Voyager Therapeutics Inc (VYGR) 2018 Q3 法說會逐字稿

Good afternoon, and welcome to the Voyager Therapeutics Third Quarter 2018 Financial Results and Corporate Highlights Conference Call. (Operator Instructions) Please be advised that this call is being recorded at the company's request.

At this time, I'd like to turn it over to Matt Osborne, Voyager's Vice President of Corporate Affairs, Communications and Investor Relations. Please proceed.

Thank you. Good afternoon, and welcome to the conference call.

This afternoon, we issued a press release which outlines the recent corporate highlights and financial results for the third quarter of 2018 and provides financial guidance for 2018. We also issued a separate press release providing an update on the longer-term clinical results with VY-AADC for Parkinson's disease. These releases are available at voyagertherapeutics.com.

Today on our call, Andre Turenne, Voyager's President and CEO, will review our recent corporate and clinical program highlights; Dinah Sah, Voyager's Chief Scientific Officer, will review updates with our preclinical pipeline program; and Allison Dorval, Voyager's Chief Financial Officer, will review the financials. And then we will open up the call for your questions.

Before we begin, just a reminder that various remarks we make during this call about the company's future expectations, plans and prospects constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. These forward-looking statements represent the company's view as of today, November 7, 2018.

Voyager disclaims any obligation to update these statements to reflect future events or circumstances. Please refer to today's press releases as well as Voyager's filings with the SEC for information concerning risk factors that could cause actual results to differ materially from those expressed or implied by such statements.

With that, I'll pass the call over to Andre.

Thank you, Matt, and good afternoon, everyone. Thank you for joining us on the call.

As we highlighted in today's press releases, the third quarter was a productive one for the company with positive new data on both our lead program, VY-AADC for Parkinson's disease, and on our pipeline programs.

We described today in a separate press release the positive longer-term results from the ongoing open-label, dose-escalating Phase Ib clinical trial of VY-AADC. At the latest time point measured for each of the 5 patient cohorts, patients in the 2 highest dose cohorts experienced mean durable improvements in good ON time, which is ON time without troublesome dyskinesia, of 1.7 hours per day at 18 months for cohort 3 and 2.7 hours per day at 2 years for cohort 2.

Importantly, these improvements in good ON time were achieved with large and sustained reduction in daily oral levodopa and related medications in these 2 highest dose cohorts. This include a 43% reduction from baseline for cohort 3 at 18 months and a 21% reduction from baseline for cohort 2 at 2 years.

Since we've selected a dose of up to 2.5 e12 vector genomes for the Phase II, which is between the doses used in cohorts 2 and 3 of the Phase Ib, combining the data from the 10 patients in these 2 cohorts provides the most relevant dataset. For this combined group of 10 patients, VY-AADC improved patients' good ON time by 2.4 hours per day at 12 months, which is the time point for the primary endpoint of the Phase II trial, and 2.6 hours per day at 18 months, which is the latest time point measured for both cohorts.

We've learned from the Phase Ib that patients with severe dyskinesia baseline could be more challenging to treat as they may take longer to settle in with good ON time after administration of VY-AADC. We've also learned from the Phase Ib that the selection of patients for the study with sufficient OFF time at baseline may meaningfully enrich the patient population to show a clinically important restoration of motor function.

We've incorporated these insights into the design of the Phase II trial.

Of the 10 patients enrolled in cohorts 2 and 3 of the Phase I trial, 7 would have likely been eligible for the Phase II based on the more stringent criteria of minimum amount of OFF time and less severe dyskinesia baseline now incorporated into the study. For these 7 patients, the improvements in good ON time were an impressive 2.8 hours at 12 months and 2.5 hours at 18 months.

Now it's worth taking a moment to characterize the potential clinical significance of these observed improvements. Good ON time is frequently used in Parkinson's clinical development and disease management and, by definition, is the time that patients are on or responding to their medication but without troublesome dyskinesia as recorded in a patient diary.

The disease burden for these patients is just the opposite. It's the sum of the time per day when patients are OFF, that is stiff and immobile and not responding to their oral medication plus the time that they are on but with troublesome dyskinesia or serious uncontrollable movement. These disease states are enormously problematic for these patients and, as they become more frequent, prevent them from carrying out their normal lives.

So for the 10 patients from cohorts 2 and 3 of the Phase 1b trial, this disease burden, again, the sum of OFF time and troublesome dyskinesia, was on average 5.5 hours per day at baseline. Following treatment with VY-AADC, this was reduced by 46% at 12 months and by 47% at 18 months with similar reductions observed in the 7 of 10 patients who would have been eligible for the Phase II study. Again, importantly, these improvements were achieved at the same time as patients had large and sustained reduction in their levodopa and related medications versus pretreatment.

For the 10 patients in cohorts 2 and 3 and the 7 among them who would have been eligible for the Phase II, the sustained average reduction in levodopa-equivalent doses were between 30% and 40% from baseline at both 18 months and 12 months. We expect to provide the next update from this Phase 1b trial in Q2 2019 once all 10 patients at these 2 highest dose cohorts have reached 2 years since treatment. Also in Q2 2019, we expect to announce 12-month results from all 8 patients from an additional Phase Ib trial in which VY-AADC was administered via the posterior infusion trajectory, which is the preferred surgical route of administration for the Phase II trial.

Now turning to the regulatory update. As previously announced, in July 2018, we received written Type C meeting feedback from the FDA indicating that the results from the Phase II randomized placebo-controlled trial, if it were to meet its primary endpoint and in the absence of major safety concerns, likely may be considered sufficient for submission of a BLA for review. In October 2018, we received an addendum from the FDA to the July 2018 written responses in which the FDA informed us that although the data from the Phase II trial may support the safety and efficacy of VY-AADC and could be considered in the BLA review, the FDA currently considers the Phase II trial an early phase exploratory study.

We plan to engage with the FDA to gain further clarity on their most recent responses. We have a scheduled Type B meeting later this year, and we'll continue to actively seek and incorporate FDA guidance through the additional mechanisms now available to us via our RMAT designation.

Operationally, on VY-AADC, we've been focused on the initiation and execution of the Phase II trial. We've selected 24 leading neurosurgical and neurology sites for the study. We are at the stage of IRB approvals, site activation and patient screening. As the first randomized placebo-controlled study of VY-AADC, great care is being applied to ensuring the blinding process at the IRB level and to enabling the rigorous coordination of patient selection, screening and surgical scheduling among the related investigative sites. We expect several additional connected neurology -- neurosurgical sites to become activated before year-end and expect to provide an update upon dosing of the first patient.

Before turning the call over to Dinah, who will discuss the exciting developments with our preclinical programs, I wanted to highlight updates on Voyager's management team. Today, we announced the appointment of Allison Dorval as Chief Financial Officer from her previous position as Vice President of Finance. I'm very pleased to have Allison serve in this role. Since joining the company in June 2017, Allison has built and led a strong finance team. With her more than 20 years of experience in finance and accounting, I'm absolutely thrilled to have Allison contribute to Voyager's growth in this new capacity.

In addition, we've also made good progress on our search for a Chief Medical Officer. We expect to finalize our selection process and look forward to also announcing this appointment soon.

With that, I'll now turn the call over to Dinah.

Thanks, Andre, and good afternoon, everyone. I'll spend the next few minutes describing some of the recent exciting preclinical data with our Huntington's disease program and our ALS program targeting the SOD1 mutation.

Before doing so, it's important to take a step back and understand our systematic approach to fully optimizing not only the payload, or in these cases, the primary microRNA cassettes, but for both programs, delivery of the vector as well.

First on payload selection. For our AAV RNAi program, we begin with the most potent RNAi sequences based on in vitro transection experiments and then placed the selected RNAi sequences within engineered primary microRNA cassettes for expression in AAV. Multiple studies have demonstrated that primary microRNA cassettes provide better precision and efficiency of processing than short hairpin RNAs. So we have chosen to use the primary microRNA cassettes in our RNAi platform.

We screened a number of primary microRNA cassettes RNAi sequences to select the most potent candidates in vitro. These were then tested head to head in the mouse for in vivo knockdown of the target. The top 3 or 4 sequences are finally tested in a lead selection study in a large mammal such as nonhuman primate for the selection of the clinical candidate.

In the in vivo studies, we not only assess knockdown of the target but also conduct deep sequencing to evaluate precision of processing and guide to passenger ratio. And recall that the guide strand is the active drug, whereas the passenger strand is just along for the ride, no intended pharmacological activity. The final selection is based on the most robust and potent pharmacology, in this case knockdown of the target, as well as most selective pharmacology.

Our first RNAi program at Voyager was the ALS SOD1 program, where we optimized this RNAi platform mostly by optimizing the primary microRNA cassette sequences. During this, we have worked, after extensive screening of numerous natural and engineered primary microRNA cassettes. We identified a handful of top primary microRNA cassettes. For the HD program, we used these top primary microRNA cassettes in essentially a plug-and-play system together with the most potent RNAi sequences targeting Huntington and, thereby, were able to go from target to candidate, that is optimized primary microRNA, in a much shorter period of time than for ALS SOD1.

So there was substantial leverage of learnings from advancing our AAV RNAi platform. For production of AAV RNAi vectors in the baculovirus sf9 system, we have also optimized our vector genome configurations using molecular engineering. This is another very important feature of our RNAi platform.

Now turning to delivery in both the PD and HD programs, we used intraputaminal infusion with MRI guidance. We'll therefore, be able to leverage our substantial learnings from the PD program, including the surgical procedure, trajectory planning and device, and apply these learnings to the HD program for intraputaminal infusion.

And in the press release today, we announced progress with our 510(k) clearance of V-TAG, a realtime intraoperative MRI-compatible neuro navigational device as an additional choice for neurosurgeons in the Parkinson's disease program. And importantly, this could also be used for our Huntington's disease program as well as other programs. We leverage the onetime delivery of these vectors in unique ways to target precisely areas of the brain and spinal cord and the relevant cell types within those regions that most prominently contribute to disease manifestations.

For Huntington's disease, this resulted in significant reduction of Huntington gene expression in deeper tissues and outer layers of the brain of large animals. And for SOD1 ALS, we achieved significant reduction of SOD1 gene expression throughout a large animal spinal cord, including importantly, almost complete reduction of SOD1 in cervical motor neurons.

Specifically for Huntington's disease, our novel delivery paradigm targets both the putamen and thalamus, which leverages more extensive and preserved neuronal pathways to the cortex than delivery to the putamen alone. This can offer the potential of a onetime treatment with VY-HTT01 to address motor, cognitive and behavioral disabilities associated with Huntington's disease.

We also conducted robust analyses, including quantitative measurement in multiple tissue punches and in more than 100,000 neuron captured by laser microdissection in order to measure Huntington knockdown to demonstrate that we are, in fact, getting the right amount of knockdown in the right tissues and in the right cell types.

Our optimized delivery paradigm resulted in reduction of Huntington messenger RNA, on average, by 68% in the caudate, 67% in the putamen, 73% in the thalamus and 32% in cortical neurons. In the context of potential therapeutic benefit to patients as well as competitive landscape for HD, these are very compelling results.

For VY-SOD102, we chose to assess the mini-pig, which has a spinal cord similar in length and diameter to the human spinal cord. We felt that it was important in this large species to test the spread of the vector up and down the spinal cord. With nonhuman primates, the spinal cord is 2x to 3x shorter than that of a human, so gradients seen with intrathecal lumbar dosing in nonhuman primates are anticipated to be further magnified in the longer human spinal cord. Therefore, we felt that it was important to assess the spread of our vector and the knockdown in a spinal cord that more closely resembles the human spinal cord in size.

Here with VY-SOD102, a novel delivery paradigm comprising a onetime intraparenchymal infusion directly to the cervical region of the spinal cord significantly reduced SOD1 mRNA in the spinal cord on average by 70%, and 50% in the cervical and thoracic regions, respectively, both of these regions being critical for respiratory function and 82% reduction of SOD1 near the site of cervical injection.

This knockdown in these regions is particularly important as most patients with ALS die of respiratory failure. Therefore, suppressing the disease-causing gene expression in this region that controls respiratory function could offer a tremendous clinical benefit. In addition, VY-SOD102 reduced SOD1 mRNA by 22% even in the lumbar region.

So in summary, we are very excited by the robust reductions of disease-causing gene expression that were achieved as part of our latest delivery optimization efforts in both our Huntington's disease and ALS programs. These data in large animals support our progress towards initiating human studies for both programs during 2019.

Now briefly turning to our Friedreich's Ataxia program and AbbVie collaboration to vectorize the tau antibody for the treatment of Alzheimer's disease and other tauopathies. Our Friedreich's Ataxia program continues to progress towards selecting a lead candidate that comprises an optimal capsid, promoter and frataxin transgene. We are conducting further studies with potential candidates, which include a novel capsid that, when administered IV, provides biodistribution to key tissues for the treatment of FA -- the dorsal root ganglion, heart and dentate nucleus -- where it is most important to restore frataxin for clinical benefit. Our AbbVie collaboration to vectorize the tau antibody for the treatment of Alzheimer's disease and other tauopathies also continues to make good progress.

With that, I'll turn it over to Allison

Thanks, Dinah. Good afternoon, everyone.

Voyager reported a GAAP net loss of $20.3 million or $0.63 per share for the third quarter ended September 30, 2018, compared to a GAAP net loss of $23.3 million or $0.89 per share for the same period in 2017. Collaboration revenues of $2.1 million for the third quarter of 2018 compared to $1.1 million for the third quarter of 2017. This increase reflects the recognition of revenue related to research services performed under the AbbVie collaboration agreement announced in February and was offset by reductions in amounts recognized under the Sanofi Genzyme collaboration. These reductions related to lower research and development services revenue as well as the impact of adopting certain accounting rules related to our recognition methodology.

Research and development expenses decreased to $16.6 million this quarter from $19.6 million in Q3 last year. This was primarily a result of higher manufacturing costs last year to support the VY-AADC clinical program. This reduction was offset by increases in personnel and facility costs to support the advancement of our clinical and preclinical programs. General and administrative expenses of $6.6 million for the third quarter of 2018 increased from $4.9 million last year, primarily due to personnel and facility costs to support the advancement of our lead and pipeline programs, our platform and our manufacturing capabilities.

We ended the quarter with cash, cash equivalents and marketable debt securities of $179.6 million. Based on our current operating plan, we expect to end 2018 with total cash, cash equivalents and marketable debt securities above the previously guided range of $125 million to $135 million. We continue to project our cash, cash equivalents and marketable debt securities to be sufficient to fund operating expenses and capital expenditure requirements into early 2020.

With that, I'll turn the call back to Andre.

Thanks, Allison. And with that, operator, we can now take questions.

(Operator Instructions) And our first question comes from Brian Skorney of Baird.

I just want to kind of dig in a little bit on the change in sort of the FDA body language here with the addendum. Was there any new data submitted between getting the minutes back from the Type C meeting and this addendum that would trigger this? And is there any way you could just 8-K the meeting minutes and the addendum for us so we have an idea of what the FDA's new change of position is?

Yes, thanks for the question, Brian. So there is no new data between the Type C meeting and this addendum. And what we're endeavoring to do next is to find out more by getting in touch with the agency, and we have a Type B meeting scheduled between now and the end of the year, and we're going to look to have access also through the channels we have via the RMAT designation. So as soon as we have greater clarity, we're going to provide the update on this, but that's the -- the path for us for next step is we to engage -- continue to engage with the agency to clarify their latest comments.

And our next question comes from Laura Christianson of Cowen.

My first one is just -- I was looking at the data you provided on the L-dopa dose reductions and particularly in cohort 2 at 24 months, saying that there's been a 21.2% reduction overall. I know previously you had mentioned there was a reduction of 34% at 6 months. So I'm just wondering if this changes your view of the long-term efficacy or whether the L-dopa reductions were just more sudden initially, and you anticipate that more gradual reductions won't yield the same result.

Yes. Thanks, Laura, for the question. So when we look at all the cohorts and the data we have to-date over time, we see clearly that we have both a sustained reduction in levodopa but one also that's different cohort by cohort. So where we're seeing the least reduction is with cohort 1, and then there's a good dose response there, where cohort 2 the dose -- the levodopa-equivalent dose remains low versus baseline, and then that's even more the case for the third cohort where we have the highest and most sustained reduction in the levodopa-equivalent doses. So for us, again, having now made a dose selection, a choice that we're adding a dose that's in between cohort 2 and 3. When we look at that relevant group, the cohort of 10 patients, there are 7, as we highlight in the comments in the press release, that would likely be eligible for that Phase II. We see a nice consistent reduction in levodopa-equivalent doses. As you go through 12 month and 18 months, it stays in the 30% to 40% reduction versus baseline. So that's quite significant because it goes at the core of the mechanism of this AADC replacement. So to be able to improve motor function while at the same time the patients have this large and sustained reduction in the levodopa-equivalent dose is to us a clear sign that the pharmacology is very active, and we're seeing something sustainable.

Got it. That's helpful. And then just a quick one on the Phase II/III. How consistent do you expect the dose concentration to be across patients in that trial with the surgeons aiming for concentration between cohorts 2 and 3 but potentially having some variability?

Yes. So the concentration is fixed. The variability is going to come from the exact volume that's delivered. That's going to vary depending on the patient. Every anatomy of the putamen is a little bit different patient by patient. So we expect the volume differences to be relatively small and, therefore, the total vector genomes delivered to -- the difference -- the range to be relatively tight with this route of administration. This is a single infusion that's required with the posterior route. And again having the -- a lot of the motor function in the posterior region of the putamen the way the surgery will work -- or works with that trajectory is that the most important area is impacted first and covered more totally with the infusate. But to answer your question, we don't expect large variation in that volume and, therefore, in the vector genomes delivered.

(Operator Instructions) And our next question comes from Jeff Hung of Morgan Stanley.

Can you provide some color on what the agency said, if anything, during the Type C meeting regarding their thoughts on the Phase II being more exploratory?

Thanks, Jeff. So as we reported after the Type C meeting -- from our Type C meeting minutes that -- responses to our question, the agency responded to us that the Phase II alone likely may be sufficient. Now if it were to prove to be effective to meet its primary endpoint and to be safe for, the submission of the BLA -- for submission. So that's the feedback that we received at that time, and that's why here we are going to seek clarity on this addendum that we just received to be able to align with the agency on the next step. What's clear is that the Phase II is the trial that -- that the right trial and is moving forward, what we'll do with once we have the benefit of getting greater clarity from the agency is that we'll consider adjustments to the overall plans if and as necessary so we can continue to be aligned with the guidance that they provide once they clarify it. But that's where we stand right now. And again, we have the means of engaging with the agency having a Type B meeting in front of us and having access, also, again to really the senior and accelerated type of engagement we can get via the RMAT designation.

And I think you just answered it, but maybe if I can push a little bit on that last part. So does the addendum change your base case assumption that the Phase III would be required regardless of the outcome of the Phase II? And would the Phase III be sufficient for filing? Or do you think additional studies will be required beyond your Phase II and Phase III?

Yes. So at this moment, we won't speculate on any changes to the plan. So we still believe that we have a robust plan with a Phase II and a Phase III staggered design, and we'll look to get the further dialog with the agency to clarify, again, any adjustments that -- if any, that we make to the current plan. But the plan for the Phase II, again, in terms of primary endpoint, in terms of the route of administration, the dose that we selected, the patient population. The first placebo-controlled study for this therapy is absolutely what we believe is the right thing to do. So we'll review with the agency the plans in totality via this Type B meeting and the other interactions we may have, and we'll provide updates as to the overall package in due time.

Okay. And then maybe one last one. You're excluding patients who are severely dyskinetic in the Phase II. Can you remind us what proportion of moderate and advanced Parkinson's patients are severely dyskinetic?

Yes. So that's a hard number to get that precise, but in our experience and working with our investigators, we think it's a small portion. It's a minority of patients with severe dyskinesia to the level that we -- that would be excluded from this trial. So it's a small percent.

So -- I just want to make sure I heard that right. So then, do you think that the 3 out of 10 excluded from the Phase Ib is representative of what you might see in the real world?

No, so there were 2 reasons why the 10 patients that were in cohorts 2 and 3 likely may not be patients that would be enrolled in the Phase II. One of the criteria was too severe of dyskinesia, but the other criteria, and it's now more stringent, is the amount of OFF time at baseline, which is the disease severity at baseline. So we had a patient population here that we had that -- it would be more stringent in a Phase II as to that minimum amount of OFF time at baseline. So it's these 2 factors that the -- are enriched, if you will, in the Phase II versus the Phase Ib experience.

And the next question comes from Jim Birchenough of Wells Fargo.

And our next question comes from Sumant Kulkarni of Canaccord.

The first one is on the AADC product. At the time you're eventually in a position to receive Phase III data, you'd have a wealth of time built up on the patients that are in the Phase I, which might inform whether this product is truly a onetime dose or not. So assuming that, for some reason, AADC does not turn out to be a onetime dose, how many years of an effect do you think it needs to have to compete credibly with deep brain stimulation?

Thanks for the question. So as you say, the durability is an important feature of the program, an appealing feature. So the evidence that we have, if you go back to the development of the program there, we have up to 15 years of a preclinical model in monkeys that show that we have durable sustained expression of AADC following treatment with VY-AADC. So that is one sign that, if you administer VY-AADC to the putamen, which does not degenerate in Parkinson, you have this potential for very long duration. From the first clinical experience with VY-AADC, there is now data to 5 years prior to the Phase Ib that we've conducted that shows, again, durable expression of AADC. And as you suggest, we have a Phase Ib that was a 3-year consent and that we will also look to have patients in an extension study to be able to continue to collect data to be able to assess -- ascertain the durability of effect in this latest active group of patients. So all of this definitely will be a part of the full picture by the time we get to a BLA filing for the durability of effect. So anything from that experience that suggests multiple years of durable improvement will be certainly a big, big improvement for these patients who otherwise -- they really have plateaued and have peaked and continue to increase their levodopa doses while they continue to lose motor function. So here it's not -- what we're seeing to-date is not just the stabilization of disease. What the data suggests is an improvement in motor function with less background therapy. And if that can be sustained, this is a very important clinical benefit, we believe.

And then given the wrinkle thrown in by the FDA addendum now, I know you said that you're going to announce when you will dose the first patient. How does the time line on that change though, if at all?

So the plan for this trial does not change. So again, this is the first placebo-controlled study that we're doing with VY-AADC. We think it's in the right patient population, and the plan has been reviewed and discussed with the agency. So I think the question here is the likelihood of the suitability of a single trial as currently sized to be sufficient for a BLA filing, and that's going to be the core of the question to continue to discuss with the agency, so we can, again, consider making any adjustments to our plans if and as necessary once we get that greater clarity, but the plan for the current study is as previously planned.

And our next question comes from Jim Birchenough of Wells Fargo.

This is Yanan dialing in for Jim. So just want to ask about the FDA's language a little bit more because the Phase II is, indeed, a randomized design. I think the design was pretty similar to the Phase III. And also given that you already have Phase Ib data, so a little curious about the language of Phase II being exploratory. So I guess -- what is your thought on that? And then secondarily, given that the Phase II, Phase III are similarly designed, the current designs are staggered starts, but do you have the ability, given that your comfort level now with all the data, do you have the ability to move the Phase III start time ahead so that you can still have the similar kind of time line for data? I guess, I will stop there, and I have a follow-up.

Yes. Thank you, Yanan, for the question. So yes, we'll have to discuss with the agency, again, to clarify their statement and their position, and we'll do as we've done to-date, we'll look to incorporate that feedback and to inform any adjustments to our plan. So this is new information to us, and we have an ability, again, to have the next set of discussion with the agency to clarify their position and for us then in turn to make any adjustments as we think helpful and necessary. And again, soon in front of us here before the end of the year, we had a scheduled Type B meeting, and again, we have the benefit once again of this RMAT designation, and that's the express purpose of this designation is to be able to have the right access and accelerated type of feedback with the agency, and we're going to absolutely look to both via the Type B meeting and via that channel to get the clarity very quickly and then consider any change, if any, to the overall plan to a BLA.

Got it. And also, on the posterior study, are we going to have some detailed data on the 6 months -- at the 6-month follow-up time point? Or is it just the 12 month in next year, that's the first time we'll hear detailed data? And also, have you shared the posterior study data with FDA yet?

Thanks for your question there. So we currently expect to share once we have the full cohort of 8 patients, those with the posterior route, get to 12 months, which is in Q2 2019. We'll expect to provide that full update at that time. And to your other question, the data is going to be submitted to the agency once we have a request for an additional meeting. We're going to provide the relevant dataset to put in front of them, whether it's from updated longer-term results of the 11 01 study or results from this 11 02 study with the posterior route. We will provide the freshest cutoff data relevant for discussions with the agencies moving forward.

Got it. Last question on the preclinical program in Huntington's. Just wondering, is there a role for coverage in this disease as it is for Parkinson's and in the coverage via the gene therapy for the putamen, and now you also mentioned thalamus is also going to be a target site. And if there is such a role in -- for coverage, then what kind of a percentage of coverage should we expect to be therapeutically relevant?

Yes, no, thank you for your questions. I'll ask Dinah to answer your question here.

Yes, it's a good question. There is a role for coverage of both the putamen and the thalamus in Huntington's disease. In the case of putamen, of course, it's involved in motor function. The medium spiny neurons throughout the putamen are degenerating. Those are the ones we want to protect by lowering Huntington. So the broader the coverage the more medium spiny neurons we protect and the more benefit to -- therapeutic benefit to function. With the thalamus, we're leveraging the widespread and preserved connections to the cortex and different regions, different nuclei of the thalamus project to different regions of the cortex. So in order to maximize the distribution of our vector to the cortex and maximize knockdown of Huntington throughout the cortex, likewise, the goal would be to maximize the distribution and coverage of the thalamus. So in both cases for both structures, the goal would be to cover a large portion of both structures.

And that concludes our question-and-answer session for today. I'd like to turn the conference back over to Andre Turenne for closing remarks.

Thank you, operator. So that concludes the call. Thank you all for attending. I appreciate all the thoughtful questions, and we'll look forward to updating you on the progress in the near future. Thank you.

Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program, and you may all disconnect. Everyone, have a great day.