Here we do. And our dosing paradigm will be driven by what we've learned from knockdown in the in vivo models as well as our preclinical. So where we go in clinic with dosing will be guided by a much more complete data set and based on the molecule itself and what it -- what was seen in these various in vivo studies.

And Mike, on the...

On the DMD, yes. And then in terms of suvodirsen data -- with suvodirsen data, basically, I mean, there's not much more to report than what we presented at the MDA meeting, where we saw quite clearly that while -- that regardless of how we looked for target engagement, we did not see it in those muscle biopsies. And it does seem that the drug was there, but 80% to 90% were -- was essentially in the extracellular matrix as opposed to getting to target. So we believe that, that's the complete story in terms of what happened with suvodirsen, and that's -- there's not anything new to report about that.

And our final question comes from Yaron Werber with Cowen.

Obviously, really exciting moving into ALS and FTD spaces there. So I just kind of wanted to touch base on how you're thinking about the timing of these clinical programs, when you think you'll actually file these INDs and if you think you'll need separate ones for each space. And if you really would try to kind of pursue them in parallel from there on out.

Yes. No, it's a great question. I'll pass it to Mike, but I appreciate your thoughts around how we think about C9orf as both as a treatment for ALS, FTD and the importance around how this disease progresses in both patients and how we're taking an approach that's looking broadly at both of those diseases. Mike, do you want to talk and speak to our strategy?

Yes. No, thank you for that. And I think that you highlight something that's very exciting about this program that we can target a single area and effect 2 very important diseases. In terms of the timing of the initial CTA, that is the second half, as we've said, and that CTA will -- is being -- the strategy behind that right now is being devised and working with the authorities on how we might be able to use that to rapidly get into both indications. I'm not prepared to get into the details there, but that is our intent. Our intent is to rapidly get into both disease indications targeting this single-gene target.

Okay. Do you think you would do like a Phase I in healthy volunteers kind of a situation and then kind of branch out into the individual indications from there on out? Or is it still a little bit in flux?

Well, I would say that we're unlikely to go into healthy volunteers in general with an intrathecally administered drug here. But I could say that the population we would go into in the first studies would set us up well to go into either indication.

Ladies and gentlemen, this now concludes our Q&A portion of today's conference. I will now turn the call back over to Dr. Paul Bolno for any closing remarks.

Thanks, everyone, for joining the call this morning to review our first quarter update. And thanks again to our employees for their hard work and commitment to patients. We look forward to updating you in the future on our ongoing progress. Stay safe and have a nice day. Thank you.

Ladies and gentlemen, thank you for attending today's conference. This now concludes our program, and you may all disconnect. Everyone, have a great day.